bluuebunny/crossref_metadata_2025_split huggingface dataset:
A computational tool to optimize clinical trial parameter selection in Duchenne muscular dystrophy: A practical guide and case studies
Authors: Wilk Jordan , Aggarwal Varun , Pauley Mike , Corey Diane , Conrado Daniela J. , Lingineni Karthik , Morales Juan Francisco , Yoon Deok Yong , Zhang Yi , Cui Zihan , Burton Jackson , Larkindale Jane , Ma Shu Chin , Hovinga Collin , Martinez Terina , Romero Klaus , Belfiore‐Oshan Ramona , Kim Sarah ,   the Duchenne Regulatory Science Consortium (D‐RSC) and the CINRG DNHS investigators
Published: November 2024

AbstractDuchenne muscular dystrophy (DMD), a rare pediatric disease, presents numerous challenges when designing clinical trials, mainly due to the scarcity of available trial participants and the heterogeneity of disease progression. A quantitative clinical trial simulator (CTS) has been developed based on previously published five disease progression models describing each of the longitudinal changes in the velocity at which individuals can complete specified timed functional tests, frequently used as clinical trial efficacy endpoints (supine‐stand, 4‐stair climb, and 10 m walk/run test or 30‐foot walk/run test), as well as each of the longitudinal changes in forced vital capacity and North Star Ambulatory Assessment total score. The model‐based CTS allows researchers to optimize the selection of numerous trial parameters for designing trials for the five functional measures commonly used as endpoints in DMD clinical trials. This case report serves as a demonstration of the tool's functionality while providing an easy‐to‐follow guide for users to reference when preparing simulations of their own design. Two case studies, using input selection based on previous DMD clinical trials, provide realistic examples of how the tool can help optimize clinical trial design without the risk of decreasing statistical significance. This optimization allows researchers to mitigate the risk of designing trials that may be longer, larger, or more inclusive/exclusive than necessary.
Adaptive EWMA Control Chart by Adjusting the Risk Factors through Artificial Neural Network
Authors: Ahmadini Abdullah Ali , Abbas Tahir , AlQadi Hadeel 
Published: November 2024

ABSTRACTThis article focuses on operationalizing a quality improvement framework to improve the quality and safety of patients in hospitals. Assessing the effectiveness of health care services, especially utilizing various patient health statuses, poses several difficulties. The artificial neural networks model assesses patient risk factors and enhances proper management. Our proposed approach extends the exponentially weighted moving average (EWMA) control chart to a risk‐adaptive EWMA chart. This chart is developed from residuals estimated from the artificial neural networks model, thus allowing an assessment of actual data from the patients undergoing cardiothoracic surgery. For patient evaluation, we employ artificial neural networks to establish the suggested control chart. The results indicate that this chart outperforms other methods, such as the risk‐adjusted EWMA chart for shift detection, which may present improvements in the healthcare system's patient care.
Green Technological Advances and Resource Rents as Levers for Carbon Reduction in BRICS: Implications for SDGs 7, 8, 9, 12, and 13
Authors: Amin Nabila , Sharif Arshian , Tayyab Muhammad , Pan Yanchun 
Published: November 2024

ABSTRACTIn recent decades, rapid development in emerging economies has heightened climate challenges, threatening environmental sustainability and quality. In response, green energy, technological innovation, and carbon pricing strategies have emerged as key tools for environmental mitigation and promoting green economic growth. These strategies are integral to the goals of COP 27, the 2030 SDGs, and the pledge to reach carbon neutrality by 2060. However, the BRICS economic bloc faces significant obstacles in balancing socio‐economic growth with environmental sustainability. This study intentions to inspect the impact of natural resource rents, research and development (R&D) expenditures, green energy, green technological innovation, and economic growth on carbon emissions in BRICS economies from 1995 to 2021. Using a cross‐sectional ARDL model, the study explores relationships between these variables, employing advanced panel methods to account for CSD and heterogeneity. The empirical findings reveal that research and development expenditure, green energy, and green technological innovation contribute to CO2 emission reductions by 0.329%, 0.211%, and 0.148%, respectively. In contrast, a 1% increase in economic growth and natural resource rents corresponds to a substantial 0.499% and 0.840% upsurge in CO2 emissions. The Dumitrescu and Hurlin panel causality test also highlights reciprocal causal relationships among the variables. Based on these findings, the study recommends policy actions to achieve SDG targets: enforce stricter CO2 emissions regulations for SDG‐13, increase renewable energy investment for SDG‐07, support green innovation for SDG‐08, enhance R&D for SDG‐09, and promote circular economy practices for SDG‐12.
Four-point functions and contact terms from higher-spin Ward identities of Chern-Simons-matter theory
Authors: Kukolj Trivko 
Published: November 2024

Abstract
Large N quasifermionic (QF) Chern-Simons-matter theories exhibit weakly-broken higher-spin symmetry and contain an infinite-dimensional algebra of almost-conserved higher-spin currents. By analyzing local higher-spin Ward identities, we constrain the higher-spin algebra of this theory, for operators of spin s < 4. The solution interpolates smoothly between Ward identities of free-fermionic and critical-bosonic U(N) models, in accordance with the bosonization duality. At finite ’t Hooft coupling, we decompose four-point current correlators involving (∂ ∙ J3)QF in terms of free theory structures and identify possible epsilon-transform relations for QF four-point functions. Additionally, we find that higher correlators of the theory develop scheme-independent higher-spin contact terms, stemming from the presence of a background Chern-Simons term in the effective action. These terms are related to similar contact terms of the associated quasibosonic Chern-Simons-matter theory via Legendre transform. The results are supplemented by perturbative checks, including collinear limit computations of ⟨T− −J+J+⟩QF, ⟨T− −J+J+O⟩QF and ⟨J− − −J+J+J+⟩QF.
Stability of axion-saxion wormholes
Authors: Hertog T. , Maenaut S. , Missoni B. , Tielemans R. , Van Riet T. 
Published: November 2024

Abstract
We reconsider the perturbative stability of Euclidean axion wormholes. The quadratic action that governs linear perturbations is derived directly in Euclidean gravity. We demonstrate explicitly that a stability analysis in which one treats the axion as a normal two-form gauge field is equivalent to one performed in the Hodge-dual formulation, where one considers the axion as a scalar with a wrong-sign kinetic term. Both analyses indicate that axion wormholes are perturbatively stable, even in the presence of a massless dilaton, or saxion, field that couples to the axion.
Development and characterization of Bioblocks: a sustainable wood-based composite utilizing MDF residues, citric acid and polyols
Authors: Lewandowski Peer Thorben , Larnøy Erik , Militz Holger 
Published: November 2024

AbstractThe study investigated the production process and properties of a new wood-based material called Bioblocks. This sustainable composite is made from medium-density-fibreboard (MDF) residues, citric acid and either sorbitol or hexanediol. The process involves mixing in-water diluted chemicals with the MDF residues and curing the mixture in a laboratory oven to esterify the sorbitol and wood components with citric acid. A design of experiment was used to determine the influence and optima of the different process factors, and an optimised trial further investigated the material properties. The density distribution, compression strength, and TS after 24 h immersion in water according to EN 317 of the Bioblocks were tested. The first trial showed that mainly the amount of water added impacts the product’s properties. The optimised material achieved a sufficient density distribution with an average density of about 420 kg/m3, a compression strength of up to 3.5 N/mm2, and a TS of about 2%. Therefore, Bioblocks are a promising natural material to use waste MDF and substitute fossil, unsustainable materials.
The role of inhibitory immune checkpoint receptors in the pathogenesis of Alzheimer’s disease
Authors: Salminen Antero 
Published: November 2024

Abstract
There is mounting evidence that microglial cells have a key role in the pathogenesis of Alzheimer’s disease (AD). In AD pathology, microglial cells not only are unable to remove β-amyloid (Aβ) plaques and invading pathogens but also are involved in synaptic pruning, chronic neuroinflammation, and neuronal degeneration. Microglial cells possess many different inhibitory immune checkpoint receptors, such as PD-1, LILRB2-4, Siglecs, and SIRPα receptors, which can be targeted by diverse cell membrane-bound and soluble ligand proteins to suppress the functions of microglia. Interestingly, in the brains of AD patients there are elevated levels of many of the inhibitory ligands acting via these inhibitory checkpoint receptors. For instance, Aβ oligomers, ApoE4, and fibronectin are able to stimulate the LILRB2-4 receptors. Increased deposition of sialoglycans, e.g., gangliosides, inhibits microglial function via Siglec receptors. AD pathology augments the accumulation of senescent cells, which are known to possess a high level of PD-L1 proteins, and thus, they can evade immune surveillance. A decrease in the expression of SIRPα receptor in microglia and its ligand CD47 in neurons enhances the phagocytic pruning of synapses in AD brains. Moreover, cerebral neurons contain inhibitory checkpoint receptors which can inhibit axonal growth, reduce synaptic plasticity, and impair learning and memory. It seems that inappropriate inhibitory immune checkpoint signaling impairs the functions of microglia and neurons thus promoting AD pathogenesis.

Key messages

Microglial cells have a major role in the pathogenesis of AD.

A decline in immune activity of microglia promotes AD pathology.

Microglial cells and neurons contain diverse inhibitory immune checkpoint receptors.

The level of ligands for inhibitory checkpoint receptors is increased in AD pathology.

Impaired signaling of inhibitory immune checkpoint receptors promotes AD pathology.
Microvascular Plug Embolization of Anterior Spinal Artery Bearing Segmental Arteries Prior Aortic Stenting: Technique and Safety
Authors: Deniz Sinan , Öcal Osman , Fabritius Matthias , Puhr-Westerheide Daniel , Abaci Gizem , Wildgruber Moritz , Ümütlü Muzaffer Reha , Gök Mustafa , Stana Jan , Rantner Barbara , Tsilimparis Nikolaos , Ricke Jens , Seidensticker Max 
Published: November 2024

Abstract
Purpose
This study aims to present our experience with superselective embolization of the anterior spinal artery-bearing segmental artery (ASAbSA) using a microvascular plug (MVP) during the minimally invasive segmental artery coil embolization (MISACE) procedure prior endovascular repair of the thoracoabdominal aortic aneurysms.

Methods
We retrospectively evaluated all MISACE procedures performed between May 2018 and July 2023, where MVP was deployed into an angiographically confirmed ASAbSA. Data were analyzed regarding interventional details, technical aspects, and safety protocols. The standard procedure for MVP embolization involves detaching the plug after 10 min, provided no neurological symptoms occur.

Results
A total of 22 patients underwent MVP deployment into the proximal segmental artery supplying the ASAbSA. There were no instances of non-target embolization or segmental artery dissection. Furthermore, none of the patients experienced temporary or permanent spinal cord ischemia.

Conclusion
MVP deployment into the ASAbSA is a safe strategy for protecting the spinal cord during preemptive embolization of segmental arteries prior to endovascular aortic repair.

Graphical Abstract
Association between placental site and successful induction of labor among postdate primiparous women
Authors: Taha Omima T. , Ghoneim Hanan M. , Marzouk Tyseer , Ali Tamer Yehia M. 
Published: November 2024

Abstract
Purpose
This study aimed to determine the association between placental site and successful labor induction.

Methods
This cross-sectional study recruited all postdate primiparous women undergoing induction of labor. Eligible women were subjected to proper history taking and clinical examination. Vaginal examination to determine the bishop score was done. Routine antenatal scan was done for fetal biometry and the placental site. Transvaginal ultrasound was done for cervical length assessment. Induction of labor was commenced and women were subdivided into those with successful induction (delivered vaginally) and those with failed induction (needed cesarean delivery).

Results
Successful induction was achieved in 73/91 (80.2%) participants. The bishop score was significantly increased among women with successful induction (4.6 ± 0.9 vs 3.9 ± 1.1, p value 0.014). In addition, the cervical length was significantly shorter among those who delivered vaginally (2.6 ± 0.5 vs 4.2 ± 0.5, p value 0.0001). There was no significant difference in the placental site among women with failed or successful induction. The cervical length was the only significant predictor for successful induction of labor (p value 0.0001). The placental site showed a non-significant role in the prediction of successful vaginal delivery (p value 0.280).

Conclusion
The placental site is not associated with the outcome of labor induction. The cervical length was the significant predictor for successful induction of labor.
Clinical comparison of laparoscopic and open surgical approaches for uterus-preserving myomectomy: a retrospective analysis on patient-reported outcome, postoperative morbidity and pregnancy outcomes
Authors: Otten Lucia Anna , Lama Subhiyeh , Otten Jakob Wilhelm , Winkler Kira , Ralser Damian Johannes , Egger Eva Katharina , Alexander Mustea 
Published: November 2024

Abstract
Purpose
Uterine fibroids pose clinical challenges due to varied symptoms and impact on fertility. Aim of this research is to compare open and laparoscopic myomectomy, with focus on evaluating their effects on patients' quality of life and analyzing their implications for pregnancy outcomes.

Methods
This retrospective study compares open and laparoscopic myomectomy outcomes in 168 patients treated October 2017 and July 2023. Preoperative characteristics and postoperative outcomes in terms of symptoms and pregnancy outcomes were examined.

Results
The patient cohort comprised patients with a high symptom burden. Only 51.2% expressing a desire for future pregnancies, highlighting diverse motivations for uterus-preservation. No significant differences were observed in preoperative symptoms. Larger and multiple myomas were associated with a higher likelihood of laparotomy. Recurrence rates were lower after laparoscopy (10.2% vs. 23.8%, p = 0.02). Cesarean section recommendations were more frequent post-laparotomy group (36.6% vs. 86.6%, p = 0.000). Morbidities and satisfaction showed no significant differences between approaches, with slightly better bleeding improvement after laparotomy. Despite similar pregnancy outcomes, a high proportion of patients did not conceive postoperatively (75.4%). Among patients who became pregnant postoperatively (n = 31), most patients conceived after one year or more, with no dependence on the surgical approach (p = 0.227).

Conclusion
Both open and laparoscopic myomectomy surgeries showed high patient satisfaction, symptom alleviation, and comparable pregnancy results. A preference emerged for laparoscopy in terms of cesarean section recommendations and recurrence risk. Laparoscopic procedures tended to offer higher operative satisfaction and fewer complications. The study emphasized the complexity of therapeutic decision-making.
COPD Risk Phenotypes in Older Smokers: Evaluation in GLI- and GOLD-Defined Respiratory Impairment
Authors: Bohadana Abraham , Wild Pascal , Rokach Ariel , Berg Assaf , Izbicki Gabriel 
Published: November 2024

Abstract
Purpose
In aging populations, the Global Initiative for Obstructive Lung Disease (GOLD) spirometry threshold may misclassify normal spirometry as airflow limitation. The Global Lung Initiative (GLI) method provides age-adjusted criteria. We investigated how the use of GOLD or GLI thresholds in an algorithm affects the classification of elderly smokers into COPD risk phenotypes.

Methods
Using a modified COPDGene algorithm, including exposure, symptoms, and abnormal spirometry, 200 smokers aged 60 years and older were classified into 4 mutually exclusive phenotypes: Phenotype A (no symptoms, normal spirometry; reference), Phenotype B (symptoms, normal spirometry; possible COPD), Phenotype C (no symptoms, abnormal spirometry; possible COPD), and Phenotype D (symptoms, abnormal spirometry; probable COPD). Abnormal spirometry was defined according to the GOLD or GLI criteria. A comparison was made between the GOLD- and GLI-defined phenotypes.

Results
Using GLI criteria/cut-offs, 18.5% (n = 37) had phenotype A (no COPD), 42% (n = 84) had phenotype B (possible COPD), 7.5% (n = 15) had phenotype C (possible COPD), and 32% (n = 64) had phenotype D (probable COPD). Using GOLD criteria cut-offs, 14.5% (n-29) had phenotype A (no COPD); 31% (n = 62) had phenotype B, 11.5% (n = 23) had phenotype C (probable COPD), and 43% (n = 86) had phenotype D (probable COPD). Eight smokers with GOLD phenotype C were reclassified as GLI phenotype A, while 22 with GOLD phenotype D were reclassified as GLI phenotype B. Smokers identified as ‟probable COPD” by GOLD alone (potential false positives) had better spirometry results than those identified as ‟probable COPD” by both GOLD and GLI.

Conclusion
The use of the GOLD threshold in an algorithm resulted in older smokers being classified into more severe COPD risk phenotypes compared to the GLI threshold. This suggests that GOLD may misclassify smokers with less affected phenotypes as having respiratory impairment, potentially leading to unnecessary and harmful treatments.
A molecular and immunohistochemical study of 37 cases of ovarian Sertoli–Leydig cell tumor
Authors: Němejcová Kristýna , Hájková Nikola , Krkavcová Eva , Kendall Bártů Michaela , Michálková Romana , Šafanda Adam , Švajdler Marián , Shatokhina Tetiana , Laco Jan , Matěj Radoslav , Hausnerová Jitka , Škarda Jozef , Náležinská Monika , Zima Tomáš , Dundr Pavel 
Published: November 2024

Abstract This study provides an analysis of 37 ovarian Sertoli–Leydig cell tumors (SLCT), focusing on their morphological, immunohistochemical, and molecular features. The cohort was comprised of 9 well-differentiated, 25 moderately differentiated, and 3 poorly differentiated tumors. The immunohistochemical analysis was performed with 28 markers, including diagnostic markers and markers with possible predictive significance. The results showed high expression of sex cord markers (FOXL2, SF1, inhibin A, CD99, calretinin, ER, PR, AR), and variable expression of other markers such as CKAE1/3 (83%), CAIX (14%), and MUC4 (1%). Loss of PTEN expression was present in 14% of cases, and CTLA4 expression was seen in 43% of cases. All tumors were MMR proficient and HER2 and PD-L1 negative. The molecular analysis showed DICER1 mutations in 54.5% of cases, and a FOXL2 mutation in 6% of tumors. In addition, we detected 2 cases with TERT promoter mutation. RNA NGS sequencing identified significant differences in mRNA expression between DICER1MUT and DICER1WT tumors. The DICER1WT tumors showed increased expression of PRKCA, HNF1A, LDLR, and MAP2K5. On the contrary, the DICER1MUT cases showed increased expression of CDK6, NOTCH2, and FGFR2. The results of our study show that SLCTs exhibit distinct molecular features based on their degree of differentiation. We have confirmed that DICER1 mutations are characteristic of moderately and poorly differentiated SLCTs, while well-differentiated SLCTs may represent a distinct entity. DICER1MUT and DICER1WT tumors showed different mRNA expression profiles. The FOXL2 mutation is less common in these tumors and is mutually exclusive with the DICER1 mutation.
Kidney lipid metabolism: impact on pediatric kidney diseases and modulation by early-life nutrition
Authors: Nüsken Eva , Voggel Jenny , Saschin Leon , Weber Lutz T. , Dötsch Jörg , Alcazar Miguel A. Alejandre , Nüsken Kai-Dietrich 
Published: November 2024

Abstract
Our review summarizes and evaluates the current state of knowledge on lipid metabolism in relation to the pathomechanisms of kidney disease with a focus on common pediatric kidney diseases. In addition, we discuss how nutrition in early childhood can alter kidney development and permanently shape kidney lipid and protein metabolism, which in turn affects kidney health and disease throughout life. Comprehensive integrated lipidomics and proteomics network analyses are becoming increasingly available and offer exciting new insights into metabolic signatures. Lipid accumulation, lipid peroxidation, oxidative stress, and dysregulated pro-inflammatory lipid mediator signaling have been identified as important mechanisms influencing the progression of minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, diabetic kidney disease, and acute kidney injury. We outline key features of metabolic homeostasis and lipid metabolic physiology in renal cells and discuss pathophysiological aspects in the pediatric context. On the one hand, special vulnerabilities such as reduced antioxidant capacity in neonates must be considered. On the other hand, there is a unique window of opportunity during kidney development, as nutrition in early life influences the composition of cellular phospholipid membranes in the growing kidney and thus affects local signaling pathways far beyond the growth phase.

Graphical Abstract
Liver fibrotic burden across the spectrum of hypothyroidism
Authors: Du Tingting , Huang Yuchai , Lv Yongman , Yuan Gang 
Published: November 2024

Abstract
Background
Data regarding the prevalence of hepatic fibrotic burden across the spectrum of hypothyroidism are scarce. Hence, we aimed to evaluate the prevalence of liver fibrotic burden across the spectrum of hypothyroidism.

Methods
30,091 individuals who attended a Health Management Centre between 2019 and 2021 were cross-sectionally analyzed. Participants were categorized as having strict-normal thyroid function, low-normal thyroid function, subclinical hypothyroidism, and overt hypothyroidism. Hepatic fibrosis was assessed by vibration-controlled transient elastography (VCTE). Significant and advanced fibrosis were defined as liver stiffness measurement in VCTE of 8.1–9.6 and 9.7–13.5 kPa, respectively.

Results
Among both men and women, low-normal thyroid function group, subclinical hypothyroidism group, and overt hypothyroidism group all have more liver fibrosis present, including mild fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis, than the strict-normal thyroid function group. The low-normal thyroid function group have the similar liver fibrotic burden to the subclinical hypothyroidism group. The highest liver fibrotic burden was noted in the overt hypothyroidism group. Both significant and advanced liver fibrosis were significantly associated with low-normal thyroid function, subclinical hypothyroidism, and overt hypothyroidism in both men and women.

Conclusions
Liver fibrotic burden are highly prevalent in subjects with overt hypothyroidism. Moreover, fibrotic burden increased across the spectrum of hypothyroidism even within the low normal thyroid function. These results suggested that screening for liver fibrosis in patients with hypothyroidism is necessary.