bluuebunny/crossref_metadata_2025 huggingface dataset:
Uric acid elevation in pediatric patients with dilated cardiomyopathy and prediction of mortality
Authors: Han Yong , Chen Cheng , Qin Suyuan , Liu Dongli , Pang Yusheng
Published: July 2024

Background and aims

Pediatric dilated cardiomyopathy (DCM) is a primary cause of heart failure, highlighting the urgent need for effective prognostic markers.

Methods

We performed a single-center retrospective study involving 145 children diagnosed with DCM, with a median follow-up period of 4.0 months (interquartile range: 6.2–108.4 months). The relationship between serum uric acid (SUA) levels and all-cause mortality was assessed using Kaplan–Meier survival curves, multivariate Cox proportional hazard models, and restricted cubic spline (RCS) models.

Results

Of the 145 children with DCM (median age 5.7 years; 61.4% male), 45 (31%) died within 1 year, and 65 (44.8%) died during the maximum follow-up period. In adjusted multivariate Cox regression models, each log2 SUA increase was linked to a higher risk of 1-year mortality [hazard ratio (HR), 2.66; 95% confidence interval (CI), 1.41–5.01] and overall mortality (HR, 1.97; 95% CI, 1.15–3.37). The highest SUA tertile showed a greater risk of mortality at 1 year (HR, 4.26; 95% CI: 1.5–12.06) and during the maximum follow-up (HR, 2.56; 95% CI: 1.06–6.16) compared with the lowest tertile. RCS models indicated an inverted L-shaped association between baseline SUA levels and overall mortality risk, with age-stratified analyses revealing a linear and U-shaped relationship in children ≤10 and >10 years, respectively. Further age-stratified analyses highlighted the modifying effect of age on this association.

Conclusion

Elevated SUA levels are a significant predictor of mortality in pediatric DCM, with a pronounced impact on children under 10 years of age. Therefore, SUA levels could serve as potential biomarkers for risk stratification in this population.
Complete vs. incomplete percutaneous revascularization in patients with chronic total coronary artery occlusion
Authors: Maestre-Luque Luis Carlos , Gonzalez-Manzanares Rafael , Suárez de Lezo Javier , Hidalgo Francisco , Barreiro-Mesa Lucas , de Juan Jaime , Gallo Ignacio , Perea Jorge , Alvarado Marco , Romero Miguel , Ojeda Soledad , Pan Manuel
Published: July 2024

Introduction

There is current controversy surrounding the benefits of percutaneous coronary intervention (PCI) of chronic total coronary occlusions (CTO). We aimed to evaluate the impact of complete percutaneous revascularization on major adverse cardiovascular events (MACE) in patients with CTO.

Methods

A retrospective observational study was conducted of consecutive patients referred for invasive coronary angiography at a single center between January 2018 and December 2019 and at least a CTO. The patients were divided into two groups according to the result of the procedure: complete revascularization of CTO (CR-CTO) versus incomplete revascularization (ICR-CTO) (patients with at least one non-recanalized CTO). Short- and mid-term clinical outcomes were evaluated. The primary endpoint was a composite of MACE that included all-cause death, non-fatal myocardial infarction, non-fatal stroke, or unplanned revascularization.

Results

In total, 359 patients with CTO were included. The median age was 68 years [interquartile range (IQR) 60–77 years], 66 (18%) were women and 169 (47.3%) had diabetes mellitus. In all, 167 (46.5%) patients received complete revascularization. After a median follow-up of 42 months (IQR 46–50 months), the primary endpoint occurred in 39 (23.4%) patients in the CR-CTO group and in 75 (39.1%) in the ICR-CTO group (HR 0.50, 95% CI 0.34–0.74; p < 0.001). This association remained significant in an inverse probability weighted model considering prognostic factors (adjusted HR 0.61, 95% CI 0.41–0.92; p = 0.018) and was driven by lower rates of all-cause death (adjusted OR 0.50, 95% CI 0.23–0.84; p = 0.01).

Conclusions

Complete revascularization of CTO was associated with a lower risk of MACE in the midterm follow up.
An automatic measure for speech intelligibility in dysarthrias—validation across multiple languages and neurological disorders
Authors: Tröger Johannes , Dörr Felix , Schwed Louisa , Linz Nicklas , König Alexandra , Thies Tabea , Barbe Michael T. , Orozco-Arroyave Juan Rafael , Rusz Jan
Published: July 2024

Introduction

Dysarthria, a motor speech disorder caused by muscle weakness or paralysis, severely impacts speech intelligibility and quality of life. The condition is prevalent in motor speech disorders such as Parkinson's disease (PD), atypical parkinsonism such as progressive supranuclear palsy (PSP), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Improving intelligibility is not only an outcome that matters to patients but can also play a critical role as an endpoint in clinical research and drug development. This study validates a digital measure for speech intelligibility, the ki: SB-M intelligibility score, across various motor speech disorders and languages following the Digital Medicine Society (DiMe) V3 framework.

Methods

The study used four datasets: healthy controls (HCs) and patients with PD, HD, PSP, and ALS from Czech, Colombian, and German populations. Participants’ speech intelligibility was assessed using the ki: SB-M intelligibility score, which is derived from automatic speech recognition (ASR) systems. Verification with inter-ASR reliability and temporal consistency, analytical validation with correlations to gold standard clinical dysarthria scores in each disease, and clinical validation with group comparisons between HCs and patients were performed.

Results

Verification showed good to excellent inter-rater reliability between ASR systems and fair to good consistency. Analytical validation revealed significant correlations between the SB-M intelligibility score and established clinical measures for speech impairments across all patient groups and languages. Clinical validation demonstrated significant differences in intelligibility scores between pathological groups and healthy controls, indicating the measure's discriminative capability.

Discussion

The ki: SB-M intelligibility score is a reliable, valid, and clinically relevant tool for assessing speech intelligibility in motor speech disorders. It holds promise for improving clinical trials through automated, objective, and scalable assessments. Future studies should explore its utility in monitoring disease progression and therapeutic efficacy as well as add data from further dysarthrias to the validation.
Identifying queer discourses and navigational strategies in mathematics for undergraduate STEM students
Authors: Voigt Matthew
Published: July 2024

Introduction

While research has explored racialized and gendered discourses in mathematics, there is a gap in understanding the experiences of Queer students and the discourses related to sexual identity in mathematics. This study aims to identify the discourses about mathematics that Queer STEM students describe in relation to their Queer identity and how they navigate these discourses.

Methods

Using phenomenology, individual interviews were conducted with 17 Queer STEM students at four universities in the United States. The interviews explored their life histories, experiences in mathematics, and responses to vignettes depicting mathematical scenarios. Grounded theory was leveraged to analyze the interviews to build a framework for Queer discourses and navigational strategies.

Results

Seven Queer discourses in mathematics were identified with underlying notions of exclusion and irrelevancy. The most prevalent discourses cast Queer identity as being irrelevant (erasure), unseen (heteronormative), or discriminated against (marginalized) in mathematics. At the same time there were some beliefs that Queer identity acceptance was unknown (ambiguous) was treated equally (normalized) or was accepted and even valued in math. Key findings from the study help theory build an exclusion-irrelevancy space to network together mathematical discourses and highlight how Queer marginalization is acted upon based on notions of rightful presence and not mathematical success.

Discussion

This study highlights the need to recognize and address the marginalization of Queer students in mathematics. By understanding the discourses and navigational strategies employed by these students, educators can create more inclusive and equitable STEM environments. It is critical to recognize and build upon the unique strengths of Queer students in mathematics, rather than focusing only on the challenges they face.
Evaluation and influencing factors of ecological resilience in tourism villages from farmers’ perspectives: a case study of Chinese minority settlement areas
Authors: Wu Jilin , Yang Yimin , Zuo Jinyou , Cao Qingqing , Guo Derong , Liu Shuiliang
Published: July 2024

Rural social-ecological systems have been significantly impacted by the development of rural tourism, creating substantial challenges for the synergistic development of rural ecological restoration and agricultural workers’ household livelihoods. In alignment with the United Nations Decade on Ecosystem Restoration action plan, it is crucial to understand the ecological resilience of tourism villages from the perspective of farmers to achieve sustainable development. Questionnaires and semi-structured interviews were conducted in this study to gather livelihood data from farmers in tourism villages in Xiangxi, China, a region primarily inhabited by ethnic minorities. A measurement index system for the ecological resilience of rural tourism was constructed based on the three dimensions: pressure, state, and response. A comprehensive index method was employed for quantitative evaluation, and influencing factors were analyzed using an obstacle model. The results show that farmers’ livelihoods can be divided into four types: tourism-led, labor-led, agriculture-led, and part-time tourism-based. Their ecological resilience indices are 0.4516, 0.4177, 0.4001, and 0.4590, respectively, representing an overall intermediate level. There are differences in various indices for different livelihood types, with the highest stress index observed in labor-led farmers (0.1655), the highest state index in agriculture-led farming households (0.1585), and the highest response index in tourism-led farming households (0.1766). Common obstacles to the ecological resilience of farmers and their villages include the number of family members engaged in tourism work, the area of forest land, and the farmers’ understanding of ecological policies affecting them. Additionally, core family members’ education levels and the area of homesteads emerged as important obstacle factors. Based on these research findings, recommendations are proposed to enhance the ecological resilience of rural farmer households in the tourism villages of ethnic minority areas. The aim is to provide valuable case studies for promoting the sustainable development of rural tourism in underdeveloped regions worldwide.
Benthic communities under methane gradient in the Laptev and East Siberian seas
Authors: Konovalova Olga , Rimskaya-Korsakova Nadezhda , Kuznetsov Petr , Osadchiev Alexander , Fedyaeva Maria , Moiseeva Iuliia , Purgina Darya , Kosmach Denis , Semiletov Igor
Published: July 2024

Introduction

Methane seeps influence surrounding benthic communities in different ways from slight changes in benthic abundance and biomass to major altering the species composition.

Materials and Methods

We studied benthic communities of 14 methane seep flares in Laptev and East Siberian seas with comparative analysis of species composition and abiotic parameters at the nearby areas not affected by methane seeps. The species diversity was comparable at seep and non-seep sites varying from 3.9 to 39.6 taxa per 100 individuals and from 4.5 to 34.8 taxa per 100 individuals, correspondingly.

Results

The Laptev Slope community corresponds with the Polychaeta-community, encircling the upper continental slope area of the entire Siberian Arctic. The Lower Shelf community described in this study apparently corresponds with the Ophiocten sericeum community identified in the shelf areas of the Kara, Laptev and East Siberian seas. The Upper Shelf community is mostly inhabited by the bivalves species such as Portlandia arctica, Ennucula tenuis and Astarte montagui communities. The Estuarine community, which is the poorest by diversity but has high values of abundance and biomass is directly influenced by the Lena River runoff in terms of lower salinities and higher sedimentation rates.

Discussion

Throughout the study area, the differences between the Estuarine, Upper Shelf, Lower Shelf and Laptev Slope communities exceeded the differences between the seep and background non-seep areas. Several taxa demonstrated correlations with different environmental factors, including the latitude, depth, temperature, salinity, pH and methane content, not depending on the revealed benthic community. Eight taxa demonstrated correlations with the methane content measured at different sediment depths. Two siboglinids taxa demonstrated high abundances at stations with highest methane content deep in the sediment. At the Siberian shelf, our geochemical data for siboglinid habitats are the first to be published so far.
Causal relationship between complement C1QB and colorectal cancer: a drug target Mendelian randomization study
Authors: Jiao Mingwen , Cui Yuying , Qiu Xiaodong , Liang Xuezhen , Li Junhan , Guo Congcong , Tian Hu
Published: July 2024

Background

Colorectal cancer is influenced by several factors such as unhealthy habits and genetic factors. C1QB has been linked to a number of malignancies. However, uncertainty surrounds the connection between C1QB and CRC. Therefore, this study aimed to explore a bidirectional causal relationship of C1QB as a drug target in CRC through Mendelian randomization (MR) analysis.

Methods

The GWASs for C1QB and CRC were obtained from the Integrative Epidemiology Unit Open GWAS database. There were five strategies to investigate MR. Sensitivity analysis was carried out via tests for heterogeneity, horizontal pleiotropy and leave-one-out effects to evaluate the dependability of the MR analysis results. Furthermore, colocalization analysis of C1QB and CRC, protein-protein interaction network and drug prediction according to exposure factors as well as phenotype scanning were performed.

Results

The results of forward MR analysis demonstrated that C1QB was a risk factor for CRC (OR = 1.104, p = 0.033). However, we did not find a causal relationship between CRC and C1QB (reverse MR). Rs294180 and rs291985 corresponded to the same linkage interval and had the potential to influence C1QB and CRC, respectively. The PPI results demonstrated that C1QB interacted with 10 genes (C1QA, C1QC, C1R, C1S, C2, C4A, C4B, CALR, SERPING1, and VSIG4). Additionally, 21 medications were predicted to match C1QB. Molecular docking data, including for benzo(a)pyrene, 1-naphthylisothiocyanate, calcitriol and medroxyprogesterone acetate, revealed excellent binding for drugs and proteins. Moreover, we identified 29 diseases that were associated with C1QB and related medicines via disease prediction and intersection methods. As a therapeutic target for CRC, phenotypic scanning revealed that C1QB does not significantly affect weight loss, liver cirrhosis, or nonalcoholic fatty liver disease, but might have protective impacts on ovarian cancer and melanoma.

Conclusion

The results highlight a causal relationship between C1QB and CRC and imply an oncogenic role for C1QB in CRC, as potential drug targets. Drugs designed to target C1QB have a greater chance of success in clinical trials and are expected to help prioritize CRC drug development and reduce drug development costs. That provided a theoretical foundation and reference for research on CRC and C1QB in MR.
TRP channel-related LncRNAs, AC092535.4 and LINC01637, as novel prognostic biomarkers for uveal melanoma
Authors: Zhang Min , Ni Jinglan , Liu Dongyue , Cui Yubo , Ma Xiaochen , Zhao Jun
Published: July 2024

Introduction

Transient receptor potential (TRP) channels function as cellular sensors with a broad impact, and their dysregulation is linked to numerous cancers. The influence of TRP channel-related long noncoding RNAs (TCRLs) on uveal melanoma (UM) remains poorly understood.

Methods

We employed bioinformatics to examine the RNA-seq data and relevant clinical information of UM in the TCGA databases. By implementing coexpression analysis, we identified differentially expressed TCRLs. Using univariate Cox regression analysis, selection operator (LASSO) algorithm and stepwise regression, five key prognostic biomarkers were chosen. The high- and low-risk groups were divided based on the risk scores. Afterwards, the prediction performance of the signature was evaluated by receiver operating characteristic (ROC) curve and Kaplan-Meier (K-M) survival analysis. The functional enrichment analysis of TCRLs was also investigated. Following that, we examined immune cell infiltration, immune checkpoint expression, and tumor immune microenvironment between patients in high and low risk groups. TCRLs were validated using Random forests and multifactor Cox analysis. Candidate biomarkers were identified and screened. Finally, the effects of the candidate biomarkers on the proliferation, migration and invasion of UM cells were detected by CCK-8 assay, migration assay and perforation invasion assay.

Results

The risk score generated by five TCRLs demonstrated robust predictive power. The high-risk group exhibited a poorer prognosis, increased immune cell infiltration, and an active tumor immune microenvironment compared to the low-risk group. Furthermore, two TCRLs of risk score, AC092535.4 and LINC01637, were screened to multiplex modelling. The in vitro experiments demonstrated that UM cells were suppressed following AC092535.4 or LINC01637 knockdown.

Discussion

Two TCRLs, AC092535.4 and LINC01637, serve as novel prognostic biomarkers for uveal melanoma and may present potential therapeutic targets.
The impact of widowhood on mental health: anxiety, depression, and stress among widowed women in Nepal
Authors: Mamidanna Pooja , Thagunna Narendra Singh , Dangi Jyotshna , Zelman Diane C.
Published: July 2024

Introduction

In South Asia, particularly in regions with strong patriarchal norms, widowhood is stigmatized, compounding the negative impact of grief and partner loss. This study measured the prevalence of mental health symptoms among widows in Nepal and its relationship to demographic variables.

Methods

This cross-sectional study surveyed 588 Nepalese widows from six districts in Nepal (mean age = 52.62, SD = 13.99) who had lost their spouses within the past two years. Participants completed the Anxiety, Depression and Stress Scale (ADSS). Analyses examined prevalence of anxiety, depression, and stress symptoms, using standard ADSS cut-points. Level of anxiety, depression, and stress symptoms measured by the ADSS in the sample were also compared with female psychiatric and nonpsychiatric normative ADSS data, and were compared with one available comparison sample (a sample of older Nepalese women). Measures of association between ADSS scores and demographic variables were computed.

Results

Results showed that a high percentage of the Nepalese widows reported moderate to severe symptoms of anxiety, depression, and stress. They also endorsed significantly higher levels of anxiety, depression, and stress symptoms relative to normative data and the comparison sample. Stress scores were significantly negatively correlated with age, Anxiety and Depression scores were associated with income under the poverty line, and Depression scores were associated with homemaker status.

Discussion

These findings confirm the high emotional distress among widowed women in Nepal, and establish the relationship between emotional distress and poverty, homemaker status, and age. These findings can inform public health efforts and mental health care providers regarding the mental health needs of widows in Nepal.
Scinderin is a potential prognostic biomarker and correlated with immunological regulation: from pan-cancer analysis to liver hepatocellular carcinoma
Authors: Zhai Shengyong , Li Yuhua , Yang Yuanyuan , Lang Wei , Liu Xiaoxia , Liu Kai , Qu Jianjun , Zhu Lingyu
Published: July 2024

Aim

This study aimed to systematically dissect the role of Scinderin (SCIN) in tumorigenesis.

Methods

Bioinformatics techniques were employed based on cancer data from TCGA, ENCORI, HPA, GEPIA2, UALCAN, Kaplan-Meier plotter, TIMER, TISIDB, cBioPortal, HCCDB, GeneMANIA and LinkedOmics database. Experiments in vitro and in vivo were conducted to dissect the role of SCIN in liver hepatocellular carcinoma (LIHC).

Results

Significantly differential expression of SCIN was found in nine types of cancers, including LIHC. Through pan-cancer analysis, the correlations between SCIN expression with prognosis and immune cell infiltration were proven, especially in LIHC, ovarian serous cystadenocarcinoma and lung adenocarcinoma. The highest frequency of alteration in SCIN (6.81%) was seen in patients with uterine corpus endometrial carcinoma, in which “mutation” was the predominant type, with a frequency of about 5.29%; meanwhile, S673F and S381Y were the two most frequent mutation sites. Furthermore, the abnormal expression of SCIN exhibited a strong relationship with immune cell subtypes, immune checkpoint genes, tumor mutation burden, microsatellite instability, neoantigen, molecular subtypes, mismatch repair signatures and DNA methyl-transferase in different cancer types. Through comparative analysis, we discovered that SCIN was dramatically up-regulated in LIHC, and associated with poor survival. Experiments in vitro and in vivo suggested the knockdown of SCIN could suppress tumor cell proliferation and improve the survival rate partly in animal models.

Conclusion

This study reveals SCIN may be a promising biomarker for prognosis and treatment in certain cancers, especially in LIHC.
“Dynamics of chromophoric dissolved organic matter in the Atlantic Ocean: unravelling province-dependent relationships, optical complexity, and environmental influences”
Authors: Sabbaghzadeh Bita , Uher Guenther , Upstill-Goddard Robert
Published: July 2024

We report on the spatial distributions and optical characteristics of chromophoric dissolved organic matter (CDOM) in the sea surface microlayer (SML), subsurface seawater (SSW), and water column profiles down to 500 m across a range of Atlantic Ocean biogeochemical provinces during two cruises of the UK Atlantic Meridional Transect program (AMT24 and AMT25). We measured the CDOM absorption coefficient at 300 nm, aCDOM(300), and determined CDOM spectral slopes across two UV wavelength ranges: S1 (275-295 nm) and S2 (350-400 nm). We used spectral slope ratios (SR: S1/S2) to infer CDOM source characteristics and transformation history. During both cruises, SML aCDOM(300) was highest in the Northern Hemisphere, particularly in the North Atlantic Drift Region (NADR). CDOM was always enriched in the SML, with enrichment factors (SML aCDOM(300) / SSW aCDOM(300)) ranging from 1.03 to 2.00, reflecting preferential accumulation of CDOM in the SML. We also found a significant inverse correlation between aCDOM(300) and S1 in both the SML (Spearman’s rank correlation coefficient, r2 = -0.75, p < 0.001, n = 114) and water column profiles (r2 = -0.74, p < 0.001, n = 845). Biogeochemical province-dependent variations in the relationships between CDOM and chlorophyll a were also observed. In high-latitude regions, elevated aCDOM(300) and low SR values indicated a dominance of terrestrially-derived CDOM, whereas oligotrophic subtropical areas showed lower aCDOM(300) and higher SR values, suggestive of aged, refractory, and photodegraded biologically-derived CDOM. Taken together, these findings reveal a complexity of drivers affecting CDOM distributions and spectral properties, which may limit the use of CDOM in predictive relationships in the oceans. However, the potential use of chlorophyll a as a CDOM proxy may prove most successful in open ocean regions devoid of terrestrial inputs, where biological production predominates.
Ocular hypertension after EyeCee One preload lens implantation: a retrospective cohort study
Authors: González-Martín-Moro Julio , Fernández Miguel Yolanda , Castro-Rebollo María , Izquierdo-Rodríguez Carlos , Prieto-Garrido Francisco Luis , Padeira Iranzo Victoria , Mittendrein Vanesa , Miralles Pechuan Vicente , Ruiz-Pomeda Alicia , Cobo-Soriano Rosario
Published: July 2024

Objective

In 2022, several cases of ocular hypertension (OHT) related to EyeCee One preloaded IOLs were reported. The aim of this study was to determine the presurgical and surgical variables associated with this response.

Methods and analysis

An analysis was conducted on patients who underwent isolated cataract surgery between September 2022 and December 2022 at the Hospital Universitario del Henares. The influence of potential factors was studied using the Kruskal–Wallis test and multiple regression analysis.

Results

A total of 353 cataract surgeries were included in the study. No significant differences between the different IOLs were found related to a change in the IOP on the first postoperative day (p = 0.395), but the change in the IOP after 1 month was higher in the EyeCee One group (p = 0.016). Approximately 6.1% of the patients who received EyeCee One had an IOP increase greater than 10 mmHg, compared to only 0.8% of the patients who received other IOLs. The odds ratio (OR) of experiencing an IOP increase greater than 10 mmHg in the EyeCee One group at the 1-month visit was 7.99 (1.52–41.99). The multiple regression analysis showed that receiving the EyeCee One lens was associated with a 2-mmHg increase in IOP. A previous history of glaucoma or OHT was not associated with greater IOP. Two patients in the EyeCee One group developed severe visual loss.

Conclusion

Patients who received the EyeCee One IOL experienced significant increases in IOP at the 1-month visit. A small number of patients might suffer visual loss secondary to the rise in IOP.
The influence of body fat content and distribution on bone mass in healthy Chinese adults
Authors: Chen Bin , Liu Gongwen , Wang Yike , Xu Youjia
Published: July 2024

Background

Previous studies have reported a close relationship between body mass index (BMI) and bone mineral density (BMD). However, the effects of fat on bone mass remain controversial, particularly for fat tissue distribution. The aim of this study was to evaluate the association between regional fat percentage and BMD using a population-based database.

Methods

This study included participants who were referred to the Department of Radio Diagnosis for dual-energy X-ray absorptiometry (DEXA) scan from January 2018 to December 2020. The relationships between BMI and regional fat percentage with BMD were assessed using multiple linear regression and generalized additive models. The risk of low bone mass was determined using logistic regression.

Results

There was a negative relationship between the regional fat percentage and femoral neck BMD (FN BMD) or lumbar spine BMD (LS BMD) in both genders (p < 0.05). In females, an inverted U-shaped relationship was observed between regional fat percentage and BMD at both the femoral neck and lumbar spine. The impact of trunk fat percentage on LS BMD was associated with the highest OR of low bone mass in females (OR 3.1, 95% CI 2.6 to 3.7, p for trend <0.001), while the impact of abdomen fat percentage on FN BMD was associated with the highest OR of low bone mass in males (OR 2.2, 95% CI 1.8 to 2.7, p for trend <0.001).

Conclusion

There was an inverted U-shaped relationship between regional fat percentage and BMD. Excessive regional fat percentage may be harmful to bone health in both genders. To promote bone health, males should restrict their abdomen circumference and avoid abdominal adiposity, while females should control their trunk circumference.
Real-world effectiveness and safety of Baloxavir Marboxil or Oseltamivir in outpatients with uncomplicated influenza A: an ambispective, observational, multi-center study
Authors: Cai Jianpeng , Wang Hongyu , Ye Xiaoting , Lu Shengjia , Tan Zhili , Li Zhonghua , Lin Dan , Qian Jiancheng , Lu Xiaoxian , Wan Jiaolong , Wang Jie , Ai Jingwen , Pu Yonglan , Qu Lihong , Wang Sen
Published: July 2024

Introduction

Baloxavir Marboxil is a per oral small-molecule antiviral for the treatment of influenza. While the efficacy and safety of Baloxavir Marboxil have been thoroughly characterized across an extensive clinical trial, studies on the effectiveness of Baloxavir Marboxil in a real-world setting are still scarce.

Methods

We conducted an ambispective, observational, multi-center study that enrolled uncomplicated in-fluenza outpatients treated with Baloxavir Marboxil or Oseltamivir in East China. The primary endpoint was time from treatment to alleviation of all influenza symptoms (TTAIS). The secondary endpoints included time from treatment to alleviation of fever (TTAF) and household transmission during the duration of influenza.

Results

A total of 509 patients were enrolled. The median TTAIS in the Baloxavir Marboxil group and the Oseltamivir group was 28.0  h (IQR, 20.0 to 50.0) and 48.0  h (IQR, 30.0 to 67.0), respectively. The median TTAF in the Baloxavir Marboxil group and the Oseltamivir group was 18  h (IQR, 10.0–24.0) and 30.0  h (IQR, 19.0–48.0). In the COX multivariable analysis, Baloxavir Marboxil reduced the duration of influenza symptoms (HR  =  1.36 [95%CI:1.12–1.64], p =  0.002) and the duration of fever (HR  =  1.93 [95%CI:1.48–2.52], p < 0.001) compared to Oseltamivir. When antiviral drugs were given within 12–48  h after symptom onset, the Baloxavir Marboxil group had a significantly shorter TTAIS compared to the Oseltamivir group. There was no significant difference in the rate of adverse events between the two group (p = 0.555).

Discussion

Baloxavir Marboxil was superior to Oseltamivir in alleviating influenza symptoms in outpatients with uncomplicated influenza. Our findings suggested that compared to Oseltamivir, Baloxavir Marboxil might be more appropriate for patients with influenza 12– 48 h after symptom onset.
ClpA affects the virulence of Paracidovorax citrulli on melon by regulating RepA
Authors: Ziye Shang , Yuqiang Zhao , Shitong Wu , Ling Cai , Chenchao Sun , Jun Wang , Weirong Gong , Yanli Tian , Baishi Hu
Published: July 2024

ClpA is a widely conserved protease in bacteria that plays a key role in virulence. To investigate its specific mechanism of action in the pathogenicity of Paracidovorax citrulli (formerly Acidovorax citrulli), we constructed a ClpA deletion mutant, ΔClpA. The ΔClpA mutant of P. citrulli displayed reduced virulence on melon seedlings, and reduced motility, swarming ability, and antioxidant capacity. On the other hand, the ClpA deletion of P. citrulli mutant reduced the resistance to elevated temperature and enhanced biofilm formation ability. Using qRT-PCR, we observed that ClpA negatively regulates the expression of the virulence-related genes virB, pilR, pilA, and fliM, while positively regulating hrpG, hrcQ, and trbC. Bacterial double hybrid and Glutathione-S-transferase pulldown (GST-pulldown) results showed that ClpA interacts directly with RepA, and negatively regulates the expression of RepA. After deletion of the RepA gene, the pathogenicity of P. citrulli was lost, biofilm formation ability was enhanced, and the expression of hrpG, pilR, and trbC was positively regulated. These results indicate that ClpA plays a key role in the regulation of several virulence traits of P. citrulli, paving the way for future studies to better elucidate the virulence mechanisms of this bacterial plant pathogen.
Defining a clinically meaningful within-patient change threshold for the Cohen-Mansfield Agitation Inventory in Alzheimer’s dementia
Authors: Meunier Juliette , Creel Kristin , Loubert Angély , Larsen Klaus Groes , Aggarwal Jyoti , Hefting Nanco , Oberdhan Dorothee
Published: July 2024

Introduction

The Cohen-Mansfield Agitation Inventory (CMAI) quantifies the frequency of agitation behaviors in elderly persons. This post hoc analysis of data from the brexpiprazole clinical program aimed to determine a meaningful within-patient change (MWPC) threshold for CMAI Total score among patients with agitation associated with dementia due to Alzheimer’s disease.

Methods

Data were included from three 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-arm trials of brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer’s disease (ClinicalTrials.gov identifiers: NCT01862640, NCT01922258, NCT03548584). Change in CMAI Total score (range 29–203; higher scores indicate higher frequency of agitation behaviors) from baseline to Week 12 was the primary endpoint in each trial. MWPC thresholds were estimated from anchor-based mean change analyses and receiver operating characteristic (ROC) curves. The Clinical Global Impression–Severity of illness (CGI-S) and Clinical Global Impression–Improvement (CGI-I) scales, both as related to agitation, were used as anchors. Empirical cumulative distribution functions (eCDFs) and probability density functions (PDFs) were plotted as supportive evidence. Distribution-based methods were also employed.

Results

Data from 898 patients were analyzed (mean age, 73.7 years; mean baseline CMAI Total score, 73.8). The mean CMAI Total score change corresponding to a difference of small improvement vs. stable (CGI-S one-point decrease vs. no change), or minimally improved vs. no change (CGI-I rating of 3 vs. 4), ranged from −10.6 to −13.5 points. The mean CMAI Total score change corresponding to a difference of moderate improvement vs. stable (CGI-S two-point decrease vs. no change), or much improved vs. no change (CGI-I rating of 2 vs. 4), ranged from −20.2 to −25.7 points. ROC curve analyses generally produced smaller estimates of meaningful change. eCDFs and PDFs showed good distribution and separation of CMAI Total score change between CGI-S/CGI-I categories. In distribution-based analyses, the minimal detectable change for CMAI Total score (10.5–11.8 points) was generally lower than anchor-suggested thresholds.

Conclusion

Triangulation of evidence from anchor- and distribution-based analyses supports an MWPC threshold for CMAI Total score of −20 points, with a threshold range of −15 to −25 points, in patients with agitation associated with dementia due to Alzheimer’s disease.
Quantification of morpho-hemodynamic changes in unruptured intracranial aneurysms with irregular pulsation during the cardiac cycle using 4D-CTA
Authors: Chen Shiyao , Zhang Wen , Cheng Yunzhang , Wang Guohui , Lv Nan
Published: July 2024

Background and purpose

Previous studies predicting the rupture risk of intracranial aneurysms (IAs) have predominantly utilized static imaging data, overlooking the dynamic blood flow and biomechanical properties of the aneurysm wall. Irregular pulsation detected by 4D-CTA is a potential predictor of aneurysm rupture, albeit with uncertain clinical significance. This study aimed to analyze the changes in morpho-hemodynamic characteristics of IAs during the cardiac cycle to elucidate the dynamic changes and the associated hemodynamic mechanisms.

Methods

A retrospective review was conducted on the 4D-CTA data of IA patients between January 2017 and September 2019. R-R intervals were segmented into 20-time phases, reconstructing 20 CT datasets to identify irregular pulsation and extract 3D aneurysm models. Computational fluid dynamics (CFD) simulations analyzed hemodynamic parameters such as oscillatory shear index (OSI) and relative residence time (RRT). Changes in morpho-hemodynamic characteristics were quantified in terms of the absolute change (parameter*) and relative change rate (parameter%). Rupture risk was assessed using the rupture resemblance model (RRS).

Results

Eleven UIAs from 10 patients were finally included, with five aneurysms showing irregular pulsation (45.45%). No significant differences in morpho-hemodynamic characteristics were observed between aneurysms with or without irregular pulsation. More remarkable changes in aneurysm size (size*: 0.59 ± 0.14 mm vs. 0.32 ± 0.12 mm, p = 0.010; size%: 10.49% ± 1.43% vs. 3.95% ± 1.79%, p < 0.001), volume (volume%: 13.72% vs. 6.39%, p = 0.009), OSI (OSI*: 0.02 ± 0.01 vs. 0.004 ± 0.005, p = 0.004; OSI%: 200% vs. 12.50%, p = 0.004) and RRT (RRT%: 97.14% vs. 43.95, p = 0.052) over the cardiac cycle were significantly linked to irregular pulsation. Aneurysms with irregular pulsation demonstrated a more unfavorable hemodynamic environment during the cardiac cycle, irrespective of the predicted rupture risk. Furthermore, irregular pulsation at the aneurysm dome exhibited higher hemodynamic instability than at the sidewall.

Conclusion

Irregular pulsation may indicate hemodynamic instability within the aneurysm, leading to an increased rupture risk in the area where irregular pulsation occurs. This proof-of-concept study could enhance understanding of dynamic changes in UIAs during the cardiac cycle and the underlying hemodynamic mechanisms.
Polygenic scores and Mendelian randomization identify plasma proteins causally implicated in Alzheimer’s disease
Authors: Cammann Davis B. , Lu Yimei , Rotter Jerome I. , Wood Alexis C. , Chen Jingchun
Published: July 2024

Background

An increasing body of evidence suggests that neuroinflammation is one of the key drivers of late-onset Alzheimer’s disease (LOAD) pathology. Due to the increased permeability of the blood–brain barrier (BBB) in older adults, peripheral plasma proteins can infiltrate the central nervous system (CNS) and drive neuroinflammation through interactions with neurons and glial cells. Because these inflammatory factors are heritable, a greater understanding of their genetic relationship with LOAD could identify new biomarkers that contribute to LOAD pathology or offer protection against it.

Methods

We used a genome-wide association study (GWAS) of 90 different plasma proteins (n = 17,747) to create polygenic scores (PGSs) in an independent discovery (cases = 1,852 and controls = 1,990) and replication (cases = 799 and controls = 778) cohort. Multivariate logistic regression was used to associate the plasma protein PGSs with LOAD diagnosis while controlling for age, sex, principal components 1–2, and the number of APOE-e4 alleles as covariates. After meta-analyzing the PGS-LOAD associations between the two cohorts, we then performed a two-sample Mendelian randomization (MR) analysis using the summary statistics of significant plasma protein level PGSs in the meta-analysis as an exposure, and a GWAS of clinically diagnosed LOAD (cases = 21,982, controls = 41,944) as an outcome to explore possible causal relationships between the two.

Results

We identified four plasma protein level PGSs that were significantly associated (FDR-adjusted p < 0.05) with LOAD in a meta-analysis of the discovery and replication cohorts: CX3CL1, hepatocyte growth factor (HGF), TIE2, and matrix metalloproteinase-3 (MMP-3). When these four plasma proteins were used as exposures in MR with LOAD liability as the outcome, plasma levels of HGF were inferred to have a negative causal relationship with the disease when single-nucleotide polymorphisms (SNPs) used as instrumental variables were not restricted to cis-variants (OR/95%CI = 0.945/0.906–0.984, p = 0.005).

Conclusion

Our results show that plasma HGF has a negative causal relationship with LOAD liability that is driven by pleiotropic SNPs possibly involved in other pathways. These findings suggest a low transferability between PGS and MR approaches, and future research should explore ways in which LOAD and the plasma proteome may interact.
Influences of noise reduction on speech intelligibility, listening effort, and sound quality among adults with severe to profound hearing loss
Authors: Dong Ruijuan , Liu Pengfei , Tian Xin , Wang Yuan , Chen Younuo , Zhang Jing , Yang Liu , Zhao Shiyang , Guan Jingjing , Wang Shuo
Published: July 2024

Introduction

Noise reduction (NR) algorithms have been integrated into modern digital hearing aids to reduce noise annoyance and enhance speech intelligibility. This study aimed to evaluate the influences of a novel hearing aid NR algorithm on individuals with severe-to-profound hearing loss.

Methods

Twenty-five participants with severe-to-profound bilateral sensorineural hearing loss underwent three tests (speech intelligibility, listening effort, and subjective sound quality in noise) to investigate the influences of NR. All three tests were performed under three NR strength levels (Off, Moderate, and Strong) for both speech in noise program (SpiN) and speech in loud noise program (SpiLN), comprising six different hearing aid conditions.

Results

NR activation significantly reduced listening effort. Subjective sound quality assessments also exhibited benefits of activated NR in terms of noise suppression, listening comfort, satisfaction, and speech clarity.

Discussion

Individuals with severe-to-profound hearing loss still experienced advantages from NR technology in both listening effort measure and subjective sound quality assessments. Importantly, these benefits did not adversely affect speech intelligibility.
Trends in three malnutrition factors in the global burden of disease: iodine deficiency, vitamin A deficiency, and protein-energy malnutrition (1990–2019)
Authors: Ji Shaorong , Zhou Yinglu , Zhao Qilong , Chen Runtong , Su Zhenni
Published: July 2024

Background

Vitamin A deficiency, iodine deficiency, and protein-energy malnutrition are prevalent malnutrition issues that disproportionately affect low-income countries and pose significant risks to the health and development of children and adolescents. This study offers a detailed examination of these deficiencies' prevalence trends and gender and regional variations using Global Burden of Disease Study data from 1990 to 2019. It also assesses the specific impact on various age groups, providing essential insights for targeted health interventions and policy-making.

Methods

Data spanning from 1990 to 2019 on Vitamin A deficiency, iodine deficiency, and protein-energy malnutrition were extracted from the 2019 Global Burden of Disease Study. Age-Standardized Incidence Rates (ASR) were computed by gender, region, and etiology, utilizing the estimated annual percentage change (EAPC) to assess temporal trends.

Results

In 2019, Central Sub-Saharan Africa had the highest prevalence of Vitamin A deficiency, particularly among males, and iodine deficiency peaked in the same region for both genders. South Asia had the highest incidence of protein-energy malnutrition for both genders. Regions with a low Socio-Demographic Index (SDI) showed lower ASR for these deficiencies. Notably, Cameroon, Equatorial Guinea, and Maldives recorded the highest ASR for vitamin A deficiency, iodine deficiency, and protein-energy malnutrition, respectively. The declining ASR trend for vitamin A deficiency, especially among males, suggests effective interventions. East Asia saw a significant increase in iodine deficiency ASR from 1990 to 2019, particularly among women, requiring targeted interventions. The rising ASR of protein-energy malnutrition in several regions, especially among men, raises concerns. Vitamin A deficiency primarily affected children and adolescents, iodine deficiency predominantly impacted adolescents and young adults, and protein-energy malnutrition was chiefly observed among children under 5 years old. These findings underscore the necessity for tailored interventions considering age-specific nutritional needs and challenges.
Efficacy and safety of radical cystectomy with ileal conduit for muscle-invasive bladder cancer in the elderly: a multicenter retrospective study
Authors: Zhang Heqian , Li Anrui , Wang Wentao , Xu Songlin , Li Changfu , Teng Lichen
Published: July 2024

Objective

Radical cystectomy with ileal conduit is the current mainstay of treatment for muscle-invasive bladder cancer and is also a high-risk procedure. Existing studies have limited targeted assessment of the efficacy and safety of this procedure, and the patient population appropriate for this procedure is still poorly defined. We sought to longitudinally analyze differences in the efficacy and safety of radical cystectomy with ileal conduit by age subgroups to assess whether the age factor should be used as an exclusion criterion when selecting this procedure.

Materials and methods

We retrospectively examined the clinicopathological data of patients with MIBC treated with RC with IC at the Cancer Hospital of Harbin Medical University between February 2014 and October 2023. Additionally, we utilized clinical and pathological data from the SEER database (2000-2020) for external validation of our findings. Patients were categorized into elderly (≥70 years at diagnosis) and non-elderly (<70 years) groups. Statistical analyses included t-tests, non-parametric tests for continuous data, chi-square tests for categorical data, and Kaplan-Meier survival analysis.

Results

In this study, 152 patients were included: 119 were categorized as non-elderly and 33 as elderly. For external validation, data from 416 patients in the SEER database were analyzed, with 172 classified as non-elderly and 244 as elderly. The results indicated that elderly patients were more likely to require ICU transfer postoperatively but exhibited a lower incidence of stoma inflammation. Additionally, both the data from our center and the external validation from the SEER database showed a concordance in cancer-specific survival (CSS) between the elderly and non-elderly groups. The efficacy of RC with IC was comparable in both elderly and non-elderly patients.

Conclusion

For longitudinal age subgroups, RC with IC for both elderly and non-elderly MIBC had good efficacy and safety, and good quality of life after surgery. Although there are surgical and perioperative risks in elderly patients, there is no significant difference compared with non-elderly patients. In elderly patients requiring RC for bladder cancer, IC should remain the preferred mode of urinary diversion, and old age should not be used as an absolute exclusion criterion for IC.
Time budgets and weight shifting as indicators of pain in hospitalized horses
Authors: Nowak Magdalena , Martin-Cirera Albert , Jenner Florien , Auer Ulrike
Published: July 2024

Introduction

Pain assessment in horses presents a significant challenge due to their nonverbal nature and their tendency to conceal signs of discomfort in the presence of potential threats, including humans. Therefore, this study aimed to identify pain-associated behaviors amenable to automated AI-based detection in video recordings. Additionally, it sought to determine correlations between pain intensity and behavioral and postural parameters by analyzing factors such as time budgets, weight shifting, and unstable resting. The ultimate goal is to facilitate the development of AI-based quantitative tools for pain assessment in horses.

Materials and methods

A cohort of 20 horses (mean age 15 ± 8) admitted to a university equine hospital underwent 24-h video recording. Behaviors were manually scored and retrospectively analyzed using Loopy® software. Three pain groups were established based on the Pain Score Vetmeduni Vienna : pain-free (P0), mild to moderate pain (P1), and severe pain (P2).

Results

Weight shifting emerged as a reliable indicator for discriminating between painful and pain-free horses, with significant differences observed between pain groups (p < 0.001) and before and after administration of analgesia. Additionally, severely painful horses (P2 group) exhibited lower frequencies of feeding and resting standing per hour compared to pain-free horses, while displaying a higher frequency of unstable resting per hour.

Discussion

The significant differences observed in these parameters between pain groups offer promising prospects for AI-based analysis and automated pain assessment in equine medicine. Further investigation is imperative to establish precise thresholds. Leveraging such technology has the potential to enable more effective pain detection and management in horses, ultimately enhancing welfare and informing clinical decision-making in equine medicine.