bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stereodivergent Transformation of Azepino[3,4,5‐cd]indoles En Route to Nature‐Inspired Scaffolds
Authors: Srikanth Gourishetty , Ravi Anil , Sebastian Anusha , Joseph Jobi , Khanfar Monther A. , El‐Gamal Mohammed I. , Al‐Qawasmeh Raed A. , Abu‐Yousef Imad A. , Majdalawieh Amin F. , Al‐Tel Taleb H. 
Published: January 2023

AbstractAzepino[3,4,5‐cd]indole derivatives represent the core scaffold of important natural products and biologically relevant compounds. Therefore, the establishment of step‐ and atom‐economic strategies to access this class of compounds is of paramount importance. To this end, complexity‐to‐diversity (CtD) strategy has become one of the most important tools that transforms complex molecules into diverse skeleta. However, many of the reactions that could be employed in CtD are restricted by the functional handles exist in these molecules. This limits the achievement of the desired skeletal diversity. Herein, an efficient and step‐economic strategy to access a diverse collection of azepino‐[3,4,5‐cd]indole architectures through a cascade that combines Pictet‐Spengler with Michael addition, is described. This was achieved by reacting cyclohexadienone acetaldehydes 2 a–2 d with indolyl‐4‐ethyl amine 1. Employing a CtD strategy on the developed azepino‐[3,4,5‐cd]indoles, a rapid rearrangement reaction that provided a modular, chemo‐ and diastereoselective access to diverse collection of spiro azepinocarbazole nature‐inspired frameworks, was encountered.
Differential pulse voltammetric determination of benznidazole loaded in nanostructured lipid carriers and urine**
Authors: Nunes Ana M. F. , da Silva Flávia L. O. , Carneiro Guilherme , Malagutti Andréa R. 
Published: January 2023

AbstractBenznidazole (BZN) is the first‐choice drug for treating Chagas disease (CD). However, it is not ideal for this purpose as it is highly toxic and has irregular pharmacokinetics due to factors such as its low aqueous solubility. These factors necessitate the development of reliable and effective alternative methods for the analytical determination of BZN in biological and pharmaceutical samples. In this context, we present a new electroanalytical method for quantifying BZN using differential pulse voltammetry (DPV) and a glassy carbon electrode (GCE). This method was applied to urine and a pharmaceutical formulation of BZN incorporated into nanostructured lipid carriers (NLC‐BZN). The proposed method provided a linear analytical range of 1.00–10.6 μmol L−1 (R=0.999), with a detection limit of 0.044 μmol L−1 and a quantification limit of 0.13 μmol L−1. The relative standard deviation of the intra‐day and inter‐day precision was below 2.50 %. Through interference studies, the methodology proved to be selective for BZN, because there was no significant potential interference in any of the samples. The recovery tests showed that the accuracy was within the limits recommended in the literature. Therefore, the developed DPV/GCE method can be successfully applied as an alternative method for detecting BZN in NLC‐BZN pharmaceutical formulations and human urine.
Prevention of DDoS attacks using an optimized deep learning approach in blockchain technology
Authors: Ilyas Benkhaddra , Kumar Abhishek , Setitra Mohamed Ali , Bensalem ZineEl Abidine , Lei Hang 
Published: January 2023

AbstractThe attack named Distributed Denial of Service (DDoS) that takes place in the large blockchain network requires an efficient and robust attack detection and prevention mechanism for authenticated access. Blockchain is a distributed network in which the attacker tries to hack the network by utilizing all the resources with the application of enormous requests. Several methods like Rival Technique, filter modular approach and so on, were developed to detect and prevent the DDoS attack in the blockchain; still, detection accuracy is a challenging task. Hence, this research introduces an efficient technique using optimization‐based deep learning by considering the blockchain network and smart contract for the detection and prevention of DDoS attacks. Based on the user request, the traffic is analyzed, and the verification using the smart contract is made to find the authenticated user. After the verification, the response is provided for the authenticated user, and the suspicious traffic is utilized for the detection of DDoS attacks using the Poaching Raptor Optimization‐based deep neural network (Poaching Raptor‐based DNN), in which the classifier is tuned using the proposed optimization algorithm to reduce the training loss. The proposed algorithm is designed by hybridizing the habitual practice of the raptor by considering the concurring behavior, hunting style along with poaching behavior of the Lobo to enhance the detection accuracy. After the attack detection, the nonattacker is responded, and the attacker is prevented by entering the IP/MAC address in the logfile. The performance of the proposed method is evaluated in terms of recall, precision, FPR, and accuracy and obtained the values of 96.3%, 98.22%, 3.33%, and 95.12%, respectively.
Skeletal Microstructure in Caribbean Hispanic Women
Authors: Agarwal Sanchita , Germosen Carmen , Bucovsky Mariana , Colon Ivelisse , Kil Nayoung , Walker Marcella 
Published: January 2023

ABSTRACTHispanic individuals are underrepresented in skeletal research. Bone mineral density (BMD) and fracture data are conflicting. We investigated skeletal health in elderly Caribbean Hispanic (HW), non‐Hispanic white (NHW), and non‐Hispanic black (NHB) women in a population‐based study in New York City. We utilized high‐resolution peripheral quantitative CT (HRpQCT), dual‐energy X‐ray absorptiometry (DXA), and finite element analysis (FEA). Of 442, 48.4% were HW, 21.3% NHW, and 30.3% NHB. Adjusted analyses are shown. Compared to NHW, HW had 8.5% (p < 0.01) lower spine areal BMD (aBMD) and 5.1% lower trabecular bone score (TBS). The frequency of morphometric vertebral fractures did not differ between HW and NHW. By HRpQCT, HW had 2.9% higher cortical (Ct) volumetric BMD (vBMD), 7.9% greater Ct area (Ct.Ar) and 9.4% greater Ct thickness (Ct.Th) at the radius compared to NHW. Results were similar at the tibia but trabecular microstructure tended to be worse. Ultimately, failure load (FL) did not differ between HW and NHW at either site. aBMD was 3.8% to 11.1% lower at the spine, femoral neck, and radius in HW compared to NHB (all p < 0.001) and vertebral fractures were twice as common. Compared to NHB, HW had 7.7% to 10.3% lower Ct.Ar at both the radius and tibia as well as 8.4% lower total vBMD, 6.3% lower trabecular number, and 10.3% lower Ct.Th at the tibia associated with 18.2% and 12.5% lower FL at both sites, respectively. In conclusion, HW had lower spine aBMD and TBS versus NHW women, whereas microstructural differences at the radius and tibia were small and not associated with differences in FL. In contrast, HW had lower aBMD, as well as deteriorated radial and tibial microstructure associated with worse FL compared to NHB women. Our results provide insight into racial/ethnic differences in skeletal health, adding to data that may be used to improve osteoporosis screening and treatment in HW. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Effect of Renal Impairment on the Pharmacokinetics of Firsocostat, an Acetyl‐Coenzyme A Carboxylase Inhibitor, and Cilofexor, a Selective Nonsteroidal Farnesoid X Receptor Agonist
Authors: Weber Elijah , Younis Islam R. , Nelson Cara , Ding Dora , Qin Ann , Xiao Deqing , Watkins Timothy R. , Othman Ahmed A. 
Published: January 2023

AbstractFirsocostat, a liver‐targeted acetyl‐coenzyme A carboxylase inhibitor, and cilofexor, a nonsteroidal farnesoid X receptor agonist, are being developed in combination for treatment of nonalcoholic steatohepatitis. This phase 1 study evaluated firsocostat and cilofexor pharmacokinetics and tolerability in participants with severe renal impairment (SRI) and healthy matched controls (HMCs). Ten participants with SRI (estimated glomerular filtration rate by Modification of Diet in Renal Disease <30 mL/min/1.73 m2), and 10 HMCs received single oral doses of firsocostat (20 mg) on day 1 and cilofexor (100 mg) on day 7 in a fasted state. Plasma concentrations of firsocostat (and nonactive metabolite GS‐834773) and cilofexor (and nonactive metabolites GS‐716070 and GS‐1056756) were collected over 96 hours and quantified; plasma exposures (area under the concentration‐time curve [AUC] and peak concentration [Cmax]) and plasma protein binding were characterized. Firsocostat AUC was ≈40% higher in SRI versus HMC, while Cmax was 8% lower. Observed exposures of the firsocostat metabolite were ≈4.6‐fold higher in SRI participants versus HMC. Exposures (AUC and Cmax) of cilofexor and metabolites and percentages of protein binding of all analytes were similar between SRI and HMC groups. Treatment‐emergent adverse events were generally mild and not considered related to study drug. A <50% increase in firsocostat exposure was observed among SRI participants but was deemed not clinically relevant. There was no apparent effect of SRI on cilofexor exposure. Based on this trial, firsocostat and cilofexor dosing are not expected to require modification in patients who are renally impaired.
Treatment of hospital wastewater: emphasis on ecotoxicity and antibiotic resistance genes
Authors: Kaliakatsos Andreas , Gounaki Iosifina , Dokianakis Spyros , Maragkaki Emmanouela , Stasinakis Athanasios S , Gyparakis Stylianos , Katsarakis Nikos , Manios Thrassyvoulos , Fountoulakis Michalis S , Venieri Danae 
Published: January 2023

AbstractBACKGROUNDHospital wastewater (HWW) charges wastewater treatment plants (WWTPs) with a mixture of contaminants such as pharmaceutically active compounds (PhACs) and pathogenic bacteria. This matrix is considered highly toxic to the ecosystem and organisms, and it may induce the development of antibiotic resistant bacteria (ARB) and the transfer of antibiotic resistance genes (ARGs) within microbial communities. Conventional WWTPs cannot treat HWW effectively, because they have not been designed to confront this challenge. Therefore, this study investigated the applicability of photocatalysis to purify HWW, regarding its ecotoxicity and the removal rates of targeted substances, selected pathogenic bacteria and specific ARGs.RESULTSThe HWW samples showed high toxicity towards the bioindicator Daphnia magna population, while they also contained significant levels of ARB and ARGs. Upon application of the photocatalytic treatment, the pharmaceutical concentrations decreased at a rate of >80% and the removal rates of the examined bacteria (Escherichia coli, Enterococci, Klebsiella sp. and Staphylococcus sp.) were >80%. Importantly, the bacteria remaining after photocatalysis were sensitive to the tested antibiotics. Conversely, the examined ARGs were present in high concentrations before and after photocatalytic treatment. For example, the concentrations of the selected genes, namely ampC, sul2, tetA and qnrA, in the effluents were from 104 to 106 gene copies L−1.CONCLUSIONSPhotocatalysis may be a promising treatment technique for the elimination of PhACs and pathogenic bacteria from HWW. Moreover, it proved capable of altering the antibiotic resistance profile of the bacteria surviving after treatment, making them sensitive to certain antibiotic compounds. However, the main concern regarding public health protection remains, as the presence of ARGs in effluents in considerable concentrations may induce antibiotic resistance in bacterial communities of aquatic environments. © 2023 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).
Delayed cutaneous hypersensitivity reactions following the use of infliximab or adalimumab in patients with coronavirus disease 2019
Authors: Wang Jing , Yin Xuedong , Yu Linlin , Cheng Weiwei , Wang Ling , Zhao Bin , Li Zhiling , Jing Xiaoping 
Published: January 2023

AbstractRecent evidence has emerged concerning delayed cutaneous hypersensitivity reactions after infliximab or adalimumab applications in patients with coronavirus disease 2019 (COVID‐19). A few real‐world studies compared the events, clinical features, and prognosis of infliximab‐ or adalimumab‐related delayed cutaneous hypersensitivity reactions in COVID‐19 patients. Disproportionality analysis and Bayesian analysis were utilized to determine the suspected adverse events of delayed cutaneous hypersensitivity reactions after infliximab or adalimumab use based on the Food and Drug Administration's Adverse Event Reporting Systems (FAERS) from May 2020 to December 2021. Additionally, the times to onset and fatality rates of delayed cutaneous hypersensitivity reactions following infliximab or adalimumab were compared. In total, 475 reports of delayed cutaneous hypersensitivity reactions were associated with infliximab or adalimumab. Females were affected almost twice more than males. Among the two therapies, infliximab had the highest association with delayed cutaneous hypersensitivity reactions based on the highest reporting odds ratio (2.14, 95% two‐sided confidence interval [CI] = 1.2–3.81), proportional reporting ratio (1.95, χ2 = 7.03), and empirical Bayesian geometric mean (1.94, 95% one‐sided CI = 1.2). Infliximab‐related delayed cutaneous hypersensitivity reactions had earlier onset (0 [interquartile range (IQR): 0–0] days vs. 166.5 (IQR: 18–889.5) days, p < 0.05), while adalimumab‐related delayed cutaneous hypersensitivity reactions have higher fatality rate (0.44% vs. 0.00%). Based on the FAERS database, we profiled delayed cutaneous hypersensitivity reactions related to infliximab or adalimumab application in patients with COVID‐19 with more points of occurrences, clinical characteristics, and prognosis.
Identification of two proposed novel human rhinovirus types: Bpat107 and Cpat58
Authors: Zhang Qiang , Xie Zhibo , Xia Baicheng , Wang Yage , Xu Wenbo , Zhang Yan 
Published: January 2023

AbstractHuman rhinovirus (RV) is an important viral pathogen associated with severe acute respiratory tract infection. The present study retrospectively identified RV types in hospitalized patients with severe acute respiratory infection (SARI) from October 2017 to June 2019 in Henan Province, China. Real‐time PCR was used to screen pharyngeal swab samples for RV. Then, the VP1 gene sequences of RV‐positive samples were amplified and sequenced with nested primer PCR; subsequently, analyses of the molecular epidemiology and genetic diversity characteristics of the RV types were performed. Seventy‐three out of 1015 respiratory samples were identified as RV‐positive, from which 65 complete VP1 sequences were successfully sequenced. These RVs were classified into 41 different types, including 26 RV‐A types, 2 RV‐B types, and 13 RV‐C types. The RVs showed an obvious seasonal distribution, with peaks in summer and autumn. The epidemic peak of RV‐C was later than that of RV‐A. In addition, two new types of species, B and C, were proposed, Bpat107 and Cpat58, respectively. Compared with other types in the same RV species, the pairwise nucleotide p‐distances of the two novel RV types were 0.262~0.402 and 0.251~0.508, respectively. This study analyzed the seasonal and genetic characteristics of RV associated with SARI cases in Henan Province, China. Two novel RV types were proposed.
European heatwaves: Link to large‐scale circulation patterns and intraseasonal drivers
Authors: Rouges Emmanuel , Ferranti Laura , Kantz Holger , Pappenberger Florian 
Published: January 2023

AbstractThis study examines the European heatwaves' predictability at subseasonal timescales. Land surface feedbacks and tropical convection, due to their variability at intraseasonal timescales, are taken into consideration and their potential role in extending the predictability beyond the medium range (10 days) is explored. A classification of European heatwaves into five heatwave types is used to discriminate the effects of surface feedbacks and of tropical variability among the different heatwave types. The classification is computed in terms of circulation patterns. By inferring the near‐surface temperature through atmospheric circulation, we aim to identify the predictable component of the heatwave events. All five heatwave circulation patterns are characterized by persistent anticyclonic anomalies located over the region with maximum temperatures. We show that soil moisture deficit is not a required precondition for the occurrence of heatwaves over most of Europe. However, heatwave events over southern Europe exhibit some sensitivity to dry conditions. We use a simplified index to describe the dominant mode of tropical convection at intraseasonal timescales. The index, based on precipitation anomalies, represents the evolution of the Boreal Summer Intraseasonal Oscillation (BSISO). We find that episodes with strong BSISO amplitudes characterized by enhanced convection over India, Bay of Bengal and China sea favour the occurrence of heatwave events over Russia. The results highlight the role of tropical intraseasonal variability in enhancing the predictability of some extreme temperature events over Europe.
Investigation on the emulsification mechanism in aqueous enzymatic extraction of edible oil from Schizochytrium sp.
Authors: Zheng Xu , Juan Ma , Kou Xiaohong , Gao Xin , Liu Jing , Li Shihao , Zheng Bowen , Liu Yazhou , Xue Zhaohui 
Published: January 2023

AbstractBACKGROUNDThe interaction between emulsified substances and lipids generates an emulsification system during the extraction of microalgae edible oil by aqueous enzymatic method. This study aimed to resolve the dynamics of interfacial protein adsorption during the extraction of microalgae oil at different enzymatic times and the effect on the stability of the interfacial membrane formed by the proteins based on interfacial effects.RESULTSAt 1.5 h of enzymatic hydrolysis, the molecular weights of the proteins/peptides were all below 35 kD. In addition, the protein–peptide structure was loose, with the lowest number of disulfide bonds, peak surface hydrophobicity, the highest number of residues, and disordered lipid acyl arrangement. At the same time, the physical stability of the emulsion was the lowest, and the interfacial membrane rupture was distinct. On excessive enzymatic hydrolysis (at 3.0 h), a more uniform interfacial membrane was re‐formed on the lipid surface.CONCLUSIONProtein is the main emulsifying substance in the emulsification system. The addition of protease affects the stability of the interfacial membrane formed by proteins. In addition, sufficient enzymatic hydrolysis (1.5 h) inhibited emulsification, while excessive enzymatic hydrolysis (3.0 h) promoted emulsification. © 2023 Society of Chemical Industry.
Gastrectomy for elderly gastric cancer patients: A propensity score‐matching analysis
Authors: Dias Andre R. , Pereira Marina A. , Ramos Marcus F. K. P. , Barchi Leandro C. , Ribeiro Ulysses , Zilberstein Bruno , Nahas Sergio C. 
Published: January 2023

AbstractBackgroundAlthough D2‐gastrectomy is the most effective treatment for resectable gastric cancer (GC), it is unclear whether elderly patients have increased risk of morbidity and worse survival. This study aimed to compare the short‐ and long‐term outcomes of older age (OA) patients with those of less advanced age (LAA).MethodsGC patients undergoing curative gastrectomy were retrospectively analyzed and divided into two groups: OA (>75 years) and LAA (<75 years). Propensity score‐matching (PSM) analysis using seven variables was conducted to reduce selection bias.ResultsAmong 586 patients, 494 (84.3%) were classified as LAA and 92 (15.7%) as OA. OA patients had worse clinical status, higher rates of D1‐lymphadenectomy, subtotal gastrectomy, and Lauren type; higher mortality and worse survival. No difference in pathological tumor‐node‐metastasis (pTNM) stage was observed between groups. Preoperative chemotherapy was performed more frequently in the LAA group. After PSM (92 OA: 92 LAA), all variables included in PSM were matched, and mortality rates and survival became similar between groups. In multivariate analysis, American Society of Anaesthesiologists score III/IV was an independent factor associated with a 90‐day mortality after PSM.ConclusionGastrectomy in elderly GC patients has similar outcomes compared with younger ones. Clinical status and disease stage are more important than the patient's age.
Multivisceral resection compared to standard gastrectomy for gastric adenocarcinoma: A propensity score‐matching analysis
Authors: Dias Andre Roncon , Pereira Marina Alessandra , Ramos Marcus Fernando Kodama Pertille , Ribeiro Ulysses , Zilberstein Bruno , Nahas Sergio Carlos 
Published: January 2023

AbstractBackgroundMultivisceral resection (MVR) in locally advanced gastric cancer (GC) is a morbid procedure. However, the precise impact of removing additional organs remains controversial. This study aimed to compare the outcomes of MVR versus standard gastrectomy (SG) in an unbiased cohort.MethodsPatients who underwent curative‐intent surgery for gastric adenocarcinoma were considered. Those submitted to SG were compared to the ones who received MVR using Propensity Score Matching (PSM) analysis.ResultsA total of 685 GC patients were included (621 SG and 64 MVR). Groups were distinct concerning the extent of the gastrectomy, tumor size, pTNM, R0, postoperative complications, and 90‐day mortality. After PSM, 57 patients were matched in each group. All variables assigned in the score were well matched. Postoperative complication, 90‐day mortality, and overall survival (OS) became similar among groups. Age >65 years old and resection of two or more organs, besides the stomach, were factors associated with 90‐day mortality. R1 and not received multimodal therapy were independent prognostic factors for worse OS.ConclusionsAfter PSM, the difference in morbidity, mortality, and survival of MVR compared to SG was no longer statistically significant, suggesting that MVR is an acceptable therapeutic strategy to patients with advanced GC.