bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioinformatics strategies to identify differences in molecular biomarkers for ischemic stroke and myocardial infarction
Authors: Wang Min , Gao Yuan , Chen Huaqiu , Shen Ying , Cheng Jianjie , Wang Guangming
Published: November 2023

Ischemic strokes (ISs) are commonly treated by intravenous thrombolysis using a recombinant tissue plasminogen activator; however, successful treatment can only occur within 3 hours after the stroke. Therefore, it is crucial to determine the causes and underlying molecular mechanisms, identify molecular biomarkers for early diagnosis, and develop precise preventive treatments for strokes. We aimed to clarify the differences in gene expression, molecular mechanisms, and drug prediction approaches between IS and myocardial infarction (MI) using comprehensive bioinformatics analysis. The pathogenesis of these diseases was explored to provide directions for future clinical research. The IS (GSE58294 and GSE16561) and MI (GSE60993 and GSE141512) datasets were downloaded from the Gene Expression Omnibus database. IS and MI transcriptome data were analyzed using bioinformatics methods, and the differentially expressed genes (DEGs) were screened. A protein–protein interaction network was constructed using the STRING database and visualized using Cytoscape, and the candidate genes with high confidence scores were identified using Degree, MCC, EPC, and DMNC in the cytoHubba plug-in. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed using the database annotation, visualization, and integrated discovery database. Network Analyst 3.0 was used to construct transcription factor (TF) – gene and microRNA (miRNA) – gene regulatory networks of the identified candidate genes. The DrugBank 5.0 database was used to identify gene–drug interactions. After bioinformatics analysis of IS and MI microarray data, 115 and 44 DEGS were obtained in IS and MI, respectively. Moreover, 8 hub genes, 2 miRNAs, and 3 TFs for IS and 8 hub genes, 13 miRNAs, and 2 TFs for MI were screened. The molecular pathology between IS and MI presented differences in terms of GO and KEGG enrichment pathways, TFs, miRNAs, and drugs. These findings provide possible directions for the diagnosis of IS and MI in the future.
Relationship between thyroid function and dietary inflammatory index in Hashimoto thyroiditis patients
Authors: Chen Si , Peng Yan , Zhang Hao , Zou Yandun
Published: November 2023

Inflammation is closely related to the changes of thyroid function in Hashimoto thyroiditis patients. Certain nutrients or dietary habits can alter the levels of autoantibodies in Hashimoto thyroiditis. However, it remains unclear whether dietary inflammation affects thyroid function in patients with Hashimoto thyroiditis. The purpose of this study was to assess the relationship between dietary inflammation and thyroid function in Hashimoto thyroiditis patients using data from the National Health and Nutrition Examination Survey. We employed weighted multivariable linear regression, subgroup analyses, and interaction analysis to explore the relationship between thyroid function and dietary inflammatory index. We found that dietary inflammatory index was positively correlated with TSH and total T4. Interaction analysis found an interaction between urinary iodine concentration and FT3, but subgroup analysis for different levels of urinary iodine concentration did not get statistically significant results. Hashimoto thyroiditis patients with more pro-inflammatory diet habits had higher levels of TSH and TT4. In order to prevent hypothyroidism more effectively in patients with Hashimoto thyroiditis, it is essential to control dietary inflammation. However, it is still necessary to design a better prospective cohort study to verify the causal relationship.
Construction and validation of a transient receptor potential-related long noncoding RNA signature for prognosis prediction in breast cancer patients
Authors: Guo Qiaonan , Qiu Pengjun , Pan Kelun , Chen Jianpeng , Wang Baiwei , Lin Jianqing
Published: November 2023

Breast cancer (BC) is the most commonly diagnosed malignancy in women around the world. Accumulating evidence suggests that transient receptor potential (TRP) channels play a significant role in tumor progression and immune cell infiltration. Hence, we conducted the study to investigate the correlation between TRP-associated lncRNAs and the prognosis of breast carcinoma. In the current study, 33 TRP-associated genes were selected from a review published by Amrita Samanta et al, and the TRP-related lncRNAs were identified by Pearson analysis. Based on the sum of the expression levels of 12 lncRNAs provided by the Cancer Genome Atlas (TCGA), a TRP-associated lncRNA signature was established by using Cox regression analysis. According to the median value of the risk score in the training set, BC patients were separated into high- and low-risk groups. Subsequently, functional enrichment analysis was conducted on the differential expression genes (DEGs) between different risk groups. The Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression (ESTIMATE) Score was calculated by ESTIMATE, and the immune cell infiltration was evaluated by ssGSEA. Finally, the immune checkpoint gene expression levels, microsatellite instability (MSI), and immunophenoscore (IPS) were further assessed. The high-risk groups exhibited lower survival rates, while the low-risk groups showed higher survival rates. As a result, the DEGs between different risk groups were highly enriched in immune cell activation and immunoregulation. Besides, the ESTIMATE scores of patients in low-risk groups were higher than those in high-risk groups. The infiltration levels of several immune cells were remarkably elevated in low-risk groups, and various immune signatures were activated with a decreased risk score. Eventually, the TRP-associated lncRNA signature was confirmed with a highly potential ability to evaluate the immunotherapy response in breast carcinoma patients. The outcomes of the current study indicated that the 12-TRP-associated-lncRNA risk model was an independent prognostic risk factor for BC patients. This risk model could be closely related to the tumor immune microenvironment in BC. Our findings will provide new insights for future immunotherapy for BC treatment.
Telocytes and inflammation: A review
Authors: Zhang Yuhua , Tian Hu
Published: November 2023

Telocytes are a new type of interstitial cell with a diverse morphology and important functions, such as mechanical support, signal transduction, immune regulation, and tissue repair. In this paper, the origin and physiological and pathological functions of telocytes as well as their role in inflammation will be discussed, and the functions and targets of telocytes in inflammation will be fully reviewed, which may contribute to a new therapeutic strategy for inflammatory diseases in the future.
Identification and verification of m6A-related miRNAs correlated with prognosis and immune microenvironment in colorectal cancer
Authors: Qiu Xinze , Chen Da , Huang Shanpei , Chen Ni , Wu Jiangni , Liang Shengmei , Peng Peng , Qin Mengbin , Huang Jiean , Liu Shiquan
Published: November 2023

It’s well known that N6-methyladenosine (m6A) modification is the most abundant modification in multiple RNA species. miRNAs play important roles in m6A modification and are closely related with occurrence and development of colorectal cancer (CRC). Thus, the aim of this study was to identify the prognostic value of m6A-related miRNAs and explore the correlation between the miRNAs and immune microenvironment in CRC. The differentially expressed m6A regulators and differentially expressed miRNAs between CRC tissues and adjacent normal tissues were identified based on TCGA dataset, and the m6A-related miRNAs were screened. The CRC patients from TCGA were randomized (1:1) into training set and validation set, and the risk score was established in the training set. Next, risk score was verified in the validation set and GSE92928 from GEO datasets. Besides, the relationship among tumor mutational burden, immune microenvironment and risk score were analyzed. What’s more, RT-qPCR were used to explore the expression levels of the miRNAs in risk score between SW480 and SW620. A total of 29 m6A-related miRNAs were screened out, and a 5-differentially expressed miRNAs risk score was established. Kaplan–Meier analysis and ROC curves revealed the risk score could predict the prognosis of CRC, accurately. Similarly, the patients in the high-risk group had shorter overall survival in GSE92928. The risk score was relevant with the tumor mutational burden and immune infiltration, and the expression of HAVCR2 was significant difference between 2 risk groups. The expression levels of miR-328-3p, miR-3934-5p, miR-664b-5p and miR-3677-3p were down-regulated in SW620 compared with SW480, only the expression level of miR-200c-5p was up-regulated in SW620. The findings provided the new insights into the correlation between miRNAs and m6A regulators. The m6A-related miRNAs could predict the prognosis of CRC and provide the valuable information of immunotherapy in CRC patients.
Confusion in the monitoring of coagulation function in pregnant and neonate patients with severe disease: A case reports and brief literature review
Authors: Wang Yuefang , He Jiajing , Zhang Xia , Zhang Ge
Published: November 2023

Rationale:

Different populations have their own unique physiological and pathological characteristics. However, in specialized maternal and child hospitals, there is currently a lack of standardized methods for assessing coagulation dysfunction, both domestically and internationally.

Patient concerns:

A 19-day-old neonate was transferred to neonatal intensive care unit with cyanosis, nasal bleeding for 6 hours, and a consciousness disorder for 5 hours. A 33-year-old woman presented with hydramnios and a 39 + 3week intrauterine pregnancy. All indicators before delivery were normal, but postpartum hemorrhage occurred after delivery.

Diagnoses:

We retrospectively analyzed 1 neonate with pulmonary hemorrhage accompanied by thrombocytopenia and 1 pregnant patient with amniotic fluid embolism.

Interventions:

The new coagulation indicators, such as thrombin-antithrombin complex, plasmin-alpha 2 antiplasmin complex, thrombomodulin, and tissue plasminogen activator-plasminogen activator inhibitor-1 complex, have been indicated to be valuable. In neonates, it is necessary to continuously monitor special items combined with specific therapeutic agents, such as tranexamic acid. In cases where postpartum hemorrhage occurs with low fibrinogen levels, it is essential to effectively identify patients with severe amniotic fluid embolism from a high incidence of specimen clotting.

Outcomes:

The neonate’s oxygen saturation stabilized, and after 5 days of treatment with low molecular weight heparin, thrombin-antithrombin complex and plasmin-alpha 2 antiplasmin complex returned to normal levels. The pregnant began to remove the remaining thrombus, the patient’s condition recovered, and she had a good prognosis.

Lessons:

For pregnant and neonatal critical illnesses, it is necessary to develop personalized coagulation monitoring programs that provide realistic and reasonable treatment recommendations. Such programs should consider the unique physiological and pathological characteristics of different populations to ensure effective management of critically ill patients.
Clinical value of glucocorticoids for severe community-acquired pneumonia: A systematic review and meta-analysis based on randomized controlled trials
Authors: Peng Biao , Li Jin , Chen Minwei , Yang Xianghui , Hao Meng , Wu Feifei , Yang ZhiChao , Liu Da
Published: November 2023

Background:

Severe community-acquired pneumonia (sCAP) is characterized by severe symptoms and a poor prognosis, especially with the recent global impact of novel coronavirus in recent years. The use of glucocorticoids in sCAP is currently a subject of debate. To evaluate the clinical efficacy and safety of glucocorticoids and provide guidance for their rational use in clinical practice, we conducted this study.

Methods:

We searched PubMed, Web of Science, and China National Knowledge Infrastructure using the following search terms: “pneumonia”, “pneumonias”, “Pulmonary Inflammation”, “Pulmonary Inflammations”, “Lung Inflammation”, and “Lung Inflammations”. The primary outcomes included mortality and the length of hospital stay. The secondary outcomes included the duration of mechanical ventilation, duration of vasoactive drug use, gastrointestinal bleeding, and multiple infections. The Cochrane Collaboration was used to assess the risk of bias of the included studies. Stata/MP14 was used for meta-analysis.

Results:

These studies contained information on 1252 patients who received glucocorticoids and 1280 patients who did not. Meta-analysis showed that there was no difference in terms of mortality [risk ratio (RR) = 0.93, 95% confidence interval (CI): 0.81–1.07, P 
> .05], gastrointestinal bleeding (RR = 1.38, 95% CI: 0.83–2.30, P 
< 
.05), multiple infections (RR = 1.17, 95% CI: 0.90–1.53, P 
> .05) and length of hospital stay (mean difference [MD] = −0.87, 95% CI: −2.35 to 0.61, P 
> .05) between the hormonal and nonhormonal groups. However, there was a significant difference in the duration of mechanical ventilation (MD = −1.54; 95% CI, −1.89 to −1.12, P 
< 
.05) and the duration of use of vasoactive drugs (MD = −14.09, 95% CI: −15.72 to −12.46, P < .05).

Conclusion:

Glucocorticoids reduced the duration of mechanical ventilation duration and vasoactive drug use in sCAP patients without increasing the risk of adverse events including hyperglycemia and multiple infections. However, there was no significant difference in mortality or length of hospital stay in sCAP patients between glucocorticoid and non-glucocorticoid groups. Glucocorticoids could be recommended for patients with sCAP with respiratory failure or hemodynamic instability.
Rezūm water vapor thermal therapy in patients with benign prostatic hyperplasia: Initial real-world data from Japan
Authors: Obinata Daisuke , Mochida Junichi , Uehara Rio , Osawa Miyu , Hashimoto Sho , Nakahara Ken , Yoshizawa Tsuyoshi , Yamaguchi Kenya , Takahashi Satoru
Published: November 2023

Benign prostatic hyperplasia (BPH) is prevalent in older men. As surgery can be high risk in this group, minimally invasive procedures are preferrable. This study aimed to assess the initial results of minimally invasive Rezūm water vapor thermal therapy (WVTT) in patients with BPH. This single-center retrospective study included 25 consecutive patients with BPH who underwent WVTT between September 2022 and July 2023. Parameters including age, Charlson Comorbidity Index and Geriatric 8 (G8) scores, operative time, and number of vapor injections were evaluated. The International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score, and Core Lower Urinary Tract Symptom Score (CLSS) were used to assess symptoms before the procedure, and at 1 and 3 months after it. Urinary function indicators such as single voiding volume, maximum flow rate (MFR), and post-void residual volume were assessed at the same time points. The mean patient age was 76.0 years and the mean prostate volume was 54.8 mL. The mean G8 score was 14.4 and the Charlson Comorbidity Index score averaged 1.2. The mean operative time was 6.84 min, and included a mean of 4.8 vapor injections. Three months after WVTT, significant improvements were observed in the maximum flow rate (P = .02), post-void residual volume (P = .001), and urine volume (P < .001), as well as in the IPSS incomplete emptying (P = .01) and weak stream (P = .01) domains. No significant changes were observed in the remaining IPSS domains or in the Overactive Bladder Symptom Score or CLSS. This study provides the first report on Rezūm WVTT outcomes in Japan using the CLSS assessment tool. The initial results indicate a promising experience with this new treatment method. With a rapidly aging population, the incidence of BPH is expected to increase, making the minimally invasive Rezūm system a valuable addition to BPH treatment options.
Upregulated TC1 and downregulated Chibby were correlated with the aberrant β-catenin expression in laryngeal squamous cell carcinoma
Authors: Ren Gang , Ma Bingliang , Wang Jianqiu , Xu Jue , Zhang Xilin , Yin Chengyi
Published: November 2023

As an important member of Wnt/β-catenin signaling pathway, the aberrant expression of β-catenin has been implicated in many cancers. Chibby, a β-catenin binding partner, is an antagonist involved in this pathway. In contrast, thyroid cancer 1 (TC1) as an activator of this pathway can relieve the antagonistic activity of Chibby on the β-catenin-mediated transcription and is high expressed in human tumors. The objectives of this study were to examine the expression of TC1, Chibby, and β-catenin and investigate the association among them in laryngeal squamous cell carcinoma (LSCC). The expression of TC1, Chibby, β-catenin, c-Myc, Cyclin D1, and matrix metalloproteinase-7 (MMP-7) were examined by immunohistochemistry in samples from 53 LSCC patients. Compared with normal laryngeal squamous epithelium (NLSE), there were upregulated expression of TC1, downregulated expression of Chibby, and aberrant cytoplasmic expression of β-catenin in the LSCC tissues (P < .001). The high expression of TC1 was correlated with the tumor site, advanced TNM and T stage, lymphovascular invasion, and poor differentiation in LSCC tissues (P < .050). There were correlations between the aberrant expression of β-catenin and the tumor site, advanced TNM and T stage, lymphovascular invasion, perineurial invasion, and poor differentiation in LSCC tissues (P < .050). Upregulated TC1 and downregulated Chibby were correlated with aberrant expression of β-catenin (P < .001), but no correlation between them (P = .076). The percent of abnormal expression of β-catenin in LSCC was 96.00% in TC1+/Chibby−, 73.68% in TC1+/Chibby+, 0.00% in TC1-/Chibby−, and 0.00% in TC1-/Chibby + group (P < .001). High expression of c-Myc, Cyclin D1, and MMP-7 was observed in LSCC tissues (P < .001). There was statistically significant about the expression of Cyclin D1 and MMP-7 among the groups of TC1+/Chibby−, TC1+/Chibby+, TC1-/Chibby−, and TC1-/Chibby + (P < .001), but was not significance about the expression of c-Myc among them (P = .339). No association was found between overall survival and the expression of TC1, Chibby, and β-catenin (P > .05). The upregulated expression of TC1 and downregulated expression of Chibby were correlated with the aberrant expression of β-catenin and the high expression of Cyclin D1 and MMP-7 in LSCC tissues.
Effect of papillary muscle and trabeculae on left ventricular function analysis via computed tomography: A cross-sectional study
Authors: Kim Minji , You Seulgi , Ha Taeyang , Kim Tae Hee , Kang Doo Kyoung
Published: November 2023

Deciding whether to include or exclude the papillary muscles and trabeculae to blood pool is essential, because quantifications of left ventricular (LV) functional parameters and myocardial mass are significantly affected. As a result, such inclusion or exclusion might produce different indices for diagnosis and therapy. Using cardiac computed tomography (CT), we obtained standard values of the portion of papillary muscle and trabeculae in normal adults, and to find out how the inclusion or exclusion of papillary muscle and trabeculae affect LV functional parameters depending on the patient group. Excluding the papillary muscles from the LV mass results in easier automated contour detection using CT. The percentage portions of papillary muscle and trabeculae to LV end-diastolic volume (EDV) and LV mass (LVM) were 11.9 ± 5.6% and 20.2 ± 4.3%, respectively, significantly affecting disease diagnosis. Imaging should be consistent at follow-up and include or exclude the papillary muscles and trabeculae to avoid introducing significant differences between measurements.
Published trends and research hotspots of central venous catheter-associated thrombosis from 1973 to 2022: A scientometric analysis
Authors: Liu Zuoyan , Chen Xinxin , Tao Shiqi , You Jiuhong , Ma Hui , Huang Cheng
Published: November 2023

This study aims to explore the intellectual landscape and research hotspots in the central venous catheter-related thrombosis (CVC-RT) research field. Studies discussing CVC-RT published from 1973 to 2022 in the Web of Science Core Collection database were retrieved on February 24th, 2022. Citespace was used to perform a scientometric analysis to identify the intellectual landscape and research hotspots in the research fields of CVC-RT. A total of 4358 studies were retrieved, with an ascending trend in publication numbers. The United States of America was the most influential country. The Journal of Vascular Access published the most studies, and McMaster University was the most prolific institution. The results showed that the focus population of CVC-RT research has changed from pediatric patients to cancer patients, the management of CVC-RT has become more formal and standardized, and the focused CVC type has shifted to port and peripherally inserted central catheters. In addition, seventeen active burst keywords were detected, such as patient safety, clinical practice guidelines, and postthrombotic syndrome. This study comprehensively reviewed publications related to CVC-RT. The research topics on patient safety, clinical practice guidelines, and postthrombotic syndrome related to CVC-RT may be future hotspots.
Management of syncope in the Emergency Department: a European prospective cohort study (SEED)
Authors: Reed Matthew J. , Karuranga Suvi , Kearns David , Alawiye Salma , Clarke Ben , Möckel Martin , Karamercan Mehmet , Janssens Kelly , Riesgo Luis Garcia-Castrillo , Torrecilla Francisco Moya , Golea Adela , Fernández Cejas Juan Antonio , Lupan-Muresan Eugenia Maria , Zaimi Edmond , Nuernberger Alexander , Rennét Ondřej , Skjaerbaek Christian , Polyzogopoulou Effie , Imecz Judit , Groff Paolo , Camilleri Rene , Cimpoesu Diana , Jovic Miljan , Miró Òscar , Anderson Rory , Laribi Said ,   on behalf of the SEED investigators
Published: November 2023

Background and importance

In 2018, the European Society of Cardiology (ESC) produced syncope guidelines that for the first-time incorporated Emergency Department (ED) management. However, very little is known about the characteristics and management of this patient group across Europe.

Objectives

To examine the prevalence, clinical presentation, assessment, investigation (ECG and laboratory testing), management and ESC and Canadian Syncope Risk Score (CSRS) categories of adult European ED patients presenting with transient loss of consciousness (TLOC, undifferentiated or suspected syncope).

Design

Prospective, multicentre, observational cohort study.

Settings and participants

Adults (≥18 years) presenting to European EDs with TLOC, either undifferentiated or thought to be of syncopal origin.

Main results

Between 00:01 Monday, September 12th to 23:59 Sunday 25 September 2022, 952 patients presenting to 41 EDs in 14 European countries were enrolled from 98 301 ED presentations (n = 40 sites). Mean age (SD) was 60.7 (21.7) years and 487 participants were male (51.2%). In total, 379 (39.8%) were admitted to hospital and 573 (60.2%) were discharged. 271 (28.5%) were admitted to an observation unit first with 143 (52.8%) of these being admitted from this. 717 (75.3%) participants were high-risk according to ESC guidelines (and not suitable for discharge from ED) and 235 (24.7%) were low risk. Admission rate increased with increasing ESC high-risk factors; 1 ESC high-risk factor; n = 259 (27.2%, admission rate=34.7%), 2; 189 (19.9%; 38.6%), 3; 106 (11.1%, 54.7%, 4; 62 (6.5%, 60.4%), 5; 48 (5.0%, 67.9%, 6+; 53 (5.6%, 67.9%). Furthermore, 660 (69.3%), 250 (26.3%), 34 (3.5%) and 8 (0.8%) participants had a low, medium, high, and very high CSRS respectively with respective admission rates of 31.4%, 56.0%, 76.5% and 75.0%. Admission rates (19.3–88.9%), use of an observation/decision unit (0–100%), and percentage high-risk (64.8–88.9%) varies widely between countries.

Conclusion

This European prospective cohort study reported a 1% prevalence of syncope in the ED. 4 in 10 patients are admitted to hospital although there is wide variation between country in syncope management. Three-quarters of patients have ESC high-risk characteristics with admission percentage rising with increasing ESC high-risk factors.
The association between levosimendan and mortality in patients with sepsis or septic shock: a systematic review and meta-analysis
Authors: Ge Zengzheng , Gao Yanxia , Lu Xin , Yu Shiyuan , Qin Mubing , Gong Chao , Walline Joseph Harold , Zhu Huadong , Li Yi
Published: November 2023

Background

Levosimendan is increasingly being used in patients with sepsis or septic shock because of its potential to improve organ function and reduce mortality. We aimed to determine if levosimendan can reduce mortality in patients with sepsis or septic shock via meta-analysis.

Evidence sources and study selection

We comprehensively searched the PubMed, Embase, Web of Science, and Cochrane Library databases from inception through 1 October 2022. Literature evaluating the efficacy of levosimendan in patients with sepsis or septic shock was included.

Data extraction and outcome measurements

Two reviewers extracted data and assessed study quality. A meta-analysis was performed to calculate an odds ratio (OR), 95% confidence intervals (CI), and P-values for 28-day mortality (primary outcome). Secondary outcomes included changes in indexes reflecting cardiac function before and after treatment, changes in serum lactate levels in the first 24 h of treatment, and the mean SOFA score during the study period. Safety outcomes included rates of tachyarrhythmias and total adverse reactions encountered with levosimendan.

Results

Eleven randomized controlled trials were identified, encompassing a total of 1044 patients. After using levosimendan, there was no statistical difference between groups for 28-day mortality (34.9% and 36.2%; OR: 0.93; 95% CI [0.72–1.2]; P = 0.57; I2 = 0%; trial sequential analysis-adjusted CI [0.6–1.42]) and sequential organ failure assessment (SOFA) score, and more adverse reactions seemed to occur in the levosimendan group, although the septic shock patient’s heart function and serum lactate level improved.

Conclusion

There was no association between the use of levosimendan and 28-day mortality and SOFA scores in patients with septic shock, though there was statistically significant improvement in cardiac function and serum lactate.
Disparities in Access to Spasticity Chemodenervation Specialists in the US: A Retrospective Cross-Sectional Study
Authors: Kazerooni Rashid , Healy Sean , Verduzco-Gutierrez Monica
Published: November 2023

Objective

Explore variations in access to spasticity chemodenervation specialists across several geographical, ethnic, racial, and population density factors.

Design

A retrospective cross-sectional study on Medicare Provider Utilization and Payment Data. Providers with substantial adult spasticity chemodenervation practices (SASCPs) were included. Ratios were assessed across geographical regions as well as hospital referral regions (HRRs). A multivariate linear regression model for the top 100 HRRs by beneficiary population was created, using backward stepwise selection to eliminate variables with p-values >0.10 from final model.

Results

A total of 566 providers with SASCPs were included. Unadjusted results showed lower access in non-urban versus urban areas in the form of higher patient:provider ratios (83,106 vs 51,897). Access was also lower in areas with ≥25% Hispanic populations (141,800 vs 58,600). Multivariate linear regression results showed similar findings with urban HRRs having significantly lower ratios (-45,764 [p = 0.004] versus non-urban) and areas with ≥25% Hispanic populations having significantly higher ratios (+96,249 [p = 0.003] versus <25% Hispanic areas).

Conclusions

Patients in non-urban and highly Hispanic communities face inequities in access to chemodenervation specialists. The Medicare data set analyzed only includes 12% of the US patient population, however this elderly national cross-sectional cohort represents a saturated share of patients needing access to spasticity chemodenervation therapy. Future studies should venture to confirm whether findings are limited to this specialization, and strategies to improve access for these underserved communities should be explored.
Application of PainDETECT in pediatric chronic pain: how well does it identify neuropathic pain and its characteristics?
Authors: Hess Courtney W. , Van Orden Amanda R. , Mesaroli Giulia , Stinson Jennifer N. , Borsook David , Simons Laura E.
Published: November 2023

Introduction:

Neuropathic pain (NP) arises from nerve damage or disease, and when not defined, it can impair function and quality of life. Early detection allows for interventions that can enhance outcomes. Diagnosis of NP can be difficult if not properly evaluated. PainDETECT is a NP screening tool developed and successfully used in adults.

Objectives:

We evaluated the validity of painDETECT in a pediatric population.

Methods:

Adolescents and young adults (10–19 years old) completed painDETECT and quantitative sensory testing (QST), which assessed mechanical allodynia and hyperalgesia, common symptoms of NP. Pain diagnoses, including neuropathic pain (n = 10), were collected through documentation in the medical chart. Descriptive statistics were used to examine age, gender, pain diagnoses, and painDETECT scores. Kruskal–Wallis H tests were conducted to examine differences in QST results across painDETECT categorizations.

Results:

Youth with chronic pain (N = 110, Mage = 15.08 ± 2.4 years, Nfemale = 88) and peers without pain (N = 55, Mage = 15.84 ± 3.9 years, Nfemale = 39) completed the painDETECT. The painDETECT scores for youth with pain (M = 12.7 ± 6.76) were significantly higher than those for peers without pain (M = 2.05 ± 2.41). PainDETECT demonstrated 80% sensitivity and 33% specificity in a pediatric population. Individuals who screened positively on the PainDETECT had significantly higher mechanical allodynia (M = 0.640 ± 0.994) compared with those who screened negatively (M = 0.186 ± 0.499; P = 0.016).

Conclusion:

PainDETECT demonstrated the ability to screen for NP, and QST mechanical allodynia results were consistent with a positive NP screen. Results of the study offer preliminary support for the ongoing assessment of the painDETECT as a brief, inexpensive, and simple-to-use screening tool for pediatric patients with primary pain complaints.
The Association of Organizational, Environmental, and Staffing Characteristics of Residential Care Facilities and the Risk Rating of Statutory Notifications: A Cross-Sectional Study in Ireland
Authors: Dunbar Paul , McGrane Niall , Keyes Laura M.
Published: November 2023

Objectives

Safety incidents (SIs) are an indicator of quality in health and social care services. Safety incident research has largely focused on acute health care settings. We aimed to examine the association of organizational, environmental, and staffing characteristics of residential care facilities (RCFs) and severity of regulatory SI notifications.

Methods

This was a retrospective analysis of SI notifications to the regulator for social care in Ireland received in 2018 and 2019. The mean risk rating of SI notifications for each RCF was used as the outcome. Regression analysis was conducted for the association of RCF characteristics (beds, staff to bed ratio, staff full-time equivalent (FTE), nurse to bed ratio, nurse FTE, number of RCF operated by the service provider, non-statutory or statutory provider) and the outcome, separately for nursing homes and residential disability services.

Results

A total of 53,268 SI notifications were received. One thousand nine hundred RCFs were operational during the period: 594 (31.3%) for RCF-Nursing home and 1304 (68.7%) for RCF-Disability. For nursing homes, in the most adjusted model, the number of RCF operated by a provider (βcoefficient [95% confidence interval] = 0.508 [0.223–0.793]) was positively associated with mean risk rating of SI. For disability services, the following characteristics were positively associated in the most adjusted model: beds (0.081; 0.060–0.101), staff to bed ratio (0.068; 0.017–0.120), nurse to bed ratio (0.356; 0.044–0.667), staff FTE (0.029; 0.015–0.042), and number of RCF operated by a provider (0.067; 0.050–0.084).

Conclusions

Various modifiable organizational, environmental, and staffing characteristics and severity of SI notifications were associated in this study, most of which were related to RCF-Disability. Policymakers and providers of social care services should be cognizant of the relationship of these characteristics and severity of SI, when designing and planning residential care.
68Ga-FAPI-04 PET/CT in Assessment of Fibroblast Activation in Keloids
Authors: Wang Jiarou , Yu Nanze , Wang Guochang , Wang Rongxi , Li Linlin , Jiang Yuanyuan , Sui Huimin , Sun Yixin , Li Zhijin , Long Xiao , Zhu Zhaohui
Published: November 2023

Purpose

Keloids are benign fibroproliferative disorders characterized by the massive proliferation of fibroblasts. Fibroblast activation plays a key role in the invasive growth of keloids. Therefore, a prospective pilot study was conducted to explore the value of 68Ga-FAPI-04 PET/CT in the assessment of keloids activity.

Patients and Methods

Twenty-five patients with keloid were enrolled to conduct 68Ga-FAPI-04 PET/CT. All patients accepted surgery to remove part of the lesions within 1 week. SUVmean and SUVmax were measured for semiquantitative analysis and compared with the Vancouver Scar Scale, Laser Speckle Contrast Imaging, pathology, and immunohistochemical stains.

Results

A total of 123 lesions were detected in 25 patients, most of which were distributed in the anterior chest wall. The 68Ga-FAPI-04 uptake was significantly different at different sites (P < 0.0001). There was uptake heterogeneity within the keloid lesions, and a significant difference was found between the edge and center of some large lesions. The SUVmax of 68Ga-FAPI-04 showed significantly correlation with the Vancouver Scar Scale (r = 0.565, P < 0.0001) moderately and the Laser Speckle Contrast Imaging parameters mildly. The SUVmax of 68Ga-FAPI-04 had a moderate correlation with FAPI expression (r = 0.520, P = 0.022). Moreover, collagen, fibroblast activator protein, and Ki-67 expression were found higher at the edges of keloid tissue than in the center.

Conclusions

68Ga-FAPI-04 PET/CT can reflect the distribution characteristics of activated fibroblasts in keloid tissue and may provide a novel method for keloid evaluation for further fibroblast-related therapies.
Elevated 18F-AIF-FAPI-04 Uptake in Hepatic Hemangioma
Authors: Sun Yuyun , Cai Xin , Wang Zheng , Sun Yun , Cheng Jingyi
Published: November 2023

A 67-year-old woman who was diagnosed with intrahepatic cholangiocellular carcinoma (CCC) by biopsy underwent 18F-FDG and 18F-AIF-FAPI-04 PET/CT for initial and treatment assessment. In addition to CCC, she had a history of hepatic hemangioma for 3 years. 18F-FDG PET/CT images showed increased uptake in CCC, but no uptake in hemangiomas. However, images on 18F-AIF-FAPI-04 PET/CT indicated negative 18F-AIF-FAPI-04 uptake in CCC, but intense activity in hemangiomas. Our case illustrates that hepatic hemangioma demonstrated intense 18F-AIF-FAPI-04 uptake, and final diagnosis should be made with caution.
The relationship between the number of COVID-19 vaccines and infection with Omicron ACE2 inhibition at 18-months post initial vaccination in an adult cohort of Canadian paramedics
Authors: Yap Justin , Kayda Iryna , Asamoah-Boaheng Michael , Haig Scott , Kirkham Tracy , Cheskes Sheldon , Demers Paul , Goldfarb David , Grunau Brian E.
Published: November 2023

The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has rapidly evolved since late 2019, due to highly transmissible Omicron variants. While most Canadian paramedics have received COVID-19 vaccination, the optimal ongoing vaccination strategy is unclear. We investigated neutralizing antibody (NtAb) response against wild-type (WT) Wuhan Hu-1 and Omicron BA.4/5 lineages based on the number of doses and past SARS-CoV-2 infection, at 18 months post-initial vaccination (with a Wuhan Hu-1 platform mRNA vaccine [BNT162b2 or mRNA-1273]). Demographic information, previous COVID-19 vaccination, infection history, and blood samples were collected from paramedics 18 months post-initial mRNA COVID-19 vaccine dose. Outcome measures were ACE2 percent inhibition against Omicron BA.4/5 and WT antigens. We compared outcomes based on number of vaccine doses (two vs. three) and previous SARS-CoV-2 infection status, using the Mann-Whitney U test. Of 657 participants, the median age was 40 years (IQR 33–50) and 251 (42 %) were females. Overall, median percent inhibition to BA.4/5 and WT was 71.61 % (IQR 39.44–92.82) and 98.60 % (IQR 83.07–99.73), respectively. Those with a past SARS-CoV-2 infection had a higher median percent inhibition to BA.4/5 and WT, when compared to uninfected individuals overall and when stratified by two or three vaccine doses. When comparing two vs. three WT vaccine doses among SARS-CoV-2 negative participants, we did not detect a difference in BA.4/5 percent inhibition, but there was a difference in WT percent inhibition. Among those with previous SARS-CoV-2 infection(s), when comparing two vs. three WT vaccine doses, there was no observed difference between groups. These findings demonstrate that additional Whttps://www.covid19immunitytaskforce.ca/citf-databank/#accessing
https://www.covid19immunitytaskforce.ca/citf-databank/#accessinguhan Hu-1 platform mRNA vaccines did not improve NtAb response to BA.4/5, but prior SARS-CoV-2 infection enhances NtAb response.
Galleria mellonella as a superficial model for Malassezia globosa and its treatment
Authors: Torres Maritza , Diaz-Ortiz Juliana , Davis Michael G , Schwartz James R. , Celis Ramírez Adriana Marcela
Published: November 2023

Introduction. Malassezia globosa is a yeast species that belongs to the mycobiota of humans and animals, associated with dermatological disorders such as dandruff. This is a chronic scalp skin disorder characterized by flaking and itching. Treatments include commercial shampoo with different formulations that contain antifungal activities like Zinc pyrithione or Piroctone Olamine. The effectiveness of these formulations have been evaluated for decades  for dandruff symptom relief of volunteers. To date, non-mammalian, in-vivo methods exist to test formulations of these actives.
Aim. To evaluate in vivo in Galleria mellonella larva, two commercial antifungal shampoos (Shampoo with 1% ZPT & 1.6% Zinc Carbonate and shampoo with 0.5% PO) against this species.
Methodology. G. mellonella larvae were inoculated with M. globosa on abraded cuticular surface. Then, integument cell viability, histological changes, and fungal burden were evaluated.
Results. Larvae inoculated with M. globosa showed higher lesion melanization and tissue damage. In addition, M. globosa population showed to increase over time. Concerning the shampoo’s effectiveness, both formulations significantly reduced M. globosa burden and tissue damage.
Conclusion. G. mellonella larvae were allowed to evaluate M. globosa superficial infection and antifungal effectiveness. Shampoos with ZPT and PO showed a positive effect on inoculated larvae.
Antiviral innate immune memory in alveolar macrophages following SARS-CoV-2 infection
Authors: Lercher Alexander , Cheong Jin-Gyu , Jiang Chenyang , Hoffmann Hans-Heinrich , Ashbrook Alison W. , Yin Yue S. , Quirk Corrine , DeGrace Emma J. , Chiriboga Luis , Rosenberg Brad R. , Josefowicz Steven Z. , Rice Charles M.
Published: November 2023

Pathogen encounter results in long-lasting epigenetic imprinting that shapes diseases caused by heterologous pathogens. The breadth of this innate immune memory is of particular interest in the context of respiratory pathogens with increased pandemic potential and wide-ranging impact on global health. Here, we investigated epigenetic imprinting across cell lineages in a disease relevant murine model of SARS-CoV-2 recovery. Past SARS-CoV-2 infection resulted in increased chromatin accessibility of type I interferon (IFN-I) related transcription factors in airway-resident macrophages. Mechanistically, establishment of this innate immune memory required viral pattern recognition and canonical IFN-I signaling and augmented secondary antiviral responses. Past SARS-CoV-2 infection ameliorated disease caused by the heterologous respiratory pathogen influenza A virus. Insights into innate immune memory and how it affects subsequent infections with heterologous pathogens to influence disease pathology could facilitate the development of broadly effective therapeutic strategies.
Safe plant Hsp90 adjuvants elicit an effective immune response against SARS-CoV2 derived RBD antigen
Authors: Ramos-Duarte Victor A. , Orlowski Alejandro , Jaquenod de Giusti Carolina , Corigliano Mariana G. , Legarralde Ariel , Mendoza-Morales Luisa F. , Atela Agustín , Sánchez Manuel A. , Sander Valeria A. , Angel Sergio O. , Clemente Marina
Published: November 2023

To better understand the role of pHsp90 adjuvant in immune response modulation, we proposed the use of the Receptor Binding Domain (RBD) of the Spike protein of SARS-CoV2, the principal candidate in the design of subunit vaccines. We evaluated the humoral and cellular immune responses against RBD through the strategy “protein mixture” (Adjuvant + Antigen). The rRBD adjuvanted with rAtHsp81.2 group showed a higher increase of the anti-rRBD IgG1, while the rRBD adjuvanted with rNbHsp90.3 group showed a significant increase of anti-rRBD IgG2b/2a. These results were consistent with the cellular immune response analysis. Spleen cell cultures from rRBD+rNbHsp90.3-immunized mice showed significantly increased IFN-γ production. In contrast, spleen cell cultures from rRBD+rAtHsp81.2-immunized mice showed significant increased IL-4 levels. Finally, vaccines adjuvanted with rNbHsp90.3 induced higher neutralizing antibody responses compared to those adjuvanted with rAtHsp81.2. To know whether both chaperones must form complexes to generate an effective immune response, we performed co-immunoprecipitation (co-IP) assays. The results indicated that the greater neutralizing capacity observed in the rRBD adjuvanted with rNbHsp90.3 group would be given by the rRBD-rNbHsp90.3 interaction rather than by the quality of the immune response triggered by the adjuvants. These results, together with our previous results, provide a comparative benchmark of these two novel and safe vaccine adjuvants for their capacity to stimulate immunity to a subunit vaccine, demonstrating the capacity of adjuvanted SARS-CoV2 subunit vaccines. Furthermore, these results revealed differences in the ability to modulate the immune response between these two pHsp90s, highlighting the importance of adjuvant selection for future rational vaccine and adjuvant design.
Temporal dynamics of skin microbiota and immune correlates in psoriasis patients receiving systemic treatment
Authors: Liu Su-Hsun , Huang Yu-Huei , Weng Hao-Jui , Tsai Tsen-Fang , Yang Huang-Yu , Chen Leslie Y , Chiu Yen-Ling , Yu Hsiao-Yun , Chiu Yi-Chieh , Ng Chao-Yu , Chang Ya-Ching , Hui Chung-Yee R , Huang Yhu-Chering
Published: November 2023

Background

How skin microbiota in psoriasis patients responded to systematic therapeutics remained unknown.

Objectives

To profile temporal shifts in transcriptionally active skin microbiota in psoriasis patients receiving systemic therapies.

Methods

We prospectively enrolled 61 psoriasis patients and 29 skin-healthy controls in 2015-2019. Using RNA-based 16S rRNA gene sequencing, we analyzed 969 samples from skin lesions and compared microbial abundance and diversity by therapeutic classes and disease severity.

Results

Lesional microbiota in patients on conventional systemics and TNF-αinhibitor was different in relative abundances in Firmicutes (7.83% higher, adjusted P < 0.001) and Proteobacteria (6.98% lower, adjusted P < 0.01) from that in patients on anti-interleukin monoclonal antibodies (anti-ILAb) at baseline. The only difference during treatment was a 1.47% lower abundance in Bacteroides associated with nonbiologics use (adjusted P < 0.01). We identified no indicator taxa by disease severity at baseline yet noticed that a minor relative reduction inCorynebacteriumsp. was associated with clinical responses to treatment.

Compared to anti-ILAb, TNF-αinhibitor and nonbiologics were associated with -0.21 lower Shannon Diversity (adjusted P < 0.01) and 0.03 higher Shannon Evenness (adjusted P < 0.01). Results of ordinated principal coordinates analysis revealed that, lesional microbiota from patients of these 3 therapeutic groups was compositionally distinct. Our work also demonstrated concurrent changes in clonal shifts in systemic T cell receptor clonotypes that were associated with systemic use of biologics.

Conclusions

Community abundances and diversities of skin microbiota may be useful in distinguishing skin microbiota from patients receiving different systemic therapeutics. Specifically, use of anti-ILAb and TNF-αinhibitor was associated with sample-wise microbial abundances and diversities, but not richness, over time. These findings highlighted the potential utility of skin microbiota as biomarkers for personalized treatment plans in patients with moderate-to-severe psoriasis.