bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical case of Cor triatriatum sinister, a dilemma of anticoagulation: A case report and literature review
Authors: Arzhangzade Alireza , Zamirian Mahmood , Nozhat Salma , Shafei Sasan , Narimani Javid Roozbeh , Salahi Sarvenaz , Khorshidi Soorena 
Published: June 2024

Key Clinical MessageCor triatriatum is a rare congenital heart abnormality in which a membrane separates the left atrium (LA; sinister) or the right atrium (dexter) into two compartments. It is also a long‐forgotten cause of atrial fibrillation (AF) and substantially higher rates of blood stagnation, particularly proximal to the additional septum in the LA. In this case report, we faced a CHA2DS2‐VASc score of 1 in patients with non‐valvular AF due to Cor triatriatum sinister (CTS). The decision to start anticoagulants in this particular case was controversial, so we reviewed the literature to assess and address it. We present our case and discuss the indication of anticoagulants in this unique clinical scenario, accompanied by a literature review. Facing this dilemma of starting anticoagulants in special cases of CTS and AF should be individualized and need more investigation. However, till this moment, based on similar reports, it seems to be rational to consider CTS Per se as an additional risk stratification marker beyond the CHA2DS2‐VASc score start anticoagulant until the surgical resection. Considering CTS as the sole indication of anticoagulant in patients with normal sinus rhythm is a complex matter that needs further investigation.
Nasogastric tube syndrome: A case of vocal cord paralysis due to a nasogastric tube
Authors: Shioya Nobuki , Inoue Nozomu , Kawamura Hitomi , Kawashima Naonori , Sato Tomohiro , Sadamoto Yoshihiro , Tsukamoto Yuki , Naito Yuki , Hazama Kohji , Shichinohe Yasuo 
Published: June 2024

Key Clinical MessageInsertion of a nasogastric tube is one of the most common methods of administering nutrition, but can cause vocal cord paralysis.
Mechanochemical Synthesis of Silylcyclopentenes via Ball Milling
Authors: Gao Pan , Li Yicheng , Zhang Duo , Zhang Guodong , Gao Liuzhou , Chen Feng 
Published: June 2024

AbstractThe development of innovative methods for synthesizing silylcyclopentene compounds is particularly important for enriching and improving the synthetical toolbox of organosilicon compounds. Herein, a facile approach has been developed for the synthesis of silylcyclopentenes promoted by mechanochemically generated organolithium species as silicon nucleophiles under ball milling conditions, avoiding the requirement of large amounts of bulk solvent. This operationally simple method demonstrates good functional group compatibility, which provides a great opportunity for further exploration of the synthetic applications of silylcyclopentenes. Density functional theory calculations indicated that the transient lithiosilole intermediates undergo a stepwise nucleophilic addition process, which governs this mechanic‐force‐promoted [4+1] cycloaddition reaction.
In Situ Generation and High Bioresistance of Trityl‐based Semiquinone Methide Radicals Under Anaerobic Conditions in Cellular Systems
Authors: Li Shuai , Deng Peng , Chang Qi , Feng Meirong , Shang Yixuan , Song Yuguang , Liu Yangping 
Published: June 2024

AbstractBioreduction of spin labels and polarizing agents (generally stable radicals) has been an obstacle limiting the in‐cell applications of pulsed electron paramagnetic resonance (EPR) spectroscopy and dynamic nuclear polarization (DNP). In this work, we have demonstrated that two semiquinone methide radicals (OXQM⋅ and CTQM⋅) can be easily produced from the trityl‐based quinone methides (OXQM and CTQM) via reduction by various reducing agents including biothiols and ascorbate under anaerobic conditions. Both radicals have relatively low pKa's and exhibit EPR single line signals at physiological pH. Moreover, the bioreduction of OXQM in three cell lysates enables quantitative generation of OXQM⋅ which was most likely mediated by flavoenzymes. Importantly, the resulting OXQM⋅ exhibited extremely high stability in the E.coli lysate under anaerobic conditions with 76‐ and 14.3‐fold slower decay kinetics as compared to the trityl OX063 and a gem‐diethyl pyrrolidine nitroxide, respectively. Intracellular delivery of OXQM into HeLa cells was also achieved by covalent conjugation with a cell‐permeable peptide as evidenced by the stable intracellular EPR signal from the OXQM⋅ moiety. Owing to extremely high resistance of OXQM⋅ towards bioreduction, OXQM and its derivatives show great application potential in in‐cell EPR and in‐cell DNP studies for various cells which can endure short‐term anoxic treatments.
Preparation of Dearomatized p‐Coumaric Acid Derivatives as DNA Damage Response Inhibitors with Potent In Vitro Antitumor Effect
Authors: Fási Laura , Gonda Tímea , Tóth Noémi , Vass Máté , Gyovai András , Nagy Viktória , Ocsovszki Imre , Zupkó István , Kúsz Norbert , Nové Márta , Spengler Gabriella , Berkecz Róbert , Wang Hui‐Chun , Chang Fang‐Rong , Hunyadi Attila 
Published: June 2024

AbstractOur research group previously identified graviquinone (1) as a promising antitumor metabolite that is formed in situ when the antioxidant methyl caffeate scavenges free radicals. Furthermore, it exerted a DNA damaging effect on cancer cells and a DNA protective effect on normal keratinocytes. To expand and explore chemical space around qraviquinone, in the current work we synthesized 9 new alkyl‐substituted derivatives and tested their in vitro antitumor potential. All new compounds bypassed ABCB1‐mediated multidrug resistance and showed highly different cell line specificity compared with 1. All compounds were more potent in MDA‐MB‐231 than on MCF‐7 cells. The n‐butyl‐substituted derivatives 2 and 8 modulated the cell cycle and inhibited the ATR‐mediated phosphorylation of checkpoint kinase‐1 in MCF‐7 cells. As a significant expansion of our previous findings, our results highlight the potential antitumor value of alkyl‐substituted graviquinone derivatives.
Structure‐Metabolism Relationships of Benzimidazole Derivatives with anti‐Trypanosoma cruzi Activity for Chagas Disease
Authors: Espinoza‐Chávez Rocío Marisol , de Oliveira Rezende Júnior Celso , Laureano de Souza Mariana , Consolin Chelucci Rafael , Michelan‐Duarte Simone , Krogh Renata , Gomes Ferreira Leonardo Luiz , Valli Marilia , Sena de Oliveira Aldo , Andricopulo Adriano D. , Carlos Dias Luiz 
Published: June 2024

AbstractThis study introduces further insights from the hit‐to‐lead optimization process involving a series of benzimidazole derivatives acting as inhibitors of the cruzain enzyme, which targets Trypanosoma cruzi, the causative parasite of Chagas disease. Here, we present the design, synthesis and biological evaluation of 30 new compounds as a third generation of benzimidazole analogues with trypanocidal activity, aiming to enhance our understanding of their pharmacokinetic profiles and establish a structure‐metabolism relationships within the series. The design of these new analogues was guided by the analysis of previous pharmacokinetic results, considering identified metabolic sites and biotransformation studies. This optimization resulted in the discovery of two compounds (42 e and 49 b) exhibiting enhanced metabolic stability, anti‐Trypanosoma cruzi activity compared to benznidazole (the reference drug for Chagas disease), as well as being non‐cruzain inhibitors, and demonstrating a satisfactory in vitro pharmacokinetic profile. These findings unveil a new subclass of aminobenzimidazole and rigid compounds, which offer potential for further exploration in the quest for discovering novel classes of antichagasic compounds.
Development of New Peptidomimetic NADPH Oxidase Inhibitors with Antithrombotic Properties
Authors: Scalia Elisabetta , Chirco Antony , Calugi Lorenzo , Lenci Elena , Pagano Patrick J. , Pula Giordano , Trabocchi Andrea 
Published: June 2024

AbstractThe ability of synthetic peptides inhibitors of NOX1 to effectively block the production of ROS by the enzyme was studied with different methodologies. Specifically, taking advantage of our understanding of the active epitope of the regulatory NOX1 subunit NOXA1 as a potent inhibitor of NOX1‐derived O2⋅− formation, a panel of peptidomimetic derivatives of this peptide were designed and synthesized with the aim of improving their activity and increasing their stability in plasma. The results highlighted that improved efficacy and potency was found for both the peptide‐peptoid hybrid GS2, whereas stapled peptide AC5 and its precursor showed higher stability despite lower biological potency. This study showed that minimal structural modifications of NOXA1 peptides are required to improve both their potency and stability to finally achieve best candidates as new potential anti‐thrombotic drugs.
Comparative Bioequivalence Study of 2 Clopidogrel 75‐mg Tablet Formulations in Moroccan Volunteers
Authors: Orche Aimen El , Khabbaz Choukri El , Cheikh Amine , Bouchafra Houda , Jawhari Samira , Abbes Faouzi My El , Cherrah Yahya 
Published: June 2024

AbstractThis study investigates the pharmacokinetic properties and bioequivalence of 2 formulations of clopidogrel tablets administered to a cohort of healthy Moroccan male volunteers. The primary objective was to assess the rate and extent of drug absorption from the test formulation in comparison to a reference formulation, focusing on critical parameters including maximum plasma concentration (Cmax), area under the concentration‐time curve from 0 to the last measurable time (AUC0‐t), and area under the concentration‐time curve extrapolated to infinity (AUC0‐∞). The results revealed that the geometric mean ratios of Cmax, AUC0‐t, and AUC0–∞ for the test formulation relative to the reference formulation were 105.7%, 105.6%, and 105.6%, respectively. The 90% confidence intervals for these parameters fell within the predefined bioequivalence range of 80%‐125%, indicating a statistically and clinically equivalent performance between the 2 formulations. This investigation sheds light on the pharmacokinetic behavior of clopidogrel in the context of the Moroccan male population, offering valuable insights into the comparability of formulations.
Structural Order in the Hydration Shell of Nonpolar Groups versus that in Bulk Water
Authors: Graziano Giuseppe 
Published: June 2024

AbstractThe poor solubility of nonpolar compounds in water around room temperature is governed by a large and negative entropy change, whose molecular cause is still debated. Since the Frank and Evans original proposal in 1945, the large and negative entropy change is usually attributed to the formation of ordered structures in the hydration shell of nonpolar groups. However, the existence of such ordered structures has never been proven. The present study is aimed at providing available structural results and thermodynamic arguments disproving the existence of ordered structures in the hydration shell of nonpolar groups.
Construction of BiVO4@ NiCo2O3 Heterojunction to Promote Photocatalytic CO2 Reduction
Authors: Fu Wenjie , Lu Guanhong , Wang Xiao , Xie Xiaofeng , Sun Jing 
Published: June 2024

AbstractConstructing a catalyst capable of reducing CO2 through photoreduction in aqueous environments presents a significant challenge. In this study, we present the synthesis of BiVO4@NiCo2O3 heterojunction using a straightforward hydrothermal method for CO2 photoreduction. The sample with the optimal loading ratio demonstrates a CO generation rate of 7.202 μmol ⋅ g−1 ⋅ h−1, which is twice that of pure BiVO4 (3.626 μmol ⋅ g−1 ⋅ h−1) and 1.5 times that of pure NiCo2O3 (4.726 μmol ⋅ g−1 ⋅ h−1). Analysis using XPS and EPR techniques suggests that electron transfer at the interface of the heterojunction facilitates the separation of photogenerated charge carriers, thereby enhancing the efficiency of the photocatalytic process. This investigation offers a viable approach for developing photocatalysts for CO2 reduction in aqueous environments.
Antimicrobial Efficacy of Photocaged β‐Lapachone in Bacillus subtilis Biofilms
Authors: Hudson Elyse , Faylinn Christabel , Lopez‐Miranda Ivonne R. , Milstein Joshua N. , Beharry Andrew A. 
Published: June 2024

AbstractWith the rise of antibiotic resistance within clinical settings, combating the growth of microbial biofilms presents a unique challenge. Biofilm‐inhabiting bacteria are embedded within a self‐produced, protective matrix, which can reduce the efficacy of treatment. The naturally derived product β‐lapachone is an appealing therapeutic agent that has been reported to inhibit biofilm growth. However, its off‐target toxicity and poor metabolic stability pose a significant hurdle for its application in vivo. Using a photo‐pharmacological approach via a coumarin‐based photocage, the reactivity of β‐lapachone can be tuned so it only becomes active once the photocage is removed. Here we report both the photo‐uncaging efficiency and the effective inhibition concentration of photocaged β‐lapachone within model Bacillus subtilis biofilms. Additionally, the mechanism of action is analyzed with results supporting catalase inhibition. This novel light‐activatable anti‐microbial has potential applications in medical settings to inhibit biofilm growth and provide synergistic treatment with traditional antibiotics.
Performing Suction Blister Skin Biopsies
Authors: MacDonald Elizabeth A. , Katz Erica L. , Pearson Todd F. , Harris John E. 
Published: June 2024

AbstractTraditional skin sampling methods include punch or shave biopsies to produce a solid tissue sample for analysis. These biopsy procedures are painful, require anesthesia, and leave permanent scars. This unit describes a suction blister skin biopsy method that can be used in place of traditional biopsy methodologies as a minimally invasive, non‐scarring skin sampling technique. The induction of suction blisters uses an instrument with a chamber that applies negative pressure and gentle heat to the skin. Blister formation occurs within 1 hr, producing up to five blisters, each 10 mm in diameter per biopsy site. Blister fluid can be extracted and centrifuged to retrieve cells from the epidermis and upper dermis for flow cytometry, single‐cell RNA sequencing, cell culture, and more without the need for digestion protocols. In addition, the blister fluid can be used to measure soluble proteins and metabolites. This unit describes the preparation of supplies and subjects, the suction blister biopsy procedure and blister formation, fluid extraction, and post‐blistering care. © 2024 Wiley Periodicals LLC.Basic Protocol 1: Preparation of supplies and subjectBasic Protocol 2: Suction blister biopsy procedure and formationBasic Protocol 3: Blister fluid extractionBasic Protocol 4: Post‐blister care and clean up
P‐NiFe2O4/N‐Doped Carbon Nanotubes/NiFe Multi‐Phase Heterojunctions for Overall Water Splitting and Urea Electrolysis
Authors: Jia Lina , Du Gaohui , Han Di , Wang Yunting , Wang Youqing , Li Huayu , Zhao Wenqi , Chen Shixian , Zhang Miao , Su Qingmei , Xu Bingshe 
Published: June 2024

AbstractThe design and construction of highly efficient electrocatalysts for overall water splitting and urea electrolysis are significantly important for promoting energy conversion and realizing green hydrogen production. In this work, we constructed a multi‐phase heterojunction through a simple hydrothermal and phosphorization process. The P‐doped NiFe2O4 (P‐NiFe2O4) nanoparticles were uniformly anchored on the bamboo‐like N‐doped carbon nanotubes (NCNTs) grown via a NiFe‐alloy autocatalysis. The electronic structure and coordination environment of active species were optimized by the synergistic action of P doping, well‐dispersed ultrafine NiFe2O4, and NCNTs matrix with good conductivity, enhancing their quantity and activity for electrocatalysis. Consequently, the P‐NiFe2O4/NCNTs/NiFe exhibits excellent HER and OER activities with an overpotential of 111 and 266 mV at 10 mA cm−2 in 1 M KOH, respectively. The symmetrical overall water‐splitting cell using P‐NiFe2O4/NCNTs/NiFe as both anode and cathode delivers 10 mA cm−2 at a voltage of 1.604 V in 1 M KOH. Notably, the two‐electrode cell requires a low voltage of 1.467 V to achieve a current density of 10 mA cm−2 in 1 M KOH solution with 0.6 M urea. This designed catalysts display outstanding reaction kinetics and catalytic stability. This work provides useful guidance for applying transition metal‐based catalysts for hydrogen production.
Tear exosome‐based PROteolysis TArgeting Chimeras nanomedicine for human immunodeficiency virus‐mediated cancer treatment
Authors: Mukerjee Nobendu 
Published: June 2024

AbstractHuman Immunodeficiency Virus (HIV) significantly increases the risk of various cancers due to chronic immune suppression and viral oncogenes. Traditional therapies, including antiretroviral therapy (ART), chemotherapy, and radiation, often face limitations such as drug resistance and systemic toxicity. PROteolysis TArgeting Chimeras (PROTACs) have emerged as a promising approach for targeted protein degradation, offering significant advantages over conventional treatments. However, effective delivery remains a challenge. This paper explores the innovative use of tear exosome‐based delivery systems for PROTACs in treating HIV‐mediated cancers. Tear exosomes, due to their natural origin, biocompatibility, and inherent targeting capabilities, present a novel and effective platform for delivering PROTACs, enhancing therapeutic specificity and reducing adverse effects. Integrating the unique properties of tear exosomes with the therapeutic potential of PROTACs could revolutionize the treatment of HIV‐mediated cancers by overcoming current therapeutic challenges and improving patient outcomes.
Chloride Modulates Central pH Sensitivity and Plasticity of Brainstem Breathing‐Related Biorhythms in Zebra Finch Embryos
Authors: Whitaker‐Fornek Jessica R. , Nelson Jennie K. , Pilarski Jason Q. 
Published: June 2024

ABSTRACTAll terrestrial vertebrate life must transition from aquatic gas exchange in the embryonic environment to aerial or pulmonary respiration at birth. In addition to being able to breathe air, neonates must possess functional sensory feedback systems for maintaining acid–base balance. Respiratory neurons in the brainstem act as pH sensors that can adjust breathing to regulate systemic pH. The central pH sensitivity of breathing‐related motor output develops over the embryonic period in the zebra finch (Taeniopygia guttata). Due to the key role of chloride ions in electrochemical stability and developmental plasticity, we tested chloride's role in the development of central pH sensitivity. We blocked gamma‐aminobutyric acid‐A receptors and cation‐chloride cotransport that subtly modulated the low‐pH effects on early breathing biorhythms. Further, chloride‐free artificial cerebrospinal fluid altered the pattern and timing of breathing biorhythms and blocked the stimulating effect of acidosis in E12–14 brainstems. Early and middle stage embryos exhibited rebound plasticity in brainstem motor outputs during low‐pH treatment, which was eliminated by chloride‐free solution. Results show that chloride modulates low‐pH sensitivity and rebound plasticity in the zebra finch embryonic brainstem, but work is needed to determine the cellular and circuit mechanisms that control functional chloride balance during acid–base disturbances.
Disturbance‐mediated changes to boreal mammal spatial networks in industrializing landscapes
Authors: Curveira‐Santos Gonçalo , Marion Solène , Sutherland Chris , Beirne Christopher , Herdman Emily J. , Tattersall Erin R. , Burgar Joanna M. , Fisher Jason T. , Burton A. Cole 
Published: June 2024

AbstractCompound effects of anthropogenic disturbances on wildlife emerge through a complex network of direct responses and species interactions. Land‐use changes driven by energy and forestry industries are known to disrupt predator–prey dynamics in boreal ecosystems, yet how these disturbance effects propagate across mammal communities remains uncertain. Using structural equation modeling, we tested disturbance‐mediated pathways governing the spatial structure of multipredator multiprey boreal mammal networks across a landscape‐scale disturbance gradient within Canada's Athabasca oil sands region. Linear disturbances had pervasive direct effects, increasing site use for all focal species, except black bears and threatened caribou, in at least one landscape. Conversely, block (polygonal) disturbance effects were negative but less common. Indirect disturbance effects were widespread and mediated by caribou avoidance of wolves, tracking of primary prey by subordinate predators, and intraguild dependencies among predators and large prey. Context‐dependent responses to linear disturbances were most common among prey and within the landscape with intermediate disturbance. Our research suggests that industrial disturbances directly affect a suite of boreal mammals by altering forage availability and movement, leading to indirect effects across a range of interacting predators and prey, including the keystone snowshoe hare. The complexity of network‐level direct and indirect disturbance effects reinforces calls for increased investment in addressing habitat degradation as the root cause of threatened species declines and broader ecosystem change.
A framework for identifying factors controlling cyanobacterium Microcystis flos‐aquae blooms by coupled CCM–ECCM Bayesian networks
Authors: Tal O. , Ostrovsky I. , Gal G. 
Published: June 2024

AbstractCyanobacterial blooms in freshwater sources are a global concern, and gaining insight into their causes is crucial for effective resource management and control. In this study, we present a novel computational framework for the causal analysis of cyanobacterial harmful algal blooms (cyanoHABs) in Lake Kinneret. Our framework integrates Convergent Cross Mapping (CCM) and Extended CCM (ECCM) causal networks with Bayesian Network (BN) models. The constructed CCM–ECCM causal networks and BN models unveil significant interactions among factors influencing cyanoHAB formation. These interactions have been validated by domain experts and supported by evidence from peer‐reviewed publications. Our findings suggest that Microcystis flos‐aquae levels are influenced not only by community structure but also by ammonium, phosphate, oxygen, and temperature levels in the weeks preceding bloom occurrences. We demonstrated a non‐parametric computational framework for causal analysis of a multivariate ecosystem. Our framework offers a more comprehensive understanding of the underlying mechanisms driving M. flos‐aquae blooms in Lake Kinneret. It captures complex interactions and provides an explainable prediction model. By considering causal relationships, temporal dynamics, and joint probabilities of environmental factors, the proposed framework enhances our understanding of cyanoHABs in Lake Kinneret.