bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between IL-10 gene polymorphisms (− 1082 A/G, -819 T/C, -592 A/C) and hepatocellular carcinoma: a meta-analysis and trial sequential analysis
Authors: Mei Teresa Tan Yen , Aung Htar Htar , Tung Wong Siew , Naing Cho
Published: September 2023

Background

The carcinogenesis of hepatocellular carcinoma is complicated, and genetic factor may have the role in the malignant transformation of liver cells. IL-10 gene polymorphisms have been investigated for their potential roles in hepatocellular carcinoma This study aimed to investigate the relationship between polymorphisms of IL-10 (-1082 A/G, -819 T/C, -592 A/C), and hepatocellular carcinoma by performing a meta-analysis with eligible individual studies.

Methods

This study followed the PRISMA 2020 Checklist. Relevant studies were searched in health-related databases. The Newcastle-Ottawa Scale criteria were used to evaluate the studies quality. Pooled odds ratio (OR) and its 95% confidence interval (CI) were used to determine the strength of association between each polymorphism and hepatocellular carcinoma using five genetic models. Stratification was done by ethnic groups. Trial sequential analysis (TSA) was performed to determine the required information size.

Results

Fifteen case-control studies (n = 8182) were identified. Overall, the heterozygous model showed a marginal significant association only between IL-10 (-1082 A/G) and hepatocellular carcinoma risk (OR: 0.82, 95% CI: 0.67-1.00, 9 studies). On stratification, IL-10 (-1082 A/G) was significantly associated with hepatocellular carcinoma risk in the non-Asian population under dominant (OR: 0.62, 95% CI: 0.45–0.86, 4 studies), heterozygous (OR: 0.60, 95% CI: 0.43–0.85) and allelic models (OR: 0.79, 95% CI: 0.64–0.99). IL-10 (-819 T/C) was significantly associated with hepatocellular carcinoma risk only among non-Asians under the dominant (OR: 1.47, 95% CI: 1.02–2.13, 8 studies), recessive (OR: 1.99, 95% CI: 1.03–3.86, and homozygous models (OR: 2.18, 95% CI: 1.13–4.23). For IL-10 (-592 A/C) with 11 studies, there was no significant association with hepatocellular carcinoma in all five genetic models (P values > 0.5). TSA plots indicated that the information size for firm evidence of effect was sufficient only for the analysis of IL-10 (-592 A/C), but not for the − 1082 A/G or -819 T/C.

Conclusions

Findings suggest that IL-10 (-1082 A/G and − 819 T/C) polymorphisms are associated with hepatocellular carcinoma in ethnic-specific manner. However, this evidence is not conclusive because the sample size was insufficient. IL-10 (-592 A/C) polymorphism was not associated with hepatocellular carcinoma albeit with sufficient information size. Future well-designed large case-control studies on IL-10 (-1082 A/G and − 819 T/C) with different ethnicities are recommended.
MicroRNA 29a therapy for CEACAM6-expressing lung adenocarcinoma
Authors: Son Seung-Myoung , Yun Jieun , Kim Dong-Wook , Jung Young-Suk , Han Sang-Bae , Lee Yong Hee , Han Hye Sook , Woo Chang Gok , Lee Ho-Chang , Lee Ok-Jun
Published: September 2023

Background

Non-coding microRNAs (miRNAs) play critical roles in tumor progression and hold great promise as therapeutic agents for multiple cancers. MicroRNA 29a (miR-29a) is a tumor suppressor miRNA that inhibits cancer cell growth and tumor progression in non-small cell lung cancer. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), which plays an important role in lung cancer progression, has been identified as a target of miR-29a. Here, we evaluated the therapeutic efficacy of a peptide vector capable of delivering miR-29a intracellularly using the acidic tumor microenvironment in a lung adenocarcinoma xenograft mouse model.

Methods

A miRNA delivery vector was constructed by tethering the peptide nucleic acid form of miR-29a to a peptide with a low pH-induced transmembrane structure (pHLIP) to enable transport of the miRNAs across the plasma membrane. Tumor suppressive effects of pHLIP-miR29a on lung adenocarcinoma development in vivo were assessed using a BALB/c xenograft model injected with A549 cells.

Results

Incubation of A549 cells with pHLIP-miR-29a at an acidic pH downregulated endogenous CEACAM6 expression and reduced cell viability. Intravenous injection of the mice with pHLIP-miR-29a inhibited tumor growth by up to 18.1%. Intraperitoneal injection of cisplatin reduced tumor volume by 29.9%. Combined pHLIP-miR-29a + cisplatin treatment had an additive effect, reducing tumor volume up to 39.7%.

Conclusions

Delivery of miR-29a to lung adenocarcinoma cells using a pHLIP-mediated method has therapeutic potential as a unique cancer treatment approach.
Association between work-related physical activity and depressive symptoms in Korean workers: data from the Korea national health and nutrition examination survey 2014, 2016, 2018, and 2020
Authors: Joo Min Jeong , Jang Ye Seul , Jang Yun Seo , Park Eun-Cheol
Published: September 2023

Background

The workplace experiences of employees can impact their mental health. Depressive symptoms, which are experienced by workers, are a mental health issue that deserves attention. Several studies have evaluated physical activity to prevent possible depression in workers in a work environment, however, research on physical activity and depression symptoms directly related to work is still insufficient. Therefore, we aimed to identify the relationship between work-related physical activity and depression among South Korean workers.

Methods

We used data from the Korean National Health and Nutrition Examination Survey conducted in 2014, 2016, 2018, and 2020, which included 31,051 participants. We excluded, participants aged < 15 years (n = 4,663), unemployed and economically inactive persons (n = 9,793), those who did not engage in work-related physical activities (n = 1,513) and leisure physical activities (n = 1,558), or those with missing data (n = 450). Therefore, the study included 13,074 participants. Work-related activity was measured by self-reporting, while depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9). Multiple logistic regression analysis was performed to investigate the association between work-related physical symptoms and depressive symptoms among workers.

Results

Individuals who engaged in work-related physical activity had higher PHQ-9 scores than those who did not (male: odds ratio [OR]: 1.71, 95% confidence interval [CI]: 1.16–2.52; female: OR: 2.33, 95% CI: 1.66–3.29). High-intensity work-related physical activity significantly increased depressive symptoms (male: OR: 2.15, 95% CI: 1.04–4.43; female: OR: 2.90, 95% CI: 1.46–5.96). When classified according to the severity of depressive symptom, the OR of depressive symptoms of workers engaged in both leisure and work-related physical activities tended to be lower than that of those engaged only in work-related physical activities.

Conclusion

Korean workers who engaged in work-related physical activities exhibited more depressive symptoms. Therefore, our findings suggest that balancing work-related and leisure physical activities can help Korean workers prevent development of depressive symptoms.
Application of impulse oscillometry to detect interstitial lung disease and airway disease in adults with rheumatoid arthritis
Authors: Cheng Wen-Chien , Chang Shih-Hsin , Chen Wei-Chun , Wu Bing-Ru , Chen Chia-Hung , Lin Chi-Chien , Hsu Wu-Huei , Lan Joung-Liang , Chen Der-Yuan
Published: September 2023

Background

We conducted a retrospective observational study to explore the potential application of impulse oscillometry (IOS) as an alternative to high-resolution computed tomography (HRCT) for detecting pulmonary involvement in patients with rheumatoid arthritis (RA) because clinically evident interstitial lung disease (ILD) and airway involvement are common in this population.

Methods

We enrolled 72 patients with RA who underwent pulmonary function tests (PFTs) and IOS between September 2021 and September 2022. We aimed to identify the PFT and IOS variables associated with lung diseases shown on HRCT images.

Results

In our cohort of 72 patients, 48 underwent HRCT; of these, 35 had airway disease or ILD and 13 showed no obvious abnormalities on HRCT. Abnormal IOS and PFT parameters were observed in 34 and 23 patients, respectively, with abnormal HRCT images. The predicted percentages for forced vital capacity, the ratio of forced expiratory volume in the first one second to forced vital capacity, and forced mid-expiratory flow value were significantly lower in patients with abnormal HRCT. Lung resistance at 5 Hz, difference in resistance between 5 and 20 Hz, resonant frequency (Fres), and reactance area were higher in these patients and reactance at 5 Hz was lower. Compared to other parameters, Fres > 14.14 was significantly associated with alterations in HRCT and may be used as an indicator for monitoring disease.

Conclusion

Fres > 14.14 is significantly associated with lung involvement in RA patients. Performance of spirometry with IOS is more beneficial than spirometry alone for evaluating lung involvement in RA patients.
Comparison of the effects of nitrogen-, sulfur- and combined nitrogen- and sulfur-deprivations on cell growth, lipid bodies and gene expressions in Chlamydomonas reinhardtii cc5373-sta6
Authors: Gonzalez David I. , Ynalvez Ruby A.
Published: September 2023

Background

Biofuel research that aims to optimize growth conditions in microalgae is critically important. Chlamydomonas reinhardtii is a green microalga that offers advantages for biofuel production research. This study compares the effects of nitrogen-, sulfur-, and nitrogen and sulfur- deprivations on the C. reinhardtii starchless mutant cc5373-sta6. Specifically, it compares growth, lipid body accumulation, and expression levels of acetyl-CoA carboxylase (ACC) and phosphoenolpyruvate carboxylase (PEPC).

Results

Among nutrient-deprived cells, TAP-S cells showed significantly higher total chlorophyll, cell density, and protein content at day 6 (p < 0.05). Confocal analysis showed a significantly higher number of lipid bodies in cells subjected to nutrient deprivation than in the control over the course of six days; N deprivation for six days significantly increased the size of lipid bodies (p < 0.01). In comparison with the control, significantly higher ACC expression was observed after 8 and 24 h of NS deprivation and only after 24 h with N deprivation. On the other hand, ACC and PEPC expression at 8 and 24 h of S deprivation was not significantly different from that in the control. A significantly lower PEPC expression was observed after 8 h of N and NS deprivation (p < 0.01), but a significantly higher PEPC expression was observed after 24 h (p < 0.01).

Conclusions

Based on our findings, it would be optimum to cultivate cc5373-sta6 cells in nutrient deprived conditions (-N, -S or –NS) for four days; whereby there is cell growth, and both a high number of lipid bodies and a larger size of lipid bodies produced.
Patients’ experiences of temporomandibular disorders and related treatment
Authors: Ilgunas Aurelia , Fjellman-Wiklund Anncristine , Häggman-Henrikson Birgitta , Lobbezoo Frank , Visscher Corine M. , Durham Justin , Lövgren Anna
Published: September 2023

Background

Temporomandibular disorders (TMD) are common and therefore managed by dentists on a daily basis. However, patients with TMD consistently go undetected and therefore untreated in dentistry. The reasons for these shortcomings have not been fully explored, specifically with regard to patients’ perspectives. Therefore, this study aimed to explore patients’ experiences of TMD and related treatment, with special focus on the experiences of having TMD, factors related to seeking care, and perspectives on received treatment.

Methods

Purposive sampling was used to recruit adult patients at the Public Dental Health services (PDHS) in the Region of Västerbotten, Sweden, during 2019. Individual semi-structured interviews were conducted and analysed using Qualitative Content Analysis. Sixteen patients were interviewed (ten women and six men, 20–65 years). The interviews probed the patients’ perspectives of having TMD, seeking care, and receiving treatment. All participants were also examined according to the Diagnostic Criteria for TMD (DC/TMD) and qualified for at least one DC/TMD diagnosis.

Results

The data analysis led to the main theme Seeking care when the situation becomes untenable, but dental care fails to meet all needs. The patients expressed worry and social discomfort because of the symptoms but still strived to have an as normal daily life as possible. However, severe symptoms and associated consequences compelled them to seek professional help. Experiences of distrust together with challenges to access the PDHS were identified and related to the patients’ unfulfilled expectations.

Conclusions

Patients’ reported experiences indicate that receiving timely and appropriate care is more of an unfulfilled expectation than the current state of management of patients with TMD in dentistry.
One year of COVID-19 in dental health services in Norway: psychological impact, risk perceptions and vaccination status
Authors: Shabestari M. , Ansteinsson V. E. , Hovden E. A. S. , Stangvaltaite-Mouhat L. , Mdala I. , Skudutyte-Rysstad R. , Uhlen-Strand M. M.
Published: September 2023

Background

Increased psychological pressure on oral healthcare professionals (OHP) due to COVID-19 has been shown, yet little is known about the long-term psychological impacts. We aimed to study the psychological impact of COVID-19 and associated factors including perceived risk and preparedness and vaccination status among OHP in the first year after the lockdown period in Norway.

Methods

A structured questionnaire sent electronically to dentists, dental hygienists and dental assistants inquired experiences and perceptions during the second year following the outbreak in Norway. The questionnaire comprised a COVID-19 fear scale and questions about risk perception, preparedness and vaccination status. Exploratory factor analysis (EFA) and Structural Equation Modeling (SEM) were used to assess psychological impact, perception of risk and preparedness according to vaccination status of the respondents.

Results

The majority of the 708 respondents were female (92.8%), had ten or more years of work experience (67.1%), and worked in public dental clinics (95.9%). Fears and concerns related to COVID-19 were common, 72.6% feared getting infected and 85.4% feared infecting others. Of the 642 respondents who agreed that their workplaces handled the situation well, 55.6% were fully vaccinated. Three factors were retrieved from EFA: Insecurity, Instability and Infection. SEM showed that females were more concerned with Infection, and respondents with long clinical experience were less likely to express fear about Instability. Fully vaccinated individuals felt more insecure about becoming infected, and those agreeing that their workplaces handled the current situation well were concerned with Insecurity.

Conclusions

Despite widespread perception of adequate preparedness and high vaccine coverage, a considerable psychological impact and high levels of fear of COVID-19 were observed among the majority of OHP. Fully vaccinated individuals had a larger psychological burden than not fully vaccinated and those with unknown vaccination status. These findings can inform means and interventions to reduce negative impacts of fear in populations with a high psychological burden.
Assessment of retrospective collection of EQ-5D-5L in a US COVID-19 population
Authors: Sun Xiaowu , Di Fusco Manuela , Puzniak Laura , Coetzer Henriette , Zamparo Joann M. , Tabak Ying P. , Cappelleri Joseph C.
Published: September 2023

Background

It is imperative to evaluate health related quality of life (HRQoL) pre-COVID-19, but there is currently no evidence of the retrospective application of the EuroQol 5-Dimension, 5 level version (EQ-5D-5L) for COVID-19 studies.

Methods

Symptomatic patients with SARS-CoV-2 at CVS Health US test sites were recruited between 01/31/2022-04/30/2022. Consented participants completed the EQ-5D-5L questionnaire twice: a modified version where all the questions were past tense to retrospectively assess pre-COVID-19 baseline QoL, and the standard version in present tense to assess current HRQoL. Duncan’s new multiple range test was adopted for post analysis of variance pairwise comparisons of EQ visual analog scale (EQ VAS) means between problem levels for each of 5 domains. A linear mixed model was applied to check whether the relationship between EQ VAS and utility index (UI) was consistent pre-COVID-19 and during COVID-19. Matching-adjusted indirect comparison was used to compare pre-COVID-19 UI and EQ VAS scores with those of the US population. Lastly, Cohen’s d was used to quantify the magnitude of difference in means between two groups.

Results

Of 676 participants, 10.2% were age 65 or more years old, 73.2% female and 71.9% white. Diabetes was reported by 4.7% participants and hypertension by 11.2%. The estimated coefficient for the interaction of UI-by-retrospective collection indicator (0 = standard prospective collection, 1 = retrospective for pre-COVID-19), -4.2 (SE: 3.2), P = 0.197, indicates that retrospective collection does not significantly alter the relationship between EQ VAS and UI. After adjusting for age, gender, diabetes, hypertension, and percent of mobility problems, the predicted means of pre-COVID-19 baseline EQ VAS and UI were 84.6 and 0.866, respectively. Both means were close to published US population norms (80.4 and 0.851) compared to those observed (87.4 and 0.924). After adjusting for age, gender, diabetes, and hypertension, the calculated ES between pre-COVID-19 and COVID-19 for UI and EQ VAS were 0.15 and 0.39, respectively. Without retrospectively collected EQ-5D-5L, using US population norms tended to underestimate the impact of COVID-19 on HRQoL.

Conclusion

At a group level the retrospectively collected pre-COVID-19 EQ-5D-5L is adequate and makes it possible to directly evaluate the impact of COVID-19 on HRQoL. (ClinicalTrials.gov NCT05160636)
Prehospital transportation of severe penetrating trauma victims in Sweden during the past decade: a police business?
Authors: Renberg Mattias , Dahlberg Martin , Gellerfors Mikael , Rostami Amir , Günther Mattias , Rostami Elham
Published: September 2023

Introduction

Sweden is facing a surge of gun violence that mandates optimized prehospital transport approaches, and a survey of current practice is fundamental for such optimization. Management of severe, penetrating trauma is time sensitive, and there may be a survival benefit in limiting prehospital interventions. An important aspect is unregulated transportation by police or private vehicles to the hospital, which may decrease time but may also be associated with adverse outcomes. It is not known whether transport of patients with penetrating trauma occurs outside the emergency medical services (EMS) in Sweden and whether it affects outcome.

Method

This was a retrospective, descriptive nationwide study of all patients with penetrating trauma and injury severity scores (ISSs) ≥ 15 registered in the Swedish national trauma registry (SweTrau) between June 13, 2011, and December 31, 2019. We hypothesized that transport by police and private vehicles occurred and that it affected mortality.

Result

A total of 657 patients were included. EMS transported 612 patients (93.2%), police 10 patients (1.5%), and private vehicles 27 patients (4.1%). Gunshot wounds (GSWs) were more common in police transport, 80% (n = 8), compared with private vehicles, 59% (n = 16), and EMS, 32% (n = 198). The Glasgow coma scale score (GCS) in the emergency department (ED) was lower for patients transported by police, 11.5 (interquartile range [IQR] 3, 15), in relation to EMS, 15 (IQR 14, 15) and private vehicles 15 (IQR 12.5, 15). The 30-day mortality for EMS was 30% (n = 184), 50% (n = 5) for police transport, and 22% (n = 6) for private vehicles. Transport by private vehicle, odds ratio (OR) 0.65, (confidence interval [CI] 0.24, 1.55, p = 0.4) and police OR 2.28 (CI 0.63, 8.3, p = 0.2) were not associated with increased mortality in relation to EMS.

Conclusion

Non-EMS transports did occur, however with a low incidence and did not affect mortality. GSWs were more common in police transport, and victims had lower GCS scorescores when arriving at the ED, which warrants further investigations of the operational management of shooting victims in Sweden.
Tuberous sclerosis complex: a case report and literature review
Authors: Li Yanlin , Si Zhihua , Zhao Wei , Xie Cong , Zhang Xu , Liu Ju , Liu Jinzhi , Xia Zhangyong
Published: September 2023

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with different initial symptoms and complex clinical manifestations. A 14-year-old female patient presented with persistent fever and severe headache. Medical imaging examinations revealed multiple abnormal intracranial lesions. The patient had previously been misdiagnosed with “encephalitis and acute disseminated encephalomyelitis” after visiting numerous hospitals. Eventually, by combing the characteristics of the case and genetic testing results, the patient was diagnosed with TSC accompanied by Mycoplasma pneumoniae infection. The purpose of this case report and literature review is to improve understanding of the clinical diagnosis and treatment of TSC so as to avoid misdiagnosis, missed diagnosis, and overtreatment.
Protocol for a randomized controlled trial of endoscopic ultrasound guided celiac plexus neurolysis (EUS-CPN) with vs without bupivacaine
Authors: Esmail Eslam , Paquin Sarto C , Sahai Anand V
Published: September 2023

Background

Pancreatic cancer is a devastating disease with less than 5% 5-year survival. Inoperable patients often present with pain. Randomized controlled trial have shown that endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) improves pain control. It is usually performed by injecting bupivacaine followed by absolute alcohol around the celiac axis.

Study design

Single center, randomized, double blind controlled trial of EUS-CPN with and without bupivacaine in patients with inoperable malignancy (pancreatic or other) involving the celiac plexus. The study was approved by research ethics board with approval number of 2022-9969, 21.151 and registered on ClinicalTrials.gov (NCT04951804).

Discussion

We hypothesize that bupivacaine is superfluous and may actually reduce pain control by diluting the neurolytic effect of alcohol. Bupivacaine is also potentially dangerous in that it may produce serious adverse events such as arrythmias and cardiac arrest if inadvertently injected intravascularly.

Conclusion

This randomized trial is designed to assess whether bupivacaine is of any value during EUS-CPN.
Genetic diversity of Aedes aegypti and Aedes albopictus from cohabiting fields in Hainan Island and the Leizhou Peninsula, China
Authors: Zhao Minghui , Ran Xin , Bai Yu , Ma Zu , Gao Jian , Xing Dan , Li Chunxiao , Guo Xiaoxia , Jian Xianyi , Liu Wei , Liao Yun , Chen Kan , Zhang Hengduan , Zhao Tongyan
Published: September 2023

Background

Aedes aegypti and Ae. albopictus are important human arbovirus vectors that can spread arboviral diseases such as yellow fever, dengue, chikungunya and Zika. These two mosquito species coexist on Hainan Island and the Leizhou Peninsula in China. Over the past 40 years, the distribution of Ae. albopictus in these areas has gradually expanded, while Ae. aegypti has declined sharply. Monitoring their genetic diversity and diffusion could help to explain the genetic influence behind this phenomenon and became key to controlling the epidemic of arboviruses.

Methods

To better understand the genetic diversity and differentiation of these two mosquitoes, the possible cohabiting areas on Hainan Island and the Leizhou Peninsula were searched between July and October 2021, and five populations were collected. Respectively nine and 11 microsatellite loci were used for population genetic analysis of Ae. aegypti and Ae. albopictus. In addition, the mitochondrial coxI gene was also selected for analysis of both mosquito species.

Results

The results showed that the mean diversity index (PIC and SI values) of Ae. albopictus (mean PIC = 0.754 and SI = 1.698) was higher than that of Ae. aegypti (mean PIC = 0.624 and SI = 1.264). The same results were also observed for the coxI gene: the genetic diversity of all populations of Ae. albopictus was higher than that of Ae. aegypti (total H = 45 and Hd = 0.89958 vs. total H = 23 and Hd = 0.76495, respectively). UPGMA dendrogram, DAPC and STRUCTURE analyses showed that Ae. aegypti populations were divided into three clusters and Ae. albopictus populations into two. The Mantel test indicated a significant positive correlation between genetic distance and geographic distance for the Ae. aegypti populations (R2 = 0.0611, P = 0.001), but the correlation was not significant for Ae. albopictus populations (R2 = 0.0011, P = 0.250).

Conclusions

The population genetic diversity of Ae. albopictus in Hainan Island and the Leizhou Peninsula was higher than that of Ae. aegypti. In terms of future vector control, the most important and effective measure was to control the spread of Ae. albopictus and monitor the population genetic dynamics of Ae. aegypti on Hainan Island and the Leizhou Peninsula, which could theoretically support the further elimination of Ae. aegypti in China.

Graphical Abstract
Novel CSF biomarkers for diagnosis and integrated analysis of neuropsychiatric systemic lupus erythematosus: based on antibody profiling
Authors: Ni Jiali , Chen Chen , Wang Shuangan , Liu Xuan , Tan Liping , Lu Li , Fan Yu , Hou Yayi , Dou Huan , Liang Jun
Published: September 2023

Background

Neuropsychiatric systemic lupus erythematosus (NPSLE), with various morbidities and multiple manifestations in the central nervous system, remains a limited standard for diagnosis. Our study was to discover novel biomarkers for improving the diagnostic efficiency for NPSLE.

Methods

We performed a quantitative planar protein antibody microarray to screen 1000 proteins in cerebrospinal fluid from controls, systemic lupus erythematosus (SLE, non-NPSLE) patients, and NPSLE patients. Differentially expressed proteins (DEPs) as candidate biomarkers were developed into a custom multiplexed protein antibody array for further validation in an independent larger cohort. Subsequently, we used least absolute shrinkage and selection operator regression (LASSO) analysis and multivariable logistic regression analysis for optimizing feature selection and constructing a diagnostic model. A receiver operating characteristic curve (ROC) was generated to assess the effectiveness of the models.

Results

The expression of 29 proteins in CSF was significantly altered in the comparison of the three groups. We selected 17 proteins as candidate biomarkers in accordance with protein interaction analysis. In the larger cohort, we identified 5 DEPs as biomarkers for NPSLE, including TCN2, CST6, KLK5, L-selectin, and Trappin-2. The diagnostic model included 3 hub proteins (CST6, TCN2, KLK5) and was best at discriminating NPSLE from SLE patients. These CSF biomarkers were also highly associated with disease activity. In addition, there were 6 molecules with remarkable changes in NPSLE CSF and hippocampus, which indicated the consistency of the environment in the brain and the promising molecular targets in the pathogenesis of NPSLE.

Conclusions

The dual-chips screening strategy demonstrated KLK5, L-selectin, Trappin-2, TCN2, and CST6 as CSF biomarkers for diagnosing NPSLE.
Severity of Schistosoma haematobium co-infection with malaria in school-children is potentially modulated by host CD14 gene variants
Authors: Oboh-Imafidon Mary A. , Torbit Sabrina M. , Jacob Swathi , Schroeter Marissa N. , Tucker Ashley R. , Ojurongbe Olusola , Thomas Bolaji N.
Published: September 2023

Objective

Schistosomiasis remains a chronic disease of global importance, especially in many rural areas of the world where co-infection with Plasmodium falciparum is common. It is critical to decipher the role of single or co-infected disease scenarios on immune system regulation in such individuals and how such co-infections can either ameliorate or complicate immune response and the consequent disease outcome. First, 10 ml of urine samples, collected between 10:00 am and 2:00 pm, was filtered for diagnosis of schistosomiasis, while egg count, indicative of disease severity, was determined by microscopy. Furthermore, genomic DNA samples extracted from dried blood spots collected on filter paper from one hundred and forty-four Schistosoma haematobium-infected school-children was tested for P. falciparum parasite positivity by an allele-specific nested-PCR analysis of merozoite surface protein (msp)-1 and -2 genes and a real-time PCR assay. In addition, among P. falciparum parasite-positive individuals, we carried out a Taqman SNP genotyping assay to extrapolate the effect of host CD14 (-159 C/T; rs2569190) genetic variants on schistosome egg count.

Results

Of the 144 individuals recruited, P. falciparum parasite positivity with msp-1 gene were 34%, 43% and 55% for MAD20, RO33 and K1 alleles respectively. Of the co-infected individuals, CD14 genetic variants ranged from 18.8% vs 21.5%, 33.3% vs 44.4%, 9.7% vs 11.8% for single versus schistosome co-infection for the wild type (CC), heterozygous (CT) and mutant (TT) variants respectively. Though the mean egg count for co-infected individuals with CD14 wild type (33.7 eggs per 10 ml of urine) and heterozygote variants (37.5 eggs per 10 ml of urine) were lower than that of schistosome infection alone (52.48 and 48.08 eggs/10 ml of urine respectively), it lacked statistical significance (p-value 0.12 and 0.29), possibly reflecting the benefit of the CD14 activation in schistosome plus malaria co-infection and not schistosome infection alone. In addition, the lower mean egg count in co-infected individuals reveal the benefit of downstream Th1 immune response mitigated by CD14 innate activation that is absent in schistosome infection alone.
REM sleep is associated with the volume of the cholinergic basal forebrain in aMCI individuals
Authors: André Claire , Martineau-Dussault Marie-Ève , Daneault Véronique , Blais Hélène , Frenette Sonia , Lorrain Dominique , Hudon Carol , Bastien Célyne , Petit Dominique , Lafrenière Alexandre , Thompson Cynthia , Montplaisir Jacques , Gosselin Nadia , Carrier Julie
Published: September 2023

Background

Rapid-eye movement (REM) sleep highly depends on the activity of cholinergic basal forebrain (BF) neurons and is reduced in Alzheimer’s disease. Here, we investigated the associations between the volume of BF nuclei and REM sleep characteristics, and the impact of cognitive status on these links, in late middle-aged and older participants.

Methods

Thirty-one cognitively healthy controls (66.8 ± 7.2 years old, 13 women) and 31 participants with amnestic Mild Cognitive Impairment (aMCI) (68.3 ± 8.8 years old, 7 women) were included in this cross-sectional study. All participants underwent polysomnography, a comprehensive neuropsychological assessment and Magnetic Resonance Imaging examination. REM sleep characteristics (i.e., percentage, latency and efficiency) were derived from polysomnographic recordings. T1-weighted images were preprocessed using CAT12 and the DARTEL algorithm, and we extracted the gray matter volume of BF regions of interest using a probabilistic atlas implemented in the JuBrain Anatomy Toolbox. Multiple linear regressions were performed between the volume of BF nuclei and REM sleep characteristics controlling for age, sex and total intracranial volume, in the whole cohort and in subgroups stratified by cognitive status.

Results

In the whole sample, lower REM sleep percentage was significantly associated to lower nucleus basalis of Meynert (Ch4) volume (β = 0.32, p = 0.009). When stratifying the cohort according to cognitive status, lower REM sleep percentage was significantly associated to both lower Ch4 (β = 0.48, p = 0.012) and total BF volumes (β = 0.44, p = 0.014) in aMCI individuals, but not in cognitively unimpaired participants. No significant associations were observed between the volume of the BF and wake after sleep onset or non-REM sleep variables.

Discussion

These results suggest that REM sleep disturbances may be an early manifestation of the degeneration of the BF cholinergic system before the onset of dementia, especially in participants with mild memory deficits.
Diagnostic and prognostic value of cerebrospinal fluid SNAP-25 and neurogranin in Creutzfeldt-Jakob disease in a clinical setting cohort of rapidly progressive dementias
Authors: Bentivenga Giuseppe Mario , Baiardi Simone , Mastrangelo Andrea , Zenesini Corrado , Mammana Angela , Polischi Barbara , Capellari Sabina , Parchi Piero
Published: September 2023

Background

The levels of synaptic markers synaptosomal-associated protein 25 (SNAP-25) and neurogranin (Ng) have been shown to increase early in the cerebrospinal fluid (CSF) of patients with Creutzfeldt-Jakob disease (CJD) and to have prognostic potential. However, no validation studies assessed these biomarkers' diagnostic and prognostic value in a large clinical setting cohort of rapidly progressive dementia.

Methods

In this retrospective study, using commercially available immunoassays, we measured the levels of SNAP-25, Ng, 14–3-3, total-tau (t-tau), neurofilament light chain (NfL), and phospho-tau181 (p-tau) in CSF samples from consecutive patients with CJD (n = 220) or non-prion rapidly progressive dementia (np-RPD) (n = 213). We evaluated and compared the diagnostic accuracy of each CSF biomarker and biomarker combination by receiver operating characteristics curve (ROC) analyses, studied SNAP-25 and Ng CSF concentrations distribution across CJD subtypes, and estimated their association with survival using multivariable Cox regression analyses.

Results

CSF SNAP-25 and Ng levels were higher in CJD than in np-RPD (SNAP-25: 582, 95% CI 240–1250 vs. 115, 95% CI 78–157 pg/ml, p < 0.0001; Ng: 841, 95% CI 411–1473 vs. 390, 95% CI 260–766 pg/ml, p < 0.001). SNAP-25 diagnostic accuracy (AUC 0.902, 95% CI 0.873–0.931) exceeded that of 14–3-3 (AUC 0.853, 95% CI 0.816–0.889), t-tau (AUC 0.878, 95% CI 0.845–0.901), and the t-tau/p-tau ratio (AUC 0.884, 95% CI 0.851–0.916). In contrast, Ng performed worse (AUC 0.697, 95% CI 0.626–0.767) than all other surrogate biomarkers, except for NfL (AUC 0.649, 95% CI 0.593–0.705). SNAP-25 maintained a relatively high diagnostic value even for atypical CJD subtypes (AUC 0.792, 95% CI 0.729–0.854). In Cox regression analyses, SNAP-25 levels were significantly associated with survival in CJD (hazard ratio [HR] 1.71 95% CI 1.40–2.09). Conversely, Ng was associated with survival only in the most rapidly progressive CJD subtypes (sCJD MM(V)1 and gCJD M1) (HR 1.81 95% CI 1.21–2.93).

Conclusions

In the clinical setting, CSF SNAP-25 is a viable alternative to t-tau, 14–3-3, and the t-tau/p-tau ratio in discriminating the CJD subtypes from other RPDs. Additionally, SNAP-25 and, to a lesser extent, Ng predict survival in CJD, showing prognostic power in the range of CSF t-tau/14–3-3 and NfL, respectively.
PRevalence of the Eosinophilic Phenotype Among SeveRE asthma patients in Lebanon: results of the PREPARE study
Authors: Abi Saleh Wajdi , Alameh Zuhair , Aoun Bacha Zeina , Bahous Joudy , Bou Khalil Pierre , Chahine Zahia , Chami Hassan , Dabar Georges , Dheiny Hassan , Dib Alfred , farhat Dany , Irani Carla , Juvelekian Georges , Kanj Nadim , Mansour Bassam , Riachi Moussa , Waked Mirna , Yassine Mohamad , Youakim Carole , Zeinedine Salah , Zaitoun Fares
Published: September 2023

Background

The prevalence of eosinophilic asthma in Lebanon, one of the most severe phenotypes among severe asthma, is not known. This study aimed at determining the prevalence of the eosinophilic phenotype defined as an eosinophil count ≥ 300 cells/mm3 among severe asthma patients in Lebanon.

Methods

The Lebanese Chapter of the PREPARE study was a national, multicenter, cross-sectional observational study. Patients aged ≥ 12 years with severe asthma were identified and prospectively enrolled during clinic visits and completed the Global Initiative for Asthma (GINA) assessment of asthma control questionnaire. Patients’ health characteristics were collected from medical records and blood samples were obtained for measurement of serum IgE levels and blood eosinophils count.

Results

Overall, 101 patients (with mean age of 46.3 ± 17.0 years and 73.27% females) with severe asthma were included and, among them, 37% had eosinophilic phenotype, 67.3% had atopic phenotype with IgE > 100 IU/mL and 25.7% patients had overlapping atopic and eosinophilic phenotypes. Close to 80% had late-onset asthma, beyond 12 years of age, and around 85% had at least one severe exacerbation in the 12 months prior to study enrolment. The majority of participants [64.4%] had uncontrolled asthma, 24.7% had partially controlled symptoms and 10.9% had controlled symptoms. 19.8% of participants were on chronic oral corticosteroids, 78.2% had short course treatment of corticosteroids and all were prescribed a combination of inhaled corticosteroids and long-acting beta-agonist.

Conclusions

The majority of patients with severe asthma were uncontrolled of which 37% present with an eosinophilic phenotype, which should be taken into consideration for better management of these patients in view of the novel phenotype-specific therapeutic options.
A case of possible anaphylaxis to ASA and structurally unrelated NSAIDs
Authors: Edgerley Sarah , Kim Harold
Published: September 2023

Background

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used classes of medications, and are among the leading causes of drug hypersensitivity. NSAIDs hypersensitivity reactions are classified by symptom involvement and NSAIDs subclass cross-reactivity. Reactions varying from cutaneous involvement to respiratory symptoms can be triggered by multiple NSAIDs subclasses. Anaphylaxis, while rare, can be induced by a single NSAID, with tolerability of other structurally unrelated subclasses. Reactions that fall outside of these traditional categories are deemed “blended reactions”. We report a unique case of possible anaphylaxis to acetylsalicylic acid (ASA) and ibuprofen, two structurally dissimilar NSAIDs, indicating a severe blended reaction outside of the typical NSAIDs hypersensitivity reaction categories.

Case presentation

An otherwise healthy 45 year old woman was referred to the Allergy and Immunology clinic after developing acute onset dyspnea, lip swelling, and generalized urticaria with ibuprofen use requiring treatment with intramuscular epinephrine in the emergency department. She previously tolerated ibuprofen, naproxen, and acetaminophen and had no history of urticaria, angioedema, asthma, or nasal polyps. She underwent an oral challenge to ASA whereby she developed urticaria and throat irritation with rebound symptoms requiring 2 doses of intramuscular epinephrine. On subsequent visits she passed treatment dose acetaminophen and celecoxib challenges. She was counseled to avoid all other NSAIDs and ASA desensitization was offered should this medication be clinically indicated in the future.

Conclusions

NSAIDs hypersensitivity reactions can be triggered by individual NSAIDs with tolerance of other subclasses or by multiple structurally unrelated NSAIDs due to COX-1 inhibition. Determining the type of reaction (NERD, NECD, NIUA, SNIUAA, or SNIDHR) allows for appropriate oral challenges and safe alternative therapy recommendations. However, not all clinical reactions fit perfectly into these categories. Patients may also develop blended reactions. Our case highlights a severe blended reaction to multiple unrelated NSAIDs, including likely anaphylaxis to ASA. We note the utility of drug provocation tests (DPTs) to identify safe alternative medication options, as well as the importance of performing DPTs in settings properly equipped to assess and manage severe hypersensitivity reactions including anaphylaxis.
Sinopharm (HB02)-associated vaccine-induced immune thrombotic thrombocytopenia: a case report
Authors: Sistanizad Mohammad , Sabaghian Tahereh , Amini Hossein , Hadavand Fahimeh , Nabavi Mahmood , Kouchek Mehran , Miri Mir Mohammad , Salarian Sara , Shojaei Seyedpouzhia , Moradi Omid
Published: September 2023

Background

Vaccine-induced thrombotic thrombocytopenia is associated with the coronavirus disease 2019 vaccines. It has been reported by vector-based vaccines. To the best of our knowledge, there is no report about vaccine-induced thrombotic thrombocytopenia in whole-virus vaccines. We are presenting the first case of vaccine-induced thrombotic thrombocytopenia with this type of vaccine.

Case presentation

An 18-year-old male Caucasian patient with complaints of severe abdominal, low back, and lower extremity pain presented to the medical center. He received the first dose of the Sinopharm (HB02) vaccine against coronavirus disease 2019 10 days before hospital attendance. In the laboratory examination, decreased platelet count and increased D-dimer were observed. During hospital admission, the diagnosis of pulmonary embolism was reached. He received vaccine-induced thrombotic thrombocytopenia therapy consisting of intravenous immune globulin and direct oral anticoagulant. Platelet count increased and he was discharged after 1 month.

Conclusion

This case highlights the possibility of vaccine-induced thrombotic thrombocytopenia occurrence by whole-virus coronavirus disease 2019 vaccines. Compared with vector-based vaccines, this phenomenon is rare for whole-virus vaccines. More studies on this type of vaccine regarding thrombotic thrombocytopenia should be considered.
Patient-specific iPSC-derived cardiomyocytes reveal aberrant activation of Wnt/β-catenin signaling in SCN5A-related Brugada syndrome
Authors: Cai Dongsheng , Wang Xiaochen , Sun Yaxun , Fan Hangping , Zhou Jingjun , Yang Zongkuai , Qiu Hangyuan , Wang Jue , Su Jun , Gong Tingyu , Jiang Chenyang , Liang Ping
Published: September 2023

Background

Mutations in the cardiac sodium channel gene SCN5A cause Brugada syndrome (BrS), an arrhythmic disorder that is a leading cause of sudden death and lacks effective treatment. An association between SCN5A and Wnt/β-catenin signaling has been recently established. However, the role of Wnt/β-catenin signaling in BrS and underlying mechanisms remains unknown.

Methods

Three healthy control subjects and one BrS patient carrying a novel frameshift mutation (T1788fs) in the SCN5A gene were recruited in this study. Control and BrS patient-specific induced pluripotent stem cells (iPSCs) were generated from skin fibroblasts using nonintegrated Sendai virus. All iPSCs were differentiated into cardiomyocytes using monolayer-based differentiation protocol. Action potentials and sodium currents were recorded from control and BrS iPSC-derived cardiomyocytes (iPSC-CMs) by single-cell patch clamp.

Results

BrS iPSC-CMs exhibited increased burden of arrhythmias and abnormal action potential profile featured by slower depolarization, decreased action potential amplitude, and increased beating interval variation. Moreover, BrS iPSC-CMs showed cardiac sodium channel (Nav1.5) loss-of-function as compared to control iPSC-CMs. Interestingly, the electrophysiological abnormalities and Nav1.5 loss-of-function observed in BrS iPSC-CMs were accompanied by aberrant activation of Wnt/β-catenin signaling. Notably, inhibition of Wnt/β-catenin significantly rescued Nav1.5 defects and arrhythmic phenotype in BrS iPSC-CMs. Mechanistically, SCN5A-encoded Nav1.5 interacts with β-catenin, and reduced expression of Nav1.5 leads to re-localization of β-catenin in BrS iPSC-CMs, which aberrantly activates Wnt/β-catenin signaling to suppress SCN5A transcription.

Conclusions

Our findings suggest that aberrant activation of Wnt/β-catenin signaling contributes to the pathogenesis of SCN5A-related BrS and point to Wnt/β-catenin as a potential therapeutic target.
In vitro-generated human muscle reserve cells are heterogeneous for Pax7 with distinct molecular states and metabolic profiles
Authors: Bouche Axelle , Borner Benoit , Richard Chloé , Grand Ysaline , Hannouche Didier , Laumonier Thomas
Published: September 2023

Background

The capacity of skeletal muscles to regenerate relies on Pax7+ muscle stem cells (MuSC). While in vitro-amplified MuSC are activated and lose part of their regenerative capacity, in vitro-generated human muscle reserve cells (MuRC) are very similar to quiescent MuSC with properties required for their use in cell-based therapies.

Methods

In the present study, we investigated the heterogeneity of human MuRC and characterized their molecular signature and metabolic profile.

Results

We observed that Notch signaling is active and essential for the generation of quiescent human Pax7+ MuRC in vitro. We also revealed, by immunofluorescence and flow cytometry, two distinct subpopulations of MuRC distinguished by their relative Pax7 expression. After 48 h in differentiation medium (DM), the Pax7High subpopulation represented 35% of the total MuRC pool and this percentage increased to 61% after 96 h in DM. Transcriptomic analysis revealed that Pax7High MuRC were less primed for myogenic differentiation as compared to Pax7Low MuRC and displayed a metabolic shift from glycolysis toward fatty acid oxidation. The bioenergetic profile of human MuRC displayed a 1.5-fold decrease in glycolysis, basal respiration and ATP-linked respiration as compared to myoblasts. We also observed that AMPKα1 expression was significantly upregulated in human MuRC that correlated with an increased phosphorylation of acetyl-CoA carboxylase (ACC). Finally, we showed that fatty acid uptake was increased in MuRC as compared to myoblasts, whereas no changes were observed for glucose uptake.

Conclusions

Overall, these data reveal that the quiescent MuRC pool is heterogeneous for Pax7 with a Pax7High subpopulation being in a deeper quiescent state, less committed to differentiation and displaying a reduced metabolic activity. Altogether, our data suggest that human Pax7High MuRC may constitute an appropriate stem cell source for potential therapeutic applications in skeletal muscle diseases.
Mesenchymal stem cells in synovial fluid increase in number in response to synovitis and display more tissue-reparative phenotypes in osteoarthritis
Authors: Furuoka Hideto , Endo Kentaro , Sekiya Ichiro
Published: September 2023

Background

Synovial fluid mesenchymal stem cells (SF-MSCs) originate in the synovium and contribute to the endogenous repair of damaged intra-articular tissues. Here, we clarified the relationship between their numbers and joint structural changes during osteoarthritis (OA) progression and investigated whether SF-MSCs had phenotypes favorable for tissue repair, even in an OA environment.

Methods

Partial medial meniscectomy (pMx) and sham surgery were performed on both knees of rats. SF and knee joints were collected from intact rats and from rats at 2, 4, and 6 weeks after surgery. SF was cultured for 1 week to calculate the numbers of colony-forming cells and colony areas. Joint structural changes were evaluated histologically to investigate their correlation with the numbers and areas of colonies. RNA sequencing was performed for SF-MSCs from intact knees and knees 4 weeks after the pMx and sham surgery.

Results

Colony-forming cell numbers and colony areas were greater in the pMx group than in the intact and sham groups and peaked at 2 and 4 weeks, respectively. Synovitis scores showed the strongest correlation with colony numbers (R = 0.583) and areas (R = 0.456). RNA sequencing revealed higher expression of genes related to extracellular matrix binding, TGF-β signaling, and superoxide dismutase activity in SF-MSCs in the pMx group than in the sham group.

Conclusion

The number of SF-MSCs was most closely correlated with the severity of synovitis in this rat OA model. Tissue-reparative gene expression patterns were observed in SF-MSCs from OA knees, but not from knees without intra-articular tissue damage.