bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgery-Related Considerations in Treating People Who Use Cannabis
Authors: Mims Mark M. , Parikh Aniruddha C. , Sandhu Zainab , DeMoss Noah , Mhawej Rachad , Queimado Lurdes
Published: August 2024

Importance

Cannabis use has experienced substantial growth. Many patients treated by otolaryngologists are using cannabis in various forms, often without the knowledge of the treating surgeon. These cannabinoid substances have various systemic effects, and it is critical for otolaryngologists to recognize how cannabis use may contribute to a patient’s care.

Observations

Cannabis use has effects that contribute to every phase of a surgeon’s care. Preoperative counseling for tapering use may prevent increased rates of adverse effects. Care with anesthesia must be observed due to increased rates of myocardial ischemia, higher tolerance to standard doses, and prolonged sedation. Although results of studies are mixed, there may be an association with cannabis use and postoperative pain, nausea, and vomiting. Postoperative wound healing may be improved through the use of topical cannabinoids. Significant drug-drug interactions exist with cannabis, most notably with several common anticoagulant medications. Care should be exercised when managing medications for people who use cannabis. While many people who use cannabis consume it infrequently, a substantial population has developed cannabis use disorder, which is associated with increased morbidity and mortality postoperatively. Screening for cannabis use disorder is important and can be done through short screening tools.

Conclusions and Relevance

Patients who use cannabis may require special attention regarding preoperative counseling and workup, intraoperative anesthesia, postoperative pain management, nausea, wound healing, and drug-drug interactions. As patient use continues to increase, otolaryngologists will find an increasing need to remain up to date on how cannabis use contributes to patient care.
Bioelectrical Impedance Vectors Analysis of Sarcopenic Older Adults Submitted to a Resistance Training Program
Authors: Quizzini Giovanni Henrique , Pereira Caroline Galan de Souza , dos Santos Vanessa Ribeiro , Batista Vitor Cabrera , Silva Bruna Spolador de Alencar , Lira Fábio Santos , Ribeiro Alex Silva , Gobbo Luís Alberto
Published: August 2024

The objective of the present study is to analyze the changes in bioimpedance vector analysis (BIVA) and phase angle (PhA) in sarcopenic older people submitted to a 12‐week resistance training (RT) program according to classic and specific analyses. To this end, 20 sarcopenic older adults of both sexes, invited through media, underwent bioimpedance analysis before and after the RT carried out three times a week, for 12 weeks. The mean impedance vectors of the groups established for the confidence ellipses (95% of the confidence ellipse) are compared using Hotelling's T2 test. The distance D from Mahalanobis is also calculated. Classic and Specific BIVA are presented. The resistance values for the classical analyses (R/H) decreased across all groups (whole group, women and men, p < 0.05), with approximate decreases ranging from 9.4% to 10%, while the classic reactance (Xc/H) decreased (p < 0.05) only for the whole group (5.9%) and men (7.7%). For the specific BIVA, trends are verified for the whole sample, with a decrease in resistance (R.sp) and an increase in reactance (Xc.sp). In conclusion, the RT program in sarcopenic individuals promoted a reduction in resistance values in classical analyses, indicating a possible increase in hydration status and, consequently, musculoskeletal mass.
Two Birds with One Stone: Guanidyl Carbon Dots with Enhanced Antioxidative and Lipolytic Functions in Metabolic Associated Fatty Liver
Authors: Cai Hao , Li Yan , Wu Xiaoyan , Yang Yuxiang , Tedesco Antonio Claudio , Li Zijian , Bi Hong
Published: August 2024

Metabolic‐associated fatty liver disease (MAFLD) has become one of the most widespread metabolic diseases nowadays, while no definitive agent is approved for practical treatment. Given excessive lipid deposition and cellular oxidative stress are two main inducers of MAFLD, developing synergistic therapeutic agents that enhance lipid metabolism and antioxidative ability are effective routes for MAFLD therapy. Herein, a novel kind of bio‐functional carbon dots (MTCDs) derived from metformin and tea polyphenols based on a fused pharmacophore strategy is developed. The surface of MTCDs retains abundant phenolic hydroxyl and guanidine groups, which are designed to reduce both lipid deposition and oxidative stress in the liver. Moreover, by finely controlling the surface charge, MTCDs exhibit excellent lysosome targeting functionality with favorable biocompatibility and low biotoxicity. Mechanistical studies further reveal that MTCDs treatment protects lysosomes from oxidative stress damage and activates hepatocyte AMP‐activated protein kinase signaling, which initiates lipophagy progress to accelerate lipolysis and lipid consumption. Collectively, these studies propose an effective “two birds with one stone” tool for MAFLD synergistic therapy and suggest a viable strategy for multi‐pharmacophore agent development.
MOF‐818 Nanozyme Suppresses Calcium Oxalate Kidney Stones by Alleviating Oxidative Stress and Inflammatory Injury
Authors: Tian Yuan , Ye Ziyu , Wang Xunrui , Guan Hantian , Liu Weifeng , Duan Xiaolu , Liu Yang , Zeng Guohua , Liu Hongxing
Published: August 2024

There remains a lack of effective drugs to alleviate the kidney stones caused by oxidative stress and inflammatory damage. The MOF‐818 nanozyme is utilized to lessen the generation of reactive oxygen species (ROS) effectively, restore the membrane potential of mitochondria, regulate the cell cycle, decrease cell death, hinder the recruitment of macrophages, and mitigate the release of inflammatory factors in macrophages. These effects are attributed to the nanozyme's ability to mimic the enzyme properties of catalase (CAT) and superoxide dismutase (SOD). It is demonstrated that this nanozyme can reduce kidney calcium oxalate crystal deposition by reducing the renal injury caused by high concentration oxalate, upregulate the expression levels of SOD and CAT in tissues, downregulate adhesion proteins and inflammatory factor IL‐6 and TNF‐α, and promote the polarization of macrophages from M1 to M2 phenotype in the rat model induced by ethylene glycol. Overall, MOF‐818 has the potential to effectively suppress oxidative stress and inflammatory harm caused by high levels of oxalate, hence lowering the likelihood of stone formation. MOF‐818 nanozyme is also expected to be used as an alternative drug for the treatment of calcium oxalate kidney stones and provide an experimental theoretical basis for the development of new nanomedicines.
Synthesis of Heteromorphic Bi2WO6 Films With an Interpenetrate 1D/2D Network Structure for Efficient and Stable Photocatalytic Degradation of VOCs
Authors: Chen Yuehui , Zhang Liang , Chen Shuo , Sun Songmei , Cheng Hui , Li Shouzhu , Yu Jianyong , Ding Bin , Yan Jianhua
Published: August 2024

2D layered Bi2WO6 (BWO) is a widely used attractive photocatalyst for degrading VOCs, but the low visible‐light utilization and the easy stacking 2D nanosheets (NSs) limit photocatalysis efficiency and stability. Here, inspired by Eucalyptus, a synergistic strategy of multiscale domain‐confinement and electrostatic force action, based on electrospinning is proposed, for fabricating a heteromorphic BWO photocatalyst. It is found that BWO NSs can grow radially in an orderly spaced arrangement along BWO nanofibers (NFs) during sintering, thereby forming 1D/2D BWO junctions like eucalyptus leaves. This interpenetrating 1D/2D network structure not only solves the easy stacking problem of BWO NSs but also selectively exposes the {010} crystal planes that exhibit efficient hole oxidation. In addition, this peculiar structure enriches electrons at the 1D/2D interface to avoid carrier recombination, thus improving the photocatalytic activity. The photocatalyst material with a reduced bandgap width from 2.56 to 2.49 eV can rapidly degrade 100% of acetaldehyde under visible light without using sacrificial agents and photosensitizers and shows superior stability for eight cycles without any decay. This study provides a feasible method to synthesize an efficient and stable BWO photocatalyst.
Excitation Wavelength Dependent Fluorescence and Phosphorescence from Organic Ionic Crystalline Powder
Authors: Gong Qi , Dai Xianyin , Yuan Chunhao , Li Jinwei , Zhang Yipeng , Zhang Jiesen , Ge Yanqing
Published: August 2024

A new type of material, organic salts in the crystal and crystalline powder state, with both excitation wavelength dependent (Ex‐De) fluorescence and Ex‐De phosphorescence under ambient conditions have been reported. The single component triphenylsulfonium chloride displays tunable fluorescent colors ranging from light purple to sky blue and tunable afterglow colors varying from green to yellowish green, to yellow (lifetimes: 57, 141, 66 ms, afterglow lasting for 2.1, 2.0, 2.3 s). The relationship between the structure and luminescence performance of 17 sulfonium salt derivatives confirms the pivotal roles of both the anions and the electronic and steric effect of substituent factors for luminescence. Single‐crystal analysis reveals that unique ionic bonding and intermolecular interaction can promote an ordered arrangement of organic salts in a crystal state, which then can facilitate molecular aggregation for phosphorescence generation. Theoretical calculations have also confirmed this viewpoint. More importantly, these sulfonium salt derivatives can be used for advanced multimodal anti‐counterfeiting and mitochondrial imaging, respectively. This study has not only expanded the scope of Ex‐De materials but also extended their applications.
Palladium‐Catalyzed Cross‐Coupling between Alkylidenecyclopropanes and Boronic Acids
Authors: Rodiño Ricardo , Mardones Fernando , Paredes Krishna , Jiménez Claudio A. , Nelson Ronald , Mascareñas José L. , López Fernando , Verdugo Felipe
Published: August 2024

The combination of a Pd(0) source and a phosphoramidite ligand promotes a formal allylic cross‐coupling between alkylidenecyclopropanes (ACPs) and boronic acids to yield synthetically appealing 1,1‐disubstituted alkenes. Remarkably, the reaction proceeds both under neutral and basic conditions, and works with both aryl‐ and alkenylboronic acids. DFT calculations suggest that the reaction entails a C−C activation/protonation mechanism instead of a hydropalladation pathway, which has been frequently proposed for other metal‐promoted hydrofunctionalizations of ACPs.
Molecular Synergistic Effect for High Efficiency Monolithic Perovskite/Perovskite/Silicon Triple‐Junction Tandem Solar Cells
Authors: Ye Tianshi , Qiao Liang , Wang Tao , Wang Pengshuai , Zhang Lin , Sun Ruitian , Kong Weiyu , Xu Menglei , Yan Xunlei , Yang Jie , Zhang Xinyu , Ma Linlin , Yang Xudong
Published: August 2024

Perovskite/perovskite/silicon triple‐junction tandem solar cells (TSCs) hold promise for high power conversion efficiencies (PCE). However, the efficiency is still relatively low due to the non‐radiative recombination losses in wide‐bandgap top cells. These losses, attributed to the interface defect states and energy level mismatches, present considerable challenges to realizing high‐performance and stable TSCs. Here, the molecular synergistic effect (MSE) is exploited to passivate interface in 1.95 eV top cells. Piperazine‐1‐carboxamide hydrochloride (PCACl) is combined, which possesses strong dipole moments and passivating functional groups that can bind with two neighboring uncoordinated lead ions and form hydrogen bonds with halide atoms at perovskite surface, with 1,3‐propane‐diammonium iodide, which can reduce interface recombination through field‐effect passivation. The MSE enabled by PCACl and PDAI2 facilitates excellent energy level alignment and reduces non‐radiative recombination losses and light‐induced phase segregation. Finally, the target perovskite/perovskite/silicon triple‐junction TSC obtains an open‐circuit voltage of 3.07 V and a champion PCE of 25.2% (for a 1.035 cm2 aperture area).
Progress and Challenges in Buffer Layers Between Cathode Materials and Sulfide Solid Electrolytes in All‐Solid‐State Batteries
Authors: Byeon Yun Seong , Kim Dongil , Han Sang A , Kim Jung Ho , Park Min‐Sik
Published: August 2024

All‐solid‐state batteries (ASSBs), configured with solid electrolytes, have received considerable attention as a future energy solution across diverse sectors of modern society. Unlike conventional liquid electrolytes in particular, sulfide solid electrolytes have various advantages, such as high ionic conductivity (>10−3 S cm−1), good ductile properties, and thermal stability. Despite these advantages, the practical application of sulfide solid electrolytes in ASSBs is still limited due to their interfacial instability with commercial cathode materials. Unfortunately, the spontaneous formation of a space charge layer (SCL) at the interface between the cathode material and the solid electrolyte leads to heightened interfacial resistance, obstructing Li+ transport. To address this issue, proper interfacial engineering is still required to facilitate smooth Li+ migration across the interfaces. In this respect, various functional materials have been under exploration as buffer layers, which are intended to suppress the formation of the SCL at these interfaces. Herein, focus is given on the critical significance of these buffer layers between cathode materials and sulfide solid electrolytes in the development of ASSBs. Considering the present limitations, future research directions for next‐generation ASSBs are discussed. These insights are poised to offer valuable guidance for the strategic design and development of highly reliable ASSBs.
Versatile and efficient fabrication of signal “turn‐on” lateral flow assay for ultrasensitive naked eye detection of small molecules based on self‐assembled fluorescent gold nanoclusters‐antigen aggregates
Authors: Chao Mengjia , Tai Shengmei , Mao Minxin , Cao Wenbo , Peng Chifang , Ma Wei , Feng Yongwei , Wang Zhouping
Published: August 2024

Fluorescence signal “turn‐on” lateral flow immunoassay (FONLFA) through nanomaterial labeled quenching fluorescent nanomaterial has shown significant potential for the detection of small molecules. However, the fluorescent nanomaterial immobilization on nitrocellulose (NC) membrane commonly requires tedious chemical modification and only a few combinations of fluorescence donor and quencher have been applied in FONLFA. In this work, bright fluorescent metal nanoclusters (Prot‐AuNCs) were prepared and self‐assembled into Prot‐AuNCs/antigen aggregates with three typical small molecule antigens, respectively. The aggregates can be readily immobilized on the surface of the NC membrane, indicating that this strip fabrication strategy has good versatility. Moreover, we evaluated the performances of this FONLFA platform by using carbendazim as a model target and investigated four typical nanomaterials as colorimetric nanoprobes and fluorescence quenchers. We found that all the nanoprobes demonstrated significantly improved naked eye detection sensitivity (vLOD) and limits of detection (LODs) in quantitative analysis. Among them, combing the Fe‐polydopamine nanoparticles as quencher with the above aggregates, the FONLFA in signal “turn‐on” mode achieved 200‐fold improved vLOD (0.05 ng mL−1) compared with conventional colorimetric AuNPs‐based lateral flow immunoassay (AuNPs‐LFA) (10 ng mL−1). In addition, the LOD in quantitative analysis also was improved by 22‐fold and the whole test process was completed within 10 min. With the advantages of efficient fabrication, extraordinary sensitization, and good biocompatibility, our FONLFA platform is expected to have great potential in the rapid detection of various small molecules.
CT1812 biomarker signature from a meta‐analysis of CSF proteomic findings from two Phase 2 clinical trials in Alzheimer's disease
Authors: Lizama Britney N. , Williams Claire , North Hilary A. , Pandey Kiran , Duong Duc , Di Caro Valentina , Mecca Adam P. , Blennow Kaj , Zetterberg Henrik , Levey Allan I. , Grundman Michael , van Dyck Christopher H. , Caggiano Anthony O. , Seyfried Nicholas T. , Hamby Mary E.
Published: August 2024

INTRODUCTION

CT1812 is in clinical development for the treatment of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) exploratory proteomics was employed to identify pharmacodynamic biomarkers of CT1812 in mild to moderate AD from two independent clinical trials.

METHODS

Unbiased analysis of tandem‐mass tag mass spectrometry (TMT‐MS) quantitative proteomics, pathway analysis and correlation analyses with volumetric magnetic resonance imaging (vMRI) were performed for the SPARC
cohort (NCT03493282). Comparative analyses and a meta‐analysis with the interim SHINE cohort (NCT03507790; SHINE‐A) followed by network analysis (weighted gene co‐expression network analysis [WGCNA]) were used to understand the biological impact of CT1812.

RESULTS

CT1812 pharmacodynamic biomarkers and biological pathways were identified that replicate across two clinical cohorts. The meta‐analysis revealed novel candidate biomarkers linked to S2R biology and AD, and network analysis revealed treatment‐associated networks driven by S2R. 

DISCUSSION

Early clinical validation of CT1812 candidate biomarkers replicating in independent cohorts strengthens the understanding of the biological impact of CT1812 in patients with AD, and supports CT1812's synaptoprotective mechanism of action and its continued clinical development.

Highlights

This exploratory proteomics study identified candidate biomarkers of CT1812 in SPARC (NCT03493282)

Comparative analyses identified biomarkers replicating across trials/cohorts

Two independent Ph2 trial cohorts (SPARC and interim SHINE [NCT03507790; SHINE‐A]) were used in a meta‐analysis

Amyloid beta (Aβ) & synaptic biology impacted by CT1812 and volumetric magnetic resonance imaging (vMRI) treatment‐related correlates emerge

Network analyses revealed sigma‐2 receptor (S2R)‐interacting proteins that may be “drivers” of changes
Tricyanmethan oder Dicyanketenimin – Silylierung macht den Unterschied
Authors: Surkau Jonas , Bresien Jonas , Michalik Dirk , Schulz Axel
Published: August 2024

Pseudohalogenide wie Tricyanmethanid, [C(CN)3]−, sind in der Chemie sowie Biochemie weit verbreitet. Die protonierte Spezies HC(CN)3, eine klassische Pseudohalogen‐Wasserstoff‐Brønsted‐Säure, ist eine sehr starke Säure mit einem pKS‐Wert von −5. HC(CN)3 ist jedoch schwer zu handhaben, da es dazu neigt, sich schnell zu zersetzen oder – genauer gesagt – zu oligo‐ und polymerisieren. Daher sind silylierte Pseudohalogenid‐Verbindungen mit dem [Me3Si]+ als „großem metallorganischen Proton“ von Interesse, die ähnliche chemische Eigenschaften, aber eine bessere kinetische Stabilisierung aufweisen. Hier wird von der schrittweisen Silylierung des Pseudohalogenid‐Anions [C(CN)3]− berichtet, wobei das schwerere Homolog von HC(CN)3, nämlich [Me3Si][C(CN)3], und in Gegenwart von zwei zusätzlichen [Me3Si]+‐Kationen sogar die dikationische Spezies [(Me3Si−NC)3C]2+ als stabiles [B(C6F5)4]‐Salz gebildet wird. Überraschenderweise erfolgt im Gegensatz zur protonierten Spezies HC(CN)3, bei der das Proton an das zentrale C‐Atom von [C(CN)3]− gebunden ist, die Silylierung des [C(CN)3]−‐Anions an einem der drei terminalen N‐Atome, wodurch das lange gesuchte Dicyanketenimin [Me3Si−NC−C(CN)2] gebildet wird. Alle weiteren Silylierungsschritte finden ausschließlich an den terminalen N‐Atomen der drei CN‐Gruppen und nicht am zentralen C‐Atom statt, bis schließlich das bis dato unbekannte, hochsymmetrische Dikation, [(Me3Si−NC)3C]2+, gebildet wird. Die experimentellen Daten werden durch quantenchemische Berechnungen in Bezug auf Thermodynamik und chemische Bindungen unterstützt.
Programmable In‐Situ Co‐Assembly of Organic Multi‐Block Nanowires for Cascade Optical Waveguides
Authors: Zhao Shuai , Zhang Jia‐Xuan , Xu Chao‐Fei , Ma Yingxin , Luo Jia‐Hua , Lin Hongtao , Shi Yingli , Wang Xue‐Dong , Liao Liang‐Sheng
Published: August 2024

Organic heterostructures (OHs) with multi‐segments exhibit special optoelectronic properties compared with monomeric structures. Nevertheless, the synthesis of multi‐block heterostructures remains challenging due to compatibility issues between segment parts, which restricts their application in optical waveguides and integrated optics. Herein, we demonstrate programmable in‐situ co‐assembly engineering, combining multi‐step spontaneous self‐assembly processes to promote the synthesis of multi‐block heterostructures with a rational arrangement of three or more segments. The rational design of segments enables exciton manipulation and ensures optical waveguides and proper output among the multi‐segment OHs. This work enables the controllable growth of segments within multi‐block OHs, providing a pathway to construct complex OHs for the rational development of future optical applications.
3‐Arylcoumarin Scaffolds From 3‐Chlorocoumarin and Arylboronic Acids via Site‐Selective CCl Bond Activation With Palladium Complexes of N∩O Chelating Hydrazones
Authors: Shalini C. , Akilesh M. , Sathiyaraj G. , Bhuvanesh N. S. P. , Neethu K. S. , Kaveri M. V. , Dharmaraj N.
Published: August 2024

Using palladium hydrazone complex as a homogeneous catalyst for SMC, we synthesized a library of 15 variant 3‐arylcoumarins. In this context, we report a set of four coordinated palladium(II) hydrazone complexes 1 and 2 having the general formula [Pd(L)(Cl)(PPh3)] by reacting the precursor complex [PdCl2(PPh3)2] with the hydrazone ligands HL1 or HL2. Single crystal XRD and conventional spectroscopic techniques were employed to characterize both complexes. From the catalytic application point of view, the new complexes 1 and 2 were tested as homogeneous catalysts towards the conversion of 3‐chlorocoumarins into 3‐arylcoumarins by activating the challenging CCl functionality. A minimal catalyst loading of complex 2 (0.01 mol%), afforded a series of 3‐arylcoumarins with a maximum of 92% yield and reusability up to five cycles. The present methodology is simple and easy to carry out at room temperature utilizing a green solvent (ethanol) in an open flask with a spectrum of aryl boronic acids.
Study of polypropylene/polyethylene terephthalate blends compatibilized with polypropylene double‐grafted maleic anhydride and epoxy resin
Authors: Xu Mengxia , Liao Jingshun , Luo Zhu , He Ruhui , Yang Shenglong , Li Hai , Yang Yehan
Published: August 2024

Polypropylene double‐grafted maleic anhydride and bisphenol A epoxy resin (PP‐g‐M‐E) was successfully prepared by a single‐step method and characterized by Fourier‐transform infrared spectroscopy. Subsequently, it was employed as a compatibilizer to fabricate polypropylene (PP)/polyethylene terephthalate (PET) blends via melt extrusion. The content of the PET dispersed phase in the composite varied from 0 to 30 phr. The microstructure and morphology of the composites were characterized using scanning electron microscopy and Raman spectroscopy. The addition of PP‐g‐M‐E increased the interfacial interaction between the two phases and improved the compatibility and thermal stability of the system. In the presence of the compatibilizer, the crystallinity of the matrix phase (PP) increased, while that of the dispersed phase (PET) decreased owing to the heterogeneous nucleation effect of uniformly distributed PET. Double grafting of the PP‐g‐M‐E compatibilizer considerably enhanced the mechanical performance of the PP/PET blend system. The elongation at break of the modified sample exceeded that of the PP/PET blends by 117.55%, and the flexural and impact properties also showed considerable improvement.
Effects of high temperature on the growth performance and midgut autophagy of thermotolerant and thermosensitive silkworm strains
Authors: Guo Huiduo , Ling Mingfa , Yang Runhuan , Gui Tao , Li Gang , Zhao Guodong , Wang Wenbin , Qian Heying
Published: August 2024

High temperature stress has long‐term negative effects on the growth and development of silkworm (Bombyx mori). Different silkworm varieties show the different tolerance to high temperature. The induction of autophagy is linked to increased thermotolerance in diverse ectothermic organisms. However, the function of autophagy in the thermotolerant and thermosensitive silkworm strains under high‐temperature conditions remains unclear. The thermotolerant Liangguang NO.2 and thermosensitive Jingsong × Haoyue strains were used to explore the role of autophagy in thermotolerance. Here, we first found that the larval body weight gain was increased in the thermosensitive Jingsong × Haoyue strain, but there was no difference in the thermotolerant Liangguang NO.2 strain under high temperature conditions. High temperature stress had a negative influence on the cocoon performance in both the Liangguang NO.2 and Jingsong × Haoyue strains. Additionally, the autophagy‐related gene Atg5 mRNA expression in the Liangguang NO.2 strain was upregulated by high temperature, while the expression of Atg12 mRNA was reduced in the Jingsong × Haoyue strain. Titers of 20‐Hydroxyecdysone and the ultraspiracle 1 mRNA expression in the Liangguang NO.2 strain were upregulated by high temperature, which might be associated with the induction of autophagy. These results demonstrate the potentially regulatory mechanism of autophagy in silkworms' tolerance to high temperature, providing a theoretical basis for exploring the physiological mechanism of thermotolerance in insects.
Cover Picture: Astron. Nachr. 7/2024
Authors: Strassmeier Klaus G. , Ilyin Ilya , Woche Manfred , Dionies Frank , Weber Michael , Järvinen Arto , Denker Carsten , Dineva Ekaterina , Verma Meetu , Granzer Thomas , Bittner Wilbert , Bauer Svend‐Marian , Paschke Jens , Önel Hakan
Published: August 2024

First‐light spectra of the Sun as a star taken by SDI‐POL, the Solar Disk Integration POLarimeter feeding the PEPSI night‐time spectrograph at the LBT. The top panel shows the full wavelength range (383 ‐ 907 nm) covered by SDI‐POL. The color of the Stokes I spectra indicates the individual cross dispersers; dark blue (=CD 1) to dark red (=CD 6). The line at the bottom represents the normalized Stokes V Q & U signal on the same intensity scale as Stokes I. The bottom panel is a zoom into the spectral region around the sodium D lines. The top spectrum is again Stokes I (plotted are dots per CCD pixel connected by a line), the bottom spectra are Stokes V Q U shifted by ‐0.10 in intensity and expanded by a factor 200 in scale with respect to Stokes I. The I Q U spectrum was taken on UT May 20, 2022, the V‐spectrum on UT June 22, 2023. The first‐light application detects a clear Stokes V/I profile indicative of a tiny but significant solar disk‐averaged line‐of‐sight net magnetic field of +0.37±0.02 Gauß on Oct. 13, 2023, as reported in the article by Strassmeier et al., this issue, e240033.

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Immunogenic cell death–related genes predict prognosis and response to immunotherapy in lung squamous cell carcinoma
Authors: Li Guoping , Chen Kai , Dong Shunli , Wei Xiang , Zhou Lingyan , Wang Bin
Published: August 2024

Lung squamous cell carcinoma (LUSC) is a malignancy with limited therapeutic options. Immunogenic cell death (ICD) has the potential to enhance the efficacy of cancer therapy by triggering immune responses. We aimed to explore the potential of ICD‐based classification in predicting prognosis and response to immunotherapy for LUSC. RNA‐seq information and clinical data of LUSC patients were obtained from The Cancer Genome Atlas (TCGA) dataset. ICD‐related gene expressions in LUSC samples were analyzed by consensus clustering. Subsequently, differentially expressed genes (DEGs) between different ICD‐related subsets were analyzed. Tumor mutation burden, immune cell infiltration, and survival analyses were conducted between different ICD subsets. Finally, an ICD‐related risk signature was constructed and evaluated in LUSC patients, and the immunotherapy responses based on the gene expressions were also forecasted. ICD‐high and ICD‐low groups were defined, and 1466 DEGs were identified between the two subtypes. These DEGs were mainly enriched in collagen‐containing extracellular matrix, cytokine–cytokine receptor interaction, the PI3K‐Akt signaling pathway, and neuroactive ligand–receptor interaction. Furthermore, the ICD‐low group exhibited a favorable prognosis, enhanced TTN and MUC16 mutation frequencies, increased infiltrating immune cells, and downregulated immune checkpoint expressions. Furthermore, we demonstrated that an ICD‐related model (based on CD4, NLRP3, NT5E, and TLR4 genes) could forecast the prognosis of LUSC, and ICD risk scores were lower in the responder group. In summary, the predicted values of ICD‐related genes (CD4, NLRP3, NT5E, and TLR4) for the prognosis and response to immunotherapy in LUSC were verified in the study, which benefits immunotherapy‐based interventions for LUSC patients.
Inhibitory effects of Gracilaria edulis and Gracilaria salicornia against the MGMT and VEGFA biomarkers involved in the onset and advancement of glioblastoma using in silico and in vitro approaches
Authors: Vasudevan Miji Thandaserry , Rangaraj Kaviyaprabha , Ramesh Ragupathi , Muthusami Sridhar , Govindasamy Chandramohan , Khan Muhammad Ibrar , Arulselvan Palanisamy , Muruganantham Bharathi
Published: August 2024

Glioblastoma (GBM), an aggressive primary brain tumor originating from glial cells, poses significant treatment challenges due to its rapid growth and invasiveness. The exact mechanisms of GBM's brain damage remain unclear. This study examines primary molecular markers commonly assessed in GBM patients, including brain‐derived neurotrophic factor (BDNF), platelet‐derived growth factor receptor A (PDGFRA), O6‐methylguanine DNA methyltransferase (MGMT), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor A (VEGFA) using computational approaches. The study revealed significant differences (p ≤ 0.05) in PDGFRA, EGFR, and VEGFA expression rates, which are particularly interesting. Additionally, MGMT and VEGFA showed higher hazard ratios. Expression levels of MGMT and VEGFA were visualized in immune and malignant cells using single‐cell RNA datasets GSE103224 and GSE148842. From a total of 48 compounds in Gracilaria edulis and 86 in Gracilaria salicornia, we identified 15 compounds capable of crossing the blood‐brain barrier. Notably, 2‐tridecanone (binding affinity [BA] = −4.2 kcal/mol; root mean square deviation [RMSD] = 1.479 Å) and decanoic acid, ethyl ester (BA = −4.2 kcal/mol; RMSD = 1.702 Å) from G. edulis interacted with MGMT via hydrogen bonds. The compound alpha‐terpineol interacted with MGMT (BA = −5.7 kcal/mol; RMSD = 0.501 Å) and VEGFA (BA = −4.7 kcal/mol; RMSD = 2.483 Å). Ethanolic and methanolic extracts from G. edulis and G. salicornia demonstrated mild anti‐cell proliferation properties in the GBM LN‐229 cell line, suggesting potential therapeutic benefits. This study highlights the significance of molecular markers and natural compounds in understanding and potentially treating GBM.
Altered gyrification in chemotherapy‐treated older long‐term breast cancer survivors
Authors: Daniel Ebenezer , Deng Frank , Patel Sunita K. , Sedrak Mina S. , Kim Heeyoung , Razavi Marianne , Sun Can‐Lan , Root James C. , Ahles Tim A. , Dale William , Chen Bihong T.
Published: August 2024

Purpose

The purpose of this prospective longitudinal study was to evaluate the changes in brain surface gyrification in older long‐term breast cancer survivors 5–15 years after chemotherapy treatment.

Methods

Older breast cancer survivors aged ≥ 65 years treated with chemotherapy (C+) or without chemotherapy (C‐) 5–15 years prior and age‐ and sex‐matched healthy controls (HC) were recruited (time point 1 (TP1)) and followed up for 2 years (time point 2 (TP2)). Study assessments for both time points included neuropsychological (NP) testing with the NIH Toolbox cognition battery and cortical gyrification analysis based on brain MRI.

Results

The study cohort with data for both TP1 and TP2 consisted of the following: 10 participants for the C+ group, 12 participants for the C‐ group, and 13 participants for the HC group. The C+ group had increased gyrification in six local gyral regions including the right fusiform, paracentral, precuneus, superior, middle temporal gyri and left pars opercularis gyrus, and it had decreased gyrification in two local gyral regions from TP1 to TP2 (p < .05, Bonferroni corrected). The C‐ and HC groups showed decreased gyrification only (p < .05, Bonferroni corrected). In the C+ group, changes in right paracentral gyrification and crystalized composite scores were negatively correlated (R = –0.76, p = .01).

Conclusions

Altered gyrification could be the neural correlate of cognitive changes in older chemotherapy‐treated long‐term breast cancer survivors.
Markers of too little effort or too much alertness during neuropsychological assessment: Demonstration with perioperative changes
Authors: Baron‐Shahaf Dana , Shahaf Goded
Published: August 2024

Objective

Cognitive assessment is based on performance in different tests. However, this performance might be hindered by lack of effective effort on the one hand, and by too much stress on the other hand. Despite their known impact, there are currently no effective tools for measuring cognitive effort or stress effect during cognitive assessment. We developed real‐time electrophysiological markers for cognitive effort and for stress effect, which could be used during cognitive assessment.

Methods

We assessed these markers during the use of the Montreal Cognitive Assessment (MoCA) before and after cardiac surgery, which is known to involve cognitive decline in up to 30%–50% of elderly patients.

Results

The major findings of the study, for the largest group of patients, with preoperative MoCA in the intermediate range, were that the decline is significantly associated (1) with higher preoperative cognitive effort and (2) with higher postoperative stress effect during the test.

Conclusions

These findings, as well as preliminary additional ones, suggest a potential importance for monitoring cognitive effort and stress effect during assessment in general, and specifically during perioperative assessment.

Significance

Easy‐to‐use markers could improve the efficacy of cognitive assessment and direct treatment generally, and specifically for perioperative decline.
Small Molecule Induces Time‐Dependent Inhibition of Stat3 Dimerization and DNA‐Binding Activity and Regresses Human Breast Tumor Xenografts
Authors: Yue Peibin , Chen Yue , Ogese Monday O. , Sun Shan , Zhang Xiaolei , Esan Taiwo , Buolamwini John K. , Turkson James
Published: August 2024

Aberrantly‐active signal transducer and activator of transcription (Stat)3 has a causal role in many human cancers and represents a validated anticancer drug target, though it has posed significant challenge to drug development. A new small molecule, JKB887, was identified through library screening and is predicted to interact with Lys591, Arg609 and Pro63 in the phospho‐tyrosine (pTyr)‐binding pocket of the Stat3 SH2 domain. JKB887 inhibited Stat3 DNA‐binding activity in vitro in a time‐dependent manner, with IC50 of 2.2–4.5 μM at 30–60‐min incubation. It directly disrupted both the Stat3 binding to the cognate, high‐affinity pTyr (pY) peptide, GpYLPQTV‐NH2 in fluorescent polarization assay with IC50 of 3.5–5.5 μM at 60–90‐min incubation, and to the IL‐6 receptor/gp130 or Src in treated malignant cells. Treatment with JKB887 selectively blocked constitutive Stat3 phosphorylation, nuclear translocation and transcriptional activity, and Stat3‐regulated gene expression, and decreased viable cell numbers, cell growth, colony formation, migration, and survival in human or mouse tumor cells. By contrast, JKB887 had minimal effects on Stat1, pErk1/2MAPK, pShc, pJAK2, or pSrc induction, or on cells that do not harbor aberrantly‐active Stat3. Additionally, JKB887 inhibited growth of human breast cancer xenografts in mice. JKB887 is a Stat3‐selective inhibitor with demonstrable antitumor effects against Stat3‐dependent human cancers.
Photoinduced Decarboxylative Thioacylation of N‐Hydroxyphthalimide Esters with Tetraalkylthiuram Disulfides
Authors: Wang Qian , Zhang Cheng‐Lin , Li Yan‐Fei , Zhou Yu‐Jing , Cui Fei‐Hu , Jiang Jing‐Chen , Pan Ying‐Ming , Duan Wen‐Gui , Tang Hai‐Tao
Published: August 2024

Dithiocarbamate is a key structural sequence in pharmaceuticals and agrochemicals, and its synthesis is crucial in organic chemistry. Although significant progress has been made in related synthesis research, developing a practical and universal synthesis method remains fascinating. Herein, we report a new visible‐light‐induced decarboxylation coupling reaction between N‐hydroxyphthalimide esters and tetraalkylthiuram disulfides, which uses Ir(ppy)3 as a photocatalyst to promote the generation of corresponding decarboxylation thioacylation product‐dithiocarbamates in high yields. This redox‐neutral protocol uses inexpensive and readily available starting material under mild reaction conditions, exhibiting broad substrate scope and wide functional group compatibility. This method can be further used for post modification of complex natural products and bioactive drugs.
Rational Design of Co(II)‐Pyridine‐Decorated Reduced Phosphomolybdate Photocatalysts for Efficient Aniline Oxidation under Mild Conditions
Authors: Liu Xiaohui , Li Hui , Xu Na , Guo Yanyan , Zhang Xiaoyan , Wang Xiuli
Published: August 2024

Comprehensive Summary

The conversion of aniline to nitrosobenzene (NSB), a key step in the synthesis of important chemicals, demands the development of environmentally friendly photocatalysts that operate under mild conditions. This process is driven by the need for sustainable methods, given toxic nature of aniline and its central role in the production of dyes, pharmaceuticals, and agricultural chemicals. This study reports on the synthesis of three reduced phosphomolybdate compounds with Co(II) centers and polypyridine ligands, which show great potential as photocatalysts for the mild oxidation of aniline to NSB. The synthesis uses 30% H2O2 as the oxidant and the compounds as the sole catalysts, achieving high conversion rates and selectivity without additional additives or photosensitizers. The integration of multidentate ligands with {P4Mo6} clusters significantly reduces the band gap, facilitating visible‐light‐driven photocatalysis. The adsorption interaction between coordinated water molecules and Co ions and H2O2 is found to enhance the conversion rate of aniline, a finding supported by DFT analyses.
Stereoselective Synthesis of C‐Vinyl Glycosides via Nickel‐Catalyzed Cross‐Electrophile Couplings of 1,2‐Glycosyl Orthoesters and Vinyl Halides
Authors: Wang Xin , Chen Anrong , Zhao Shiyin , Tao Qiang , Yang Bo , Zhang Xing , Zhu Feng
Published: August 2024

Comprehensive Summary

A highly stereoselective nickel‐catalyzed cross‐electrophile coupling of readily accessible, novel, stable oxygen‐based glycosyl radical precursors, specifically 1,2‐glycosyl orthoesters, is developed. This approach offers an effective pathway to synthesize diverse C‐vinyl glycosides, characterized by good yields, excellent stereoselectivity, mild reaction conditions, a broad substrate scope, and versatile transformations of the resulting products.
Effect of Obesity on the Use of Antiarrhythmics in Adults With Atrial Fibrillation: A Narrative Review
Authors: Shaikh Fahad , Wynne Rochelle , Castelino Ronald L. , Davidson Patricia M. , Inglis Sally C. , Ferguson Caleb
Published: August 2024

Background

Atrial fibrillation (AF) and obesity coexist in approximately 37.6 million and 650 million people globally, respectively. The anatomical and physiological changes in individuals with obesity may influence the pharmacokinetic properties of drugs.

Aim

This review aimed to describe the evidence of the effect of obesity on the pharmacokinetics of antiarrhythmics in people with AF.

Methods

Three databases were searched from inception to June 2023. Original studies that addressed the use of antiarrhythmics in adults with AF and concomitant obesity were included.

Results

A total of 4549 de‐duplicated articles were screened, and 114 articles underwent full‐text review. Ten studies were included in this narrative synthesis: seven cohort studies, two pharmacokinetic studies, and a single case report. Samples ranged from 1 to 371 participants, predominately males (41%–85%), aged 59–75 years, with a body mass index (BMI) of 23–66 kg/m2. The two most frequently investigated antiarrhythmics were amiodarone and dofetilide. Other drugs investigated included diltiazem, flecainide, disopyramide, propafenone, dronedarone, sotalol, vernakalant, and ibutilide. Findings indicate that obesity may affect the pharmacokinetics of amiodarone and sodium channel blockers (e.g., flecainide, disopyramide, and propafenone). Factors such as drug lipophilicity may also influence the pharmacokinetics of the drug and the need for dose modification.

Discussion

Antiarrhythmics are not uniformly affected by obesity. This observation is based on heterogeneous studies of participants with an average BMI and poorly controlled confounding factors such as multimorbidity, concomitant medications, varying routes of administration, and assessment of obesity. Controlled trials with stratification at the time of recruitment for obesity are necessary to determine the significance of these findings.
The blockchain‐based privacy‐preserving searchable attribute‐based encryption scheme for federated learning model in IoMT
Authors: Zhou Ziyu , Wang Na , Liu Jianwei , Fu Junsong , Deng Lunzhi
Published: August 2024

Federated learning enables training healthcare diagnostic models across multiple decentralized devices containing local private health data samples, without transferring data to a central server, providing privacy‐preserving services for healthcare professionals. However, for a model of a specific field, some medical data from non‐target participants may be included in model training, compromising model accuracy. Moreover, diagnostic queries for healthcare models stored in cloud servers may result in the leakage of the privacy of healthcare participants and the parameters of models. Furthermore, the records of model searching and usage could be tracked causing privacy disclosure risk. To address these issues, we propose a blockchain‐based privacy‐preserving searchable attribute‐based encryption scheme for the diagnostic model federated learning in the Internet of Medical Things (BSAEM‐FL). We first adopt fine‐grained model trainer participation policies for federated learning, using the attribute‐based encryption (ABE) mechanism, to realize model accuracy and local data privacy. Then, We employ searchable encryption technology for model training and usage to protect the security of models stored in the cloud server. Blockchain is utilized to implement distributed healthcare models' keyword‐based search and model users' attribute‐based authentication. Lastly, we transfer most of the computational overhead of user terminals in model searching and decryption to edge nodes, achieving lightweight computation of IoMT terminals. The security analysis proves the security of the proposed healthcare scheme. The performance evaluation indicates our scheme is of better feasibility, efficiency, and decentralization.
Increased Netrin downstream of overactive Hedgehog signaling disrupts optic fissure formation
Authors: Lusk Sarah , LaPotin Sarah , Presnell Jason S. , Kwan Kristen M.
Published: August 2024

Background

Uveal coloboma, a developmental eye defect, is caused by failed development of the optic fissure, a ventral structure in the optic stalk and cup where axons exit the eye and vasculature enters. The Hedgehog (Hh) signaling pathway regulates optic fissure development: loss‐of‐function mutations in the Hh receptor ptch2 produce overactive Hh signaling and can result in coloboma. We previously proposed a model where overactive Hh signaling disrupts optic fissure formation by upregulating transcriptional targets acting both cell‐ and non‐cell‐autonomously. Here, we examine the Netrin family of secreted ligands as candidate Hh target genes.

Results

We find multiple Netrin ligands upregulated in the zebrafish ptch2 mutant during optic fissure development. Using a gain‐of‐function approach to overexpress Netrin in a spatiotemporally specific manner, we find that netrin1a or netrin1b overexpression is sufficient to cause coloboma and disrupt wild‐type optic fissure formation. We used loss‐of‐function alleles, CRISPR/Cas9 mutagenesis, and morpholino knockdown to test if loss of Netrin can rescue coloboma in the ptch2 mutant: loss of netrin genes does not rescue the ptch2 mutant phenotype.

Conclusion

These results suggest that Netrin is sufficient but not required to disrupt optic fissure formation downstream of overactive Hh signaling in the ptch2 mutant.
Differences in heart failure with preserved ejection fraction management between care providers: an international survey
Authors: Guidetti Federica , Giraldo Clara Inés Saldarriaga , Shchendrygina Anastasia , Kida Keisuke , Niederseer David , Basic Carmen , Rainer Peter P. , Załęska‐Kocięcka Marta , Ogola Elijah , Mohty Dania , Lanfranchi Giuseppina , Sari Novi Yanti , Einarsson Hafsteinn , Zurek Marzena , Ruschitzka Frank , Savarese Gianluigi , Mewton Nathan
Published: August 2024

Aims

Heart failure (HF) with preserved ejection fraction (HFpEF) is characterized by growing incidence and poor outcomes. A large majority of HFpEF patients are cared by non‐cardiologists. The availability of sodium–glucose cotransporter 2 inhibitors (SGLT2i) as recommended therapy raises the importance of prompt and accurate identification and treatment of HFpEF across diverse healthcare settings. We evaluated HFpEF management across specialties through a survey targeting cardiologists, HF specialists, and non‐cardiologists.

Methods and results

An independent web‐based survey was distributed globally between May and July 2023. We performed a post‐hoc analysis, comparing cardiologists, HF specialists, and non‐cardiologists. A total of 1460 physicians (61% male, median age 41[34–49]) from 95 countries completed the survey; 20% were HF specialists, 65% cardiologists, and 15% non‐cardiologists. Compared with HF specialists, non‐cardiologists and cardiologists were less likely to use natriuretic peptides (p = 0.003) and HFpEF scores (p = 0.004) for diagnosis, and were also less likely to have access to or consider specific echocardiographic parameters (p < 0.001) for identifying HFpEF. Diastolic stress tests were used in less than 30% of the cases, regardless of the specialty (p = 1.12). Multidrug treatment strategies were similar across different specialties. While SGLT2i and diuretics were the preferred drugs, angiotensin receptor blockers and angiotensin receptor–neprilysin inhibitors were the least frequently prescribed in all three groups. However, when constrained to choose one drug, the proportion of physicians favoring SGLT2i varied significantly among specialties (66% HF specialists, 52% cardiologists, 51% non‐cardiologists). Additionally, 10% of non‐cardiologists and 8% of cardiologists considered beta blocker the drug of choice for HFpEF.

Conclusion

Significant differences among specialty groups were observed in HFpEF management, particularly in the diagnostic work‐up. Our results highlight a substantial risk of underdiagnosis and undertreatment of HFpEF patients, especially among non‐HF specialists.