bluuebunny/crossref_metadata_2025 huggingface dataset:
A case study of an undetected expanded polytetrafluoroethylene implant material mimicking a nasal dorsal hump
Authors: Lee Sae Bin , Min Hyun Jin
Published: August 2022

Augmentation rhinoplasty using alloplastic materials is a relatively standard procedure in Asian patients. Expanded polytetrafluoroethylene (ePTFE) is one of the commonly used alloplastic materials because it has a high biocompatibility and is easy to handle. Recently, a patient who had previously undergone augmentation rhinoplasty using ePTFE as the implant material visited our clinic. She had the implant material surgically removed after three years and visited our clinic with a nasal dorsal hump. The patient underwent revision rhinoplasty at our institution. Unexpectedly, we found some ePTFE material that was not identified on the preoperative X-rays. After removing the ePTFE material, the nasal dorsal hump was corrected, and we did not need to perform a nasal dorsal hump reduction.
Examining the Factor Structure and Measurement Invariance of the Difficulties in Emotion Regulation Scale Across Taiwanese and American University Students
Authors: Yeh Yun-Jy , Chen Jyun-Hong , Tsai William , Kimel Sasha
Published: August 2022

The Difficulties in Emotion Regulation Scale (DERS) is a widely used measure of emotion dysregulation. However, limited research has examined its factor structure and measurement invariance in cross-national samples. The present study tested competing measurement models and the measurement invariance of the DERS in university student samples from the United States ( n = 324) and Taiwan ( n = 399). Results indicated that the bifactor model with the Awareness subscale items removed demonstrated the best fit. The results of model-based indices provided evidence for the general emotion dysregulation factor of the DERS. Cross-national measurement invariance testing found partial strong invariance. These findings indicate that DERS would best be used as a measure of general emotion dysregulation among college students in the United States and Taiwan. These findings emphasize that future work is needed to examine cross-national differences in the construct and assessment of emotion dysregulation.
Reducing waiting times from 65 to under 40 days for children and adolescents receiving mental health services using a new scheduling policy
Authors: Gullhav Anders N , Skomsvoll Johan F , Heimstad Runa , Schultz Joseph S
Published: August 2022

The aim of this study is to conduct an intervention that tests whether a new scheduling policy designed to reduce waiting times actually will lead to a reduction in waiting times. The new scheduling policy was developed using mixed methods. Qualitative data was gathered to fully understand current planning processes, while quantitative methods were used to model and predict future waiting times. If current planning practices are continued, waiting times will only increase. Additionally, the findings show that simulation modeling can be used to predict the capacity needed for intakes (first appointment) to reduce and maintain target waiting times over time. In our study, this meant a slight increase in capacity for intakes. This new scheduling policy led to a reduction in waiting times from 65 days in 2016, to under 40 days post-intervention in 2017. Waiting times have been held under 40 days since implementation of the new policy, 2017–2020. Our study shows that setting appropriate (weekly) intake goals, will lead to maintaining acceptable levels of variation in waiting times. This theory was tested and proven to be effective.
Association between feline hyperthyroidism and thoracic radiographic evaluation of cardiomegaly and pulmonary hyperinflation
Authors: Young Victoria , Rao Sangeeta , Shropshire Sarah B , Marolf Angela J
Published: August 2022

Objectives

Hyperthyroidism frequently affects middle-to-older-aged cats that can present with cardiorespiratory signs. The effects of hyperthyroidism on cardiac size and function have been previously documented. Anecdotally, pulmonary hyperinflation identified on thoracic radiographs may also be associated with hyperthyroidism; however, there is no literature to support this claim. The goal of this study was to determine any association between hyperthyroidism, pulmonary hyperinflation and cardiomegaly with the following hypotheses: (1) hyperthyroid cats would not have evidence of radiographic pulmonary hyperinflation compared with control cats; and (2) hyperthyroid cats were more likely to have evidence of radiographic cardiomegaly than control cats.

Methods

In this retrospective case-control study, the thoracic radiographs of 52 hyperthyroid cats and 46 non-hyperthyroid cats were evaluated for subjective and objective measurements of pulmonary hyperinflation and cardiomegaly.

Results

There were no statistically significant differences between hyperthyroid and non-hyperthyroid cats for any variable indicative of pulmonary hyperinflation. The mean ± SD vertebral heart score on lateral views for hyperthyroid cats was 7.75 ± 0.53 and for control cats was 7.55 ± 0.54, which was significantly different ( P = 0.05). Among all cats, a more severe total elevation in thyroxine (T4) was correlated with a larger vertebral heart score on lateral views (Spearman’s correlation coefficient = 0.23, P = 0.02).

Conclusions and relevance

While the results of this study suggest that hyperthyroid cats are more likely to have a larger vertebral heart score on lateral views than control cats, the clinical relevance of this finding is unclear given the large degree of overlap between hyperthyroid and non-hyperthyroid cats. In addition, among all cats, a greater total T4 elevation was weakly correlated with a larger vertebral heart score. Hyperthyroidism is not associated with radiographic pulmonary hyperinflation and is an unlikely differential for this radiographic finding.
Using a Socio-Ecological Framework to Understand Romantic Relationship Satisfaction Among Emerging Adults During the COVID-19 Pandemic
Authors: Figueroa Jennifer M. , DeLuca Bishop Haylee K. , Baker Elizabeth A.
Published: August 2022

The formation and maintenance of satisfying romantic relationships, a developmental milestone for many emerging adults, has been challenged by the negative impact of the COVID-19 pandemic. Yet, the impact of COVID-19 stress on relationship satisfaction has not been explored within the context of individual and relationship factors. Guided by a socio-ecological framework, this study used a longitudinal design to investigate the impact of individual-level (i.e., growth beliefs, destiny beliefs), couple-level (i.e., daily criticism), and societal-level (i.e., COVID-19 stress) factors on relationship satisfaction during Fall 2021. We also explored the moderating effects of destiny beliefs and growth beliefs. Results revealed relationship satisfaction was negatively associated with daily criticism, but not directly associated with destiny beliefs, growth beliefs, or COVID-19 stress. However, growth beliefs buffered against the negative impact of criticism on relationship satisfaction. These findings are consistent with the notion that growth beliefs may play a protective role in relationship processes.
Engineering T cells to suppress acute GVHD and leukemia relapse after allogeneic hematopoietic stem cell transplantation
Authors: Mo Feiyan , Watanabe Norihiro , Omdahl Kayleigh I. , Burkhardt Phillip M. , Ding Xiaoyun , Hayase Eiko , Panoskaltsis-Mortari Angela , Jenq Robert R. , Heslop Helen E. , Kean Leslie S. , Brenner Malcolm K. , Tkachev Victor , Mamonkin Maksim
Published: August 2022

Acute graft-versus-host disease (aGVHD) limits the therapeutic benefit of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and requires immunosuppressive prophylaxis that compromises antitumor and antipathogen immunity. OX40 is a costimulatory receptor upregulated on circulating T cells in aGVHD and plays a central role in driving the expansion of alloreactive T cells. Here, we show that OX40 is also upregulated on T cells infiltrating GVHD target organs in a rhesus macaque model, supporting the hypothesis that targeted ablation of OX40+ T cells will mitigate GVHD pathogenesis. We thus created an OX40-specific cytotoxic receptor that, when expressed on human T cells, enables selective elimination of OX40+ T cells. Because OX40 is primarily upregulated on CD4+ T cells upon activation, engineered OX40-specific T cells mediated potent cytotoxicity against activated CD4+ T cells and suppressed alloreactive T-cell expansion in a mixed lymphocyte reaction model. OX40 targeting did not inhibit antiviral activity of memory T cells specific to Epstein-Barr virus, cytomegalovirus, and adenoviral antigens. Systemic administration of OX40-targeting T cells fully protected mice from fatal xenogeneic GVHD mediated by human peripheral blood mononuclear cells. Furthermore, combining OX40 targeting with a leukemia-specific chimeric antigen receptor in a single T cell product provides simultaneous protection against leukemia and aGVHD in a mouse xenograft model of residual disease posttransplant. These results underscore the central role of OX40+ T cells in mediating aGVHD pathogenesis and support the feasibility of a bifunctional engineered T-cell product derived from the stem cell donor to suppress both disease relapse and aGVHD following allo-HSCT.
Phenotypic characteristics and variability in CHARGE syndrome: a PRISMA compliant systematic review and meta-analysis
Authors: Thomas Andrea T. , Waite Jane , Williams Caitlin A. , Kirk Jeremy , Oliver Chris , Richards Caroline
Published: August 2022

Background

CHARGE syndrome (OMIM #214800) is a phenotypically complex genetic condition characterised by multi-system, multi-sensory impairments. Behavioural, psychological, cognitive and sleep difficulties are not well delineated and are likely associated with biopsychosocial factors.

Methods

This meta-analysis investigated the prevalence of clinical features, physical characteristics and conditions, behavioural, psychological, cognitive and sleep characteristics in CHARGE syndrome, and statistically evaluated directional associations between these characteristics. Pooled prevalence estimates were calculated using reliable, prespecified quality weighting criteria, and meta-regression was conducted to identify associations between characteristics.

Results

Of the 42 eligible studies, data could be extracted for 1675 participants. Prevalence estimates were highest for developmental delay (84%), intellectual disability (64%), aggressive behaviour (48%), self-injurious behaviour (44%) and sleep difficulties (45%). Meta-regression indicated significant associations between intellectual disability and choanal atresia, intellectual disability and inner ear anomalies, sleep difficulties and growth deficiency, and sleep difficulties and gross motor difficulties.

Conclusions

Our comprehensive review of clinical features, behavioural, psychological, cognitive and physical characteristics, conditions and comorbidities in CHARGE syndrome provides an empirically based foundation to further research and practice.
Spinal cord infarction secondary to pulmonary embolism-induced cardiac arrest: a case report
Authors: Xu Jianfei , Zhou Xiaoyang , Liu Zhicheng , Xu Zhaojun
Published: August 2022

Background

Pulmonary embolism is a common cause of cardiac arrest. Pulmonary embolism-induced cardiac arrest typically suffers from ischemic injuries to various organs, including the central nervous system. However, spinal cord infarction is a rare complication of pulmonary embolism-induced cardiac arrest. At present, there is no case report on the occurrence of spinal cord infarction secondary to pulmonary embolism-induced cardiac arrest without accompanied cerebral complications.

Case presentation

A 72-year-old woman with dyspnea and chest tightness was admitted to the emergency room. Cardiac arrest occurred within a short period after admission. Subsequent computed tomographic pulmonary angiography revealed multiple pulmonary thromboses, which were highly suspected to be the cause of cardiac arrest. Thrombolytic therapy with alteplase was given after the return of spontaneous circulation. Unfortunately, she was found to be paraplegic in both lower extremities after regaining consciousness. Spinal cord infarction was confirmed by thoracic magnetic resonance imaging.

Conclusions

Despite receiving high-quality cardiopulmonary resuscitation, patients with cardiac arrest are at high risk of ischemic injury to the central nervous system. After the recovery of consciousness, clinicians should pay more attention to preclude the possibility of spinal cord infarction.
Premature ventricular contractions with acute successful radiofrequency catheter ablation near the atrioventricular node using reversed C curve technique
Authors: Hu Zhonghui , Jiang Yunsheng , Wang Su
Published: August 2022

Background

We sought to clarify the electrophysiological (EP) characteristics of premature ventricular contractions (PVCs) with acute successful radiofrequency catheter ablation (RFCA) near the atrioventricular node (AVN).

Methods and results

Eighteen patients with acute successful RFCA near the AVN were included in this study. Systematic mapping was performed with two mapping methods: antegrade mapping technique (group A) and reversed C curve mapping technique (group R). RFCA was preferentially performed underneath the tricuspid valve (TV) with reversed C curve technique in all patients. The a amplitude/v amplitude ratio during sinus rhythm in group A was significantly larger than in group B (0.19 ± 0.10 vs 0.06 ± 0.02, p < 0.01). The earliest bipolar activation preceded the QRS onset in group A was significantly smaller than in group R (19.6 ± 4.9 vs 24.4 ± 6.6 ms (ms), p < 0.01). Pace mapping in group A and group R demonstrated perfect QRS morphology (12/12) match only in 5.6% (one patient) and 16.7% (3 patients) of patients, respectively. The mean duration of successful RFCA was 8.2 ± 2.4 s in 13 patients (72.2%). Early (within 3 days) and late (one-year) recurrence rates were 5.6% (one patient) and 16.7% (3 patients), respectively. No atrioventricular block occurred during RFCA or the one-year follow up.

Conclusions

PVCs near the AVN are a subgroup of idiopathic PVCs with distinctive EP features. RFCA using reversed C curve technique is effective and safe for the acute elimination of these challenging AVN-PVCs.
Procalcitonin in early allograft dysfunction after orthotopic liver transplantation: a retrospective single centre study
Authors: Frick Katja , Beller Elisabeth A. , Kalisvaart Marit , Dutkowski Philipp , Schüpbach Reto A. , Klinzing Stephanie
Published: August 2022

Background

Ischemia–reperfusion injury (IRI) is the pathophysiological hallmark of hepatic dysfunction after orthotopic liver transplantation (OLT). Related to IRI, early allograft dysfunction (EAD) after OLT affects short- and long-term outcome. During inflammatory states, the liver seems to be the main source of procalcitonin (PCT), which has been shown to increase independently of bacterial infection. This study investigates the association of PCT, IRI and EAD as well as the predictive value of PCT during the first postoperative week in terms of short- and long-term outcome after OLT.

Methods

Patients ≥ 18 years undergoing OLT between January 2016 and April 2020 at the University Hospital of Zurich were eligible for this retrospective study. Patients with incomplete PCT data on postoperative days (POD) 1 + 2 or combined liver-kidney transplantation were excluded. The PCT course during the first postoperative week, its association with EAD, defined by the criteria of Olthoff, and IRI, defined as aminotransferase level > 2000 IU/L within 2 PODs, were analysed. Finally, 90-day as well as 12-month graft and patient survival were assessed.

Results

Of 234 patients undergoing OLT, 110 patients were included. Overall, EAD and IRI patients had significantly higher median PCT values on POD 2 [31.3 (9.7–53.8) mcg/l vs. 11.1 (5.3–25.0) mcg/l; p < 0.001 and 27.7 (9.7–51.9) mcg/l vs. 11.5 (5.5–25.2) mcg/l; p < 0.001] and impaired 90-day graft survival (79.2% vs. 95.2%; p = 0.01 and 80.4% vs. 93.8%; p = 0.033). IRI patients with PCT < 15 mcg/l on POD 2 had reduced 90-day graft and patient survival (57.9% vs. 93.8%; p = 0.001 and 68.4% vs. 93.8%; p = 0.008) as well as impaired 12-month graft and patient survival (57.9% vs. 96.3%; p = 0.001 and 68.4% vs. 96.3%; p = 0.008), while the outcome of IRI patients with PCT > 15 mcg/l on POD 2 was comparable to that of patients without IRI/EAD.

Conclusion

Generally, PCT is increased in the early postoperative phase after OLT. Patients with EAD and IRI have a significantly increased PCT maximum on POD 2, and impaired 90-day graft survival. PCT measurement may have potential as an additional outcome predictor in the early phase after OLT, as in our subanalysis of IRI patients, PCT values < 15 mcg/l were associated with impaired outcome.
Clinical characteristics of lacrimal drainage pathway disease-associated keratopathy
Authors: Inoue Hidenori , Toriyama Koji , Ikegawa Wakako , Hiramatsu Yukako , Mitani Arisa , Takezawa Yuki , Sakane Yuri , Kamao Tomoyuki , Hara Yuko , Shiraishi Atsushi
Published: August 2022

Purpose

To report the clinical characteristics of 13 cases of noninfectious corneal ulceration related to lacrimal drainage pathway disease.

Methods

Medical records of 13 patients with lacrimal drainage pathway disease-associated keratopathy who were examined at Ehime University Hospital between April 2007 and December 2021 were analyzed.

Results

The predisposing lacrimal drainage pathway diseases for corneal ulceration were chronic dacryocystitis in seven patients and lacrimal canaliculitis in six patients. The corneal ulcers were located at the peripheral cornea in 10 patients and the paracentral cornea in three patients. All patients indicated few cellular infiltrations of the ulcerated area at the slit-lamp examination. Corneal perforation was found in seven patients. The primary identified organisms were Streptococcus spp. in chronic dacryocystitis and Actinomycetes spp. in lacrimal canaliculitis. All patients showed rapid healing of the epithelial defects after treatment of the lacrimal drainage pathway disease. The mean time elapsed between treatment of the lacrimal drainage pathway disease and re-epithelialization of corneal ulcer was 14.5 ± 4.8 days.

Conclusion

Lacrimal drainage pathway disease-associated keratopathy may be characterized by peripheral corneal ulcer with few cellular infiltrations, occasionally leading to corneal perforation. Treatment of the lacrimal drainage pathway disease could be the most effective treatment for lacrimal drainage pathway disease-associated keratopathy.
Time-series analysis of trends in the incidence rates of successful and attempted suicides in Thailand in 2013–2019 and their predictors
Authors: Arunpongpaisal Suwanna , Assanagkornchai Sawitri , Chongsuvivatwong Virasakdi , Jampathong Nattakorn
Published: August 2022

Background

Suicide rates are of increasing concern worldwide. There are approximately 4000–5000 deaths by suicide each year in Thailand. This study examined trends in annual incidence rates and predictors of successful and attempted suicides in Thailand (2013–2019).

Methods

Secondary data analysis was conducted on data from two national-level databases: The National Health Security Office and the National Death Certification Registry System. Time-related trends and predictors of successful and attempted suicides were calculated using joinpoint regression and multivariable logistic regression analyses, respectively.

Results

Of all successful suicide cases from 2013 to 2019, about 80% involved men, with an average age of 45.37 (± 16.43) years. Predictors of successful suicide included male sex, older age, using highly lethal methods, and no prior psychiatric treatment. Among individuals admitted to hospitals following a suicide attempt from 2013– to 2019, the average age at first admission was 38.83 ± 22.47 years, with women more heavily represented than men. Only 2.3% of these patients received psychiatric treatment in the hospital. Predictors of attempted suicide included female sex; adolescent or adult; and mental, alcohol, or substance-related disorder(s). Age-standardized annual rates per 100,000 people showed that, through 2019, suicide incidence increased slightly, and attempts decreased.

Conclusions

There was a significantly increasing trend in successful suicide during the 7 years; the increase was more notable among men. The study highlights sex-related gaps in public health owing to an identified higher incidence of suicide among men, and a higher incidence of suicide attempts in women adolescents, emphasizing the need to consider sex-sensitive issues in individual as well as societal contexts.
Clinical evaluation of an automated TSI bridge immunoassay in the diagnosis of Graves’ disease and its relationship to the degree of hyperthyroidism
Authors: Liu Tianqi , Zhang Xiuying , Long Li , Zhou Lingli , Chen Jing , Li Meng , Gao Ying , Zhou Xianghai , Han Xueyao , Ji Linong
Published: August 2022

Background

The rapid and accurate detection of thyroid-stimulating hormone (TSH) receptor antibodies has always been an urgent need for the clinical diagnosis and management of Graves’ disease (GD). We aimed to evaluate the use of an automated thyroid-stimulating immunoglobulin (TSI) bridge immunoassay in the diagnosis of GD and to analyze the relationship between TSI and the degree of hyperthyroidism.

Methods

A total of 227 new-onset GD patients, 29 Hashimoto thyroiditis, 43 non-autoimmune thyroid diseases and 37 euthyroid controls were consecutively recruited. All participants accepted the measurement of their serum thyroid function and thyroid-associated antibodies, including TSI being measured by an Immulite 2000 bridge immunoassay and TSH receptor autoantibodies (TRAb) being measured by a third-generation Roche electrochemiluminescence immunoassay. The quantitative consistency between the TSI and TRAb detection methods was analyzed by using Passing-Bablok regression and Bland–Altman plots. The diagnostic performance for GD was assessed by receiver operating characteristic (ROC) curve analysis.

Results

Among 227 GD patients (174 females and 53 males, with a mean age of 39 years), the quantitative TSI was positively correlated with TRAb (r = 0.8099). According to the cut-off values proposed by the manufacturers (TSI: 0.55 IU/L, TRAb: 1.75 IU/L), the positive rates of TSI and TRAb in new-onset GD patients were 96.92% and 95.15%, respectively. Both TSI and TRAb levels positively correlated with FT4 levels (TSI: r = 0.243, TRAb: r = 0.317; all P < 0.001) and FT3 levels (TSI: r = 0.288, TRAb: r = 0.360; all P < 0.001) in new-onset GD patients. The ROC analysis showed that the optimal TSI cut-off value was 0.577 IU/L for GD diagnosis in this Chinese population, with a sensitivity of 96.92% and a specificity of 97.25%, respectively. The optimal TRAb cut-off value of was 1.38 IU/L, with a sensitivity of 96.92% and a specificity of 99.08%. There were no significant differences between the cut-off values obtained through the ROC analysis and those provided by the manufacturer for both TSI and TRAb when calculating their sensitivity and specificity in diagnosing GD. Among the 8 newly diagnosed GD cases with discordant qualitative antibody results, TSI was more likely than TRAb to match the clinical diagnosis of GD (6 TSI-positive vs. 2 TRAb-positive patients).

Conclusion

The automated TSI bridge immunoassay was positively correlated with thyroxine levels in new-onset GD patients and was more likely to be consistent with the clinical diagnosis of GD than with that of TRAb. The positive Immulite 2000 TSI cut-off value of 0.577 IU/L for GD diagnosis in the Chinese population were close to the value recommended by the manufacturer.
Association of glycated hemoglobin with non-alcoholic fatty liver disease patients and the severity of liver steatosis and fibrosis measured by transient elastography in adults without diabetes
Authors: Xie Yilian , Kong Weiliang , Wang Xuepeng , Wu Zhouxiao
Published: August 2022

Background

Type 2 diabetes mellitus (T2DM) is a well-known independent risk factor for non-alcoholic fatty liver disease (NAFLD). However, research exploring the association between blood glucose management and the risk of NAFLD status in subjects without diabetes was insufficient. This study aimed to explore the association of glycated hemoglobin (HbA1c) with NAFLD status and the severity of liver steatosis and fibrosis in non-diabetic people.

Methods

A cross-sectional analysis was conducted on 2998 non-diabetic American adults using data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 cycle. We used multivariable logistic regression models to evaluate the association between HbA1c and NAFLD status and the severity of liver steatosis and fibrosis. Interaction and stratified analyses were additionally performed.

Results

The multivariate regression analyses showed that HbA1c was associated independently with NAFLD status in all the models (model1: OR = 2.834, 95%CI: 2.321, 3.461; model 2: OR = 2.900, 95%CI: 2.312, 3.637 and model 3: OR = 1.664, 95%CI: 1.284, 2.156). We further performed the interaction and stratified analyses and discovered a significant interaction between HbA1c and BMI (Pinteraction < 0.05). Finally, a robust link was shown between HbA1c level and the severity of liver steatosis, which was mainly significant in the prediabetes group, while the correlation was not significant in HbA1c level and severity of liver fibrosis after controlling for all the potential confounders.

Conclusions

We concluded that HbA1c level was positively correlated to the risk of developing NAFLD in a large non-diabetic American population. Moreover, HbA1c level was associated with the severity of liver steatosis in subjects with prediabetes, suggesting that routine screening for HbA1c among individuals with prediabetes is necessary.
Genetic evidence for a causal relationship between type 2 diabetes and peripheral artery disease in both Europeans and East Asians
Authors: Xiu Xuehao , Zhang Haoyang , Xue Angli , Cooper David N. , Yan Li , Yang Yuedong , Yang Yuanhao , Zhao Huiying
Published: August 2022

Background

Observational studies have revealed that type 2 diabetes (T2D) is associated with an increased risk of peripheral artery disease (PAD). However, whether the two diseases share a genetic basis and whether the relationship is causal remain unclear. It is also unclear as to whether these relationships differ between ethnic groups.

Methods

By leveraging large-scale genome-wide association study (GWAS) summary statistics of T2D (European-based:Ncase= 21,926,Ncontrol= 342,747; East Asian-based:Ncase= 36,614,Ncontrol= 155,150) and PAD (European-based:Ncase= 5673,Ncontrol= 359,551; East Asian-based:Ncase= 3593,Ncontrol= 208,860), we explored the genetic correlation and putative causal relationship between T2D and PAD in both Europeans and East Asians using linkage disequilibrium score regression and seven Mendelian randomization (MR) models. We also performed multi-trait analysis of GWAS and two gene-based analyses to reveal candidate variants and risk genes involved in the shared genetic basis between T2D and PAD.

Results

We observed a strong genetic correlation (rg) between T2D and PAD in both Europeans (rg= 0.51;p-value = 9.34 × 10−15) and East Asians (rg= 0.46;p-value = 1.67 × 10−12). The MR analyses provided consistent evidence for a causal effect of T2D on PAD in both ethnicities (odds ratio [OR] = 1.05 to 1.28 for Europeans and 1.15 to 1.27 for East Asians) but not PAD on T2D. This putative causal effect was not influenced by total cholesterol, body mass index, systolic blood pressure, or smoking initiation according to multivariable MR analysis, and the genetic overlap between T2D and PAD was further explored employing an independent European sample through polygenic risk score regression. Multi-trait analysis of GWAS revealed two novel European-specific single nucleotide polymorphisms (rs927742 and rs1734409) associated with the shared genetic basis of T2D and PAD. Gene-based analyses consistently identified one geneANKFY1and gene-gene interactions (e.g.,STARD10[European-specific] toAP3S2[East Asian-specific];KCNJ11[European-specific] toKCNQ1[East Asian-specific]) associated with the trans-ethnic genetic overlap between T2D and PAD, reflecting a common genetic basis for the co-occurrence of T2D and PAD in both Europeans and East Asians.

Conclusions

Our study provides the first evidence for a genetically causal effect of T2D on PAD in both Europeans and East Asians. Several candidate variants and risk genes were identified as being associated with this genetic overlap. Our findings emphasize the importance of monitoring PAD status in T2D patients and suggest new genetic biomarkers for screening PAD risk among patients with T2D.
Evaluation of plasma nucleosome concentrations in dogs with a variety of common cancers and in healthy dogs
Authors: Wilson-Robles H. M. , Bygott T. , Kelly T. K. , Miller T. M. , Miller P. , Matsushita M. , Terrell J. , Bougoussa M. , Butera T.
Published: August 2022

Background

Cell free DNA, in the form of nucleosomes, is released into circulation during apoptosis and necrosis in a variety of diseases. They are small fragments of chromosomes that are composed of DNA wrapped around a histone core made of four duplicate histone proteins forming an octamer. The nucleosome compartment is a relatively uninvestigated area of circulating tumor biomarkers in dogs. The objectives of this study were to quantify and better characterize nucleosome concentrations in 528 dogs with various common malignancies and compare them to 134 healthy dogs.

Results

The sensitivity of increased circulating nucleosome concentrations for the detection of cancer in all dogs was 49.8% with a specificity of 97% with an area under the curve of 68.74%. The top 4 malignancies detected by the test included lymphoma, hemangiosarcoma, histiocytic sarcoma and malignant melanoma. The malignancies least likely to be detected were soft tissue sarcomas, osteosarcoma and mast cell tumors.

Conclusions

A variety of tumor types may cause increased nucleosome concentrations in dogs. Tumors of hematopoietic origin are most likely to cause elevations and local tumors such as soft tissue sarcomas are least likely to cause elevations in plasma nucleosome concentrations.
The effects of epithelial–mesenchymal transitions in COPD induced by cigarette smoke: an update
Authors: Su Xiaoshan , Wu Weijing , Zhu Zhixing , Lin Xiaoping , Zeng Yiming
Published: August 2022

Cigarette smoke is a complex aerosol containing a large number of compounds with a variety of toxicity and carcinogenicity. Long-term exposure to cigarette smoke significantly increases the risk of a variety of diseases, including chronic obstructive pulmonary disease (COPD) and lung cancer. Epithelial–mesenchymal transition (EMT) is a unique biological process, that refers to epithelial cells losing their polarity and transforming into mobile mesenchymal cells, playing a crucial role in organ development, fibrosis, and cancer progression. Numerous recent studies have shown that EMT is an important pathophysiological process involved in airway fibrosis, airway remodeling, and malignant transformation of COPD. In this review, we summarized the effects of cigarette smoke on the development and progression of COPD and focus on the specific changes and underlying mechanisms of EMT in COPD induced by cigarette smoke. We spotlighted the signaling pathways involved in EMT induced by cigarette smoke and summarize the current research and treatment approaches for EMT in COPD, aiming to provide ideas for potential new treatment and research directions.
An ischemia-homing bioengineered nano-scavenger for specifically alleviating multiple pathogeneses in ischemic stroke
Authors: Duan Ranran , Sun Ke , Fang Fang , Wang Ning , He Ruya , Gao Yang , Jing Lijun , Li Yanfei , Gong Zhe , Yao Yaobing , Luan Tingting , Zhang Chaopeng , Zhang Jinwei , Zhao Yi , Xie Haojie , Zhou Yongyan , Teng Junfang , Zhang Jinfeng , Jia Yanjie
Published: August 2022

Background

Ischemic stroke is one of the most serious global public health problems. However, the performance of current therapeutic regimens is limited due to their poor target specificity, narrow therapeutic time window, and compromised therapeutic effect. To overcome these barriers, we designed an ischemia-homing bioengineered nano-scavenger by camouflaging a catalase (CAT)-loaded self-assembled tannic acid (TA) nanoparticle with a M2-type microglia membrane (TPC@M2 NPs) for ischemic stroke treatment.

Results

The TPC@M2 NPs can on-demand release TA molecules to chelate excessive Fe2+, while acid-responsively liberating CAT to synergistically scavenge multiple ROS (·OH, ·O2−, and H2O2). Besides, the M2 microglia membrane not only can be served as bioinspired therapeutic agents to repolarize M1 microglia into M2 phenotype but also endows the nano-scavenger with ischemia-homing and BBB-crossing capabilities.

Conclusions

The nano-scavenger for specific clearance of multiple pathogenic elements to alleviate inflammation and protect neurons holds great promise for combating ischemic stroke and other inflammation-related diseases.
Synthesis of doxorubicin-loaded peptosomes hybridized with gold nanorod for targeted drug delivery and CT imaging of metastatic breast cancer
Authors: Hasannia Maliheh , Abnous Khalil , Taghdisi Seyed Mohammad , Nekooei Sirous , Ramezani Mohammad , Alibolandi Mona
Published: August 2022

Background

Cancer nanomedicines based on synthetic polypeptides have attracted much attention due to their superior biocompatibility and biodegradability, stimuli responsive capability through secondary conformation change, adjustable functionalities for various cargos such as peptides, proteins, nucleic acids and small therapeutic molecules. Recently, a few nanoformulations based on polypeptides comprising NK105, NC6004, NK911, CT2103, have entered phase I-III clinical trials for advanced solid tumors therapy. In the current study, we prepared polypeptide-based vesicles called peptosome via self-assembly of amphiphilic polypeptide-based PEG-PBLG diblock copolymer.

Results

In this regard, poly(γ-benzyl L-glutamate (PBLG) was synthesized via ring opening polymerization (ROP) of γ-benzyl L-glutamate-N-carboxyanhydride (BLG-NCA) using N-hexylamine as initiator. Then amine-terminated PBLG was covalently conjugated to heterofuctional maleimide PEG-carboxylic acid or methyl-PEG-carboxylic acid. The PEG-PBLG peptosomes were prepared through double emulsion method for the co-delivery of doxorubicin.HCl and gold nanorods as hydrophilic and hydrophobic agents in interior compartment and membrane of peptosomes, respectively (Pep@MUA.GNR-DOX) that DOX encapsulation efficiency and loading capacity were determined 42 ± 3.6 and 1.68 ± 3.6. Then, theranostic peptosomes were decorated with thiol-functionalized EpCAM aptamer throught thiol-maleimide reaction producing Apt-Pep@MUA.GNR-DOX for targeted delivery. The non-targeted and targeted peptosomes showed 165.5 ± 1.1 and 185 ± 4.7 nm diameters, respectively while providing sustained, controlled release of DOX. Furthermore, non-targeted and targeted peptosomes showed considerable serum stability. In vitro study on MCF-7 and 4T1 cells showed significantly higher cytotoxicity for Apt-Pep@MUA.GNR-DOX in comparison with Pep@MUA.GNR-DOX while both system did not show any difference in cytotoxicity against CHO cell line. Furthermore, Apt-Pep@MUA.GNR-DOX illustrated higher cellular uptake toward EpCAM-overexpressing 4T1 cells compared to Pep@MUA.GNR-DOX. In preclinical stage, therapeutic and diagnostic capability of the prepared Pep@MUA.GNR-DOX and Apt-Pep@MUA.GNR-DOX were investigated implementing subcutaneous 4T1 tumor model in BALB/c mice. The obtained data indicated highest therapeutic index for Apt-Pep@MUA.GNR-DOX compared to Pep@MUA.GNR-DOX and free DOX. Moreover, the prepared system showed capability of CT imaging of tumor tissue in 4T1 tumorized mice through tumor accumulation even 24 h post-administration.

Conclusion

In this regard, the synthesized theranostic peptosomes offer innovative hybrid multipurpose platform for fighting against breast cancer.

Graphical Abstract
Colchicine versus cimetidine: the better choice for Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome prophylaxis, and the role of MEFV gene mutations
Authors: Raeeskarami Seyed Reza , Sadeghi Payman , Vahedi Mahdieh , Asna Ashari Kosar , Mousavi T. Mahdieh , Ziaee Vahid
Published: August 2022

Background

During childhood, the most common periodic fever is periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. The effective treatment and prevention of febrile attacks improve these patients' and their families’ quality of life. However, there is no single strategy or evidence-based guideline to manage this syndrome, and most of them are based on consensus treatment plans.

Methods

This randomized controlled trial was carried out on 67 PFAPA patients referred to three tertiary centers of pediatric rheumatology. The patients were divided into two groups, including group 1 (n = 36) receiving prednisolone plus colchicine and group 2 (n = 31) receiving prednisolone plus cimetidine. Demographic characteristics and the number of febrile episodes were compared between the two groups before and after the intervention.

Results

In both groups, the number of febrile episodes after the treatment decreased (P ≤ 0.001). Statistical Analysis showed no significant difference between the two groups (P = 0.88). Moreover, 44 patients from both groups were checked for the MEFV gene. There were no statistical differences between MEFV positive and negative subgroups in response to colchicine (P = 1).

Conclusion

This study showed that both drug regimens are significantly effective in preventing febrile attacks in PFAPA syndrome, and the presence of a MEFV gene mutation might not be the only significant risk factor for a response to colchicine.

Trial registration

IRCT, IRCT20191222045847N1. Registered 23 October 2019,https://fa.irct.ir/search/result?query=IRCT20191222045847N1
Clinical outcome of bioceramic sealer iRoot SP extrusion in root canal treatment: a retrospective analysis
Authors: Li Jing , Chen Liuchi , Zeng Chunmei , Liu Yiwen , Gong Qimei , Jiang Hongwei
Published: August 2022

Background

During the obturation procedure, sealer extrusion occurs in some cases. iRoot SP is a kind of bioceramic sealer with superior physicochemical and biological properties. This article reports the outcome of iRoot SP extrusion in root canal treatment and the potential factors associated with the outcome.

Methods

Ninety-nine patients and one hundred and eighty-five teeth treated between 2014 and 2020 were included in this retrospective study. All of the cases were filled with a single-cone technique and the iRoot SP sealer. The minimum follow-up visit period was 1 year. The outcome was evaluated by clinical examination and radiographic examination at recall and was classified as healed, healing (success), or not healed (failure).

Results

The overall success rate of all teeth was 96.8%. The success rate of adequately filled teeth was 97.3%, while that of iRoot SP extrusion was 95.8%; the difference was not statistically significant. Factors such as gender, age, tooth position, follow-up visit period, size of periapical lesion, treatment type and extruding sealer amount had no influence on the outcome of iRoot SP extruded teeth.

Conclusions

The results suggested that iRoot SP extrusion has no adverse effect on the outcome of root canal treatment, which may contribute to the endodontic treatment.
Evaluation of the efficacy and safety of Escherichia coli-derived recombinant human bone morphogenetic protein-2 in transforaminal lumbar interbody fusion to treat degenerative spinal disease: a protocol of prospective, randomized controlled, assessor-blinded, open-label, multicenter trial
Authors: Choi Jun-Young , Park Hyun-Jin , Park Sang-Min , Kang Chang-Nam , Song Kwang-Sup
Published: August 2022

Background

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been widely used as an alternative bone graft in spine fusion surgery. However, clinical outcome such as effects and complications has not yet been revealed for transforaminal lumbar interbody fusion (TLIF). Although previous studies have reported some results, the evidence is weak. Therefore, the purpose of this trial is to evaluate the effectiveness and safety of Escherichia coli-derived rhBMP-2 combined with hydroxyapatite (HA) in TLIF.

Methods

This trial is designed as a prospective, assessor-blinded, open-label, multicenter, randomized controlled study. Participants will be recruited from six tertiary teaching hospitals. All randomized participants will be undergoing one- or two-level TLIF with rhBMP-2 (77 participants) as the active experimental group or with an auto-iliac bone graft (77 participants) as the control group. The primary interbody fusion rate outcome will be evaluated using computed tomography (CT) 12 months after surgery. The secondary outcomes will be as follows: clinical outcomes (visual analog scale score, EuroQol-5-dimensions-5-level score, Oswestry Disability Index score, and some surgery-related variables) and adverse effects (radiculitis, heterotrophic ossification, endplate resorption, and osteolysis). Radiological outcomes will be evaluated using simple radiography or CT. All outcomes will be measured, collected, and evaluated before surgery and at 12, 24, and 52 weeks postoperatively.

Discussion

This study will be the primary of its kind to evaluate the effectiveness and safety of E. coli-derived rhBMP-2 with HA in one- or two-level TLIF. It is designed to evaluate the equivalence of the results between rhBMP-2 with HA and auto-iliac bone graft using an appropriate sample size, assessor-blinded analyses, and prospective registration to avoid bias. This study will set up clear conclusions for using E. coli-derived rhBMP-2 with HA in TLIF.

Trial registration: This study protocol was registered at Korea Clinical Research Information Service (https://cris.nih.go.kr; number identifier: KCT0005610) on 19 November 2020. And protocol version is v1.1, January 2022.
The outcomes of ultrafiltration in on-pump versus off-pump coronary artery bypass grafting in patients with renal impairment
Authors: Phothikun Amarit , Nawarawong Weerachai , Tantraworasin Apichat , Tepsuwan Thitipong
Published: August 2022

Objective

In chronic kidney disease (CKD), using cardiopulmonary bypass (CPB) may contribute to renal dysfunction. Off-pump coronary artery bypass grafting (OPCAB) is one technique that preserved renal function, but the procedure may not be possible in certain situations. The ultrafiltration (UF) can remove excess fluid and inflammatory mediators that result from exposure to the CPB. Coronary artery bypass grafting (CABG) with UF could be an alternative way to preserve renal function.

Method

A retrospective study of CKD patients who underwent CABG. The renal outcomes were compared between the patients who underwent CABG with UF and OPCAB. A repeated measure adjusted by propensity score was used for comparing the renal outcome. Univariable and multivariable logistic regression was used to identify the risk factors for acute renal failure (AKI) and adverse outcomes.

Results

From January 2009 and June 2020, there were 220 CKD patients, 109 (49.55%) patients underwent CABG with UF, and 111 (50.45%) patients underwent OPCAB. There were statistically significant differences in the change of the average level of creatinine between CABG with UF (increased + 0.09 mg/dl) and OPCAB (decreased − 0.05 mg/dl) (p = 0.043). Also, patients who underwent CABG with UF had a significantly increased risk for AKI (OR 5.38, 95%CI 1.09, 26.5).

Conclusion

The UF adjunct technique in CABG with CPB tends to provide a lower protective effect for renal function and had a significantly higher incidence of post-cardiac surgery AKI when compared to OPCAB. If technically feasible, OPCAB would be a preferable choice for CKD patients.

Study registration number: SUR-2562-06607/Research ID: 6607.
Classification of avulsion fractures of the fifth metatarsal base using three‐dimensional CT mapping and anatomical assessment: a retrospective case series study
Authors: He Wenbao , Zhou Haichao , Zhang Yingqi , Yu Tao , Xia Jiang , Zhao Youguang , Yang Yunfeng , Li Bing
Published: August 2022

Background

To clarify the injury mechanism of the avulsion fracture of the fifth metatarsal combining 3‐dimensional (3D) fracture mapping with anatomical measurements.

Methods

Two hundred twenty‐two patients with the avulsion fractures of the fifth metatarsal base, who were admitted to our hospital from August 2015 to August 2020. The computed tomography (CT) scans were used to generate the 3‐D images of all mapped fracture lines for the avulsion fractures of the fifth metatarsal base were compiled in an overall 3D image. The fifth metatarsal base of 8 unpaired lower limbs of adult Asian frozen cadaveric specimens were also dissected to observe and measure the specific locations of the attachment points of the peroneus brevis, lateral band of the plantar fascia, and peroneus tertius to the fifth metatarsal base.

Results

Based on the type of fracture line produced and the specific locations of the attachment points of the tendons or fascia, the avulsion fractures of the fifth metatarsal base can be classified into three types: type I predominantly involves the action of the lateral band of the plantar fascia; type II predominantly involves the action of the peroneus brevis; type IIIA involves the joint action of the peroneus brevis and lateral band of the plantar fascia with one fracture line, and type IIIB involves the joint action of the peroneus brevis and lateral band of the plantar fascia with two fracture lines.

Conclusion

The lateral band of the plantar fascia and peroneus brevis play a major role, either separately or together, in avulsion fractures of the fifth metatarsal base. With this knowledge, we propose a novel classification based on the injury mechanism, which can serve as a reference for clinical treatment and diagnosis.

Level of evidence

Level III, retrospective case series.