bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of graphene oxide–iron oxide hybrid nanocomposite on the high-velocity impact performance of Kevlar fabrics impregnated with nanosilica/polyethylene glycol shear thickening fluid
Authors: Naghizadeh Amirhosein , Khoramishad Hadi , Jalaly Maisam
Published: February 2023

In this paper, the influence of graphene oxide (GO) and GO–Fe3O4 hybrid nanocomposite (GFHN) as additives for nanosilica/polyethylene glycol shear thickening fluid (STF) was investigated on the fiber pull-out response and high-velocity impact performance of Kevlar fabrics. To fabricate GFHN nanofillers, the Fe3O4 nanoparticles were linked onto the graphene oxide surfaces using the electrostatic self-assembly method. The GO sheets and GFHN nanofillers were separately incorporated into STF containing fumed silica nanoparticles and the Kevlar fabrics were impregnated with the obtained STF-GO and STF-GFHN nano-mixtures. The pull-out test results of the impregnated Kevlar fabric indicated that the STF-GO nano-mixture decreased while the STF-GFHN nano-mixture increased the friction between the yarns of the impregnated fabric. This was in correlation with the high-velocity impact test results in which the STF-GO nano-mixture deteriorated while the STF-GFHN nano-mixture considerably improved the high-velocity impact resistance of the impregnated Kevlar fabric. The Kevlar fabric impregnated with STF-GFHN nano-mixture containing 0.4 wt% GFHN nanofillers experienced the maximum pull-out force and impact energy absorption with 163% and 73% improvements, respectively, compared to the neat fabric.
Kienböck’s disease: preventing disease progression in early-stage disease
Authors: Salva-Coll Guillem , Esplugas Mireia , Carreño Ana , Lluch-Bergada Alex
Published: February 2023

Currently Kienböck’s disease remains an ‘unsolved’ problem in hand surgery. Different factors have been associated with the avascular necrosis of the lunate. Mechanical, vascular and biological factors, alone or in combination, may have an influence in the aetiopathogenesis and determine the progress of the disease and even the results of the treatment. This is especially relevant in the early stages, in which conservative or surgical treatment may modify the natural history of the disease, maintaining the lunate structure and thus preserving the joint surfaces. There are multiple surgical treatments for Kienböck’s disease in the early stages, before lunate collapse; each one is based on one of the possible factors that can cause avascular necrosis of the lunate. The objective is not only to treat symptoms but to prevent progression. This article is a review of the most frequent treatments used in the early stages and a personal view of the authors.

Level of evidence: V
CXCL8/CXCR2 signaling mediates bone marrow fibrosis and represents a therapeutic target in myelofibrosis
Authors: Dunbar Andrew , Kim Dongjoo , Lu Min , Farina Mirko , Bowman Robert L. , Yang Julie L. , Park Young C. , Karzai Abdul , Xiao Wenbin , Zaroogian Zach , O'Connor Kavi , Mowla Shoron , Gobbo Francesca , Verachi Paola , Martelli Fabrizio , Sarli Giuseppe , Xia Lijuan , Elmansy Nada , Kleppe Maria , Chen Zhuo , Xiao Yang , McGovern Erin M , Snyder Jenna , Krishnan Aishwarya , Hill Corinne E. , Cordner Keith Bryan , Zouak Anouar , Salama Mohamed E. , Yohai Jayden , Tucker Eric , Chen Jonathan J , Zhou Jing , McConnell Timothy S , Migliaccio Anna Rita , Koche Richard Patrick , Rampal Raajit K. , Fan Rong , Levine Ross L , Hoffman Ronald
Published: February 2023

Pro-inflammatory signaling is a hallmark feature of human cancer, including in myeloproliferative neoplasms (MPNs), most notably myelofibrosis (MF). Dysregulated inflammatory signaling contributes to fibrotic progression in MF; however, the individual cytokine mediators elicited by malignant MPN cells to promote collagen-producing fibrosis and disease evolution remain yet to be fully elucidated. Previously we identified a critical role for combined constitutive JAK/STAT and aberrant NF-kB pro-inflammatory signaling in myelofibrosis development. Using single-cell transcriptional and cytokine-secretion studies of primary MF patient cells and the hMPLW515L murine model of myelofibrosis, we extend this previous work and delineate the role of CXCL8/CXCR2 signaling in MF pathogenesis and bone marrow fibrosis progression. MF patient hematopoietic stem/progenitor cells are enriched for a CXCL8/CXCR2 gene signature and display enhanced proliferation and fitness in response to exogenous CXCL8 ligand in vitro. Genetic deletion of Cxcr2 in the hMPLW515L adoptive transfer model abrogates fibrosis and extends overall survival, and pharmacologic inhibition of the CXCR1/2 pathway improves hematologic parameters, attenuates bone marrow fibrosis, and synergizes with JAK inhibitor therapy. Our mechanistic insights provide a rationale for therapeutic targeting of the CXCL8/CXCR2 pathway in MF patients.
The Use of Prognostic Models in Allogeneic Transplants: A Perspective Guide for Clinicians and Investigators
Authors: Sorror Mohamed Lotfy
Published: February 2023

Allogeneic hematopoietic cell transplantation (HCT) can cure many hematologic diseases, but it carries the potential risks of increased morbidity and mortality rates. Prognostic evaluation is a scientific entity at the core of care for potential recipients of HCT. It improves the decision-making process of transplant versus not and of which transplant strategy and allows for future trials targeting patients' intolerances to transplant; hence it ultimately improves transplant outcomes. Prognostic models are key for appropriate actuarial outcome estimates, which has been frequently shown to be better than physicians' subjective estimates. To make the most accurate prognostic evaluation for HCT, one should rely on more than one prognostic model. For relapse and relapse-related mortality risks, the refined disease risk index is currently the most informative model. It can be supplemented by disease-specific models that consider genetic mutations as predictors in addition to information on measurable residual disease. For non-relapse mortality and HCT-related morbidity risks, the HCT-comorbidity index and Karnofsky performance status have proven to be the most reliable and most accepted by physicians. These can be supplemented by gait speed as a measure of frailty. Some other global prognostic models might add additional prognostic information. Physicians' educated perceptions can then put all this information in context taking into consideration conditioning regimen and donor choices. The future of transplantation mandates 1) clinical investigators specifically trained in prognostication, 2) increased reliance on geriatric assessment, 3) the use of novel biomarkers such as genetic variants, and 4) successfully applying novel statistical methods such as machine-learning.
In vivo HSC prime editing rescues Sickle Cell Disease in a mouse model
Authors: Li Chang , Georgakopoulou Aphrodite , Newby Gregory A , Chen Peter J , Everette Kelcee A , Paschoudi Kiriaki , Vlachaki Efthimia , Gil Sucheol , Anderson Anna K , Koob Theodore , Huang Lishan , Wang Hongjie , Kiem Hans-Peter , Liu David R , Yannaki Evangelia , Lieber André
Published: February 2023

Sickle Cell Disease (SCD) is a monogenic disease caused by a nucleotide mutation in the β-globin gene. Current gene therapy studies are mainly focused on lentivirus vector-mediated gene addition or CRISPR/Cas9-mediated fetal globin reactivation, leaving the root cause unfixed. We developed a vectorized prime editing system that can directly repair the SCD mutation in hematopoietic stem cells (HSCs) in vivo in a SCD mouse model (CD46/Townes mice). Our approach involved a single intravenous injection of a non-integrating, prime editor-expressing virus vector into mobilized CD46/Townes mice and low-dose drug selection in vivo. This procedure resulted in the correction of ~40% of bS alleles in HSCs. On average 43% of HbS was replaced by HbA thereby greatly mitigating the SCD phenotypes. Transplantation in secondary recipients demonstrated that long-term repopulating HSCs were edited. Highly efficient target site editing was achieved with minimal generation of insertions and deletions and no detectable off-target editing. Because of its simplicity and portability, our in vivo prime editing approach has the potential for application in resource-poor countries where SCD is prevalent.
HTLV-1 persistence and the oncogenesis of adult T cell leukemia/lymphoma
Authors: Bangham Charles R M
Published: February 2023

Human T-cell leukemia virus type 1 (HTLV-1), also known as human T-lymphotropic virus type 1, causes the aggressive malignancy known as adult T-cell leukemia/lymphoma (ATL) in 5% of infected people, and a chronic progressive inflammatory disease of the central nervous system - HTLV-1-associated myelopathy (HAM) - in a further 0.3% to 4%, varying between endemic regions. Reliable treatments are lacking for both conditions, although there have been promising recent advances in the prevention and treatment of ATL. Since ATL typically develops after several decades of infection, it is necessary to understand how the virus persists in the host despite a strong immune response, and how this persistence results in oncogenesis.
Pathogen detection in RNA-seq data with Pathonoia
Authors: Liebhoff Anna-Maria , Menden Kevin , Laschtowitz Alena , Franke Andre , Schramm Christoph , Bonn Stefan
Published: February 2023

Background

Bacterial and viral infections may cause or exacerbate various human diseases and to detect microbes in tissue, one method of choice is RNA sequencing. The detection of specific microbes using RNA sequencing offers good sensitivity and specificity, but untargeted approaches suffer from high false positive rates and a lack of sensitivity for lowly abundant organisms.

Results

We introduce Pathonoia, an algorithm that detects viruses and bacteria in RNA sequencing data with high precision and recall. Pathonoia first applies an established k-mer based method for species identification and then aggregates this evidence over all reads in a sample. In addition, we provide an easy-to-use analysis framework that highlights potential microbe-host interactions by correlating the microbial to the host gene expression. Pathonoia outperforms state-of-the-art methods in microbial detection specificity, both on in silico and real datasets.

Conclusion

Two case studies in human liver and brain show how Pathonoia can support novel hypotheses on microbial infection exacerbating disease. The Python package for Pathonoia sample analysis and a guided analysis Jupyter notebook for bulk RNAseq datasets are available on GitHub.
Effect of surgical pleth index-guided remifentanil administration on perioperative outcomes in elderly patients: a prospective randomized controlled trial
Authors: Won Young Ju , Oh Seok Kyeong , Lim Byung Gun , Kim Young Sung , Lee Do Yeop , Lee Jae Hak
Published: February 2023

Background

During general anesthesia, the surgical pleth index (SPI) monitors nociception. The evidence of SPI in the elderly remains scarce. We aimed to investigate whether there is a difference in perioperative outcomes following intraoperative opioid administration according to the surgical pleth index (SPI) value versus hemodynamic parameters (heart rate or blood pressure) in elderly patients.

Methods

Patients aged 65–90 years who underwent laparoscopic colorectal cancer surgery under sevoflurane/remifentanil anesthesia were randomized to receive remifentanil guided by SPI (SPI group) or conventional clinical judgment based on hemodynamic parameters (conventional group). The primary endpoint was intraoperative remifentanil consumption. Secondary endpoints were intraoperative hemodynamic instability, pain score, fentanyl consumption and delirium in the post-anesthesia care unit (PACU), and perioperative changes in interleukin-6 and natural killer (NK) cell activity.

Results

Seventy-five patients (38, SPI; 37, conventional) were included in the study. The SPI group consumed significantly more remifentanil intraoperatively than the conventional group (mean ± SD, 0.13 ± 0.05 vs. 0.06 ± 0.04 μg/kg/min, P < 0.001). Intraoperative hypertension and tachycardia were more common in the conventional group than in the SPI group. Pain score in the PACU (P = 0.013) and the incidence of delirium in the PACU were significantly lower in the SPI group than the conventional group (5.2% vs. 24.3%, P = 0.02). There was no significant difference in NK cell activity and interleukin-6 level.

Conclusions

In the elderly patients, SPI-guided analgesia provided appropriate analgesia with sufficient intraoperative remifentanil consumption, lower incidence of hypertension/ tachycardia events, and a lower incidence of delirium in the PACU than the conventional analgesia. However, SPI-guided analgesia may not prevent perioperative immune system deterioration.

Trial registration

The randomized controlled trial was retrospectively registered in the UMIN Clinical Trials Registry (trial number: UMIN000048351; date of registration: 12/07/2022).
A food bank program to help food pantries improve healthy food choices: mixed methods evaluation of The Greater Boston Food Bank’s Healthy Pantry Program
Authors: Jia Jenny , Burgun Rachel , Reilly Alexa , Sonnenblick Ross , Fiechtner Lauren , Zack Rachel M. , Porneala Bianca , Thorndike Anne N.
Published: February 2023

Background

The Greater Boston Food Bank’s (GBFB) Healthy Pantry Program (HPP) is an online training that teaches food pantry staff to implement behavioral nudges (e.g., traffic-light nutrition labels, choice architecture) to promote healthier client choices. This study assessed if HPP was associated with healthier food bank orders by food pantries and identified implementation facilitators and barriers.

Methods

This mixed methods study collected quantitative data from a matched cohort of 10 HPP food pantries and 99 matched control food pantries in eastern Massachusetts that allow clients to choose their own food, and qualitative data from structured individual interviews with 8 HPP pantry staff. A difference-in-differences analysis compared changes in percentage of pantries’ food bank orders (by weight) of foods labeled green/yellow (healthier choices) and fresh produce from baseline to 6 and 10 months between HPP and control pantries. Interviews were coded for implementation facilitators and barriers.

Results

Before starting HPP, green-yellow ordering was 92.0% (SD 4.9) in control and 87.4% (SD 5.4) in HPP pantries. Participation in HPP was not associated with changes in green-yellow or fresh produce ordering at 6 or 10 months. HPP implementation facilitators included HPP training being accessible (sub-themes: customizable, motivating) and compatible with client-choice values. Barriers included resource limitations (sub-themes: staff shortage, limited space) and concerns about stigmatizing client food choices with use of labels for unhealthy foods.

Conclusions

An online program to help pantries promote healthier client choices was not associated with changes in how much healthy food pantries ordered from the food bank, suggesting it did not substantially change client choices. Implementation challenges and high baseline healthy ordering may have influenced HPP’s effectiveness.
Elderly people’s preferences for healthcare facilities in Shanghai: gender features and influencing factor analysis
Authors: Yang Shangguang , Liu Luxue , Wang Chunlan , Lo Kevin , Wang Danyang
Published: February 2023

Background

China has one of the fastest paces of the growing aging population, High-level policymakers have recently recognized the aging population presents significant challenges to the Chinese healthcare system. In this context, the healthcare-seeking behaviors of the elderly population have become an essential field of study. It is necessary to understand their access to health services and to improve their quality of life, as well as to help policymakers to formulate healthcare policy. The study empirically investigates the factors influencing the elderly population’s healthcare-seeking behaviors in Shanghai, China, especially in choosing the quality of healthcare facilities to visit.

Methods

We designed a cross-sectional study. The data of this study were derived from the “Shanghai elderly medical demand characteristics questionnaire” in the middle of November to early December 2017. A total of 625 individuals were included in the final sample. Logistic regression was adopted to investigate the differences in healthcare-seeking behaviors between elderly people when suffer from mild illness, severe illness and follow-up treatment. Next, the differences in gender were also discussed.

Results

Factors affecting the healthcare-seeking behaviors of the elderly differ in mild illness and severe illness situations. For mild illness, demographic factors (gender and age) and socioeconomic factors (income and employment) play an important role in elderly healthcare choices. Female and older elderlies are more likely to choose local, lower-quality facilities, whereas those with high income and private employment are more likely to choose higher-quality facilities. For severe illness, socioeconomic factors (income and employment) are important. Furthermore, individuals with basic medical insurance are more likely to choose lower-quality facilities.

Conclusion

This study has shown that the affordability of public health services should be addressed. Medical policy support may be an important way to reduce the gap in access to medical services. We should pay attention to the gender differences in the elderly’s choice of medical treatment behavior, consider the differences in the needs of male and female elderly. our findings are only for elderly Chinese participants in the greater Shanghai area.
Development of machine learning models for detection of vision threatening Behçet’s disease (BD) using Egyptian College of Rheumatology (ECR)–BD cohort
Authors: Hammam Nevin , Bakhiet Ali , El-Latif Eiman Abd , El-Gazzar Iman I. , Samy Nermeen , Noor Rasha A. Abdel , El-Shebeiny Emad , El-Najjar Amany R. , Eesa Nahla N. , Salem Mohamed N. , Ibrahim Soha E. , El-Essawi Dina F. , Elsaman Ahmed M. , Fathi Hanan M. , Sallam Rehab A. , El Shereef Rawhya R. , Ismail Faten , Abd-Elazeem Mervat I. , Said Emtethal A. , Khalil Noha M. , Shahin Dina , El-Saadany Hanan M. , ElKhalifa Marwa , Nasef Samah I. , Abdalla Ahmed M. , Noshy Nermeen , Fawzy Rasha M. , Saad Ehab , Moshrif Abdelhafeez , El-Shanawany Amira T. , Abdel-Fattah Yousra H. , Khalil Hossam M. , Hammam Osman , Fathy Aly Ahmed , Gheita Tamer A.
Published: February 2023

Background

Eye lesions, occur in nearly half of patients with Behçet’s Disease (BD), can lead to irreversible damage and vision loss; however, limited studies are available on identifying risk factors for the development of vision-threatening BD (VTBD). Using an Egyptian college of rheumatology (ECR)-BD, a national cohort of BD patients, we examined the performance of machine-learning (ML) models in predicting VTBD compared to logistic regression (LR) analysis. We identified the risk factors for the development of VTBD.

Methods

Patients with complete ocular data were included. VTBD was determined by the presence of any retinal disease, optic nerve involvement, or occurrence of blindness. Various ML-models were developed and examined for VTBD prediction. The Shapley additive explanation value was used for the interpretability of the predictors.

Results

A total of 1094 BD patients [71.5% were men, mean ± SD age 36.1 ± 10 years] were included. 549 (50.2%) individuals had VTBD. Extreme Gradient Boosting was the best-performing ML model (AUROC 0.85, 95% CI 0.81, 0.90) compared with logistic regression (AUROC 0.64, 95%CI 0.58, 0.71). Higher disease activity, thrombocytosis, ever smoking, and daily steroid dose were the top factors associated with VTBD.

Conclusions

Using information obtained in the clinical settings, the Extreme Gradient Boosting identified patients at higher risk of VTBD better than the conventional statistical method. Further longitudinal studies to evaluate the clinical utility of the proposed prediction model are needed.
Barriers and facilitators in the implementation of mobilization robots in hospitals from the perspective of clinical experts and developers
Authors: Warmbein Angelika , Rathgeber Ivanka , Seif Janesca , Mehler-Klamt Amrei C. , Schmidbauer Lena , Scharf Christina , Hübner Lucas , Schroeder Ines , Biebl Johanna , Gutmann Marcus , Eberl Inge , Zoller Michael , Fischer Uli
Published: February 2023

Background

Early mobilization can help reduce severe side effects such as muscle atrophy that occur during hospitalization. However, due to time and staff shortages in intensive and critical care as well as safety risks for patients, it is often difficult to adhere to the recommended therapy time of twenty minutes twice a day. New robotic technologies might be one approach to achieve early mobilization effectively for patients and also relieve users from physical effort. Nevertheless, currently there is a lack of knowledge regarding the factors that are important for integrating of these technologies into complex treatment settings like intensive care units or rehabilitation units.

Methods

European experts from science, technical development and end-users of robotic systems (n = 13) were interviewed using a semi-structured interview guideline to identify barriers and facilitating factors for the integration of robotic systems into daily clinical practice. They were asked about structural, personnel and environmental factors that had an impact on integration and how they had solved challenges. A latent content analysis was performed regarding the COREQ criteria.

Results

We found relevant factors regarding the development, introduction, and routine of the robotic system. In this context, costs, process adjustments, a lack of exemptions, and a lack of support from the manufacturers/developers were identified as challenges. Easy handling, joint decision making between the end-users and the decision makers in the hospital, an accurate process design and the joint development of the robotic system of end-users and technical experts were found to be facilitating factors.

Conclusion

The integration and preparation for the integration of robotic assistance systems into the inpatient setting is a complex intervention that involves many parties. This study provides evidence for hospitals or manufacturers to simplify the planning of integrations for permanent use.

Trial registration

DRKS-ID: DRKS00023848; registered 10/12/2020.
CLEC5A mediates Zika virus-induced testicular damage
Authors: Wang Hsin-Wei , Li Hsing-Han , Wu Shih-Cheng , Tang Cheng-Kang , Yu Hui-Ying , Chang Ya-Chen , Sung Pei-Shan , Liu Wei-Liang , Su Matthew P. , Yu Guann-Yi , Huang Li-Rung , Chen Chun-Hong , Hsieh Shie-Liang
Published: February 2023

Background

Zika virus (ZIKV) infection is clinically known to induce testicular swelling, termed orchitis, and potentially impact male sterility, but the underlying mechanisms remain unclear. Previous reports suggested that C-type lectins play important roles in mediating virus-induced inflammatory reactions and pathogenesis. We thus investigated whether C-type lectins modulate ZIKV-induced testicular damage.

Methods

C-type lectin domain family 5 member A (CLEC5A) knockout mice were generated in a STAT1-deficient immunocompromised background (denoted clec5a−/−stat1−/−) to enable testing of the role played by CLEC5A after ZIKV infection in a mosquito-to-mouse disease model. Following ZIKV infection, mice were subjected to an array of analyses to evaluate testicular damage, including ZIKV infectivity and neutrophil infiltration estimation via quantitative RT-PCR or histology and immunohistochemistry, inflammatory cytokine and testosterone detection, and spermatozoon counting. Furthermore, DNAX-activating proteins for 12 kDa (DAP12) knockout mice (dap12−/−stat1−/−) were generated and used to evaluate ZIKV infectivity, inflammation, and spermatozoa function in order to investigate the potential mechanisms engaged by CLEC5A.

Results

Compared to experiments conducted in ZIKV-infected stat1−/− mice, infected clec5a−/−stat1−/− mice showed reductions in testicular ZIKV titer, local inflammation and apoptosis in testis and epididymis, neutrophil invasion, and sperm count and motility. CLEC5A, a myeloid pattern recognition receptor, therefore appears involved in the pathogenesis of ZIKV-induced orchitis and oligospermia. Furthermore, DAP12 expression was found to be decreased in the testis and epididymis tissues of clec5a−/−stat1−/− mice. As for CLEC5A deficient mice, ZIKV-infected DAP12-deficient mice also showed reductions in testicular ZIKV titer and local inflammation, as well as improved spermatozoa function, as compared to controls. CLEC5A-associated DAP12 signaling appears to in part regulate ZIKV-induced testicular damage.

Conclusions

Our analyses reveal a critical role for CLEC5A in ZIKV-induced proinflammatory responses, as CLEC5A enables leukocytes to infiltrate past the blood-testis barrier and induce testicular and epididymal tissue damage. CLEC5A is thus a potential therapeutic target for the prevention of injuries to male reproductive organs in ZIKV patients.
Targeting of G-protein coupled receptor 40 alleviates airway hyperresponsiveness through RhoA/ROCK1 signaling pathway in obese asthmatic mice
Authors: Lin Xixi , Wang Like , Lu Xiaojie , Zhang Yuanyuan , Zheng Rongying , Chen Ruijie , Zhang Weixi
Published: February 2023

Obesity increases the severity of airway hyperresponsiveness (AHR) in individuals with asthma, but the mechanism is not well elucidated. G-protein coupled receptor 40 (GPR40) has been found to induce airway smooth muscle contraction after activated by long-chain fatty acids (LC-FFAs), suggesting a close correlation between GPR40 and AHR in obese. In this study, C57BL/6 mice were fed a high-fat diet (HFD) to induce obesity with or without ovalbumin (OVA) sensitization, the regulatory effects of GPR40 on AHR, inflammatory cells infiltration, and the expression of Th1/Th2 cytokines were evaluated by using a small-molecule antagonist of GPR40, DC260126. We found that the free fatty acids (FFAs) level and GPR40 expression were greatly elevated in the pulmonary tissues of obese asthmatic mice. DC260126 greatly reduced methacholine-induced AHR, ameliorated pulmonary pathological changes and decreased inflammatory cell infiltration in the airways in obese asthma. In addition, DC260126 could down-regulate the levels of Th2 cytokines (IL-4, IL-5, and IL-13) and pro-inflammatory cytokines (IL-1β, TNF-α), but elevated Th1 cytokine (IFN-γ) expression. In vitro, DC260126 could remarkedly reduce oleic acid (OA)-induced cell proliferation and migration in HASM cells. Mechanistically, the effects that DC260126 alleviated obese asthma was correlated with the down-regulation of GTP-RhoA and Rho-associated coiled-coil-forming protein kinase 1 (ROCK1). Herein, we proved that targeting of GPR40 with its antagonist helped to mitigate multiple parameters of obese asthma effectively.
Effect of vitamin E intake on glycemic control and insulin resistance in diabetic patients: an updated systematic review and meta-analysis of randomized controlled trials
Authors: Asbaghi Omid , Nazarian Behzad , Yousefi Mojtaba , Anjom-Shoae Javad , Rasekhi Hamid , Sadeghi Omid
Published: February 2023

Since a 2014 meta-analysis, several randomized controlled trials (RCTs) evaluating the effect of vitamin E intake on glycemic indices and insulin resistance in adults with diabetes have reached inconsistent conclusions. Therefore, we updated the previous meta-analysis to summarize the current evidence in this regard. Online databases including PubMed, Scopus, ISI Web of Science, and Google Scholar were searched to identify relevant studies published up to September 30, 2021, using relevant keywords. Random-effects models were used to obtain overall mean difference (MD) comparing vitamin E intake with a control group. In total, 38 RCTs with a total sample size of 2171 diabetic patients (1110 in vitamin E groups and 1061 in control groups) were included. Combining the results from 28 RCTs on fasting blood glucose, 32 RCTs on HbA1c, 13 RCTs on fasting insulin, and 9 studies on homeostatic model assessment for insulin resistance (HOMA-IR) showed a summary MD of -3.35 mg/dL (95% CI: -8.10 to 1.40, P = 0.16), -0.21% (95% CI: -0.33 to -0.09, P = 0.001), -1.05 µIU/mL (95% CI: -1.53 to -0.58, P < 0.001), and -0.44 (95% CI: -0.82 to -0.05, P = 0.02), respectively. This indicates a significant lowering effect of vitamin E on HbA1c, fasting insulin and HOMA-IR, while no significant effect on fasting blood glucose in diabetic patients. However, in subgroup analyses, we found that vitamin E intake significantly reduced fasting blood glucose in studies with an intervention duration of < 10 weeks. In conclusion, vitamin E intake has a beneficial role in improving HbA1c and insulin resistance in a population with diabetes. Moreover, short-term interventions with vitamin E have resulted in lower fasting blood glucose in these patients. This meta-analysis was registered in PROSPERO with code CRD42022343118.
Hyaluronic acid-FGF2-derived peptide bioconjugates for suppression of FGFR2 and AR simultaneously as an acne antagonist
Authors: Su Zijian , Zhang Yibo , Cao Jieqiong , Sun Yuanmeng , Cai Yuling , Zhang Bihui , He Liu , Zhang Zilei , Xie Junye , Meng Qilin , Luo Lin , Li Fu , Li Jingsheng , Zhang Jinting , Chen Xiaojia , Hong An
Published: February 2023

Acne is a chronic skin condition that has serious consequences for mental and social well-being because it frequently occurs on the face. Several acne treatment approaches have commonly been used but have been hampered by side effects or weak activity. Thus, the investigation of the safety and efficacy of anti-acne compounds is of considerable medical importance. Herein, an endogenous peptide (P5) derived from fibroblast growth factors 2 (FGF2) was conjugated to the polysaccharide hyaluronic acid (HA) to generate the bioconjugate nanoparticle HA-P5, which suppresses fibroblast growth factor receptors (FGFRs) to significantly rehabilitate acne lesions and reduce sebum accumulation in vivo and in vitro. Moreover, our results show that HA-P5 inhibits both fibroblast growth factor receptor 2 (FGFR2) and androgen receptor (AR) signalling in SZ95 cells, reverses the acne-prone transcriptome, and decreases sebum secretion. Furthermore, the cosuppression mechanism revealed that HA-P5 blocks FGFR2 activation, as well as the YTH N6-methyladenosine RNA binding protein F3 (YTHDF3) downstream molecules, including an N6-methyladenosine (m6A) reader that facilitates AR translation. More importantly, a significant difference between HA-P5 and the commercial FGFR inhibitor AZD4547 is that HA-P5 does not trigger the overexpression of aldo-keto reductase family 1 member C3 (AKR1C3), which blocks acne treatment by catalyzing the synthesis of testosterone. Overall, we demonstrate that a polysaccharide-conjugated and naturally derived oligopeptide HA-P5 can alleviate acne and act as an optimal FGFR2 inhibitor and reveal that YTHDF3 plays a crucial role in signalling between FGFR2 and AR.

Graphical Abstract
microRNA-128-3p inhibits proliferation and accelerates apoptosis of gastric cancer cells via inhibition of TUFT1
Authors: Du Xiong , Li Yanxin , Lian Bin , Yin Xiangli
Published: February 2023

Objective

Gastric cancer (GC) is a malignant tumor rooting in the gastric mucosal epithelium, ranking the first among various malignant tumors. Therefore, the influence of microRNA-128-3p (miR-128-3p) by regulation of Tuftelin1 (TUFT1) on GC cells was investigated.

Methods

The expression levels of miR-128-3p and TUFT1 in GC tissues and cells were detected. The correlation between miR-128-3p expression and overall survival of GC patients was analyzed. Human GC cells MGC803 were transfected with miR-128-3p or TUFT1-related oligonucleotides to figure their roles in viability, apoptosis, invasion, as well as epithelial-mesenchymal transition (EMT). The relationship between miR-128-3p and TUFT1 was validated.

Results

miR-128-3p expression was low and TUFT1 expression was high in GC tissues. miR-128-3p expression was positively correlated with the overall survival of patients with GC. miR-128-3p targeted TUFT1. Up-regulated miR-128-3p or suppressed TUFT1 repressed viability, invasion, and EMT, and accelerated apoptosis of GC cells. Overexpressed TUFT1 reduced miR-128-3p-mediated growth inhibition of GC cells.

Conclusion

The study stresses that miR-128-3p can inhibit TUFT1 expression, thereby repressing GC cell activities.
Digital interventions for substance use disorders in young people: rapid review
Authors: Monarque Marika , Sabetti Judith , Ferrari Manuela
Published: February 2023

Background

Young people are disproportionately more likely than other age groups to use substances. The rise in substance use and related harms, including overdose, during the Covid-19 pandemic has created a critical need for more innovative and accessible substance use interventions. Digital interventions have shown effectiveness and can provide more engaging, less stigmatizing, and accessible interventions that meet the needs of young people. This review provides an overview of recent literature on the nature of recently published digital interventions for young people in terms of technologies used, substances targeted, intended outcomes and theoretical or therapeutic models employed.

Methods

Rapid review methodology was used to identify and assess the literature on digital interventions for young people. An initial keyword search was conducted using MEDLINE, the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database (HTA) and PROSPERO for the years 2015–2020, and later updated to December 2021. Following a title/abstract and full-text screening of articles, and consensus decision on study inclusion, the data extraction process proceeded using an extraction grid developed for the study. Data synthesis relied on an adapted conceptual framework by Stockings, et al. that involved a three-level treatment spectrum for youth substance use (prevention, early intervention, and treatment) for any type of substance.

Results

In total, the review identified 43 articles describing 39 different digital interventions. Most were early interventions (n = 28), followed by prevention interventions (n = 6) and treatment interventions (n = 5). The identified digital technologies included web-based (n = 14), game-based (n = 10), mobile-based (n = 7), and computer-based (n = 5) technologies, and virtual reality (n = 3). Most interventions targeted alcohol use (n = 20) followed by tobacco/nicotine (n = 5), cannabis (n = 2), opioids (n = 2), ketamine (n = 1) and multiple, or any substances (n = 9). Most interventions used a personalized or normative feedback approach and aimed to effect behaviour change as the intended outcome. Interestingly, a harm reduction approach guided only one of the 39 interventions.

Conclusions

While web-based interventions represented the most common type of technology, more recently developed immersive and interactive technologies such as virtual reality and game-based interventions call for further exploration. Digital interventions focused mainly on alcohol use, reflecting less concern for tobacco, cannabis, co-occurring substance use, and illicit drug use. Specifically, the recent exacerbation in the opioid crisis throughout North American underlines the urgent need for more prevention-oriented digital interventions for opioid use. The uptake of digital interventions among youth also depends on the incorporation of harm reduction approaches.
Arthroscopically assisted versus open reduction internal fixation for ankle fractures: a systematic review and meta-analysis
Authors: Zhang Guangming , Chen Nong , Ji Linfeng , Sun Chengyi , Ding Sheng-Long
Published: February 2023

Background

Open reduction and internal fixation were routinely used to treat patients with unstable ankle fractures (ORIF). However, some patients may experience persistent ankle pain and disability following ORIF due to untreated intra-articular lesions. Moreover, ankle fractures may be treated with arthroscopically assisted reduction and internal fixation (ARIF). This study aimed to compare the feasibility and benefits of ARIF versus ORIF for ankle fractures.

Methods

We performed this meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A systematic search was conducted for comparative studies comparing ARIF and ORIF for ankle fractures. Nine studies were included in the analysis of clinical and secondary outcomes. In summary, we calculated the mean difference (MD), risk ratio (RR), confidence interval, and p value.

Results

This meta-analysis demonstrated that the ARIF group achieved a higher Olerud–Molander Ankle (OMA) score (MD: 6.6; 95% CI 0.20 to 13.0; p = 0.04) and lower visual analog scale (VAS) score (MD: − 0.36; 95% CI − 0.64 to − 0.10; p = 0.01) at the final follow-up. Nevertheless, the smallest treatment effect of OMA score and VAS score did not exceed the minimum clinically important difference (MCID). There were longer surgery time (MD: 15.0; 95% CI 10.7 to 19.3; p < 0.01) and lower complication rates (RR: 0.53; 95% CI 0.31 to 0.89; p = 0.02) in ARIF compared with ORIF. The random-effect model suggested no significant difference in the arthritis change rate between the two groups.

Conclusion

In summary, the results of this meta-analysis indicated that ARIF and ORIF are comparable in terms of providing pain relief and improving function for patients with ankle fractures. Therefore, the choice between the two techniques should be based on the patient's individual factors and the surgeon's personal preference.
Tricuspid repair in mitral regurgitation surgery: a systematic review and meta-analysis
Authors: Cardoso João Lopes , Ferraz Costa Gonçalo Nuno , Neves Fátima , Gonçalves Lino , Teixeira Rogério
Published: February 2023

Background

Concomitant tricuspid repair in MR surgery is indicated in patients with severa tricuspid regurgitation, however, concomitant repair in less-than-severe TR patients is still a matter of debate.

Methods

In December 2021, we systematically searched PubMed, Embase and Cochrane databases for randomised control trials (RCTs) comparing isolated MR surgery versus MR surgery with concomitant TR annuloplasty. Four studies were included, resulting in 651 patients (323 in the prophylactic tricuspid intervention group and 328 in the no tricuspid intervention group).

Results

Our meta-analysis showed a similar all-cause mortality and perioperative mortality for concomitant prophylactic tricuspid repair when compared with no tricuspid intervention (pooled odds ratio (OR), 0.54; 95% confidence interval (CI): 0.25–1.15, P = 0.11; I2 = 0% and pooled OR, 0.54; 95% CI: 0.25–1.15, P = 0.11; I2 = 0%, respectively) in patients undergoing MV surgery. despite a significantly lower TR progression (pooled OR, 0.06; 95% CI: 0.02–0.24, P < 0.01; I2 = 0%). Additionally, similar New York Heart Association (NYHA) classes III and IV were identified in both concomitant prophylactic tricuspid repair and no tricuspid intervention, despite a lower trend in the tricuspid intervention group (pooled OR, 0.63; 95% CI: 0.38–1.06, P = 0.08; I2 = 0%).

Conclusions

Our pooled analyses suggested that TV repair at the time of MV surgery in patients with moderate or less-than-moderate TR did not impact on perioperative or postoperative all-cause mortality, despite reducing TR severity and TR progression following the intervention.
Long term respiratory morbidity in patients with vascular rings: a review
Authors: Porcaro Federica , Ciliberti Paolo , Petreschi Francesca , Secinaro Aurelio , Allegorico Annalisa , Coretti Antonella , Cutrera Renato
Published: February 2023

Abnormalities in position and/or branching of the aortic arch can lead to vascular rings that may cause narrowing of the tracheal lumen due to external compression, or constriction of the oesophagus, causing symptoms that vary in relation to the anatomical vascular pattern and the relationship between these structures. Respiratory morbidity related to external airways compression is a major concern in children affected by vascular rings. Clinical presentation depends on the severity of the tracheal lumen reduction and the presence of associated tracheomalacia. Recurrent respiratory infections, wheezing, atelectasis, and hyperinflation are mostly reported. As they are nonspecific and therefore difficult to recognize, attention should be given to all children with history of respiratory distress, extubation failure, noisy breathing, and recurrent respiratory infections. Early diagnosis and referral to specialized centres can prevent the long-term complications and improve the respiratory outcomes of these patients.
The transgenic IG-DMR sequence of the mouse Dlk1-Dio3 domain acquired imprinted DNA methylation during the post-fertilization period
Authors: Matsuzaki Hitomi , Sugihara Shokichi , Tanimoto Keiji
Published: February 2023

Background

Allele-specific methylation of the imprinting control region (ICR) is the molecular basis for the genomic imprinting phenomenon that is unique to placental mammals. We previously showed that the ICR at the mouse H19 gene locus (H19 ICR) was unexpectedly established after fertilization and not during spermatogenesis in transgenic mice (TgM), and that the same activity was essential for the maintenance of paternal methylation of the H19 ICR at the endogenous locus in pre-implantation embryos. To examine the universality of post-fertilization imprinted methylation across animal species or imprinted loci, we generated TgM with two additional sequences.

Results

The rat H19 ICR, which is very similar in structure to the mouse H19 ICR, unexpectedly did not acquire imprinted methylation even after fertilization, suggesting a lack of essential sequences in the transgene fragment. In contrast, the mouse IG-DMR, the methylation of which is acquired during spermatogenesis at the endogenous locus, did not acquire methylation in the sperm of TgM, yet became highly methylated in blastocysts after fertilization, but only when the transgene was paternally inherited. Since these two sequences were evaluated at the same genomic site by employing the transgene co-placement strategy, it is likely that the phenotype reflects the intrinsic activity of these fragments rather than position-effect variegation.

Conclusions

Our results suggested that post-fertilization imprinted methylation is a versatile mechanism for protecting paternal imprinted methylation from reprogramming during the pre-implantation period.
Relationship of systemic type I interferon activity with clinical phenotypes, disease activity, and damage accrual in systemic lupus erythematosus in treatment-naive patients: a retrospective longitudinal analysis
Authors: Miyachi Kazusa , Iwamoto Taro , Kojima Shotaro , Ida Tomoaki , Suzuki Junya , Yamamoto Takuya , Mimura Norihiro , Sugiyama Takahiro , Tanaka Shigeru , Furuta Shunsuke , Ikeda Kei , Suzuki Kotaro , Niewold Timothy B. , Nakajima Hiroshi
Published: February 2023

Background

Systemic lupus erythematosus (SLE) is heterogeneous in organ involvement and disease severity, presenting a broad clinical phenotype. Systemic type I interferon (IFN) activity has been shown to be associated with lupus nephritis, autoantibodies, and disease activity in treated SLE patients; however, these relationships are unknown in treatment-naive patients. We aimed to determine the relationship of systemic IFN activity with clinical phenotypes, disease activity, and damage accrual in treatment-naive SLE patients before and after induction and maintenance therapy.

Methods

Forty treatment-naive SLE patients were enrolled for this retrospective longitudinal observational study to examine the relationship between serum IFN activity and clinical manifestations of EULAR/ACR-2019 criteria domains, disease activity measures, and damage accrual. As controls, 59 other treatment-naive rheumatic disease patients and 33 healthy individuals were recruited. Serum IFN activity was measured by WISH bioassay and presented as an IFN activity score.

Results

Treatment-naive SLE patients had significantly higher serum IFN activity than other rheumatic disease patients (score: 97.6 and 0.0, respectively, p < 0.001). High serum IFN activity was significantly associated with fever, hematologic disorders (leukopenia), and mucocutaneous manifestations (acute cutaneous lupus and oral ulcer) of EULAR/ACR-2019 criteria domains in treatment-naive SLE patients. Serum IFN activity at baseline significantly correlated with SLEDAI-2K scores and decreased along with a decrease in SLEDAI-2K scores after induction and maintenance therapy (R2 = 0.112, p = 0.034). SLE patients who developed organ damage (SDI ≥ 1) had higher serum IFN activity at baseline than those who did not (SDI = 0) (150.0 versus 57.3, p= 0.018), but the multivariate analysis did not detect its independent significance (p = 0.132).

Conclusions

Serum IFN activity is characteristically high and is linked to fever, hematologic disorders, and mucocutaneous manifestations in treatment-naive SLE patients. Serum IFN activity at baseline correlates with disease activity and decreases in parallel with a decrease in disease activity after induction and maintenance therapy. Our results suggest that IFN plays an important role in the pathophysiology of SLE and that serum IFN activity at baseline may be a potential biomarker for the disease activity in treatment-naive SLE patients.
Lung cancer embolization causing acute limb ischemia: a case report
Authors: Hussain Syed Mohammad Asim
Published: February 2023

Background

Acute tumour embolism to the popliteal artery resulting in limb-threatening ischemia is a rare complication of neoplastic disease. Generally, tumors embolize to the pulmonary circulation via the venous system. In this case, the originating tumor was a lung cancer of a large size and advanced stage that had invaded the left atrium of the heart and disseminated in the systemic circulation. The tumor likely fragmented, resulting in showering to the right popliteal artery, superior mesenteric artery, and left renal artery, which is a unique presentation of tumor embolism.

Case report

We present a case of a 62-year-old Caucasian gentleman with a large left lower lobe squamous cell lung cancer that had invaded into the left atrium via the pulmonary veins. He presented with acute limb threatening ischemia. A computed tomographic angiogram revealed an occlusion of the left popliteal artery as well as embolization to the superior mesenteric artery and the right renal artery. He was started on intravenous heparin and underwent an emergency popliteal embolectomy and calf fasciotomies, which was limb saving. His fasciotomy wounds were closed after 1 week and he was discharged on anticoagulation.

Conclusion

This is a rare case of tumor embolism resulting in both an embolectomy and calf fasciotomies. In the light of such cases, we suggest that tumors invading the bloodstream should be considered high risk for embolization and hypothesize that prophylactic antithrombotic therapy may avoid major morbidity.