bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct characteristics of BTLA/HVEM axis expression on Tregs and its impact on the expansion and attributes of Tregs in patients with active pulmonary tuberculosis
Authors: Tang Peijun , Shen Xinghua , Gao Jianling , Zhang Jianping , Feng Yanjun , Zhang Ji , Huang Ziyi , Wang Xuefeng
Published: September 2024

Introduction

Pulmonary tuberculosis (PTB) remains one of the deadliest infectious diseases. Understanding PTB immunity is of potential value for exploring immunotherapy for treating chemotherapy-resistant PTB. CD4+CD25+Foxp3+ regulatory T cells (Tregs) are key players that impair immune responses to Mycobacteria tuberculosis (MTB). Currently, the intrinsic factors governing Treg expansion and influencing the immunosuppressive attributes of Tregs in PTB patients are far from clear.

Methods

Here, we employed flow cytometry to determine the frequency of Tregs and the expression of B and T lymphocyte attenuator (BTLA) and its ligand, herpesvirus entry mediator (HVEM), on Tregs in patients with active PTB. Furthermore, the expression of conventional T cells and of programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) on Tregs in patients with active PTB was determined. We then examined the characteristics of BTLA/HVEM expression and its correlation with Treg frequency and PD-L1 and PD-1 expression on Tregs in PTB patients.

Results

The frequency of Tregs was increased in PTB patients and it had a relevance to PTB progression. Intriguingly, the axis of cosignal molecules, BTLA and HVEM, were both downregulated on the Tregs of PTB patients compared with healthy controls (HCs), which was the opposite of their upregulation on conventional T cells. Unexpectedly, their expression levels were positively correlated with the frequency of Tregs, respectively. These seemingly contradictory results may be interpreted as follows: the downregulation of BTLA and HVEM may alleviate BTLA/HVEM cis-interaction-mediated coinhibitory signals pressing on naïve Tregs, helping their activation, while the BTLA/HVEM axis on effector Tregs induces a costimulatory signal, promoting their expansion. Certainly, the mechanism underlying such complex effects remains to be explored. Additionally, PD-L1 and PD-1, regarded as two of the markers characterizing the immunosuppressive attributes and differentiation potential of Tregs, were upregulated on the Tregs of PTB patients. Further analysis revealed that the expression levels of BTLA and HVEM were positively correlated with the frequency of PD-1+Tregs and PD-L1+Tregs, respectively.

Conclusion

Our study illuminated distinct characteristics of BTLA/HVEM axis expression on Tregs and uncovered its impact on the expansion and attributes of Tregs in patients with active PTB. Therefore, blockade of the BTLA/HVEM axis may be a promising potential pathway to reduce Treg expansion for the improvement of anti-MTB immune responses.
Making the most of big qualitative datasets: a living systematic review of analysis methods
Authors: Chandrasekar Abinaya , Clark Sigrún Eyrúnardóttir , Martin Sam , Vanderslott Samantha , Flores Elaine C. , Aceituno David , Barnett Phoebe , Vindrola-Padros Cecilia , Vera San Juan Norha
Published: September 2024

Introduction

Qualitative data provides deep insights into an individual's behaviors and beliefs, and the contextual factors that may shape these. Big qualitative data analysis is an emerging field that aims to identify trends and patterns in large qualitative datasets. The purpose of this review was to identify the methods used to analyse large bodies of qualitative data, their cited strengths and limitations and comparisons between manual and digital analysis approaches.

Methods

A multifaceted approach has been taken to develop the review relying on academic, gray and media-based literature, using approaches such as iterative analysis, frequency analysis, text network analysis and team discussion.

Results

The review identified 520 articles that detailed analysis approaches of big qualitative data. From these publications a diverse range of methods and software used for analysis were identified, with thematic analysis and basic software being most common. Studies were most commonly conducted in high-income countries, and the most common data sources were open-ended survey responses, interview transcripts, and first-person narratives.

Discussion

We identified an emerging trend to expand the sources of qualitative data (e.g., using social media data, images, or videos), and develop new methods and software for analysis. As the qualitative analysis field may continue to change, it will be necessary to conduct further research to compare the utility of different big qualitative analysis methods and to develop standardized guidelines to raise awareness and support researchers in the use of more novel approaches for big qualitative analysis.

Systematic review registration

https://osf.io/hbvsy/?view_only=.
A framework for comparing large-scale survey assessments: contrasting India’s NAS, United States’ NAEP, and OECD’s PISA
Authors: van Rijn Peter , Por Han-Hui , McCaffrey Daniel F. , Bhaduri Indrani , Bertling Jonas
Published: September 2024

Large-scale survey assessments (LSAs) are important tools for measuring educational outcomes and shaping policy decisions. We present a framework for comparing LSAs to facilitate studying the impact of design choice on the precision of results, contrasting India’s National Achievement Survey (NAS), the United States’ National Assessment of Educational Progress (NAEP), and the OECD’s Programme for International Student Assessment (PISA). Our framework focuses on four key elements: sampling design, assessment design, analysis methodology, and reporting. The notion of total survey error, which is the accumulation of errors across the four key elements, can be used for both designing and evaluating LSAs. As example, we compare statistics that are commonly (but not always) reported from NAS, NAEP, and PISA to summarize outcomes related to sampling, measurement, and reporting. Our examination reveals several key similarities and differences among the three assessments, thereby highlighting the nuanced ways in which each LSA is tailored to meet the specific needs of their purpose and the challenges they face.
Toward a new model for the successful implementation of information and communication technologies in education
Authors: Lamalif Latifa , Machkour Mounia , Faris Sophia , Mansouri Khalifa
Published: September 2024

The design of our Information and Communication Technologies for Education (ICT4E) implementation model highlights its adaptability to local realities, considering available resources, existing technological infrastructures, and the specific needs of learners. However, it is crucial to recognize that the inherent variability of educational contexts and resource constraints can present challenges to a generalized application of the model. In addition, the rapid pace of technological change can have an impact on the ongoing training of teachers, requiring constant vigilance to maintain the relevance of their pedagogical skills. Despite these challenges, our model stands out for its adaptable approach, encouraging ongoing adjustments to respond effectively to the diversity of educational environments. In addition, the prospect of research and innovation, the promotion of interdisciplinary collaboration and the adoption of holistic evaluation are essential strategies for strengthening the robustness of our model. However, it is imperative to remain attentive to ethical considerations, the issue of equity and inclusion, and the long-term impact of integrating ICT into education. Ultimately, our model aspires to be a balanced solution, aware of the challenges and open to the developments needed to ensure the harmonious and optimal integration of ICT into today’s educational landscape.
Evolution of agricultural carbon emission research in China: a historical analysis and emerging trends
Authors: Chen Ziying , Liu Na
Published: September 2024

Agricultural activities constitute the second-largest contributor to greenhouse gas emissions. Proactively mitigating agricultural carbon emissions is crucial for safeguarding the ecological en-vironment, improving agricultural productivity, and fostering long-term ecological sustainability. This paper employs bibliometric analysis to examine the research status, hot topics, and devel-opment trends of agricultural carbon emissions in China over the past 2 decades. Based on Citespace software, the study primarily conducts visual analysis on 660 academic articles on ag-ricultural carbon emissions collected from the China National Knowledge Infrastructure (CNKI) between 2001 and May 2023, including publications indexed in Peking University Chinese Core Journals (PKU Core), Chinese Social Sciences Citation Index and Chinese Science Citation Database. The analysis covers publication quantity, author cooperation, institution cooperation, keyword co-occurrence, keyword clustering, keyword burst, keyword timeline, and keyword timezone. Research results indicate: (1) From the annual publication volume changes perspective, research on China’s agricultural carbon emissions demonstrates a rapid upward trend in the new era, with increasing research interest. (2) The core net-work of research authors has been established, primarily concentrated in agricultural and forestry universities, and the core network of institutions in this field is gradually forming. However, collaboration networks between authors and research institutions are relatively dispersed, necessitating strengthened collaboration among institutions. (3) Current research on agricultural carbon emissions predominantly focuses on the challenges of reducing agricultural carbon emissions in China under the “dual carbon” goals, measures, and pathways to achieve agricultural carbon emission reductions; performance evaluation of agricultural carbon emissions, factors affecting these emissions, and their reduction potential; as well as the relationship between agricultural carbon emissions and agricultural economic growth. Future research should delve deeper into the precise accounting of agricultural carbon emissions under the “dual carbon” goals, their underlying mechanisms, and issues related to precise and differentiated agricultural carbon reduction strategies. (4) The development trajectory of domestic agricultural carbon emissions research shows a period of germination from 2001 to 2009, a development stage from 2010 to 2015, and a deepening stage from 2016 to 2023, with a notable increase in publications in 2021, signifying a new upward phase in research output.
Novel spatio-temporal attention causal convolutional neural network for multi-site PM2.5 prediction
Authors: Wang Yong , Tian Shuang , Zhang Panxing
Published: September 2024

Multi-site PM2.5 prediction has emerged as a crucial approach, given that the accuracy of prediction models based solely on data from a single monitoring station may be constrained. However, existing multi-site PM2.5 prediction methods predominantly rely on recurrent networks for extracting temporal dependencies and overlook the domain knowledge related to air quality pollutant dispersion. This study aims to explore whether a superior prediction architecture exists that not only approximates the prediction performance of recurrent networks through feedforward networks but also integrates domain knowledge of PM2.5. Consequently, we propose a novel spatio-temporal attention causal convolutional neural network (Causal-STAN) architecture for predicting PM2.5 concentrations at multiple sites in the Yangtze River Delta region of China. Causal-STAN comprises two components: a multi-site spatio-temporal feature integration module, which identifies temporal local correlation trends and spatial correlations in the spatio-temporal data, and extracts inter-site PM2.5 concentrations from the directional residual block to delineate directional features of PM2.5 concentration dispersion between sites; and a temporal causal attention convolutional network that captures the internal correlation information and long-term dependencies in the time series. Causal-STAN was evaluated using one-year data from 247 sites in mainland China. Compared to six state-of-the-art baseline models, Causal-STAN achieves optimal performance in 6-hour future predictions, surpassing the recurrent network model and reducing the prediction error by 8%–10%.
Ecological vulnerability assessment and spatial-temporal variations analysis in typical ecologically vulnerable areas of China
Authors: Xu Min , Cao Chunxiang , Zhong Shaobo , Yang Xinwei , Bashir Barjeece , Wang Kaiming , Guo Heyi , Gao Xiaotong , Li Jingbo , Yang Yujie
Published: September 2024

Ecological vulnerability assessment is crucial for environment protection, ecological restoration and resource utilization. However, many former studies have limitations in the indicator system of the assessment, which were not comparable for different types of ecologically vulnerable areas. It is difficult to apply directly to the ecological vulnerability assessment of different types and in various regions. Aiming to solve these problems, the study proposed a well-established and comprehensive indicator system for ecological vulnerability assessment and conducted ecological vulnerability assessment application of five types of typical ecologically vulnerable areas of China based on remote sensing, meteorological, geographic and other data. The results show that the average EVIs value of Zhangbei County ranging from 0.525 to 0.559 are the highest among the five research areas during the four periods, followed by Zoige region and Xiamen bay. However, the region with the lowest average EVI value varies. In 2005 and 2015, it was Taihe County, while in 2010 and 2020, it was the Sanjiangyuan region. The variation of average EVIs in the five typical areas presents slight fluctuation and remains generally stable from 2005 to 2020. It indicates that the environmental protection measures and projects undertaken by the Chinese government in recent years have had a striking effect, curbing the trend of ecological environment deterioration.
Digital transformation of the future of forestry: an exploration of key concepts in the principles behind Forest 4.0
Authors: Damaševičius Robertas , Mozgeris Gintautas , Kurti Arianit , Maskeliūnas Rytis
Published: September 2024

This paper looks at the incorporation of blockchain and Internet of Things (IoT) technologies into Forest 4.0, a sector that harnesses advanced tools such as artificial intelligence and big data for efficient and sustainable forest monitoring and management. The synergy of blockchain and IoT has gained significant attention, offering a secure and decentralized framework for data management, traceability, and supply chain oversight. The provided use cases demonstrate how these technologies improve forest practices, with insight into smart contract implementation and decentralized systems for sustainable forest management. The major findings imply that digital technologies such as blockchain, IoT, AI, WSNs, etc. can help improve forest management sustainability, efficiency and transparency, and integration of these technologies can provide significant information for decision-making and resource allocation, as well as improve supply chain transparency and sustainable forest practices.
ML-GAP: machine learning-enhanced genomic analysis pipeline using autoencoders and data augmentation
Authors: Agraz Melih , Goksuluk Dincer , Zhang Peng , Choi Bum-Rak , Clements Richard T. , Choudhary Gaurav , Karniadakis George Em
Published: September 2024

Introduction

The advent of RNA sequencing (RNA-Seq) has significantly advanced our understanding of the transcriptomic landscape, revealing intricate gene expression patterns across biological states and conditions. However, the complexity and volume of RNA-Seq data pose challenges in identifying differentially expressed genes (DEGs), critical for understanding the molecular basis of diseases like cancer.

Methods

We introduce a novel Machine Learning-Enhanced Genomic Data Analysis Pipeline (ML-GAP) that incorporates autoencoders and innovative data augmentation strategies, notably the MixUp method, to overcome these challenges. By creating synthetic training examples through a linear combination of input pairs and their labels, MixUp significantly enhances the model’s ability to generalize from the training data to unseen examples.

Results

Our results demonstrate the ML-GAP’s superiority in accuracy, efficiency, and insights, particularly crediting the MixUp method for its substantial contribution to the pipeline’s effectiveness, advancing greatly genomic data analysis and setting a new standard in the field.

Discussion

This, in turn, suggests that ML-GAP has the potential to perform more accurate detection of DEGs but also offers new avenues for therapeutic intervention and research. By integrating explainable artificial intelligence (XAI) techniques, ML-GAP ensures a transparent and interpretable analysis, highlighting the significance of identified genetic markers.
Elevated levels of damage-associated molecular patterns HMGB1 and S100A8/A9 coupled with toll-like receptor-triggered monocyte activation are associated with inflammation in patients with myelofibrosis
Authors: De Luca Geraldine , Goette Nora P. , Lev Paola R. , Baroni Pietto Maria C. , Marin Oyarzún Cecilia P. , Castro Ríos Miguel A. , Moiraghi Beatriz , Sackmann Federico , Kamiya Laureano J. , Verri Veronica , Caula Victoria , Fernandez Vanina , Vicente Angeles , Pose Cabarcos Julio , Caruso Vanesa , Camacho Maria F. , Larripa Irene B. , Khoury Marina , Marta Rosana F. , Glembotsky Ana C. , Heller Paula G.
Published: September 2024

Inflammation plays a pivotal role in the pathogenesis of primary and post-essential thrombocythemia or post-polycythemia vera myelofibrosis (MF) in close cooperation with the underlying molecular drivers. This inflammatory state is induced by a dynamic spectrum of inflammatory cytokines, although recent evidence points to the participation of additional soluble inflammatory mediators. Damage-associated molecular patterns (DAMPs) represent endogenous signals released upon cell death or damage which trigger a potent innate immune response. We assessed the contribution of two prototypical DAMPs, HMGB1 and S100A8/A9, to MF inflammation. Circulating HMGB1 and S100A8/A9 were elevated in MF patients in parallel to the degree of systemic inflammation and levels increased progressively during advanced disease stages. Patients with elevated DAMPs had higher frequency of adverse clinical features, such as anemia, and inferior survival, suggesting their contribution to disease progression. Monocytes, which are key players in MF inflammation, were identified as a source of S100A8/A9 but not HMGB1 release, while both DAMPs correlated with cell death parameters, such as serum LDH and cell-free DNA, indicating that passive release is an additional mechanism leading to increased DAMPs. HMGB1 and S100A8/A9 promote inflammation through binding to Toll-like receptor (TLR) 4, whereas the former also binds TLR2. Monocytes from MF patients were shown to be hyperactivated at baseline, as reflected by higher CD11b and tissue factor exposure and increased expression levels of proinflammatory cytokines IL-1β and IL-6. Patient monocytes showed preserved TLR4 and TLR2 expression and were able to mount normal or even exacerbated functional responses and cytokine upregulation following stimulation of TLR4 and TLR2. Elevated levels of endogenous TLR ligands HMGB1 and S100A8/A9 coupled to the finding of preserved or hyperreactive TLR-triggered responses indicate that DAMPs may promote monocyte activation and cytokine production in MF, fueling inflammation. Plasma IL-1β and IL-6 were elevated in MF and correlated with DAMPs levels, raising the possibility that DAMPs could contribute to cytokine generation in vivo. In conclusion, this study highlights that, in cooperation with classic proinflammatory cytokines, DAMPs represent additional inflammatory mediators that may participate in the generation of MF inflammatory state, potentially providing novel biomarkers of disease progression and new therapeutic targets.
Case report: sub-clinical extramedullary B-ALL in the setting of relapse following targeted therapy
Authors: Johns Claire , Erickson Courtney , Jacobs Ashley , Moon Jennifer , Baggott Christina , Dagher Regina , Nadel Helen , Balagtas Jay , Aftandilian Catherine , Ramakrishna Sneha , Lacayo Norman , Davis Kara L. , Stieglitz Elliot , Schultz Liora
Published: September 2024

Standard testing for disease evaluation in B-cell acute lymphoblastic leukemia (B-ALL) includes examination of the bone marrow and cerebrospinal fluid. Radiographic or functional imaging are indicated when clinical signs of non-CNS extramedullary disease are present but are not standard in the relapsed/refractory setting. We describe two cases of patients with relapsed/refractory B-ALL with prior exposure to blinatumomab and/or inotuzumab ozogamicin presenting for CAR-T cell treatment. Both patients were thought to only have minimal residual disease (MRD) at the pre-CAR disease assessment, with MRD of 6,648 (0.66%) and 100 (0.01%) cells per million cells, respectively, as measured by next-generation sequencing (NGS) in their bone marrows. Both patients for distinct reasons unrelated to non-CNS extra-medullary (EM) symptoms had PET-MRIs prior to lymphodepletion and CAR T cell infusion. In both cases patients were found to have significant bulky subclinical EM disease that required changes in clinical management. In the newly-emergent era of antigen-targeted immunotherapy, it is foundational that incidence and relapse patterns following targeted therapy are well-understood. Herein we contribute to a growing body of literature addressing this fundamental clinical gap and highlight a future role for formal prospective imaging studies to better establish response, toxicity and relapse patterns following CAR-T cell therapy in EM B-ALL.
Metabolite, immunocyte phenotype, and lymphoma: a Mendelian randomization study
Authors: Fan Chenyang , Yuan Pengying , Yang Xiangdong , Zhang Weifeng , Wang Xingli , Xie Juan , He Jing , Chen Haijing , Yan Lixiang , Shi Zhexin
Published: September 2024

Background

Recent studies have confirmed that metabolites and immunocyte phenotype may be associated with the risk of lymphoma. However, the bidirectional causality between metabolites, immunocyte phenotype, disease risk, and whether immunity is an intermediate mediator between metabolism and lymphoma causality is still unclear.

Objective

To elucidate the causal relationship between metabolites, immune cell phenotypes, and lymphomas, we used two-sample Mendelian randomization (MR) and two-step MR analysis.

Methods

Applying large-scale genome-wide association studies (GWAS) pooled data, we selected 1400 metabolites and 731 immunocyte phenotypes with eight lymphoma subtypes for two-sample bi-directional MR analysis. In addition, we used two-step MR to quantify the proportion of metabolite effects on lymphomas mediated by immunocyte phenotype.

Results

This study yielded a bidirectional causal relationship between 17 metabolites and lymphoma and a bidirectional causal relationship between 12 immunocyte phenotypes and lymphoma. In addition, we found causal associations between metabolites and lymphomas, three groups of which were mediated by immunocyte phenotypes. Among them, CD27 on plasmablast/plasma cell (PB/PC) was a mediator of the positive association of arginine to glutamate ratio with chronic lymphocytic leukemia, with a mediator ratio of 14.60% (95% CI=1.29-28.00%, P=3.17 × 10-2). Natural killer (NK) cells as a percentage of all lymphocytes(NK %lymphocyte) was a mediator of the negative association of X-18922(unknown metabolite) levels with diffuse large B-cell lymphoma, with a mediation proportion of -8.940% (95% CI=-0.063-(-17.800) %, P=4.84 × 10-2). CD25 on IgD- CD24- B cell was the mediator of the positive association between X-24531(unknown metabolite) levels and diffuse large B-cell lymphoma, with a mediation proportion of 13.200% (95% CI=-0.156-26.200%, P=4.73 × 10-2).

Conclusion

In the present study, we identified a causal relationship between metabolites and lymphoma, in which immunocyte phenotypes as mediators are involved in only a minor part. The mediators by which most metabolites affect the risk of lymphoma development remain unclear and require further exploration in the future.
Selected stem cell populations in pediatric acute lymphoblastic leukemia
Authors: Krętowska-Grunwald Anna , Sawicka-Żukowska Małgorzata , Starosz Aleksandra , Krawczuk-Rybak Maryna , Moniuszko Marcin , Grubczak Kamil
Published: September 2024

Introduction

Acute lymphoblastic leukemia is characterized by a disturbed maturation of hematopoietic stem cells (HSCs) resulting in development of a malignant clone. Despite relatively positive outcome, there are still instances of disease relapse occurring due to ineffective disease eradication or primary leukemic clone alterations. Unclear significance of stem cells in the course of ALL led us to investigate and establish crucial changes in two stem cell populations - very small embryonic-like stem cells (VSELs) and HSCs during the induction phase of treatment.

Methods

In a retrospective study selected stem cells in peripheral blood and bone marrow of 60 pediatric ALL subjects and 48 healthy controls were subjected to flow cytometric analysis at 4 different time points.

Results

Both VSELs and HSCs were elevated at the moment of ALL diagnosis compared to healthy controls, but profoundly decline until day 15. Further observations revealed an increase in HSCs with a concomitant depletion of VSELs until week 12. ALL patients with high HSCs showed positive correlation with bone marrow blasts at diagnosis. Patients with lower VSELs or HSCs at diagnosis had slightly improved response to applied therapy. We observed higher initial bone marrow lymphoblast values in patients with lower VSELs or higher HSCs in the high-risk group. The significance of VSELs in predicting treatment outcome can be illustrated by lower day 15 MRD level of patients with lower VSELs at diagnosis.

Discussion

We found HSCs and VSELs to be valid participants in pediatric ALL with possible contribution in the neoplastic process and prediction of initial treatment outcome.
A case report: Comorbidity of Rhinocerebral mucormycosis and pulmonary aspergillosis with challenging diagnosis
Authors: Wang Qi , Huang YangYiYi , Ma HaiNa , Fan Guo-Kang
Published: September 2024

Background

Mucormycosis is a rare opportunistic invasive fungal disease. Rhinocerebral mucormycosis (RCM) is clinically difficult to diagnose, and patients often die due to delayed diagnosis.

Case description

A patient with concurrent pulmonary aspergillosis was diagnosed with RCM caused by Rhizopus through metagenomic Next-Generation Sequencing (mNGS). Despite comprehensive treatment including surgery, amphotericin B, and posaconazole, the patient tragically passed away. The treatment was delayed due to repeated cultures of secretions were negative and pathological examination could not clarify which fungus is infected.

Conclusion

The clinical manifestations of RCM are not specific in the early stage, but the infection progresses rapidly. Therefore, early and accurate diagnosis is very important. mNGS is helpful for patients suspected of RCM, especially when conventional microbiology tests were negative.
Translation, cultural debugging, and validation of the Chinese version of the Sour Seven Questionnaire: a cross-sectional study
Authors: Zhu Shichao , Liu Shiqing , Li Liming , Xing Huanmin , Xia Ming , Dong Guangyan
Published: September 2024

Introduction

Intensive care unit delirium (ICUD) is an acute cerebral dysfunction accompanied by a change of level of consciousness, disorientation, and cognitive dysfunction, typically occurring over a short duration ranging from hours to days and resulting from underlying medical causes. Family members may sometimes detect changes in consciousness earlier than medical staff. The Sour Seven Questionnaire is a tool to assist family members in screening for delirium, but there is currently no Chinese version. This study aimed to translate and cross-culturally debug the Sour Seven Questionnaire and test the effectiveness of the Chinese version in screening for ICUD by family members.

Methods

To create the Chinese version of the questionnaire, the questionnaire was first translated and then culturally debugged through expert consultation and cognitive interviews. Patients and their family members admitted to three ICUs in a Chinese hospital were selected to test the Chinese version of the Sour Seven Questionnaire and the results were compared with those of the validated and recommended Confusion Assessment Method for the intensive care unit (CAM-ICU) assessment.

Results

A total of 190 ICU patients and their families were included in this study. Results of the CAM-ICU assessment showed that 73 (38.4%) patients developed ICUD compared to the 66 (34.7%) using the Chinese version of the Sour Seven Questionnaire, which had a Cohen’s kappa coefficient of 0.853, a sensitivity of 0.863, and a specificity of 0.974. The positive predictive value was 0.954 and the negative predictive value was 0.919.

Discussion

The Chinese version of the Sour Seven Questionnaire is a valid assessment tool for helping families screen for ICUD, and it is effective in identifying altered consciousness in patients even during online visits.
Identifying metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus using clinic-based prediction tools
Authors: Alkaabi Juma , Afandi Bachar , Alhaj Omar , Kanwal Darakhshan , Agha Adnan
Published: September 2024

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a global cause of chronic liver disease. The prevalence of MASLD is high in patients with type 2 diabetes mellitus (T2DM). Various non-invasive tools such as the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS), liver ultrasound, and FibroScan can aid in the detection of liver fibrosis in MASLD, while the Hamaguchi ultrasound-based liver grading system has demonstrated high sensitivity and specificity comparable to liver biopsy.

Objective

We assessed the frequency of MASLD in patients with T2DM using the liver ultrasound Hamaguchi score and the accuracy of NFS and Fib-4 in identifying MASLD.

Patients and methods

We retrospectively collected data and reviewed the charts of all patients with T2DM who underwent liver ultrasound and laboratory tests during the past 5 years.

Results

A total of 6,214 medical records were screened, and only 153 patients (68.6% women; mean age, 59 ± 12.2 years) fulfilled the selection criteria. MASLD was diagnosed using the Hamaguchi grading criteria in 45.1% of patients. A high/intermediate NFS had a higher sensitivity (79.7%) for diagnosing MASLD with a specificity of 10.7%, while a high/intermediate Fib-4 score showed only 30.4% sensitivity but a higher specificity of 54.8%.

Conclusion

Our study indicates that MASLD is frequent in patients with T2DM, and clinical prediction tools such as NFS and Fib-4 can be applied in clinic/primary care settings with variable results.
Efficacy of lower limb strengthening exercises based on different muscle contraction characteristics for knee osteoarthritis: a systematic review and network meta-analysis
Authors: Ding Xiaoqing , Yang Yi , Xing Ying , Jia Qingsong , Liu Qingguo , Zhang Jie
Published: September 2024

Purpose

While strengthening exercises are recommended for knee osteoarthritis (KOA) treatment, the optimal type of muscle contraction remains unclear, with current research showing conflicting results. This network meta-analysis (NMA) aims to evaluate the efficacy of lower limb strengthening exercises based on different muscle contraction characteristics for KOA patients and provide clinical references.

Methods

We conducted the NMA following the PRISMA-NMA. A comprehensive search of five databases (PubMed, Web of Science, CENTRAL, Embase, and SPORTDiscus) up to August 2024 identified randomized controlled trials (RCTs) investigating lower limb strengthening exercises in KOA patients. Control groups included receiving usual care, only providing health education, or no intervention at all. Outcomes analyzed included pain, physical function, quality of life, and muscle strength.

Results

Forty-one studies (2,251 participants) were included. Twenty-eight studies used rigorous randomization; eighteen reported allocation concealment. All had high performance bias risk due to exercise interventions. Regarding efficacy, isokinetic exercise ranked highest in pain relief (SMD = 0.70, 95% CI: 0.50–0.91, SUCRA = 82.6%), function improvement (SMD = 0.75, 95% CI: 0.57–0.92, SUCRA = 96.1%), and enhancement in muscle strength (SMD = 0.56, 95% CI: 0.34–0.78, SUCRA = 90.1%). Isometric exercise ranked highest in improving quality of life (SMD = 0.80, 95% CI: 0.28–1.31, SUCRA = 90.5%). Mixed strengthening exercise ranked lowest across all outcomes. High-frequency interventions (≥5 times/week) showed superior pain relief compared with low-frequency (≤3 times/week) for isotonic, isometric, and isokinetic exercise.

Conclusion

This NMA suggests isokinetic exercise may be most effective for pain, function, and muscle strength in KOA patients, while isometric exercise benefits quality of life most. Mixed strengthening exercise ranked lowest across all outcomes. High-frequency interventions appear more effective than low-frequency ones. These findings support personalized KOA treatment, considering efficacy, accessibility, and patient-specific factors. Study biases, heterogeneity, and other limitations may affect result reliability. Future research should focus on high-quality studies with standardized protocols and analyze dose–response relationships to refine KOA treatment strategies.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024582525, identifier: CRD42024582525.
The neutrophil-lymphocyte ratio predicts all-cause and cardiovascular mortality among United States adults with COPD: results from NHANES 1999–2018
Authors: Chen Zhao , Li Wenqiang , Tang Yuanchun , Zhou Peng , He Qian , Deng Zhiping
Published: September 2024

Background

Neutrophil-to-lymphocyte ratio (NLR) is considered a biomarker of systemic inflammation and immune activation. However, its relationship with the risk of mortality in patients with chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to investigate the association between NLR and the risk of all-cause and cardiovascular mortality in patients with COPD.

Methods

Data were collected from the National Health and Nutrition Examination Survey (NHANES) from January 1999 to December 2018. The calculation method of NLR involves dividing the neutrophil count by the lymphocyte count in the total blood cell count. The optimal NLR threshold associated with survival outcomes was determined using the maximally selected rank statistics method (MSRSM). The relationship between NLR and the risk of all-cause mortality and cardiovascular mortality in COPD was investigated using a weighted multivariable Cox regression model. Additionally, restricted cubic spline (RCS) was employed to discuss the potential relationship between NLR patients in different groups and the risk of mortality.

Results

In this study, 716 adults with COPD were included using the maximally selected rank statistics method, among whom 208 had higher NLR (≥2.56) and 508 had lower NLR (<2.56). During a median follow-up of 111.5 months, 162 COPD patients died from all causes, and 49 patients died from cardiovascular diseases. After adjusting for demographic, socioeconomic status, and lifestyle factors, the risk of all-cause mortality (HR = 2.07, 95%CI: 1.46–2.94) and cardiovascular mortality (HR = 3.03, 95%CI: 1.63–5.65) in patients with higher NLR was increased by 2–3 times compared to those with lower NLR. Kaplan–Meier analysis revealed significantly lower survival rates in patients with higher NLR for all-cause mortality and cardiovascular mortality (p < 0.05). Restricted cubic spline analysis showed a linear correlation between NLR and the risk of all-cause mortality and cardiovascular mortality.

Conclusion

NLR has a high value in independently predicting long-term all-cause and cardiovascular mortality risks in community-dwelling COPD patients. Therefore, NLR can serve as a cost-effective and widely available indicator for assessing the prognosis of COPD patients.
A comparative study of interhemispheric functional connectivity in patients with basal ganglia ischemic stroke
Authors: Zhang Jian , Chen Shijian , Yang Chengmin , Liang Huo , Quan Xuemei , Liu Yayuan , Liang Zhijian
Published: September 2024

Background

Voxel-mirrored homotopic connectivity (VMHC) is utilized to assess the functional connectivity of neural networks by quantifying the similarity between corresponding regions in the bilateral hemispheres of the brain. The exploration of VMHC abnormalities in basal ganglia ischemic stroke (BGIS) patients across different cerebral hemispheres has been limited. This study seeks to establish a foundation for understanding the functional connectivity status of both brain hemispheres in BGIS patients through the utilization of VMHC analysis utilizing resting-state functional magnetic resonance imaging (rs-fMRI).

Methods

This study examined a total of 38 patients with left basal ganglia ischemic stroke (LBGIS), 44 patients with right basal ganglia ischemic stroke (RBGIS), and 41 individuals in a healthy control (HC) group. Rs-fMRI studies were performed on these patients, and the pre-processed rs-fMRI data were analyzed using VMHC method. Subsequently, the VMHC values were compared between three groups using a one-way ANOVA and post hoc analysis. Correlation analysis with clinical scales was also conducted.

Results

The results indicated that compared to the HC group, significant differences were detected in postcentral gyrus, extending to precentral gyrus in both BGIS groups. Post hoc analysis showed that in the pairwise ROI-based comparison, individuals with LBGIS and RBGIS exhibited reduced VMHC values compared to HC groups. There was no significant difference between the LBGIS and RBGIS groups. In the LBGIS group, the VMHC value showed a negative correlation with NIHSS and a positive correlation with BI.

Conclusion

The analysis of VMHC in rs-fMRI revealed a pattern of brain functional remodeling in patients with unilateral BGIS, marked by reduced synchronization and coordination between hemispheres. This may contribute to the understanding of the neurological mechanisms underlying motor dysfunction in these patients.
Functional activity, functional connectivity and complex network biomarkers of progressive hyposmia Parkinson’s disease with no cognitive impairment: evidences from resting-state fMRI study
Authors: Geng Lei , Cao Wenfei , Zuo Juan , Yan Hongjie , Wan Jinxin , Sun Yi , Wang Nizhuan
Published: September 2024

Background

Olfactory dysfunction stands as one of the most prevalent non-motor symptoms in the initial stage of Parkinson’s disease (PD). Nevertheless, the intricate mechanisms underlying olfactory deficits in Parkinson’s disease still remain elusive.

Methods

This study collected rs-fMRI data from 30 PD patients [15 with severe hyposmia (PD-SH) and 15 with no/mild hyposmia (PD-N/MH)] and 15 healthy controls (HC). To investigate functional segregation, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were utilized. Functional connectivity (FC) analysis was performed to explore the functional integration across diverse brain regions. Additionally, the graph theory-based network analysis was employed to assess functional networks in PD patients. Furthermore, Pearson correlation analysis was conducted to delve deeper into the relationship between the severity of olfactory dysfunction and various functional metrics.

Results

We discovered pronounced variations in ALFF, ReHo, FC, and topological brain network attributes across the three groups, with several of these disparities exhibiting a correlation with olfactory scores.

Conclusion

Using fMRI, our study analyzed brain function in PD-SH, PD-N/MH, and HC groups, revealing impaired segregation and integration in PD-SH and PD-N/MH. We hypothesize that changes in temporal, frontal, occipital, and cerebellar activities, along with aberrant cerebellum-insula connectivity and node degree and betweenness disparities, may be linked to olfactory dysfunction in PD patients.
Gender disparity in access to advanced therapies for patients with Parkinson’s disease: a retrospective real-word study
Authors: Maccarrone Giuseppe , Saporito Gennaro , Sucapane Patrizia , Rizi Chiara , Bruno Federico , Catalucci Alessia , Pistoia Maria Letizia , Splendiani Alessandra , Ricci Alessandro , Di Cesare Ernesto , Rizzo Marina , Totaro Rocco , Pistoia Francesca
Published: September 2024

Background

Gender differences in the access to advanced therapies for Parkinson’s disease (PD) are poorly investigated.

Objective

The objective of this study was to investigate the presence of any gender disparity in the access to advanced therapies for PD.

Design

Retrospective study.

Methods

Data from patients with consistent access to the Parkinson’s and Movement Disorder Center of L’Aquila over the last 10-year period were screened. Patients selected for advanced therapies were included.

Results

Out of 1,252 patients, 200 (mean age ± SD 71.02 ± 9.70; 72% males; median Hoen Yahr level: 3, minimum 1 maximum 5) were selected for advanced therapies: 133 for Magnetic Resonance guided Focused Ultrasound (MRgFUS) thalamotomy (mean age ± SD 70.0 ± 8.9; 77% males), 49 for Levodopa/Carbidopa Intestinal Gel (LCIG) infusion (mean age ± SD 74.3 ± 11.4; 59% males), 12 for Deep Brain Stimulation (DBS) (mean age ± SD 71.2 ± 6.3; 75% males), and 7 for Continuous Subcutaneous Apomorphine Infusion (CSAI) (mean age ± SD 69.7 ± 5.5; 43% males). No sex differences were found in relation to age (MRgFUS group: males vs. females 70.2 ± 8.9 vs. 70.8 ± 8.9, p-value = 0.809; LCIG group: males vs. females 73.5 ± 13.0 vs. 75.5 ± 8.5, p-value = 0.557; DBS group: males vs. females 77.2 ± 8.1 vs. 67.3 ± 8.6, p-value = 0.843; CSAI group: males vs. females 73.3 ± 4.0 vs. 67.0 ± 5.2, p-value = 0.144) and disease duration (MRgFUS group: males vs. females 8.3 ± 4.4 vs. 9.6 ± 6.7, p-value = 0.419; LCIG group: males vs. females 14.5 ± 5.81 vs. 17.3 ± 5.5; p-value = 0.205; DBS group: males vs. females 15.0 ± 9.6 vs. 15.5 ± 7.7, p-value = 0.796; CSAI group: males vs. females 11.7 ± 3.7 vs. 10.3 ± 3.7, p-value = 0.505).

Conclusion

The predominance of males is higher than that expected based on the higher prevalence of PD in men. Women are less confident in selecting advanced therapies during the natural progression of their disease. Factors accounting for this discrepancy deserve further investigation.
Neuromodulation effect of temporal interference stimulation based on network computational model
Authors: Karimi Nafiseh , Amirfattahi Rassoul , Zeidaabadi Nezhad Abolghasem
Published: September 2024

Deep brain stimulation (DBS) has long been the conventional method for targeting deep brain structures, but noninvasive alternatives like transcranial Temporal Interference Stimulation (tTIS) are gaining traction. Research has shown that alternating current influences brain oscillations through neural modulation. Understanding how neurons respond to the stimulus envelope, particularly considering tTIS’s high-frequency carrier, is vital for elucidating its mechanism of neuronal engagement. This study aims to explore the focal effects of tTIS across varying amplitudes and modulation depths in different brain regions. An excitatory-inhibitory network using the Izhikevich neuron model was employed to investigate responses to tTIS and compare them with transcranial Alternating Current Stimulation (tACS). We utilized a multi-scale model that integrates brain tissue modeling and network computational modeling to gain insights into the neuromodulatory effects of tTIS on the human brain. By analyzing the parametric space, we delved into phase, amplitude, and frequency entrainment to elucidate how tTIS modulates endogenous alpha oscillations. Our findings highlight a significant difference in current intensity requirements between tTIS and tACS, with tTIS requiring notably higher intensity. We observed distinct network entrainment patterns, primarily due to tTIS’s high-frequency component, whereas tACS exhibited harmonic entrainment that tTIS lacked. Spatial resolution analysis of tTIS, conducted via computational modeling and brain field distribution at a 13 Hz stimulation frequency, revealed modulation in deep brain areas, with minimal effects on the surface. Notably, we observed increased power within intrinsic and stimulation bands beneath the electrodes, attributed to the high stimulus signal amplitude. Additionally, Phase Locking Value (PLV) showed slight increments in non-deep areas. Our analysis indicates focal stimulation using tTIS, prompting further investigation into the necessity of high amplitudes to significantly affect deep brain regions, which warrants validation through clinical experiments.
The complexities of salt taste reception: insights into the role of TMC4 in chloride taste detection
Authors: Kasahara Yoichi , Narukawa Masataka , Saito Yoshikazu , Abe Keiko , Asakura Tomiko
Published: September 2024

Although salt is an essential substance vital to life, excessive salt intake could cause various health issues. Therefore, new technologies and strategies should be developed to reduce salt intake without compromising taste. However, the underlying physiological mechanisms of salt taste reception is complex and not completely understood. Sodium chloride is a typical salty substance. It is widely believed that only sodium is important for the generation of salty taste. On the other hand, from a psychophysical perspective, the importance of chloride in salty taste has been indicated. Thus, understanding the mechanisms of both sodium- and chloride-tastes generation is necessary to completely comprehended the fundamentals of salt taste reception. However, the mechanism for detecting chloride taste has remained unclear for many years. Recently, we have identified transmembrane channel-like 4 (TMC4) as the first molecule that mediates the reception of chloride taste. TMC4 functions as a voltage-dependent chloride channel and plays an important role in the reception of the chloride taste by detecting chloride ions. In this mini-review, we first introduce the known reception mechanism of salty taste, and then discuss the roles of TMC4 in the salt taste reception. The finding of TMC4 may serve as a basis for developing new technologies and formulating strategies to reduce salt intake without compromising taste.