bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasound inhibits tumor growth and selectively eliminates malignant brain tumor in vivo
Authors: Buaron Nitsa , Mangraviti Antonella , Wang Yuan , Liu Ann , Pedone Mariangela , Sankey Eric , Adar Itay , Nyska Abraham , Goldbart Riki , Traitel Tamar , Brem Henry , Tyler Betty , Kost Joseph 
Published: April 2024

AbstractGlioma is one of the most common primary malignant brain tumors. Despite progress in therapeutic approaches, the median survival of patients with glioma remains less than 2 years, generating the need for new therapeutic approaches. Ultrasound (US) is widely used in medical fields and is used as a therapeutic tool mainly for improving the performance of therapeutic entities. In this study, we examined a novel approach using low frequency US (20 kHz) (LFUS) as an independent treatment tool for malignant glioma, since primary studies showed that cancer cells are more susceptible to LFUS than healthy cells. LFUS safety and efficacy were examined in a 9L gliosarcoma‐bearing female Fischer 344 rats. Two LFUS protocols were examined: a one‐time treatment (US1X), and two treatments 24 h apart (US2X). For safety evaluation, rats were monitored for weight change and pain measurements. For efficacy, tumor volume was measured as a function of time and the tumor structural chances were examined histopathologically. LFUS treatment showed rapid inhibition of tumor growth, seen as soon as 12 h after US application. In addition, LFUS was found to affect the tumor structure, which was more extensive (>60% of tumor area) in smaller tumors. In US2X, the tumor tissue was completely destroyed, and an extensive immune response was observed. Importantly, the treatment was highly selective, keeping the healthy tissue surrounding the tumor unharmed. We developed a highly efficient and selective therapeutic protocol for treating malignant glioma with minimal side effects based solely on LFUS.
Association between novel genetic variants of Notch signaling pathway genes and survival of hepatitis B virus‐related hepatocellular carcinoma
Authors: Qin Liming , Qiu Moqin , Lin Qiuling , Jiang Binbin , Zhan Shicheng , Wei Xueyan , Wei Junjie , Liu Yingchun , Wen Qiuping , Chen Peiqin , Jiang Yanji , Zhou Zihan , Liang Xiumei , Cao Ji , Gong Yizhen , Wei Yuying , Wei Xiaoxia , Yu Hongping 
Published: April 2024

AbstractBackgroundAlthough the Notch pathway plays an important role in formation and progression of hepatocellular carcinoma (HCC), few studies have reported the associations between functional genetic variants and the survival of hepatitis B virus (HBV)‐related HCC.MethodsIn the present study, we performed multivariable Cox proportional hazard regression analysis to evaluate associations between 36,101 SNPs in 264 Notch pathway‐related genes and overall survival (OS) of 866 patients with HBV‐related HCC.ResultsIt was found that three independent SNPs (NEURL1B rs4868192, CNTN1 rs444927 and FCER2 rs1990975) were significantly associated with the HBV‐related HCC OS. The number of protective genotypes (NPGs) were significantly associated with better survival in a dose‐response manner (ptrend <0.001). Compared with the model with sole clinical factors, the addition of protective genotypes to the predict models significantly increased the AUC, i.e., from 72.72% to 75.13% (p = 0.002) and from 72.04% to 74.76 (p = 0.004) for 3‐year and 5‐year OS, respectively. The expression quantitative trait loci (eQTL) analysis further revealed that the rs4868192 C allele was associated with lower mRNA expression levels of NEURL1B in the whole blood (p = 1.71 × 10‐3), while the rs1990975 T allele was correlated with higher mRNA expression levels of FCER2 in the whole blood and normal liver tissues (p = 3.51 × 10−5 and 0.033, respectively).ConclusionsThree potentially functional SNPs of NEURL1B, CNTN1 and FCER2 may serve as potential prognostic biomarkers for HBV‐related HCC.
Impact of Fermentation on the Phytochemical Profile and Bioactivity Characteristics of Aqueous Matricaria recutita L. Root Extracts
Authors: Mailänder Lilo K. , Nosrati Gazafroudi Khadijeh , Greiß Marit , Lorenz Peter , Nicolay Sven , Gründemann Carsten , Stintzing Florian C. , Daniels Rolf , Kammerer Dietmar R. 
Published: April 2024

AbstractWhile the flowers of Matricaria recutita L., German chamomile, are widely used for medicinal and cosmetic purposes, little is known about its roots, which are used in complementary medicine for the preparation of aqueous fermented extracts for the treatment of cramps and anxiety. To broaden the understanding of the active principles involved, a model fermentation approach was developed and fermentates were compared to commercially manufactured tinctures. Coumarins and hydroxycinnamates were among the major secondary metabolites characterized using HPLC‐MSn. After six months of fermentation and storage, low‐molecular organic acids were detected by GC‐MS. Fermentation contributed to the stabilization of antioxidant and radical scavenging activities, which were in a range of about 8–10 mg gallic acid equivalents/g dry weight and 20–24 mg trolox equivalents/g dry weight, determined by Folin‐Ciocalteu and DPPH assays, respectively. In addition, antibacterial activities of the extracts against Gram‐positive and ‐negative bacteria increased during the first week of fermentation. Fermentates were neither cytotoxic nor pro‐ or anti‐inflammatory. Thus, fermentation of chamomile roots is a suitable method for the safe production of biofunctional aqueous chamomile root extracts that remain stable without the addition of synthetic preservatives.
Bile Salt Hydrolase Activity‐Based Probes for Monitoring Gut Microbial Bile Acid Metabolism
Authors: Han Lin , Xu Raymond , Conwell Amanda N. , Takahashi Sola , Parasar Bibudha , Chang Pamela V. 
Published: April 2024

AbstractBile acids are bioactive metabolites that are biotransformed into secondary bile acids by the gut microbiota, a vast consortium of microbes that inhabit the intestines. The first step in intestinal secondary bile acid metabolism is carried out by a critical enzyme, bile salt hydrolase (BSH), that catalyzes the gateway reaction that precedes all subsequent microbial metabolism of these important metabolites. As gut microbial metabolic activity is difficult to probe due to the complex nature of the gut microbiome, approaches are needed to profile gut microbiota‐associated enzymes such as BSH. Here, we develop a panel of BSH activity‐based probes (ABPs) to determine how changes in diurnal rhythmicity of gut microbiota‐associated metabolism affects BSH activity and substrate preference. This panel of covalent probes enables determination of BSH activity and substrate specificity from multiple gut anerobic bacteria derived from the human and mouse gut microbiome. We found that both gut microbiota‐associated BSH activity and substrate preference is rhythmic, likely due to feeding patterns of the mice. These results indicate that this ABP‐based approach can be used to profile changes in BSH activity in physiological and disease states that are regulated by circadian rhythms.
Antimicrobial‐associated encephalopathy due to ampicillin
Authors: Mizutani Naoya , Kenzaka Tsuneaki 
Published: April 2024

Key Clinical MessageBecause the β‐lactam ring has a molecular structure similar to that of gamma‐aminobutyric acid (GABA) neurotransmitters, it binds to GABA A receptors and inhibits GABAergic transmission, causing AAE. The possibility of antimicrobial‐associated encephalopathy should be considered in cases of neurological or psychiatric symptoms after initiating an antimicrobial regimen.
On the Mechanism of the Lysosomal Enzyme Iduronate‐2‐sulfatase. A Multiscale Approach
Authors: Prejanò Mario , Romeo Isabella , Talerico Cristina , Parise Angela , Russo Nino , Marino Tiziana 
Published: April 2024

AbstractIduronate‐2‐sulfatase (IDS) is a Ca2+‐dependent enzyme belonging to the family of sulfatases that catalyzes the hydrolysis of sulphurylated glycosaminoglycans (GAGs), like dermatan and heparan sulphate. Its deficiency or modification leads to the accumulation of GAGs in the human body and to the occurrence of severe conditions, such as Hunter disease, or Mucopolysaccharidosis type II. Due to its involvement in this syndrome, it is of interest to understand the action mechanism of the enzyme to design new drugs for more efficient medical strategies. In the present work, we carried out a detailed multiscale modelling‐based investigation, adopting molecular dynamics simulation (MDs) and QM/MM calculations to study the enzyme‐dermatan sulfate interactions and to investigate the reaction mechanism of IDS. The analysis of molecular dynamics trajectories helped to shed light on the contribution of the individual residues of the active site in the recognition of dermatan sulfate. The role of FGly84 and His229, investigated in both neutral and protonated states in the case of the latter, is highlighted for the binding of the substrate. QM/MM calculations demonstrated that the reaction mechanism is a two‐steps process occurring via a sulphurylation‐desulphurylation mechanism where the FGly84 first attacks the sulphate group of the dermatan sulphate (DS), and later is desulphurylated.
Selective Transition Enhancement in a g‐Engineered Diradical
Authors: Komeda Joe , Boudalis Athanassios K. , Montenegro‐Pohlhammer Nicolas , Antheaume Cyril , Mizuno Asato , Turek Philippe , Ruben Mario 
Published: April 2024

AbstractA diradical with engineered g‐asymmetry was synthesized by grafting a nitroxide radical onto the [Y(Pc)2]⋅ radical platform. Various spectroscopic techniques and computational studies revealed that the electronic structures of the two spin systems remained minimally affected within the diradical system. Fluid‐solution Electron Paramagnetic Resonance (EPR) experiments revealed a weak exchange coupling with |J| ~ 0.014 cm−1, subsequently rationalized by CAS‐SCF calculations. Frozen solution continuous‐wave (CW) EPR experiments showed a complicated and power‐dependent spectrum that eluded analysis using the point‐dipole model. Pulse EPR manipulations with varying microwave powers, or under varying magnetic fields, demonstrated that different resonances could be selectively enhanced or suppressed, based on their different tipping angles. In particular, Field‐Swept Echo‐Detected (FSED) spectra revealed absorptions of MW power‐dependent intensities, while Field‐Swept Spin Nutation (FSSN) experiments revealed two distinct Rabi frequencies. This study introduces a methodology to synthesize and characterize g‐asymmetric two‐spin systems, of interest in the implementation of spin‐based CNOT gates.
Indenoannulated Tridecacyclene: An All‐Carbon Seven‐Stage Redox‐Amphoter
Authors: Misselwitz Erik , Spengler Jonas , Rominger Frank , Kivala Milan 
Published: April 2024

AbstractWe disclose an indenoannulated tridecacyclene comprising a central cyclooctatetraene moiety with multiple adjacent pentagonal rings which is accessible in a concise synthetic sequence. The saddle‐shaped geometry of the non‐benzenoid polycyclic scaffold and its unique packing behavior in the solid state were characterized by X‐ray crystallography. In electrochemical studies, the compound undergoes seven reversible redox events comprising five reductions and two oxidations. The dicationic and dianionic species obtained by chemical oxidation and reduction, respectively, were characterized spectroscopically in solution. Density functional theory calculations were applied to provide insights into aromaticity evolution in the respective charged species, highlighting the beneficial effect of the non‐benzenoid moieties on charge stabilization
Advances in the Continuous Flow Synthesis of 3‐ and 4‐Membered Ring Systems
Authors: Donnelly Kian , Baumann Marcus 
Published: April 2024

AbstractSmall carbo‐ and heterocyclic ring systems have experienced a significant increase in importance in recent years due to their relevance in modern pharmaceuticals, as building blocks for designer materials or as synthetic intermediates. This necessitated the development of new synthetic methods for the preparation of these strained ring systems focusing on effectiveness and scalability. The high ring strain of these entities as well as the use of high‐energy reagents and intermediates has often challenged their synthesis. Continuous flow approaches have thus emerged as highly effective means to safely and reliably access these strained scaffolds. In this short review, key developments in this field are summarised showcasing the power of continuous flow approaches for accessing 3‐ and 4‐membered ring systems via thermal, photo‐ and electrochemical processes.
PROTOCOL: Key characteristics of effective preschool‐based interventions to promote self‐regulation: A systematic review and meta‐analysis
Authors: Kanayama Atsushi , Siraj Iram , Moeyaert Mariola , Steiner Kat , Yu Elie ChingYen , Ereky‐Stevens Katharina , Iwasa Kaoru , Ishikawa Moeko , Kahlon Mehar , Warnatsch Rahel , Dascalu Andreea , He Ruoying , Mehta Pinal P. , Robinson Natasha , Shi Yining 
Published: April 2024

AbstractThis is the protocol for a Campbell Systematic Review. The objectives are as follows: The aim of this systematic review is to advance our understanding of the key characteristics of effective preschool‐based interventions designed to foster self‐regulation. To accomplish this, the review addresses the following questions: 1. What types of preschool‐based interventions have been developed to promote self‐regulation? 2. What is the average effect of these preschool‐based interventions on self‐regulation, focusing on four key constructs: integrative effortful control, integrative executive function, self‐regulation, and self‐regulated learning? 3. What characteristics—such as Resource Allocation, Activity Type, and Instruction Method—could potentially contribute to the effects of preschool‐based interventions in promoting self‐regulation?
Cabozantinib with immune checkpoint inhibitor versus cabozantinib monotherapy in patients with metastatic clear cell renal cell carcinoma progressing after prior immune checkpoint inhibitor
Authors: Gebrael Georges , Jo Yeonjung , Mathew Thomas Vinay , Li Haoran , Sayegh Nicolas , Tripathi Nishita , Srivastava Ayana , Nordblad Blake , Dal Emre , Narang Arshit , Brundage James , Campbell Patrick , Galarza Fortuna Gliceida , Hage Chehade Chadi , Maughan Benjamin L. , Agarwal Neeraj , Swami Umang 
Published: April 2024

AbstractIntroductionRechallenge with antibodies targeting programmed cell death protein‐1 or its ligand (PD‐1/L1) after discontinuation or disease progression in solid tumors following a prior PD‐1/L1 treatment is often practiced in clinic. This study aimed to investigate if adding PD‐1/L1 inhibitors to cabozantinib, the most used second‐line treatment in real‐world patients with metastatic clear cell renal cell carcinoma (mccRCC), offers additional benefits.MethodsUsing de‐identified patient‐level data from a large real‐world US‐based database, patients diagnosed with mccRCC, who received any PD‐1/L1‐based combination in first‐line (1L) setting, followed by second‐line (2L) therapy with either cabozantinib alone or in combination with PD‐1/L1 inhibitors were included. Patients given a cabozantinib‐containing regimen in 1L were excluded. The study end points were real‐world time to next therapy (rwTTNT) and real‐world overall survival (rwOS) by 2L.ResultsOf 12,285 patients with metastatic renal cell carcinoma in the data set, 348 patients met eligibility and were included in the analysis. After propensity score matching weighting, cabozantinib with PD‐1/L1 inhibitors versus cabozantinib (ref.) had similar rwTTNT and rwOS in the 2L setting. Hazard ratios and 95% confidence interval (CI) for rwTTNT and rwOS are 0.74 (95% CI, 0.49–1.12) and 1.15 (95% CI, 0.73–1.79), respectively.ConclusionIn this study, the results align with the phase 3 CONTACT‐03 trial results, which showed no additional benefit of adding PD‐L1 inhibitor to cabozantinib compared to cabozantinib alone in 2L following PD‐1/L1–based therapies in 1L. These results from real‐world patients strengthen the evidence regarding the futility of rechallenge with PD‐1/L1 inhibitors.
Molecular analysis using SalvGlandDx improves risk of malignancy estimation and diagnosis of salivary gland cytopathology: An exploratory multicenter study
Authors: Freiberger Sandra N. , Ikenberg Kristian , van Egmond Demi , Claerhout Sofie , van Wezel Tom , Bempt Isabelle Vanden , van Rossem Jeroen N. , Mueller Simon A. , Clement Paul M , Poorten Vincent Vander , Cohen Danielle , Hauben Esther , Rupp Niels J. 
Published: April 2024

AbstractBackgroundDiagnosis of salivary gland neoplasms is challenging, especially on cytological specimens acquired by fine‐needle aspiration. The recently implemented standardized Milan system for reporting salivary gland cytopathology provides an estimated risk of malignancy (ROM); yet, for two of the categories, the diagnosis of the lesion remains unclear. However, a precise diagnosis is desirable for optimal patient management, including planning of surgery and imaging procedures.MethodsCytological specimens (n = 106) were subjected to molecular analysis using the SalvGlandDx panel. The risk of malignancy was calculated for each detected alteration based on the diagnosis of the resection specimen. By taking into account the molecular alterations, their associated ROM, the clinical and cytological features, and the current literature, the Milan category was evaluated.ResultsOf n = 63 technically valid cases, 76% revealed a molecular alteration. A total of 94% of these molecularly altered cases could be assigned to a different Milan category when additionally taking molecular results into account. In only 2% of the salivary gland neoplasms of uncertain malignant potential, in which a molecular alteration was detected, the classification remained salivary gland neoplasms of uncertain malignant potential.ConclusionMolecular analysis of cytological specimens provides a benefit in classifying salivary gland neoplasms on fine‐needle aspiration. It can improve the ROM estimation and thus help to assign cases of formerly unknown malignant potential to clearly benign or malignant categories.
Sustainability reporting quality in Malaysia: The intricacy of family controlled and politically connected firms
Authors: Elaigwu Moses , Abdulmalik Salau Olarinoye , Alghorbany Abdelkader , Che‐Ahmad Ayoib 
Published: April 2024

AbstractThe study contributes to the existing literature by examining the relationship between family‐controlled firms (FCFs), politically connected firms (PCFs), and sustainability reporting quality (SRQ) in Malaysia. The study utilizes panel regression techniques to test the hypotheses. The study's findings revealed that FCFs have a significant negative effect on SRQ. On the other hand, PCFs show a positive significant effect on SRQ. Moreover, the study uncovers a significant and positive interacting effect of PCFs in the relationship between FCFs and SRQ. The implication of this is that politically connected family‐controlled firms (PCFCFs) exhibit higher levels of sustainability performance and disclosure quality. The study offers valuable implications for regulators, scholars, and practitioners. Policymakers can use the insights from this paper to develop regulations and guidelines that encourage family‐controlled firms to improve the quality of their sustainability disclosures. Furthermore, the study provides a foundation for further research in this domain to confirm the result of the present investigation.
Unlocking sustainability potential: The impact of green finance reform on corporate ESG performance
Authors: Gao Da , Zhou Xiaotian , Wan Jing 
Published: April 2024

AbstractImproving the incentive mechanism and institutional framework of green finance policy is important to promote the synchronization of environmental management and enterprise development. Based on China's green finance reform and innovation pilot (GFRIP) policy in 2017, this study constructs a quasi‐natural experiment with a sample of A‐share listed companies and draws the following conclusions. (1) The effectiveness of GFRIP policy in significantly promoting enterprises' ESG performance in pilot areas, robustness tests such as propensity score matching and placebo tests reconfirm conclusions. (2) The GFRIP policy can effectively improve enterprise ESG performance by easing financing constraints, promoting green investment, and improving managers' green cognition. (3) Both external environmental law enforcement and internal manager environmental awareness can enhance the promotion effect of the GFRIP policy on ESG performance. (4) Heterogeneity analysis shows that the ESG performance of state‐owned enterprises, large enterprises, and high‐polluting enterprises is more affected by pilot policy. The results of the study provide a valuable perspective on how the government can promote green finance policies and implications for enterprises' sustainable development.
Circularly polarized implantable MIMO antenna for skin, brain and heart implantation with wide axial ratio bandwidth
Authors: Kangeyan Rajagopal , Karthikeyan Madurakavi 
Published: April 2024

SummaryA unique MIMO antenna with circular polarization characteristics that works similarly for skin, brain and heart phantoms has been proposed in this paper. The twin rectangular X‐shaped slot that serves as the basic structure of the proposed antenna is entirely planar and low‐profile but has a defective ground plane. For three different phantoms, the proposed antenna resonates at 2.4–2.45 GHz ISM band. With a dimension of
, the antenna exhibits compactness. Rogers RT/duroid 6010 substrate material has been used to fabricate the antenna in order to validate the designed antenna structure. Utilizing the high dielectric material for both substrate and superstrate, both skin‐mimicking gel and minced hog meat were employed in the experiment setup at 2.45 GHz ISM band. At ISM band, −28.3 dBi has been observed has realized peak gain. The obtained fractional bandwidth (FBW) and Axial Ratio Bandwidth (ARBW) values are 30.67% and 45%, respectively. Also, the maximum specific absorption rate (SAR) values are found to be in the acceptable limit regulated by IEEE.