bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spray-dried, Biodegradable, Linezolid-loaded Microspheres for Use in the Treatment of Lung Diseases
Authors: Al-Gharsan Mazen Gharsan , Harsha Sree 
Published: October 2023

Introduction: Researchers worldwide are currently seeking innovative treatment options to combat the alarming increase in bacterial resistance to antimicrobial drugs. Staphylococcus aureus, a frequently encountered and potentially life-threatening bacterium, has become particularly problematic. Linezolid is one of the few medicines on the market that can treat bacteria resistant to other antibiotics. This is the first antibacterial oxazolidinone that has shown to be therapeutically efficacious. Linezolid is a new Oxazolidinone medicine. It kills a broad spectrum of bacteria, including Staphylococcus aureus.
Objectives: To reduce non-target organ adverse effects associated with frequent and chronic Linezolid usage, we developed biodegradable, lung-targeted microspheres with sustained release profile.
Methods: In this work, a Buchi B-90 nanospray drier was used to prepare a Linezolid-loaded carbopol microsphere (CLSMO)-based formulation. The spray-drying process was optimized using a face-centered central composite design (CCD).
Results: The average particle size was 7.516 µm, and the surface of the microspheres was shriveled, according to scanning electron microscope imaging. Drug content and yield were determined to be 73% 3.1% and 72% ± 2.4%., respectively, and drug release (99.1%) peaked for up to 12 hours in vitro. FTIR spectral analysis results suggest that there are no significant physical and chemical interactions between the functional groups of Linezolid and carbopol 934P polymer which ultimately form a stable blend. Linezolid, Carbopol, and CLSMO all had XRD patterns that showed the linezolid would be molecularly dispersed in the polymer. The DSC findings revealed the drug's amorphous nature, which explains the absence of characteristic peaks, indicating a lack of well-defined crystalline structure.
Conclusion: The optimized formulation shows significant potential for use as a drug-delivery system in in-vivo applications, particularly in targeted drug delivery to the lungs.
Analysis of sodium phenylbutyrate and taurursodiol survival effect in ALS using external controls
Authors: Paganoni Sabrina , Quintana Melanie , Sherman Alexander V. , Vestrucci Matteo , Wu Yuehui , Timmons Jamie , Cudkowicz Merit ,   the Pooled Resource Open‐Access ALS Clinical Trials Consortium
Published: October 2023

AbstractObjectiveSodium phenylbutyrate and taurursodiol (PB and TURSO) was evaluated in amyotrophic lateral sclerosis (ALS) in the CENTAUR trial encompassing randomized placebo‐controlled and open‐label extension phases. On intent‐to‐treat (ITT) survival analysis, median overall survival (OS) was 4.8 months longer and risk of death 36% lower in those originally randomized to an initial 6‐month double‐blind period of PB and TURSO versus placebo. To estimate PB and TURSO treatment effect without placebo‐to‐active crossover, we performed a post hoc survival analysis comparing PB and TURSO‐randomized participants from CENTAUR and a propensity score–matched, PB and TURSO‐naïve external control cohort from the Pooled Resource Open‐Access ALS Clinical Trials (PRO‐ACT) database.MethodsClinical trial control participants from the PRO‐ACT database who met prespecified eligibility criteria were propensity score matched 1:1 with PB and TURSO‐randomized CENTAUR participants using prognostically significant covariates in ALS.ResultsBaseline characteristics including propensity score–matched covariates were generally well balanced between CENTAUR PB and TURSO (n = 89) and PRO‐ACT external control (n = 85) groups. Estimated median (IQR) OS was 23.54 (14.56–39.32) months in the CENTAUR PB and TURSO group and 13.15 (9.83–19.20) months in the PRO‐ACT external control group; hazard of death was 52% lower in the former group (hazard ratio, 0.48; 95% CI, 0.31–0.72; p = 0.00048).InterpretationThis analysis suggests potentially greater survival benefit with PB and TURSO in ALS without placebo‐to‐active crossover than seen on ITT analysis in CENTAUR. Analyses using well‐matched external controls may provide additional context for evaluating survival effects in future ALS trials.
Self‐Luminous Probe with One‐Step Energy Conversion from Bioluminescence to NIR‐IIb
Authors: Jiang Zhao , Yang Zhiwen , Li Wanwan 
Published: October 2023

AbstractSelf‐luminous probes with near‐infrared (NIR) emission are powerful tools for deep‐penetration and autofluorescence‐free imaging, owing to the joint optimization of both excitation and emission. However, the limited emission wavelength and requirement for multistep energy transfer limit its potency. In this study, the concept of direct wavelength conversion is established from visible light (vis) to NIR‐IIb using an exquisitely designed sensitizer–activator ion pair. The manipulation of the doping hosts enables a pair of energy levels between the sensitizer and activator. Based on this a class of broadband vis‐responsive nanocrystals with intense NIR‐II emission is prepared. The stability and quantum yield (up to 7.4%) of the nanocrystals are further enhanced by ZnS passivation via coherent epitaxial growth. By coupling luciferase, the self‐luminous probe can convert bioluminescence to NIR‐IIb luminescence (>1500 nm) through a one‐step energy transfer. A maximum penetrable thickness of 6 mm is achieved in the porcine tissue model. Collectively, the distinctive photon‐conversion performance of this probe offers the prospect of high‐resolution labeling of deep‐seated lesions.
Ultrasmall Bi/Cu Coordination Polymer Combined with Glucose Oxidase for Tumor Enhanced Chemodynamic Therapy by Starvation and Photothermal Treatment
Authors: Zhang Lin , Fu Jin‐Mei , Song Lai‐Bo , Cheng Kai , Zhang Fang , Tan Wen‐Hui , Fan Jin‐Xuan , Zhao Yuan‐Di 
Published: October 2023

AbstractMulti‐modal combination therapy for tumor is expected to have superior therapeutic effect compared with monotherapy. In this study, a super‐small bismuth/copper‐gallic acid coordination polymer nanoparticle (BCN) protected by polyvinylpyrrolidone is designed, which is co‐encapsulated with glucose oxidase (GOX) by phospholipid to obtain nanoprobe BCGN@L. It shows that BCN has an average size of 1.8 ± 0.7 nm, and photothermal conversion of BCGN@L is 31.35% for photothermal imaging and photothermal therapy (PTT). During the treatment process of 4T1 tumor‐bearing nude mice, GOX catalyzes glucose in the tumor to generate gluconic acid and hydrogen peroxide (H2O2), which reacts with copper ions (Cu2+) to produce toxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT) and new fresh oxygen (O2) to supply to GOX for further catalysis, preventing tumor hypoxia. These reactions increase glucose depletion for starvation therapy , decrease heat shock protein expression, and enhance tumor sensitivity to low‐temperature PTT. The in vitro and in vivo results demonstrate that the combination of CDT with other treatments produces excellent tumor growth inhibition. Blood biochemistry and histology analysis suggests that the nanoprobe has negligible toxicity. All the positive results reveal that the nanoprobe can be a promising approach for incorporation into multi‐modal anticancer therapy.
Cooperative Photoredox and N‐Heterocyclic Carbene Catalyzed Fluoroaroylation for the Synthesis of α‐Trifluoromethyl‐Substituted Ketones
Authors: Yu Xiaoye , Maity Anirban , Studer Armido 
Published: October 2023

Abstractα‐Trifluoromethylated ketones have attracted significant attention as valuable building blocks in organic synthesis. Such compounds are generally accessed through trifluoromethylation of ketones. Here we report an alternative disconnection approach for the construction of α‐CF3 carbonyl compounds by using aroyl fluorides as bifunctional reagents for fluoroaroylation of gem‐difluoroalkenes through cooperative photoredox and N‐heterocyclic carbene (NHC) catalysis. This strategy bypasses the use of expensive or sensitive trifluoromethylation reagents and/or the requirement for ketone pre‐functionalization, thus enabling an efficient and general synthetic method to access α‐CF3‐substituted ketones. A wide variety of gem‐difluoroalkenes and aroyl fluorides bearing a diverse set of functional groups are eligible substrates. Notably, the developed methodology also provides rapid access to mono‐ or difluoroalkyl ketones. Mechanistic studies reveal that merging photoredox catalysis with NHC catalysis is essential for the reaction.
Heteroditopic NHC Ligand Supported Manganese(I) Complexes: Synthesis, Characterization, and Activity as Non‐bifunctional Phosphine‐Free Catalyst for the α‐Alkylation of Nitriles
Authors: Donthireddy Siva Nagendra Reddy , Rit Arnab 
Published: October 2023

AbstractIn the present work, several manganese(I) complexes of chelating heteroditopic ligands Mn1–3, featuring ImNHC (imidazol‐2‐ylidene) connected to a 1,2,3‐triazole‐N or tzNHC (1,2,3‐triazol‐5‐ylidene) donors via a methylene spacer, with possible modifications at the triazole backbone have been synthesized and completely characterized. Notably, the CO stretching frequencies, electrochemical analysis, and frontier orbital analysis certainly suggest that the chelating ImNHC‐tzNHC ligands have stronger donation capabilities than the related ImNHC‐Ntz ligand in the synthesized complexes. Moreover, these well‐defined phosphine‐free Mn(I)−NHC complexes have been found to be effective non‐bifunctional catalysts for the α‐alkylation of nitriles using alcohols and importantly, the catalyst Mn1 containing ImNHC connected to a weaker triazole‐N donor displayed higher activity compared to Mn2/Mn3 containing an unsymmetrical bis‐carbene donors (ImNHC and tzNHC). A wide range of aryl nitriles were coupled with diverse (hetero)aromatic as well as aliphatic alcohols to get the corresponding products in good to excellent yields (32 examples, up to 95 % yield). The detailed mechanistic studies including deuterium labelling experiments reveal that the reaction follows a Borrowing Hydrogen pathway.
Bisbenzamidine and Bisbenzguanidine Ureas Act as Antibacterial Agents against Pseudomonas aeruginosa
Authors: Kellogg Casey N. , Pugh Bryce A. , Starr Isaak M. , Parmar Dhruvi J. , Troxler A'Zane D. , Wolfe Amanda L. 
Published: October 2023

AbstractDue to the global rise in the number of antibiotic resistant bacterial infections over the past 20 years, there is a dire need for the development of small molecule antibiotics capable of overcoming resistance mechanisms in pathogenic bacteria. Antibiotic development against Gram‐negative pathogens, such as Pseudomonas aeruginosa, is especially challenging due to their additional outer membrane which reduces antibiotic entry. Recently, it has been shown that a broad range of nitrogen functionality, including guanidines, amidines, primary amines, imidazolines, and imidazoles, promote antibiotic and adjuvant activity in Gram‐negative bacteria, but few of these have been targeted towards Pseudomonas aeruginosa specifically despite this pathogen being deemed a critical threat by the United States Centers for Disease Control and Prevention. Herein, we examined a small series of known and unknown nitrogenous dimers, with guanidine, amidine, dimethyl amine, and pyridine functionality, for antibacterial activity against multidrug resistant Pseudomonas aeruginosa. We found that two, with bisbenzguanidine and bisbenzamidine functionality, are potent against clinical isolates of multidrug resistant and biofilm forming Pseudomonas aeruginosa.
Isolation of Extracellular Vesicles from Phloem Sap by Size Exclusion Chromatography
Authors: Garzo Elisa , Sánchez‐López Christian M. , Fereres Alberto , Soler Carla , Marcilla Antonio , Pérez‐Bermúdez Pedro 
Published: October 2023

AbstractExtracellular vesicles (EVs) are nanoparticles that are released by cells and participate in the transfer of information. It is now known that EVs from mammalian cells are involved in different physiological and pathophysiological processes (antigen presentation, tissue regeneration, cancer, inflammation, diabetes, etc.). In the past few years, several studies on plants have demonstrated that EVs are also key tools for plant intercellular and cross‐kingdom communications, suggesting that these nanostructures may contribute to distinct aspects of plant physiology such as development, defense, reproduction, symbiotic relationships, etc. These findings are challenging the traditional view of signaling in plants.EVs are probably involved in the phloem's transport system, since this vascular tissue plays a crucial role in translocating nutrients, defensive compounds, and informational signals throughout the plant. The collection of phloem is experimentally challenging because sap is under high turgor pressure inside the sieve elements, which have a small diameter and are hidden within the plant organs. The goals of this work are to develop new protocols that allow us to detect EVs for the first time in the phloem of the plants, and to isolate these nanovesicles for in‐depth analysis and characterization.Our protocols describe two distinct methods to collect the phloem sap from rice and melon. The first method (Basic Protocol 1) involves ‘Aphid stylectomy by radiofrequency microcautery’ using rice plants and the aphid Sitobion avenae. This is considered the least invasive method for collecting phloem sap. The second method, ‘Stem incision’, involves cutting the stem of melon plants for collecting the exuded sap. Phloem sap EVs are then isolated by size exclusion chromatography. The results obtained in this study represent the first report on typical EVs isolated from in vivo–collected phloem sap. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: Isolation of EVs from phloem sap: Aphid stylectomy by radiofrequency microcauteryBasic Protocol 2: Isolation of EVs from phloem sap: Stem incision method
Effect of uptake of improved seed potato and donor‐funded training on smallholder farmers’ market participation
Authors: Kangogo Ednah , Otieno David Jakinda , Okello Julius , Mwenye Obed , Kapalasa Eliya 
Published: October 2023

AbstractEnhancing the productivity of crops through the adoption and uptake of technologies improves farmers' socioeconomic status through increased market participation. However, smallholder farmers in Sub‐Saharan Africa (SSA) face a myriad of challenges that make it difficult for them to access and participate in the output markets. Like most SSA countries, the uptake of improved technologies is still low in Malawi. This study examines the relationship between the uptake of improved potato seed and donor‐funded training on market participation. Using secondary data from 393 potato farmers in Malawi, the study applied a triple‐hurdle model to examine the extent to which such interventions and other socioeconomic and institutional factors influence market participation. The results showed that male‐headed farm households, more experienced farmers, and those who participated in International Potato Center (CIP)‐led training were likely to market their potato output. Further, farmers closer to urban centers, those with off‐farm income, those who had participated in potato training, use of improved potato seed, and quantity of output positively influenced the decision to sell in high‐value markets such as supermarkets. On the other hand, land size, ownership of transport equipment, group membership, and access to credit had positive effects on the amount of potatoes sold, while the distance to the markets reduced the quantity sold. Based on these findings, there is a need to set up a seed system within the local communities where farmers can easily access the seeds. Additionally, there is a need for a collaborative effort between public and private sector stakeholders to invest in the production of improved potato seeds that would help to address the shortfall in supply. Finally, institutional support interventions that utilize farmer groups as a key entry point in sustaining training on improved potato seed, relaxing credit constraints, and promoting diversification into off‐farm enterprises would enhance potato production and marketing.
Breeding of high seed oil oleate levels into Upland cotton from wild Gossypium barbadense L. germplasm
Authors: Dowd Michael K. , Shockey Jay , McCarty Jack C. , Jenkins Johnie N. 
Published: October 2023

AbstractA high seed oil oleate trait identified in wild Gossypium barbadense L. cotton accession GB713 (PI 608139) was bred into Upland cotton (Gossypium hirsutum L.) cultivar Sure‐Grow 747 (SG747, PVP 9800118). Starting from the F2 generation of an initial cross between GB713 and SG747, plants were selected by measuring the seed oil fatty acid distributions by gas chromatography. Selected F3 plants were crossed to M Rk‐Rn 6, a line previously created from GB713 and SG747 for improved nematode resistance. High‐oleate plants were selected in the F2 population. Selected plants were then crossed to HOa1 (a ∼35% oleate line derived from M Rk‐Rn 1, a sibling line to M Rk‐Rn 6), and high‐oleate plants were again selected in the F2 population. F3 plants were re‐selected for the high‐oleate trait, and four selected F4 lines were evaluated in 2022 field plots. The four lines had oleate levels between 52% and 57%, approximately triple that found in normal cottonseed oil (15%–19%) and higher than in either the high‐oleate wild GB713 parent (∼40%) or in the previously released HOa cotton plant lines (33%–35%). The increased oleate levels occurred with an approximately equal reduction in linoleic acid. Other seed and fiber properties were largely like those of SG747, although some residual GB713 character existed within the lines. The resulting oil composition should be ideal for use in deep fat frying, with the high level of oleic acid improving the oil's oxidative stability but with sufficient linoleic acid to maintain frying flavor.
Radical Thiocyano(Selenocyano)trifluoromethylations of Alkenes on Water
Authors: Gao Chi , Liu Yang , Zhu Hong‐Ye , Wang Mang 
Published: October 2023

AbstractTrifluoromethylation‐based difunctionalization of alkenes provides a step‐economical route to CF3‐containing polyfunctionalized organics. New and scalable processes are highly desired in this field. Here, we report a simple and environmentally benign method for olefinic thiocyanotrifluoromethylation. Using PhICF3Cl as unique CF3 agent and NaSCN as the SCN source, the difunctionalization of alkenes selectively occurs on water at ambient condition. Mechanism studies suggest a radical process in which SCN anion is proposed to act as not only reductive initiator but also S‐nucleophile. All tested reactions are compatible with mono‐, di‐, tri‐, and tetra‐substituted alkenes and with high functional group tolerance. This method is also suitable for the selenocyanotrifluoromethylation of alkenes. Therefore, a sustainable platform has been established to synthesize valuable β‐trifluoromethylated thio(seleno)cyanates in a green way.
Photoinduced 1,3‐Dipolar Cycloadditions of Cyclic Enones and 2,5‐Disubstituted Tetrazoles: An Unprecedented Pathway to Polysubstituted Pyrazolines and Pyrazoles
Authors: Labassi Chiraz , Fournier‐Le Ray Nicolas , Gauffre Fabienne , Fillaut Jean‐Luc , Gatri Rafik 
Published: October 2023

AbstractWe report herein the syntheses of original pyrazolines and pyrazoles through 1,3‐dipolar cycloaddition of cyclic enones with 2,5‐disubstituted nitrile imines achieved via photochemical activation of 2,5‐diaryl substituted tetrazoles. Monitoring of the reactions, similar to nitrile imine‐mediated tetrazole‐ene cycloadditions (NITEC), could be performed by means of UV‐vis absorption and emission measurements. The presence or absence of substituents in the alpha position of the ketone function makes it possible to direct these reactions towards the selective formation of pyrazoles or pyrazolines. The choice of the cyclic enones and 2,5‐disubstituted tetrazoles proved crucial for the fluorescence properties of the polycyclic derivatives obtained.
Decreasing the mean subtree order by adding k edges
Authors: Cambie Stijn , Chen Guantao , Hao Yanli , Tokar Nizamettin 
Published: October 2023

AbstractThe mean subtree order of a given graph , denoted , is the average number of vertices in a subtree of . Let be a connected graph. Chin et al. conjectured that if is a proper spanning supergraph of , then . Cameron and Mol disproved this conjecture by showing that there are infinitely many pairs of graphs and with , and such that . They also conjectured that for every positive integer , there exists a pair of graphs and with , , and such that . Furthermore, they proposed that provided . In this note, we confirm these two conjectures.
Association of hospital spending with care patterns and mortality in patients hospitalized with community‐acquired pneumonia
Authors: Latif Marina , Guo Ning , Tereshchenko Larisa G. , Rothberg Michael B. 
Published: October 2023

AbstractBackgroundPneumonia is a leading cause of mortality and intensive therapy is costly. However, it is unclear whether more spending is associated with better patient outcomes or how hospitals could decrease costs.ObjectivesThis study investigates the association between hospital spending and 14‐day inpatient mortality among community‐acquired pneumonia inpatients.MethodsThis retrospective cohort study focused on adult pneumonia patients discharged between July 2010 and June 2015 from 260 US hospitals in the Premier database. Hospitals were divided into four pneumonia cost‐of‐care quartiles and average cost was calculated for each hospital. Odds of 14‐day inpatient mortality and care practices were compared among high and low‐cost hospitals.ResultsThe study population comprised 534,038 patients with a mean age 69.5 (SD 16.3); 51.9% were female, 75% White, and 71.9% covered by Medicare. Hospitals were largely medium‐sized (40.4%), located in the South (49.2%), and in urban areas (82.3%). The fully adjusted population‐averaged cost was 14,486 US dollars (95% confidence interval [CI] 13,982–14,867). Hospital practices associated with cost included intensity of diagnostic work‐up +$14 (95% CI +12 to +18; p < .0001) and de‐escalation of antibiotic therapy, +$6836 (95% CI +2291 to +11,160; p = .004). There was no significant difference in odds of 14‐day inpatient mortality between hospitals in the highest and lowest cost quartiles.ConclusionsGreater spending at the hospital level was not associated with lower mortality. Lower diagnostic costs were associated with lower cost of care, suggesting that judicious use of diagnostic testing might reduce costs without worsening patient outcomes.