bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toll-like receptors and their role in neuropathic pain and migraine
Authors: Liu Xuejiao , Yang Wenping , Zhu Chenlu , Sun Songtang , Wu Shouyi , Wang Longde , Wang Yonggang , Ge Zhaoming 
Published: August 2022

AbstractMigraine is a complex neurological disease of unknown etiology involving both genetic and environmental factors. It has previously been reported that persistent pain may be mediated by the immune and inflammatory systems. Toll-like receptors (TLRs) play a significant role in immune and inflammatory responses and are expressed by microglia and astrocytes. One of the fundamental mechanisms of the innate immune system in coordinating inflammatory signal transduction is through TLRs, which protect the host organism by initiating inflammatory signaling cascades in response to tissue damage or stress. TLRs reside at the neuroimmune interface, and accumulating evidence has suggested that the inflammatory consequences of TLR activation on glia (mainly microglia and astrocytes), sensory neurons, and other cell types can influence nociceptive processing and lead to pain. Several studies have shown that TLRs may play a key role in neuropathic pain and migraine etiology by activating the microglia. The pathogenesis of migraine may involve a TLR-mediated crosstalk between neurons and immune cells. Innate responses in the central nervous system (CNS) occur during neuroinflammatory phenomena, including migraine. Antigens found in the environment play a crucial role in the inflammatory response, causing a broad range of diseases, including migraines. These can be recognized by several innate immune cells, including macrophages, microglia, and dendritic cells, and can be activated through TLR signaling. Given the prevalence of migraine and the insufficient efficacy and safety of current treatment options, a deeper understanding of TLRs is expected to provide novel therapies for managing chronic migraine. This review aimed to justify the view that TLRs may be involved in migraine.
Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial
Authors: Muti Paola , Sacconi Andrea , Pulito Claudio , Orlandi Giulia , Donzelli Sara , Morrone Aldo , Jiulian James , Cox Gerard P. , Kolb Martin , Pond Gregory , Kavsak Peter , Levine Mark Norman , Blandino Giovanni , Strano Sabrina 
Published: August 2022

Abstract
Background
Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor prognosis. Mesothelioma has the potential to represent an appropriate disease to prevent because of its strong association with asbestos exposure and the long latency from exposure to the disease on-set.

Methods
In the present study, we tested biological activity and toxicity of an artichoke freeze-dried extract (AWPC) as potential complementary preventive/early stage treatment agent for mesothelioma. This phase II clinical study then was conducted in 18 male-patients with evidence of radiographic characteristics related to asbestos exposure such as asbestosis or benign pleural disease as surrogate disease for mesothelioma clinical model.

Results
We investigate AWPC biological activity assessing its effect on mesothelin serum level, a glycoprotein with low expression in normal mesothelial cells and high expression in mesothelioma and asbestos related diseases. We also assess the AWPC effect on circulating miRNAs, as novel biomarkers of both cancer risk and response to therapeutic targets. While we found a small and not significant effect of AWPC on mesothelin serum levels, we observed that AWPC intake modulated 11 serum miRNAs related to gene-pathways connected to mesothelioma etiology and development. In terms of toxicity, we also did not observe any severe adverse effects associated to AWPC treatment, only gastro-intestinal symptoms were reported by five study participants.

Conclusions
We observed an interesting AWPC effect on miRNAs which targets modulate mesothelioma development. New and much larger clinical studies based on follow-up of workers exposed to asbestos are needed to corroborate the role of AWPC in prevention and early treatment of mesothelioma.

Trial registration
ClinicalTrials.gov, NCT02076672. Registered 03/03/2014.
Routine bacterial culture of proximal bone specimens during minor amputation in patients with diabetes‐related foot infections has little clinical utility in predicting re‐operation or ulcer healing
Authors: Voon Kimberly , Vo Uyen G. , Hand Robert , Hiew Jonathan , Ritter Jens Carsten , Hamilton Emma J. , Manning Laurens 
Published: August 2022

AbstractBackgroundTrans‐phalangeal and trans‐metatarsal amputation, collectively termed ‘minor amputations' are important procedures for managing infections of diabetes‐related foot ulcers (DFU). Following minor amputation, international guidelines recommend a prolonged course of antibiotics if residual infected bone on intra‐operative bone samples are identified, but the quality of the evidence underpinning these guidelines is low. In this study, we examined the concordance of microbiological results from proximal bone cultures compared to results from superficial wound swabs in relation to patient outcomes; with the aim of determining the utility of routinely obtaining marginal bone specimens.MethodsData was retrospectively collected on 144 individuals who underwent minor amputations for infected DFU at a large Australian tertiary hospital. Concordance was identified for patients with both superficial wound swabs and intra‐operative bone samples available. Patient outcomes were monitored up to 6 months post‐amputation. The primary outcome was complete healing at 6 months; and secondary outcome measures included further surgery and death. Mann Whitney U testing was performed for bivariate analyses of continuous variables, Chi‐Squared testing used for categorical variables and a logistic regression was performed with healing as the dependent variable.ResultsA moderate‐high degree of concordance was observed between microbiological samples, with 38/111 (35%) of patients having discordant wound swab and bone sample microbiology. Discordant results were not associated with adverse outcomes (67.2% with concordant results achieved complete healing compared with 68.6% patients with discordant results; P = 0.89). Revascularisation during admission (0.37 [0.13–0.96], P = 0.04) and amputation of the 5th ray (0.45 [0.21–0.94], P = 0.03) were independent risk factors for non‐healing.ConclusionThere was a moderate‐high degree of concordance between superficial wound swab results and intra‐operative bone sample microbiology in this patient cohort. Discordance was not associated with adverse outcomes. These results suggest there is little clinical utility in routinely collecting proximal bone as an adjunct to routine wound swabs for culture during minor amputation for an infected DFU.
Analysis of the risk factors and clinical features of Mycoplasma pneumoniae pneumonia with embolism in children: a retrospective study
Authors: Han Chunjiao , Zhang Tongqiang , Zheng Jiafeng , Jin Peng , Zhang Qi , Guo Wei , Xu Yongsheng 
Published: August 2022

Abstract
Background
Mycoplasmapneumoniae pneumonia (MPP) is a prevalent disease in community-acquired pneumonia among children. However, in addition to respiratory manifestations, it may also develop extra-pulmonary complications. Embolism is one of the uncommon extra-respiratory manifestations prone to severe sequelae and even death. This study aims to analyze the clinical features of MPP with embolism in children, and explore the associated risk factors of embolism in MPP patients.

Methods
A retrospective case–control analysis was performed on 48 children with MPP admitted to our hospital wards between January 2010 and December 2021. Embolism group comprised children with embolism by CTA or MRA results, whereas the non-embolism group comprised children with clinical suspicion of embolism but negative diagnostic imaging support. The clinical features, laboratory findings and imaging were analyzed to explore the risk factors for embolism in children with MPP.

Results
A total of 48 children with MPP were enrolled in the study (16 cases and 32 controls). In the embolism group, 10 patients (62.5%) had pulmonary embolism, 3 patients (18.75%) presented ventricle embolism, 2 patients (12.5%) presented cerebral and carotid artery embolism, one patient (6.25%) had a cerebral embolism, limb, and spleen, respectively. The univariate analysis revealed the maximum body temperature (Tmax), CRP, D-dimer (closest to CTA/MRA), the percentage of neutrophils (N%), pulmonary consolidation (⩾ 2/3 lobe), pleural effusion and atelectasis have significant differences between the embolism group and non-embolism group (P < 0.05). Multivariate logistic regression analysis showed that D-dimer (closest to CTA/MRA) > 3.55 mg/L [OR = 1.255 (95% CI: 1.025—1.537), P < 0.05], pulmonary consolidation (⩾ 2/3 lobe) [OR = 8.050 (95% CI: 1.341—48.327), P < 0.05], and pleural effusion [OR = 25.321 (95% CI: 2.738—234.205), P < 0.01] were independent risk factors for embolism in children with MPP.

Conclusion
In conclusion, MPP with embolism patients have more D-dimer values and severe radiologic manifestations.
Effectiveness and adherence to closed face shields in the prevention of COVID-19 transmission: a non-inferiority randomized controlled trial in a middle-income setting (COVPROSHIELD)
Authors: Varela Andrea Ramirez , Gurruchaga Alejandro Pacheco , Restrepo Silvia Restrepo , Martin Juan David , Landazabal Yessica Daniela Campaz , Tamayo-Cabeza Guillermo , Contreras-Arrieta Sandra , Caballero-Díaz Yuldor , Florez Luis Jorge Hernandez , González John Mario , Santos-Barbosa Juan Carlos , Pinzón José David , Yepes-Nuñez Juan José , Laajaj Rachid , Buitrago Gutierrez Giancarlo , Florez Martha Vives , Fuentes Castillo Janner , Quinche Vargas Gianni , Casas Andres , Medina Antonio , Behrentz Eduardo ,   on behalf of the CoVIDA Working Group, Guevara Yenny Paola Rueda , Sanchez Daniela Rodriguez , Guevara-Suarez Marcela , Hidalgo Marylin , Betancourt Paola 
Published: August 2022

Abstract
Background
The use of respiratory devices can mitigate the spread of diseases such as COVID-19 in community settings. We aimed to determine the effectiveness of closed face shields with surgical face masks to prevent SARS-CoV-2 transmission in working adults during the COVID-19 pandemic in Bogotá, Colombia.

Methods
An open-label non-inferiority randomized controlled trial that randomly assigned participants to one of two groups: the intervention group was instructed to wear closed face shields with surgical face masks, and the active control group was instructed to wear only surgical face masks. The primary outcome was a positive reverse transcription polymerase chain reaction test, IgG/IgM antibody test for SARS-CoV-2 detection, or both during and at the end of the follow-up period of 21 days. The non-inferiority limit was established at − 5%.

Results
A total of 316 participants were randomized, 160 participants were assigned to the intervention group and 156 to the active control group. In total, 141 (88.1%) participants in the intervention group and 142 (91.0%) in the active control group completed the follow-up. Primary outcome: a positive SARS-CoV-2 test result was identified in one (0.71%) participant in the intervention group and three (2.1%) in the active control group. In the intention-to-treat analysis, the absolute risk difference was − 1.40% (95% CI [− 4.14%, 1.33%]), and in the per-protocol analysis, the risk difference was − 1.40% (95% CI [− 4.20, 1.40]), indicating non-inferiority of the closed face shield plus face mask (did not cross the non-inferiority limit).

Conclusions
The use of closed face shields and surgical face masks was non-inferior to the surgical face mask alone in the prevention of SARS-CoV-2 infection in highly exposed groups. Settings with highly active viral transmission and conditions such as poor ventilation, crowding, and high mobility due to occupation may benefit from the combined use of masks and closed face shields to mitigate SARS-CoV-2 transmission.

Trial registration
ClinicalTrials.gov NCT04647305. Registered on November 30, 2020
Effect of high-flow nasal therapy on patient-centred outcomes in patients at high risk of postoperative pulmonary complications after cardiac surgery: a statistical analysis plan for NOTACS, a multicentre adaptive randomised controlled trial
Authors: Dawson Sarah N. , Chiu Yi-Da , Klein Andrew A. , Earwaker Melissa , Villar Sofia S. 
Published: August 2022

Abstract
Background
The NOTACS trial will assess the efficacy, safety and cost-effectiveness of high-flow nasal therapy (HFNT) compared to standard oxygen therapy (SOT) on the outcomes of patients after cardiac surgery.

Methods/design
NOTACS is an adaptive, international, multicentre, parallel-group, randomised controlled trial, with a pre-planned interim sample size re-estimation (SSR). A minimum of 850 patients will be randomised 1:1 to receive either HFNT or SOT. The primary outcome is days alive and at home in the first 90 days after the planned surgery (DAH90), with a number of secondary analyses and cost-effectiveness analyses also planned. The interim SSR will take place after a minimum of 300 patients have been followed up for 90 days and will allow for the sample size to increase up to a maximum of 1152 patients.

Results
This manuscript provides detailed descriptions of the design of the NOTACS trial, and the analyses to be undertaken at the interim and final analyses. The main purpose of the interim analysis is to assess safety and to perform a sample size re-estimation. The main purpose of the final analysis is to examine the safety, efficacy and cost-effectiveness of HFNT compared to SOT on the outcomes of patients after cardiac surgery.

Discussion
This manuscript outlines the key features of the NOTACS statistical analysis plan and was submitted to the journal before the interim analysis in order to preserve scientific integrity under an adaptive design framework. The NOTACS SAP closely follows published guidelines for the content of SAPs in clinical trials.

Trial registration
ISRCTN14092678. Registered on 13 May 2020.
Efficacy of manual acupuncture, electro-acupuncture, and warm acupuncture for knee osteoarthritis: study protocol for a randomized controlled trial
Authors: Chang Yiniu , Wu Nan , Zhang Zhenhua , Zhang Zhaoyang , Ren Binbin , Liu Feilai , Song Xiaolei , Wu Mingli , Feng Xiaodong , Yin Shuai 
Published: August 2022

Abstract
Background
Acupuncture is one of the most popular complementary and alternative treatments for knee osteoarthritis (KOA). There are many methods of acupuncture in the treatment of KOA, and the effects are different. According to our clinical observations and researches, it is found that manual acupuncture (MA), electro-acupuncture (EA), and warm acupuncture (WA) are used more frequently in the treatment of KOA, and the curative effects are satisfactory. However, there is currently a lack of efficacy comparison of efficacy between different acupuncture treatments, as well as a lack of standardized clinical research on the acupuncture treatment of KOA. Therefore, we will carry out a high-quality clinical randomized controlled trial to research the effect laws of MA, EA, and WA on KOA.

Methods/design
A total of 200 eligible participants with KOA will be randomly assigned to group A, B, C, or D in a ratio of 1:1:1:1. Patients in group A will receive MA, while those in group B, group C, and group D will be treated with EA, WA, and sham acupuncture (SA), respectively. Patients will be treated with acupuncture once a day, 30 min per session, 5 sessions per week for 4 weeks. The primary outcome is the change of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at week 4. The secondary outcomes include WOMAC, visual analog scale (VAS), Arthritis Quality of Life Measurement Scale Simplified Scale (AIMS2-SF), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and Credibility/Expectancy Questionnaire. The evaluation will be performed at baseline and weeks 4, 8, and 12 respectively after randomization.

Discussion
This is a randomized controlled trial. We will observe the clinical effect of MA, EA, and WA on KOA to research the effect laws of these three acupuncture treatments on KOA and set up standardized treatment programs for acupuncture for KOA.

Trial registration
China Clinical Trials Registry ChiCTR2100049526. Registered on August 2, 2021
Mesenchymal stem cells and their microenvironment
Authors: Liu Jiaxi , Gao Jinfang , Liang Zixie , Gao Chong , Niu Qing , Wu Fengping , Zhang Liyun 
Published: August 2022

AbstractMesenchymal stem cells (MSCs), coming from a wide range of sources, have multi-directional differentiation ability. MSCs play vital roles in immunomodulation, hematopoiesis and tissue repair. The microenvironment of cells often refers to the intercellular matrix, other cells, cytokines and humoral components. It is also the place for cells’ interaction. The stability of the microenvironment is pivotal for maintaining cell proliferation, differentiation, metabolism and functional activities. Abnormal changes in microenvironment components can interfere cell functions. In some diseases, MSCs can interact with the microenvironment and accelerate disease progression. This review will discuss the characteristics of MSCs and their microenvironment, as well as the interaction between MSCs and microenvironment in disease.
Scaffold-based delivery of mesenchymal stromal cells to diabetic wounds
Authors: Du Shanshan , Zeugolis Dimitrios I. , O’Brien Timothy 
Published: August 2022

AbstractFoot ulceration is a major complication of diabetes mellitus, which results in significant human suffering and a major burden on healthcare systems. The cause of impaired wound healing in diabetic patients is multifactorial with contributions from hyperglycaemia, impaired vascularization and neuropathy. Patients with non-healing diabetic ulcers may require amputation, creating an urgent need for new reparative treatments. Delivery of stem cells may be a promising approach to enhance wound healing because of their paracrine properties, including the secretion of angiogenic, immunomodulatory and anti-inflammatory factors. While a number of different cell types have been studied, the therapeutic use of mesenchymal stromal cells (MSCs) has been widely reported to improve delayed wound healing. However, topical administration of MSCs via direct injection has several disadvantages, including low cell viability and poor cell localization at the wound bed. To this end, various biomaterial conformations have emerged as MSC delivery vehicles to enhance cell viability and persistence at the site of implantation. This paper discusses biomaterial-based MSCs therapies in diabetic wound healing and highlights the low conversion rate to clinical trials and commercially available therapeutic products.
Immune recognition of syngeneic, allogeneic and xenogeneic stromal cell transplants in healthy retinas
Authors: Norte-Muñoz María , Gallego-Ortega Alejandro , Lucas-Ruiz Fernando , González-Riquelme María J. , Changa-Espinoza Yazmín I. , Galindo-Romero Caridad , Ponsaerts Peter , Vidal-Sanz Manuel , García-Bernal David , Agudo-Barriuso Marta 
Published: August 2022

AbstractBackgroundAdvanced therapies using adult mesenchymal stromal cells (MSCs) for neurodegenerative diseases are not effectively translated into the clinic. The cross talk between the transplanted cells and the host tissue is something that, despite its importance, is not being systematically investigated.MethodsWe have compared the response of the mouse healthy retina to the intravitreal transplantation of MSCs derived from the bone marrow in four modalities: syngeneic, allogeneic, xenogeneic and allogeneic with immunosuppression using functional analysis in vivo and histology, cytometry and protein measurementpost-mortem. Data were considered significant (p < 0.05) after nonparametric suitable statistical tests.ResultsTransplanted cells remain in the vitreous and are cleared by microglial cells a process that is quicker in allotransplants regardless of immunosuppression. All transplants cause anatomical remodelling which is more severe after xenotransplants. Xeno- and allotransplants with or without immunosuppression cause macro- and microglial activation and retinal functional impairment, being xenotransplants the most detrimental and the only ones that recruit CD45+Iba1−cells. The profile of proinflammatory cytokines changes in all transplantation settings. However, none of these changes affect the retinal ganglion cell population.ConclusionsWe show here a specific functional and anatomical retinal response depending on the MSC transplantation modality, an aspect that should be taken into consideration when conducting preclinical studies if we intend a more realistic translation into clinical practice.
Towards establishing human body-on-a-chip systems
Authors: Li Zhong Alan , Tuan Rocky S. 
Published: August 2022

AbstractBody-on-a-chip (BoC) platforms are established from multiple organs-on-chips (OoCs) to recapitulate the interactions between different tissues. Recently, Vunjak-Novakovic and colleagues reported the creation of a BoC system comprising four fluidically linked OoCs. Herein, the major innovations in their BoC system are discussed, followed by our future perspectives on enhancing the physiological relevance and scalability of BoCs for applications in studying disease mechanisms, testing potential therapeutics, and developing personalized medicine.