bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomass to Aromatic Amine Module: Alkali Catalytic Conversion of N‐Acetylglucosamine into Unsubstituted 3‐Acetamidofuran by Retro‐Aldol Condensation
Authors: Lin Changqu , Yang Hao , Gao Xin , Zhuang Yue , Feng Caojian , Wu Hongli , Gan Haifeng , Cao Fei , Wei Ping , Ouyang Pingkai 
Published: March 2023

AbstractAminofurans are widely used in drug synthesis as aromatic modules analogous to aniline. However, unsubstituted aminofuran compounds are difficult to prepare. In this study, a process for the selective conversion of N‐acetyl‐d‐glucosamine (NAG) into unsubstituted 3‐acetamidofuran (3AF) is developed. The yield of 3AF from NAG catalyzed by a ternary Ba(OH)2−H3BO3−NaCl catalytic system in N‐methylpyrrolidone at 180 °C for 20 min can reach 73.9 %. Mechanistic studies reveal that the pathway to 3AF starts with a base‐promoted retro‐aldol condensation of the ring‐opened NAG, affording the key intermediate N‐acetylerythrosamine. Judicious selection of the catalyst system and conditions enables the selective conversion of biomass‐derived NAG into 3AF or 3‐acetamido‐5‐acetylfuran.
Novel insights in the pathomechanism of Brugada syndrome and fever‐related type 1 ECG changes in a preclinical study using human‐induced pluripotent stem cell‐derived cardiomyocytes
Authors: Li Yingrui , Dinkel Hendrik , Pakalniskyte Dalia , Busley Alexandra Viktoria , Cyganek Lukas , Zhong Rujia , Zhang Feng , Xu Qiang , Maywald Lasse , Aweimer Assem , Huang Mengying , Liao Zhenxing , Meng Zenghui , Yan Chen , Prädel Timo , Rose Lena , Moscu‐Gregor Alexander , Hohn Alyssa , Yang Zhen , Qiao Lin , Mügge Andreas , Zhou Xiaobo , Akin Ibrahim , El‐Battrawy Ibrahim 
Published: March 2023

AbstractBackgroundBrugada syndrome (BrS) is causing sudden cardiac death (SCD) mainly at young age. Studying the underlying mechanisms associated with BrS type I electrocardiogram (ECG) changes in the presence of fever and roles of autophagy for BrS remains lacking.ObjectivesWe sought to study the pathogenic role of an SCN5A gene variant for BrS with fever‐induced type 1 ECG phenotype. In addition, we studied the role of inflammation and autophagy in the pathomechanism of BrS.MethodsHuman‐induced pluripotent stem cell (hiPSC) lines from a BrS patient harboring a pathogenic variant (c.3148G>A/p. Ala1050Thr) in SCN5A and two healthy donors (non‐BrS) and a CRISPR/Cas9 site‐corrected cell line (BrS‐corr) were differentiated into cardiomyocytes (hiPSC‐CMs) for the study.ResultsReductions of Nav1.5 expression, peak sodium channel current (INa) and upstroke velocity (Vmax) of action potentials with an increase in arrhythmic events were detected in BrS compared to non‐BrS and BrS‐corr cells. Increasing the cell culture temperature from 37 to 40°C (fever‐like state) exacerbated the phenotypic changes in BrS cells. The fever‐effects were enhanced by protein kinase A (PKA) inhibitor but reversed by PKA activator. Lipopolysaccharides (LPS) but not increased temperature up to 40°C enhanced the autophagy level in BrS‐hiPSC‐CMs by increasing reactive oxidative species and inhibiting PI3K/AKT signalling, and hence exacerbated the phenotypic changes. LPS enhanced high temperature‐related effect on peak INa shown in BrS hiPSC‐CMs. Effects of LPS and high temperature were not detected in non‐BrS cells.ConclusionsThe study demonstrated that the SCN5A variant (c.3148G>A/p.Ala1050Thr) caused loss‐of‐function of sodium channels and increased the channel sensitivity to high temperature and LPS challenge in hiPSC‐CMs from a BrS cell line with this variant but not in two non‐BrS hiPSC‐CM lines. The results suggest that LPS may exacerbate BrS phenotype via enhancing autophagy, whereas fever may exacerbate BrS phenotype via inhibiting PKA‐signalling in BrS cardiomyocytes with but probably not limited to this variant.
Association of osteocalcin, osteoprotegerin, and osteopontin with cardiovascular disease and retinopathy in type 2 diabetes
Authors: Maddaloni Ernesto , Coraggio Lucia , Amendolara Rocco , Baroni Marco G. , Cavallo Maria G. , Copetti Massimiliano , Cossu Efisio , D’Angelo Paola , D’Onofrio Luca , Cosmo Salvatore De , Leonetti Frida , Morano Susanna , Morviducci Lelio , Napoli Nicola , Prudente Sabrina , Pugliese Giuseppe , Park Kyoungmin , Holman Rury R. , Trischitta Vincenzo , Buzzetti Raffaella ,   for the SUMMER Study in Diabetes Group
Published: March 2023

AbstractBackgroundNovel biomarkers of vascular disease in diabetes could help identify new mechanistic pathways. Osteocalcin, osteoprotegerin, and osteopontin are key molecules involved in bone and vascular calcification processes, both of which are compromised in diabetes. We aimed to evaluate possible associations of osteocalcin, osteoprotegerin, and osteopontin with cardiovascular disease (CVD) and diabetic retinopathy (DR) among people with type 2 diabetes (T2D).Materials and MethodsOsteocalcin, osteoprotegerin, and osteopontin concentrations were measured at enrolment in 848 participants with T2D from the Sapienza University Mortality and Morbidity Event Rate (SUMMER) Study (ClinicalTrials.gov: NCT02311244). Logistic regression models and propensity score matching were used to assess possible associations of osteocalcin, osteoprotegerin, and osteopontin with a history of CVD and with evidence of any grade of DR adjusting for confounders.ResultsPrevious CVD was reported in 139 (16.4%) participants, while 144 (17.0%) had DR. After adjusting for possible confounders, osteocalcin but not osteoprotegerin or osteopontin concentrations were associated with a history of CVD (Odds Ratio [OR] and 95% CI for one standard deviation (SD) increase in osteocalcin concentrations (natural log): 1.35 (1.06–1.72), p = 0.014). Associations with prevalent DR were seen for osteoprotegerin (OR for one SD increase in osteoprotegerin concentrations (natural log): 1.25 (1.01–1.55), p = 0.047) and osteopontin (OR for one SD increase in osteopontin concentrations (natural log): 1.25 (1.02–1.53), p = 0.022), but not osteocalcin.ConclusionsIn T2D, higher serum osteocalcin concentrations are associated with macrovascular complications and higher osteoprotegerin and osteopontin concentrations with microvascular complications, suggesting that these osteokines might be involved in pathways directly related to vascular disease.
Seasonality of pollinators in montane habitats: Cool‐blooded bees for early‐blooming plants
Authors: Herrera Carlos M. , Núñez Alejandro , Aguado Luis O. , Alonso Conchita 
Published: March 2023

AbstractUnderstanding the factors that drive community‐wide assembly of plant‐pollinator systems along environmental gradients has considerable evolutionary, ecological, and applied significance. Variation in thermal environments combined with intrinsic differences among pollinators in thermal biology have been proposed as drivers of community‐wide pollinator gradients, but this suggestion remains largely speculative. We test the hypothesis that seasonality in bee pollinator composition in Mediterranean montane habitats of southeastern Spain, which largely reflects the prevalence during the early flowering season of mining bees (Andrena), is a consequence of the latter's thermal biology. Quantitative information on seasonality of Andrena bees in the whole plant community (275 plant species) and their thermal microenvironment was combined with field and laboratory data on key aspects of the thermal biology of 30 species of Andrena (endothermic ability, warming constant, relationships of body temperature with ambient and operative temperatures). Andrena bees were a conspicuous, albeit strongly seasonal component of the pollinator assemblage of the regional plant community, visiting flowers of 153 different plant species (57% of total). The proportion of Andrena relative to all bees reached a maximum among plant species which flowered in late winter and early spring, and declined precipitously from May onward. Andrena were recorded only during the cooler segment of the annual range of air temperatures experienced at flowers by the whole bee assemblage. These patterns can be explained by features of Andrena's thermal biology: null to weak endothermy; ability to forage at much lower body temperature than strongly endothermic bees (difference ~ 10°C); low upper tolerable limit of body temperature, beyond which thermal stress presumably precluded foraging at the warmest period of year; weak thermoregulatory capacity; and high warming constant enhancing ectothermic warming. Our results demonstrate the importance of lineage‐specific pollinator traits as drivers of seasonality in community‐wide pollinator composition; show that exploitation of cooler microclimates by bees does not require strong endothermy; and suggest that intense endothermy and precise thermoregulation probably apply to a minority of bees. Medium‐ and large‐sized bees with low upper thermal limits and weak thermoregulatory ability can actually be more adversely affected by climate warming than large, hot‐blooded, extremely endothermic species.
Moss and underlying soil bacterial community structures are linked to moss functional traits
Authors: Klarenberg Ingeborg J. , Keuschnig Christoph , Salazar Alejandro , Benning Liane G. , Vilhelmsson Oddur 
Published: March 2023

AbstractMosses are among the first colonizing organisms after glacier retreat and can develop into thick moss mats during later successional stages. They are key players in N2 fixation through their microbiome, which is an important process for nutrient buildup during primary succession. How these moss–microbe interactions develop during succession is not well studied and is relevant in the light of climate change and increased glacier retreat. We examined how the bacterial communities associated with two moss species of the genus Racomitrium and the underlying soil, as well as moss traits and nitrogen fixation, develop along a successional gradient in the glacier forefield of Fláajökull in southeast Iceland. In addition, we tested whether moss functional traits, such as total carbon (TC) and total nitrogen (TN) contents, moss moisture content, and moss shoot length are drivers of moss and underlying soil bacterial communities. Although time since deglaciation did not affect TN and moss moisture contents, TC and shoot length increased with time since deglaciation. Moss and underlying soil bacterial communities were distinct. While the soil bacterial community structure was driven by moss C/N ratios, the moss bacterial community structure was linked to time since deglaciation, moss C/N ratio, and moss moisture content. Moss N2‐fixation rates were linked to bacterial community composition and nifH gene abundance rather than moss TN or time since deglaciation. This was accompanied by a shift from autotrophic to heterotrophic diazotrophs. Overall, our results suggest that there is little lateral transfer between moss and soil bacterial communities and that moss traits affect moss and soil bacterial community structure. Only moss bacterial community changed with time since deglaciation. In addition, moss N2‐fixation rates are determined by bacterial community structure, rather than moss traits or time since deglaciation. This study on the interplay between succession, mosses, soils, and their bacterial communities will inform future work on the fate of newly exposed areas as a result of glacier retreat.
Machine‐learning‐based optimization framework to support recovery‐based design
Authors: Issa Omar , Silva‐Lopez Rodrigo , Baker Jack W. , Burton Henry V. 
Published: March 2023

AbstractRecovery‐based design links building‐level engineering and broader community resilience objectives. However, the relationship between above‐code engineering improvements and recovery performance is highly nonlinear and varies on a building‐ and site‐specific basis, presenting a challenge to both individual owners and code developers. In addition, downtime simulations are computationally expensive and hinder exploration of the full design space. In this paper, we present an optimization framework to identify optimal above‐code design improvements to achieve building‐specific recovery objectives. We supplement the optimization with a workflow to develop surrogate models that (i) rapidly estimate recovery performance under a range of user‐defined improvements, and (ii) enable complex and informative optimization techniques that can be repeated for different stakeholder priorities. We explore the implementation of the framework using a case study office building, with a 50th percentile baseline functional recovery time of 155 days at the 475‐year ground‐motion return period. To optimally achieve a target recovery time of 21 days, we find that nonstructural component enhancements are required, and that increasing structural strength (through increase of the importance factor) can be detrimental. However, for less ambitious target recovery times, we find that the use of larger importance factors eliminates the need for nonstructural component improvements. Such results demonstrate that the relative efficacy of a given recovery‐based design strategy will depend strongly on the design criteria set by the user.
Patient and health care delays in large (class T3–T4) oral, oropharyngeal, and laryngeal carcinomas
Authors: Atula Markus , Aro Katri , Irjala Heikki , Halme Elina , Jouppila‐Mättö Anna , Koivunen Petri , Wilkman Tommy , Blomster Henry , Mäkitie Antti , Atula Timo 
Published: March 2023

AbstractBackgroundHead and neck cancers (HNCs) are often diagnosed at an advanced stage. We investigated the lengths and factors associated with patient, primary health care (PHC), and specialist care (SC) delays in T3–T4 oral, oropharyngeal, and laryngeal cancer.MethodsA nationwide prospective questionnaire‐based study (n = 203) with the 3‐year long data collection period.ResultsThe median patient, PHC and SC delays were 58, 13, and 43 days, respectively. Lower level of education, heavy alcohol use, hoarseness, difficulties breathing, and eventual palliative treatment associated with a longer patient delay. A lump on the neck or facial swelling associated with a shorter PHC delay. Conversely, if symptoms were treated as an infection, PHC delay was longer. The treatment modality and tumor site affected SC delay.ConclusionsPatient delay stands as the most notable factor contributing to delays before treatment. HNC symptom awareness thus remains especially important among HNC risk groups.
Loss of individualized behavioral trajectories in adult neurogenesis‐deficient cyclin D2 knockout mice
Authors: Lopes Jadna Bogado , Małz Monika , Senko Anna N. , Zocher Sara , Kempermann Gerd 
Published: March 2023

AbstractThere is still limited mechanistic insight into how the interaction of individuals with their environment results in the emergence of individuality in behavior and brain structure. Nevertheless, the idea that personal activity shapes the brain is implicit in strategies for healthy cognitive aging as well as in the idea that individuality is reflected in the brain's connectome. We have shown that even isogenic mice kept in a shared enriched environment (ENR) developed divergent and stable social and exploratory trajectories. As these trajectories—measured as roaming entropy (RE)—positively correlated with adult hippocampal neurogenesis, we hypothesized that a feedback between behavioral activity and adult hippocampal neurogenesis might be a causal factor in brain individualization. We used cyclin D2 knockout mice with constitutively extremely low levels of adult hippocampal neurogenesis and their wild‐type littermates. We housed them for 3 months in a novel ENR paradigm, consisting of 70 connected cages equipped with radio frequency identification antennae for longitudinal tracking. Cognitive performance was evaluated in the Morris Water Maze task (MWM). With immunohistochemistry we confirmed that adult neurogenesis correlated with RE in both genotypes and that D2 knockout mice had the expected impaired performance in the reversal phase of the MWM. But whereas the wild‐type animals developed stable exploratory trajectories with increasing variance, correlating with adult neurogenesis, this individualizing phenotype was absent in D2 knockout mice. Here the behaviors started out more random and revealed less habituation and low variance. Together, these findings suggest that adult neurogenesis contributes to experience‐dependent brain individualization.
Methods for assessing the bioaccumulation of hydrocarbons and related substances in terrestrial organisms: A critical review
Authors: Gobas Frank A. P. C. , Lee Yung-Shan , Fremlin Katharine M. , Stelmachuk Stephanie C. , Redman Aaron D. 
Published: March 2023

Abstract
This study investigates and reviews methods for the assessment of the terrestrial bioaccumulation potential of hydrocarbons and related organic substances. The study concludes that the unitless biomagnification factor (BMF) and/or the trophic magnification factor (TMF) are appropriate, practical, and thermodynamically meaningful metrics for identifying bioaccumulative substances in terrestrial food chains. The study shows that various methods, including physical–chemical properties like the KOA and KOW, in vitro biotransformation assays, quantitative structure–activity relationships, in vivo pharmacokinetic and dietary bioaccumulation tests, and field-based trophic magnification studies, can inform on whether a substance has the potential to biomagnify in a terrestrial food chain as defined by a unitless BMF exceeding 1. The study further illustrates how these methods can be arranged in a four-tier evaluation scheme for the purpose of screening assessments that aim to minimize effort and costs and expediate bioaccumulation assessment of the vast numbers of organic substances in commerce, identifies knowledge gaps, and provides recommendations for further research to improve bioaccumulation assessment. Integr Environ Assess Manag 2023;19:1433–1456. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
Quantitative detection of Epstein‐Barr virus DNA methylation in the diagnosis of nasopharyngeal carcinoma by blind brush sampling
Authors: Zheng Xiao‐Hui , Li Xi‐Zhao , Zhou Ting , Jiang Cheng‐Tao , Tang Cao‐Li , Deng Chang‐Mi , Liao Ying , He Yong‐Qiao , Wang Tong‐Min , Jia Wei‐Hua 
Published: March 2023

AbstractDetecting EBV DNA load in nasopharyngeal (NP) brushing samples for the diagnosis of nasopharyngeal carcinoma (NPC) has attracted widespread attentions. Currently, NP brush sampling mostly relies on endoscopic guidance, and there are few reports on diagnostic markers suitable for nonguided conditions (blind brush sampling), which is of great significance for extending its application. One hundred seventy nasopharyngeal brushing samples were taken from 98 NPC patients and 72 non‐NPC controls under the guidance of endoscope, and 305 blind brushing samples were taken without endoscopic guidance from 164 NPC patients and 141 non‐NPC controls (divided into discovery and validation sets). Among these, 38 cases of NPC underwent both endoscopy‐guided NP brushing and blind brushing. EBV DNA load targeting BamHI‐W region and EBV DNA methylation targeting 11029 bp CpG site located at Cp‐promoter region were detected by quantitative polymerase chain reaction (q‐PCR). EBV DNA load showed good classification accuracy for NPC in endoscopy‐guided brushing samples (AUC = 0.984). However, in blind bushing samples, the diagnostic performance was greatly reduced (AUC = 0.865). Unlike EBV DNA load, the accuracy of EBV DNA methylation was less affected by brush sampling methods, whether in endoscopy‐guided brushing (AUC = 0.923) or blind brushing (AUC = 0.928 in discovery set and AUC = 0.902 in validation set). Importantly, EBV DNA methylation achieved a better diagnostic accuracy than EBV DNA load in blind brushing samples. Overall, detection of EBV DNA methylation with blind brush sampling shows great potential in the diagnosis of NPC and may facilitate its use in nonclinical screening of NPC.
Impact of critical care pharmacist‐led interventions on pain, agitation, and delirium in mechanically ventilated adults: A systematic review
Authors: Buckley Mitchell S. , Roberts Russel J. , Yerondopoulos Melanie J. , Bushway Audrey K. , Korkames Grace C. , Kane‐Gill Sandra L. 
Published: March 2023

AbstractBest practices of pain, agitation, and delirium (PAD) management require coordinated, bundled care among an interprofessional intensive care unit (ICU) team. Clinical pharmacists are essential health care team members in optimizing sedation and analgesia management in critically ill patients. The purpose of this systematic review is to summarize the clinical impact of pharmacist‐led interventions targeting PAD in mechanically ventilated adult ICU patients. A literature search was conducted using MEDLINE, EMBASE, CINAHL, SCOPUS, and the Cochrane Central Register of Controlled Trials between January 1, 2000 and September 1, 2022. Randomized controlled trials, quasi‐experimental, or observational studies comparing pharmacist‐led interventions aimed at PAD management best practices and usual care in adult (≥18 years) ICU patients were included. Clinical (mechanical ventilation duration, hospital length of stay, and mortality) and economic outcomes as well as sedation and analgesia utilization were evaluated. A total of 1418 citations were identified with 9 studies (n = 3769 patients) meeting eligibility. The types of pharmacist‐led intervention strategies were inconsistent among included studies. Four of the 9 studies showed that pharmacist‐led interventions were associated with a significant reduction in mechanical ventilation duration ranging from 4.0 to 8.5 days compared with approximately 5.6 to 14.0 days in the control groups. Three (50%) of 6 studies evaluating length of stay showed significant reductions with the intervention group compared with controls. No impact on mortality and ICU‐acquired delirium/coma rates was shown. The pharmacist‐led intervention group was also associated with significant reductions in opioid analgesia and sedative utilization. Only two studies evaluated the financial impact of the intervention group with one study finding a positive benefit attributed to decreased drug utilization, while the other report failed to find an impact on total hospital stay costs. Pharmacist‐led interventions promote PAD best practices in the ICU, although the impact on patient‐centered outcomes remains controversial.
Synthesis of aryl‐functionalized, 1,5‐disubstituted 1,2,3‐triazoles and derivatives by arylation of zwitterionic ruthenium triazolato complexes
Authors: Chang Chao‐Wan , Sung Hui‐Ling , Lee Chi‐Rung , Lee Gene‐Hsiang 
Published: March 2023

AbstractThe synthesis of a series of ruthenium 1,5‐disubstituted 1,2,3‐triazolato complexes, 1,5‐disubstituted 1,2,3‐triazoles, and a triazolium salt is reported. Treatment of the ruthenium azido complex [Ru]‐N3 (1, [Ru] = (η5‐C5H5)(dppe)Ru, dppe = Ph2PCH2CH2PPh2) with an excess of ethyl propiolate results in the formation of a mixture of the Z‐ and E‐forms of zwitterionic N(1)‐bound N(3)‐ethyl acryl‐4‐carboxylate triazolato complexes [Ru]N3(CH=CHCO2Et)C2H(CO2) (Z‐2) and (E‐2). The arylation of 2 with aromatic bromides gives a series of cationic N(1)‐bound N(3)‐ethyl acryl‐4‐alkoxycarbonyl triazolato complexes {[Ru]N3(CH=CHCO2Et)C2H(CO2CH2R)}[Br] (3a, R = Ph; 3b, R = C6F5; 3c, R = 4‐C6H4CN, 3d, R = 2,6‐C6H3F2) and the subsequent cleavage of the Ru‐N bond of 3a–d gives 1,5‐disubstituted 1,2,3‐triazoles N3(CH=CHCO2Et)C2H(CO2CH2R) (4a, R = Ph; 4b, R = C6F5; 4c, R = 4‐C6H4CN; 4d, R = 2,6‐C6H3F2) and [Ru]‐Br. A 1,2,3‐triazolium salt [N3(CH=CHCO2Et)(CH2C6F5)C2H2][Br] (5) was formed by transformation of 4b in BrCH2C6F5/chloroform mixture. The structures of Z‐3a and Z‐5 were confirmed by single‐crystal x‐ray diffraction analysis and both complexes participate in non‐covalent aromatic interactions in the solid‐state structures which can be favorable in the binding of DNA/biomolecular targets and have shown great potential in the application of biologically active anticancer drugs.