bluuebunny/crossref_metadata_2025 huggingface dataset:
Experience with a novel high frequency optical coherence tomography device for intracoronary imaging: a case series
Authors: Garin Dorian , Cook Stéphane , Togni Mario , Meier Pascal , Wenaweser Peter , Puricel Serban , Arroyo Diego
Published: June 2024

Introduction

Intravascular imaging, especially optical coherence tomography (OCT), has significantly improved percutaneous coronary intervention (PCI), yet its routine clinical application faces challenges. This case series introduces the Gentuity® High-Frequency Optical Coherence Tomography (HF-OCT), a novel device designed to enhance intracoronary imaging with a significantly faster pullback and smaller catheter size, potentially offering enhanced navigability in complex lesions. We aimed to assess the image quality of Gentuity® HF-OCT in complex vessel conditions, as well as presenting a case series to illustrate the application of the device in various clinical scenarios.

Methods

In this case series, we included all patients who underwent intracoronary HF-OCT imaging at our center. The primary endpoint was image quality assessed by clear image length (CIL). Image quality was assessed in relation to (1) lesion severity assessed by minimum lumen area (MLA); (2) vessel size, differentiating between larger (diameter ≥ 4 mm) and smaller vessel segments; (3) pre- vs. post-PCI conditions, and (4) vessel tortuosity, categorized into none, moderate, and severe.

Results

Twenty-four HF-OCT runs from 14 patients were included. No significant differences in CIL were observed across lesion severity terciles (p = 0.449), between small and large vessel segments [mean CIL% difference 1.3%; confidence interval (CI), −9.3 to 11.8; p = 0.802], and pre- vs. post-PCI conditions (mean CIL difference −3.9 mm; CI, −14.0 to 6.1; p = 0.373). Vessel tortuosity significantly impacted image quality, with clear reductions in CIL observed in cases of moderate (74.8; CI, 73.5 to 76.0; vs. 63.9; CI, 56.2 to 71.5; p = 0.043) and severe tortuosity (74.8; CI, 73.5 to 76.0; vs. 65.0; CI, 62.1 to 67.9; p = 0.002) compared to vessels with no tortuosity. Overall, the HF-OCT demonstrated excellent catheter deliverability and crossability, with very satisfactory image quality and no significant adverse events.

Conclusion

The Gentuity® HF-OCT is a new OCT device capable of navigating both small- and large-diameter vessels, with similar image quality, but vessel tortuosity seems to have an impact on image quality. It appears to be as usable as conventional OCT for pre-PCI diagnosis and OCT-guided PCI, potentially bringing additional benefits in terms of deliverability, lesion crossover and ease of use in routine clinical practice.
Blood urea nitrogen to creatinine ratio is associated with in-hospital mortality in critically ill patients with venous thromboembolism: a retrospective cohort study
Authors: Puri Anju , Giri Mohan , Huang Huanhuan , Zhao Qinghua
Published: June 2024

Background

The relationship between the blood urea nitrogen to creatinine ratio (BCR) and the risk of in-hospital mortality among intensive care unit (ICU) patients diagnosed with venous thromboembolism (VTE) remains unclear. This study aimed to assess the relationship between BCR upon admission to the ICU and in-hospital mortality in critically ill patients with VTE.

Methods

This retrospective cohort study included patients diagnosed with VTE from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary endpoint was in-hospital mortality. Univariate and multivariate logistic regression analyses were conducted to evaluate the prognostic significance of the BCR. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal cut-off value of BCR. Additionally, survival analysis using a Kaplan–Meier curve was performed.

Results

A total of 2,560 patients were included, with a median age of 64.5 years, and 55.5% were male. Overall, the in-hospital mortality rate was 14.6%. The optimal cut-off value of the BCR for predicting in-hospital mortality in critically ill VTE patients was 26.84. The rate of in-hospital mortality among patients categorized in the high BCR group was significantly higher compared to those in the low BCR group (22.6% vs. 12.2%, P < 0.001). The multivariable logistic regression analysis results indicated that, even after accounting for potential confounding factors, patients with elevated BCR demonstrated a notably increased in-hospital mortality rate compared to those with lower BCR levels (all P < 0.05), regardless of the model used. Patients in the high BCR group exhibited a 77.77% higher risk of in-hospital mortality than those in the low BCR group [hazard ratio (HR): 1.7777; 95% CI: 1.4016–2.2547].

Conclusion

An elevated BCR level was independently linked with an increased risk of in-hospital mortality among critically ill patients diagnosed with VTE. Given its widespread availability and ease of measurement, BCR could be a valuable tool for risk stratification and prognostic prediction in VTE patients.
WhatsApp groups: The nexus between retention, reciprocity, and user satisfaction
Authors: Ali Ismail Mohamed , Mohamed Mohamud Ahmed , Ahmed Yahye Abukar
Published: June 2024

High dropout rates in higher education pose a significant challenge, prompting a need for effective retention strategies. Research shows promoting students’ engagement as key factor in retention. This is most effectively nurtured through regular activities that explicitly connect to academic goals and involve all students. This study proposes to investigate the role of reciprocity which involves the exchange of knowledge and resources on the basis of mutual benefits, and considers WhatsApp groups as an interactive medium for connecting and sharing. Data from an online questionnaire of 309 university students was used to test the research model. Data analysis was performed using the partial least squares method. The findings revealed that that information quality (IQ) and service quality (SERQ) exert a positive influence on satisfaction (SAT), while system quality (SQ) does not. Similarly, reciprocity has a positive influence on both SAT and intention to stay (INTENT). Moreover, our study reaffirmed the established positive relationship between SAT and INTENT. Online platforms like WhatsApp groups, supported by reciprocity and a higher quality of contents and services, can promote satisfaction and knowledge sharing among students, ultimately addressing the challenge of student retention in higher education.
Case report: The success of empagliflozin therapy for glycogen storage disease type 1b
Authors: Klinc Ana , Groselj Urh , Mlinaric Matej , Homan Matjaz , Markelj Gasper , Mezek Novak Ajda , Sirca Campa Andreja , Sikonja Jaka , Battelino Tadej , Zerjav Tansek Mojca , Drole Torkar Ana
Published: June 2024

Introduction

Glycogen storage disease type 1b (GSD-1b) is characterized by neutropenia and neutrophil dysfunction generated by the accumulation of 1,5-anhydroglucitol-6-phosphate in neutrophils. Sodium-glucose co-transporter 2 inhibitors, such as empagliflozin, facilitate the removal of this toxic metabolite and ameliorate neutropenia-related symptoms, including severe infections and inflammatory bowel disease (IBD). Our case series presents the treatment of three pediatric GSD-1b patients with empagliflozin over a follow-up of three years; the most extended reported follow-up period to date.

Cases description

A retrospective analysis of empagliflozin treatment of three pediatric GSD-1b patients (two male and one female; ages at treatment initiation: 4.5, 2.5 and 6 years) was performed. Clinical and laboratory data from a symmetrical period of up to three years before and after the therapy introduction was reported. Data on the clinical course of the treatment, IBD activity, the need for antibiotic treatment and hospitalizations, neutrophil count and function, and markers of inflammation were assessed. Prior the introduction of empagliflozin, patients had recurrent oral mucosa lesions and infections, abdominal pain, and anemia. During empagliflozin treatment, the resolution of aphthous stomatitis, termination of abdominal pain, reduced frequency and severity of infections, anemia resolution, increased appetite, and improved wound healing was observed in all patients, as well as an increased body mass index in two of them. In a patient with IBD, long-term deep remission was confirmed. An increased and stabilized neutrophil count and an improved neutrophil function enabled the discontinuation of G-CSF treatment in all patients. A trend of decreasing inflammation markers was detected.

Conclusions

During the three-year follow-up period, empagliflozin treatment significantly improved clinical symptoms and increased the neutrophil count and function, suggesting that targeted metabolic treatment could improve the immune function in GSD-1b patients.
Causal link between hypothyroidism and gastric cancer risk: insights gained through multivariable Mendelian randomization and mediation analysis
Authors: Zhang Tianyue , Qiao Jie , Wang Yuanyou , Zhou Yinying , Jabbar Abdl Sattar Hamoudi Hammza , Hendi Mhd Alaa Al , Wang Jun
Published: June 2024

Background

Gastric cancer (GC) is the third leading cause of cancer death worldwide, and hypothyroidism has been identified as a potential influencing factor. Despite known associations between hypothyroidism and various cancers, the causal link between hypothyroidism and GC and potential mediators of this relationship remains unclear. This study aimed to clarify these relationships using Mendelian randomization (MR).

Methods

Utilizing genetic variant information from the FinnGen and MRC Integrative Epidemiology Unit open genome-wide association studies (GWAS) databases, we conducted univariable and multivariable MR analyses to explore the causal relationship between hypothyroidism and GC risk. The analysis was adjusted for confounders such as BMI, smoking status, and alcohol intake, and included mediator MR analysis to examine the role of high cholesterol.

Results

We identified a significant inverse association between hypothyroidism and GC risk (OR = 0.93, 95% CI= 0.89–0.98, P = 0.003), with no evidence of reverse causation or pleiotropy. Adjustments for Helicobacter pylori infection weakened this association. Mediator analysis highlighted high cholesterol levels, chronic hepatitis B infection, and diabetes/endocrine disease status as significant mediators of the protective effect of hypothyroidism on GC risk.

Conclusion

Our findings suggest that hypothyroidism may confer a protective effect against GC, mediated in part by high cholesterol and other factors. These results underscore the importance of thyroid function and metabolic health in GC risk, offering new insights for preventive strategies and highlighting the need for further research into these complex associations.
A meta-analysis: elucidating diagnostic thresholds of peak systolic flow velocities in thyroid arteries for the discrimination of Graves’ disease and destructive thyrotoxicosis
Authors: Li Sinong , Ding Zheng , Li Xiang , Fu Miao , Sang Li , Yang Mingxia , Tang Rubo , Gu Tianxiang , Sang Liang
Published: June 2024

Objective

This meta-analysis examines peak systolic velocities (PSVs) in thyroid arteries as potential biomarkers for thyroid disorders, which includes treated and untreated Graves’ disease(GD) and destructive thyrotoxicosis(DT).

Methods

A search across databases including PubMed, Google Scholar, Embase, and Web of Science identified studies assessing peak systolic flow velocity in the inferior thyroid artery (ITA-PSV) and superior thyroid artery (STA-PSV) diagnostic efficacy in GD and DT.And the search was restricted to publications in the English language.The analysis compared STA-PSV and ITA-PSV across patient groups, evaluating intra-group variances and synthesizing sensitivity and specificity data.

Results

The analysis covered 18 studies with 1276 GD, 564 DT patients, and 544 controls. The difference of STA-PSV between GD group, DT group and normal group and the difference of ITA-PSV were analyzed in subgroups, and there was no statistical significance between subgroups when comparing any two groups. Normal subjects displayed intra-group ITA-PSV and STA-PSV differences with established cut-off values of 20.33 cm/s (95% CI, 17.48-23.18) for ITA-PSV and 25.61 cm/s (95% CI, 20.37-30.85) for STA-PSV. However, no significant intra-group differences were observed in the STA-PSV and ITA-PSV cut-off values among groups with GD or DT. The combined cut-off values for these patient groups and normal subjects were 68.63 cm/s (95% CI, 59.12-78.13), 32.08 cm/s (95% CI, 25.90-38.27), and 23.18 cm/s (95% CI, 20.09-26.28), respectively. The diagnostic odds ratio(DOR) for these values was 35.86 (95% CI, 18.21-70.60), and the area under the summary receiver operating characteristic (SROC) curve was 0.91, with a sensitivity estimate of 0.842 (95% CI, 0.772-0.866).

Conclusion

PSVs in thyroid arteries are useful diagnostic tools in distinguishing DT from GD. A PSV above 68.63 cm/s significantly improves GD diagnosis with up to 91% efficacy. No notable differences were found between superior and inferior thyroid arteries in these conditions.
Diabetes care and outcomes of pediatric refugees and migrants from Ukraine and Syria/Afghanistan with type 1 diabetes in German-speaking countries
Authors: Auzanneau Marie , Reinauer Christina , Ziegler Julian , Golembowski Sven , de Beaufort Carine , Schöttler Hannah , Hahn Eva , Mirza Joaquina , Galler Angela , Wurm Michael , Holl Reinhard W.
Published: June 2024

Introduction

Currently, over two million war refugees live in Germany. Exposure to war and flight is associated with a high burden of diseases, not limited to mental disorders and infections. We aimed to analyze diabetes treatment and outcomes of pediatric refugees and migrants from Ukraine and Syria/Afghanistan with type 1 diabetes (T1D) in German-speaking countries.

Materials and methods

We included patients with T1D documented between January 2013 and June 2023 in the German/Austrian/Luxembourgian/Swiss DPV registry, aged < 20 years, born in Ukraine [U], in Syria or Afghanistan [S/A], or without migration background [C]. Using logistic, linear, and negative binomial regression models, we compared diabetes technology use, BMI-SDS, HbA1c values, as well as severe hypoglycemia and DKA rates between groups in the first year of treatment in the host country. Results were adjusted for sex, age, diabetes duration, and time spent in the host country.

Results

Among all patients with T1D aged < 20 years, 615 were born in Ukraine [U], 624 in Syria or Afghanistan [S/A], and 28,106 had no migration background [C]. Compared to the two other groups, patients from Syria or Afghanistan had a higher adjusted BMI-SDS (0.34 [95%-CI: 0.21–0.48] [S/A] vs. 0.13 [- 0.02–0.27] [U] and 0.20 [0.19–0.21] [C]; all p<0.001), a lower use of CGM or AID system (57.6% and 4.6%, respectively [S/A] vs. 83.7% and 7.8% [U], and 87.7% and 21.8% [C], all p<0.05) and a higher rate of severe hypoglycemia (15.3/100 PY [S/A] vs. 7.6/100 PY [C], and vs. 4.8/100 PY [U], all p<0.05). Compared to the two other groups, patients from Ukraine had a lower adjusted HbA1c (6.96% [95%-CI: 6.77–7.14] [U] vs. 7.49% [7.32–7.66] [S/A] and 7.37% [7.36–7.39] [C], all p<0.001).

Discussion

In their first treatment year in the host country, young Syrian or Afghan refugees had higher BMI-SDS, lower use of diabetes technology, higher HbA1c, and a higher rate of severe hypoglycemia compared to young Ukrainian refugees. Diabetologists should be aware of the different cultural and socioeconomic backgrounds of refugees to adapt diabetes treatment and education to specific needs.
Non-diabetic elderly populations: the MHR as a protective factor against bone abnormalities
Authors: Li Xiang , Yan Manli , Ji Jiali , Ma Zhuohao
Published: June 2024

Objectives

In China, osteoporosis has become a major health concern among elderly population, imposing significant burden on the country’s social and economic systems. The monocyte to high-density lipoprotein ratio (MHR) has been currently recommended as a novel marker of inflammation and oxidative stress associated with osteoporosis in type 2 diabetes mellitus (T2DM). However, its reliability in non-diabetic elderly populations remains unclear. The present study was to evaluate the association between MHR and osteoporosis in a non-diabetic elderly population.

Methods

The clinical data of 240 non-diabetic elderly subjects (115 in the osteoporosis group and 125 in the normal bone group) were retrospectively analyzed and all statistical analyses were performed by using SPSS 26.0.

Results

Differences in age, neutrophils, lymphocytes, monocytes, MHR, uric acid, creatinine, triglycerides,and high-density lipoprotein cholesterol were found to be statistically significant between the two groups. A binary logistic regression model was conducted by including age, MHR, UA and Cr as variables. The results showed that age was an independent risk factor and MHR was an independent protective factor for bone abnormality in the non-diabetic elderly population. The ROC analysis showed that the area under the curve for the predictive effect of MHR, age and their combined test on osteoporosis in non-diabetic elderly populations was 0.623, 0.728 and 0.761, respectively; the correlation analysis showed that MHR was positively correlated with lumbar and hip BMD, and negatively associated with femoral neck stress ratio, femoral intertrochanteric stress ratio, and femoral stem stress ratio, showing statistically significant differences (P<0.05).

Conclusions

For the non-diabetic elderly population: the MHR is a protective factor against bone abnormalities and was significantly higher in the normal bone group than in the abnormal bone group.
Construction of a 3-year risk prediction model for developing diabetes in patients with pre-diabetes
Authors: Yang Jianshu , Liu Dan , Du Qiaoqiao , Zhu Jing , Lu Li , Wu Zhengyan , Zhang Daiyi , Ji Xiaodong , Zheng Xiang
Published: June 2024

Introduction

To analyze the influencing factors for progression from newly diagnosed prediabetes (PreDM) to diabetes within 3 years and establish a prediction model to assess the 3-year risk of developing diabetes in patients with PreDM.

Methods

Subjects who were diagnosed with new-onset PreDM at the Physical Examination Center of the First Affiliated Hospital of Soochow University from October 1, 2015 to May 31, 2023 and completed the 3-year follow-up were selected as the study population. Data on gender, age, body mass index (BMI), waist circumference, etc. were collected. After 3 years of follow-up, subjects were divided into a diabetes group and a non-diabetes group. Baseline data between the two groups were compared. A prediction model based on logistic regression was established with nomogram drawn. The calibration was also depicted.

Results

Comparison between diabetes group and non-diabetes group: Differences in 24 indicators including gender, age, history of hypertension, fatty liver, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, HbA1c, etc. were statistically significant between the two groups (P<0.05). Differences in smoking, creatinine and platelet count were not statistically significant between the two groups (P>0.05). Logistic regression analysis showed that ageing, elevated BMI, male gender, high fasting blood glucose, increased LDL-C, fatty liver, liver dysfunction were risk factors for progression from PreDM to diabetes within 3 years (P<0.05), while HDL-C was a protective factor (P<0.05). The derived formula was: In(p/1-p)=0.181×age (40-54 years old)/0.973×age (55-74 years old)/1.868×age (≥75 years old)-0.192×gender (male)+0.151×blood glucose-0.538×BMI (24-28)-0.538×BMI (≥28)-0.109×HDL-C+0.021×LDL-C+0.365×fatty liver (yes)+0.444×liver dysfunction (yes)-10.038. The AUC of the model for predicting progression from PreDM to diabetes within 3 years was 0.787, indicating good predictive ability of the model.

Conclusions

The risk prediction model for developing diabetes within 3 years in patients with PreDM constructed based on 8 influencing factors including age, BMI, gender, fasting blood glucose, LDL-C, HDL-C, fatty liver and liver dysfunction showed good discrimination and calibration.
Free iron oxides modulate the surface properties of Benggang soil on Southern China: insights into erosive mechanisms
Authors: Jiang Ling , Chen Jie , You Le-Xing , Jiang Fang-Shi , Zhang Yue , Lin Jin-Shi , Huang Yan-He
Published: June 2024

Benggang, an erosional phenomenon located in southern China, exhibits distinctive characteristics that can have profound ecological and agricultural consequences as well as pose risks to human life. Previous investigations have primarily focused on elucidating the relationships between the physical and chemical attributes of soils collected from Benggang. However, the precise role of free iron oxides in the surface properties of Benggang soil and its contribution to the formation of Benggang remains largely unexplored. In this study, we aim to investigate the role of free iron oxides in Benggang soil by removing them and subsequently introducing goethite to evaluate their impact on the soil’s surface properties. Our results reveal a decrease in the surface charge density of soil colloidal particles with increasing soil depth. Specifically, the uppermost red soil layer exhibits the highest value, followed by the sandy soil and the lowermost clastic layer. Upon removing free iron oxide, we documented reductions of 44.28% (red soil), 20.62% (sandy soil), and 8.70% (clastic layer) in the surface charge density of colloidal particles. The red soil layer presented an over 18-fold increase compared to the initial linear shrinkage, followed by the sandy soil and clastic layer. Notably, the addition of goethite to the iron oxide-free soil layers resulted in the recovery of approximately 81.93%, 121.13%, and 104.35% of the initial surface charge density, respectively. Moreover, significant changes in volume shrinkage were observed, with approximately 97.54% (red soil), 94.75% (sandy soil), and 89.72% (clastic layer) of the initial values being influenced. These findings underscore the substantial influence of free iron oxide on the physicochemical properties of Benggang soil and contribute to a comprehensive understanding of the erosive mechanisms underlying Benggang formation.
Genetic Landscape of SH3TC2 variants in Russian patients with Charcot–Marie–Tooth disease
Authors: Shchagina Olga , Murtazina Aysylu , Chausova Polina , Orlova Mariya , Dadali Elena , Kurbatov Sergei , Kutsev Sergey , Polyakov Aleksander
Published: June 2024

Introduction:

Charcot–Marie–Tooth disease type 4C (CMT4C) OMIM#601596 stands out as one of the most prevalent forms of recessive motor sensory neuropathy worldwide. This disorder results from biallelic pathogenic variants in the SH3TC2 gene.

Methods:

Within a cohort comprising 700 unrelated Russian patients diagnosed with Charcot–Marie–Tooth disease, we conducted a gene panel analysis encompassing 21 genes associated with hereditary neuropathies. Among the cohort, 394 individuals exhibited demyelinating motor and sensory neuropathy.

Results and discussion:

Notably, 10 cases of CMT4C were identified within this cohort. The prevalence of CMT4C among Russian demyelinating CMT patients lacking the PMP22 duplication is estimated at 2.5%, significantly differing from observations in European populations. In total, 4 novel and 9 previously reported variants in the SH3TC2 gene were identified. No accumulation of a major variant was detected. Three previously reported variants, c.2860C>T p. (Arg954*), p. (Arg658Cys) and c.279G>A p. (Lys93Lys), recurrently detected in unrelated families. Nucleotide alteration p. (Arg954*) is present in most of our patients (30%).
Phylogenetic insight into ABCE gene subfamily in plants
Authors: Jakobson Liina , Mõttus Jelena , Suurväli Jaanus , Sõmera Merike , Tarassova Jemilia , Nigul Lenne , Smolander Olli-Pekka , Sarmiento Cecilia
Published: June 2024

ATP-BINDING CASSETTE SUBFAMILY E MEMBER (ABCE) proteins are one of the most conserved proteins across eukaryotes and archaea. Yeast and most animals possess a single ABCE gene encoding the critical translational factor ABCE1. In several plant species, including Arabidopsis thaliana and Oryza sativa, two or more ABCE gene copies have been identified, however information related to plant ABCE gene family is still missing. In this study we retrieved ABCE gene sequences of 76 plant species from public genome databases and comprehensively analyzed them with the reference to A. thaliana ABCE2 gene (AtABCE2). Using bioinformatic approach we assessed the conservation and phylogeny of plant ABCEs. In addition, we performed haplotype analysis of AtABCE2 and its paralogue AtABCE1 using genomic sequences of 1,135 A. thaliana ecotypes. Plant ABCE proteins showed overall high sequence conservation, sharing at least 78% of amino acid sequence identity with AtABCE2. We found that over half of the selected species have two to eight ABCE genes, suggesting that in plants ABCE genes can be classified as a low-copy gene family, rather than a single-copy gene family. The phylogenetic trees of ABCE protein sequences and the corresponding coding sequences demonstrated that Brassicaceae and Poaceae families have independently undergone lineage-specific split of the ancestral ABCE gene. Other plant species have gained ABCE gene copies through more recent duplication events. We also noticed that ploidy level but not ancient whole genome duplications experienced by a species impacts ABCE gene family size. Deeper analysis of AtABCE2 and AtABCE1 from 1,135 A. thaliana ecotypes revealed four and 35 non-synonymous SNPs, respectively. The lower natural variation in AtABCE2 compared to AtABCE1 is in consistence with its crucial role for plant viability. Overall, while the sequence of the ABCE protein family is highly conserved in the plant kingdom, many plants have evolved to have more than one copy of this essential translational factor.
Serum albumin and derived neutrophil-to-lymphocyte ratio are potential predictive biomarkers for immune checkpoint inhibitors in small cell lung cancer
Authors: Kuang Zhanpeng , Miao Jessica , Zhang Xiaoli
Published: June 2024

Background

Immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of small cell lung cancer (SCLC), but only a minority of patients benefit from this therapy. Therefore, it is critical to identify potential risk factors that could predict the efficacy of ICI treatment in SCLC patients and identify patient subgroups who may benefit the most from ICI therapy.

Methods

Our study included a total of 183 SCLC patients who had received at least one dose of ICI treatment. We utilized both logistic regression and Cox proportional hazard regression to evaluate whether various patient clinical factors and serum biomarkers could serve as predictors of patient response to treatment and overall survival (OS) during ICI therapy.

Results

Logistic regression showed that patients with a history of surgery (p=0.003, OR 9.06, 95% CI: (2.17, 37.9)) and no metastasis (p=0.008, OR 7.82, 95% CI: (1.73, 35.4)) exhibited a higher odds of response to ICI treatment. Cox regression analyses demonstrated that pretreatment blood albumin (p=0.003, HR 1.72, 95% CI: (1.21, 2.45)) and derived neutrophil to lymphocyte ratio (dNLR) (p=0.003, HR 1.71, 95% CI: (1.20–2.44)) were independent predictors for OS in SCLC patients. By establishing a pre-treatment prognostic scoring system based on baseline albumin and dNLR, we found that patients with high albumin and low dNLR exhibited a significantly better prognosis than those with low albumin and high dNLR in both the full (P<.0001, HR 0.33, 95% CI: 0.20–0.55) and the metastatic cohort (P<.0001, HR 0.28, 95% CI: 0.15–0.51). The better prognostic group also had younger age, higher BMI and lower systemic inflammatory biomarker values than the unfavorable group (P<.0001).

Conclusion

Our data reveals the significant role of metastasis status and treatment history in predicting the initial response of SCLC patients to ICI treatment. However, baseline serum albumin and dNLR provide a more precise prognostic prediction for patient OS. The scoring system based on albumin and dNLR enhances the ability to stratify patient prognosis and holds the potential to guide clinical decision-making for SCLC patients undergoing ICI therapy.
Proof of concept of a new plasma complement Factor H from waste plasma fraction
Authors: Mori Filippo , Pascali Giancarlo , Berra Silvia , Lazzarotti Alessandra , Panetta Daniele , Rocchiccioli Silvia , Ceccherini Elisa , Norelli Francesco , Morlando Antonio , Donadelli Roberta , Clivio Alberto , Farina Claudio , Noris Marina , Salvadori Piero A. , Remuzzi Giuseppe
Published: June 2024

Introduction

Complement factor H (FH) is a major regulator of the complement alternative pathway, its mutations predispose to an uncontrolled activation in the kidney and on blood cells and to secondary C3 deficiency. Plasma exchange has been used to correct for FH deficiency and although the therapeutic potential of purified FH has been suggested by in vivo experiments in animal models, a clinical approved FH concentrate is not yet available. We aimed to develop a purification process of FH from a waste fraction rather than whole plasma allowing a more efficient and ethical use of blood and plasma donations.

Methods

Waste fractions from industrial plasma fractionation (pooled human plasma) were analyzed for FH content by ELISA. FH was purified from unused fraction III and its decay acceleration, cofactor, and C3 binding capacity were characterized in vitro. Biodistribution was assessed by high-resolution dynamic PET imaging. Finally, the efficacy of the purified FH preparation was tested in the mouse model of C3 glomerulopathy (Cfh−/− mice).

Results

Our purification method resulted in a high yield of highly purified (92,07%), pathogen-safe FH. FH concentrate is intact and fully functional as demonstrated by in vitro functional assays. The biodistribution revealed lower renal and liver clearance of human FH in Cfh-/- mice than in wt mice. Treatment of Cfh-/- mice documented its efficacy in limiting C3 activation and promoting the clearance of C3 glomerular deposits.

Conclusion

We developed an efficient and economical system for purifying intact and functional FH, starting from waste material of industrial plasma fractionation. The FH concentrate could therefore constitute possible treatments options of patients with C3 glomerulopathy, particularly for those with FH deficiency, but also for patients with other diseases associated with alternative pathway activation.
Neointimal hyperplasia after endoluminal injury in mice is dependent on tissue factor- and angiopoietin-2 dependent interferon gamma production by fibrocytes and macrophages
Authors: Chen Daxin , Li Ke , Wei Lin-Lin , Ma Ning , McVey John H. , Dorling Anthony
Published: June 2024

Background

The intimal hyperplasia (IH) and vascular remodelling that follows endovascular injury, for instance after post-angioplasty re-stenosis, results in downstream ischaemia and progressive end organ damage. Interferon gamma (IFNγ) is known to play a critical role in this process. In mouse models we have previously shown that fibrocytes expressing tissue factor (TF) are recruited early to the site of injury. Through thrombin generation and protease activated receptor-1 (PAR-1) activation, fibrocytes secrete angiopoietin-2, stimulate neointimal cell proliferation, inhibit apoptosis and induce CXCL-12 production, all of which contribute to the progressive IH that then develops. In this study we investigated the relationship between TF, angiopoietin-2 and IFNγ.

Methods and results

IH developing in carotid arteries of wild-type mice 4 weeks after endoluminal injury contained a significant proportion of IFNγ+ fibrocytes and macrophages, which we show, using a previously defined adoptive transfer model, were derived from circulating CD34+ cells. IH did not develop after injury in IFNγ-deficient mice, except after transplantation of WT bone marrow or adoptive transfer of WT CD34+ cells. In vitro, CD34+ cells isolated from post-injury mice did not express IFNγ, but this was induced when provided with FVIIa and FX, and enhanced when prothrombin was also provided: In both cases IFNγ secretion was TF-dependent and mediated mainly through protease activated PAR-1. IFNγ was predominantly expressed by fibrocytes. In vivo, all IFNγ+ neointimal cells in WT mice co-expressed angiopoietin-2, as did the small numbers of neointimal cells recruited in IFNγ-/- mice. Adoptively transferred WT CD34+ cells treated with either an anti-TIE-2 antibody, or with siRNA against angiopoetin-2 inhibited the expression of IFNγ and the development of IH.

Conclusion

TF-dependent angiopoietin-2 production by newly recruited fibrocytes, and to a lesser extent macrophages, switches on IFNγ expression, and this is necessary for the IH to develop. These novel findings enhance our understanding of the pathophysiology of IH and expose potential targets for therapeutic intervention.
Preoperative inflammatory biomarkers reveal renal involvement in postsurgical mortality in hip fracture patients: an exploratory study
Authors: Valdes Ana M. , Ikram Adeel , Taylor Lauren A. , Zheng Amy , Kouraki Afroditi , Kelly Anthony , Ashraf Waheed , Vijay Amrita , Miller Suzanne , Nightingale Jessica , Selby Nicholas M. , Ollivere Benjamin J.
Published: June 2024

Background

Hip fractures in frail patients result in excess mortality not accounted for by age or comorbidities. The mechanisms behind the high risk of mortality remain undetermined but are hypothesized to be related to the inflammatory status of frail patients.

Methods

In a prospective observational exploratory cohort study of hospitalized frail hip fracture patients, 92 inflammatory markers were tested in pre-operative serum samples and markers were tested against 6-month survival post-hip fracture surgery and incidence of acute kidney injury (AKI). After correcting for multiple testing, adjustments for comorbidities and demographics were performed on the statistically significant markers.

Results

Of the 92 markers tested, circulating levels of fibroblast growth factor 23 (FGF-23) and interleukin-15 receptor alpha (IL15RA), both involved in renal disease, were significantly correlated with 6-month mortality (27.5% overall) after correcting for multiple testing. The incidence of postoperative AKI (25.4%) was strongly associated with 6-month mortality, odds ratio = 10.57; 95% CI [2.76–40.51], and with both markers plus estimated glomerular filtration rate (eGFR)– cystatin C (CYSC) but not eGFR-CRE. The effect of these markers on mortality was significantly mediated by their effect on postoperative AKI.

Conclusion

High postoperative mortality in frail hip fracture patients is highly correlated with preoperative biomarkers of renal function in this pilot study. The effect of preoperative circulating levels of FGF-23, IL15RA, and eGFR-CYSC on 6-month mortality is in part mediated by their effect on postoperative AKI. Creatinine-derived preoperative renal function measures were very poorly correlated with postoperative outcomes in this group.
A highly effective ferritin-based divalent nanoparticle vaccine shields Syrian hamsters against lethal Nipah virus
Authors: Yin Chunhong , Yao Yan Feng , Yang Peipei , Liu Hang , Gao Ge , Peng Yun , Chen Miaoyu , Lu Mingqing , Zhang Xuekai , Guo Weiwei , Zhang Zihan , Hu Xue , Yuan Zhiming , Shan Chao
Published: June 2024

The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related henipaviruses infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous henipavirus. These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic henipaviruses challenges.
Treatment goals in ANCA-associated vasculitis: defining success in a new era
Authors: Alberici Federico , Tedesco Martina , Popov Tamara , Balcells-Oliver Monica , Mescia Federica
Published: June 2024

Health-related quality of life is a key contributor to overall well-being, and this is becoming an increasingly prominent factor when making therapeutic choices in the management of ANCA-associated vasculitis (AAV). Progress in available therapeutic strategies for AAV has resulted in this historically acute disease with a potentially fatal short-term outcome, becoming a relapsing-remitting chronic disorder. This new perspective on AAV means that patient survival should no longer be considered as the only major treatment target. Additional outcomes in this context that should be portrayed in order to consider a therapeutic approach as successful include patient quality of life, as well as the burden of treatment-induced morbidity. Comorbidities and impaired quality of life in patients with AAV, as with many other autoimmune diseases, may be a consequence of the disease itself as well as a result of the therapy employed. The AAV disease process may induce organ damage, including kidney failure and structural lung damage, and increase the risk of cardiovascular disease. On top of this, treatments employed to manage the disease may contribute further to the overall comorbidities burden. Furthermore, pre-existing comorbidities can increase AAV severity and may also be contraindications that limit potential therapeutic options. Quality of life is another central topic that can have a huge impact on patient wellbeing as well as adherence to treatment. Ongoing monitoring of comorbidity risk and of quality of life is thus key for successful AAV management. This process, however, may be complicated; the identification of the correct parameters on which to focus is not always straightforward and, more importantly, it is sometimes the symptoms that may appear trivial to physicians that are most detrimental to a patient’s quality of life. With these shifts in treatment capabilities and understanding of patient burden, it is necessary to adjust the treatment paradigm accordingly. Treatment success is no longer defined solely by the control of disease activity; treatment success requires holistic improvement determined through the assessment of all aspects of the disease, ranging from disease control to comorbidity risk through to the assessment of health-related quality of life. This review explores the burden of AAV itself as well as treatment-related side effects with a special focus on the tools available to measure outcomes. The management of AAV has entered a new era with a strong focus on both the management and prevention of comorbidities as well as patient-reported outcomes, both of which are now considered key factors in defining treatment success.
Comparative studies on the intestinal health of wild and cultured ricefield eel (Monopterus albus)
Authors: Yang Hang , Yuan Quan , Rahman Mohammad Mizanur , Lv Weiwei , Huang Weiwei , Hu Wei , Zhou Wenzong
Published: June 2024

Fish intestinal health under intensive aquaculture mode plays an important role in growth, development, and immune function. The present study was aimed to systematically investigate the differences of intestinal health between wild and cultured Monopterus albus by biochemical parameters, histomorphology, and molecular biology. A total of 15 healthy M. albus per group, with an average body weight of 45 g, were sampled to analyze intestinal health parameters. Compared with wild fish, the cultured M. albus in the foregut had lower trypsin, lipase, SOD, CAT, T-AOC, and GSH-Px activities (P < 0.05) and higher amylase activity and MDA content (P < 0.05). The villus circumference and goblet cells in the cultured group were significantly lower than those in the wild group (P < 0.05). In addition, the cultured fish showed lower relative expression levels of occludin, zo-1, zo-2, claudin-12, claudin-15, mucin5, mucin15, lysozyme, complement 3, il-10, tgf-β1, tgf-β2, and tgf-β3 (P < 0.05) and higher il-1β, il-6, il-8, tnf-a, and ifnγ mRNA expressions than those of wild fish (P < 0.05). In terms of gut microbiota, the cultured group at the phylum level displayed higher percentages of Chlamydiae and Spirochaetes and lower percentages of Firmicutes, Bacteroidetes, Actinobacteria, Cyanobacteria, and Verrucomicrobia compared to the wild group (P < 0.05). At the genus level, higher abundances of Pseudomonadaceae_Pseudomonas and Spironema and lower abundances of Lactococcus and Cetobacterium were observed in the cultured group than in the wild group (P < 0.05). To our knowledge, this is the first investigation of the intestinal health status between wild and cultured M. albus in terms of biochemistry, histology, and molecular biology levels. Overall, the present study showed significant differences in intestinal health between wild and cultured M. albus and the main manifestations that wild M. albus had higher intestinal digestion, antioxidant capacity, and intestinal barrier functions than cultured M. albus. These results would provide theoretical basis for the subsequent upgrading of healthy aquaculture technology and nutrient regulation of intestinal health of cultured M. albus.
Albumin and multiple sclerosis: a prospective study from UK Biobank
Authors: Chen Ke , Li Chunyu , Zhao Bi , Shang Huifang
Published: June 2024

Background

Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system. While previous studies have indicated that albumin, the primary protein in human plasma, may exert influence on the inflammatory process and confer beneficial effects in neurodegenerative disorders, its role in the context of MS has been underexplored. Here, we aimed to explore the link between albumin and the risk of MS.

Methods

Employing data from the UK Biobank, we investigated the association between baseline levels of serum and urine albumin and the risk of MS using Cox proportional hazards regression analysis.

Results

A higher baseline level of serum albumin was associated with a lower risk of incident MS (HR=0.94, 95% CI: 0.91–0.98, P=7.66E-04). Subgroup analysis revealed a more pronounced effect in females, as well as participants with younger ages, less smoking and deficient levels of vitamin D. Conversely, no association was identified between baseline microalbuminuria level and risk of incident MS.

Conclusion

Higher serum albumin level at baseline is linked to a reduced risk of MS. These results contribute to an enhanced understanding of albumin’s role in MS, propose the potential use of albumin as a biomarker for MS, and have implications for the design of therapeutic interventions targeting albumin in clinical trials.
Gut Subdoligranulum variabile ameliorates rheumatoid arthritis by promoting TSG-6 synthesis from joint cells
Authors: Li Hongfeng , Dai Junhui , Zhao Changying , Hu Tianqi , Zhao Guoping , Wang Qinghua , Zhang Lei
Published: June 2024

Background

A burgeoning body of evidence has substantiated the association between alterations in the composition of the gut microbiota and rheumatoid arthritis (RA). Nevertheless, our understanding of the intricate mechanisms underpinning this association is limited.

Methods

To investigate whether the gut microbiota influences the pathogenesis of RA through metabolism or immunity, we performed rigorous synthesis analyses using aggregated statistics from published genome-wide association studies (GWAS) using two-sample Mendelian randomization (MR) and mediated MR techniques, including two-step MR and multivariate MR analyses. Subsequently, we conducted in vitro cellular validation of the analyzed Microbial-Cytokine-RA pathway. We determined the optimal culture conditions through co-culture experiments involving concentration and time. Cell Counting Kit-8 (CCK-8) assays were employed to assess cellular viability, and enzyme-linked immunosorbent assays (ELISA) were performed to assess tumor necrosis factor-inducible gene 6 protein (TSG-6) and tumor necrosis factor-α (TNF-α) levels.

Results

Our univariable MR results confirmed 15 microbial traits, 7 metabolites and 2 cytokines that may be causally associated with RA (PFDR < 0.05). Mediation analysis revealed that microbial traits influence the risk of RA through metabolite or cytokine (proportion mediated: 7.75% - 58.22%). In vitro experiments demonstrated that TSG-6 was highly expressed in the Subdoligranulum variabile treatment group and was correlated with decreased RA severity (reduced TNF-α expression). Silencing the TSG-6 gene significantly increased TNF-α expression, regardless of treatment with S. variabile. Additionally, S. variabile-secreted exosomes exhibited the same effect.

Conclusion

The results of this study suggest that S. variabile has the potential to promote TSG-6 secretion, thereby reducing RA inflammation.
Spatial and seasonal variations of chlorophyll a in Zhanjiang Bay, China, and controlling factors
Authors: Wang Shuangling , Zhou Fengxia , Chen Fajin , Zhu Qingmei , Meng Yafei
Published: June 2024

Based on on-site survey data from 26 stations in the surface seawater of Zhanjiang Bay in April (spring), July (summer), September (autumn), and December (winter) of 2017, the spatial distribution characteristics of chlorophyll a (Chl a) and nutrients in the surface seawater of Zhanjiang Bay in different seasons were analyzed, and the regulatory mechanism of chlorophyll a spatiotemporal changes was discussed. The results showed that the Chl a concentrations in the surface water of Zhanjiang Bay are 0.44–37.43 μg/L, and are highest in summer and lowest in spring (summer: 11.6 µg/L; winter: 11.5 µg/L; autumn: 10.7 µg/L; spring: 1.8 µg/L). The spatial distribution of surface seawater Chl a in different seasons shows an opposite trend to the spatial distribution of nutrients. The study revealed that the low Chl a concentration in spring is mainly limited by SiO3-Si, while the high Chl a concentration in winter is closely related to climate conditions and coastal currents. This study suggests that based on the influence of monsoon climate and land rainfall erosion, the particulate organic carbon (POC) in Zhanjiang Bay in spring and summer is derived from land-based inputs, while in autumn and winter, the POC in the surface water of Zhanjiang Bay is mainly derived from in situ phytoplankton production. The dominant factors affecting the distribution of Chl a in the surface water of Zhanjiang Bay vary in different seasons, and are comprehensively influenced by terrestrial nutrient transport, artificial aquaculture, climate conditions, hydrodynamic conditions in the bay, and the coastal current of western Guangdong outside of the bay. The results of this study can provide scientific basis for improving the environment of Zhanjiang bay.