bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine Learning‐Driven Discovery of Structurally Related Natural Products as Activators of the Cardiac Calcium Pump SERCA2a
Authors: Cruz‐Cortés Carlos , Fernández‐de Gortari Eli , Aguayo‐Ortiz Rodrigo , Šeflová Jaroslava , Ard Adam , Clasby Martin , Anumonwo Justus , Michel Espinoza‐Fonseca L. 
Published: January 2025

AbstractA key molecular dysfunction in heart failure is the reduced activity of the cardiac sarcoplasmic reticulum Ca2+‐ATPase (SERCA2a) in cardiac muscle cells. Reactivating SERCA2a improves cardiac function in heart failure models, making it a validated target and an attractive therapeutic approach for heart failure therapy. However, finding small‐molecule SERCA2a activators is challenging. In this study, we used a machine learning‐based virtual screening to identify SERCA2a activators among 57,423 natural products. The machine learning model identified ten structurally related natural products from Zingiber officinale, Aframomum melegueta, Alpinia officinarum, Alpinia oxyphylla, and Capsicum (chili peppers) as SERCA2a activators. Initial ATPase assays showed seven of these activate SERCA at low micromolar concentrations. Notably, two natural products, Yakuchinone A and Alpinoid D displayed robust concentration‐dependent responses in primary ATPase activity assays, efficient lipid bilayer binding and permeation in atomistic simulations, and enhanced intracellular Ca2+ transport in adult mouse cardiac cells. While these natural products exert off‐target effects on Ca2+ signaling, these compounds offer promising avenues for the design and optimization of lead compounds. In conclusion, this study increases the array of calcium pump effectors and provides new scaffolds for the development of novel SERCA2a activators as new therapies for heart failure.
A phase 2 basket study of talabostat, a small‐molecule inhibitor of dipeptidyl peptidases, administered in combination with pembrolizumab in patients with advanced solid cancers
Authors: Ahmed Jibran , Janku Filip , Karp Daniel D. , Piha‐Paul Sarina A. , Tsimberidou Apostolia M. , Yap Timothy Anthony , Stephen Bettzy , Yang Yali , Gurses Serdar , Liu Qian , Song Juhee , Meric‐Bernstam Funda , Naing Aung 
Published: January 2025

AbstractBackgroundTalabostat, an oral small molecule inhibitor of dipeptidyl peptidases (DPP4 and DPP8/9), has shown synergistic activity with immune checkpoint inhibitors in preclinical studies. This open label, phase 2 basket trial assessed the antitumor activity of combining talabostat and pembrolizumab (anti–programmed death‐1 antibody) in advanced solid tumor patients.MethodsThe primary objective was assessment of dose‐limiting toxicity (DLT) rates in the first six patients (lead‐in stage) and response rate (efficacy stage; included cohort A [checkpoint inhibitor (ICI) naive] and cohort B [ICI pretreated]) for the study treatment using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune RECIST (iRECIST). Efficacy was assessed using a Bayesian optimal phase 2 design.ResultsA total of 31 patients enrolled in this trial (14 in cohort A, 17 in cohort B). The median age was 61 years; 17 (55%) patients were male and 21 (68%) patients were White. Among 19 (61%) patients evaluable for response, the best response was stable disease in nine patients, unconfirmed progressive disease in seven patients, and clinical progressive disease in three patients based on iRECIST. Disease control rate was 47%. One patient with programmed death‐ligand 1 negative, microsatellite stable endometrial cancer had unconfirmed partial response. Median progression‐free survival was 2.7 months; median overall survival was 20.5 months. One patient (cohort A) experienced a grade 4 hypotension as a DLT and treatment discontinuation. The most common toxicities were hypotension (22.6%), fatigue (9.7%), diarrhea, rash, thrombocytopenia, vomiting, syncope, general disorders and administration site conditions‐other, and skin and subcutaneous tissue disorders‐other, each in 6.5% of patients.ConclusionsThis study of the combination of talabostat and pembrolizumab in patients with advanced solid tumors demonstrated predictable adverse events and limited activity. The combination was shown to be safe. Efficacy data shows immune stable disease in nine of 19 evaluable patients, and an unconfirmed immune partial response in a patient with endometrial cancer.
Sex Differences in Lung Cancer Characteristics at Diagnosis: A Nationwide Register‐Based Study From the Faroe Islands (2015–2020)
Authors: Lindenskov Annika H. , Potts Halla , Kristiansen Marnar F. , Petersen Maria S. , Strøm Marin 
Published: January 2025

ABSTRACTBackgroundSex differences in lung cancer survival are well‐established, but the gap between Faroese men and women is especially pronounced. Faroese women have some of the highest 1‐ and 5‐year relative survival rates in the Nordic region, while Faroese men have some of the lowest. This study investigates these survival disparities by analyzing demographic, clinical, and temporal factors in Faroese lung cancer patients from 2015 to 2020.MethodsAll lung cancer cases registered in the Faroese Cancer Registry from 2015 to 2020 were included. Data on age, sex, civil status, cancer type, stage, smoking history, comorbidities, and performance status were extracted from electronic patient records. Sex‐based differences were analyzed and overall survival rates were estimated using Kaplan–Meier plots.ResultsSignificant sex differences were observed in cancer staging at diagnosis (p = 0.03), with 25.8% of women diagnosed at Stage I compared to 8.8% of men. Gender‐specific patterns also emerged: women hadlonger symptomatic periods, while men experienced longer diagnostic and treatment times, though with overlapping confidence intervals.ConclusionsOur findings reveal significant sex disparities in lung cancer staging at diagnosis in the Faroe Islands, which may the survival differences. The longer diagnostic period in men likely contributes to their lower survival rates. These results highlight the need for targeted interventions to reduce these disparities and improve patient outcomes.
Recurrent Thymic Carcinoma Treated With Median Sternotomy, Innominate Vein Replacement for Superior Vena Cava, and Iodide Implantation: A Case Report and Review of the Literature
Authors: Chen Zhong‐zheng , Qu Wen‐dong , Zhang Xing‐shu , Song Yong‐xiang 
Published: January 2025

ABSTRACTBackgroundNeuroendocrine tumors of the thymus (NETT) are rare and malignant tumors that arise in the anterior mediastinum. These tumors can exhibit aggressive behavior and may involve surrounding critical structures, such as the superior vena cava. This case contributes to the literature by presenting a recurrent thymic carcinoma with invasion of major blood vessels, including the superior vena cava, and the complexities involved in its surgical management.CaseA 51‐year‐old male with no significant medical history presented with eyelid edema and a mediastinal mass. Diagnostic imaging, including positron emission tomography/computed tomography (PET/CT), revealed a malignant anterior mediastinal mass with possible metastasis. The patient underwent thoracoscopic resection of the tumor and wedge resection of the left upper lobe of the lung. Postoperative pathology confirmed a neuroendocrine carcinoma (G3), staged as Masaoka IVa. Despite aggressive surgery, the patient developed recurrent metastasis involving mediastinal lymph nodes and the superior vena cava. The patient underwent complex surgery involving vascular replacement, pericardial resection, and superior vena cava reconstruction, followed by adjuvant chemotherapy, radiotherapy, and immunotherapy.ConclusionThis case highlights the challenges of managing advanced NETT, particularly with invasion of major vascular structures. It emphasizes the importance of early diagnosis, complete surgical resection, and tailored adjuvant therapies, including chemotherapy, radiotherapy, and immunotherapy, to improve survival outcomes. The lessons learned from this case contribute to refining treatment strategies for similar cases, advocating for aggressive surgical approaches and the potential benefit of novel therapeutic agents in the management of advanced NETT.
The Critical Role of Retailers in Leveraging Sustainability of a Global Supply Chain
Authors: Wright Dale R. , Bekessy Sarah A. , Gordon Ascelin , Bennett Ruth E. , Rodewald Amanda D. , Garrard Georgia E. , Lentini Pia E. , Selinske Matthew J. 
Published: January 2025

ABSTRACTShade‐grown coffee farming supports biodiversity and generates additional sustainability outcomes, though the drivers of this approach are poorly understood. Previous research on coffee sustainability has focused on producers or consumers, potentially overlooking the role of retailers in commodity supply chains. We conducted semi‐structured interviews with 19 coffee traders, roasters and retailers in Melbourne, Australia to understand their coffee purchasing decisions, sustainability initiatives and their underlying motivations. Our findings indicate that retailers occupy a critical point in a supply chain from which to leverage sustainability transformations: they can support sustainable approaches at origin, in partnership with farmers and other actors, whilst also undertaking initiatives at the consumer end of the supply chain, thereby exerting bidirectional influence in supply chains. Place‐based environmental initiatives were especially likely to be implemented by large multinational traders and independent roasters operating with purpose‐driven business models that aim to deliver positive environmental, social and economic outcomes for all stakeholders. Behaviour change interventions should target retailers in global supply chains to support sustainability outcomes.
Mapping the Literature Trends of Corporate Social Responsibility and Cost of Capital: A Systematic Literature Review
Authors: AL‐Akheli Aseer , Tan HongTao , A. Hazaea Saddam , ELfarra Barakat , Al‐Zubairi Ammar 
Published: January 2025

ABSTRACTCorporate social responsibility (CSR) has emerged as a strategic framework for enhancing corporate reputation, mitigating financial risks and improving access to capital. However, empirical evidence on its financial implications remains inconsistent, highlighting notable gaps in understanding the relationship between CSR practices and the cost of capital (COC). This systematic literature review (SLR) analyses 104 Scopus‐indexed studies published between 2010 and 2023 to examine this relationship. The findings suggest that CSR initiatives contribute to improved financial performance, enhance firm reputation, and reduce capital costs. Proactive CSR strategies not only align with ethical imperatives but also deliver long‐term value by fostering stakeholder confidence and mitigating financing risks. The review emphasises the critical role of CSR, particularly in environmental compliance, as an integral component of financial strategy and risk management. It provides evidence that CSR initiatives enhance investment efficiency and lower financing costs, offering a refined perspective on their financial significance. Moreover, it paves the way for future research on global reporting standards and evaluation methods. These insights are highly relevant to policymakers, regulators, investors, creditors, and practitioners aiming to integrate sustainability with economic goals while reducing the COC.
Nature of Solvent/Nonsolvent Strategy in Achieving Superior Polybenzimidazole Membrane for Vanadium Redox Flow Battery
Authors: Su Yuke , Liu Suqin , Zhu Weiwei , Huang Kui , Mu Guangyuan , Jiang Peng , Liu Jianhui , Yang Guang , He Zhen , Wang Jue 
Published: January 2025

AbstractThe tightly connected structure of polybenzimidazole (PBI) membrane can be relaxed by solvent/nonsolvent solution to achieve a high proton conductivity for vanadium redox flow battery (VRFB). However, the nature behind the solvent/nonsolvent strategy is not unraveled. This work proposes a guideline to analyze the effect of PBI membrane relaxing formulas based on the interactions between different components in membranes. The supreme‐efficient PBI membrane derived by the DMSO/formamide formula according to the guideline displays a marvelous performance for VRFB, with the proton conductivity boosted by 4300 % (from 1.93 to 83.33 mS cm−1), and VRFB assembled with this membrane achieves an outstanding energy efficiency of 82.5 % under 200 mA cm−2. Moreover, this work profoundly unravels the structure, property and performance relationship of PBI membrane, which is of great value for the development of membranes.
2D/3D Heterojunction Engineering for Hole Transport Layer‐Free Carbon‐Based Perovskite Solar Cells
Authors: Li Lingcong , Lai Yinlong , Rao Huashang , Cai Weizi , Zhong Xinhua , Guo Huishi , Pan Zhenxiao 
Published: January 2025

AbstractHole transport layer (HTL)‐free carbon‐based perovskite solar cells (C‐PSCs) own outstanding potential for commercial applications due to their attractive advantages of low cost and superior stability. However, the abundant defects and mismatched energy levels at the interface of the perovskite/carbon electrode severely limit the device efficiency and stability. Constructing a 2D layer on the surface of 3D perovskite films to form 2D/3D heterojunctions has been demonstrated to be an effective method of passivating surface defects and optimizing the energy level alignment in almost all kinds of PSCs. Due to the unique structure of HTL‐free C‐PSCs, 2D/3D heterojunctions play especially important roles. This review article summarizes the reports of 2D/3D perovskite heterojunctions in HTL‐free C‐PSCs. It describes the contributions of 2D/3D heterojunctions in terms of their roles in defect passivation, energy level optimization, and stability improvement. Finally, challenges and prospects of 2D/3D heterojunction for further development of HTL‐free C‐PSCs are highlighted.
Size‐Dependency of Electrochemically Grown Copper Nanoclusters Derived from Single Copper Atoms for the CO Reduction Reaction
Authors: Ohashi Keitaro , Nishimura Kosei , Nagita Kaito , Hashimoto Takuya , Nakahata Shoko , Harada Takashi , Ina Toshiaki , Nakanishi Shuji , Kamiya Kazuhide 
Published: January 2025

AbstractElectrochemically grown copper nanoclusters (CuNCs: <3 nm) from single‐atom catalysts have recently attracted intensive attention as electrocatalysts for CO2 and CO reduction reaction (CO2RR/CORR) because they exhibit distinct product selectivity compared with conventional Cu nanoparticles (typically larger than 10nm). Herein, we conducted a detailed investigation into the size dependence of CuNCs on selectivity for multicarbon (C2+) production in CORR. These nanoclusters were electrochemically grown from single Cu atoms dispersed on covalent triazine frameworks (Cu‐CTFs). Operando X‐ray absorption fine structure analysis revealed that Cu‐CTFs containing 1.21 wt % and 0.41 wt % Cu (Cu(h)‐CTFs and Cu(l)‐CTFs, respectively) formed CuNCs of 2.0 and 1.1 nm, respectively, at −1.0 V vs. RHE. The selectivity for CORR products was particularly dependent on the size of CuNCs, with the Faraday efficiencies of C2+ products being 52.3 % and 32.7 % at −1.0 V vs. RHE with Cu(h)‐CTFs and Cu(l)‐CTFs, respectively. Spherical CuNCs modeling revealed that larger cluster sizes led to a greater proportion of a surface coordination number (SCN) of 8 or 9. Density functional calculations revealed that the CO dimerization reaction was more likely to proceed at SCNs of 8 or 9 compared to SCN of 7 because of the stability of the *OCCO intermediate.
Energy Harvesting–Assisted Two‐User Cooperative NOMA With Ambient Backscattering
Authors: Ghosh Priyanka , Dhar Roy Sanjay , Kundu Sumit 
Published: January 2025

ABSTRACTRecently, ambient backscatter‐based communication is considered as an appealing approach, which enables energy‐constrained nodes to transmit by backscattering ambient signals, and it has the potential of being integrated with RF‐powered NOMA network. In this paper, we analyze the outage performance of a two‐node system that works on ambient backscattered signal. One energy harvesting relay, working in time switching relaying (TSR) mode, which assists the transmission of NOMA signal of two users, acts as a backscatter device (BD) to transmit its information to a closely located IoT node by backscattering the signal received from two users. The IoT node transmits its information to the relay by backscattering the signal while the relay transmits downlink NOMA to two destination users. We evaluate the outage performance of backscattered signal at the relay and IoT node. System outage of the NOMA users and throughput of the backscattered transmission are also derived. The effect of backscattering factor on individual and system outage of NOMA users, outage of BD users, and backscattered throughput is indicated. Further, we show the impact of time switching factor on outage and throughput of backscattered network. Ergodic capacity of backscattered network is also evaluated.
Endocytosis mediated by megalin and cubilin is involved in enamel development
Authors: Wang Aijia , Chen Yangxi , Zhang Xinye , Liu Ming , Liu Shumin , Kozyraki Renata , Chen Zhi 
Published: January 2025

AbstractBackgroundEndocytosis of enamel matrix proteins (EMPs) by ameloblasts is a key process in the mineralization of enamel during the maturation stage of amelogenesis. However, the relevant receptor mediating endocytosis of EMPs is still unclear. The aim of this study was to explore potential endocytic receptors involved in this process.ResultsTwo endocytic receptors, megalin, and cubilin, were found to be distributed in ameloblasts of mouse incisors and molars during the secretory and maturation stages. Megalin was located at the distal end of ameloblasts during the maturation stage when proteolysis and recycling were the most active. Megalin and cubilin were also expressed in an ameloblast‐lineage cell (ALC) line. The immunoelectron microscopy results showed that megalin was positively labeled on the vesicle structures of ALC, where endocytosis happened. Immunofluorescence showed that megalin and cubilin were colocalized with amelogenin, and the absorption of amelogenin was significantly reduced when megalin and cubilin were inhibited by their inhibitor, receptor‐associated protein (RAP). Knockdown of megalin and cubilin with siRNA also reduced the ability of ALC to absorb amelogenin.ConclusionsThe results of this study suggest that megalin and cubilin are involved in the absorption process of ameloblasts during amelogenesis.
Maintenance of Genetic Diversity Despite Population Fluctuations in the Lesser Prairie‐Chicken (Tympanuchus pallidicinctus)
Authors: Lawrence Andrew J. , Carleton Scott A. , Oyler‐McCance Sara J. , DeYoung Randy W. , Nichols Clay T. , Wright Timothy F. 
Published: January 2025

ABSTRACTAssessments of genetic diversity, structure, history, and effective population size (Ne) are critical for the conservation of imperiled populations. The lesser prairie‐chicken (Tympanuchus pallidicinctus) has experienced declines due to habitat loss, degradation, and fragmentation in addition to substantial population fluctuations with unknown effects on genetic diversity. Our objectives were to: (i) compare genetic diversity across three temporally discrete sampling periods (2002, 2007–2010, and 2013–2014) that are characterized by low or high population abundance; (ii) examine genetic diversity at lek and lek cluster spatial scales; (ii) identify potential bottlenecks and characterize genetic structure and relatedness; and (iii) estimate the regional Ne. We analyzed 194 samples across the shinnery oak prairie region of eastern New Mexico and western Texas using 13 microsatellite loci. Mean heterozygosity, allelic richness, and inbreeding coefficient were not significantly different between discrete sampling periods, suggesting that this population has maintained its genetic diversity across the sampled population fluctuations. We did not detect genetic structure using multiple Bayesian clustering approaches. Furthermore, there was no support for recent genetic bottlenecks, and we estimated that the Ne ranged from 229.5 (pcrit = 0.05, 95% CIs = 121.2–1023.1) to 349.1 (pcrit = 0.02, 95% CIs = 176.4–2895.2) during our final sampling period (2013–2014). Although we provide evidence for gene flow within this region, continued habitat loss and fragmentation that leads to population declines and isolation could increase the risk of genetic consequences. Continued monitoring of genetic diversity and increasing available habitat that supports robust populations of lesser prairie‐chickens may improve the likelihood of the species' persistence.
Voxel Volumes and Biomass: Estimating Vegetation Volume and Litter Accumulation of Exotic Annual Grasses Using Automated Ultra‐High‐Resolution SfM and Advanced Classification Techniques
Authors: Enterkine Josh , Hojatimalekshah Ahmad , Vermillion Monica , Van Der Weide Thomas , Arispe Sergio A. , Price William J. , Hulet April , Glenn Nancy F. 
Published: January 2025

ABSTRACTIn much of the northern Great Basin of the western United States, rangelands, and semi‐arid ecosystems invaded by exotic annual grasses such as cheatgrass (Bromus tectorum) and medusahead (Taeniatherum caput‐medusae) are experiencing an increasingly short fire cycle, which is compounding and persistent. Improving and expanding ground‐based field methods for measuring the above‐ground biomass (AGB) may enable more sample collections across a landscape and over succession regimes and better harmonize with other remote sensing techniques. Developments and increased adoption of unoccupied aerial systems (UAS) and instrumentation for vegetation monitoring enable greater understanding of vegetation in many ecosystems. Research to understand the relationship of traditional field measurements with remotely sensed data in rangeland environments is growing rapidly, and there is increasing interest in the use of aerial platforms to quantify AGB and fine‐fuel load at pasture and landscape scales. Our study uses relatively inexpensive handheld photography with custom quadrat sampling frames to collect and automatically reconstruct 3D models of the vegetation within 0.2 m2 quadrats (n = 288). Next, we examine the relationship between volumetric estimates of vegetation with biomass. We found that volumes calculated with 0.5 cm voxel sizes (0.125 cm3) most closely represented the range of biomass weights. We further develop methods to classify ground points, finding a 2% reduction in predictive ability compared with validation ground surface reconstructions. This finding is significant given that our study site is characterized by a dense litter layer covering the ground surface, making reconstruction challenging. Overall, our best reconstruction workflow had an R2 of 0.42, further emphasizing the importance of high‐resolution imagery and reconstruction techniques. Ultimately, we conclude that more work is needed of increasing extents (such as from UAS) to better understand and constrain uncertainties in volumetric estimations of biomass in ecosystems with high amounts of invasive annual grasses and fine‐fuel litter.
A Two‐Step, One‐Pot Baeyer‐Villiger Oxidation of Biomass‐Derived Levoglucosenone Derivatives to Chiral, C4‐Sustituted 5‐Hydroxymethyl Butyrolactones
Authors: Cummings Andrew , Rice Clare , Sheldrake Gary N. , Murnaghan Christopher W. J. 
Published: January 2025

AbstractA two‐step one‐pot rapid microwave assisted method has been developed for the Baeyer‐Villiger oxidation of biomass derived levoglucosenone (LGO) analogues. This method uses the acidic resin Amberlyst 15 as the catalyst and hydrogen peroxide as the oxidant in ethanol solution. A small library of C4‐substituted LGO analogues have been synthesised and oxidised using this method giving high yields in short times in each case. The purity of the recovered products was very high removing the need for chromatographic separation.