bluuebunny/crossref_metadata_2025 huggingface dataset:
Low‐Density Polyethylene Films Containing Cellulose‐Encapsulated Thymol With Prolonged Anti‐Mold Activity and Its Potential in Hay Preservation
Authors: Shlosman Koranit , Rein Dmitry M. , Shemesh Rotem , Caspi Ayelet , Kleinerman Olga , Cohen Yachin
Published: November 2024

The use of many pesticides in agricultural crop protection has been banned due to their harmful effects on health and the environment, leaving farmers with limited crop protection options. A natural nontoxic alternative is thymol (TY), the main component in thyme essential oil (EO), which is known to have pesticidal and anti‐mold properties. TY can be incorporated into plastic films, widely used in agricultural applications. However, its volatility and susceptibility to heat limits its use in polymeric systems. By encapsulating TY using natural biopolymer such as cellulose, TY can be protected during high‐temperature plastic processing, thus enabling to achieve an active plastic packaging. In this study, cellulose‐encapsulated TY was melt‐compounded with low‐density polyethylene (LDPE) and 100 μm‐thick films were fabricated and compared with similar compounds containing free TY. Scanning electron microscopy with energy dispersive X‐ray spectroscopy confirmed the presence of TY‐loaded particles and demonstrated that they had no significant effects on the LDPE matrix morphology. LDPE films containing encapsulated TY offered higher anti‐mold protection functionality to postharvest alfalfa plants, in comparison to films containing free TY. Fourier transform infrared spectroscopy supported by thermo gravimetric analysis further confirmed successful incorporation of TY‐loaded particles in the LDPE films. Taken together, the application range of EOs and their synthetic compounds such as TY, can be broadened by encapsulation with cellulose. Incorporation of cellulose‐encapsulated TY in plastic composites can serve as a useful natural alternative to toxic pesticides in agricultural applications.
School Refusal and Determinants: Parental Psychopathology, Family Functioning, Attachment and Temperament
Authors: Eroglu Mehtap , Mentese Babayigit Tugba , Bilgen Ulgar Sermin , Ozturk Polat Ezgi , Erguven Demirtas Merve , Gul Alic Betül , Temelturk Duygu , Yaksi Nese
Published: November 2024

In the current study investigated the psychopathologies of parents, family functioning, child temperament characteristics, and attachment of kindergarten and primary school‐age children who were brought to the child and adolescent psychiatry outpatient clinic due to school refusal behavior. Fifty‐two children with school refusal and 64 children without school refusal and their parents participated in the current study. School Refusal Assessment Scale, Systemic Family Functionality Scale(SFFS), Family Harmony Scale(FHS), Kerns Secure Attachment Scale(KSAS), Temperament Scale for Children(TSC), and Depression Anxiety Stress Scales(DASS) for parents were used. It was determined that, compared to children without school refusal, the children with school refusal had lower KSAS score(mother)(p = 0.049), higher DASS‐stress and anxiety(mother) scores(p = 0.014 and p = 0.020, respectively), lower TSC‐Responsiveness/Reactivity subscale score (p = 0.005), lower SFFS‐intrafamilial support and SFFS‐intrafamilial connection scores (p = 0.002 and p < 0.001, respectively), and lower FHS‐total score (p = 0.002). It was determined that school refusal was 11 times more common in children who had difficulty adjusting to school in previous years. Each point increase in the SFFS‐intrafamilial connection score reduced school refusal by 30%. In the current study shows that among the interventions required for treatment, the family should also be targeted in addition to the child and adolescent. Therefore, it is essential to identify factors such as parents' psychopathology and their roles in the family, family functioning, and family harmony in school refusal. Because parents play a crucial role in both the development and maintenance of school refusal, using more parent‐targeted strategies or techniques is necessary to improve interventions.
The High‐Resolution Structure of a Variable Lymphocyte Receptor From Petromyzon marinus Capable of Binding to the Brain Extracellular Matrix
Authors: Appelt Elizabeth A. , Thoden James B. , Gehrke Seth A. , Bachmeier Hannah D. , Rayment Ivan , Shusta Eric V. , Holden Hazel M.
Published: November 2024

Variable lymphocyte receptors (VLRs) are antigen receptors derived from the adaptive immune system of jawless vertebrates such as lamprey (Petromyzon marinus). First discovered in 2004, VLRs have been the subject of numerous biochemical and structural investigations. Due to their unique antigen binding properties, VLRs have been leveraged as possible drug delivery agents. One such VLR, previously identified and referred to as P1C10, was shown to bind to the brain extracellular matrix. Here, we present the high‐resolution X‐ray crystal structure of this VLR determined to 1.3 Å resolution. The fold is dominated by a six‐stranded mixed β‐sheet which provides a concave surface for possible antigen binding. Electron density corresponding to a 4‐(2‐hydroxyethyl)piperazine‐1‐propanesulfonic acid buffer molecule (HEPPS) was found in this region. By comparing the P1C10 molecular architecture and its buffer binding residues with those of other VLRs previously reported, it was possible to illustrate how this unique class of proteins can accommodate diverse binding partners. Additionally, we provide an analysis of the experimentally determined structure compared to the models generated by the commonly used AlphaFold and iTASSER structure prediction software packages.
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

Duchenne 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.
253 GHz fT Graded‐Channel AlGaN/GaN High‐Electron‐Mobility Transistors with New Cliff Barrier for Millimeter Wave High‐Frequency Applications
Authors: Angen Franklin S. , I. V. Binola K. Jebalin , Chander Subhash , Juliet Rani Sylvia , Nirmal D.
Published: November 2024

In this research work, a graded‐channel AlGaN/GaN high‐electron‐mobility transistor (HEMT) featuring a cliff AlGaN barrier with a gate length of 60 nm is investigated. The inclusion of a foot cliff barrier layer confines the 3DEG distribution, thereby reducing electron scattering and potentially improving carrier mobility. The cliff‐graded‐channel device shows a peak cutoff frequency fT of 253 GHz and power‐added efficiency of 68% at 30 GHz, which represents a significant 60% improvement in comparison with conventional graded‐channel devices. These results clearly indicate that the graded‐channel AlGaN/GaN HEMT with a new cliff barrier design has great potential for mmW applications.
Adaptive EWMA Control Chart by Adjusting the Risk Factors through Artificial Neural Network
Authors: Ahmadini Abdullah Ali , Abbas Tahir , AlQadi Hadeel
Published: November 2024

This 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

In 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.
Violence, Volition, and Volatility: The Embodied Subjectivity of Women in Cults
Authors: Bar‐Lev Shirly , Morag Michal
Published: November 2024

This paper explores the embodied experience of 25 women who are former cult members. By delving into the stories of three protagonists, we examine how these women engaged with and possibly redefined the cult's socially constructed notion of womanhood. Building on Elizabeth Grosz's theory of subjective embodiment, we demonstrate how these feminine subjectivities were born at the convergence of three distinct forms of authority: charismatic leadership, the influence of Jewish tradition, and the principles of New Age spirituality. Through these lenses, these women formed their own ideals of motherhood and 'maternal instincts, thus subverting the corporal and symbolic norms dictated by the cult. This multi‐faceted approach illuminates how former cult members navigate and resist prescribed roles, ultimately fostering a nuanced understanding of the interplay between authority, tradition, and personal agency in their experiences.
Seasonal fine‐scale resource selection of elk in the central Appalachian Mountains
Authors: Verch Mallory B. , Padilla Benjamin J. , Duchamp Joseph E. , Banfield Jeremiah E. , Larkin Jeffery L.
Published: November 2024

Resource selection by animals varies depending on spatial and temporal context, thus it is important to account for these factors when conducting studies that examine this behavior relative to the availability and distribution of resources. Many resource selection studies combine fine‐scale animal location data obtained using global positioning system (GPS) technology and coarse‐scale, remotely sensed, spatial layers. Fewer studies combine fine‐scale animal location data with vegetation data collected in the field, which can identify important fine‐scale drivers of resource selection. Understanding fine‐scale resource selection of ungulates inhabiting regions dominated by closed‐canopy forests may provide important information regarding management actions that improve habitat quality. From April 2021 to August 2022, we conducted vegetation surveys at locations (n = 1294) used by 39 GPS‐collared elk Cervus canadensis and at paired random locations (n = 2509) available to elk. We used conditional logistic regressions to compare seasonal (spring, summer, fall, winter) vegetation characteristics between used and available locations. We also conducted a species indicator analysis to compare plant species found at used and available locations during peak foraging periods (dawn/dusk). Regardless of season, the probability of use by elk increased as tree basal area (m2/ha) decreased, and the presence of herbaceous plants increased. Clovers (Trifolium spp.) were indicators of locations used by elk during primary foraging periods regardless of season. Other plants that were indicators of locations used by elk during at least one season included purple‐crown vetch Securigera varia, bird's foot trefoil Lotus corniculatus, and black medick Medicago lupulina. This research highlights the importance of managed openings, ecotones, and other communities characterized by reduced tree cover and increased herbaceous plants to meet the foraging needs of elk in landscapes dominated by closed‐canopy forests. Creating and maintaining managed herbaceous openings and restoring open‐forest communities will likely facilitate elk population growth and expansion.
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

The 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

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

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

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

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

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

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

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

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.
New strategy of early surgery for infective endocarditis complicated by intracranial hemorrhage
Authors: Hasegawa Shota , Takahashi Hiroaki , Yamanaka Katsuhiro , Okada Kenji
Published: November 2024

Purpose

Early surgery for infective endocarditis with intracranial hemorrhage can cause severe bleeding, which is correlated with an increased mortality. In 2005, we started using nafamostat mesilate and low-dose heparin as anticoagulants during cardiopulmonary bypass for early surgery. The outcomes of this strategy have been reviewed.

Methods

All patients who underwent cardiac surgery for active infective endocarditis with intracranial hemorrhage between 2005 and 2023 were evaluated.

Results

There were 23 consecutive patients (median age 62 years old). Ten patients (43%) had neurologic deficits. The indication for early surgery in most patients was the presence of mobile vegetation or existing embolic events (18 of 23, 78%). No complications were associated with cardiopulmonary bypass. The median interval between the diagnosis and surgery was two days. There was 1 early death (4%) due to sepsis. There was no exacerbation of intracranial hemorrhage. One patient had new ectopic microbleeds without deterioration of neurologic findings. One patient had a new-onset cerebral infarction with neurologic deficits. None of the patients exhibited neurologic deterioration. The median follow-up duration was 26 months. overall survival was 90.7% after 5 years.

Conclusions

Our strategy of using nafamostat mesilate enabled us to safely perform early surgery in patients with intracranial hemorrhage without hemorrhage exacerbation.
Predictors of perioperative morbidity in elderly patients undergoing colorectal cancer resection
Authors: Parnasa S. Y. , Lev-Cohain N. , Bader R. , Shweiki A. , Mizrahi I. , Abu-Gazala M. , Pikarsky A. J. , Shussman N.
Published: November 2024

Aim

Colorectal cancer resection in the elderly may be associated with significant morbidity. This study aimed to assess perioperative morbidity in elderly patients undergoing colorectal cancer resection and to investigate risk factors for postoperative complications.

Materials and Methods

Consecutive patients aged ≥ 75 years undergoing colorectal cancer resection with curative intent between January 2014 and December 2021 at our institution were included. We evaluated risk factors for postoperative complications, length of hospital stays (LOS), 30-day readmission, and 90-day mortality rates.

Results

A total of 843 patients underwent colorectal cancer resection during the study period, of whom 202 patients were 75 years or older. Advanced age was associated with postoperative complications (Clavien–Dindo score > 3b, p = 0.001). Sarcopenia, preoperative plasma albumin < 3.5 g/dL, and open and urgent surgery were significantly correlated with major complications (p = 0.015, p = 0.022, p = 0.003, and p < 0.001, respectively). LOS was longer in elderly patients with a modified 5-item Frailty Index (5-mFI) ≥ 2 and low preoperative serum albumin levels, as well as following open surgery (p = 0.006, p = 0.001 and p < 0.001, respectively). Sarcopenia and preoperative plasma albumin < 3.5 g/dL were predictors for 90-day mortality (p = 0.004 and p > 0.001).

Conclusion

Advanced age, sarcopenia, preoperative hypoalbuminemia, 5-mFI ≥ 2, and open or urgent surgery may serve as predictors for postoperative morbidity in the elderly population.
Seasonal variation in home-range size of the White-backed Woodpecker
Authors: Ettwein Antonia , Lanz Michael , Pasinelli Gilberto
Published: November 2024

Knowing a species’ area requirements is fundamental for species conservation. For the nominate subspecies of the White-backed Woodpecker Dendrocopos leucotos, a species of high conservation concern in Europe, estimates of the seasonal and year-round area requirements based on telemetry are missing. In the present study, we radio-tracked adult White-backed Woodpeckers in Central Europe and investigated bi-monthly home-range sizes based on three home-range estimators in relation to season, sex, body weight, and year. Home-range size of 49 radio-tracked individuals varied depending on the used home-range estimator, with minimum convex polygons (MCP) and autocorrelated kernel density estimation (AKDE) producing 1.6–1.8 and 2–3.3 times larger seasonal home ranges than traditional kernel density estimation (KDE). Moreover, home-range sizes varied between seasons. Home ranges were smallest in February/March (predicted median home-range sizes ranged from 35 ha with KDE to 88 ha with AKDE) and April/May (KDE: 30 ha, AKDE: 55 ha) and larger during the rest of the year (KDE: 48–67 ha, AKDE: 136–184 ha). The mean home-range size of six individuals tracked in all seasons (calculated with all locations per individual) was 116 ha with KDE, 304 ha with MCP and 350 ha with AKDE. Our results highlight the importance of considering the full annual cycle when addressing area requirements of White-backed Woodpeckers and likely also of other species. Furthermore, our study shows that using multiple methods for home-range estimation may be useful to obtain results that are both comparable with those of other studies and capture the range in which the true home-range size is likely to be. For the conservation of the White-backed Woodpecker, we conclude that at least 116–350 ha of forest should be present for a pair.
Reflexive symmetric differentials and quotients of bounded symmetric domains
Authors: Patel Aryaman
Published: November 2024

For each classical irreducible bounded symmetric domain

$$\mathcal {D}$$

D

, Klingler has computed the minimum number

$$m_{\mathcal {D}}$$

m
D

such that any smooth projective quotient

$$X=\mathcal {D}/\Gamma $$

X
=
D
/
Γ

, for

$$\Gamma \in \text {Aut}^0(\mathcal {D})$$

Γ
∈

Aut
0

(
D
)

, satisfies

$$H^0(X,\textrm{Sym}^i\Omega ^1_X)=0$$

H
0

(
X
,

Sym
i

Ω
X
1

)

=
0

for

$$0<i<m_{\mathcal {D}}$$

0
<
i
<

m
D

. In this article, we extend Klingler’s result to the case when X is normal and projective. This, together with a normal version of Arapura’s result about the relationship between the vanishing of global symmetric differentials on X and the rigidity of finite dimensional representations of

$$\pi _1(X)$$

π
1

(
X
)

, gives rigidity statements for representations of

$$\pi _1(X)$$

π
1

(
X
)

and

$$\pi _1(X_{reg})$$

π
1

(

X

reg

)

in a low dimensional range, when X is a normal projective quotient of a bounded symmetric domain.
Multi-Grid Reaction-Diffusion Master Equation: Applications to Morphogen Gradient Modelling
Authors: Erban Radek , Winkelmann Stefanie
Published: November 2024

The multi-grid reaction-diffusion master equation (mgRDME) provides a generalization of stochastic compartment-based reaction-diffusion modelling described by the standard reaction-diffusion master equation (RDME). By enabling different resolutions on lattices for biochemical species with different diffusion constants, the mgRDME approach improves both accuracy and efficiency of compartment-based reaction-diffusion simulations. The mgRDME framework is examined through its application to morphogen gradient formation in stochastic reaction-diffusion scenarios, using both an analytically tractable first-order reaction network and a model with a second-order reaction. The results obtained by the mgRDME modelling are compared with the standard RDME model and with the (more detailed) particle-based Brownian dynamics simulations. The dependence of error and numerical cost on the compartment sizes is defined and investigated through a multi-objective optimization problem.
Recent Strategies and Advances in Hydrogel-Based Delivery Platforms for Bone Regeneration
Authors: Wang Xiao , Zeng Jia , Gan Donglin , Ling Kun , He Mingfang , Li Jianshu , Lu Yongping
Published: November 2024

Bioactive molecules have shown great promise for effectively regulating various bone formation processes, rendering them attractive therapeutics for bone regeneration. However, the widespread application of bioactive molecules is limited by their low accumulation and short half-lives in vivo. Hydrogels have emerged as ideal carriers to address these challenges, offering the potential to prolong retention times at lesion sites, extend half-lives in vivo and mitigate side effects, avoid burst release, and promote adsorption under physiological conditions. This review systematically summarizes the recent advances in the development of bioactive molecule-loaded hydrogels for bone regeneration, encompassing applications in cranial defect repair, femoral defect repair, periodontal bone regeneration, and bone regeneration with underlying diseases. Additionally, this review discusses the current strategies aimed at improving the release profiles of bioactive molecules through stimuli-responsive delivery, carrier-assisted delivery, and sequential delivery. Finally, this review elucidates the existing challenges and future directions of hydrogel encapsulated bioactive molecules in the field of bone regeneration.
Two stage iterative approach for addressing missing values in small-scale water quality data
Authors: Wang Fangyu , Cui Xiaoying , Gui Yuying , Qiao Yanxin
Published: November 2024

Handling missing values in real water quality monitoring systems is essential for environmental analysis, particularly in some small-scale datasets. In the case of insufficient data size, the observed data cannot provide adequate information, inhibiting some imputing methods from working well. This study proposes a two-stage approach for addressing missing water quality data of small size on the basis of accuracy assessment. Missingness is formulated as the coexistence of ‘random missing over short periods’ and ‘long-term continuous missing’. In the first stage, the traditional mean imputation, median imputation, linear interpolation, k-nearest neighbor imputation, random forest imputation, and multiple imputation by chained equations are compared to select the optimal method. As the most suitable method across all variables, linear interpolation is used to fill in small random missing portions of the original data, providing an opportunity to expand the dataset to perform subsequent imputation. In the second stage, together with the autoregressive integrated moving average, the filling methods are similarly evaluated on the basis of data already filled in the first step. The most suitable method obtained from the comparison is used to populate the remaining long-term continuous missing data. The efficacy of the proposed approach is validated on a real water quality dataset. The results demonstrate that the two-stage iterative approach offers a feasible roadmap to impute missing values on the small-scale water quality dataset.
Heidegger's Concept of Science
Authors: Goldberg Paul
Published: November 2024

This Element argues that Heidegger's concept of science has two core features. Heidegger critiques a security-oriented concept of science, which he associates with the dominance of physics in modern science and metaphysics and with a progressive resistance among philosophers and scientists to ontological questioning. Meanwhile, Heidegger advances an access-oriented concept of science, on which science is essentially founded on ontological disclosures but also constantly open to the possibility of new revolutionary disclosures. This Element discusses how these commitments develop in Heidegger's early and later thinking, and argues that they inform his views on the history of Western metaphysics and on the possibilities for human flourishing that modernity, and modern science specifically, affords. The Element also discusses Heidegger's dialogue with Werner Heisenberg about quantum physics; and throughout, it highlights points of contact and divergence between Heidegger and other philosophers of science such as Karl Popper, Thomas Kuhn, Paul Feyerabend, and Helen Longino.
Disturbed areas promote more parental care and less nesting preference in females of broad-snouted caiman (Caiman latirostris)
Authors: Barboza Rafael Sa Leitao , Correia Jozelia Maria de Sousa , Souto Antonio , Schiel Nicola
Published: November 2024

The successful survival of crocodilian hatchlings is largely dependent upon nest care by females. Nonetheless, it is crucial to understand how environmental degradation affects nest site selection and parental behaviour in female crocodilians. Therefore, our objective was to evaluate the relationship between anthropogenic disturbances and nesting behaviour in free-living broad-snouted caiman (Caiman latirostris). We compared nests in a disturbed and a non-disturbed area, and anticipated differences in nest density, hatching success, female size, egg number and biomass, and parental care behaviour. We monitored 44 nests over four years in Brazil, covering 58.25 km, in a disturbed area (n = 8) and a non-disturbed area (n = 36). According to our findings, nest density was significantly higher in the non-disturbed area (1.31 nests per linear km) compared to the disturbed area (0.25 nests per linear km). However, there was a significantly higher frequency of parental care behaviour (86%) in the disturbed area compared to the non-disturbed area (34%). The other factors studied showed no statistical difference between the two areas. The results indicate that females prefer to nest in healthier, preserved environments, away from anthropogenic disturbances. Yet, presumably at the cost of extra energy expenditure, increased parental care appears to buffer against a reduction in hatching success. Despite the behavioural buffer, the clear preference for non-disturbed nesting and nursery locations underscores the need to identify and protect the remaining non-disturbed areas inhabited by these animals. Our findings suggest that these measures should positively impact the welfare and protection of C. latirostris and other crocodilian species.