bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design, synthesis, and molecular docking of novel 3,5‐disubstituted‐1,3,4‐oxadiazole derivatives as iNOS inhibitors
Authors: Koksal Meric , Dedeoglu‐Erdogan Ayca , Bader Marwa , Gurdal Enise E. , Sippl Wolfgang , Reis Rengin , Ozgurbuz Melda , Sipahi Hande , Celik Turgay 
Published: May 2021

AbstractTo obtain new anti‐inflammatory agents, recent studies have aimed to replace the carboxylate functionality of nonsteroidal anti‐inflammatory drugs with less acidic heterocyclic bioisosteres like 1,3,4‐oxadiazole to protect the gastric mucosa from free carboxylate moieties. In view of these observations, we designed and synthesized a series of 3,5‐disubstituted‐1,3,4‐oxadiazole derivatives as inhibitors of prostaglandin E2 (PGE2) and NO production with an improved activity profile. As initial screening, and to examine the anti‐inflammatory activities of the compounds, the inhibitions of the productions of lipopolysaccharide‐induced NO and PGE2 in RAW 264.7 macrophages were evaluated. The biological assays showed that, compared with indomethacin, compounds 5a, 5g, and 5h significantly inhibited NO production with 12.61 ± 1.16, 12.61 ± 1.16, and 18.95 ± 3.57 µM, respectively. Consequently, the three compounds were evaluated for their in vivo anti‐inflammatory activities. Compounds 5a, 5g, and 5h showed a potent anti‐inflammatory activity profile almost equivalent to indomethacin at the same dose in the carrageenan‐induced paw edema test. Moreover, the treatment with 40 mg/kg of 5h produced significant anti‐inflammatory activity data. Furthermore, docking studies were performed to reveal possible interactions with the inducible nitric oxide synthase enzyme. Docking results were able to rationalize the biological activity data of the studied inhibitors. In summary, our data suggest that compound 5h is identified as a promising candidate for further anti‐inflammatory drug development with an extended safety profile.
Adaptive decentralized control for large‐scale nonlinear systems with finite‐time output constraints by multi‐ dimensional Taylor network
Authors: Chu Lei , Gao Tian , Wang Ming‐Xin , Han Yu‐Qun , Zhu Shan‐Liang 
Published: May 2021

AbstractThis paper investigates the adaptive decentralized control problem for a class of large‐scale nonlinear systems with finite‐time output constraints. In order to ensure that the tracking errors are constrained within a predefined boundary in finite time, a novel adaptive barrier Lyapunov function (BLF) control method is proposed by combining the modified finite‐time performance function (FTPF) in the first step of backstepping process. Besides, the mean value theorem and regulating functions are employed to handle the difficulties caused by interconnection functions in large‐scale systems. Subsequently, with the approximation performance of multi‐dimensional Taylor network (MTN), a MTN‐based adaptive decentralized tracking control scheme is developed to guarantee that the tracking errors satisfy the prescribed performance and all signals of the closed‐loop systems are bounded. Finally, the stability theory analysis and simulation results demonstrate the effectiveness of the proposed method.
Short‐term trajectories of restricted and repetitive behaviors in minimally verbal children with autism spectrum disorder
Authors: Harrop Clare , Sterrett Kyle , Shih Wendy , Landa Rebecca , Kaiser Ann , Kasari Connie 
Published: May 2021

AbstractVery little is known about the 30% of children with Autism Spectrum Disorder (ASD) who remain minimally verbal when they enter school. Restricted and repetitive behaviors (RRBs) are well‐characterized in younger, preschool, and toddler samples. However, the prevalence and impact of RRBs has not been characterized in older, minimally verbal children. The goal of this study was to characterize this core diagnostic feature in minimally verbal children with ASD ages 5–8 years over a 9‐month period to better understand how these behaviors manifest in this crucially understudied population. RRBs were coded from caregiver‐child interactions (CCX) at four timepoints. Upon entry into the study, children demonstrated an average of 17 RRBs during a 10‐min CCX. The most common category was Verbal. RRBs remained constant over 6 months; however, a slight reduction was observed at the final timepoint. Compared to prior literature on younger samples, minimally verbal children with ASD demonstrated higher rates of RRBs and higher rates of verbal RRBs. Further work is required to understand the function and impact of RRBs in minimally verbal children.Lay AbstractApproximately one‐third of children with autism spectrum disorder (ASD) remain minimally verbal at the time of school entry. In this study, we sought to characterize the presence of restricted and repetitive behaviors (RRBs) in school‐aged children (5–8) who were minimally verbal. Compared to prior studies, minimally verbal children with ASD had higher frequencies of RRBs and demonstrated a different profile of behaviors, including more verbal RRBs.
A correlation study of intestinal microflora and first‐episode depression in Chinese patients and healthy volunteers
Authors: Zheng Shaojun , Zhu Yubing , Wu Weidong , Zhang Qi , Wang Yongqian , Wang Zhiren , Yang Fude 
Published: May 2021

AbstractObjectiveThis research examines the intestinal‐associated flora of patients with depression compared with healthy volunteers to identify the characteristics and differences of flora associated with depression. It provides a theoretical basis for the prevention and treatment of depression through intestinal micro‐ecological regulation.MethodsWe recruited 30 patients with depression to participate in the patient group (PG), and 30 volunteers were recruited for the healthy control group (HG) from the Beijing Hui‐long‐guan Hospital. Thereafter, the 16S rRNA high‐throughput sequencing method, using the Hamilton Depression Scale, was applied to analyze patient and healthy groups.ResultsPG and HG microflora were different regarding phylum, Family, Genus, and Order. The results showed that Barnesiella was the dominant flora in depression patients, while Lachnospiraceae and Alloprevotella were the dominant bacteria in healthy participants. The proportion of Betaproteobateria (Proteobacteria), Alcaligenaceae (proinflammatory), Peptostreptococcaceae, Catenibacterium, Romboutsia, Sutterella, and Burkholderiales in the anxiety‐negative depressed group was significantly higher than in the anxiety‐positive group; and the proportion of Anaerostipes (inflammation) and Faecalibacterium (anti‐inflammatory) bacteria was significantly lower than that of patients with anxiety.ConclusionResults showed there were differences in intestinal micro‐ecology between patients with depression and healthy volunteers. We found that the level of inflammation‐related bacteria in anxiety‐positive patients was lower than that in anxiety‐negative patients. These results enrich the knowledge of relationships between depression and intestinal flora and provide a theoretical basis for probiotics to assist in the treatment of depression.
Conscious sedation compared to general anesthesia for intracranial mechanical thrombectomy: A meta‐analysis
Authors: Shen Huasu , Ma Xiaoyu , Wu Zhen , Shao Xian , Cui Jingjing , Zhang Bao , Abdelrahim Mohamed EA , Zhang Jin 
Published: May 2021

AbstractIntroductionEndovascular therapy is the standard of care for severe acute ischemic stroke caused by large‐vessel occlusion in the anterior circulation, but there is a debate on the optimal anesthetic approach during this therapy. Meta‐analyses of observational studies suggest that general anesthesia increases disability and death compared with conscious sedation However, their results are conflicting. This meta‐analysis study was performed to assess the relationship between the effects of general anesthesia compared to conscious sedation during endovascular therapy for acute ischemic stroke.MethodsThrough a systematic literature search up to August 2020, 18 studies included 4,802 subjects at baseline with endovascular therapy for acute ischemic stroke and reported a total of 1,711 subjects using general anesthesia and 1,961 subjects using conscious sedation were found. They recorded relationships between the effects of general anesthesia compared to conscious sedation during endovascular therapy for acute ischemic stroke. Odds ratio (OR) or Mean differences (MD) with 95% confidence intervals (CIs) were calculated between the effect of general anesthesia compared to conscious sedation during endovascular therapy for acute ischemic stroke using the dichotomous or contentious methods with a random or fixed‐effect model.ResultsNo significant difference were found between general anesthesia and conscious sedation during the endovascular therapy for acute ischemic stroke in functional independence at 90 days (OR, 0.78; 95% CI, 0.44–1.40, p = 40); successful recanalization at 24 hr (OR, 1.23; 95% CI, 0.62–2.41, p = 55); mortality at 90 days (OR, 1.36; 95% CI, 0.83–2.24, p = .22); interventional complication (OR, 1.24; 95% CI, 0.76–2.02, p = .40); symptomatic intracranial hemorrhage (OR, 0.64; 95% CI, 0.41–0.99, p = .05); aspiration pneumonia (OR, 0.96; 95% CI, 0.58–1.58, p = .87); and National Institute of Health Stroke Scale score after 24 hr (MD, 0.38; 95% CI, −1.15–1.91, p = .62); with relative relationship favoring general anesthesia only in decreasing the symptomatic intracranial hemorrhage.ConclusionsGeneral anesthesia has no independent relationship compared to conscious sedation during the endovascular therapy for acute ischemic stroke with a relative relationship favoring general anesthesia only in decreasing the symptomatic intracranial hemorrhage.This relationship encouraged us to recommend either anesthetic strategy during the endovascular therapy for acute ischemic stroke with no possible fear of higher complication.
On the processing of optimal performances: Studying arousal evoked by being correct and fast
Authors: Valt Christian , Stürmer Birgit 
Published: May 2021

AbstractIntroductionResponses are optimal when they are accurate and fast. The present experiment investigated whether optimal responses evoke physiological arousal and whether performance affects the processing and evaluation of subsequent emotional material.MethodsParticipants performed a response‐choice task, where feedback was a colored square reflecting performance quality or a face whose expression (happy or angry) did not indicate any aspect of performance. In the occurrence of an emotional stimulus, participants had to express a judgment about the emotional strength. The experiment focused on differences in the electrodermal and brain electrophysiological activities evoked by optimal (correct‐fast) and suboptimal (correct‐slow) responses, along with modulations on the processing and interpretation of facial emotions.ResultsThe results showed that, compared to correct responses, incorrect responses elicited an augmented phasic skin conductance response (SCR) and enhanced response‐locked event‐related potentials. Importantly, among correct responses, the SCR and the correct‐related negativity (CRN) were larger for correct‐fast than correct‐slow responses. Performance also affected the processing of faces, irrespective of the emotion, but it did not change the subjective interpretation. The EPN evoked by angry and happy faces was less negative after optimal than suboptimal responses.ConclusionThese results indicate that the monitoring system is sensitive to detect correct‐fast responses, resulting in a state of physiological arousal that might guide the reinforcement of optimal performances.
Altered ripple density inside seizure onset zone in patients with focal cortical dysplasia‐associated epilepsy
Authors: Xu Cuiping , Zhang Xiaohua , Zhang Guojun , Yan Xiaoming , Ma Kai , Qiao Liang , Wang Xueyuan , Zhang Xi , Yu Tao , Wang Yuping , Li Yongjie 
Published: May 2021

AbstractPurposeTo evaluate the clinical and stereoelectroencephalography (SEEG) features and postsurgical outcome in a uniform series of patients who underwent epilepsy surgery and had pathologically confirmation of focal cortical dysplasia (FCD).MethodsWe studied consecutive patients with drug‐refractory epilepsy who underwent SEEG recording. The high‐frequency oscillations (HFOs) features of SEEG, clinical characteristics, and surgical outcome were evaluated.ResultsSixty patients (31 FCD type I, 13 II, and 16 III) were analyzed retrospectively. Patients with type II tended to have their seizures at an earlier age than those with I and III (p < .01). Six different ictal onset patterns (IOPs) were identified. In patients with temporal lobe epilepsy (TLE), the most common patterns were rhythmic spikes or spike waves and LFRS, and in patients with extratemporal epilepsy, the most common patterns were low‐voltage fast activity (LVFA) and rhythmic spikes or spike waves. In addition, ripple density was found to increase significantly from the interictal to ictal onset sections and from the ictal onset to ictal evolution sections in patients with FCD I (p < .001). Regarding the distinct IOPs, ripple density continued to increase significantly between the interictal and ictal onset sections in LVFA, rhythmic spikes or spike waves, and burst of high‐amplitude polyspikes (p < .05). Ripple density decreased between ictal onset and ictal evolution sections in patterns of LVFA and rhythmic spikes or spike waves (p < .05). The mean follow‐up duration was 2.7 years (range 1–4.2), and 66.7% (n = 40) were class I. Patients with subtypes III and II had favorable surgical outcome than those with I.ConclusionThe clinical expression of seizure may depend on the pathological types with FCD II patients exhibiting their seizures at an earlier age. Distinct IOPs may demonstrate different ripple features and distinguishing the IOPs is very necessary to have an insight into the electrophysiological characteristics.
Real‐world utility of next‐generation sequencing for targeted gene analysis and its application to treatment in lung adenocarcinoma
Authors: Kim Jwa Hoon , Yoon Shinkyo , Lee Dae Ho , Jang Se Jin , Chun Sung‐Min , Kim Sang‐We 
Published: May 2021

AbstractPurposeThis study investigated the clinical utility of next‐generation sequencing (NGS) for detection of genetic alterations and its implications on treatment of lung adenocarcinoma in real‐world practice.Patients and MethodsData were reviewed for 391 patients with lung adenocarcinoma who underwent NGS between March 2017 and October 2018. Formalin‐fixed, paraffin‐embedded archival samples were used for performing NGS targeting 382 genes, including all exons of 199 genes, 184 hotspots, and the partial introns of 8 genes often rearranged in cancer. Survival analysis was performed for stage IV disease.ResultsAmong the 391 patients, at least one actionable mutation was identified in 294 patients (75.2%). The most commonly mutated gene was EGFR (n = 130, 33.2%), involving EGFR exon 19 deletion (n = 48, 12.3%), L858R (n = 47, 12%), and others (n = 35, 9%), followed by KRAS (n = 48, 12.3%), ALK (n = 40, 10.2%), RET (6%), MET (3%), ROS‐1 (3%), and BRAF (2%) mutations. TP53 (46.9%) and CDKN2A (12.6%) mutations were common co‐mutations in patients with AMs. With a median follow‐up duration of 16.8 months, median overall survival was 36.8 months in patients with stage IV disease. Patients treated with the corresponding targeted therapy for AMs based on NGS reports lived significantly longer than those not treated with such therapy (p < 0.001). After multivariate analysis, targeted therapy for AM was a significantly favorable factor for survival (AM without targeted therapy vs. AM with targeted therapy, hazard ratio 2.58, 95% confidence interval 1.57–4.25; p < 0.001).ConclusionThis study revealed that AMs could be comparably detected using NGS. Based on these NGS results, a suitable targeted therapy can be selected, which may improve survival in patients with lung adenocarcinoma. This NGS‐based approach is useful in real‐world practice to provide guidance when selecting targeted therapy.
The debatable presence of PIWI‐interacting RNAs in invasive breast cancer
Authors: Kärkkäinen Emmi , Heikkinen Sami , Tengström Maria , Kosma Veli‐Matti , Mannermaa Arto , Hartikainen Jaana M. 
Published: May 2021

AbstractNumerous factors influence breast cancer (BC) prognosis, thus complicating the prediction of outcome. By identifying biomarkers that would distinguish the cases with poorer response to therapy already at the time of diagnosis, the rate of survival could be improved. Lately, Piwi‐interacting RNAs (piRNAs) have been introduced as potential cancer biomarkers, however, due to the recently raised challenges in piRNA annotations, further evaluation of piRNAs’ involvement in cancer is required. We performed small RNA sequencing in 227 fresh‐frozen breast tissue samples from the Eastern Finnish Kuopio Breast Cancer Project material to study the presence of piRNAs in BC and their associations with the clinicopathological features and outcome of BC patients. We observed the presence of three small RNAs annotated as piRNA database entries (DQ596932, DQ570994, and DQ571955) in our samples. The actual species of these RNAs however remain uncertain. All three small RNAs were upregulated in grade III tumors and DQ596932 additionally in estrogen receptor negative tumors. Furthermore, patients with estrogen receptor positive BC and higher DQ571955 had shorter relapse‐free survival and poorer BC‐specific survival, thus indicating DQ571955 as a candidate predictive marker for radiotherapy response in estrogen receptor positive BC. DQ596932 showed possible prognostic value in BC, whereas DQ570994 was identified as a candidate predictive marker for tamoxifen and chemotherapy response. These three small RNAs appear as candidate biomarkers for BC, which could after further investigation provide novel approaches for the treatment of therapy resistant BC. Overall, our results indicate that the prevalence of piRNAs in cancer is most likely not as comprehensive as has been previously thought.
CDK5 positively regulates Notch1 signaling in pancreatic cancer cells by phosphorylation
Authors: Chu Qiaoyun , Wang Liyong , Zhang Jie , Wang Wei , Wang Youxin 
Published: May 2021

AbstractThe marked overexpression of cyclin‐dependent kinase 5 (CDK5) or Notch1 receptor, which plays critical roles in pancreatic ductal adenocarcinoma (PDAC) development, has been detected in numerous PDAC cell lines and tissues. Although, a previous study has demonstrated that CDK5 inhibition disrupts Notch1 functions in human umbilical vein endothelial cells, the mechanism underlying Notch1 activation regulated by CDK5 remains unclear. Herein, we identified a physical interaction between CDK5 and Notch1 in PDAC cells, with the Notch1 peptide phosphorylated by CDK5/p25 kinase. CDK5 blockade resulted in the profound inhibition of Notch signaling. Accordingly, CDK5 inhibition sensitized PDAC cell proliferation and migration following Notch inhibition. In conclusion, CDK5 positively regulates Notch1 function via phosphorylation, which in turn promotes cell proliferation and migration. The combinational inhibition of CDK5 and Notch signaling may be an effective strategy in the treatment of PDAC.
Finding my voice: A qualitative exploration into the perceived impact of person‐centred counsellor training upon counsellors who were adopted as a baby
Authors: Parkes Charlotte Hannah , Mintz Rita 
Published: May 2021

AbstractThis small‐scale qualitative study explored how qualified person‐centred counsellors who were adopted as a baby perceived the impact of their person‐centred counselling training. The study focused on the adoptees’ experiences of adoption and how these influenced their experience of person‐centred counselling training. Data were analysed using interpretative phenomenological analysis to gain insight into how the participants made sense of their lived experience. The findings supported the difficulties associated with adoption, which not only are present in existing literature and research but also placed an emphasis on the particular vulnerabilities associated with being adopted as a baby. The findings further highlighted the positive impact of person‐centred counselling training on the participants’ personal development, which included the following: increased self‐awareness, self‐acceptance, identity development and ‘having a voice’. The findings confer implications for clinical practice in understanding the experience of adoptees who were adopted as a baby and for trainers in the planning and provision of person‐centred training. The research also identifies the healing aspects of person‐centred counselling training, which facilitated the participants’ positive self‐development. In addition, unique opportunities for counsellors who were also adopted as a baby are suggested and the need for the Adoption Support Fund to be extended to allow an adoptee of any age to access therapeutic support is also identified. The links made between adoption and person‐centred training are an original area of research and are worthy of further exploration.
Competency‐based nursing: Reducing cost while maintaining or improving quality
Authors: Hossler Chuck , James Alton 
Published: May 2021

AbstractThe advent of COVID‐19 and subsequent social disruption has exacerbated existing nursing workforce shortages. As nursing education programs and healthcare providers struggle to meet the care needs of their respective communities, the ever‐present challenge of replenishing nursing candidates persists—particularly when those candidates face financial hardships to complete their education. In an effort to mitigate financial hardships, competency‐based education (CBE) nursing offers the opportunity for students to self‐pace their learning and potentially complete their education more quickly. In addition to CBE programs typically being more affordable that traditional “seat time” credit‐based programs, students can potentially yield even more significant savings. Therefore, considering some healthcare providers, accreditors, and candidates may be concerned with CBE program quality, this study assesses the merit of that assertion. Through a comparative of analysis of Western Governors University's (WGU) CBE Nursing Program to similar traditional education state nursing programs, this research finds that CBE nursing programs can reduce cost while maintaining or even improving program quality by a measure of NCLEX pass rates.
Inhibition ofPlasmodium falciparumLysyl‐tRNA Synthetase via a Piperidine‐Ring Scaffold Inspired Cladosporin Analogues
Authors: Babbar Palak , Sato Mizuki , Manickam Yogavel , Mishra Siddhartha , Harlos Karl , Gupta Swati , Parvez Suhel , Kikuchi Haruhisa , Sharma Amit 
Published: May 2021

AbstractPlasmodium falciparumlysyl‐tRNA synthetase (PfKRS) represents a promising therapeutic anti‐malarial target. Cladosporin was identified as a selective and potentPfKRS inhibitor but lacks metabolic stability. Here, we report chemical synthesis, biological evaluation and structural characterization of analogues where the tetrahydropyran (THP) frame of cladosporin is replaced with the piperidine ring bearing functional group variations. Thermal binding, enzymatic, kinetic and parasitic assays complemented with X‐ray crystallography reveal compounds that are moderate in potency. Co‐crystals ofCla−BandCla−CwithPfKRS reveal key atomic configurations that allow drug binding to and inhibition of the enzyme. Collectively these piperidine ring scaffold inhibitors lay a framework for further structural editing and functional modifications of the cladosporin scaffold to obtain a potent lead.
Severe anaphylactic reaction after blue dye injection for sentinel lymph node biopsy in breast surgery: Report of two cases and literature review
Authors: Frountzas Maximos , Theodoropoulos Charalampos , Karathanasis Panagiotis , Nikolaou Christina , Zografos Constantinos G. , Larentzakis Andreas , Zografos George C. , Michalopoulos Nikolaos V. 
Published: May 2021

AbstractAnaphylactic reactions, and especially the severe ones (types III and IV), should be kept in mind as considerable adverse effects while using blue dyes for SLNB.