bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Trials Portfolio and Regulatory History of Idelalisib in Indolent Non-Hodgkin Lymphoma
Authors: Banerjee Titas , Kim Myung Sun , Haslam Alyson , Prasad Vinay 
Published: March 2023

ImportanceIdelalisib is a first-in-class phosphatidylinositol 3-kinase inhibitor that received US Food and Drug Administration accelerated approval in July 2014 as a single-agent treatment for relapsed follicular lymphoma (FL) and small lymphocytic lymphoma (SLL). Serious adverse effects were reported in 2016 leading to termination of postmarketing registry trials. However, idelalisib remained on the market until 2022 when Gilead voluntarily withdrew the drug for the accelerated approval indication.ObjectiveEvaluate the regulatory oversight of the accelerated approval pathway and evidence generation for idelalisib during premarketing (2008-2014), postmarketing (2014-2016), and premarketing withdrawal periods (2016-2022).Data SourcesClinicalTrials.gov, FDA.gov, PubMed database.Study SelectionClinical trials investigating the safety and effectiveness of idelalisib.Data Extraction and SynthesisStudy characteristics and relative risk (RR) of safety outcomes were abstracted. Data were pooled using random effects meta-analysis. The analysis was performed in October of 2022.Main Outcomes and MeasuresTrial status, recruitment status, publication status, serious adverse events (SAEs), fatal adverse events (FAEs), and all-cause mortality.ResultsOverall, 31 idelalisib trials met selection criteria. In total, 20 of 30 (65%) included SLL and/or FL; 13 (42%) trials were completed, 13 (42%) had published results, and 7 (23%) were randomized clinical trials (RCTs). Overall, 6 RCTs of idelalisib had publicly available data on safety outcomes. By the initial postmarketing period (2016), the cumulative RR for SAEs was 1.86 (95% CI, 1.63-2.11), for FAEs was 3.30 (95% CI, 1.56-7.00), and for death was 1.35 (95% CI, 0.85-2.12). In the premarketing withdrawal period, only a single phase 3 trial was enrolling patients for FL and was terminated. However, idelalisib was not withdrawn from the market until 2022. Gilead reported cumulative sales revenue of $842 million during market authorization (2014-2022) and annual sales had a steady decline from $168 million to $62 million during the premarketing withdrawal period (2016-2021).Conclusions and RelevanceFindings of this systematic review and meta-analysis show that serious risks of SAE, FAE, and death with idelalisib treatment were evident by 2016. However, idelalisib remained on the market for another 6 years, with minimal evidence generation. It was voluntarily withdrawn for FL and SLL accelerated approval indications coinciding with decreasing revenue generation. Closer attention for safety and effectiveness of drugs reaching market by accelerated approval is needed.
Rationale and processes of residential buyout programs: A review on buyout regulations and consequences in Japan and the U.S.
Authors: Ghezelloo Yegane , Kondo Tamiyo , Maly Elizabeth , Stanley Michelle , Meyer Michelle 
Published: March 2023

AbstractGovernment acquisition of residential land has played a growing role in the reconstruction of housing in safer places and reduction of water‐related risks. This paper explores how the rationales and processes of residential buyouts may result in different consequences for coastal recovery, mitigation, and residents' wellbeing referring to government documents and existing literature, we explored the characteristics of buyout programs in Japan and the U.S., identified consequences of mitigation and recovery, and deduced the effects of community buyouts. Our study revealed buyout programs could reduce risk exposure, enhance sustainable and resilient coastal rewilding, housing recovery, and building of community resilience. However, they could also contribute to limiting homeowners' opportunities to make their own choices to stay or relocate, the distribution of residents into unfamiliar communities, creation of checkerboard patterns of acquired properties, and un‐utilized vast vacant lands. These results suggest that planners and disaster managers need careful consideration to redesign and manage property acquisition programs that not only increase regional resilience, but also are equitable for affected residents and utilization of acquired lands.
Sustained‐Drug‐Release, Strong, and Anti‐Swelling Water‐Lipid Biphasic Hydrogels Prepared via Digital Light Processing 3D Printing for Protection against Osteoarthritis: Demonstration in a Porcine Model
Authors: Ding Guocheng , He Yangyang , Shi Yuanyuan , Maimaitimin Maihemuti , Zhang Xin , Huang Hongjie , Huang Wei , Yu Ran , Wang Jianquan 
Published: March 2023

AbstractOsteoarthritis is a serious disease affecting joint cartilage. Owing to poor blood supply, the meniscus and acetabular labrum of joints heal poorly after injury. However, the development of artificial alternatives to these components that have similar mechanical properties and cartilage‐protection ability is challenging. In this study, a strong hydrogel with a biomimetic microstructure is prepared with an emulsion‐type photosensitive resin, where both hydrophilic and hydrophobic monomers, photo‐initiator, and drugs can be adopted. In this system, the hydrophobic monomer forms uniformly dispersed aggregates after curing, improving the mechanical properties of the hydrogel significantly. Furthermore, the coordination bonds between nontoxic Zr4+ cations and sulfonic acid groups prevent hydrogel swelling. In addition, the water–oil biphasic hydrogel ink enables the loading of water‐ and lipid‐soluble drugs, yielding hydrogel scaffolds with sustained dual‐drug release ability. Crucially, hydrogel scaffolds having excellent mechanical properties, low swelling, and sustained biphasic drug release ability can be prepared using digital light processing 3D printing technology, owing to the high curing rate of the hydrophobic photo‐initiator. These hydrogel scaffolds are applied as meniscal and labral replacements in a porcine model and show great promise for the prevention of secondary osteoarthritis, demonstrating the broad potential clinical applications of this material.
Recent Advancements on Self‐Immolative System Based on Dynamic Covalent Bonds for Delivering Heterogeneous Payloads
Authors: Wang Qingbing , Serda Maciej , Li Quan , Sun Tao 
Published: March 2023

AbstractThe precisely spatial‐temporal delivery of heterogeneous payloads from a single system with the same pulse is in great demand in realizing versatile and synergistic functions. Very few molecular architectures can satisfy the strict requirements of dual‐release translated from single triggers, while the self‐immolative systems based on dynamic covalent bonds represent the “state‐of‐art” of ultimate solution strategy. Embedding heterogeneous payloads symmetrically onto the self‐immolative backbone with dynamic covalent bonds as the trigger, can respond to the quasi‐bio‐orthogonal hallmarks which are higher at the disease's microenvironment to simultaneously yield the heterogeneous payloads (drug A/drug B or drug/reporter). In this review, the modular design principles are concentrated to illustrate the rules in tailoring useful structures, then the rational applications are enumerated on the aspects of drug codelivery and visualized drug‐delivery. This review, hopefully, can give the general readers a comprehensive understanding of the self‐immolative systems based on dynamic covalent bonds for delivering heterogeneous payloads.
Disulfide‐Bridged Dendritic Organosilicas‐Based Biodegradable Molecularly Imprinted Polymers for Multiple Targeting and pH/Redox‐Responsive Drug Release toward Chemical/Photodynamic Synergistic Tumor Therapy
Authors: Liu Shiwei , Han Shuang , Song Yuzhuo , Sun Ruonan , Zhao Le , Yan Chen 
Published: March 2023

AbstractIn this study, a sialic acid (SA) and transferrin (TF) imprinted biodegradable disulfide bridging organosilicas‐based drug delivery system (SS‐DMONS/DOX‐Ce6@MIPs) for targeted cancer therapy is constructed, for the first time. Disulfide bridged dendritic mesoporous organosilicas nanoparticles (SS‐DMONs) not only enhance drug loading as the drug repository, but also provide enough specific surface area for the molecular imprinting shell to expose more degradation and imprinted sites on the surface. In addition, SS can be disturbed in a highly reducing tumor microenvironment to achieve degradation. The biodegradable imprinting film, prepared with customized 2‐amino‐N‐(3,4‐dihydroxyphenethyl)‐3‐mercaptopropanamide and 4‐mercaptophenylboronic acid as functional monomers, endows SS‐DMONs with active targeting capacity, and responsive drug release through degradation under acidic and highly reductive tumor microenvironment. SS‐DMONS/DOX‐Ce6@MIPs after binding of TF can target tumor cells actively through multiple interactions, including the affinity between antigen and antibody, and the specific recognition between molecularly imprinted polymers and template molecules. Under laser irradiation the loaded chlorin e6 (Ce6) that can produce toxic reactive oxygen, combined with the doxorubicin (DOX), achieves chemical/photodynamic synergistic anticancer effects. SS‐DMONS/DOX‐Ce6@MIPs present excellent tumor targeting and dual‐responsive drug release, which provides an effective strategy for chemical/photodynamic antitumor therapy.
Sequential Dual‐Biofactor Release from the Scaffold of Mesoporous HA Microspheres and PLGA Matrix for Boosting Endogenous Bone Regeneration
Authors: Wei Jiawei , Xia Xue , Xiao Shiqi , Jin Shue , Zou Qin , Zuo Yi , Li Yubao , Li Jidong 
Published: March 2023

AbstractThe combined design of scaffold structure and multi‐biological factors is a prominent strategy to promote bone regeneration. Herein, a composite scaffold of mesoporous hydroxyapatite (HA) microspheres loaded with the bone morphogenetic protein‐2 (BMP‐2) and a poly(DL‐lactic‐co‐glycolic acid) (PLGA) matrix is constructed by 3D printing. Furthermore, the chemokine stromal cell‐derived factor‐1α (SDF‐1α) is adsorbed on a scaffold surface to achieve the sequential release of the dual‐biofactors. The results indicate that the rapid release of SDF‐1α chemokine on the scaffold surface effectively recruits bone marrow‐derived mesenchymal stem cells (BMSCs) to the target defect area, whereas the long‐term sustained release of BMP‐2 from the HA microspheres in the degradable PLGA matrix successfully triggers the osteogenic differentiation in the recruited BMSCs, significantly promoting bone regeneration and reconstruction. In addition, these structures/biofactors specially combining scaffold exhibit significantly better biological performance than that of other combined scaffolds, including the bare HA/PLGA scaffold, the scaffold loaded with SDF‐1α or BMP‐2 biofactor alone, and the scaffold with surface SDF‐1α and BMP‐2 dual‐biofactors. The utilization of mesoporous HA, the assembly method, and sequential release of the two biofactors in the 3D printed composite scaffold present a new method for future design of high‐performance bone repairing scaffolds.
Pillararene‐Based Supramolecular Polymers for Adsorption and Separation
Authors: Wang Zhuo‐Qin , Wang Xin , Yang Ying‐Wei 
Published: March 2023

AbstractSupramolecular polymers have attracted increasing attention in recent years due to their perfect combination of supramolecular chemistry and traditional polymer chemistry. The design and synthesis of macrocycles have driven the rapid development of supramolecular chemistry and polymer science. Pillar[n]arenes, a new generation of macrocyclic compounds possessing unique pillar‐shaped structures, nano‐sized cavities, multi‐functionalized groups, and excellent host–guest complexation abilities, are promising candidates to construct supramolecular polymer materials with enhanced properties and functionalities. This review summarizes recent progress in the design and synthesis of pillararene‐based supramolecular polymers (PSPs) and illustrates their diverse applications as adsorption and separation materials. All performances are evaluated and analyzed in terms of efficiency, selectivity, and recyclability. Typically, PSPs can be categorized into three typical types according to their topologies, including linear, cross‐linked, and hybrid structures. The advances made in the area of functional supramolecular polymeric adsorbents formed by new pillararene derivatives are also described in detail. Finally, the remaining challenges and future perspectives of PSPs for separation‐based materials science are discussed. This review will inspire researchers in different fields and stimulate creative designs of supramolecular polymeric materials based on pillararenes and other macrocycles for effective adsorption and separation of a variety of targets.
An Ultra‐Thin, Ultra‐High Capacitance Density Tantalum Capacitor for 3D Packaging
Authors: Zhao Jiping , Xu Youlong , Hou Wenqiang , Li Yizhuo , Ding Xiangdong 
Published: March 2023

AbstractAlthough embedded capacitors have been applied and researched for many years, their large‐scale application still faces challenges such as low capacitance density, high thickness, high cost, and incompatibility with integrated processes. In this work, a breakthrough has been made in the fabrication of ultra‐thin tantalum (Ta) capacitors with ultra‐high capacitance density that can be used for 3D packaging. The key to these excellent performances is the application of Ta foil with nano‐porous structure to the anode of the capacitor. The Ta foil with high specific surface area (SSA) is successfully prepared by direct current pulse etching. At a current density of 15 mA cm−2, a pulse frequency of 50 Hz, and a duty cycle of 30%, the SSA of Ta foil is increased by 76 times after etching in an electrolyte with 0.01 v% TOA for 30 min. Based on this, Ta capacitors with a form factor of less than 40 µm, showing a capacitance density of 750 nF mm−2 and a leakage current of less than 2.1 × 10−7 A at 8 V is successfully fabricated. To the best of the authors’ knowledge, this is the highest capacitance density reported to date for the mentioned form factors.
Efficacy of using sunflower meal as an ingredient, and partial fishmeal‐replacer, in practical feed formulated for stinging catfish (Heteropneustes fossilis)
Authors: Hossain Anamika , Hossain Md. Amzad , Rasul Md. Golam , Akter Taslima , Zaman Md. Farid Uz , Islam Md. Rabiul 
Published: March 2023

AbstractThis study was conducted to determine the growth performance, body composition, and haematological profile of Heteropneustes fossilis in response to the replacement of fish meal (FM) by sunflower meal (SFM). The experiment was conducted in a completely randomized design (CRD) with five treatments and three replications. The fish (initial average body weight of 2.42 ± 0.01 g) were reared in 15 glass aquaria (40 fish/aquarium) with a 150‐L water capacity. Five isoproteic (35%) diets were prepared by replacing FM protein with SFM protein at a rate of 0% (T0), 10% (T10), 20% (T20), 30% (T30), and 40% (T40). Fish were fed with experimental diet twice a day (9.00 and 16.00), 7 days a week for 8 weeks. Fish were sampled at the end of the experimental period of 8 weeks. At the end of the rearing period, the highest weight gain (6.25 ± 0.11g), % weight gain (163.32%), and specific growth rate (1.61 ± 0.03%/day) were observed in the control (T0) treatment, but the difference was not significant (p > 0.05) with T10 and T20 treatments. However, all the growth factors were decreased with the further inclusion level of SFM in replacement of FM, and the lowest growth performance was observed in T40 treatment. The protein efficiency ratio (PER) and feed conversion ratio (FCR) followed the same pattern as the growth parameters. It was found that the whole‐body proximate composition of fish was also affected significantly (p < 0.05). Haematological parameters significantly (P < 0.05) altered at 30% and 40% levels of replacement of FM with SFM. Based on these results, it can be concluded that 20% FM protein can be substituted with SFM protein in the diet of H. fossilis without compromising growth performance, feed utilization, chemical composition, and haematological status. However, according to polynomial regression analysis, the optimum level of replacement of FM protein with SFM protein was determined to be 14.3% in the diet of H. fossilis.
Diversity, distribution, and conservation of the Trichoptera and their habitats in north‐eastern Algeria
Authors: Boucenna Hayat , Satour Abdellatif , Hezil Wissem , Taferghoust Meriem , Samraoui Farrah , Samraoui Boudjéma 
Published: March 2023

Abstract

Community patterns are generated by multiple processes and constraints generated at different spatial and temporal scales.
A large‐scale study was carried out on the Trichoptera of four Algerian regions with contrasting climates, vegetation cover, and human pressures.
Overall, 22 identified taxa were recorded, including nine families and 14 genera. The genus Hydropsyche was represented by eight species, with Hydropsyche maroccana and Hydropsyche lobata being the most abundant species.
With one exception, localities in the subhumid Collo and the high‐altitude Batna were the most species rich, whereas localities in the semi‐arid Oum el Bouaghi were the most species poor.
Nonmetric multidimensional scaling (NMDS) separated the caddisflies recorded into four assemblages organized by a set of constraining environmental factors (land use, altitude, water depth, helophyte cover, and flow velocity gradients) acting at different scales.
As inadequate knowledge of insect biodiversity is a major limitation to their conservation, this article discusses how these results might help predict caddisfly communities in adjacent regions and enhance conservation efforts.
Effect of the metallicity of the intergalactic medium in the Lyman‐α forest correlation function
Authors: Muñoz‐Gutiérrez Andrea , de la Macorra Axel 
Published: March 2023

AbstractThe Lyman‐α (Lyα) forest allows to constraint cosmological parameters at redshifts above using the technique of standard rulers determined by baryon acoustic oscillations. This makes it an important tracer for the study of the universe at high redshift. For this work, several synthetic datasets have been generated to understand the astrophysical effects and contaminants that contribute to the shape of the Lyα flux correlation function, and to be able to reproduce the correlation function measured with data spectra from different galaxy surveys (extended Baryon Oscillation Spectroscopic Survey and Dark Energy Spectroscopic Instrument). Among these phenomena the presence of metals in the intergalactic medium translate into an important bias in the flux correlation function with respect to the flux correlation function calculated considering an only Hydrogen in the intergalactic medium. In this work we study the influence of the metallicity in the Lyα flux correlation function, simulating the presence of four Silicon transitions in synthetic spectra developed in preparation for the Dark Energy Spectroscopic Instrument and compared with the data obtained in the 14th data release of the extended Baryon Oscillation Spectroscopic Survey. These results were used for the analysis of the 16th data release of the extended Baryon Oscillation Spectroscopic Survey, and are currently being used for the analysis of the first data release of the Dark Energy Spectroscopic Instrument survey.
Effect of prenatal stress and extremely low‐frequency electromagnetic fields on anxiety‐like behavior in female rats: With an emphasis on prefrontal cortex and hippocampus
Authors: Hosseini Ehsan , Kianifard Davoud 
Published: March 2023

AbstractObjectivePrenatal stress (PS) is a problematic situation resulting in psychological implications such as social anxiety. Ubiquitous extremely low‐frequency electromagnetic fields (ELF‐EMF) have been confirmed as a potential physiological stressor; however, useful neuroregenerative effect of these types of electromagnetic fields has also frequently been reported. The aim of the present study was to survey the interaction of PS and ELF‐EMF on anxiety‐like behavior.MethodA total of 24 female rats 40 days of age were distributed into four groups of 6 rats each: control, stress (their mothers were exposed to stress), EMF (their mothers underwent to ELF‐EMF), and EMF/stress (their mothers concurrently underwent to stress and ELF‐EMF). The rats were assayed using elevated plus‐maze and open field tests.ResultsExpressions of the hippocampus GAP‐43, BDNF, and caspase‐3 (cas‐3) were detected by immunohistochemistry in Cornu Ammonis 1 (CA1) and dentate gyrus (DG) of the hippocampus and prefrontal cortex (PFC). Anxiety‐like behavior increased in all treatment groups. Rats in the EMF/stress group presented more serious anxiety‐like behavior. In all treatment groups, upregulated expression of cas‐3 was seen in PFC, DG, and CA1 and downregulated expression of BDNF and GAP‐43 was seen in PFC and DG and the CA1. Histomorphological study showed vast neurodegenerative changes in the hippocampus and PFC.ConclusionThe results showed ,female rats that underwent PS or/and EMF exhibited critical anxiety‐like behavior and this process may be attributed to neurodegeneration in PFC and DG of the hippocampus and possibly decreased synaptic plasticity so‐called areas.
Antifungal γ‐Pyrone and Isoprenylated Cyclohexanoids from the Fungus Beenakia informis
Authors: Rincón Yuliet A. , Siless Gastón E. , D'Jonsiles Fernanda , Dansey Virginia , Grassi Emanuel , Schenone Nahuel , Cabrera Gabriela M. 
Published: March 2023

AbstractChemical investigation of the extract of the macroscopic fungus Beenakia informis led to the isolation of a previously unreported γ‐pyrone and two new isoprenylated cyclohexanoids, together with speciocin N. Their structures were elucidated spectroscopically and the absolute configuration was determined by comparison of the experimental vs. calculated ECD curves. Three of the compounds showed very good to moderate activity against phytopathogenic fungi.
COVID‐19‐associated AMPA‐R and CRMP‐5 autoimmune encephalitis in a patient with thymoma and myasthenia gravis
Authors: Raynowska Jenelle , Wu Victoria , Kazer Max , LaBuzetta Jamie Nicole , Ferrey Dominic , Dunn‐Pirio Anastasie 
Published: March 2023

AbstractThymomas are associated with autoimmune disease, most commonly myasthenia gravis, and rarely with autoimmune encephalitis. More recently, viral triggers including COVID‐19 have also been implicated in autoimmunity. We present a case of antibody‐positive autoimmune encephalitis that developed in the setting of COVID‐19 in a patient with thymomatous myasthenia gravis.
Hemophagocytic Lymphohistiocytosis syndrome (HLH) associated with acute pancreatitis: A case report
Authors: Mechi Ahmed Mohamad , Al‐Khalidi Alhan Abbas , Hasan Thulfiqar Azeez 
Published: March 2023

AbstractHemophagocytic Lymphohistiocytosis syndrome is fatal hyper‐inflammatory condition due to over‐activation of the immune system, being of primary and secondary types. This case report emphasizes the difficulty and challenge in and of the HLH diagnosis, and therapy should be employed promptly given the high mortality associated with HLH.
C21orf2 variants causing inherited retinal disease: A review of what we know and a report of two new suspected cases
Authors: Shinbashi Meagan , Jewell Ann , Randolph Jessica , Couser Natario 
Published: March 2023

AbstractVariants in the C21orf2 (CFAP410) gene have recently been associated with the development of retinitis pigmentosa, an inherited condition characterized by degeneration of the retina. In this article, we describe 34 previously reported cases of C21orf2 variant‐associated retinopathies and present two new suspected cases.