bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pleiotrophin Overexpression Reduces Adolescent Ethanol Consumption and Modulates Ethanol‐Induced Glial Responses and Changes in the Perineuronal Nets in the Mouse Hippocampus
Authors: Galán‐Llario Milagros , Rodríguez‐Zapata María , Fontán‐Baselga Teresa , Cañeque‐Rufo Héctor , García‐Guerra Alba , Fernández Beatriz , Gramage Esther , Herradón Gonzalo 
Published: December 2024

ABSTRACTAimsTo investigate whether pleiotrophin (PTN) overexpression influences ethanol consumption during adolescence and its effects on glial responses, neurogenesis, and perineuronal nets (PNNs) in the mouse hippocampus.MethodsMale and female adolescent transgenic mice with elevated PTN levels (Ptn‐Tg) and controls underwent an intermittent access to ethanol (IAE) 2‐bottle choice protocol. Ethanol consumption, PTN levels, neurogenesis, and glial responses were measured in the hippocampus. Immunohistochemistry was used to assess changes in new neurons, microglial and astrocyte populations, and PNNs.ResultsPtn‐Tg mice consumed significantly less ethanol compared to controls, irrespective of sex. Chronic alcohol exposure reduced PTN levels in the hippocampus. PTN overexpression decreased the number of new neurons in the dentate gyrus (DG) and prevented ethanol‐induced microglial activation. Ptn‐Tg mice had significantly more astrocytes and fewer PNNs, with a higher percentage of parvalbumin (PV) positive cells surrounded by PNNs under basal conditions. However, ethanol drastically reduced the number of PV+ cells in the DG of Ptn‐Tg mice, despite the presence of PNNs.ConclusionPTN overexpression reduces adolescent ethanol consumption and influences ethanol‐induced effects on hippocampal neurogenesis, glial responses, and PNN remodeling. These findings underscore the importance of PTN in modulating alcohol‐induced neurotoxicity.
Effect of organic biocolourants on lightfastness and mechanical properties of polylactic acid
Authors: Jordan J. , Lima T. A. de M. de , Nugent M. , Laaksonen P. 
Published: December 2024

AbstractMost modern colourants are acquired from petroleum‐based sources or mining, which often causes environmental degradation. Consequently, alternative colouring solutions are sought, such as using biocolourants, which are organic colourants from bio‐based sources. Although biocolourant research is prevalent in the textile dyeing field, biocoloration of thermoplastics remains relatively unexplored. Thus, our study presents lightfastness and mechanical properties of polylactic acid (PLA) biocoloured with biochar, kraft lignin, indigo from Isatis tinctoria, madder extract from Rubia tinctorum, and weld extract from Reseda luteola. Indigo, madder extract, and weld extract are common bio‐based textile dyes, whereas biochar and lignin are more known as easily accessible filler additives than as colourants. Stemming from promising results with bio‐based indigo in our previous studies, this study broadens the scope with new colourants and analysis methods. In this study, mixtures of biocolourant powder and PLA granules were heated to a viscous state, blended inside an injection screw, and injection moulded into plastic specimens. The PLA‐biocolourant specimens were inspected with scanning electron microscopy (SEM) and subjected to ASTM D638 tensile test. Furthermore, the specimens were exposed to ISO 105‐B02 lightfastness test under xenon arc light. Before and after xenon light exposure, the specimens were analysed with visual inspection, reflectance spectrophotometry, hyperspectral imaging, and Fourier‐transform infrared (FTIR) spectroscopy. The results showed that most of the biocolourants produced an even colour with adequate lightfastness. Moreover, lignin, biochar, and madder extract substantially improved photodegradation resistance and tensile properties of PLA. Thus, further development of biocolourants, especially lignin, as functional PLA additives is recommended.
Identifying subgroups benefiting from intensive glycaemic treatment to improve renal outcomes in type 2 diabetes: Insights from the ACCORD trial
Authors: Wang Yiqin , Wen Qiong , Lu Yuewen , Yang Jiayi , Huang Naya , Chen Wei 
Published: December 2024

AbstractAimsThe ACCORD trial showed that intensive glucose‐lowering therapy has a limited impact on renal function decline. We aimed to identify subgroups in the ACCORD population that might derive renal benefits from intensive glucose‐lowering therapy.Materials and MethodsThe primary renal outcome included a ≥50% decline in baseline estimated glomerular filtration rate or end‐stage renal disease (ESRD). Using the causal tree model, we employed internal cross‐validation to identify five pivotal variables influencing the renal efficacy of intensive glycaemic control. These variables were integrated into the model‐based recursive partitioning approach, yielding a visualizable tree model that depicted benefitting subgroups.ResultsNode 4, characterized by no cardiovascular history, systolic blood pressure (SBP) ≤142.67 mm Hg, and triglycerides ≤172 mg/dL, showed significantly reduced hazards of the composite renal outcome (fully adjusted hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.49–0.89; p = 0.006) and doubling of serum creatinine (fully adjusted HR 0.59, 95% CI 0.36–0.98; p = 0.041). Node 7 (no cardiovascular history and SBP 142.67–154 mm Hg) showed reduced hazards of the primary renal outcome (fully adjusted HR 0.67, 95% CI 0.49–0.93; p = 0.016) and ESRD (fully adjusted HR 0.35, 95% CI 0.17–0.74; p = 0.0057). Encouragingly, neither node 4 nor node 7 displayed elevated cardiovascular risk or hypoglycaemic events.ConclusionsThrough innovative machine learning, we identified ACCORD subgroups benefitting significantly from intensive glycaemic therapy for renal outcomes, without increased cardiovascular or hypoglycaemic risks.
Subtyping strokes using blood‐based protein biomarkers: A high‐throughput proteomics and machine learning approach
Authors: Misra Shubham , Singh Praveen , Sengupta Shantanu , Kushwaha Manoj , Rahman Zuhaibur , Bhalla Divya , Talwar Pumanshi , Nath Manabesh , Chakraborty Rahul , Kumar Pradeep , Kumar Amit , Aggarwal Praveen , Srivastava Achal K. , Pandit Awadh K. , Mohania Dheeraj , Prasad Kameshwar , Mishra Nishant K. , Vibha Deepti 
Published: December 2024

AbstractBackgroundRapid diagnosis of stroke and its subtypes is critical in early stages. We aimed to discover and validate blood‐based protein biomarkers to differentiate ischemic stroke (IS) from intracerebral haemorrhage (ICH) using high‐throughput proteomics.MethodsWe collected serum samples within 24 h from acute stroke (IS & ICH) and mimics patients. In the discovery phase, SWATH‐MS proteomics identified differentially expressed proteins, which were validated using targeted proteomics in the validation phase. We conducted interaction network and pathway analyses using Cytoscape 3.10.0. We determined cut‐off points using the Youden Index. We developed three prediction models using multivariable logistic regression analyses. We assessed the model performance using statistical tests.ResultsWe included 20 IS and 20 ICH in the discovery phase and 150 IS, 150 ICH, and six stroke mimics in the validation phase. We quantified 375 proteins using SWATH‐MS. Between IS and ICH, we discovered 20 differentially expressed proteins. In the validation phase, the combined prediction model including three biomarkers: GFAP (aOR 0.04; 95%CI .02–.11), MMP‐9 (aOR .09; .03–.28), APO‐C1 (aOR 5.76; 2.66–12.47) and clinical variables independently differentiated IS from ICH (accuracy: 92%, negative predictive value: 94%). Adding biomarkers to clinical variables improved discrimination by 26% (p < .001). Additionally, nine biomarkers differentiated IS from ICH within 6 h, while three biomarkers differentiated IS from mimics.ConclusionsOur study demonstrated that GFAP, MMP‐9 and APO‐C1 biomarkers independently differentiated IS from ICH within 24 h and significantly improved the discrimination ability of prediction models. Temporal profiling of these biomarkers in the acute phase of stroke is warranted.
Metacognitive Awareness and EFL Learners' Perceptions and Experiences in Utilising ChatGPT for Writing Feedback
Authors: Teng Mark Feng 
Published: December 2024

ABSTRACTThe present study explored EFL students' perceptions and experiences in utilising ChatGPT to seek feedback for writing. The present study also examined how levels of metacognitive awareness (MA) influenced these perceptions and experiences. Utilising a mixed‐method research design, the study collected data from a total of 40 EFL undergraduates over a semester‐long writing course. Data collection methods included self‐report questionnaires and semi‐structured interviews. Data analyses comprised both quantitative and qualitative approaches. Quantitatively, t‐tests and Mann–Whitney U tests were used to compare group differences, while regression analyses were conducted to explore relationships between variables. Qualitatively, thematic analysis was employed to identify and interpret patterns within the data. Quantitative analysis revealed significant differences in writing experiences and perceptions, including motivation for writing, engagement, self‐efficacy and collaborative writing tendency. Furthermore, a positive correlation was found between MA scores and students' perceptions and practices of using ChatGPT. Analysis of interview data highlighted a range of perceptions and experiences between the high and low MA students, with behaviours spanning from mere copying words from ChatGPT to effective use of ChatGPT for writing feedback. Key factors that influenced the effective use of ChatGPT for writing assistance included metacognitive awareness, critical thinking skills and cognitive efforts. The findings highlight implications for writing teachers and students in teaching and learning English as a foreign language.
Secondary Malignancies After Autologous Stem Cell Transplantations in Patients With Malignant Lymphoma and Multiple Myeloma
Authors: Metzner Bernd , Müller Thomas H. , Casper Jochen , Kimmich Christoph , Petershofen Eduard K. , Thole Ruth , Voß Andreas , Köhne Claus Henning 
Published: December 2024

ABSTRACTBackgroundSecondary malignancies are potential complications after high‐dose therapy and autologous stem cell transplantation (ASCT). Information on the detailed course of such events is scarce, yet may be essential to minimize the impact of these sequelae.Patients and MethodsWe regularly monitored 877 patients for up to 31 years after ASCT in our outpatient department.ResultsFour‐hundred and five patients with malignant lymphoma and 472 patients with multiple myeloma were analysed with a median follow‐up from the initial malignant diagnosis of 7.0 years (0.5–35.5), from ASCT of 4.8 years (range 0.2–31.3). Eighty‐nine of these patients suffered from 94 invasive secondary malignancies (30 haematologic malignancies, 64 solid tumours). In 29 patients a non‐melanoma skin cancer was observed. 31/64 (48%) patients with solid tumours were diagnosed in an early stage of the disease (UICC 0–2) and had a chance of cure. 5% of the patients developed an invasive malignancy within 5 years, 12% within 10 years, 21% within 20 years. Risk factors were advanced age, the diagnosis lymphoma and in lymphoma patients additionally male sex.ConclusionsSecondary malignancies after ASCT are relatively frequent complications. Our findings suggest that systematic life‐long cancer screening after ASCT is essential to improve the prognosis of these adverse events.
Determinants of long‐term disability in chronic inflammatory demyelinating polyradiculoneuropathy: A multicenter Korea/UK study of 144 patients
Authors: Min Young Gi , Jeon Jaehyun , Kim Sung‐Min , Hong Yoon‐Ho , Englezou Christina , Sung Jung‐Joon , Rajabally Yusuf A. 
Published: December 2024

AbstractBackgroundDespite standard‐of‐care treatment, therapeutic outcomes in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are often incomplete. We aimed to evaluate the impact of clinical and therapeutic factors on long‐term disability in CIDP, from cohorts from Korea and the UK.MethodsWe conducted a retrospective multicenter cohort study of 144 patients with CIDP. Baseline characteristics and treatment data were collected, and disability was assessed using the Overall Neuropathy Limitation Scale (ONLS) for the UK cohort, Inflammatory Neuropathy Cause and Treatment (INCAT) scores for the Korean cohort, and Inflammatory Rasch‐built Overall Disability Scale (I‐RODS) for the combined cohort. Univariate and multivariate linear regression analyses were performed to identify independent prognostic factors. Subgroup analyses were conducted according to important clinical features to gain further insights into which patients are most likely to benefit from early treatment.ResultsTreatment initiation within 1 year of onset was significantly associated with lesser post‐treatment disability and greater amplitude of treatment response, in each cohort separately, and in the combined cohort. This association remained significant after adjusting for covariates in multivariate regression. Subgroup analyses demonstrated early treatment benefits in older patients (≥60 years), those with typical CIDP, and those with a chronic mode of onset. The type of first‐line therapy and baseline disability levels did not influence outcomes. Other identified independent prognostic factors included comorbidity and pre‐treatment disability level.DiscussionEarly treatment initiation is a key modifiable determinant of favorable long‐term disability in CIDP. These findings underscore the importance of timely diagnosis and prompt treatment to prevent irreversible axonal damage.
Spontaneous intracranial hypotension — Neurological symptoms, diagnosis, and outcome
Authors: Dalby Sebastian Worsaae , Smilkov Emil Andonov , Santos Sofia Gaspar , Olesen Viola , Skjolding Anders Daehli , Vukovic‐Cvetkovic Vlasta , Jensen Rigmor Højland , Schytz Henrik Winther 
Published: December 2024

AbstractBackgroundSpontaneous intracranial hypotension (SIH) is a rare secondary headache disorder caused by spinal leakage of cerebrospinal fluid. Specialized treatment of SIH consists of epidural blood patches (EBPs), fibrin patching, endovascular sealing, and surgery. The aim of this paper was to characterize SIH patients identified at a tertiary headache center.MethodsEighty patients with SIH identified at the Danish Headache Center were included in this clinical cohort study. Data on demographics, clinical presentation, imaging findings, effect of EBPs, and invasive procedures were collected in a standardized manner. Prognostic elements of EBP treatment outcome were evaluated statistically with success defined as a minimum 30% intensity reduction sustained for at least 1 month.ResultsThe average age was 47 years and 53% were female. Peracute and subacute onset was noted in 35% and 36%, respectively. Orthostatic headache was noted in 85% of cases. The median Bern score was 4, and of identified leaks, 52% were type 1, 22% type 2, 22% type 3, and 4% type 4 (defined as peripheral leakage distally for the root pouch).Successful treatment response was 34% for EBPs and 90% for invasive procedures. Prepontine cistern effacement was more prevalent in patients with successful first EBP than without (p = 0.013).ConclusionSIH patients presented with a wide variety of symptoms with high prevalence of orthostatic headache. Peracute onset was noted in 35% and calls for more awareness in the acute setting. We found prepontine cistern effacement to be a potential predictor of a successful first epidural blood patch.
Sex‐related differences in amyotrophic lateral sclerosis: A 2‐[18F]FDG‐PET study
Authors: Canosa Antonio , Martino Alessio , Manera Umberto , Giuliani Alessandro , Vasta Rosario , Palumbo Francesca , Grassano Maurizio , Morbelli Silvia Daniela , Pardini Matteo , Chiaravalloti Agostino , Schillaci Orazio , Leenders Klaus Leonard , Kogan Rosalie Vered , Polverari Giulia , Zocco Grazia , Pede Francesca Di , Mattei Filippo De , Cabras Sara , Matteoni Enrico , Moglia Cristina , Calvo Andrea , Chiò Adriano , Pagani Marco 
Published: December 2024

AbstractPurposeWe investigated sex‐related brain metabolic differences in Amyotrophic Lateral Sclerosis (ALS) and healthy controls (HC).MethodsWe collected two equal‐sized groups of male (m‐ALS) and female ALS (f‐ALS) patients (n = 130 each), who underwent 2‐[18F]FDG‐PET at diagnosis, matched for site of onset, cognitive status and King's stage. We included 168 age‐matched healthy controls, half female (f‐HC) and half male (m‐HC). We compared brain metabolism of males and females separately for ALS and HC, including age as covariate. A differential network analysis was performed to evaluate brain connectivity.ResultsM‐ALS showed relative hypometabolism of bilateral medial frontal, parietal and occipital cortices, and left temporal cortex, compared to f‐ALS. In node‐wise comparison, f‐ALS showed significantly higher connectivity in right middle cingulate cortex and left superior and medial frontal gyrus. In HC we did not find any sex‐related differences.ConclusionSex resulted a major determinant of brain metabolism and connectivity in ALS patients.
Asymmetric dynamics of GABAergic system and paradoxical responses of GABAergic neurons in piriform seizures
Authors: Tao Yan , Zhao Yuxin , Zhong Wenqi , Zhu Hongyan , Shao Ziyue , Wu Ruiqi 
Published: December 2024

AbstractObjectiveThe piriform cortex (PC) plays a critical role in ictogenesis, where an excitation/inhibition imbalance contributes to epilepsy etiology. However, the epileptic dynamics of the gamma‐aminobutyric acid (GABA) system and the precise role of GABAergic neurons within the PC in epilepsy remain unclear.MethodsWe combined Ca2+ and GABA sensors to investigate the dynamics of Gad2‐expressing neurons and GABA levels, and selectively manipulated GABAergic neurons in the PC through chemogenetic inhibition and caspase3‐mediated apoptosis targeting Gad2 interneurons.ResultsGABAergic system dynamics in the PC were bidirectional and asymmetric, accompanied by PC optokindling‐induced seizures, notably characterized by a robust response of Gad2 neurons but a rapid descent of GABA content during seizures. Chemogenetic inhibition of PC Gad2 neurons induced seizure‐like behavior, with a discrepancy between the GABAergic neuron activities and GABA levels, signifying a transition from interictal to ictal states. Surprisingly, selective inhibition of Gad2 neurons in the PC produced paradoxical activation in a subset of Gad2 neurons. Moreover, the chronic deficiency of PC Gad2 neurons triggered spontaneous recurrent seizures.SignificanceOur findings uncover the dynamic interplay within PC inhibitory components and elaborate counteractive mechanisms in seizure regulation. These insights could inform future therapeutic strategies targeting GABAergic neurons to control epileptic activity.
Development of individualized risk assessment models for predicting post‐traumatic epilepsy 1 and 2 years after moderate‐to‐severe traumatic brain injury: A traumatic brain injury model system study
Authors: Awan Nabil , Kumar Raj G. , Juengst Shannon B. , DiSanto Dominic , Harrison‐Felix Cynthia , Dams‐O'Connor Kristen , Pugh Mary Jo , Zafonte Ross D. , Walker William C. , Szaflarski Jerzy P. , Krafty Robert T. , Wagner Amy K. 
Published: December 2024

AbstractObjectiveAlthough traumatic brain injury (TBI) and post‐traumatic epilepsy (PTE) are common, there are no prospective models quantifying individual epilepsy risk after moderate‐to‐severe TBI (msTBI). We generated parsimonious prediction models to quantify individual epilepsy risk between acute inpatient rehabilitation for individuals 2 years after msTBI.MethodsWe used data from 6089 prospectively enrolled participants (≥16 years) in the TBI Model Systems National Database. Of these, 4126 individuals had complete seizure data collected over a 2‐year period post‐injury. We performed a case‐complete analysis to generate multiple prediction models using least absolute shrinkage and selection operator logistic regression. Baseline predictors were used to assess 2‐year seizure risk (Model 1). Then a 2‐year seizure risk was assessed excluding the acute care variables (Model 2). In addition, we generated prognostic models predicting new/recurrent seizures during Year 2 post‐msTBI (Model 3) and predicting new seizures only during Year 2 (Model 4). We assessed model sensitivity when keeping specificity ≥.60, area under the receiver‐operating characteristic curve (AUROC), and AUROC model performance through 5‐fold cross‐validation (CV).ResultsModel 1 (73.8% men, 44.1 ± 19.7 years, 76.1% moderate TBI) had a model sensitivity = 76.00% and average AUROC = .73 ± .02 in 5‐fold CV. Model 2 had a model sensitivity = 72.16% and average AUROC = .70 ± .02 in 5‐fold CV. Model 3 had a sensitivity = 86.63% and average AUROC = .84 ± .03 in 5‐fold CV. Model 4 had a sensitivity = 73.68% and average AUROC = .67 ± .03 in 5‐fold CV. Cranial surgeries, acute care seizures, intracranial fragments, and traumatic hemorrhages were consistent predictors across all models. Demographic and mental health variables contributed to some models. Simulated, clinical examples model individual PTE predictions.SignificanceUsing information available, acute‐care, and year‐1 post‐injury data, parsimonious quantitative epilepsy prediction models following msTBI may facilitate timely evidence‐based PTE prognostication within a 2‐year period. We developed interactive web‐based tools for testing prediction model external validity among independent cohorts. Individualized PTE risk may inform clinical trial development/design and clinical decision support tools for this population.
Bridging the conversational gap in epilepsy: Using large language models to reveal insights into patient behavior and concerns from online discussions
Authors: Fennig Uriel , Yom‐Tov Elad , Savitzky Leehe , Nissan Johnatan , Altman Keren , Loebenstein Roni , Boxer Marina , Weinberg Nitai , Gofrit Shany Guly , Maggio Nicola 
Published: December 2024

AbstractObjectiveThis study was undertaken to explore the experiences and concerns of people living with epilepsy by analyzing discussions in an online epilepsy community, using large language models (LLMs) to identify themes, demographic patterns, and associations with emotional distress, substance use, and suicidal ideation.MethodsWe analyzed 56 970 posts and responses to them from 21 906 users on the epilepsy forum (subreddit) of Reddit and 768 504 posts from the same users in other subreddits, between 2010 and 2023. LLMs, validated against human labeling, were used to identify 23 recurring themes, assess demographic differences, and examine cross‐posting to depression‐ and suicide‐related subreddits. Hazard ratios (HRs) were calculated to assess the association between specific themes and activity in mental health forums.ResultsProminent topics included seizure descriptions, medication management, stigma, drug and alcohol use, and emotional well‐being. The posts on topics less likely to be discussed in clinical settings had the highest engagement. Younger users focused on stigma and emotional issues, whereas older users discussed medical treatments. Posts about emotional distress (HR = 1.3), postictal state (HR = 1.4), surgical treatment (HR = .7), and work challenges (HR = 1.6) predicted activity in a subreddit associated with suicidal ideation, whereas emotional distress (HR = 1.5), surgical treatment (HR = .6), and stigma (HR = 1.3) predicted activity in the depression subreddit. Substance use discussions showed a temporal pattern of association with seizure descriptions, implying possible opportunities for intervention.SignificanceLLM analysis of online epilepsy communities provides novel insights into patient concerns often overlooked in clinical settings. These findings may improve patient–provider communication, inform personalized interventions, and support the development of patient‐reported outcome measures. Additionally, hazard models can help identify at‐risk individuals, offering opportunities for early mental health interventions.