bluuebunny/crossref_metadata_2025_split huggingface dataset:
An empirical analysis of overall survival in drug approvals by the US FDA (2006–2023)
Authors: Elbaz Josh , Haslam Alyson , Prasad Vinay 
Published: April 2024

AbstractBackgroundThe US Food and Drug Administration (FDA) has expanded the use of surrogate markers in drugs approved for oncology/hematology indications. This has likely resulted in a greater number of approvals and possibly drugs coming to market faster, but it is unknown whether these drugs also improve overall survival (OS) for patients taking them.MethodsWe sought to estimate the percentage of oncology drugs that have shown to improve OS in a cross‐sectional analysis of US FDA oncology drug approvals (2006–2023). We searched for OS data in registration trials and the peer‐reviewed literature.ResultsWe found 392 oncology drug approvals. Eighty‐seven (22%) drug approvals were based on OS, 147 drug approvals were later tested for OS benefit (38% of all approvals and 48% of drugs approved on a surrogate), and 130 (33%) have yet to be tested for OS benefit. Of the 147 drug approvals later tested for OS, 109 (28% of all approvals and 74% of drugs later tested for OS) have yet to show OS benefit, whereas 38 (10% of all approvals and 26% of drugs later tested for OS benefit) were later shown to have OS benefit. In total, 125 out of 392 (32%) drugs approved for any indication have been shown to improve OS benefit at some point, and 267 (68%) have yet to show approval.ConclusionAbout 32% of all oncology drug approvals have evidence for an improvement in OS. Higher standards are needed in drug regulation to ensure that approved drugs are delivering better patient outcomes, specifically in regards to survival.
Endogenous Antimicrobial‐Immunomodulatory Molecules: Networking Biomolecules of Innate Immunity
Authors: Weaver Donald F. 
Published: April 2024

AbstractEndogenous antimicrobial‐immunomodulatory molecules (EAIMs) are essential to immune‐mediated human health and evolution. Conventionally, antimicrobial peptides (AMPs) have been regarded as the dominant endogenous antimicrobial molecule; however, AMPs are not sufficient to account for the full spectrum of antimicrobial‐immunomodulatory duality occurring within the human body. The threat posed by pathogenic microbes is pervasive with the capacity for widespread impact across many organ systems and multiple biochemical pathways; accordingly, the host needs the capacity to react with an equally diverse response. This can be attained by having EAIMs that traverse the full range of molecular size (small to large molecules) and structural diversity (including molecules other than peptides). This review identifies multiple molecules (peptide/protein, lipid, carbohydrate, nucleic acid, small organic molecule, and metallic cation) as EAIMs and discusses the possibility of cooperative, additive effects amongst the various EAIM classes during the host response to a microbial assault. This comprehensive consideration of the full molecular diversity of EAIMs enables the conclusion that EAIMs constitute a previously uncatalogued structurally diverse and collectively underappreciated immuno‐active group of integrated molecular responders within the innate immune system's first line of defence.
Screening and identification of fetal alcohol spectrum disorder in criminal legal settings: A realist review
Authors: Jewell Emma , Dunleavy Bianka , Faitakis Martina , Pun Jessica W. , Moss Sarah , Pei Jacqueline , Mela Mansfield , Flannigan Katherine , Tremblay Melissa , McLachlan Kaitlyn 
Published: April 2024

AbstractBackgroundScreening for fetal alcohol spectrum disorder (FASD) has been identified as a promising approach to improve recognition, understanding and effective response to the unique needs of those with FASD in criminal legal settings. However, to date, there has been limited synthesis of relevant screening tools, indicators, or implementation considerations in this context.AimsThe present review aimed to synthesise evidence and develop a conceptual framework for understanding how, when, why, for whom and by whom FASD screening tools, items and/or indicators and characteristics serve to accurately identify people with FASD in criminal legal contexts, with consideration of individual and system needs relevant to effective implementation and response.MethodsA preregistered search was conducted using a modified realist review framework for both peer‐reviewed articles and grey literature. Included sources were available in English, which focused on individuals with prenatal alcohol exposure and/or FASD with criminal legal involvement and offered new empirical evidence. Sources were reviewed using the Quality Control Tool for Screening Titles and Abstracts by Second Reviewer framework, extracted using a structured coding form and narratively synthesised.ResultsThe search yielded 52 sources, 11 FASD screening tools designed for or applied in criminal legal settings and 38 potential FASD indicators or characteristics relevant to identifying people who may have FASD in criminal legal settings, organised into six conceptually related domains. There was limited evidence supporting the psychometric properties of screening tools across populations or settings, though growing evidence highlights the promise of some instruments. Although few studies characterised potential considerations to be made when implementing a screening tool or approach, both system and individual level needs related to recognising and effectively responding to FASD in criminal legal contexts were identified, and findings revealed strong support among legal and clinical professionals regarding the need for FASD screening in these settings.ConclusionsFindings of this review can be used to inform the development, selection, implementation and evaluation of FASD screening tools in criminal legal settings and underscore a continued need for enhanced resources, policy and cross‐sectoral response to better support the needs of people with FASD in the criminal legal contexts.
Hepatic micro‐abscesses as an unusual initial presentation of systemic lupus erythematosus: A case report
Authors: Sasi Sreethish , Eltahir Mugahid , Ibrahim Ezzeddin , Padmakumari Aishwariya , Kolleri Jouhar , Abdallah Tasneem , Shehatta Ahmed Labib , Hadwan Nawal , Jaouni Hani , Al‐Maslamani Muna 
Published: April 2024

Key Clinical MessageHepatic micro‐abscesses can be a rare initial presentation of systemic lupus erythematosus (SLE). This case highlights the importance of considering autoimmune etiologies when infectious causes are ruled out and emphasizes the need for early recognition and appropriate treatment of atypical hepatic manifestations in SLE to achieve favorable outcomes.AbstractSystemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs, including the liver. While hepatic involvement in SLE is typically subclinical or associated with mild liver enzyme elevations, rare manifestations such as hepatic micro‐abscesses and hepatic vasculitis have been reported. We report the case of a 27‐year‐old female who presented with persistent high‐grade fever, bilateral exudative lymphocytic pleural effusion, hepatic micro‐abscesses, anemia, and lymphopenia. Despite extensive investigations and antibiotic therapy, the patient's condition continued to worsen. The diagnosis of hepatic vasculitis, a rare manifestation of SLE, was ultimately made based on clinical suspicion, positive autoimmune markers, and negative septic workup. The patient responded well to high‐dose corticosteroid therapy and intravenous immunoglobulin, with resolution of liver lesions and clinical improvement. Hepatic involvement in SLE is diverse, and atypical presentations can pose diagnostic challenges. Hepatic vasculitis, although rare, should be considered in SLE patients presenting with liver lesions. The management involves immunosuppressive therapy, and prompt diagnosis is crucial to prevent further vascular damage. Hepatic micro‐abscesses, another rare manifestation of SLE, are thought to result from immune complex deposition. The exact pathogenesis remains unclear. Hepatic micro‐abscesses can have both infectious and non‐infectious causes, and it is very important to rule out common microbial pathogens. Treatment focuses on managing the underlying SLE activity with immunosuppressive agents. This case highlights the diagnostic challenges and management considerations in atypical hepatic manifestations of SLE. Awareness of rare presentations and collaboration among multiple specialties are essential for accurate diagnosis and appropriate treatment.
Be prepared for the unexpected: Mind‐stretching in ST‐elevation myocardial infarction with situs inversus totalis
Authors: Viggiani Giacomo , Ibrahim Tareq , Allescher Julia , Steger Alexander 
Published: April 2024

Key Clinical MessageSitus inversus totalis is a rare diagnosis, but the likelihood of experiencing myocardial infarction is presumed to be comparable to the general population average. In individuals exhibiting situs inversus with suspected myocardial infarction, ECG recording, including right precordial leads, is crucial for diagnostic assessment. Coronary angiography and intervention should be performed with standard equipment using inverted maneuvers and radiographic projections.
Unlocking the Potential of Bismuth‐Based Materials in Supercapacitor Technology: A Comprehensive Review
Authors: Yetiman Sevda , Peçenek Hilal , Dokan Fatma Kılıç , Sanduvaç Senem , Serdar Onses Mustafa , Yılmaz Erkan , Sahmetlioglu Ertugrul 
Published: April 2024

AbstractSupercapacitors (SCs) have attracted significant attention in the realm of energy storage devices due to their exceptional features, such as enhanced charge storage capacity, fast charge‐discharge rates, and high power density. The emergence of cost‐effective and highly productive SCs is a topic of interest among industrial and scientific communities. Ferrites with a perovskite crystal structure are often considered excellent electrode materials due to their intrinsic properties, affordability, low environmental impact, and widespread availability. An in‐depth investigation of perovskite ferrites in the context of SCs is necessary to advance the understanding of these materials. The techniques used in the synthesis of ABO3‐type perovskite bismuth ferrite materials are comprehensively reviewed in this review. The review starts by analyzing various types of SCs classified based on their electrode materials. The review provides a comprehensive understanding of the design and functionality of these devices, serving as an important source of inspiration for new methods of synthesis and fabrication methodologies that aim to produce environmentally friendly SCs.
Probing Carbon Materials Towards the Vanadium(IV)/(V) Reaction by Scanning Electrochemical Microscopy
Authors: Steimecke Matthias , Carthäuser Jens , Fiedler Lena , Dieterich Emil , Bron Michael 
Published: April 2024

AbstractA method is presented to quantitatively analyze the reduction of vanadium(V) to vanadium(IV) over two flat carbon substrates (glassy carbon and graphite foil) using the feedback mode of scanning electrochemical microscopy. A pulse profile is validated and applied during approach curve experiments of a 10 μm Pt microelectrode. By fitting the approach curve data, electron transfer constants are calculated for various potentials and k0 is extracted from the corresponding Tafel plot. Furthermore, surface functional groups were introduced to the carbon substrates by acid treatment; however, kinetic parameters of the sluggish reduction reaction were only influenced to a minor extent. Finally, the same approach, combined with in situ‐Raman microscopy, is applied to a single graphene layer using a 2.7 μm Pt microelectrode. In this case, increased activity for both, the vanadium(V) reduction and vanadium(IV) oxidation reaction, was found close to the graphene edge sites by means of electrochemical microscopy for the first time.
Senolysis of gemcitabine‐induced senescent human pancreatic cancer cells
Authors: Hoque Mohammad Mahbubul , Iida Yuichi , Kotani Hitoshi , Harada Mamoru 
Published: April 2024

AbstractIntroductionGemcitabine (GEM) is often used to treat pancreatic cancer. Many anti‐cancer drugs induce cancer cell death, but some cells survive after cell cycle arrest. Such a response to DNA damage is termed cellular senescence. Certain drugs, including the Bcl‐2‐family inhibitor ABT‐263, kill senescent cells; this is termed senolysis. In this study, we examined the therapeutic benefits of ABT‐263 in GEM‐induced senescence of human pancreatic cancer cells.Methods and ResultsOf four pancreatic cancer cell lines (PANC‐1, AsPC‐1, CFPAC‐1, and PANC10.05), GEM induced senescent features in PANC‐1 and AsPC‐1 cells, including increases in the cell sizes and expression levels of mRNAs encoding interleukin (IL)‐6/IL‐8 and induction of β‐galactosidase. Successive treatment with GEM and ABT‐263 triggered apoptosis in PANC‐1 and AsPC‐1 cells and suppressed colony formation significantly. Senolysis of GEM‐induced senescent pancreatic cancer cells by ABT‐263 was triggered by a Bcl‐xL inhibitor, but not by a Bcl‐2 inhibitor, suggesting a central role for Bcl‐xL in senolysis. In a xenograft mouse model, combined treatment with GEM and ABT‐737 (an ABT‐263 analog exhibiting the same specificity) suppressed in vivo growth of AsPC‐1 significantly.ConclusionTogether, our results indicate that sequential treatment with GEM and senolytic drugs effectively kill human pancreatic cancer cells.
Principal Singlet Fission Properties Of Twisted Acenes
Authors: Stanger Amnon 
Published: April 2024

AbstractAcenes, especially tetracene derivatives, are used as singlet fission materials. The recent synthesis of Dodecaphenyl tetracene (showing end‐to‐end twist angles of 96–98 degrees) and twisted anthracene derivatives show that the synthesis of twisted linear oligoacenes is possible. Energy calculations and NICS‐X‐scan studies predict that twisted acenes may be better singlet fission materials compared to their planar analogues.
Unlocking the Secrets of Soil: Exploring the Microbiome and Its Applications—Part 2
Authors: Ghimire Om Prakash , Nepal Jaya , Poudel Pratima , Powar Suraj 
Published: April 2024

AbstractThe term “microbiome” refers to a collective assembly of microorganisms within a specific environment, including fungi, bacteria, and viruses, influencing dynamic functions within the system. Microbes play a pivotal role in the production of various food items, wines, and medicinal compounds. Their significance in agriculture and ecology is monumental, which will be explored in this two‐part article. In this second part, we’ll discuss the microbiome’s role in plant adaptation and driving the biogeochemical processes in soil across scales, mathematical and statistical modeling of plant–soil–microbe interactions, and areas of future research.
N6‐methyladenosine‐modified circTEAD1 stabilizes Yap1 mRNA to promote chordoma tumorigenesis
Authors: Li Hanwen , Tang Yingchuang , Ruan Xingbang , Zhang Junxin , Liu Hao , Yu Shiyu , Chen Hao , Yang Huilin , Zhang Kai , Chen Kangwu 
Published: April 2024

AbstractBackgroundChordoma, a rare bone tumour with aggressive local invasion and high recurrence rate with limited understanding of its molecular mechanisms. Circular RNAs (circRNAs) have been extensively implicated in tumorigenesis, yet their involvement in chordoma remains largely unexplored. N6‐methyladenosine (m6A) modification holds a crucial function in regulating protein translation, RNA degradation and transcription.MethodsInitially, screening and validation of circTEAD1 in chordoma were conducted by high‐throughput sequencing. Subsequently, sh‐circTEAD1 and an overexpression plasmid were constructed. Colony formation assays, cell counting kit‐8, Transwell and wound healing assays were utilized to validate the function of circTEAD1 in vitro. RNA pull‐down assays identified the binding proteins of circTEAD1, which underwent verification through RNA immunoprecipitation (RIP). Methylated RIP assays were conducted to detect the m6A binding sites. Following this, luciferase assay, RT‐qPCR, RIP and Western blotting analyses were conducted, revealing that Yap1 was the direct target of circTEAD1. Afterwards, the same methods were utilized for the validation of the function of Yap1 in chordoma in vitro. Finally, the regulatory relationship between circTEAD1 and Yap1 in chordoma was verified by an in vivo tumour formation assay.ResultsCircTEAD1 was identified as an upregulated circRNA in chordoma specimens, with heightened circTEAD1 expression emerging as a prognostic indicator. In vitro experiments convincingly demonstrated that circTEAD1 significantly promoted chordoma cell invasion, migration and aggressiveness. Furthermore, the analysis revealed that methyltransferase‐like 3‐mediated m6A modification facilitated the cytoplasmic export of circTEAD1. The circTEAD1/IGF2BP3/Yap1 mRNA RNA‐protein ternary complex not only bolstered the stability of Yap1 mRNA but also exerted a pivotal role in driving chordoma tumorigenesis.ConclusionsIn this study, the role of m6A‐modified circTEAD1 in chordoma was identified. The findings offer novel insights into the potential molecular targets for chordoma therapy, shedding light on the intricate interplay between circRNAs, m6A modification and Yap1 mRNA in chordoma pathogenesis.
Chaos quantum optimization‐based layered diagnosis framework for faulty sensor node diagnosis and classification in wireless sensor networks
Authors: Babu Nagarajan , Santhosh Kumar Sripathi Venkata Naga 
Published: April 2024

SummaryNode faults are often influenced by factors such as physical component failure, communication module errors, battery exhaustion, and environmental factors. Various researchers have contributed to addressing the problem of detecting, diagnosing, and classifying faults in sensor networks. However, computational complexity and fault occurrence probability increase with the size of the network. In this context, an enhanced optimized layered diagnosis framework (OLDF) is proposed for detecting, diagnosing, and classifying sensor node faults. OLDF utilizes a deep belief network (DBN) with chaos quantum‐behaved particle swarm optimization (CQ‐PSO) for efficient diagnosis and classification of various sensor faults in the network. The proposed OLDF consists of two layers. In the first layer, optimized DBN with CQ‐PSO algorithm is employed to determine the fault type of the sensor nodes. Then, the fault type of sensor nodes that are classified in the first layer is given as input into the second layer of the OLDF algorithm to determine the fault severity in the network. Experimentation has been carried out by using the NS3 simulator for the OLDF framework with performance metrics such as classification accuracy, diagnosis accuracy, false positives, fault alarm rate, and average energy consumption. The validity of the proposed framework has been verified through comparisons with existing works such as MFD, INSA, FDRFC, and HFD. From the comparative analysis carried out, it is apparent that the proposed framework achieves a high classification accuracy of 89.94% and diagnosis accuracy of 93.21%, with less false positive rate, and utilizes minimum energy when compared with its counterparts.
Scale‐dependent effects of herbivory on moss communities in Arctic wetlands: A 25‐year experiment
Authors: Liu Chao , Gauthier Gilles , Gignac Charles , Lévesque Esther , Rochefort Line 
Published: April 2024

AbstractArctic ecosystems are undergoing rapid changes, including increasing disturbance by herbivore populations, which can affect plant species coexistence and community assemblages. Although the significance of mosses in Arctic wetlands is well recognized, the long‐term influence of medium‐sized herbivores on the composition of moss communities has received limited attention. We used data from a long‐term (25 years) Greater Snow Goose (Anser caerulescens atlanticus) exclusion experiment in Arctic tundra wetlands to assess changes in the composition of moss communities at multiple spatial scales (cell, 4 cm2; quadrat, 100 cm2; exclosure, 16 m2). We investigated how snow goose grazing and grubbing can alter the composition of the moss community by measuring changes in alpha and beta diversity, as well as in the strength of plant interspecific interactions between moss species. Our results indicate that goose foraging significantly increased species diversity (richness, evenness, and inverse Simpson index) of moss communities at the cell and quadrat scales but not the exclosure scale. Goose foraging reduced the dissimilarity (beta diversity) of moss communities at all three scales, mainly due to decreased species turnover. Furthermore, goose foraging increased positive interaction between moss species pairs. These findings emphasize the critical role of geese in promoting moss species coexistence and increasing homogeneity in Arctic wetlands. This study illustrates how top‐down regulation by herbivores can alter plant communities in Arctic wetlands and highlights the importance of considering herbivores when examining the response of Arctic plant biodiversity to future climate change.
Efficacy of catheter ablation for atrial fibrillation in heart failure: a meta‐analysis of randomized controlled trials
Authors: Zhang Zhongyin , Zheng Yan , He Wenxiu , Wei Jiahe , Li Pengzhan , Zhong Guoqiang , Jiang Zhiyuan 
Published: April 2024

AbstractThe study aims to evaluate whether rhythm control by catheter ablation is superior to medical therapy for the patients with atrial fibrillation (AF) and heart failure (HF). The literatures were searched by using PubMed, Cochrane Library, Embase, and Web of Science databases up to 12 October 2023. The randomized controlled trials (RCTs) comparing rhythm control using catheter ablation vs. medical therapy in AF patients with HF were pooled. The primary outcomes included all‐cause mortality, HF re‐hospitalization, and stroke, and the secondary outcomes included left ventricular ejection fraction (LVEF), atrial tachyarrythmia recurrence, quality of life (Minnesota Living with Heart Failure Questionnaire score, MLHFQ score), 6 min walking distance (6MWD), the level of N‐terminal B‐type natriuretic peptide precursor (NT‐proBNP), and adverse events. Nine RCTs involving in 2293 patients met the inclusion criteria. Compared with medical therapy, catheter ablation reduced all‐cause mortality [10.07% (121/1201) vs. 15.26% (175/1147), risk ratio (RR):0.60, 95% confidence interval (CI): 0.48–0.74, P < 0.00001, I2 = 0%] and the rate of HF re‐hospitalization (RR: 0.65, P = 0.02, 95% CI: 0.45 to 0.94, I2 = 74%), but had no obvious difference in incidence of stroke (RR: 0.67, P = 0.27, 95% CI: 0.32 to 1.38, I2 = 0%). Catheter ablation enhanced LVEF [mean difference (MD), 6.26%, P < 0.00001, I2 = 89%], reduced AT recurrence (RR: 0.37, P < 0.00001, 95% CI: 0.26 to 0.52, I2 = 89%), improved the quality of life (MLHFQ score) (MD: −6.83, P = 0.003, I2 = 67%), elevated 6MWD (MD: 15.92, P = 0.006, I2 = 76%), and diminished the level NT‐proBNP (MD: −44.19, P < 0.00001, I2 = 75%), but had no significant difference in adverse events [25.81% (310/1201) vs. 30.25% (347/1147), RR: 0.81, 95% CI: 0.65–1.01, P = 0.06, I2 = 55%]. Catheter ablation as rhythm control strategy substantially enhances the survival rate, reduces HF re‐hospitalization, increases the rate of sinus rhythm maintenance, improves the left ventricular function and the quality of life for AF patients with HF, and has similar safety, compared with medical therapy. The rhythm control by catheter ablation may be a better strategy for the AF patients with HF.