bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of spatiotemporal variation in marine resources on the occupancy dynamics of a terrestrial avian predator
Authors: Schmidt Joshua H. , Coletti Heather A. , Cutting Kyle A. , Wilson Tammy L. , Mangipane Buck A. , Schultz Carlene N. , Schertz Dylan T.
Published: November 2024

Identifying how species respond to system drivers such as weather, climate, habitat, and resource availability is critical for understanding population change. In coastal areas, the transfer of nutrients across the marine and terrestrial interface increases complexity. Nesting populations of bald eagles (Haliaeetus leucocephalus) along the Pacific coast of North America, although terrestrial, are largely dependent on marine resources during the breeding season and therefore represent a good focal species for understanding the linkages of nutrients between terrestrial and marine systems. Due to their location, coastal eagle populations are susceptible to a variety of climate‐induced perturbations, from both land and sea. The northeast Pacific Marine Heatwave (PMH) of 2014–2016 had wide‐ranging impacts on the marine ecosystem and provided an opportunity to explore how marine conditions can impact terrestrial wildlife populations. We used a spatially explicit multistate occupancy modeling framework to analyze >30 years of bald eagle nest occupancy data collected in four large national parks along a coastal interior gradient in Alaska, USA. We assessed occupancy state in relation to weather conditions, salmon abundance, access to alternate prey resources, and the PMH event to help elucidate the factors affecting bald eagle occupancy dynamics over time. We found that occupancy probability was higher in areas where prey resources were concentrated (e.g., near seabird colonies, where bears facilitate access to salmon carcasses). We also found that the probability of reproductive success was higher during warmer, drier springs with higher‐than‐average salmon abundance. After the onset of the PMH, success declined in the areas most dependent on non‐salmon marine resources. These findings confirm the importance of spring weather conditions and access to salmon resources during the critical chick‐rearing period, but also reveal that marine heatwaves may have important secondary effects through a reduction in the overall quantity or quality of prey available to bald eagles. Given ongoing warming at high latitudes and the expectation that marine heatwaves will become more common, our findings are useful for understanding ongoing and future changes in the transfer of nutrients from marine to terrestrial ecosystems and how such changes may impact terrestrial species such as bald eagles.
DMAP‐Catalyzed Efficient Diastereo‐ and Regioselective Synthesis of Isoxazolone‐Based Bisspiroheterocyclic Oxindoles
Authors: Zhu Rong‐Rong , Du Da‐Ming
Published: November 2024

A strategic approach to incorporate CF3 group into oxindoles, pyrrolidines, and isoxazolones to construct spiro heterocyclic skeletons with quaternary carbon stereocenters was developed. Using a DMAP catalyst under mild conditions, the controllable synthesis of spiro oxindole‐pyrrolidine‐isoxazoline derivatives was achieved via concerted 1,3‐dipolar cycloaddition reactions of arylidene isoxazolones with N‐(2,2,2‐trifluoroethyl)isatin ketimines. This method exhibits robust regioselectivity and provides a series of isoxazolone‐based bispiro heterocycles in good to high yields (72 %–99 %) with excellent diastereoselectivity (in all cases >20 : 1 dr), offering new candidate compounds for drug screen.
Tailoring Ni/Fe Doping for Superior Thermoelectric Performance of Zr2Ni2−xFexSnSb (x = 0.30, 0.35, 0.40) High‐Entropy Alloys
Authors: Adamo Chalchisa Getachew , Srivastava Ashutosh , Kumar Dipanjan , Legese Surafel Shiferaw , Sreeram Punathil Raman , Mangalassery Neethu Mohan , Kawamura Yoshihito , Olu Femi Emmanuel , Tiwary Chandra Sekhar , Singh Abhishek Kumar , Chattopadhyay Kamanio
Published: November 2024

Half‐Heusler (hH) compounds are emerging as promising materials for thermoelectric applications, owing to their exceptional mechanical and thermal stability, combined with the absence of toxic elements. These characteristics make hH compounds an attractive subject for detailed study and potential use in advanced thermoelectric systems. However, its thermoelectric applicability is limited because of high lattice thermal conductivity (κl). Various strategies, such as phase separation, grain‐boundary scatterings, and electron–phonon interactions, have been used to reduce κl, which enhances phonon scatterings. Recently, high‐entropy hH alloys have gained significant attention due to their distorted structure that inherently incorporates high phonon scattering features, addressing the key issue of hH. Herein, hH high‐entropy alloys (Zr2Ni2−xFexSnSb; x = 0.30, 0.35, 0.40) have been synthesized by arc melting and heat treatment. A significantly reduced lattice thermal conductivities (<2.25 W mK−1 at 985 K) are obtained due to the presence of multicomponents, which scatter phonon significantly. Experimental observation is very well complimented with density functional theory findings by analyzing phonon dispersions, chemical bonding, group velocities, and anharmonicity. Thereby, it is demonstrated that a high thermoelectric figure of merit is achieved in the proposed hH high‐entropy alloys by strengthening the phonon scatterings.
Charging Ahead: The Evolution and Reliability of Nickel‐Zinc Battery Solutions
Authors: Bello Idris Temitope , Raza Hassan , Michael Alabi Tobi , Muneeswara Madithedu , Tewari Neha , Bingsen Wang , Cheung Yin Nee , Choi Zungsun , Boles Steven T.
Published: November 2024

Nickel‐Zinc (Ni‐Zn) batteries offer an interesting alternative for the expanding electrochemical energy storage industry due to their high‐power density, low cost, and environmental friendliness. However, significant reliability challenges such as capacity fading, self‐discharge, thermal instability, and electrode degradation detract from their competitiveness in the market, hindering their widespread adoption. This study thoroughly examines the degradation mechanisms and approaches to improve the reliability of Ni‐Zn batteries: Starting with their basic chemistry, operating principles, and degradation pathways, strategies for improvement are explored including material modification, electrolyte optimization, cell design approaches, and thermal management techniques. Advanced characterization methods for data collection and reliability assessment are discussed, including electrochemical, structural, spectroscopic, and in situ techniques which are noted for their ability to identify key areas of concern for this cell chemistry. We further consider emerging trends such as novel materials, hybridization with other energy technologies, and the challenges of large‐scale implementation, emphasizing the need for standardized reliability testing protocols. Opportunities for the integration of advanced sensing, such as fiber Bragg grating (FBG) sensors for real‐time monitoring and anomaly detection, along with machine learning (ML) and prognostics and health management of Ni‐Zn batteries are highlighted, as these open the door to future research directions. This comprehensive review should serve as a resource for researchers, engineers, and industry experts aiming to advance and commercialize dependable, high‐performing Ni‐Zn battery technology for a sustainable energy future.

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Greenhouse gas emission driving factors and reduction strategies for operational phase of urban rail transit in China
Authors: Guo Hao
Published: November 2024

To promote the sustainable development of urban rail transit (URT) in China, it is necessary to quantitatively analyze the greenhouse gas (GHG) emissions and its internal driving factors. Based on the LMDI algorithm, this research constructs an assessment model and makes a quantitative analysis of internal driving factors for GHG emissions in the operational phase of the URT system in China. According to the official investigated data, the GHG emission of URT in the operational phase is between 600 × 104 and 2000 × 104 tons of carbon dioxide equivalent (CO2e) per year from 2012 to 2023. The results of the driving factors decomposition showed that the passenger demand intensity was the key and positive factor affecting carbon emissions in the operational phase and the contribution rate was 12.93%–60.81% from 2013 to 2023. Therefore, it is necessary to formulate targeted policies in terms of management and technical means to reduce the average traveling distance demanded by passengers and reasonably control the scale of the line network for GHG reduction in the Chinese URT system.
Water, Energy, Food, and Environment Nexus for Achieving Sustainable Transition, Addressing Gaps, and Implementing Solutions for Global and Iranian Cases
Authors: Zahedi Rahim , Aslani Alireza , Yousefi Hossein , Noorollahi Younes , Astaraei Fatemeh Razi
Published: November 2024

The challenge of providing water, energy, food, and managing the environment (WEFEN) is widely recognized as a significant barrier to global advancement in light of the increasing population. The interconnections among water, energy, food, and the environment constitute a comprehensive framework for achieving sustainability. Based on projections, it is anticipated that the global community will encounter crises pertaining to water, energy, food, and the environment in the foreseeable future. The objective of this paper is to analyze global research endeavors pertaining to the interconnections among water, energy, food, and the environment. Additionally, it aims to address the challenges and imperatives of investigating this nexus within the context of the world. This framework aims to achieve a harmonious equilibrium by considering the diverse objectives, interests, and requirements of both human societies and the natural environment. The correlation established by WEFEN has the potential to provide valuable insights for informing future global sustainable development policies in relation to environmental and water crises. This review study critically analyzes the existing body of research pertaining to the interplay between water, energy, food, and the environment in Iran and globally. Additionally, it highlights the challenges encountered in studying this intricate relationship and underscores the imperative for further investigation in this domain. This study reveals that the main barriers to achieving global integration of water, energy, food, and the environment are sector‐specific policies and a dearth of integrated management approaches. The findings of this study encompass recommendations for enhancing the interplay between water, energy, food, and the environment. Additionally, establishing a dedicated policy‐making institution and reaching a consensus on a comprehensive plan are crucial steps. Furthermore, it is imperative to develop and enhance the infrastructure of the clearing market to address pertinent matters effectively.
Enhancing Electronic Nose Performance for Differentiating Civet and Non‐Civet Roasted Bean Coffee Using Polynomial Feature Extraction Methods
Authors: Ihsan Nasrul , Kombo Kombo Othman , Kusuma Frendy Jaya , Syahputra Tri Siswandi , Puspita Mayumi , Wahyono  , Triyana Kuwat
Published: November 2024

Coffee, a popular beverage worldwide, requires thorough quality assessment to ensure its authenticity and meet consumer demands. Traditional methods in the industry are often subjective, expensive, and time‐consuming. This study used a compact, portable electronic nose (e‐nose) with machine learning models to classify and distinguish between civet and non‐civet roasted beans. The polynomial feature extraction method was used to extract important parameters from the sensor response and improve system performance. Classification models like linear discriminant analysis (LDA), logistic regression (LR), quadratic discriminant analysis (QDA), and support vector machines (SVM) were applied to classify the samples. Among these, the LDA model with polynomial features yielded the highest validation and test accuracies, with values of 0.89 ± 0.04 and 0.93, respectively. This was higher than the statistical feature methods, which obtained validation and test accuracies of 0.80 ± 0.07 and 0.87, respectively. The acquired e‐nose results were correlated with compound concentrations in roasted coffee beans measured by gas chromatography–mass spectrometry (GC–MS). These findings demonstrate the e‐nose system's promising potential to effectively distinguish civet from non‐civet roasted coffee beans based on their aroma profiles using polynomial feature extraction methods.
Elucidation of Volatile and Morphological Properties of Saffron (Crocus sativus) Flower as Affected by Controlled Drought Stress Induced by Polyethylene Glycol
Authors: Sevindik Başar
Published: November 2024

Crocus sativus L., known as saffron, is one of the major crops among ornamental and medicinal aromatic plants. Polyethylene glycol (PEG) 6000 is one of the well‐known and efficient simulators used for this purpose. In this study, saffron corms were cultivated in pots containing perlite, and the PEG 6000 solution was applied at 5%, 10% and 15% concentrations. A HS‐SPME‐GC–MS system was used to elucidate volatiles of saffron flowers, and a total of 28 volatiles was detected. Safranal was measured as the most dominant volatile compound in saffron flowers, and the release of marker volatiles was dramatically increased with the increasing PEG 6000 dosage. Eucarvone was found to be an important ketone compound, Phenethyl alcohol was found to be the most abundant volatile alcohol compound. Additionally, ketones pyrrole, lactone, esters and other sulphurous components increased with PEG 6000 application. According to the morphological observations, decreases were observed in plant dry weight (PDW), plant fresh weight (PFW), corm diameter (CD), daughter corm (DCN), and flower number (FN), between the control plants and those treated with PEG 6000. However, an increase was detected in root number (RN) and root length (RL). Leaf length (LL), on the other hand, increased with a 5% PEG application but decreased with higher concentrations.
Developing Guidelines for the Future of Visual Art Education: A Delphi Study of the Croatian Case
Authors: Skender Lana , Dubovicki Snježana
Published: November 2024

The qualitative research examined how the Delphi method could be used to develop guidelines for the future of Visual Arts education in Croatia. The study gathered insights from eight experts across various disciplines, including art history, art pedagogy, visual culture, and curriculum theory, to assess the impact of visual culture on Visual Arts education. The experts discussed changes in teaching methods, the influence of visual culture on young people, its effect on curricula, the relationship between fine art and visual culture, and the importance of an interdisciplinary approach. The findings suggest that this methodology could serve as a model for future educational policy reforms and for innovating and creating new Visual Arts curricula.
Early Salience Signals Predict Interindividual Asymmetry in Decision Accuracy Across Rewarding and Punishing Contexts
Authors: Westwood Sean , Philiastides Marios G.
Published: November 2024

Asymmetry in choice patterns across rewarding and punishing contexts has long been observed in behavioural economics. Within existing theories of reinforcement learning, the mechanistic account of these behavioural differences is still debated. We propose that motivational salience—the degree of bottom‐up attention attracted by a stimulus with relation to motivational goals—offers a potential mechanism to modulate stimulus value updating and decision policy. In a probabilistic reversal learning task, we identified post‐feedback signals from EEG and pupillometry that captured differential activity with respect to rewarding and punishing contexts. We show that the degree of between‐context distinction in these signals predicts interindividual asymmetries in decision accuracy. Finally, we contextualise these effects in relation to the neural pathways that are currently centred in theories of reward and punishment learning, demonstrating how the motivational salience network could plausibly fit into a range of existing frameworks.
The Efficacy and Safety of Negative‐Pressure Wound Therapy Combined With Platelet‐Rich Plasma in Chronic Refractory Wounds: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
Authors: Hao Ran , Luo Mao , Xiao Yanting , Li Jing , Lv Xinyue , Peng Yumei , Wu Yuxuan , Shen Yan , Jiang Wei
Published: November 2024

Background and Aims

Chronic refractory wound is a disease that seriously impairs the quality of life of patients. Negative pressure wound therapy and platelet‐rich plasma are commonly used to treat various types of wounds. Further research is necessary to explore the efficacy and safety of the combination of negative pressure wound therapy and platelet‐rich plasma in treating chronic refractory wounds.

Methods

PubMed, Web of Science, EMBASE, Cochrane, CINAHL, CNKI, Sino Med, and Wanfang Med Online up until March 2024 were searched(PROSPERO No. CRD42024507963). Two investigators screened literature according to inclusion and exclusion criteria, evaluated bias and certainty of evidence using RoB 2.0 and GRADE. Stata 12.0 was used to analyze the data.

Results

A total of 35 randomized controlled trials involving 2495 participants were included. 34 studies were assessed as having some concerns, and 1 study as having high risk in the risk of bias assessment. The results of meta‐analysis showed that effective rate (RR1.23, 95% CI [1.17, 1.30], p < 0.001; I2 = 44.7%, p = 0.013), healing time (WMD‐9.32, 95% CI [−10.60, −8.03], p < 0.001; I² = 91.00%, p < 0.001), healing rate (RR1.76, 95% CI [1.50, 2.07], p < 0.001; I2 = 62.6%, p < 0.001), positive rate of bacterial(RR0.25, 95% CI [0.15, 0.40], p < 0.001; I² = 0%, p = 0.841), pain score (WMD‐1.43, 95% CI [−2.14, −0.72], p < 0.001; I² = 96.5%, p < 0.001), incidence of complications (RR0.45, 95% CI [0.30, 0.68], p < 0.001; I² = 46.3%, p = 0.098), length of hospital stay (WMD‐9.88, 95% CI [−13.42, 6.34], p < 0.001; I2 = 98.9%, p < 0.001), number of dressing changes (WMD‐2.56, 95% CI [−4.28, −0.83], p = 0.004; I² = 98.9%, p < 0.001), white blood cell level (WMD‐1.71, 95% CI [−2.00, −1.41], p < 0.001; I² = 33.9%, p = 0.195), c‐reactive protein level (WMD‐0.68, 95% CI [−1.04, −0.33], p < 0.001; I² = 88.8%, p < 0.001), erythrocyte sedimentation rate (WMD‐6.09, 95% CI [−8.05, −4.13], p < 0.001; I² = 13%, p = 0.32), score of vancouver scar scale (WMD‐1.78, 95% CI [−1.89, −1.66], p < 0.001; I² = 38.3%, p = 0.166) and preparation time of secondary repair (WMD‐4.95, 95% CI [−7.03, −2.87], p < 0.001; I² = 84.7%, p < 0.001) had statistically significant effects. However, hospitalization costs (WMD1423.56, 95% CI [−4588.93, 7436.06], p = 0.643; I2 = 100%, p < 0.001) had no significant difference.

Conclusions

This study demonstrates that the combination of negative‐pressure wound therapy and platelet‐rich plasma can improve the efficacy and safety on chronic refractory wounds. Optimal parameter combinations, elucidation of pathogenesis and treatment mechanisms can be explored in the future.
Opposite effects of systemic and local conditional CD11c+ myeloid cell depletion during bleomycin‐induced inflammation and fibrosis in mice
Authors: Lopes Gabriel Augusto Oliveira , Lima Braulio Henrique Freire , Freitas Camila Simões , Peixoto Andiara Cardoso , Soriani Frederico Marianetti , Cassali Geovanni Dantas , Ryffel Bernhard , Teixeira Mauro Martins , Machado Fabiana Simão , Russo Remo Castro
Published: November 2024

Rationale

Elevated levels of CD11c+ myeloid cells are observed in various pulmonary disorders, including Idiopathic Pulmonary Fibrosis (IPF). Dendritic cells (DCs) and macrophages (MΦ) are critical antigen‐presenting cells (APCs) that direct adaptive immunity. However, the role of CD11c+ myeloid cells in lung extracellular matrix (ECM) accumulation and pulmonary fibrosis is poorly understood.

Objective

We aimed to investigate the impact of depleting CD11c+ myeloid cells, including DCs and macrophages, during bleomycin‐induced pulmonary fibrosis in mice.

Methods

We used a diphtheria toxin (DTx) receptor (DTR) transgenic mouse model (CD11c‐DTR‐Tg) to deplete CD11c+ myeloid cells through two methods: Systemic Depletion (SD) via intraperitoneal injection (i.p.) and local depletion (LD) via intranasal instillation (i.n.). We then assessed the effects of CD11c+ cell depletion during bleomycin‐induced lung inflammation and fibrosis.

Results

Fourteen days after bleomycin instillation, there was a progressive accumulation of myeloid cells, specifically F4/80‐MHCII+CD11c+ DCs and F4/80 + MHCII+CD11c+ MΦ, preceding mortality and pulmonary fibrosis. Systemic depletion of CD11c+ DCs and MΦ via i.p. DTx administration in CD11c‐DTR‐Tg mice protected against bleomycin‐induced mortality and pulmonary fibrosis compared to wild‐type (WT) mice. Systemic depletion reduced myeloid cells, airway inflammation (total leukocytes, neutrophils, and CD4+ lymphocytes in bronchoalveolar lavage (BAL), inflammatory and fibrogenic mediators, and fibrosis‐related mRNAs (Collagen‐1α1 and α‐SMA). Increased anti‐inflammatory cytokine IL‐10 and CXCL9 levels were observed, resulting in lower lung hydroxyproline content and Ashcroft fibrosis score. Conversely, local depletion of CD11c+ cells increased mortality by acute leukocyte influx (predominantly neutrophils, DCs, and MΦ in BAL) correlated to IL‐1β, with lung hyper‐inflammation and early fibrosis development.

Conclusion

Systemic depletion of CD11c+ cells confers protection against inflammation and fibrosis induced by Bleomycin, underscoring the significance of myeloid cells expressing F4/80‐MHCII+CD11c+ DCs and F4/80 + MHCII+CD11c+ MΦ orchestrating the inflammatory milieu within the lungs, potentially as a source of cytokines sustaining pulmonary chronic inflammation leading to progressive fibrosis and mortality.
CL‐20/4,5‐MDNI crystal growth and morphology under different conditions: A molecular dynamics simulation
Authors: Zhou Xuan , Song Liang , Li Xing , Zeng Xiu‐Lin , Ju Xue‐Hai
Published: November 2024

CL‐20/4,5‐MDNI exists in two cocrystal forms with different stoichiometric ratios of 1:1 and 1:3. The properties (such as blast performance, thermal performance, sensitivity, and density) of the two cocrystals are significantly different, but both cocrystals are expected to become new high‐energy insensitive explosives and have good applications. The AE model and molecular dynamics were used to simulate the crystal morphology and important crystal planes of 1:1 and 1:3 CL‐20/4,5‐MDNI under vacuum conditions, as well as in five solvents and different temperatures. 1:1 CL‐20/4,5‐MDNI has five main growth crystal planes of (002), (102), (111), (020) and (021), of which (002) has the largest proportion. 1:3 CL‐20/4,5‐MDNI has six main growth crystal planes of (001), (010), (011), (100), (101) and (111), of which (001) accounts for the largest proportion. The crystal morphology aspect ratio of 1:3 CL‐20/4,5‐MDNI in acetonitrile and 1:1 CL‐20/4,5‐MDNI in methanol are 1.936 and 1.680, respectively. The results were consistent with the experiments, which has certain guiding significance for CL‐20/4,5‐MDNI to obtain a crystal morphology closer to spherical shape.
Successful treatment of low‐risk myelodysplastic syndrome‐related anemia in patients with chronic kidney disease with daprodustat: A report of two cases
Authors: Kunimoto Hiroyoshi , Sakuma Takayuki , Ohashi Takuma , Shirafuta Mayoko , Teranaka Hiroshi , Nakajima Hideaki
Published: November 2024

Anemia is a major clinical manifestation seen in myelodysplastic syndromes (MDS). Treatment options for anemia in low‐risk MDS are limited. Especially, oral medication which is uniformly effective for anemia in low‐risk MDS is required. Hypoxia‐inducible factor (HIF) prolyl hydroxylase (HIF‐PH) inhibitors, such as daprodustat, are oral tablets effective for renal anemia. Pharmacological restoration of HIF activity by HIF‐PH inhibitors may be beneficial for MDS‐related anemia as well. Yet, their efficacy and safety against low‐risk MDS are unclear. Here, we report two cases of low‐risk MDS complicated with chronic kidney disease whose anemia responded to daprodustat treatment.
Synthesis of 5‐Aryltetrahydrobenzazepines
Authors: Thoti Naveenkumar , Gupta Deepika , Lal Heera , Aidhen Indrapal Singh
Published: November 2024

Envisaging 5‐aryltetrahydrobenzazepinone and 5‐aryltetrahydrobenzazepines as conformationally locked potential B0AT1 inhibitors, a convenient synthetic route has been developed for their access. The synthetic route banks on using the Schmidt reaction for quick access to symmetrical/unsymmetrical 5‐aryltetrahydrobenzazepinone and 5‐aryltetrahydrobenzazepines.
Streamlining diuresis: A quality improvement approach to implementing a sodium‐based predictive diuresis protocol
Authors: Rai Karan , Western Hillary Landau , Patel Moksha , Porter Samuel
Published: November 2024

Diuresis for hospitalized patients with acute decompensated heart failure is a routine clinical practice but one that remains reliant on error‐prone and resource‐intensive intake and output and weight measurements and is subject to wide provider variation. We sought to use quality improvement approaches to implement a data‐driven predictive diuresis protocol based on natriuresis using the electronic health record to titrate dosing. Our initiative did not result in significant reductions in length of stay but did demonstrate a significant increase in the use of urine studies to guide diuresis and signals toward more aggressive diuretic dosing without an increase in adverse outcomes.
Human glyoxylate metabolism revisited: New insights pointing to multi‐organ involvement with implications for siRNA‐based therapies in primary hyperoxaluria
Authors: Wanders Ronald J. A. , Groothoff Jaap W. , Deesker Lisa J. , Salido Eduardo , Garrelfs Sander F.
Published: November 2024

Glyoxylate is a toxic metabolite because of its rapid conversion into oxalate, as catalyzed by the ubiquitous enzyme lactate dehydrogenase. This requires the presence of efficient glyoxylate detoxification systems in multiple subcellular compartments, as glyoxylate is produced in peroxisomes, mitochondria, and the cytosol. Alanine glyoxylate aminotransferase (AGT) and glyoxylate reductase/hydroxypyruvate reductase (GRHPR) are the key enzymes involved in glyoxylate detoxification. Bi‐allelic mutations in the genes coding for these enzymes cause primary hyperoxaluria type 1 (PH1) and 2 (PH2), respectively. Glyoxylate is derived from various sources, including 4‐hydroxyproline, which is degraded in mitochondria, generating pyruvate and glyoxylate, as catalyzed by the mitochondrial enzyme 4‐hydroxy‐2‐oxoglutarate aldolase (HOGA); however, counterintuitively, a defect in HOGA1 is the molecular basis of primary hyperoxaluria type 3 (PH3). Irrespective of its underlying cause, hyperoxaluria in humans leads to nephrocalcinosis, recurrent urolithiasis, and kidney damage, which may culminate in kidney failure requiring combined liver‐kidney transplantation in severely affected patients. In the past few years, therapeutic options, especially for primary hyperoxaluria type 1 (PH1), have greatly been improved thanks to the introduction of two RNAi‐based therapies that inhibit either the production of glycolate oxidase (lumasiran) or lactate dehydrogenase (nedosiran). While lumasiran only targets PH1 patients, nedosiran was specifically developed to target all three subtypes of PH. Inspired by the findings reported in the literature that nedosiran effectively reduced urinary oxalate excretion in PH1 patients but not in PH2 or PH3 patients, we have now revisited glyoxylate metabolism in humans and performed a thorough literature study which revealed that glyoxylate/oxalate metabolism is not confined to the liver but instead involves multiple different organs. This new view on glyoxylate/oxalate metabolism in humans may well explain the disappointing results of nedosiran in PH2 and PH3, and provides new clues for the future generation of new therapeutic strategies for PH2 and PH3.
My path to citrin deficiency
Authors: Walker John E.
Published: November 2024

Citrin belongs to the SLC25 transport protein family found mostly in inner mitochondrial membranes. The family prototype, the ADP–ATP carrier, delivers ATP made inside mitochondria to the cellular cytoplasm and returns ADP to the mitochondrion for resynthesis of ATP. In pre‐genomic 1981, I noticed that the protein sequence of the bovine ADP–ATP carrier consists of three related sequences, each containing two transmembrane α‐helices traveling in opposite senses. Colleagues and I demonstrated that two other mitochondrial carriers had similar features. From emergent genomic sequences, it became apparent that they represented a large family of transport proteins with the same characteristic threefold repeats. The human genome encodes 53 members, but the functions of many were unknown. So, colleagues and I determined how to make these proteins in Escherichia coli and introduce them into liposomes to allow exploration of their transport functions. The 27 human family members to have been thus identified include citrin and the closely related protein aralar. Both exchange aspartate from the mitochondrial matrix for cytosolic glutamate plus a proton. Citrin is expressed predominantly in liver and non‐excitable tissues, whereas aralar is the dominant form in the brain. Each has a membrane extrinsic N‐terminal Ca2+‐binding domain, a transport domain, and a C‐terminal amphipathic α‐helix. Human mutations in citrin impair the urea cycle, malate–aspartate shuttle, gluconeogenesis, amino acid breakdown, and energy metabolism leading to citrin deficiency. Currently, the complex etiology of this condition is poorly understood and new knowledge would help to improve diagnosis, therapies, and finding a cure. My aims are to seek a basic understanding of the etiology of citrin deficiency and to use that knowledge in improving diagnostic procedures and in developing new treatments and a cure.
The clinical utility in hospital‐wide use of growth differentiation factor 15 as a biomarker for mitochondrial DNA‐related disorders
Authors: Fernández Andrea Cortés , Estrella Jane , Oglesbee Devin , Larson Austin A. , Van Hove Johan L.K.
Published: November 2024

Clinical recognition of primary mitochondrial disorders (PMD) is difficult due to the clinical and genetic heterogeneity. Whereas lactate has low sensitivity and specificity, in structured clinical studies growth differentiation factor 15 (GDF15) has shown promise with elevations in mitochondrial DNA (mtDNA)‐related PMD, but its specificity has been questioned. In a tertiary care hospital‐wide study, medical records were retrospectively reviewed from 418 cases where GDF15 levels were obtained by clinicians. Patients were classified into patients with PMD due to mtDNA‐related defects (mtDNA maintenance, mtDNA deletions, and mtDNA‐encoded tRNA variants), PMD due to structural defects or other nuclear causes, and in non‐mitochondrial disease. Patients with liver disease or systemic critical illness were excluded. GDF15 was assayed in a clinical laboratory with a cutoff of 750 ng/L. There were 38 mtDNA‐related PMD (GDF15 >750 pg/mL in 76%), 35 other nuclear DNA‐encoded PMD or structural subunits (31% elevated GDF15), 309 non‐mitochondrial disorders (13% elevated GDF15). Based on the highest Youden J‐index, the optimal cut‐off value to identify these target mtDNA‐related disorders was 815 pg/mL, with sensitivity 76%, specificity 88%, positive predictive value of 41% and negative predictive value of 97%. At this optimized cutoff level, mtDNA‐encoded PMD patients had elevated GDF15 in 76%, nuclear DNA‐encoded PMD in 26%, and non‐mitochondrial disorders in 11% of patients. Thus, in a real‐life clinical setting, after excluding abnormal liver function and critical illness, GDF15 had good clinical utility increasing the odds at predicting mtDNA‐related primary mitochondrial disorders 14‐fold, but not for structural or other nuclear‐encoded primary mitochondrial disorders.
Telehealth noninferior to in person for vocational counseling: A comparison study of “Asking for Help” group intervention to improve soft skills
Authors: Lu Weili , Oursler Janice , Herrick Samantha J. , Gao Ni , Silberman Harosh Ariella , Wang Ke , Beninato John , Morales Maritza , Diviney Jason , Mevawala Janki
Published: November 2024

Employment success often hinges on crucial work‐related soft skills, such as the ability to seek help and solve problems. This pilot study aimed to assess the practicality of a group intervention based upon a direct skills teaching (DST) approach to teach work‐related help‐seeking skills to individuals with disabilities. The “Asking for Help” intervention, conducted in either in person or via telehealth, involved 152 participants with disabilities. Both modalities showed improvement in participants’ perceptions of work‐related soft skill of asking for help. Participants experienced increased confidence in asking for help at employment settings and expressed high satisfaction with the intervention. Both groups increased career adaptabilities, while the telehealth group also increased occupational self‐efficacy, and the in‐person group showed increased work‐related soft skills. Both groups showed comparable positive results, supporting their effectiveness in teaching help‐seeking skills using a preplanned curriculum. Implications of findings are discussed.
Time‐dependent changes in medial meniscus kinematics and attachment strength after anterior root injury and repair in a large animal model
Authors: Meadows Kyle D. , Peloquin John M. , Boyes Madeline , Stoeckl Brendan D. , Benson Jamie , Bansal Sonia , Steinberg David R. , Zgonis Miltiadis H. , Schaer Thomas P. , Mauck Robert L. , Elliott Dawn M.
Published: November 2024

This study investigated joint kinematics and attachment tensile mechanics following resection of the medial meniscus anterior attachment. A secondary objective investigated the repair of the attachment. Yucatan minipigs underwent unilateral surgery for either Injury (en bloc) resection of the anterior attachment of the insertional ligament, (a portion of the cranial medial meniscotibial ligament) or Repair (immediate repair with a suture anchor), with the contralateral knee as Intact control. Evaluation at 6 weeks and 6 months included joint kinematics measured from MRI acquired under knee compression and tensile testing of the attachment. Injury resulted in large levels of meniscus extrusion, despite the development of a fibrovascular scar. At 6 weeks, the meniscus extruded 1.95 mm more than Intact; at 6 months, this extrusion was reduced to 0.77 mm. Under an applied 1× body weight load, the meniscus further extruded and was not different with treatment or time. During attachment tensile testing, elongation was 0.6 mm for Intact, following Injury, elongation was 2.7 mm at 6 weeks and was partially restored to 1.5 mm at 6 months. Despite this, the cartilage wear worsened over time. Repair was inadequate to avoid the extrusion or cartilage wear seen in the injury group at 6 weeks, so it was not continued for the 6‐month group. This study demonstrates that while meniscus injury is useful to study cartilage degeneration, a holistic consideration of the role of the meniscus itself, including its changing material properties and its impact on joint mechanics during injury, repair, and rehabilitation, are key factors contributing to overall joint health.
Blow‐up for a nonlocal semilinear pseudo‐parabolic p‐Laplacian type equation
Authors: Xie Changping , Fang Shaomei
Published: November 2024

In this paper, a nonlocal semilinear pseudo‐parabolic
‐Laplacian type equation is considered, and finite time blow‐up of solution with different initial energy is proved. More precisely, the upper bound for the blow‐up time of solution with subcritical initial energy is established by potential well method and concavity argument. When the initial energy is supercritical, we prove the finite time blow‐up of solution and obtain the upper bound for the blow‐up time by different invariant set and concavity inequality. Moreover, by constructing a new control functional and providing careful estimates, the lower bound for the blow‐up time of solution is given.
Clinical Characteristics and Variation in Musculoskeletal Complexity of Different Ethnic Populations Accessing Sandwell and West Birmingham Hospital's MSK Service: A Service Evaluation
Authors: Shah Wasim , Newham Roger , Casey Carolyn , Burgess Roanna
Published: November 2024

Introduction

Health inequality is a global public health challenge, limited by insufficient high‐quality data and analysis. Musculoskeletal (MSK) pain disorders are more prevalent among ethnic minority groups disproportionately affected by socioeconomic disparities and poor health outcomes. Ethnicity data collection enables NHS organisations and policymakers to understand specific healthcare needs and ensure equitable access and care provision.

Objective

To understand the baseline clinical characteristics across ethnic population groups accessing MSK care at Sandwell and West Birmingham (SWB) NHS Trust.

Methods

Retrospective analysis of routine data collected using patient self‐report surveys (August 2020–February 2023). Core metrics included demographics, pain characteristics, and Patient Reported Outcome Measures (PROMs) including the Musculoskeletal Health Questionnaire (MSK‐HQ) and Numeric Pain Rating Scale (NPRS). Descriptive statistics and statistical tests were undertaken, with means, percentage values and variation by ethnic groups across baseline MSK‐HQ and pain scores reported.

Results

Survey data were provided by 13,248 patients, with 7295 (55.06%) stating their ethnicity. Statistical differences were found between baseline MSK‐HQ and NPRS scores between ethnic groups. The mean MSK‐HQ score was 24.1 overall, lowest in the Asian group (22.3) and highest in the Mixed group (24.8). Mean baseline pain intensity was (7.8), highest in the Asian group (8.3). One or more comorbidities were present in 46% of patients, with the highest percentage in the White and Black groups sequentially.

Conclusion

Baseline health inequalities exist among ethnic groups accessing the SWB MSK service. Disparities may be associated with patient or system barriers and require further exploration.
In vivo rat brain mapping of multiple gray matter water populations using nonparametric D(ω)‐R1‐R2 distributions MRI
Authors: Yon Maxime , Narvaez Omar , Topgaard Daniel , Sierra Alejandra
Published: November 2024

Massively multidimensional diffusion magnetic resonance imaging combines tensor‐valued encoding, oscillating gradients, and diffusion‐relaxation correlation to provide multicomponent subvoxel parameters depicting some tissue microstructural features. This method was successfully implemented ex vivo in microimaging systems and clinical conditions with tensor‐valued gradient waveform of variable duration giving access to a narrow diffusion frequency (ω) range. We demonstrate here its preclinical in vivo implementation with a protocol of 389 contrast images probing a wide diffusion frequency range of 18 to 92 Hz at b‐values up to 2.1 ms/μm2 enabled by the use of modulated gradient waveforms and combined with multislice high‐resolution and low‐distortion echo planar imaging acquisition with segmented and full reversed phase‐encode acquisition. This framework allows the identification of diffusion ω‐dependence in the rat cerebellum and olfactory bulb gray matter (GM), and the parameter distributions are shown to resolve two water pools in the cerebellum GM with different diffusion coefficients, shapes, ω‐dependence, relaxation rates, and spatial repartition whose attribution to specific microstructure could modify the current understanding of the origin of restriction in GM.
Potential application of andrographolide in vital pulp therapy by inducing expression of human β defensin 4
Authors: Zhai Yue , Lv Yue , Li Yue , Yu Guoxia
Published: November 2024

Aim

This study aimed to investigate the ability of andrographolide to induce human β defensin 4 (HBD4) expression in dental pulp stem cells and its effect on inflammatory pulp tissue in rats in vivo.

Methods

The expression of HBD4 in andrographolide‐induced dental pulp stem cells was examined using quantitative polymerase chain reaction and immunofluorescence staining. High‐throughput analysis of protein acetylation was conducted to screen the mechanism of andrographolide‐induced HBD4 expression. Colony‐forming unit methods were used to study the antimicrobial ability of andrographolide‐induced HBD4 on Porphyromonas gingivalis. Finally, the ability of andrographolide to preserve vital pulp was examined using Wistar rats with irreversible pulpitis.

Results

HBD4 expression level increased after andrographolide stimulation, which was related to histone acetylation modification, as revealed by acetylome analyses. Antibacterial testing confirmed that andrographolide‐induced HBD4 was sensitive to P. gingivalis. Furthermore, andrographolide controlled pulp inflammation in a Wistar rat irreversible pulpitis model and induced the restorative dentin formation.

Conclusion

We concluded that andrographolide induced the expression of HBD4 in dental pulp stem cells through histone acetylation modification and exerted inhibitory effects on pulp tissue inflammation in vivo.
Mandibular cortical morphology in patients with osteoporosis using computer‐aided detection with dental panoramic imaging: A pilot study of the relation to age and bone‐modifying agents
Authors: Shirai Ai , Ogawa Ruri , Kobayashi Eizaburo , Ogura Ichiro
Published: November 2024

Aim

Mandibular cortical morphology with panoramic radiography is considered to be a useful technique for identifying at risk of osteoporosis. The aim of the study was to investigate the mandibular cortical morphology in patients with osteoporosis using computer‐aided detection (CAD) with dental panoramic imaging, especially the relation to age and bone‐modifying agents.

Methods

One hundred and thirteen patients with osteoporosis were underwent panoramic radiography. The mandibular cortical morphology, such as mandibular cortical index (MCI) and degree of deformation of mandibular inferior cortex, was analyzed automatically with a CAD with dental panoramic imaging “PanoSCOPE.” Those were analyzed in relation to age and bone‐modifying agents.

Results

Regarding Class 3 (severely eroded) of the MCI classifications, the frequency in 61–70, 71–80, and 81–90 years were 22.2%, 38.6%, and 26.3%, respectively, and the MCI in bisphosphonate and denosumab were 29.8% and 42.1%, respectively. The degree of deformation in 61–70, 71–80, and 81–90 years were 45.9 ± 22.6, 58.8 ± 20.0, and 52.6 ± 21.5, respectively, and those in bisphosphonate and denosumab were 54.1 ± 20.6 and 57.5 ± 25.0, respectively. The MCI and degree of deformation in patients with osteoporosis were not significant differences for age and bone‐modifying agents.

Conclusion

This study suggests that the CAD using PanoSCOPE can perform a quantitative analysis of mandibular cortical morphology in patients with osteoporosis.
Synthesis and Properties of a Shape Memory–Assisted Self‐Healing Supramolecular Polyurethane Coating Based on Quadrupole Hydrogen Bonding
Authors: Karimi Alavijeh Soheila , Khorasani Saied Nouri , Masoomi Mahmood , Neisiany Rasoul Esmaeely , Dinari Mohammad , Gomes Diego Ribas , Pei Yutao , Raffa Patrizio
Published: November 2024

In this research, the synthesis and characterization of a shape memory–assisted self‐healing polyurethane (SHSMPU) coating based on strong quadrupole hydrogen bonding interaction have been investigated. The coating was fabricated with an acrylic polyol, an isocyanate functionalized ureidopyrimidinone (UPy‐NCO) as a hydrogen bonding provider, and methylene diphenyl diisocyanate (MDI) as chain extender. Fourier‐transform infrared spectroscopy (FT‐IR) confirmed that by incorporating the UPy‐NCO dimer in the polyurethane (PU) structure, strong hydrogen bonding appears, which can provide the healing function of the polymer. In addition, differential scanning calorimetry (DSC) showed that by increasing the UPy‐NCO amount, the overall Tg decreased and the material becomes more flexible. A rheometric investigation revealed that a sample containing 45% of UPy‐NCO as total diisocyanate shows good shape recovery and an healing efficiency of macroscale cracks of around 94.2%, which is much higher than the corresponding sample without UPy‐NCO (50.4%). Even better performances were obtained with microcracks, where tested samples were significantly healed at around 80°C in 10 min. Furthermore, the introduction of polyethylene glycol 400 (PEG400) into the polymer's backbone led to a reduced Tg and thus higher flexibility at room temperature. The combination of the observed properties makes these materials promising for application as durable and flexible polyurethane coatings.
Proteomic analysis of non‐muscle invasive and muscle invasive bladder cancer highlights distinct subgroups with metabolic, matrisomal, and immune hallmarks and emphasizes importance of the stromal compartment
Authors: Dinh Thien‐Ly Julia , Rogg Manuel , Cosenza‐Contreras Miguel , Li Mujia , Zirngibl Max , Pinter Niko , Kurowski Konrad , Hause Frank , Pauli Lena , Imberg Fiona , Huynh Alana , Schmid Marlene , Glavinsky Ievgen , Braun Luisa , Van Wymersch Clara , Bergmann Luise , Ungefug Xenia , Kunz Marion , Werner Tilman , Bernhard Patrick , Espadas Guadalupe , Brombacher Eva , Schueler Julia , Sabido Eduard , Kreutz Clemens , Gratzke Christian , Werner Martin , Grabbert Markus , Bronsert Peter , Schell Christoph , Schilling Oliver
Published: November 2024

We present the proteomic profiling of 79 bladder cancers, including treatment‐naïve non‐muscle‐invasive bladder cancer (NMIBC, n = 17), muscle‐invasive bladder cancer (MIBC, n = 51), and neoadjuvant‐treated MIBC (n = 11). Proteins were extracted from formalin‐fixed, paraffin‐embedded samples and analyzed using data‐independent acquisition, yielding >8,000 quantified proteins. MIBC, compared to NMIBC, shows an extracellular matrix (ECM) and immune response signature as well as alteration of the metabolic proteome together with concomitant depletion of proteins involved in cell–cell adhesion and lipid metabolism. Neoadjuvant treatment did not consistently impact the proteome of the residual tumor mass. NMIBC presents two proteomic subgroups that correlate with histological grade and feature signatures of cell adhesion or lipid/DNA metabolism. Treatment‐naïve MIBC presents three proteomic subgroups with resemblance to the basal‐squamous, stroma‐rich, or luminal subtypes and signatures of metabolism, immune functionality, or ECM. The metabolic subgroup presents an immune‐depleted microenvironment, whereas the ECM and immune subgroups are enriched for markers of M2‐like tumor‐associated macrophages and dendritic cells. Markers for natural killer cells are exclusive for the ECM subgroup, and markers for cytotoxic T cells are a hallmark of the immune subgroup. Endogenous proteolysis is increased in MIBC alongside upregulation of matrix metalloproteases, including MMP‐14. Genomic panel sequencing yielded the prototypical profile of prevalent FGRF3 alterations in NMIBC and TP53 alterations in MIBC. Tumor–stroma interactions of MIBC were investigated by proteomic analysis of patient‐derived xenografts, highlighting specific tumor and stroma contributions to the matrisome and tumor‐induced stromal proteome phenotypes. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.