bluuebunny/crossref_metadata_2025 huggingface dataset:
The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study
Authors: Jiang Zong , Cai Xin , Yao Xiaoling , Zhang Shaoqin , Lan Weiya , Jin Zexu , Tang Fang , Ma Wukai , Yao Xueming , Chen Changming , Lan Tianzuo
Published: January 2024

Objective

Osteoarthritis (OA) is the most prevalent joint disease globally, serving as a primary cause of pain and disability. However, the pathological processes underlying OA remain incompletely understood. Several studies have noted an association between cytokines and OA, yet the causal link between them remains ambiguous. This study aims to identify cytokines potentially causally related to OA using Mendelian randomization (MR) analysis, informing early clinical diagnosis and treatment decisions.

Methods

We conducted a genome-wide association study (GWAS) on 12 OA traits involving 177,517 cases and 649,173 controls from 9 international cohorts. For discovery MR analysis, we used 103 cytokines from two European populations as instrumental variables (IVs). Concurrently, another European population OA GWAS database (36,185 cases and 135,185 controls) was used to replicate MR analysis, employing the inverse variance weighted (IVW) method as the primary analytic approach. Additional methods tested included MR Egger, Weighted median, and Weighted mode. We merged the MR findings through meta-analysis. Heterogeneity testing, level pleiotropy testing (MR Egger intercept test and MRPRESSO), and sensitivity analysis via Leave One Out (LOO) were conducted to verify result robustness. Lastly, reverse MR analysis was performed.

Results

The meta-analysis merger revealed a correlation between CX3CL1 cycle levels and increased OA risk (OR=1.070, 95% CI: 1.040-1.110; P<0.010). We also observed associations between MCP4 (OR=0.930, 95% CI: 0.890-0.970; P<0.010) and CCL25 (OR=0.930, 95% CI: 0.890-0.970; P<0.010) with reduced OA risk. The sensitivity analysis results corroborate the robustness of these findings.

Conclusion

Our MR analysis indicates a potential causal relationship between CX3CL1, MCP4, CCL25, and OA risk changes. Further research is warranted to explore the influence of cytokines on OA development.
Sediment source variation using REEs, Sr, and Nd isotopic compositions: a case study in MD05-2901, northwestern South China Sea
Authors: You Chen-Feng , Liao Wei-Lan , Huang Kuo-Fang , Chung Chuan-Hisung , Liu Zhifei
Published: January 2024

The South China Sea (SCS) is the largest marginal sea in the western Pacific, fed by large Asian rivers, characterized by substantial volumes of sediment derived from surrounding Asian continents and islands. This study utilizes the rare earth elements (REEs), Sr isotopes (87Sr/86Sr), and Nd isotopes (ƐNd) in detritus fractions of MD05-2901 sediments in northwestern SCS, to evaluate the relative contribution among the Mekong River, the Red River, the Pearl River, and rivers in SW Taiwan over the last 32 ka. This deep-sea core is located off the coast of central Vietnam, an upwelling region with only minor continental inputs, and this study is important for a better understanding of the main sources of terrigenous material and their temporal variations in the region. In addition, potential particle exchange is examined using the same proxies in the Fe-Mn oxyhydroxide fractions. The obtained records are systematically compared with the available climatic archives in the region. The REEs in the Fe-Mn oxyhydroxides support the argument of water mass signature separation in bulk sediments by chemical leaching procedures. These 87Sr/86Sr in the Fe-Mn oxyhydroxides phase fall in a range between 0.709262 and 0.709313, deviating significantly from the modern seawater. ƐNd values vary >3Ɛ, being more radiogenic in the Fe-Mn oxyhydroxides, where the lowest value occurred in the Bølling/Allerød (B/A) and higher values occurred during the Younger Dryas (YD). The latter implies increased contribution of loess dusts or Taiwanese rivers under dry/cold climatic conditions, compared with the situation in modern times. The Red River and the Mekong River together may have contributed >60% during the Last Glacial Maximum (LGM) and YD. In contrast, the Pearl River components have increased sharply to ~60% during the warm B/A. These results demonstrate that the MD05-2901 sediments sensitively record changes in weathering intensity on land and transport pathways in the coastal regions in the Holocene.
Effect of strain profiling on anisotropic opto-electronic properties of As2X3 (X =S, Te) monolayers from first principles
Authors: Andharia Eesha , Alqurashi Hind , Erikat Ihsan , Hamad Bothina , Manasreh M. O.
Published: January 2024

Strain Engineering is a widely adopted approach to modulate the opto-electronic performance of 2-Dimensional (2D) materials. Recently, anisotropic Van der Waals (vdW) based 2D As2S3 monolayer has gained significant attention within the scientific community due to its stability in ambient conditions. Similar compounds like As2Te3 have also been theoretically explored. However, its indirect bandgap nature limits its application in optical devices. In this study, a systematic study of compressive and tensile strain on three profiles–Uniaxial along a-axis, Uniaxial along b-axis and biaxial strain from −10% to +10%, is performed for As2S3 and As2Te3 monolayers. Certain strain profiles like Uniaxial tensile strain of 8% along b-axis results in transition to direct bandgap material. Similarly, for As2Te3, shear strain of (−10%, +8%) along (a, b) axis results in direct bandgap material. In addition, the anisotropic optical absorption spectrum is obtained for unstrained and strained monolayers within the random phase approximation (RPA).
Retrospective cohort study to evaluate the continuous use of anticholesterolemics and diuretics in patients with COVID-19
Authors: Oliveira Fabrício Marcus Silva , Caetano Mônica Maria Magalhães , Godoy Ana Raquel Viana de , Oliveira Larissa Lilian de , Melo Mambrini Juliana Vaz de , Rezende Marina Santos , Fantini Marina Pinheiro Rocha , Oliveira Mendes Tiago Antônio De , Medeiros Nayara Ingrid , Guimarães Henrique Cerqueira , Fiuza Jacqueline Araújo , Gaze Soraya Torres
Published: January 2024

Purpose

The purpose of this study is to evaluate the interference of the continuous use of drug classes in the expression of biomarkers during the first week of hospitalization and in the prognosis of patients with COVID-19.

Methods

The patients diagnosed with COVID-19 and confirmed with SARS-CoV-2 by RT-qPCR assay underwent the collection of fasting whole blood samples for further analysis. Other data also extracted for this study included age, sex, clinical symptoms, related comorbidities, smoking status, and classes of continuous use. Routine serum biochemical parameters, including alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, C-reactive protein, N-terminal fragment of B-type natriuretic peptide, and cardiac troponin, were measured.

Results

In this cross-sectional study, a total of 176 patients with COVID-19 hospitalizations were included. Among them, 155 patients were discharged (88.5%), and 21 patients died (12%). Among the drug classes evaluated, we verified that the continuous use of diuretic 4.800 (1.853–11.67) (p = 0.0007) and antihypercholesterolemic 3.188 (1.215–7.997) (p = 0.0171) drug classes presented a significant relative risk of death as an outcome when compared to the group of patients who were discharged. We evaluated biomarkers in patients who used continuous antihypercholesterolemic and diuretic drug classes in the first week of hospitalization. We observed significant positive correlations between the levels of CRP with cardiac troponin (r = 0.714), IL-6 (r = 0.600), and IL-10 (r = 0.900) in patients who used continuous anticholesterolemic and diuretic drug classes and were deceased. In these patients, we also evaluated the possible correlations between the biomarkers AST, NT-ProBNP, cardiac troponin, IL-6, IL-8, and IL-10. We observed a significantly negative correlations in AST levels with NT-ProBNP (r = −0.500), cardiac troponin (r = −1.00), IL-6 (r = −1.00), and IL-10 (r = −1.00) and a positive correlation with IL-8 (r = 0.500). We also observed significant negative correlation in the levels of NT-ProBNP with IL-10 (r = −0.800) and a positive correlation with cardiac troponin (r = 0.800). IL-6 levels exhibited positive correlations with cardiac troponin (r = 0.800) and IL-10 (r = 0.700).

Conclusion

In this study, we observed that hospitalized COVID-19 patients who continued using anticholesterolemic and diuretic medications showed a higher number of correlations between biomarkers, indicating a poorer clinical prognosis. These correlations suggest an imbalanced immune response to injuries caused by SARS-CoV-2.
Progressive pulmonary fibrosis in myositis-specific antibody-positive interstitial pneumonia: a retrospective cohort study
Authors: Wang Huijuan , Wang Yuanying , Sun Di , Yu Shiwen , Du Xuqin , Ye Qiao
Published: January 2024

Objectives

Idiopathic inflammatory myopathy (IIM) frequently coexists with interstitial pneumonia (IP) and is commonly the initial or sole manifestation accompanied by positive myositis-specific autoantibodies (MSAs), even in the absence of meeting diagnostic criteria. This study aims to evaluate the proportion of progressive pulmonary fibrosis (PPF) and identify potential predictors influencing the progression of pulmonary fibrosis in patients with MSA-IP.

Methods

This descriptive study employed a retrospective cohort design, enrolling patients diagnosed with interstitial pneumonia and positive MSAs at Beijing Chao-Yang Hospital in a sequential manner. Clinical data were systematically collected from the patients’ medical records during regular follow-up visits conducted every 3 to 6 months. Cox regression analysis was utilized to identify independent predictors of PPF in patients with positive MSAs and interstitial pneumonia.

Results

A total of 307 patients were included in the study, with 30.6% of them developing PPF during a median follow-up period of 22 months. Kaplan–Meier survival curves demonstrated a significantly lower survival in the PPF patients compared to the non-PPF patients (median 11.6 months vs. 31 months, p = 0.000). An acute/subacute onset of interstitial pneumonia (HR 3.231, 95%CI 1.936–5.392, p = 0.000), lower diffusing capacity of the lungs for carbon monoxide (DLCO) % predicted (HR 6.435, 95%CI 4.072–10.017, p = 0.001), and the presence of diffuse alveolar damage (DAD) on high-resolution computed tomography (HRCT) (HR 8.679, 95%CI 1.974–38.157, p = 0.004) emerged as independent predictors of PPF. Notably, the implementation of triple therapy comprising glucocorticoids, immunosuppressants, and antifibrotic drugs was associated with a reduced risk of developing PPF (HR 0.322, 95%CI 0.115–0.899, p = 0.031).

Conclusion

Approximately 30.6% of patients with MSA-IP may develop PPF within the follow-up period. Patients presenting with an acute/subacute onset of interstitial pneumonia, lower predicted DLCO SB% and evidence of DAD on HRCT are more susceptible to developing PPF. Conversely, the administration of triple therapy appears to serve as a protective factor against the development of PPF in patients with MSA-IP.
Systemic inflammation among adults with diagnosed and undiagnosed cardiometabolic conditions: a potential missed opportunity for cardiovascular disease prevention
Authors: Mainous Arch G. , Sharma Pooja , Jo Ara
Published: January 2024

Context

Systemic inflammation is associated with cardiovascular morbidity and mortality. Since inflammation is not screened in the population, the prevalence, particularly among individuals with undiagnosed cardiometabolic disease, is unclear.

Objective

To assess the prevalence of elevated inflammation using high sensitivity C-reactive protein (hs-CRP) (>0.30 mg/dL) in adults with no cardiometabolic disease, undiagnosed disease and diagnosed disease.

Methods

We conducted a cross-sectional analysis of the 2015–2020 National Health and Nutrition Examination Survey which allows for population estimates of the US population. Adults > = 20 years old were included. HsCRP levels >0.30 mg/dL represented inflammation. Individuals were classified into disease defined as having one or more of the following: diagnosed disease--diabetes, hypertension, hyperlipidemia, or obesity by diagnosis; undiagnosed disease (self-report of no doctor diagnosis but positive biomarker); no disease.

Results

12,946 unweighted individuals representing 315,354,183 adults in the US population were assessed. The proportion of adults with systemic inflammation is 34.63%. The proportion of individuals aged 20 years and older with no disease, undiagnosed disease and diagnosed disease and inflammation was 15.1, 29.1 and 41.8%, respectively. When stratifying by race/ethnicity among individuals with elevated inflammation Non-Hispanic Black people have the highest prevalence (50.35%) in individuals with diagnosed disease followed by Hispanics (46.13%) and Non-Hispanic White people (40.15%) (p < 0.01). In logistic regressions adjusted for sociodemographic variables, individuals with undiagnosed cardiometabolic disease have an increased risk of elevated inflammation as measured by CRP (OR 2.38; 95%CI = 1.90–2.99).

Conclusion

In conclusion, a substantial proportion of the adult population, particularly minority and low socioeconomic populations, have elevated inflammation. Systemic inflammation may be a potential focus for disease prevention and disease progression in primary care.
Surgical therapy and outcome of descending necrotizing mediastinitis in Chinese: a single-center series
Authors: Zhao Zhewei , Ma Dongjie , Xu Yuan , Guo Chao , Li Shanqing , Wang Jian , Wang Mu , Qin Yingzhi , Liu Hongsheng
Published: January 2024

Background

Descending Necrotizing Mediastinitis (DNM) is an acute and often fatal infection that affects the neck and mediastinum. DNM treatment consists of broad-spectrum antibiotics, early diagnosis, and surgical debridement with multidisciplinary cooperation. However, owing to the rarity and complexity of this disease, the mortality rate is high. This retrospective study analyzed a single-center experience of managing DNM in Chinese patients over the last 10 years.

Methods

A single-center, retrospective, observational, and descriptive study was conducted on 31 patients with DNM at Peking Union Medical College Hospital from 2012 to 2022. Case report forms were used to collect data which were then analyzed with a focus on surgical management and outcomes.

Results

This study examined the outcomes of 31 patients diagnosed with DNM at our hospital. The most common comorbidities on admission were hypertension (48%) and diabetes mellitus (42%). The degree of diffusion of DNM according to Endo’s classification was classified as follows: type I in 7 patients (22.6%), type IIA in 5 (16.1%), and type IIB in 19 patients (61.3%). Among these patients, 13 (41.9%) were found to have a single microbial infection, while 16 (51.6%) were found to have polymicrobial infections. In all cases, neck drainage was performed via cervicotomy, with multiple drains (64.5%) and vacuum sealing drainage (VSD) (35.5%). Mediastinal drainage was performed via a cervical mediastinotomy (51.6%), video-assisted thoracic surgery (VATS) (41.9%), or thoracotomy (6.5%). The 30-day mortality rate was 25.8% and 24.0 days of the average length of hospital stay.

Conclusion

Early accurate diagnosis and timely intervention have been shown to be correlated with a positive prognosis. Cervicothoracic CT (computed tomography) is essential for the diagnosis, staging, and evaluation of the optimal surgical treatment. Cervicotomy and video-assisted thoracoscopic surgery with percutaneous drainage is effective, even in advanced cases. Additionally, the application of VSD in cervical incision did not improve prognosis but may shorten the length of ICU (intensive care unit) and hospital stays.
Christensenella minuta, a new candidate next-generation probiotic: current evidence and future trajectories
Authors: Ignatyeva Olga , Tolyneva Darya , Kovalyov Aleksandr , Matkava Lorena , Terekhov Mikhail , Kashtanova Daria , Zagainova Anzhelika , Ivanov Mikhail , Yudin Vladimir , Makarov Valentin , Keskinov Anton , Kraevoy Sergey , Yudin Sergey
Published: January 2024

Background

As the field of probiotic research continues to expand, new beneficial strains are being discovered. The Christensenellaceae family and its newly described member, Christensenella minuta, have been shown to offer great health benefits. We aimed to extensively review the existing literature on these microorganisms to highlight the advantages of their use as probiotics and address some of the most challenging aspects of their commercial production and potential solutions.

Methods

We applied a simple search algorithm using the key words “Christensenellaceae” and “Christensenella minuta” to find all articles reporting the biotherapeutic effects of these microorganisms. Only articles reporting evidence-based results were reviewed.

Results

The review showed that Christensenella minuta has demonstrated numerous beneficial properties and a wider range of uses than previously thought. Moreover, it has been shown to be oxygen-tolerant, which is an immense advantage in the manufacturing and production of Christensenella minuta-based biotherapeutics. The results suggest that Christensenellaceae and Christensenella munita specifically can play a crucial role in maintaining a healthy gut microbiome. Furthermore, Christensenellaceae have been associated with weight management. Preliminary studies suggest that this probiotic strain could have a positive impact on metabolic disorders like diabetes and obesity, as well as inflammatory bowel disease.

Conclusion

Christensenellaceae and Christensenella munita specifically offer immense health benefits and could be used in the management and therapy of a wide range of health conditions. In addition to the impressive biotherapeutic effect, Christensenella munita is oxygen-tolerant, which facilitates commercial production and storage.
Increase in invasive group A streptococcal infections in Milan, Italy: a genomic and clinical characterization
Authors: Mangioni Davide , Fox Valeria , Saltini Paola , Lombardi Andrea , Bussini Linda , Carella Francesco , Cariani Lisa , Comelli Agnese , Matinato Caterina , Muscatello Antonio , Teri Antonio , Terranova Leonardo , Cento Valeria , Carloni Sara , Bartoletti Michele , Alteri Claudia , Bandera Alessandra
Published: January 2024

Background

Group A Streptococcus (GAS) causes multiple clinical manifestations, including invasive (iGAS) or even life-threatening (severe-iGAS) infections. After the drop in cases during COVID-19 pandemic, in 2022 a sharp increase of GAS was reported globally.

Methods

GAS strains collected in 09/2022–03/2023 in two university hospitals in Milan, Italy were retrospectively analyzed. Clinical/epidemiological data were combined with whole-genome sequencing to: (i) define resistome/virulome, (ii) identify putative transmission chains, (iii) explore associations between emm-types and clinical severity.

Results

Twenty-eight isolates were available, 19/28 (67.9%) from adults and 9/28 (32.1%) from pediatric population. The criteria for iGAS were met by 19/28 cases (67.9%), of which 11/19 (39.3%) met the further criteria for severe-iGAS. Pediatric cases were mainly non-invasive infections (8/9, 88.9%), adult cases were iGAS and severe-iGAS in 18/19 (94.7%) and 10/19 (52.6%), respectively. Thirteen emm-types were detected, the most prevalent being emm1 and emm12 (6/28 strains each, 21.4%). Single nucleotide polymorphism (SNP) analysis of emm1.0 and emm12.0 strains revealed pairwise SNP distance always >10, inconsistent with unique transmission chains. Emm12.0-type, found to almost exclusively carry virulence factors speH and speI, was mainly detected in children and in no-iGAS infections (55.6 vs. 5.3%, p = 0.007 and 66.7 vs. 0.0%, p < 0.001, respectively), while emm1.0-type was mainly detected in severe-iGAS (0.0 vs. 45.5%, p = 0.045).

Conclusions

This study showed that multiple emm-types contributed to a 2022/2023 GAS infection increase in two hospitals in Milan, with no evidence of direct transmission chains. Specific emm-types could be associated with disease severity or invasiveness. Overall, these results support the integration of classical epidemiological studies with genomic investigation to appropriately manage severe infections and improve surveillance.
Seasonal and spatial variations of Synechococcus in abundance, pigment types, and genetic diversity in a temperate semi-enclosed bay
Authors: Li Suheng , Dong Yi , Sun Xiaoxia , Zhao Yuan , Zhao Li , Zhang Wuchang , Xiao Tian
Published: January 2024

Synechococcus is abundant and globally widespread in various marine environments. Seasonal and spatial variations in Synechococcus abundance, pigment types, and genetic diversity were investigated based on flow cytometric analysis and high-throughput sequencing of cpcBA operon (encoding phycocyanin) and rpoC1 gene (encoding RNA polymerase) in a temperate semi-enclosed bay. Synechococcus abundance exhibited seasonal variations with the highest value in summer and the lowest value in winter, which was consistent with temperature variation. Three pigment types of Synechococcus type 1, type 2, and type 3 were distinguished based on cpcBA operon, which displayed obvious variations spatially between the inner and the outer bay. Freshwater discharge and water turbidity played important roles in regulating Synechococcus pigment types. Synechococcus assemblages were phylogenetically diverse (12 different lineages) based on rpoC1 gene and dominated by three core lineages S5.1-I, S5.1-IX, and S5.2-CB5 in different seasons. Our study demonstrated that Synechococcus abundance, pigment types, and genetic diversity displayed variations seasonally and spatially by different techniques, which were mainly driven by temperature, salinity, nutrients, and turbidity. The combination of more technical means provides more information for studying Synechococcus distribution. In this study, three pigment types of Synechococcus were discriminated simultaneously by dual lasers flow cytometer for the first time.
A porcine circovirus type 2d-based virus-like particle vaccine induces humoral and cellular immune responses and effectively protects pigs against PCV2d challenge
Authors: Kim Kiju , Choi Kyusung , Shin Minna , Hahn Tae-Wook
Published: January 2024

The pathogenic porcine circovirus type 2 (PCV2) leads to significant economic losses in pig production. PCV2d is currently the dominant genotype causing porcine circovirus-associated disease (PCVAD) worldwide. Therefore, development of a recombinant PCV2d-based vaccine is required to elicit complete protection against PCV2d infection. In this study, we generated virus-like particles of PCV2d-based capsid protein (Bac-2dCP) using a baculovirus expression system and evaluated its protective efficacy against PCV2d infection in specific pathogen-free (SPF) pigs. Three-week-old SPF miniature pigs were intramuscularly immunized with purified Bac-2dCP and intranasally challenged with PCV2d at 4 weeks post-vaccination. The Bac-2dCP group showed significantly higher IgG levels and neutralizing antibodies against PCV2b and PCV2d genotypes, as well as increased interferon-γ levels, and increased body weight and average daily weight gain compared with positive (challenged) and negative (unchallenged) controls. In particular, the Bac-2dCP group showed almost complete absence of PCV2d DNA in serum, nasal, and rectal swabs and in lung, lymph node, and kidney tissue samples. However, the positive control group exhibited low levels of neutralizing antibody, and high levels of PCV2 DNA in serum, swab, and tissue samples, resulting in PCV2-associated pathological lesions. The results of this study demonstrated that a recombinant Bac-2dCP vaccine conferred complete protection against a PCV2d challenge in SPF miniature pigs.
Shrub expansion raises both aboveground and underground multifunctionality on a subtropical plateau grassland: coupling multitrophic community assembly to multifunctionality and functional trade-off
Authors: Ding Leilei , Chen Hong , Wang Mengya , Wang Puchang
Published: January 2024

Introduction

Shrubs have expanded into grasslands globally. However, the relative importance of aboveground and underground diversity and the relative importance of underground community assembly and diversity in shaping multifunctionality and functional trade-offs over shrub expansion remains unknown.

Methods

In this study, aboveground and underground multitrophic communities (abundant and rare archaea, bacteria, fungi, nematodes, and protists) and 208 aboveground and underground ecosystem properties or indicators were measured at three stages (Grass, Mosaic, Shrub) of shrub expansion on the Guizhou subtropical plateau grassland to study multifunctionality and functional trade-offs.

Results

The results showed that shrub expansion significantly enhanced aboveground, underground, and entire ecosystem multifunctionality. The functional trade-off intensities of the aboveground, underground, and entire ecosystems showed significant V-shaped changes with shrub expansion. Shrub expansion improved plant species richness and changed the assembly process and species richness of soil abundant and rare subcommunities. Plant species diversity had a greater impact on multifunctionality than soil microbial diversity by more than 16%. The effect of plant species diversity on functional trade-offs was only one-fifth of the effect of soil microbial diversity. The soil microbial species richness did not affect multifunctionality, however, the assembly process of soil microbial communities did. Rather than the assembly process of soil microbial communities, the soil microbial species richness affected functional trade-offs.

Discussion

Our study is the first to couple multitrophic community assemblies to multifunctionality and functional trade-offs. Our results would boost the understanding of the role of aboveground and underground diversity in multifunctionality and functional trade-offs.
Proteomic analysis of holocarboxylase synthetase deficient-MDA-MB-231 breast cancer cells revealed the biochemical changes associated with cell death, impaired growth signaling, and metabolism
Authors: Sukjoi Witchuda , Young Clifford , Acland Mitchell , Siritutsoontorn Siraprapa , Roytrakul Sittiruk , Klingler-Hoffmann Manuela , Hoffmann Peter , Jitrapakdee Sarawut
Published: January 2024

We have previously shown that the holocarboxylase synthetase (HLCS) is overexpressed in breast cancer tissue of patients, and silencing of its expression in triple-negative cancer cell line inhibits growth and migration. Here we investigated the global biochemical changes associated with HLCS knockdown in MDA-MB-231 cells to discern the pathways that involve HLCS. Proteomic analysis of two independent HLCS knockdown cell lines identified 347 differentially expressed proteins (DEPs) whose expression change > 2-fold (p < 0.05) relative to the control cell line. GO enrichment analysis showed that these DEPs were mainly associated with the cellular process such as cellular metabolic process, cellular response to stimulus, and cellular component organization or biogenesis, metabolic process, biological regulation, response to stimuli, localization, and signaling. Among the 347 identified DEPs, 64 proteins were commonly found in both HLCS knockdown clones, confirming their authenticity. Validation of some of these DEPs by Western blot analysis showed that plasminogen activator inhibitor type 2 (SerpinB2) and interstitial collagenase (MMP1) were approximately 90% decreased in HLCS knockdown cells, consistent with a 50%–60% decrease in invasion ability of knockdown cells. Notably, argininosuccinate synthase 1 (ASS1), one of the enzymes in the urea cycle, showed approximately a 10-fold increase in the knockdown cells, suggesting the crucial role of HLCS in supporting the urea cycle in the triple-negative cancer cell line. Collectively, our proteomic data provide biochemical insights into how suppression of HLCS expression perturbs global changes in cellular processes and metabolic pathways, impairing cell growth and invasion.
Novel attentional gait index reveals a cognitive ability-related decline in gait automaticity during dual-task walking
Authors: Liu Shuqi , Rosso Andrea L. , Baillargeon Emma M. , Weinstein Andrea M. , Rosano Caterina , Torres-Oviedo Gelsy
Published: January 2024

Introduction

Gait automaticity refers to the ability to walk with minimal recruitment of attentional networks typically mediated through the prefrontal cortex (PFC). Reduced gait automaticity (i.e., greater use of attentional resources during walking) is common with aging, contributing to an increased risk of falls and reduced quality of life. A common assessment of gait automaticity involves examining PFC activation using near-infrared spectroscopy (fNIRS) during dual-task (DT) paradigms, such as walking while performing a cognitive task. However, neither PFC activity nor task performance in isolation measures automaticity accurately. For example, greater PFC activation could be interpreted as worse gait automaticity when accompanied by poorer DT performance, but when accompanied by better DT performance, it could be seen as successful compensation. Thus, there is a need to incorporate behavioral performance and PFC measurements for a more comprehensive evaluation of gait automaticity. To address this need, we propose a novel attentional gait index as an analytical approach that combines changes in PFC activity with changes in DT performance to quantify automaticity, where a reduction in automaticity will be reflected as an increased need for attentional gait control (i.e., larger index).

Methods

The index was validated in 173 participants (≥65 y/o) who completed DTs with two levels of difficulty while PFC activation was recorded with fNIRS. The two DTs consisted of reciting every other letter of the alphabet while walking over either an even or uneven surface.

Results

As DT difficulty increases, more participants showed the anticipated increase in the attentional control of gait (i.e., less automaticity) as measured by the novel index compared to PFC activation. Furthermore, when comparing across individuals, lower cognitive function was related to higher attentional gait index, but not PFC activation or DT performance.

Conclusion

The proposed index better quantified the differences in attentional control of gait between tasks and individuals by providing a unified measure that includes both brain activation and performance. This new approach opens exciting possibilities to assess participant-specific deficits and compare rehabilitation outcomes from gait automaticity interventions.
Mild traumatic brain injury, PTSD symptom severity, and behavioral dyscontrol: a LIMBIC-CENC study
Authors: Stromberg Kelsee M. , Martindale Sarah L. , Walker William C. , Ou Zhining , Pogoda Terri K. , Miles Shannon R. , Dismuke-Greer Clara E. , Carlson Kathleen F. , Rowland Jared A. , O’Neil Maya E. , Pugh Mary Jo
Published: January 2024

Background

Behavioral dyscontrol occurs commonly in the general population and in United States service members and Veterans (SM/V). This condition merits special attention in SM/V, particularly in the aftermath of deployments. Military deployments frequently give rise to posttraumatic stress disorder (PTSD) and deployment-related mild TBI traumatic brain injury (TBI), potentially leading to manifestations of behavioral dyscontrol.

Objective

Examine associations among PTSD symptom severity, deployment-related mild traumatic brain injury, and behavioral dyscontrol among SM/V.

Design

Secondary cross-sectional data analysis from the Long-Term Impact of Military-Relevant Brain Injury Consortium – Chronic Effects of Neurotrauma Consortium prospective longitudinal study among SM/V (N = 1,808).

Methods

Univariable and multivariable linear regression models assessed the association and interaction effects between PTSD symptom severity, as assessed by the PTSD Checklist for the Diagnostic and Statistical Manual, 5th edition (PCL-5), and deployment-related mild TBI on behavioral dyscontrol, adjusting for demographics, pain, social support, resilience, and general self-efficacy.

Results

Among the 1,808 individuals in our sample, PTSD symptom severity (B = 0.23, 95% CI: 0.22, 0.25, p < 0.001) and deployment-related mild TBI (B = 3.27, 95% CI: 2.63, 3.90, p < 0.001) were significantly associated with behavioral dyscontrol in univariable analysis. Interaction effects were significant between PTSD symptom severity and deployment mild TBI (B = −0.03, 95% CI: −0.06, −0.01, p = 0.029) in multivariable analysis, indicating that the effect of mild TBI on behavioral dyscontrol is no longer significant among those with a PCL-5 score > 22.96.

Conclusion

Results indicated an association between PTSD symptom severity, deployment-related mild TBI, and behavioral dyscontrol among SM/V. Notably, the effect of deployment-related mild TBI was pronounced for individuals with lower PTSD symptom severity. Higher social support scores were associated with lower dyscontrol, emphasizing the potential for social support to be a protective factor. General self-efficacy was also associated with reduced behavioral dyscontrol.
Case report: Sphenoid wing dural arteriovenous fistula draining into ophthalmic veins inducing pulsatile tinnitus as the sole symptom and its spontaneous closure
Authors: Hsieh Yue-Lin , Zhong Jiake , Chen Xi , Wang Wuqing
Published: January 2024

This case report discusses a unique instance of pulsatile tinnitus (PT) caused by a rare type of intracranial dural arteriovenous fistula (DAVF) located in the sphenoid wing (SW) region, with PT being the sole presenting symptom. The patient initially received multiple misdiagnoses and sought medical attention at various hospitals before being correctly diagnosed. Imaging studies revealed the DAVF’s presence in the SW region, which led to the patient’s referral to interventional radiology/neurology, although she chose conservative observation without surgical intervention. Remarkably, the patient’s PT spontaneously ceased after 30 months without any apparent cause, and follow-up imaging confirmed the absence of DAVF-related abnormalities. The case highlights the importance of considering DAVF as a potential cause of PT, even when there are no evident abnormalities in proximity to the auditory apparatus. It also emphasizes the need for otolaryngologists to extend their examination to include regions beyond the temporal bone, such as the sphenoid bone and orbital areas, when PT is the exclusive symptom. The case underscores the significance of early detection and intervention for DAVFs, as they can lead to debilitating complications, despite the rare occurrence of spontaneous symptom resolution in this case.
Genetically predicted chronic rhinosinusitis and the risk of stroke: a two-sample Mendelian randomization study
Authors: Hu Jingjing , Wang Hui , Zhou Yidan
Published: January 2024

Objective

The causal association between chronic rhinosinusitis (CRS) and stroke remains uncertain due to the susceptibility of observational studies to confounding and the possibility of reverse causality. This study aims to examine the potential causal relationship between CRS and the risk of stroke, encompassing various subtypes.

Methods

In this research, we utilized genome-wide association study (GWAS) data for CRS from FinnGen. We identified significant single-nucleotide polymorphisms (SNPs) associated with CRS and used them as instrumental variables (IVs). GWAS data for any ischemic stroke (AIS), ischemic stroke (IS), large-artery atherosclerotic stroke (LAS), small-vessel strokes (SVS), cardioembolic strokes (CES), intracerebral hemorrhage (ICH), lobar ICH, and non-lobar ICH came from multi-ancestry GWAS datasets. We conducted two-sample Mendelian randomization (MR) analyses using inverse variance weighting (IVW), weighted median, and MR-Egger regression methods to investigate potential causal relationships between CRS and stroke. Both heterogeneity and pleiotropy were evaluated by sensitivity analyses.

Result

The IVW analysis revealed no significant associations between CRS and AIS (OR = 0.99, 95% CI [0.93–1.05], p = 0.73), IS (OR = 0.97, 95% CI [0.81–1.17], p = 0.09), SVS (OR = 0.96, 95% CI [0.82–1.12], p = 0.58), LAS (OR = 0.91, 95% CI [0.77–1.08], p = 0.09), CES (OR = 0.97, 95% CI [0.81–1.17], p = 0.79), ICH (OR = 1.28, 95% CI [0.74–2.22], p = 0.28), lobar ICH (OR = 1.22, 95% CI [0.60–2.50], p = 0.28), and non-lobar ICH (OR = 1.25, 95% CI [0.65–2.40], p = 0.79). Sensitivity analysis found no evidence of horizontal pleiotropy.

Conclusion

According to genetic evidence, this Mendelian randomization (MR) study does not indicate a causal relationship between CRS and stroke in European populations. However, further studies are necessary to comprehensively evaluate the potential association between CRS and stroke.
Effects of modified external ventricular drainage vs. an Ommaya reservoir in the management of hydrocephalus with intracranial infection in pediatric patients
Authors: Chen Liuyin , He Mingzhe , Shi Lei , Yue Yanke , Luo Pengyuan , Fang Jiangshun , Wang Na , Cheng Zhenghai , Qu Yi , Yang Zhiguo , Sun Yaning
Published: January 2024

Background

Hydrocephalus with intracranial infection (HII) may cause pathological changes in brain tissue structure and irreversible damage to the nervous system. However, intracranial infection is a contraindication to ventriculo-peritoneal (VP) shunt surgery, and the prognosis is improved by early infection control and intracranial pressure reduction. This study evaluated the safety and efficacy of the Ommaya reservoir vs. modified external ventricular drainage (M-EVD) in the management of HII in pediatric patients.

Methods

This retrospective controlled study included 45 pediatric patients with HII treated with an Ommaya reservoir (n = 24) or M-EVD (n = 21) between January 2018 and December 2022. Clinical outcomes, cerebrospinal fluid (CSF) test results, complications, and outcomes were compared between the Ommaya reservoir and M-EVD groups.

Results

No patient died during the follow-up period. The two groups were similar regarding age, sex, admission temperature, weight, preoperative serum protein and albumin concentrations, CSF analysis (white blood cell count, glucose concentration, and protein content), and clinical symptoms (P > 0.05). Both groups had significant changes in the CSF test results postoperatively compared with preoperatively (P < 0.05). In the M-EVD group, the median days for 13 children to remove the external drainage tube and receive VP shunt was 19 days. The longest drainage tube retention time was 61 days, and there was no intracranial infection or serious complication related to the drainage tube. After the placement of the Ommaya, the median time required for CSF to return to normal was 21 days, and a total of 15 patients underwent VP shunt surgery.

Conclusion

The Ommaya reservoir and M-EVD are safe and effective for pediatric patients with HII. Both methods reduce the intracranial pressure and alleviate the symptoms of hydrocephalus, although there are differences between the two methods.
Predictive value of ApoB/ApoA-I for recurrence within 1 year after first incident stroke
Authors: Lin Jie , Si Zhihua , Wang Aihua
Published: January 2024

Background

ApoB/ApoA-I ratio is a reliable indicator of cholesterol balance, particularly in the prediction of ischemic events risk. The aim of this study was to investigate the prognostic value of ApoB/ApoA-I for stroke recurrence within 1 year after the first incident.

Methods

We retrospectively included patients who were first diagnosed with acute (<7 days after onset) ischemic stroke. Blood samples were collected on admission, and serum ApoB and ApoA-I concentrations were measured. We analyzed the relationship between ApoB/ApoA-I ratio and ischemic stroke recurrence within 1 year.

Results

A total of 722 patients with acute ischemic stroke were included, of whom 102 experienced stroke recurrence within 1 year, with a recurrence rate of 14.1%. Serum ApoB/ApoA-I concentrations on admission were higher in patients with stroke recurrence at 1 year compared with those with a good prognosis (P < 0.001). The Kaplan-Meier survival curve revealed a significant difference in cumulative stroke recurrence rates across ApoB/ApoA-I tertiles (log-rank P-value < 0.001). A positive correlation between the ApoB/ApoA-I ratio and the risk of stroke recurrence within 1 year was demonstrated using Cox regression analysis, which remained significant after adjusting for traditional risk factors [hazard ratio (HR) 4.007, 95% confidence interval (CI) 1.661–9.666]. This relationship was particularly strong in patients with LAA stroke (HR 4.955, 95% CI 1.591–15.434). Subgroup analysis further revealed that a high ApoB/ApoA-I ratio was strongly associated with stroke recurrence regardless of whether patients had high or low LDL-C levels.

Discussion

ApoB/ApoA-I ratio, measured during the acute phase of the first stroke, was positively correlated with the risk of stroke recurrence within 1 year.
A case report of acute intermittent porphyria leading to severe disability
Authors: Lin Jie , Liu Jinzhi , Wang Aihua , Si Zhihua
Published: January 2024

Acute intermittent porphyria (AIP) is a rare inherited metabolic disorder resulting from increased production of porphyrins and their precursors, δ-aminolevulinic acid (ALA) and porphobilinogen (PBG), due to deficiencies in the enzymatic activity of the heme synthesis pathway. The disease is typically characterized by a triad of abdominal pain, neurologic impairment symptoms, and psychiatric abnormalities. However, only a small percentage of patients present with this classic triad of symptoms. Our female patient, aged 23, was admitted to the hospital with a 4-year history of abnormal mood episodes and weakness in the limbs for over 1 week. She had a previous medical history of intestinal obstruction. After admission, a cranial MRI revealed reversible posterior leukoencephalopathy imaging manifestations, and the patient exhibited weakness of the extremities, respiratory failure, seizures, and severely reduced serum sodium concentration. The diagnosis of AIP was ultimately confirmed by a positive urine PBG-sunlight test and analysis of HMBS gene variants. The absence of typical triadic signs in acute attacks of AIP can make early recognition of the disease challenging. We present a case with multiple typical clinical manifestations of AIP in the hope of aiding clinicians in fully recognizing acute intermittent porphyria.
The outcome and risk factors associated with central and peripheral nervous system involvement in hospitalized COVID-19 patients: a retrospective cohort study
Authors: Hanganu Andreea Raluca , Niculae Cristian-Mihail , Dulămea Adriana Octaviana , Moisă Emanuel , Constantin Rareș , Neagu Georgiana , Hristea Adriana
Published: January 2024

Introduction

SARS-CoV-2 infection can affect any organ, including both the central nervous system (CNS) and peripheral nervous system (PNS). The aim of this study was to explore the outcome and risk factors associated with the involvement of either CNS or PNS in a cohort of hospitalized COVID-19 patients.

Methods

We performed a retrospective observational cohort study of hospitalized adult patients with COVID-19, between May 2020 and December 2022, presenting with new onset neurological disabilities any time after admission.

Results

We included 115 patients, 72 with CNS manifestations and 43 with PNS involvement. The CNS manifestations were COVID-19-associated encephalopathy, headache, neurovascular events, and seizures in 80.5, 43, 31.9, and 11.1% of patients, respectively. The neurovascular events were ischemic stroke in 17 (23.6%) patients, hemorrhagic stroke in 6 (8.3%) patients, venous thrombosis in 1 (1.4%) patient, and subarachnoid hemorrhage in 1 (1.4%) patient. Cranial nerve involvement was the most frequent PNS manifestation in 34 (79%) cases, followed by mononeuritis in 5 (11.6%) patients and polyneuropathy in 4 (9.3%) patients. The affected cranial nerves were the vestibulocochlear nerve in 26 (60.5%) patients, the olfactory nerve in 24 (55.8%) patients, the oculomotor nerves in 5 (11.6%) patients, and the facial nerve in 1 (2.3%) patient. Two patients (9.3%) presented with polyneuritis cranialis. Older age (HR = 1.02, 95% CI: 1.003–1.037, p = 0.01), COVID severity (HR = 2.53, 95% CI: 1.42–4.5, p = 0.002), ischemic cardiac disease (HR = 2.42, 95% CI: 1.05–5.6, p = 0.03), and increased D-dimers (HR = 1.00, 95% CI: 1.00–1.00, p = 0.02) were independently associated with the development of CNS manifestations. The factors associated with in-hospital mortality were age (HR = 1.059, 95% CI: 1.024–1.096, p = 0.001), C-reactive protein (HR = 1.006, 95% CI: 1.00–1.011, p = 0.03), CNS involvement (HR = 9.155, 95% CI: 1.185–70.74, p = 0.03), and leucocyte number (HR = 1.053, 95% CI: 1.026–1.081, p < 0.001).

Conclusion

COVID-19-associated encephalopathy was the most common CNS manifestation in our study, but neurovascular events are also important considering the overlap between inflammatory and prothrombotic pathways, especially in severe cases. CNS involvement was associated with in-hospital all-cause mortality. PNS findings were various, involving mostly the cranial nerves, especially the vestibulocochlear nerve.
Gamma music: a new acoustic stimulus for gamma-frequency auditory steady-state response
Authors: Yokota Yusuke , Tanaka Kenta , Chang Ming , Naruse Yasushi , Imamura Yasuhiko , Fujii Shinya
Published: January 2024

A frequency range exceeding approximately 30 Hz, denoted as the gamma frequency range, is associated with various cognitive functions, consciousness, sensory integration, short-term memory, working memory, encoding and maintenance of episodic memory, and retrieval processes. In this study, we proposed a new form of gamma stimulation, called gamma music, combining 40 Hz auditory stimuli and music. This gamma music consists of drums, bass, and keyboard sounds, each containing a 40 Hz frequency oscillation. Since 40 Hz stimuli are known to induce an auditory steady-state response (ASSR), we used the 40 Hz power and phase locking index (PLI) as indices of neural activity during sound stimulation. We also recorded subjective ratings of each sound through a questionnaire using a visual analog scale. The gamma music, gamma drums, gamma bass, and gamma keyboard sounds showed significantly higher values in 40 Hz power and PLI compared to the control music without a 40 Hz oscillation. Particularly, the gamma keyboard sound showed a potential to induce strong ASSR, showing high values in these indices. In the subjective ratings, the gamma music, especially the gamma keyboard sound, received more relaxed, comfortable, preferred, pleasant, and natural impressions compared to the control music with conventional gamma stimulation. These results indicate that our proposed gamma music has potential as a new method for inducing ASSR. Particularly, the gamma keyboard sound proved to be an effective acoustic source for inducing a strong ASSR while preserving the comfortable and pleasant sensation of listening to music. Our developed gamma music, characterized by its pleasantness to the human ear, offers a significant advantage for the long-term use of gamma stimulation. The utilization of this music could potentially reduce the physical and psychological burden on participants compared to conventional 40 Hz stimuli. This music is not only expected to contribute to fundamental neuroscience research utilizing ASSR but also to facilitate the implementation of gamma music-based interventions aimed at enhancing human cognitive functions in everyday life.