bluuebunny/crossref_metadata_2025 huggingface dataset:
Drafting a blueprint for designing successful clinical trials in clonal haematopoiesis
Authors: Patel Shyam A. , Weeks Lachelle D.
Published: December 2024

‘As our understanding of the biology of clonal hematopoiesis expands, a pressing need in the field becomes the design and implementation of clinical trials to help mitigate the risk for progression to overt myeloid neoplasm. Effective clinical trial design will be informed by use of personalized genetic risk to determine eligibility, strategic endpoint selection, and identification of suitable interventions with a goldilocks balance of toxicity and reduced risk of progression. We will only reach this milestone through collaboration’.

Commentary on: Haque et al. A blueprint for pursuing therapeutic interventions and early phase clinical trials in clonal haematopoiesis. Br J Haematol 2025; 206:416‐427.
With a little help from my friends: Social support, hope and climate change engagement
Authors: Geiger Nathaniel , Swim Janet K. , Fraser John
Published: December 2024

Hope is a future‐oriented emotion that attunes people to the possibility of positive change, and thus could potentially catalyse societal engagement with climate change. A recent meta‐analysis suggests that the relationship between hope and climate action is most robust when the target of hope is climate engagement (i.e. action hope) rather than climate change more broadly. Yet, this previous meta‐analysis also suggests that fostering action hope and climate engagement may be challenging via typical short media messages used in many studies. Here we consider an alternative source of action hope: receiving social support. Two studies tested whether social support motivates climate action via increased action hope. Study 1 (correlational online survey, pre‐registered, N = 887) demonstrates that, as predicted, both instrumental and emotional support predict intentions to take civic action and these effects are explained by action hope. Study 2 (field study, Neducators = 84, Ncontacts = 520) mostly replicates and extends these findings in a field setting, demonstrating that social support recipients' action hope is also associated with social support reported by support providers (here, environmental educators) and that this action hope again explains a possible relationship between social support and climate engagement.
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

Aims

To 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.

Methods

Male 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.

Results

Ptn‐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.

Conclusion

PTN 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

Most 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

Aims

The 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 Methods

The 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.

Results

Node 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.

Conclusions

Through 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

Background

Rapid 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.

Methods

We 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.

Results

We 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.

Conclusions

Our 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

The 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

Background

Secondary 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 Methods

We regularly monitored 877 patients for up to 31 years after ASCT in our outpatient department.

Results

Four‐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.

Conclusions

Secondary 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

Background

Despite 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.

Methods

We 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.

Results

Treatment 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.

Discussion

Early 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

Background

Spontaneous 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.

Methods

Eighty 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.

Results

The 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).

Conclusion

SIH 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

Purpose

We investigated sex‐related brain metabolic differences in Amyotrophic Lateral Sclerosis (ALS) and healthy controls (HC).

Methods

We 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.

Results

M‐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.

Conclusion

Sex 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

Objective

The 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.

Methods

We 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.

Results

GABAergic 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.

Significance

Our 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

Objective

Although 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.

Methods

We 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).

Results

Model 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.

Significance

Using 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

Objective

This 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.

Methods

We 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.

Results

Prominent 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.

Significance

LLM 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.
Comparing Different Procedures for Calculating Flexural Cracking Toughness Using Edge‐Notched Disc Bend Specimen Under Modes I and III
Authors: Hoseini Seyed Omid , Sohrabi Mohammad Reza , Mousavi Seyed Roohollah , Ghasemi Mohammad , Aliha M. R. M.
Published: December 2024

This research used 30%, 40%, 50%, and 60% coarse aggregates and 0.15%, 0.3%, and 0.45% wavy steel fibers to make end‐notched disc bend self‐compacting concrete specimens for calculating and comparing flexural cracking toughness index by ASTM C1609, JSCE SF‐4, and JG/T 472‐2015 methods under pure modes I and III. The variation trends of different procedures under pure mode I was more affected by coarse aggregates and fibers had no noticeable influence. But under pure mode III increasing both fibers and aggregates improved the flexural cracking toughness. The estimation of JG/T 472‐2015 method was better than other methods under pure mode I. In pure mode III, due to positive effect of fibers on the pre‐peak, peak, and post‐peak areas, the deflection exceeds 1 mm. Hence, calculating the area under the load–displacement curve is facilitated for the ASTM C1609 and JSCE SF‐4 methods up to L/150 deflections.
Heterogeneity in the effects of bank lines of credit on capital investment efficiency
Authors: Wu Wei‐Shao , Suardi Sandy
Published: December 2024

This paper explores the effects of bank lines of credit on corporate investment efficiency. Credit lines impact capital investment efficiency by influencing fundamental growth opportunities and non‐fundamental stock valuations in Tobin's Q. Furthermore, firms with credit lines reduce under‐investment, contributing to an overall improvement in investment efficiency. Although credit lines enhance capital investment efficiency, their positive impact diminishes during economic downturns, low market sentiment, and stringent lending standards. Firms characterized by specific traits, such as high financial constraints, high leverage, and short operating cycles, tend to derive greater benefits in capital investment efficiency through access to credit lines.
A Retrospective Study to Investigate the Relationship Between Body Mass Index and Hemodynamic Characteristics in Hypertensive Patients
Authors: Xiao Wenqi , Han Ping , Song Liping , Yang Jingwen , Zhou Lin , Deng Xiangning , Ma Zheng J. , Lang Yukun , Zhao Hai , Zhao Yuzhuo , Chen Hui , Zhang Wenjing , Huang Huixian , Sun Ningling
Published: December 2024

The relationship between hemodynamic parameters and body mass index (BMI) in the context of blood pressure regulation in hypertension is unclear. Here, we analyzed data from 1368 uncontrolled hypertensive patients, including key hemodynamic indicators such as heart rate (HR), cardiac index (CI), arterial stiffness (AS), systemic vascular resistance index (SVRI), and thoracic blood ratio (TBR). In this cohort, the average BMI across all hypertension patients was 26.859 ± 3.897 (kg/m2), with obese patients (BMI ≥ 28 kg/m2) averaging 31.01 ± 2.87 kg/m2 and non‐obese (BMI<28 kg/m2) averaging 24.70 ± 2.28 kg/m2. Younger obese patients exhibited higher diastolic pressures than non‐obese peers (p < 0.01). Hemodynamic analysis showed obese patients had increased HR and SVRI but lower CI and AS (p < 0.01). Hypertensive males aged under 60 with obesity displayed a more prominent peripheral vascular phenotype (p < 0.05) and volemic phenotype (p < 0.01) than non‐obese males. Obese females aged under 60 showed a higher incidence of cardiac phenotype (p < 0.01). Across genders, obese hypertensive patients aged over 60 had a greater prevalence of volemic phenotype than non‐obese patients (p < 0.05, p < 0.01, respectively). BMI inversely correlated with CI and positively with SVRI across age and gender categories (p < 0.01). Taken together, we find that patients with hypertension exhibit diverse hemodynamic profiles, and BMI significantly correlates with hemodynamic parameters such as SVRI and CI. Our research identifies BMI as a valuable target for personalized hypertension treatment.
Role of Autophagy in Type 2 Diabetes Mellitus: The Metabolic Clash
Authors: Alanazi Yousef Abud , Al‐kuraishy Haydar M. , Al‐Gareeb Ali I. , Alexiou Athanasios , Papadakis Marios , Bahaa Mostafa M. , Negm Walaa A. , AlAnazi Faisal Holil , Alrouji Mohammed , Batiha Gaber El‐Saber
Published: December 2024

Type 2 diabetes mellitus (T2DM) is developed due to the development of insulin resistance (IR) and pancreatic β cell dysfunction with subsequent hyperglycaemia. Hyperglycaemia‐induced oxidative stress and endoplasmic reticulum (ER) stress enhances inflammatory disorders, leading to further pancreatic β cell dysfunction. These changes trigger autophagy activation, which recycles cytoplasmic components and injured organelles. Autophagy regulates pancreatic β cell functions by different mechanisms. Though the exact role of autophagy in T2DM is not completely elucidated, that could be beneficial or detrimental. Therefore, this review aims to discuss the exact role of autophagy in the pathogenesis of T2DM.
S‐Nitrosylation of NOTCH1 Regulates Mesenchymal Stem Cells Differentiation Into Hepatocyte‐Like Cells by Inhibiting Notch Signalling Pathway
Authors: Wang Xuesong , Xu Yan , Wang Yue , Tang Xingkun , Zhou Xiaolei , Lu Wenming , Chen Wenjie , Li Lincai , Zhou Lin , Ye Junsong
Published: December 2024

The differentiation of mesenchymal stem cells (MSCs) into hepatocyte‐like cells (HLCs) is considered one of the most promising strategies for alternative hepatocyte transplantation to treat end‐stage liver disease. To advance this method, it is crucial to gain a deeper understanding of the mechanisms governing hepatogenic differentiation. The study demonstrated that suppression of the intracellular domain release of the Notch pathway receptor via the γ‐secretase inhibitor N‐[(3, 5‐difluorophenyl)acetyl]‐L‐alanyl‐2‐phenylglycine‐1, 1‐dimethylethyl ester (DAPT) significantly promotes the expression of hepatocyte‐related genes and proteins in HLCs. Increased expression of intracellular inducible NO synthase (iNOS) during differentiation led to elevated endogenous NO production. Biotin switch assays revealed a gradual increase in S‐nitrosylation (SNO)‐NOTCH1 and a decrease in overall NOTCH1 expression during hepatogenic differentiation. The addition of the exogenous NO donor S‐nitrosoglutathione (GSNO) and the SNO inhibitor dithiothreitol (DTT) further demonstrated that the elevated expression of SNO‐NOTCH1 promotes the differentiation of MSCs into mature hepatocytes. Briefly, our results fully demonstrated that the modification of the extracellular domain of NOTCH1 by NO, leading to the formation of SNO‐NOTCH1, significantly promotes hepatogenic differentiation by inhibiting the Notch signalling pathway. Our study highlights the critical role of SNO‐NOTCH1 in regulating the Notch signalling pathway and offers new insights into the mechanisms driving this differentiation process.
Schisandrin B Inhibits LPS‐Induced Endometritis Through Attenuating Ferroptosis via AMPK/PGC1α/Nrf2 Signalling Pathway
Authors: Yu Jing , Li Xuewei , Zhou Min , Lu Min , Ruan Zheng , Zou Wenshuang , Yu Shaohui
Published: December 2024

Endometritis is one of the common reproductive diseases in human and animal. In recent years, a number of studies have found that Schisandra B (Sch B), as a natural Chinese medicine extract, has antioxidant, anti‐inflammatory and other biological activities. Based on the above, in this study, mice were used to conduct an in vivo experiment to investigate the effect and mechanism of Sch B on lipopolysaccharide (LPS)‐induced endometritis. Haematoxylin and eosin (H&E) staining was used to detect the pathological changes of uterine tissue and western blot was used to detect the expression levels of signalling pathways and key genes for ferroptosis. The results showed that Sch B significantly inhibited the pathological injury of uterine tissue, myeloperoxidase (MPO) activity, the activation of NF‐κB pathway and the production of TNF‐α and IL‐1β. Furthermore, Sch B effectively inhibited ferroptosis by inhibiting malondialdehyde (MDA) and iron production and promoting the expression of ferroptosis suppressor genes GPX4 and ferritin. In conclusion, Sch B inhibited LPS‐induced endometritis through alleviating inflammatory response and ferroptosis via AMPK/PGC1α/Nrf2 signalling pathway.
Extrusion‐Based 3D Printing Technology in Soy Protein‐Based Meat Analogs: A Review
Authors: Maxy Dianna , Khalid Nurul Izzah , Teh Huey Fang , Kamalbatcha Zainebbeevi , Sulaiman Rabiha , Noh Teh Ubaidah , Yong Seng Ping Amanda , Mohd Ramli Sharifah Hafiza
Published: December 2024

Extrusion‐based 3D printing technology has emerged as a promising method for developing soy protein‐based meat analogs, addressing the urgent demand for sustainable and nutritious alternatives to traditional meat sources. There is a growing global interest in soy protein‐based diets, driven by environmental sustainability, health, and animal welfare concerns. Extrusion‐based 3D printing involves pushing soy protein pastes through a nozzle to develop layers that build up into three‐dimensional objects and enable the production of structures closely mimicking the texture and appearance of real meat. Soy proteins, characterized by their high protein content and balanced amino acid profile, are ideal for producing meat‐like textures and flavors. This review explores the application of extrusion and 3D printing technologies in soy protein‐based meat analog production, emphasizing their potential to replicate the sensory qualities of animal meat. It discusses the advantages and challenges associated with these technologies, including the optimization of printing parameters for consistency and quality. Rheological studies are conducted to achieve smooth extrusion and proper layer formation whereas integrating fats, fibers, and natural flavors to enhance texture and taste. The review provides an overview of extrusion processes, highlighting rheological studies optimizing the flow behavior of soy protein pastes for effective 3D printing. Additionally, it examines textural studies aimed at mimicking the mouthfeel and bite of real meat, as well as printing performance evaluated through shape retention, layer resolution, structural strength, and printing accuracy. Consumer acceptance of soy protein‐based meat analogs is also discussed, highlighting the familiarity with soy products and the increasing demand for plant‐based alternatives. The review concludes by considering prospects for these technologies, focusing on innovations in extrusion and 3D printing, market trends, and evolving consumer preferences.
The Impact of Smoking on Ulcerative Colitis and Interaction With Family History: A Population‐Based Cohort Study
Authors: Ahn Hyeong Sik , Swan Heather , Kazmi Sayada Zartasha , Kim Young Shin , Hong Gahwi , Choi Seeun , Kang Taeuk , Kim Minjung , Cha Jaewoo , Hann Hoo Jae , Kim Hyun Jung
Published: December 2024

Background

The impact of smoking on ulcerative colitis (UC) among Asian populations is controversial, and interactions between genetic factors and smoking are not well studied. We evaluated the association between smoking and UC and assessed interactions between smoking and family history.

Methods

Using the National Health Insurance database, we identified 5.5 million individuals from 2002 to 2019 with information on familial relationships and smoking history. Cox proportional hazard regression was used to examine the association between UC and current/former smoking and estimate familial risk. Interactions between family history and smoking were assessed on an additive scale using relative excess risk due to interaction (RERI).

Results

Current smoking was associated with a decreased risk of disease (hazard ratio [HR] 0.53 95% CI 0.49–0.56), whereas former smoking was associated with an increased risk (HR 1.62 95% CI 1.53–1.71), compared to nonsmokers. Familial risk was HR 7.51 (95% CI 6.68–8.48). The protective effect of current smoking was more pronounced among those with a family history, as their combined effect was lower than the sum of their individual risks (HR 4.37 vs. 7.55), whereas the harmful effect of former smoking was more prominent among this group, and their combined effect exceeded the sum of their individual effects (HR 10.20 vs. 8.57), indicating statistically significant interactions (RERI current: −3.18 95% CI −4.89 to −1.47; former: 1.63 95% CI −1.00–4.25).

Conclusion

The effects of smoking on UC do not appear to differ between Asian and Western populations. Possible gene‐smoking interactions were observed but in opposing directions for current/former smoking.
Weighing the global built environment: High‐resolution mapping and quantification of material stocks in buildings
Authors: Haberl Helmut , Baumgart André , Zeidler Julian , Schug Franz , Frantz David , Palacios‐Lopez Daniela , Fishman Tomer , Peled Yoav , Cai Bowen , Virág Doris , Hostert Patrick , Wiedenhofer Dominik , Esch Thomas
Published: December 2024

Buildings provide indispensable services for human well‐being, but their construction and use are responsible for a substantial fraction of societies’ resource requirements and greenhouse gas emissions. Mapping and quantifying the material stocks in buildings is a key research frontier in industrial ecology. Reliable and spatially highly resolved maps of material stocks in buildings worldwide are so far not available. Existing approaches based on nighttime light data allow large‐scale coverage, but their spatial resolution is usually ∼0.5–1 km. Other methods using light detection and ranging (LiDAR) and cadaster data achieve higher resolution and accuracy, but do not allow wall‐to‐wall mapping of large regions. Based on high‐resolution Earth Observation data combined with material intensity factors (kg per m3 of building volume), we quantify and map material stocks in buildings at the unprecedented resolution of 90 m globally. We distinguish 18 types of materials in five types of buildings. We find that global material stocks in buildings amount to 547 (391–672) Gt, approximately half of total global societal material stocks. We find highly unequal distributions of material stocks in buildings per capita and per unit area of each country. Our results agree well with previous detailed estimates of material stocks in buildings in dedicated regions or individual cities. Improved and harmonized material intensity factors emerge as a key research area for improving the accuracy of material stock maps. Our results are available as data products with high spatial and thematic resolution to facilitate future studies; for example, of secondary resource potentials. This article met the requirements for a gold‐gold JIE data openness badge described at http://jie.click/badges.
Linking regional MFA models: Understanding disparities within the global zinc cycle
Authors: Rostek L. , Loibl A.
Published: December 2024

Circular economy and criticality assessments require comprehensive monitoring of anthropogenic material flows and stocks at a regional level. Therefore, this study presents a multiregional trade‐linked dynamic MFA model for zinc. The model covers the entire life cycle from mining to recycling for the regions China, Europe, North America, Latin America, and Asia. The dynamic approach allows the analysis of the development of the cycles from 1995 to 2020. The interregional trade is quantified at each life cycle stage by using the Comtrade database. Sensitivity analysis is applied to account for uncertainties in the exogenous data. The results reveal large regional disparities in the zinc industry. While China shows enormous growth, Europe has already reached a steady state in zinc consumption and anthropogenic stock. The current global consumption is strongly driven by China, leading to a strong increase of its zinc stock in use. However, Europe has the largest zinc stock in use, especially on a per capita basis. North America's zinc consumption is decoupled from its economic growth, as evidenced by the recent decline in its zinc stock in use. In terms of recycling, Europe shows the highest volumes and the best circular performance, as indicated by high recycling rates, partly due to the extensive use of more easily recyclable product types. In all regions, there is potential for increased recycling by treatment of zinc‐bearing steelmaking dusts. China's strict regulation successfully triggered large‐scale implementation of respective recovery processes, leading to increasing recycling rates. This article met the requirements for a gold‐gold JIE data openness badge described at http://jie.click/badges.
Nanobodies against the myelin enzyme CNPase as tools for structural and functional studies
Authors: Markusson Sigurbjörn , Raasakka Arne , Schröder Marcel , Sograte‐Idrissi Shama , Rahimi Amir Mohammad , Asadpour Ommolbanin , Körner Henrike , Lodygin Dmitri , Eichel‐Vogel Maria A. , Chowdhury Risha , Sutinen Aleksi , Muruganandam Gopinath , Iyer Manasi , Cooper Madeline H. , Weigel Maya K. , Ambiel Nicholas , Werner Hauke B. , Zuchero J. Bradley , Opazo Felipe , Kursula Petri
Published: December 2024

2′,3′‐Cyclic nucleotide 3′‐phosphodiesterase (CNPase) is an abundant constituent of central nervous system non‐compact myelin, and its loss in mice and humans causes neurodegeneration. Additionally, CNPase is frequently used as a marker antigen for myelinating cells. The catalytic activity of CNPase, the 3′‐hydrolysis of 2′,3′‐cyclic nucleotides, is well characterised in vitro, but the in vivo function of CNPase remains unclear. CNPase interacts with the actin cytoskeleton to counteract the developmental closure of cytoplasmic channels that travel through compact myelin; its enzymatic activity may be involved in adenosine metabolism and RNA degradation. We developed a set of high‐affinity nanobodies recognising the phosphodiesterase domain of CNPase, and the crystal structures of each complex show that the five nanobodies have distinct epitopes. One of the nanobodies bound deep into the CNPase active site and acted as an inhibitor. Moreover, the nanobodies were characterised in imaging applications and as intrabodies, expressed in mammalian cells, such as primary oligodendrocytes. Fluorescently labelled nanobodies functioned in imaging of teased nerve fibres and whole brain tissue sections, as well as super‐resolution microscopy. These anti‐CNPase nanobodies provide new tools for structural and functional studies on myelin formation, dynamics, and disease, including high‐resolution imaging of nerve tissue.

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Evaluation of the Participation of Brazilian Women in Research in Oral Pathology and Oral Medicine
Authors: Ferreira Luiz Miguel , Nascimento João Pedro Santos , de Sousa Árlen Almeida Duarte , de Oliveira Fabrício Emanuel Soares , Martelli Daniella Reis B. , Santos‐Silva Alan Roger , Martelli‐Júnior Hercílio
Published: December 2024

Background

Despite recent advancements, women still encounter significant challenges in various fields, including dentistry. However, the increasing interest in female participation in science acknowledges its fundamental role in the advancement of knowledge. This study aims to assess indicators of women's involvement in Brazilian research in the areas of Oral Pathology and Oral Medicine.

Methods

This cross‐sectional study evaluated 197 professionals affiliated with the Brazilian Society of Stomatology and Oral Pathology in 2023. Data were collected from publicly available Lattes curriculum and organized into three sets of information: researcher profile, scientific production and human resources formation. Both the data from the researcher's entire career and from the last 5 years (2019–2023) were assessed separately. Descriptive analyses of categorical variables were performed, while the Mann–Whitney test was employed to compare the numerical variables regarding researchers' gender.

Results

Of 197 professionals, 117 (59.4%) were female. Although there was no significant difference in scientific production between genders, men had more publications, received approximately twice as many citations, and exhibited higher H‐index values compared to women. Notably, women surpassed men in undergraduate student supervision, while men predominated in supervising master's and PhD students.

Conclusions

This study highlighted the relevance of female participation in Oral Pathology and Oral Medicine research in Brazil. However, disparities persist regarding women participation, especially in scientific article citations and postgraduate students' supervision.