bluuebunny/crossref_metadata_2025_split huggingface dataset:
Completion Rate and Positive Results Reporting Among Immunotherapy Trials in Breast Cancer, 2004-2023
Authors: Mariani Marco , Viale Giulia , Galbardi Barbara , Licata Luca , Bosi Carlo , Dugo Matteo , Notini Giulia , Naldini Matteo M. , Callari Maurizio , Criscitiello Carmen , Pusztai Lajos , Bianchini Giampaolo 
Published: July 2024

ImportanceClinical trials are the path to test and introduce new therapies in the clinic. Trials that are unable to produce results represent inefficiency in the system and may also undermine patient confidence in the new drug development process.ObjectivesTo survey the immunotherapy clinical trial landscape of breast cancer between January 2004 and April 2023 and examine what fraction of trials with primary completion date up to November 30, 2022, failed to report outcome, assessing the proportion of trials that yielded positive results and describing trial features associated with these 2 outcomes.Design, Setting, and ParticipantsThis cross-sectional study included breast cancer immunotherapy trials identified in ClinicalTrials.gov. Trial details and results were retrieved in December 2023. Google Scholar, PubMed, and LARVOL CLIN websites were also searched for reports.Main Outcomes and MeasuresTrial outcome reported as abstract or manuscript. Reported trials were categorized as positive (ie, met its end point) or negative. Association between reporting and trial features were tested using Fisher exact test.ResultsA total of 331 immuno-oncology trials were initiated in breast cancer by April 2023; 242 trials were phase II, 47 were phase I, and 42 phase III. By setting, 212 studies (64.0%) were conducted in metastatic, 94 (28.4%) in neoadjuvant, and 25 (7.6%) in adjuvant settings. Among phase II and III trials, 168 (59.2%) were nonrandomized. One hundred twenty trials had primary completion dates up to November 30, 2022, of which 30 (25.0%; enrolling a combined 2428 patients) failed to report their outcomes; 7 phase I trials (31.8%), 21 phase II trials (23.6%), and 2 phase III trials (22.2%) were unreported. Single-center studies were significantly more likely to be unreported than multicenter studies (19 of 54 [35.2%] vs 9 of 60 [15.0%]; P = .02). Of the 90 reported trials, 47 (52.2%) and 43 (47.8%) were positive and negative, respectively. Seventeen of 19 (89.5%) of the reported randomized trials (accruing a total of 4189 patients) were negative.Conclusions and RelevanceIn this cross-sectional study of immunotherapy breast cancer trials, the large number of trials yielded modest clinical impact. Single-center trials commonly failed to report their outcomes and many phase II studies have not translated into corresponding successful phase III trials.
Combined Effect of Oxygen Vacancies and Mesopore Sizes in ZnO/SiO2 Adsorbents on Boosting the H2S Removal Efficiency in Moist Conditions
Authors: Yang Chao , Liu Zhilong , Su Zhelin , Wang Yeshuang , Liang Meisheng , Fan Huiling , Bandosz Teresa J. 
Published: July 2024

AbstractWhile both pore sizes and oxygen vacancies benefit desulfurization on ZnO, their specific roles and the combined effect on the efficiency of this process are still unclear. To address this, ZnO‐based adsorbents with tunable mesopore sizes and concentrations of oxygen vacancies are synthesized. These two features are directly regulated through varying the carbon chain length of dihydric alcohol, which is used as a precursor in the synthesis process. They influenced the desulfurization performance through affecting the diffusion and dissociation of H2S. The sizes of mesopores determined the amounts of adsorbed water/ thickness of a water film while the amount of oxygen vacancies controlled the contents of hydroxyl groups. The latter not only are replaced by (bi)sulfide anions but also promote the dissociation of H2S through acid‐base interaction. Adsorbed water contributed to hydroxylation of the surface until the cease of desulfurization. However, too much‐adsorbed water increased the resistance of H2S diffusion through the water film to the surface of ZnO, deteriorating the performance. The optimal amounts of adsorbed water/thickness of water film and a sufficient amount of oxygen vacancies/hydroxyl groups are provided in the adsorbent with a mesopore size of ∼10 nm leading to a maximum H2S removal capacity of 151.9 mg g−1.
Decarboxylative Iodination of Coumarin‐3‐carboxylic Acids: A Facile Access to 3‐Iodocoumarins
Authors: Thotathil Vandana , Sidiq Naheed , Idoudi Souha , Al‐Zoubi Raed M. , Shkoor Mohanad , Dawoud Bani‐Yaseen Abdulilah 
Published: July 2024

AbstractA straightforward protocol for the direct conversion of readily available coumarin‐3‐carboxylic acids to the corresponding 3‐iodocoumarins is described herein. Heating acetonitrile solution of coumarin‐3‐carboxylic acids, molecular iodine and potassium hydrogen phosphate resulted in the decarboxylative iodination of coumarin‐3‐carboxylic acids via radical mechanism. Various electron rich and electron poor coumarin‐3‐carboxylic acids were compatible with the established reaction conditions and consequently afforded the corresponding 3‐iodocoumarins in (46–93 %) reaction yields with minimum purification efforts. The formed products serve as valuable precursors to streamline more complex organic compounds incorporating coumarin core.
Concentration‐driven morphology change of a self‐aggregated amino acid‐inspired fluorescence‐active copolymer for sustained release of hydrophobic drug
Authors: Manna Kalipada , Roy Arpita , Dey Shaon , Kumar Abhay , Pal Sagar 
Published: July 2024

AbstractThe development of amphiphiles for sustained drug delivery represents a promising approach in biomedical fields. Polymeric self‐assembly with a hydrophobic core offers plenty of opportunities to encapsulate hydrophobic drugs for facilitating targeted delivery to the specific sites of action. Herein, N‐Boc tryptophan has been used to develop a hydrophobic monomer, Boc‐tryptophan‐HEMA (HBT). The HBT monomer has further been grafted on modified alginic acid through the RAFT technique to synthesize a unique amphiphilic copolymer with fluorescence characteristics. The advanced polymer chromatography demonstrates a narrow distribution curve, signifying the living nature of polymerization. The copolymer has exhibited self‐aggregation behavior with two distinct shapes at two different critical aggregation concentrations (CAC). The concentration‐dependent shape variation has been investigated using FESEM and TEM analyses, further supported by a small‐angle x‐ray scattering analysis. The self‐aggregation behavior of the copolymer facilitates the uptake of a model hydrophobic drug (naproxen) and its release in a sustained manner with varied rates at two different concentrations.
Fabrication and characterization of Ecklonia cava phlorotannin‐loaded PVA/PVP blend electrospun nanofibers as a potential diabetic wound dressing biomaterial
Authors: Teh Huey Xhin , Phang Shou Jin , Neo Yun Ping , Looi Mee Lee , Kuppusamy Umah Rani , Arumugam Bavani 
Published: July 2024

AbstractDiabetic wound healing remains a challenging issue, necessitating advanced dressings with active therapeutic agents to reduce inflammation and promote healing. Ecklonia cava phlorotannin (ECP) possesses therapeutic potential for wound healing including anti‐microbial, antioxidant, and anti‐inflammatory properties. Our previous study demonstrates the therapeutic efficacy of ECP‐loaded nanofibers in an in vitro hyperglycemic wound model. The present paper focuses on the detailed characterization of the polyvinyl alcohol (PVA)/polyvinylpyrrolidone (PVP) blend nanofiber incorporated with ECP. The ideal ratio, PVA80:PVP20, is selected to incorporate with ECP via the blend electrospinning method. To confirm the successful loading of ECP (0.5% and 1%), physicochemical characterization is conducted using scanning electron microscopy, Fourier‐transform infrared spectroscopy, and thermal analysis. Functionality assays are performed to evaluate their applicability as dressing biomaterials. Physicochemical analyses confirm the successful loading of ECP into the nanofibers. Overall, the ECP‐loaded PVA/PVP nanofiber membranes exhibit favorable wound dressing criteria, which attributed to high water absorption capacity (200%–400%), sufficient water vapor transmission rate (1550–1650 g/m2/d), high loading efficiency and slow release. Bioactivity tests indicate that the ECP's effectiveness is unaffected by the electrospinning process. Importantly, these membranes exhibit biocompatibility and nontoxicity to human dermal fibroblasts, indicating their potential as good diabetic wound dressings.
Gut Microbiome and Osteoarthritis: Insights From the Naturally Occurring Canine Model of Osteoarthritis
Authors: Stevens Christina , Norris Samantha , Arbeeva Liubov , Carter Scott , Enomoto Masataka , Nelson Amanda E. , Lascelles B. Duncan X. 
Published: July 2024

ObjectiveThe purpose of this study was to enhance the current knowledge of the relationship between the gut microbiome and osteoarthritis (OA) and associated pain using pet dogs as a clinically relevant translational model.MethodsFecal samples were collected from 93 owned pet dogs. Dogs were designated as either clinically healthy or OA pain using validated methods. Metagenomic profiling was performed through shotgun sequencing using the Illumina NovaSeq platform. MetaPhlAn2 and HUMAnN2 were used to evaluate bacterial taxonomic and pathway relative abundance. Comparisons between healthy and OA‐pain groups were performed individually for each taxa using nonparametric tests following Benjamini and Hochberg adjustment for multiple comparisons. Permutation analysis of variance was performed using Bray‐Curtis distance matrices. All downstream analyses were completed in R.ResultsNo significant differences between healthy and OA‐pain dogs were observed for alpha and beta diversity. We found 13 taxa with nominally significant (P < 0.05) associations with OA case status, but none of the associations remained significant after adjustment for multiple comparisons. No differences in alpha or beta diversities or the Firmicutes to Bacteroidetes ratio were found regarding pain severity, mobility or activity level, age, or body composition score.ConclusionSimilar to recent studies in humans, the present study did not demonstrate a significant difference in the fecal microbial communities between dogs with OA pain and healthy control dogs. Future research in this naturally occurring model should expand on these data and relate the gut microbiome to gut permeability and circulating proinflammatory and anti‐inflammatory molecules to better understand the influence of the gut microbiome on OA and OA pain.
Optimizing the production of dsRNA biocontrols in microbial systems using multiple transcriptional terminators
Authors: Ross Sebastian J. , Owen Gareth R. , Hough James , Philips Annelies , Maddelein Wendy , Ray John , Kilby Peter M. , Dickman Mark J. 
Published: July 2024

AbstractCrop pests and pathogens annually cause over $220 billion in global crop damage, with insects consuming 5%–20% of major grain crops. Current crop pest and disease control strategies rely on insecticidal and fungicidal sprays, plant genetic resistance, transgenes, and agricultural practices. Double‐stranded RNA (dsRNA) is emerging as a novel sustainable method of plant protection as an alternative to traditional chemical pesticides. Successful commercialization of dsRNA‐based biocontrols requires the economical production of large quantities of dsRNA combined with suitable delivery methods to ensure RNAi efficacy against the target pest. In this study, we have optimized the design of plasmid DNA constructs to produce dsRNA biocontrols in Escherichia coli, by employing a wide range of alternative synthetic transcriptional terminators before measurement of dsRNA yield. We demonstrate that a 7.8‐fold increase of dsRNA was achieved using triple synthetic transcriptional terminators within a dual T7 dsRNA production system compared to the absence of transcriptional terminators. Moreover, our data demonstrate that batch fermentation production dsRNA using multiple transcriptional terminators is scalable and generates significantly higher yields of dsRNA generated in the absence of transcriptional terminators at both small‐scale batch culture and large‐scale fermentation. In addition, we show that application of these dsRNA biocontrols expressed in E. coli cells results in increased insect mortality. Finally, novel mass spectrometry analysis was performed to determine the precise sites of transcriptional termination at the different transcriptional terminators providing important further mechanistic insight.
Real‐world first‐line treatment with pembrolizumab for non‐small cell lung carcinoma with high PD‐L1 expression: Updated analysis
Authors: Ikezawa Yasuyuki , Morita Ryo , Mizugaki Hidenori , Tateishi Kazunari , Yokoo Keiki , Sumi Toshiyuki , Kikuchi Hajime , Kitamura Yasuo , Nakamura Atsushi , Kobayashi Maki , Aso Mari , Kimura Nozomu , Yoshiike Fumiaki , Megumi Furuta , Tanaka Hisashi , Sekikawa Motoki , Hachiya Tsutomu , Nakamura Keiichi , Hommura Fumihiro , Sukoh Noriaki , Ito Kenichiro , Kikuchi Takashi , Agatsuma Toshihiko , Yokouchi Hiroshi 
Published: July 2024

AbstractBackgroundSelecting pembrolizumab monotherapy (MONO) or pembrolizumab plus platinum‐based chemotherapy (COMB) for patients with nonsmall cell lung cancer (NSCLC) and high programmed death‐ligand 1 (PD‐L1) expression is an important issue in clinical practice. We previously conducted a retrospective multicenter observational study of patients with NSCLC and high PD‐L1 expression who received MONO or COMB as a first‐line treatment. Here, we report updated data and evaluate the long‐term outcomes.MethodsWe performed a retrospective multicenter study of 298 patients with NSCLC and high PD‐L1 expression who received MONO or COMB as first‐line treatment between December 2018 and January 2020. We reviewed the medical records and assessed the clinical efficacy and toxicity using a prolonged data cutoff.ResultsIn total, 164 (median age: 74 years) and 134 (median age: 68 years) patients received MONO and COMB, respectively; patients who received COMB were younger and had better performance statuses (0–1). At the prolonged data cutoff, the median follow‐up was 20.2 (range: 0.1–41.4) months. The median progression‐free survivals were 7.5 and 13.1 months, and overall survivals (OSs) were 17.2 and 33.7 months for MONO and COMB, respectively. Treatment discontinuation rates were 21.9% and 20.1% for the MONO and COMB, respectively. With prolonged follow‐up, although COMB demonstrated an OS benefit and higher objective response rate than MONO, in the propensity score matching analysis COMB didn't demonstrate a significant benefit compared to the MONO.ConclusionsCOMB may be effective as a first‐line treatment for NSCLC with high PD‐L1 expression in a selected subset of patients.
A review of emerging trends, challenges, and opportunities for utilization of metal nanoclusters in CO2 capturing
Authors: Kapoor Atul , Rajput Jaspreet Kaur 
Published: July 2024

AbstractCO2, a predominant anthropogenic greenhouse gas, emerges as a primary factor in climate change due to the increasing utilization of fossil fuels, necessitating immediate efforts for the development and implementation of strategies like carbon capture and storage (CCS) to mitigate emissions, considering the ongoing dependence on unsustainable energy and transportation resources. The research endeavours to meet the critical requirement for effective CO2 capture through the exploration of novel sorbent materials, with a specific focus on molecularly precise nanoclusters (NCs), aiming to enhance understanding of the catalytic mechanisms in CO2 reduction and design stable, high‐performance sorbents with controllable properties. Advancing the field, the study delves into the synthesis and examination of molecularly precise nanoclusters (NCs), an emerging domain in nanoscience, with a particular emphasis on well‐defined nanoclusters like thiolate‐protected Au, Ag, and Cu NCs. This strategy provides a distinctive foundation for attaining atomic‐level understanding of electrocatalytic CO2 reduction mechanisms, offering a more precise and customized synthesis to overcome challenges associated with polydispersity in conventional nanoparticles. The study highlights the exceptional catalytic activity of specific Au NCs like Au25 in converting CO2 to CO. It surpasses thermodynamic limits. The study also investigates the influence of surface properties, electrostatic, and steric stability on preventing nanocluster aggregation. It emphasizes the potential of molecularly precise nanoclusters as catalysts for CO2 reduction. Additionally, it suggests avenues for advanced sorbent development with improved performance and stability.
Phosphate‐Containing Glycolipids: A Review on Synthesis and Bioactivity
Authors: Pinheiro Luís , Freitas Marisa , Branco Paula S. 
Published: July 2024

AbstractPhosphate‐containing glycolipids (PcGL) are scarcer than the better understood glycolipids. They are composed of arrangements of phosphate, carbohydrates and glycerol units and are always found associated with lipids. PcGL are often found associated with cell membranes, suggesting they play roles in cell membrane structure and intercellular interactions. This article aims to provide an up‐to‐date overview of the existing knowledge and research on PcGL, emphasizing their synthesis and wide range of biological activities. When it comes to the synthesis of PcGL compounds, the strategies for glycosylation mainly rely on the thioglycoside donor, the trichloroacetamidate donor and halide donor strategies, while phosphorylation is stapled and falls on either phosphite chemistry or phosphoryl chloride chemistry. Certain bacteria utilize PcGLs in their pathogenicity, triggering an inflammatory response within the host's defense mechanisms. The best‐known examples of these structures are teichoic acids, lipopolysaccharide and the capsular polysaccharide found in bacteria, all of which are frequently implicated in bacterial infections. Given the degree of variability within PcGL structures, they were found to display a wide range of bioactivities. PcGL compounds were found to: (1) have anti‐metastatic properties, (2) behave as agonists or antagonists of platelet aggregation, (3) be mostly pro‐inflammatory, (4) display antifungal and antibiotic activity and (5) have neurogenic activity.
Spatial proteomic profiling of tumor and stromal compartments in non‐small‐cell lung cancer identifies signatures associated with overall survival
Authors: Yaghoubi Naei Vahid , Monkman James , Sadeghirad Habib , Mehdi Ahmed , Blick Tony , Mullally William , O'Byrne Ken , Warkiani Majid Ebrahimi , Kulasinghe Arutha 
Published: July 2024

AbstractObjectivesNon‐small‐cell lung carcinoma (NSCLC) is the most prevalent and lethal form of lung cancer. The need for biomarker‐informed stratification of targeted therapies has underpinned the need to uncover the underlying properties of the tumor microenvironment (TME) through high‐plex quantitative assays.MethodsIn this study, we profiled resected NSCLC tissues from 102 patients by targeted spatial proteomics of 78 proteins across tumor, immune activation, immune cell typing, immune‐oncology, drug targets, cell death and PI3K/AKT modules to identify the tumor and stromal signatures associated with overall survival (OS).ResultsSurvival analysis revealed that stromal CD56 (HR = 0.384, P = 0.06) and tumoral TIM3 (HR = 0.703, P = 0.05) were associated with better survival in univariate Cox models. In contrast, after adjusting for stage, BCLXL (HR = 2.093, P = 0.02) and cleaved caspase 9 (HR = 1.575, P = 0.1) negatively influenced survival. Delta testing indicated the protective effect of TIM‐3 (HR = 0.614, P = 0.04) on OS. In multivariate analysis, CD56 (HR = 0.172, P = 0.001) was associated with better survival in the stroma, while B7.H3 (HR = 1.72, P = 0.008) was linked to poorer survival in the tumor.ConclusionsDeciphering the TME using high‐plex spatially resolved methods is giving us new insights into compartmentalised tumor and stromal protein signatures associated with clinical endpoints in NSCLC.
Antiplasmodial action of 4‐nitrobenzenesulfonamide chalcones: Design, synthesis, characterisation, in vitro and in silico evaluation against blood stages of Plasmodium falciparum 3D7
Authors: Tom Anju Agnes , Rajendran Vinoth , Thottasseri Ahammed Ameen , Goswami Koustav , Roy Souvik , Gopan Gopika , Mani Maheswaran , Kannan Tharanikkarasu 
Published: July 2024

AbstractMalaria is an intracellular protozoan parasitic disease caused by Plasmodium species with significant morbidity and mortality in endemic regions. The complex lifecycle of the parasite and the emergence of drug‐resistant Plasmodium falciparum have hampered the efficacy of current anti‐malarial agents. To circumvent this situation, the present study attempts to demonstrate the blood‐stage anti‐plasmodial action of 26 hybrid compounds containing the three privileged bioactive scaffolds (sulfonamide, chalcone, and nitro group) with synergistic and multitarget action. These three parent scaffolds exhibit divergent activities, such as antibacterial, anti‐malarial, anti‐fungal, anti‐inflammatory, and anticancer. All the synthesised compounds were characterised using various spectroscopic techniques. The in vitro blood‐stage inhibitory activity of 26 hybrid compounds was evaluated against mixed‐stage culture (asynchronize) of human malarial parasite P. falciparum, Pf 3D7 at different concentrations ranging from 25.0 µg/mL to 0.78 µg/mL using SYBR 1 green assay, with IC50 values determined after 48 h of treatment based on the drug‐response curves. Two potent compounds (11 and 10), with 2‐Br and 2,6‐diCl substitutions, showed pronounced activity with IC50 values of 5.4 µg/mL and 5.6 µg/mL, whereas others displayed varied activity with IC50 values ranging from 7.0 µg/mL to 22.0 µg/mL. Both 11 and 10 showed greater susceptibility towards mature‐stage trophozoites than ring‐stage parasites. The hemolytic and in vitro cytotoxicity assays revealed that compounds 11 and 10 did not cause any toxic effects on host red blood cells (uninfected), human‐derived Mo7e cells, and murine‐derived BA/F3 cells. The in vitro observations are consistent with the in silico studies using P. falciparum‐dihydrofolate reductase, where 11 and 10 showed a binding affinity of −10.4 Kcal/mol. This is the first report of the hybrid scaffold, 4‐nitrobenzenesulfonamide chalcones, demonstrating its potential as an anti‐plasmodial agent.