bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic inflammation is an important risk factor and predictor of graft loss and mortality one year after kidney transplantation
Authors: Heldal Torbjørn F. , Åsberg Anders , Ueland Thor , Reisæter Anna V. , Pischke Søren E. , Mollnes Tom E. , Aukrust Pål , Reinholt Finn P. , Hartmann Anders , Heldal Kristian , Jenssen Trond G.
Published: February 2025

Background

An inflammatory environment following kidney transplantation is associated with increased risk of graft loss and mortality, however, evaluation of systemic inflammation is not implemented in structured risk assessment in kidney transplant recipients. Long-term results after transplantation are not satisfactory, and thus tools addressing these issues are needed. In this study, we tested the associations and predictive abilities of a predefined systemic inflammation score one year after transplantation on death-censored graft loss and mortality.

Methods

We included 805 patients who underwent kidney transplantation between 2013 and 2017 at the Oslo University Hospital, Rikshospitalet. The inflammation score included five specifically selected biomarkers known to reflect various inflammatory pathways and to be associated with adverse outcomes following transplantation. The score was assessed in relation to outcomes in models with established risk factors. Discriminatory analyses were performed using Harrell´s C-statistic, and model assessment were evaluated using internal validation, calibration, and likelihood ratio tests.

Results

The median follow-up time was 6.4 years. There were 168 deaths (20.9%) and 42 graft losses (5.2%). The inflammation score one year after transplantation was significantly associated with graft loss (P<0.001) and mortality (P<0.001). The diagnostic performance of the model for graft loss revealed a c-statistic of 0.77 both with and without histological data. The diagnostic performance for mortality displayed a c-statistic of 0.79. In all tested scenarios, the model fit significantly improved after including the inflammation score.

Conclusions

These results suggest a strong association between systemic inflammation one year after transplantation and both graft loss and mortality. Predictive models including the inflammation score and established risk factors were particularly informative when considering mortality. Evaluation of systemic inflammation using this score could be an important tool for risk-assessment after transplantation.
Aberrant lipid profiles and lymphocyte counts in systemic sclerosis population, reassessing predictive value for concurrent cardiovascular diseases
Authors: Guo Ronghong , Gao Jinfang , Yang Yanli , Xu Ke
Published: February 2025

Objective

To investigate alterations in blood lipid profiles and T cell subsets among systemic sclerosis (SSc) patients, and to assess their potential utility in predicting cardiovascular disease (CVD) risk.

Methods

105 SSc patients and 80 age- and sex-matched healthy controls (HCs) were enrolled. Flow cytometry was employed to quantify T cell subsets. Multivariate logistic regression analysis investigated the association between blood lipid profile, T cell subsets, SSc occurrence, and CVD risk. Additionally, a prediction model was developed to assess the potential predictive value of CVD risk.

Results

In the SSc patients, low-density lipoprotein cholesterol (LDL-C) (OR = 3.212, 95%CI = 1.132-9.113, p= 0.028), ESR (OR = 1.218, 95%CI = 1.086-1.367, p= 0.001), CRP (OR = 2.156, 95% CI = 1.393-3.338, p = 0.001), T helper (Th)cells (OR = 1.004, 95% CI = 1.001-1.008, p = 0.034) were positively correlated with the risk of SSc. Further studies found that absolute increases in Th cells in SSc patients were positively associated with the risk of CVD (OR=1.002, 95%CI=1.001-1.005, p =0.011) and were independent predictors of CVD risk in SSc. When Th cells exceeded 866.53 cells/μL, the risk of CVD in SSc patients was greatly increased (p<0.001).

Conclusion

Altered lipid profiles and dysregulated Th cell expression in SSc patients, with a significant elevation of Th cells specifically noted in SSc-CVD patients, suggesting that Th cells may serve as a potential predictive biomarker for CVD in SSc patients, thereby aiding in early diagnosis. The underlying mechanism of this association requires further investigation.
Chronic hypoxia has differential effects on constitutive and antigen-stimulated immune function in Atlantic salmon (Salmo salar)
Authors: Rojas Isis , de Mello Mariana M. M. , Zanuzzo Fábio S. , Sandrelli Rebeccah M. , Peroni Ellen de Fátima C. , Hall Jennifer R. , Rise Matthew L. , Urbinati Elisabeth C. , Gamperl Anthony K.
Published: February 2025

Chronic hypoxia events are a common occurrence in Atlantic salmon (Salmo salar) sea-cages, especially during the summer, and their frequency and severity are predicted to increase with climate change. Although hypoxia is considered a very important fish health and welfare issue by the aquaculture industry, few studies have investigated the impact of chronic hypoxia on the fish immune system and its response to pathogen exposure. We exposed post-smolt Atlantic salmon to hypoxia (40% air sat.) for 6 weeks. Thereafter, we sampled fish prior to (i.e., at Time 0, to assess constitutive immune function), and after they were intraperitoneally injected with PBS (phosphate buffered saline) or formalin-killed Aeromonas salmonicida. We measured several innate immune parameters including: hematological immune responses [respiratory burst (RB), hemolytic activity of alternate complement system and plasma lysozyme concentration], and the relative percentage of circulating blood cells (erythrocytes/immature erythrocytes, monocytes, and granulocytes and lymphocytes) at Time 0 and at 24 hours post-injection (hpi); and the transcript expression levels of 8 anti-bacterial biomarkers in the head kidney [interleukin-1 beta (il1b), interleukin-8a (il8a), cyclooxygenase-2 (cox2), toll-like receptor 5, secreted (strl5), CC chemokine-like 19b (ccl19b), serum amyloid A5 (saa5), hepcidin anti-microbial peptide a (hampa) and cathelicidin anti-microbial peptide b (campb)] at Time 0 and at 6 and 24 hpi. In addition, we measured serum immunoglobulin (IgM) levels at Time 0 and at 8 weeks post-injection (4 weeks after a ‘boost’ injection). Fish exposed to chronic hypoxia had greater numbers of monocytes, which was consistent with the increase in RB, plasma lysozyme concentration and upregulated head kidney anti-bacterial gene expression (i.e., campb, ccl19b, hampa, il8a, stlr5). In contrast, chronic hypoxia: reduced RB and leukocyte numbers at 24 hpi in Asal compared to PBS-injected fish, and the transcript levels of campb, il1b, saa5, il8a and stlr5 at 6- and/or 24- hpi; but had no effect on constitutive or post-stimulation serum IgM titers. Overall, our results indicate that chronic hypoxia has differential effects on salmon constitutive innate immune function vs. following antigen exposure, and thus, it is still unclear how chronic hypoxia will impact the capacity of fish to defend against pathogens.
Progress on diagnosis and treatment of multisystem inflammatory syndrome in children
Authors: Peng Zhe , Zhou Gang
Published: February 2025

Since the emergence of COVID-19 in December 2019, the novel SARS-CoV-2 virus has primarily affected adults, with children representing a smaller proportion of cases. However, the escalation of the pandemic has led to a notable increase in pediatric cases of Multisystem Inflammatory Syndrome in Children (MIS-C). The pathogenesis of MIS-C is largely attributed to immune-mediated mechanisms, such as cytokine storms and endothelial damage, following SARS-CoV-2 infection. In this review, we comprehensively describe MIS-C, including its definitions as proposed by the CDC, WHO, and RCPCH, which emphasize persistent fever, excessive inflammatory responses, and multi-organ involvement. Additionally, we summarize current treatment approaches, prioritizing immunotherapy with intravenous immunoglobulin and corticosteroids, along with anticoagulation therapy, and monoclonal antibodies in severe cases.
Na+/K+-ATPase: a multifunctional target in type 2 diabetes and pancreatic islets
Authors: Mou Lisha , Fu Zhenkun , Wang Tony Bowei , Chen Yuxian , Luo Ziqi , Wang Xinyu , Pu Zuhui
Published: February 2025

Type 2 diabetes (T2D) is a widespread metabolic disorder marked by hyperglycemia, arising from insulin resistance and relative insulin deficiency. This review investigates the critical role of Na+/K+-ATPase (NKA), a transmembrane protein essential for maintaining cellular ion gradients, in the pathophysiology of T2D. We provide an overview of NKA’s biological functions, emphasizing its involvement in cellular signaling pathways, insulin secretion, and glucose homeostasis. The potential of NKA as a therapeutic target for T2D is analyzed, showcasing innovative strategies such as NKA activators, gene therapy, and stem cell therapy aimed at enhancing NKA activity to achieve better glycemic control. Additionally, NKA’s multifunctional role in maintaining cell viability and modulating immune responses in islet transplantation may offer potential benefits for improving transplant outcomes. By elucidating the complex interactions between NKA and T2D, this review aims to shed light on developing novel therapeutic interventions that meet the multifaceted needs of individuals suffering from this chronic condition, ultimately improving their health outcomes.
Rare SRRM2 mutation in neurodevelopmental disorders involving hyperphagia triggering severe obesity and other complication
Authors: Chang Si-Hua , Wang Xia , Jin Jie-Yuan , Wang Qin , Wu Li-Ping
Published: February 2025

SRRM2 encodes a nuclear protein, with functions in pre-mRNA splicing and the formation of nuclear speckles via liquid-liquid phase separation. Despite its critical role in cellular function, the association between SRRM2 and neurodevelopmental disorders is not well-understood. In this study, we reported a case of a patient exhibiting developmental delay, intellectual disability, delayed language development, facial dysmorphism, macrocephaly, short hands and feet, hyperphagia, and hypotonia, which are similar to the characteristics of previously reported cases of SRRM2-associated neurodevelopmental disorders. Notably, the patient became overweight and subsequently developed several obesity-related complications due to uncontrolled hyperphagia. Employing whole exome sequencing (WES) and Sanger sequencing, we identified a novel missense mutation in SRRM2 (NM_016333: c.4661A > T, p.Q1554L). This mutation is classified as “Likely Pathogenic” based on the American College of Medical Genetics and Genomics (ACMG) guideline. Overall, this study contributes to the expanding spectrum of known mutations in SRRM2, enhances our understanding of its clinical implications, and offers crucial data for the diagnosis and management of affected individuals.
Artificial intelligence in healthcare education: evaluating the accuracy of ChatGPT, Copilot, and Google Gemini in cardiovascular pharmacology
Authors: Salman Ibrahim M. , Ameer Omar Z. , Khanfar Mohammad A. , Hsieh Yee-Hsee
Published: February 2025

Background

Artificial intelligence (AI) is revolutionizing medical education; however, its limitations remain underexplored. This study evaluated the accuracy of three generative AI tools—ChatGPT-4, Copilot, and Google Gemini—in answering multiple-choice questions (MCQ) and short-answer questions (SAQ) related to cardiovascular pharmacology, a key subject in healthcare education.

Methods

Using free versions of each AI tool, we administered 45 MCQs and 30 SAQs across three difficulty levels: easy, intermediate, and advanced. AI-generated answers were reviewed by three pharmacology experts. The accuracy of MCQ responses was recorded as correct or incorrect, while SAQ responses were rated on a 1–5 scale based on relevance, completeness, and correctness.

Results

ChatGPT, Copilot, and Gemini demonstrated high accuracy scores in easy and intermediate MCQs (87–100%). While all AI models showed a decline in performance on the advanced MCQ section, only Copilot (53% accuracy) and Gemini (20% accuracy) had significantly lower scores compared to their performance on easy-intermediate levels. SAQ evaluations revealed high accuracy scores for ChatGPT (overall 4.7 ± 0.3) and Copilot (overall 4.5 ± 0.4) across all difficulty levels, with no significant differences between the two tools. In contrast, Gemini’s SAQ performance was markedly lower across all levels (overall 3.3 ± 1.0).

Conclusion

ChatGPT-4 demonstrates the highest accuracy in addressing both MCQ and SAQ cardiovascular pharmacology questions, regardless of difficulty level. Copilot ranks second after ChatGPT, while Google Gemini shows significant limitations in handling complex MCQs and providing accurate responses to SAQ-type questions in this field. These findings can guide the ongoing refinement of AI tools for specialized medical education.
Impact of preoperative frailty on new disability or death after cardiac surgery in elderly patients: a prospective cohort study
Authors: Ma Wenwen , Shui Weikang , Peng Qian , Zhu Chaoyang , Zhao Wenjing , Fan Guanglei , Zhu Shanshan
Published: February 2025

Background

Disability may be a potential adverse outcome of exposure to stressors in frail patients, and assessment of frailty may provide additional information for preoperative decision-making, but there is a lack of research on the impact of preoperative frailty on death or new disability after cardiac surgery. The main objective of this study was to evaluate the effect of preoperative frailty on short-term death or new disability after cardiac surgery in elderly individuals.

Patients and methods

This prospective cohort study included 351 patients aged ≥60 years who were scheduled to undergo elective open heart surgery at the Affiliated Hospital of Xuzhou Medical University from March 2023 to March 2024. Patients were examined prospectively using the Comprehensive Assessment of Frailty (CAF) score, which separated patients into frail and non-frail groups. The primary outcome was 90-day disability or death. Multivariate logistic regression models were used to estimate the association between frailty and 90-day new disability or death.

Results

An assessment of frailty was performed on 351 patients, and 325 patients were included in the final analysis. The prevalence of frailty was found to be 23.08%. New disability or death occurred within 90 days after surgery in 41 (12.6%) of our patients. In multivariate analysis, frailty [OR, 3.31; 95% CI, 1.43–7.62] was independently associated with 90-day new disability or death. Empirical ROC analysis showed that CAF (AUC = 0.762) predicted 90-day new disability or death postoperatively more reliably than the traditional risk assessment tools ASA + age (AUC = 0.656) and EuroSCORE II (AUC = 0.643).

Conclusion

The study demonstrates that preoperative frailty, bypass time, diabetes, BMI and EuroSCORE II are independent risk factors for 90-day new disability or death after cardiac surgery in elderly patients. Notably, frailty was a more effective predictor of 90-day new disability or death than the traditional risk predictors EuroSCORE II and ASA + age.
Systematic review and meta-analysis of the effectiveness of moxibustion therapy for primary dysmenorrhea
Authors: Song ShiWei , Chen Hao
Published: February 2025

Background

Primary dysmenorrhea is a common gynecological disease. Compared with traditional Chinese medicine treatment, moxibustion has advantages as a main treatment method. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy of simple moxibustion therapy for primary dysmenorrhea.

Methods

Randomized controlled trials were searched from PubMed, Web of Science, Embase, The Cochrane Library, China National Knowledge Infrastructure, Wan-fang database and VIP database. In the literature included in these databases, clinical reporters evaluated the efficacy of moxibustion as the treatment for primary dysmenorrhea. All included literature was assessed for risk bias by using Risk of Bias assessment tool 2.0, and meta-analysis was conducted using Rev. Man 5.4.

Results

The findings demonstrated that the moxibustion group exhibited a statistically significant response in comparison to the control group. The improvement observed in the Cox Menstrual Symptom Scale and the visual analogue scale score between the two groups exhibited heterogeneity, with a statistically significant difference noted. In terms of Traditional Chinese Medicine symptom scores, the experimental group demonstrated superiority over the control group. Furthermore, the progesterone levels in the moxibustion treatment were found to be higher than in the control group, while the estrogen levels in the experimental group were lower than in the control group, with a statistically significant difference observed (p < 0.05). Conversely, the levels of β-EP and PGE2 in the observation group were higher than those in the control group.

Conclusion

Moxibustion therapy shows significantly better efficacy in treating primary dysmenorrhea. However, a large sample, multi-center, high-quality RCT is still needed to evaluate its safety and efficacy.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, Identifier CRD42024580466.
Intravitreal aflibercept for diabetic macular edema: structural and functional improvements
Authors: Zhang Chuanhe , Chen Tianyu , Jia Ru , Gong Di , Liu Zhigao , Wu Changlong , Shu Xiangwen , Han Fangju , Gong Bin
Published: February 2025

Introduction

The aim of this study was to evaluate the changes in macular structure and visual function of patients with diabetic macular edema (DME) after intravitreal aflibercept injection.

Methods

Twenty-five patients (43 eyes) diagnosed with DME were included in this study. All patients underwent aflibercept monthly for 3 months. The study’s endpoints included the best corrected visual acuity (BCVA), central retinal thickness (CRT), fovea avascular zone (FAZ) area, vessel density of superficial retinal capillary plexus (SVD), vessel density of deep retinal capillary plexus (DVD), mean light sensitivity (MLS), 2° fixation rate (P1) and 4° fixation rate (P2).

Results

Before treatment and after the third treatment, the LogMAR BCVA was 0.69 ± 0.27 and 0.40 ± 0.18, the CRT was 471.10 ± 159.93 μm and 319.84 ± 113.51 μm, the MLS was 18.14 ± 3.97 dB and 21.68 ± 3.55 dB, P1 was 69 (47, 87)% and 88 (72, 92)%, and P2 was 90 (83, 97)% and 97 (93, 99)%, respectively. After treatment, CRT decreased, BVCA, MLS, and fixation stability improved (all p < 0.001). Post-treatment, FAZ area, SVD, and DVD showed no significant changes (all P > 0.05). MLS was negatively correlated with LogMAR BCVA and CRT, and positively correlated with P1 and P2.

Conclusion

In short term, aflibercept was effective in reducing CRT and improving BCVA, MLS, and fixation stability in DME patients.
Prognostic analysis of sepsis-induced myocardial injury patients using propensity score matching and doubly robust analysis with machine learning-based risk prediction model development
Authors: Guo Pan , Xue Li , Tao Fang , Yang Kuan , Gao YuXia , Pei Chongzhe
Published: February 2025

Background

Sepsis-induced myocardial injury (SIMI) is a severe and common complication of sepsis; However, its definition remains unclear. Prognostic analyses may vary depending on the definition applied. Early prediction of SIMI is crucial for timely intervention, ultimately improving patient outcomes. This study aimed to evaluate the prognostic impact of SIMI and develop validated predictive models using advanced machine learning (ML) algorithms for identifying SIMI in critically ill sepsis patients.

Methods

Data were sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV, v3.0) database. Patients meeting Sepsis-3.0 criteria were included, and SIMI was defined as troponin T (TNT) levels ≥0.1 ng/mL. Prognostic evaluation involved propensity score matching, inverse probability weighting, doubly robust analysis, logistic regression, and Cox regression. Patients were divided into training and testing datasets in a 7:3 ratio. Least absolute shrinkage and selection operator (LASSO) regression was used for variable selection to simplify the model. Twelve hyperparameter-tuned ML models were developed and evaluated using visualized heatmaps. The best-performing model was deployed as a web-based application.

Results

Among 2,435 patients analyzed, 571 (23.45%) developed SIMI following intensive care unit (ICU) admission. Boruta and LASSO identified 46 and 10 key variables, respectively, for prognostic and predictive modeling. Doubly robust analysis revealed significantly worse short- and intermediate-term outcomes for SIMI patients, including increased in-ICU mortality [odds ratio (OR) 1.39, 95% confidence interval (CI) 1.02–1.85, p < 0.05], 28-day mortality (OR 1.35, 95% CI 1.02–1.79, p < 0.05), and 180-day mortality [hazard ratio (HR) 1.21, 95% CI 1.01–1.44, p < 0.05]. However, one-year mortality showed no significant difference (HR 1.03, 95% CI 0.99–1.08, p = 0.169). The XGBoost model outperformed others, achieving an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% CI 0.79–0.87). SHapley Additive exPlanations (SHAP) analysis highlighted the top five predictive features: creatine kinase-myocardial band (CKMB), creatinine, alanine aminotransferase (ALT), lactate, and blood urea nitrogen (BUN). A web-based application was subsequently developed for real-world use.

Conclusion

SIMI significantly worsens patient prognosis, while the XGBoost model demonstrated excellent predictive performance. The development of a web-based application provides clinicians with a practical tool for timely intervention, potentially improving outcomes for septic patients.
Impact of circuit configuration on the mechanical performance of CPAP therapy devices: an experimental study
Authors: De Luca Margherita , Formaggio Andrea , Terzini Mara , Borrelli Simone , Putame Giovanni , Moretto Francesca , Esposito Teresa , Vaschetto Rosanna , Morbiducci Umberto , Olivieri Carlo , Audenino Alberto L.
Published: February 2025

Introduction

CPAP therapy treats various respiratory disorders. The overall performance of therapy delivery can be affected by the adopted circuit configuration. Recently, parallel to the canonical open configuration (OC), closed configurations (CC) have been proposed with potential advantages in terms of oxygen consumption, noise, airway dryness and contamination. However, the mechanical performance of CPAP devices in CC has been marginally investigated. The aim of this study is to clarify whether CPAP therapy delivered in CC configuration retains mechanical performances equivalent to that achieved in the canonical OC stipulated by the manufacturers.

Methods

OCs and CCs implemented on seven different ventilation devices, classified as flowmeter, obstructive sleep apnoea device, and mechanical ventilator, were tested at different set CPAP levels. Mask and helmet interfaces were tested, and healthy, post-surgery and ARDS respiratory conditions were simulated. The mechanical performance was compared in terms of mean static pressure (Pmean), pressure oscillations, areas between pressure curve and Pmean during inspiration (Ai) and expiration (Ae), and the time in which the pressure curve remains above the Pmean along the expiration phase (T%).

Results

The mechanical performances of CCs with helmet interface were comparable to canonical OCs used with mask interface. Globally, a CC supplied a reduced Pmean (on average, −1.3 cmH2O for the mask and −0.3 cmH2O for the helmet) and an increased ΔP, Ae and Ai (on average +0.5, +2.5, +2 times, respectively).

Conclusion

The closed configuration proved its capability to effectively deliver CPAP therapy, thus making its intrinsic advantages available for future clinical use.
Non-enveloped virus inactivation potency of sodium dodecyl sulfate with citric and glutamic acids
Authors: Tan Yong Wah , Bok Chwee Fern , Lim Brenda Jun Fang , Kong Li Ying , Goo Kian Sim , Ishida Yoshiki , Liu Jiquan , Chua Chun Song , Chu Justin Jang Hann
Published: February 2025

Disinfection is one of the most important methods by which transmission of infectious diseases can be blocked, and efficacies differ depending on how they are used and the target organism. Small non-enveloped viruses are considerably less sensitive to disinfectants than enveloped viruses and vegetative bacteria or fungi and generally require strong protein-disrupting chemicals for effective inactivation, limiting their application in personal care products due to associated side effects. Sodium dodecyl sulfate (SDS) is a common anionic surfactant and relatively safe ingredient used in many personal care and hygiene products possessing protein-denaturing properties and has been reported to have antimicrobial efficacy against enveloped viruses and bacteria. With the aim of identifying milder disinfectants with broad-spectrum activity, including efficacy against non-enveloped viruses that are more difficult to inactivate, this study focused on evaluating the combinatorial efficacy of sodium dodecyl sulfate with organic acid (i.e., citric acid) and amino acid (i.e., glutamic acid) on feline calicivirus. Using an in vitro quantitative suspension test and electron microscopy, we have demonstrated the virucidal efficacy of SDS combinations with citric or glutamic acids on FCV. In addition, the spectrum of virucidal efficacy may potentially be extended to some human enteroviruses, and further research into their variable sensitivity to virus inactivation would be useful in developing these combinations into consumer products that target non-enveloped viruses.
Bordetella pertussis bacteremia in infants co-infected with cytomegalovirus and respiratory syncytial virus
Authors: Sun Wenqiang , Li Mengzhao , Zhu Xueping
Published: February 2025

Introduction

Hematogenous infections caused by Bordetella pertussis are rare. This study aimed to increase clinicians’ knowledge of B. pertussis bacteremia.

Methods

We described a case of an infant with B. pertussis bacteremia, searched and reviewed for B. pertussis bacteremia-related literatures published in the PubMed database between 1946 to 2022.

Results

A 3-month-old male infant was admitted to the hospital with a respiratory tract infection. Respiratory pathogen testing indicated the presence of B. pertussis, cytomegalovirus, and respiratory syncytial viruses. Blood metagenomic next-generation sequencing (mNGS) confirmed B. pertussis bacteremia. After 32 days of anti-infective treatment and supportive therapy, the patient’s condition improved, and he was discharged. The literature review found that B. pertussis bacteremia is rare, often with fever as the first symptom, and is most common in individuals with underlying diseases or prolonged immunosuppressive therapy.

Discussion

In infants lacking specific protective antibodies against B. pertussis, B. pertussis bacteremia should be considered when bacteremia-associated clinical manifestations are present and the causative organism remains undetected. Timely refinement of mNGS can help clarify the diagnosis.
Efficacy of transcranial direct current stimulation on cognitive function in patients with Parkinson's disease: a systematic review and meta-analysis
Authors: Ma Shenhong , Zhuang Weisheng , Wang Xu , Zhang Di , Wang Heling , Han Qiaohua , Ding Qixin , Li Yuefang , Li Wanyue , Li Tianshu
Published: February 2025

Objective

To assess the therapeutic effect of tDCS on cognitive function in patients with Parkinson's disease.

Methods

From the start of the library's construction until June 24, 2024, we searched the following databases for literature: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, China Science and Technology Journal Database (VIP), and China Biomedical Literature Database (CBM). We also looked through the references in the articles. The improvement of overall cognition in patients with Parkinson's disease with tDCS was the primary outcome indicator. The improvement of executive function, memory, attention, language, quality of life, and depression with tDCS were the secondary outcome indicators. Two researchers extracted data independently, with a third researcher mediating in the event of a dispute. The Cochrane risk of bias tool was used to evaluate the quality of the included literature.

Results

A total of 23 articles encompassing 874 subjects were included. tDCS has shown significant efficacy on overall cognition (SMD = 0.73, 95% CI = 0.57 to 0.89, I2 = 0%, P < 0.00001), particularly in the areas of executive function (SMD = −0.32, 95% CI = −0.56 to −0.07, I2 = 0%, P = 0.01) and language function (SMD = 0.5, 95% CI = 0.2 to 0.8, I2 = 0%, P = 0.001). Furthermore, the clinical efficacy of tDCS was enhanced with a stimulation intensity of 2 mA (SMD = 0.76, 95% CI = 0.58 to 0.93, I2 = 7%, P < 0.00001), a stimulation duration of ≥25 min (SMD = 0.70, 95% CI = 0.49 to 0.91, I2 = 6%, P < 0.00001), and a minimum of 10 stimulation sessions (SMD = 0.74, 95% CI = 0.56 to 0.92, I2 = 0%, P < 0.00001). Furthermore, tDCS has shown efficacy in alleviating depressive mood (SMD = −0.46, 95% CI = −0.79 to −0.13, I2 = 0%, P = 0.006).

Conclusion

tDCS demonstrated substantial efficacy in enhancing overall cognition in patients with PD. The efficacy of tDCS was obvious in executive function, language, and depressive mood. Nonetheless, a substantial quantity of rigorous clinical trials on tDCS for cognitive function in patients with PD remains necessary in the future.
Adolescent binge alcohol exposure accelerates Alzheimer’s disease-associated basal forebrain neuropathology through proinflammatory HMGB1 signaling
Authors: Fisher Rachael P. , Matheny Lindsay , Ankeny Sarrah , Qin Liya , Coleman Leon G. , Vetreno Ryan P.
Published: February 2025

Human studies suggest that heavy alcohol use may be an etiological factor contributing to the development of Alzheimer’s disease (AD) neuropathology. Both alcohol use disorder (AUD) and AD share common underlying neuropathology, including proinflammatory high-mobility group box 1 (HMGB1)-mediated neuroimmune signaling and basal forebrain cholinergic neuron degeneration. Adolescent onset of binge drinking represents a significant risk factor for later development of an AUD, and accumulating evidence suggests that adolescent initiation of heavy alcohol use induces HMGB1 signaling and causes degeneration of the basal forebrain cholinergic system that persists into adulthood. However, it is unknown whether adolescent binge drinking confers increased risk for later development of AD-associated neuropathology through persistent induction of proinflammatory HMGB1 neuroimmune signaling. To investigate this question, we first (Experiment 1) assessed AD-associated neuropathology in the post-mortem human basal forebrain of individuals with AUD and an adolescent age of drinking onset relative to age-matched moderate drinking controls (CONs). In Experiment 2, we treated non-transgenic and 5xFAD male and female mice, which overexpress both mutant human APP and PS1, with adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g. 2-days on/2-days off; postnatal day [P]30 – P55), and assessed AD-associated neuropathology in the adult (P100) basal forebrain. In Experiment 3, 5xFAD female mice received AIE treatment followed by glycyrrhizic acid (150 mg/L), an HMGB1 inhibitor, in drinking water from P56 to P100, and basal forebrain tissue was collected on P100 for assessment of AD-associated neuropathology. In the post-mortem human AUD basal forebrain (Experiment 1), we report upregulation of Hmgb1 and the HMGB1 receptors Rage and Tlr4 as well as microglial activation and increased intraneuronal Aβ1–42 accumulation in association with reduced cholinergic neuron marker expression (ChAT). In the 5xFAD mouse model (Experiment 2), AIE accelerated AD-associated induction of Hmgb1 proinflammatory neuroimmune genes, microglial activation, and reductions of ChAT+ basal forebrain cholinergic neurons in the adult female, but not male, basal forebrain. In Experiment 3, post-AIE treatment with glycyrrhizic acid rescued the AIE-induced acceleration of AD-associated increases in proinflammatory HMGB1 neuroimmune signaling, microglial activation, and persistent reductions of basal forebrain cholinergic neurons in adult 5xFAD female mice. Together, these findings suggest that adolescent binge ethanol exposure may represent an underappreciated etiological factor contributing to onset of AD-associated neuropathology in adulthood through HMGB1- mediated neuroimmune signaling.
Unraveling progressive verbal memory deficits in Huntington’s disease: insights from the LASSI-L
Authors: Sierra Luis A. , Kaur Japleen , Frank Samuel A. , Halko Mark A. , Curiel Cid Rosie E. , Loewenstein David A. , Corey-Bloom Jody , Laganiere Simon
Published: February 2025

Background and objectives

Huntington’s disease (HD) is characterized by progressive cognitive decline, with early deficits often preceding motor symptoms. The Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) captures many types of deficits in verbal memory including susceptibility to interference. The current study aims to delineate the progression of these deficits across different stages of HD.

Methods

151 participants (89 HD, 62 healthy controls) were recruited across three sites. HD participants were classified into three groups using a PIN score and TMS: >10 years from manifest HD, <10 years from manifest HD, and manifest HD. Group comparisons on the LASSI-L were assessed using multiple ANCOVAs adjusting for age, followed by post-hoc pairwise comparisons and a Bonferroni correction.

Results

Sequential group differences for susceptibility to interference effects were observed on the LASSI-L. Proactive Semantic Interference (PSI) deficits emerged >10 years before manifest HD, Failure to Recover from PSI (frPSI) emerged <10 years before manifest HD, and in the Manifest HD stage, participants exhibited additional deficits in Retroactive Semantic Interference (RSI). Based on cutoff scores derived from healthy control performance, 98% (87/89) of the HD cohort demonstrated either normal performance or significant impairments, primarily in PSI, with some showing concurrent deficits in frPSI and/or RSI. Furthermore, 88% of participants adhered to the full sequential decline pattern, progressing from deficits in PSI, to frPSI, and then to RSI.

Discussion

The LASSI-L appears to be a useful tool for detecting early and progressive cognitive changes in Huntington’s disease, particularly by capturing the sequential nature of verbal memory deficits, including early vulnerability to interference. These findings suggest that the LASSI-L may help refine HD staging by integrating sequential neuropsychological markers of cognitive decline.
A prospective multicenter study on prognostic factors and quality of care in Severe Acquired Brain Injury rehabilitation units: a project from the Tiresia network
Authors: Nattino Giovanni , Acler Michele , Bargellesi Stefano , Bertagnoni Giannettore , Carrara Greta , De Tanti Antonio , Estraneo Anna , Ghilardi Giulia Irene , Lavezzi Susanna , Lombardi Francesco , Lucca Lucia Francesca , Mancuso Mauro , Montis Andrea , Mulè Chiara , Navarro Jorge , Posteraro Federico , Rossato Elena , Simoncini Laura , Bertolini Guido
Published: February 2025

Background

Severe Acquired Brain Injury (sABI) presents significant challenges in clinical management and rehabilitation due to its diverse and complex nature. The primary objective of the Tiresia project is to identify medium and medium-to-long-term prognostic factors for patients with sABI and to develop outcome indicators to evaluate the quality of care in rehabilitation units.

Methods

This paper outlines the protocol for a prospective observational multicenter study conducted within the Tiresia Network. The study relies on a comprehensive data collection with stringent quality control measures. Ethical considerations emphasize patient privacy protection and adherence to regulatory standards. All of the Italian intensive rehabilitation units dedicated to sABI patients were eligible to participate in the study. Twenty-seven of them joined the project and started the data collection.

Discussion

The present study represents a comprehensive effort to address critical gaps in sABI research and practice through a multicenter, prospective study design. Through rigorous data collection, analysis, and ethical oversight, the Tiresia project endorses the commitment of the research community to advancing evidence-based care and optimizing patient outcomes in sABI rehabilitation.

Clinical trial registration

The study was registered on ClinicalTrials.gov (ID: NCT04905264), on 24 May 2021.
P300 as an index of speech-in-noise understanding in complex acoustic environments in young and older adults
Authors: Pearson Dylan V. , Shen Yi , Hetrick William P. , O’Donnell Brian F. , Lundin Nancy B. , McAuley J. Devin , Kidd Gary R.
Published: February 2025

Introduction

Aging is associated with decrements in speech-in-noise perception which make communication in real world environments difficult. However, the neural correlates of these difficulties are not well characterized and finding correlations between speech-in-noise performance and electrophysiological measures has been difficult due in part to the fact that speech-in-noise perception is a multi-faceted process. The current study used a wide range of speech-in-noise tasks in an attempt to more completely capture speech-in-noise performance and compared these with electrophysiological measures.

Methods

P300 event related brain responses were elicited in young and older adult listeners to spoken isochronous syllable sequences presented in quiet and noisy (i.e., multi-talker babble) background conditions. To investigate the extent to which P300 responses are associated with speech-in-noise understanding, listeners also completed a separate battery of speech-in-noise recognition tasks.

Results

Overall P300 amplitudes measured in noisy conditions, but not in quiet conditions, were associated with performance on a variety of speech recognition tasks and were positively correlated with a composite measure of speech understanding in noise based on the full battery. In addition, older adults had P300 responses to deviant and omitted speech stimuli with lower amplitudes, longer latencies, and relatively greater frontal topographies than young adults.

Discussion

The results demonstrate that P300 amplitudes elicited in competing noise were a strong predictor of speech-in-noise understanding. This, in addition to the age-related differences in P300 responses, highlights the relevance of neural attentional mechanisms for understanding age-related differences in speech understanding in noise.
Clinical efficacy and potential mechanisms of acupuncture for Parkinson’s disease: the role of GABAergic signaling
Authors: Lu Wenhui , Zhang Ting , Li Minghui , Zhang Jun , Liu Ningning , Yang Lanfang , Huang Guomin
Published: February 2025

Parkinson’s disease (PD), a common neurodegenerative disease, seriously impacts the quality of life of patients. In recent years, research has revealed that the GABAergic signaling pathway plays an important role in the occurrence and development of PD. GABA is an important inhibitory neurotransmitter in the central nervous system (CNS), synthesized through the alpha decarboxylation reaction of glutamate (Glu) under the action of glutamic acid decarboxylase (GAD) in GABAergic neurons. It works by binding to specific receptors (GABAA/GABAB). In PD patients, the activity of GABAergic neurons in the basal ganglia (BG) changes, leading to an imbalance between direct and indirect pathways and causing motor symptoms. Meanwhile, the GABAergic signaling pathway is closely related to non-motor symptoms such as anxiety, depression, and sleep disorders. At present, the treatment methods for PD mainly include drug therapy, surgical treatment, and rehabilitation therapy. Acupuncture, as a complementary and alternative therapy, has shown promising efficacy in the clinical treatment of PD. This review comprehensively and thoroughly explores the therapeutic effect of acupuncture on PD and its mechanism of action with GABAergic signaling. By systematically summarizing relevant research results, it was found that acupuncture may exert a complex mechanism of therapeutic effect by regulating the GABAergic signaling pathway. Further clarification of these mechanisms of action will be beneficial for promoting the application and development of acupuncture in the treatment of PD and is expected to provide new targets and strategies.
Case report: LMNB1 duplication-mediated autosomal dominant adult leukodystrophy in a Chinese family and literature review of Chinese patients
Authors: Jiang Yumeng , Han Lu , Li Yaqi , Zhao Zhihong , Xin Zikai , Zhu Zilong
Published: February 2025

Adult-onset autosomal dominant leukodystrophy (ADLD) is a rare, slowly progressive, and fatal neurodegenerative disorder characterized by central nervous system white matter loss due to LMNB1 gene abnormalities encoding laminB1. However, not all LMNB1 mutations lead to ADLD. Currently, two genetic alterations have been identified in association with the pathogenesis of ADLD: LMNB1 gene tandem duplication and LMNB1 gene upstream deletions. We report a case of a 60-year-old man diagnosed with ADLD, with pyramidal tract dysfunction and autonomic abnormalities as the main clinical manifestations. MRI revealed bilateral symmetric high signal intensities in the white matter of the medulla oblongata, middle cerebellar peduncles, cerebral peduncle, periventricular white matter, centrum semi vale, and the pressure region of the corpus callosum. Whole exome sequencing results indicated 73.6Kb duplicate copy number variation signals in the 5q23.2 region of the proband’s chromosome. The Multiplex ligation-dependent probe amplification (MLPA) experiment results indicate recurrent mutations across all exons (exon1–11) of the LMNB1 gene. This is the eighth ADLD pedigree from China. We conducted a literature review of all ADLD pedigrees in China and summarized the characteristics of Chinese patients with ADLD to raise awareness of ADLD disease.
Input–output organization of the mouse BLA-projecting IL neurons
Authors: Li Zhuo , Qu Yu , Wu Qi-Lin , Tang Li , Dong Yuan , Xu Xu-Feng
Published: February 2025

Introduction

The infralimbic cortex (IL), a critical subregion within the ventromedial prefrontal cortex (vmPFC), modulates emotion, memory, and social functions via robust projections to the basolateral amygdala (BLA). However, the afferent brain regions that innervate BLA-projecting IL neurons (IL-BLA PNs) and their efferent targets have not been systematically characterized.

Methods

We employed tracing techniques integrating adeno-associated virus (AAV) and monosynaptic rabies to systematically investigate the presynaptic inputs and axonal outputs of IL-BLA PNs.

Results

Our findings revealed widespread synaptic inputs to IL-BLA PNs from subcortical areas, with the strongest inputs originating from the dorsomedial thalamus (MD) and anterior medial thalamus (AM) in the thalamic region, as well as from the ventral hippocampus (vHPC) and piriform cortex (Pir) in the limbic system. Sparse labeling of the virus demonstrated that IL-BLA PNs collateralize to innervate various subcortical regions, including the horizontal diagonal band (HDB), lateral preoptic area (LPO), ventral pallidum (VP), and lateral hypothalamus (LH).

Discussion

This work establishes essential theoretical frameworks for the functional investigation and targeted intervention in neurological disorders.
Impaired cerebrospinal fluid circulation and cerebral lymphatic drainage in a rat model of chronic hydrocephalus
Authors: Back Dong Bin , Choi Bo-Ryoung , Kwon Kyoung Ja , Choi Dong-Hee , Shin Chan Young , Lee Jongmin , Kim Hahn Young
Published: February 2025

The cerebrospinal fluid (CSF) not only protects the brain but also maintains homeostasis by removing metabolic waste produced by brain activity. This study hypothesizes that chronic CSF circulatory dysfunction, such as chronic hydrocephalus or normal pressure hydrocephalus (NPH), may be a critical condition in neurodegenerative diseases associated with metabolic waste accumulation. To investigate the CSF circulation and cerebral lymphatic drainage in a rat model of chronic hydrocephalus induced by kaolin injection, we performed time-dependent evaluations of intraparenchymal injection of tracers as well as intraventricular injection of Evans blue. The study systemically evaluated the dysfunction of CSF circulation and lymphatic drainage in the brain from various perspectives, including the glymphatic system, transependymal CSF flow, subarachnoid CSF flow, meningeal lymphatic drainage, and peripheral lymphatic drainage to deep cervical lymph nodes. The results indicated delayed CSF circulation, including glymphatic system, and cerebral lymphatic drainage in the kaolin-induced chronic hydrocephalus model. Based on these findings, our research indicated that dysfunction of CSF circulation, as observed in conditions such as chronic hydrocephalus or NPH, may act as an initiating or exacerbating factor in neurodegenerative diseases. This can lead to the accumulation of metabolic waste, as seen in Alzheimer’s disease. Our research can help identify risk factors and provide insight into the underlying pathophysiology of neurodegenerative diseases, which may lead to the development of novel therapeutic strategies.
Evaluating robotic actions: spatiotemporal brain dynamics of performance assessment in robot-assisted laparoscopic training
Authors: Lingelbach Katharina , Rips Jennifer , Karstensen Lennart , Mathis-Ullrich Franziska , Vukelić Mathias
Published: February 2025

Introduction

Enhancing medical robot training traditionally relies on explicit feedback from physicians to identify optimal and suboptimal robotic actions during surgery. Passive brain-computer interfaces (BCIs) offer an emerging alternative by enabling implicit brain-based performance evaluations. However, effectively decoding these evaluations of robot performance requires a comprehensive understanding of the spatiotemporal brain dynamics identifying optimal and suboptimal robot actions within realistic settings.

Methods

We conducted an electroencephalographic study with 16 participants who mentally assessed the quality of robotic actions while observing simulated robot-assisted laparoscopic surgery scenarios designed to approximate real-world conditions. We aimed to identify key spatiotemporal dynamics using the surface Laplacian technique and two complementary data-driven methods: a mass-univariate permutation-based clustering and multivariate pattern analysis (MVPA)-based temporal decoding. A second goal was to identify the optimal time interval of evoked brain signatures for single-trial classification.

Results

Our analyses revealed three distinct spatiotemporal brain dynamics differentiating the quality assessment of optimal vs. suboptimal robotic actions during video-based laparoscopic training observations. Specifically, an enhanced left fronto-temporal current source, consistent with P300, LPP, and P600 components, indicated heightened attentional allocation and sustained evaluation processes during suboptimal robot actions. Additionally, amplified current sinks in right frontal and mid-occipito-parietal regions suggested prediction-based processing and conflict detection, consistent with the oERN and interaction-based ERN/N400. Both mass-univariate clustering and MVPA provided convergent evidence supporting these neural distinctions.

Discussion

The identified neural signatures propose that suboptimal robotic actions elicit enhanced, sustained brain dynamics linked to continuous attention allocation, action monitoring, conflict detection, and ongoing evaluative processing. The findings highlight the importance of prioritizing late evaluative brain signatures in BCIs to classify robotic actions reliably. These insights have significant implications for advancing machine-learning-based training paradigms.