bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pitfalls and pointers: An accessible guide to marker gene amplicon sequencing in ecological applications
Authors: Porath‐Krause Anita , Strauss Alexander T. , Henning Jeremiah A. , Seabloom Eric W. , Borer Elizabeth T. 
Published: November 2021

Abstract

Next‐Generation Sequencing (NGS) is a powerful tool that has been rapidly adopted by many ecologists studying microbial communities. Despite the exciting demonstration of NGS technology as a tool for ecological research, cryptic pitfalls inherent to its use can obscure correct interpretation of NGS data. Here, we provide an accessible overview of a NGS process that uses marker gene amplicon sequences (MGAS) that will allow scientists, particularly community ecologists, to make appropriate methodological choices and understand limits on inference about community composition and diversity that can be drawn from MGAS data.

We describe the MGAS pipeline, focusing specifically on cryptic sources of variation that have received less emphasis in the ecological literature, but which may substantially impact inference about microbial community diversity and composition. By simulating communities from published microbiome data, we demonstrate how these sources of variation can generate inaccurate or misleading patterns.

We specifically highlight sample dilution without researcher awareness and lane‐to‐lane variability, two cryptic sources of variation arising during the MGAS pipeline. These sources of variation affect estimates of species presence and relative abundance, particularly for species with moderate to low abundances. Each of these sources of bias can lead to errors in the estimation of both absolute and relative abundance within, and turnover among, microbial communities.

Awareness and understanding of what happens and, specifically, why it happens during MGAS generation is key to generating a strong dataset and building a robust community matrix. Requesting sample dilution information from the sequencing centre, including technical replicates across sequencing lanes, and understanding how sampling intensity and community taxa distribution patterns shape the measurement of community richness, evenness and diversity are critical for drawing correct ecological inferences using MGAS data.
Spectrogram cross‐correlation can be used to measure the complexity of bird vocalizations
Authors: Sawant Suyash , Arvind Chiti , Joshi Viral , Robin V. V. 
Published: November 2021

Abstract

Birdsong is an important signal in mate attraction and territorial defence. Quantifying the complexity of these songs can shed light on individual fitness, sexual selection and behaviour. Several techniques have been used to quantify song complexity and be broadly categorized into measures of sequential variations and measures of diversity. However, these methods are unable to account for important acoustic features like the frequency bandwidth and the variety in the spectro‐temporal shape of notes which are an integral part of these vocal signals. This study proposes a new complexity method that considers intra‐song note variability and calculates a weighted index for birdsongs using spectral cross‐correlation.

We first compared previously described methods to understand their advantages and limitations based on the factors that would affect the complexity of songs. We then developed a new method, Note Variability Index (NVI), which incorporates the spectral features of notes to quantify complexity. This method alleviates the need for manual classification of notes that can be error‐prone. We used spectrogram cross‐correlation to compare notes within a song and used the output values to quantify song complexity.

To evaluate the efficacy of the new method, we generated synthetic songs to caricature extremes in song complexity and compared selected conventional complexity methods along with the NVI. We provide case‐specific limitations of these methods. Additionally, to examine the efficacy of this new method in real‐world scenarios, we used natural birdsongs from multiple species across the globe with varying song structures to compare conventional methods with NVI.

To our knowledge, NVI is the only song complexity method that captures the variation of spectro‐temporal shapes of the notes in songs where the conventional methods fail to distinguish between similar song structures with different note types. Furthermore, as NVI does not need a manual classification of notes, it can be easily implemented for any type of birdsong with existing sound analysis software; it is quick, avoids the possible subjectivity in note classification and can be automated for large datasets.
The impact of intermittent exercise on mouse ethanol drinking and abstinence‐associated affective behavior and physiology
Authors: Centanni Samuel W. , Conley Sara Y. , Luchsinger Joseph R. , Lantier Louise , Winder Danny G. 
Published: November 2021

AbstractBackgroundNegative emotional states are associated with the initiation and maintenance of alcohol use and drive relapse to drinking during withdrawal and protracted abstinence. Physical exercise is correlated with decreased negative affective symptoms, although a direct relationship between drinking patterns and exercise level has not been fully elucidated.MethodsWe incorporated intermittent running wheel access into a chronic continuous access, two‐bottle choice alcohol drinking model in female C57BL/6J mice. Wheel access was granted intermittently once mice established a preference for alcohol over water. After 6 weeks, alcohol was removed (forced abstinence) and mice were given continuous access to unlocked or locked wheels. Negative affect‐like behavior, home cage behavior, and metabolic activity were measured during protracted abstinence.ResultsWheel access shifted drinking patterns in the mice, increasing drinking when the wheel was locked, and decreasing drinking when unlocked. Moreover, alcohol preference and consumption were strongly negatively correlated with the amount of running. An assessment of negative affect‐like behavior in abstinence via the novelty suppressed feeding and saccharin preference tests (SPT) showed that unlimited wheel access mitigated abstinence‐induced latency increases. Mice in abstinence also spent more time sleeping during the active dark cycle than control mice, providing additional evidence for abstinence‐induced anhedonia‐ and depression‐like behavior. Furthermore, running wheel access in abstinence decreased dark cycle sleep to comparable alcohol‐ and wheel‐naïve mice. Given the positive impact of exercise and the negative impact of alcohol on metabolic health, we compared metabolic phenotypes of alcohol‐abstinent mice with and without wheel access. Wheel access increased energy expenditure, carbon dioxide production, and oxygen consumption, providing a potential metabolic mechanism through which wheel access improves affective state.ConclusionsThis study suggests that including exercise in AUD treatment regimens has the potential to reduce drinking, improve affective state during abstinence and could serve as a non‐pharmacological approach to prevent the development of an AUD in high‐risk individuals.
A lifelong quest to make home hemodialysis simple, safe, and effective: A review of outcomes of 12 major projects
Authors: Ash Stephen R. 
Published: November 2021

AbstractIn the course of over four decades, I have worked with an R&D team on 12 major R&D projects, all with the goal of making hemodialysis simple, safe, effective, and suitable for use in the home. Our team has worked within a University and in private companies and has collaborated with major healthcare drug and device companies. As a practicing nephrologist, my definition of success is when I see the device or drug we helped to develop in widespread clinical use. By this measure, two of the projects were highly successful, but seven failed. Most failures were due to decisions made by various corporations, governmental agencies, and venture capital groups, out of the hands or control of the R&D company. Three projects are still ongoing. There is no shortage of creativity or new ideas in nephrology and in dialysis. The major challenge is in the commercialization of the products.
Sputum biomarkers during acute severe asthma attacks in children—a case‐control study
Authors: Ramphul Manisha , Welsh Kathryn G. , May Richard D. , Ghebre Michael A. , Rapley Laura , Cohen Emma Suzanne , Herath Athula , Monteiro William , Rousseau Karine , Thornton David J. , Brightling Christopher E. , Gaillard Erol A. 
Published: November 2021

AbstractAimTo study sputum mediator profiles pattern in children with acute severe asthma, compared with stable asthma and healthy controls. The mechanisms of acute severe asthma attacks, such as biomarkers cascades and immunological responses, are poorly understood.MethodsWe conducted a prospective observational case‐control study of children aged 5 to 17 years, who presented to hospital with an asthma attack. Children with stable asthma were recruited during outpatient asthma clinic visits. Control children without an asthma diagnosis were recruited from surgical wards. Sputum mediator profiles were measured, and sputum leukocyte differential cell counts were generated.ResultsSputum data were available in 48 children (acute asthma; n = 18, stable asthma; n = 17, healthy controls; n = 13). Acute‐phase biomarkers and neutrophil attractants such as IL‐6 and its receptor, IL‐8 and cytokines linked with bacterial signals, including TNF‐R1 and TNF‐R2, were elevated in asthma attacks versus stable asthma and healthy controls. T‐cell attractant cytokines, associated with viral infections, such as CCL‐5, CXCL‐10 and CXCL‐11, and CXCL‐9 (secreted from eosinophils after a viral trigger) were also raised.ConclusionMediator profiles consistent with bacterial and viral respiratory infections, and T2 inflammation markers co‐exist in the sputum of children with acute severe asthma attacks.
Can people talk about their past practices? Challenges, opportunities, and practical applications of biographic inquiry for geographic research on consumption
Authors: Greene Mary , Royston Sarah 
Published: November 2021

AbstractWithin human geography, there is increasing interest in the application of theories of practice for understanding resource consumption and for pursuing sustainability goals. In stressing the routine, performative, and contextual dimensions of action, research on geographies of practice is faced with particular methodological challenges. A lively debate concerns the utility of talk‐based methods for investigating routine practices, such as those relating to everyday consumption. While it has been compellingly argued that people can talk individually or in groups about their practice, as of yet, these methodological debates have not been extended to the question of whether people can talk about past practices over the life course. This is despite the fact that attending to practice dynamics at the life‐course scale can reveal important insights into the intersections of structure, agency, time, and space in consumption practices. Seeking to address this gap, this methodology‐focused paper explores biographic inquiry as an empirical strategy for research on geographies of practice and consumption. After identifying significant challenges in representation associated with researching routine action in general, and past practices in particular, it outlines key learnings garnered during a biographic study on domestic consumption in Ireland. Central methodological features supporting talk‐elicitation include zooming‐in‐and‐out of temporal registers, multi‐modality, and phased implementation. The paper concludes that people can talk about past practices in often very detailed, intricate ways and that retrospective talk is a valuable tool for understanding practice dynamics at the life‐course scale.
The effects of task‐irrelevant threatening stimuli on orienting‐ and executive attentional processes under cognitive load
Authors: Zsidó Andras N. , Stecina Diana T. , Cseh Rebecca , Hout Michael C. 
Published: November 2021

AbstractHuman visual attention is biased to rapidly detect threats in the environment so that our nervous system can initiate quick reactions. The processes underlying threat detection (and how they operate under cognitive load), however, are still poorly understood. Thus, we sought to test the impact of task‐irrelevant threatening stimuli on the salience network and executive control of attention during low and high cognitive load. Participants were exposed to neutral or threatening pictures (with moderate and high arousal levels) as task‐irrelevant distractors in near (parafoveal) and far (peripheral) positions while searching for numbers in ascending order in a matrix array. We measured reaction times and recorded eye‐movements. Our results showed that task‐irrelevant distractors primarily influenced behavioural measures during high cognitive load. The distracting effect of threatening images with moderate arousal level slowed reaction times for finding the first number. However, this slowing was offset by high arousal threatening stimuli, leading to overall shorter search times. Eye‐tracking measures showed that participants fixated threatening pictures more later and for shorter durations compared to neutral images. Together, our results indicate a complex relationship between threats and attention that results not in a unitary bias but in a sequence of effects that unfold over time.
A non‐inferiority comparative analysis of micro‐ultrasonography and MRI‐targeted biopsy in men at risk of prostate cancer
Authors: Hofbauer Sebastian L. , Luger Ferdinand , Harland Niklas , Plage Henning , Reimann Maximillian , Hollenbach Markus , Gusenleitner Andreas , Stenzl Arnulf , Schlomm Thorsten , Wiemer Laura , Cash Hannes 
Published: November 2021

ObjectiveTo compare the efficacy of multiparametric magnetic resonance imaging (mpMRI)‐directed and micro‐ultrasonography (micro‐US)‐directed biopsy for detecting clinically significant (Grade Group >1) prostate cancer (csPCa).Materials and MethodsA total of 203 patients were prospectively enrolled at three institutions across Germany and Austria in the period from January 2019 to December 2019. During each biopsy, the urologist was blinded to the mpMRI report until after the micro‐US targets had been assessed. After unblinding, targets were then sampled using software‐assisted fusion, followed by systematic samples. The primary outcome measure was non‐inferiority of micro‐US to detect csPCa, with a detection ratio of at least 80% that of mpMRI.ResultsA total of 79 csPCa cases were detected overall (39%). Micro‐US‐targeted biopsy detected 58/79 cases (73%), while mpMRI‐targeted biopsy detected 60/79 (76%) and non‐targeted (completion sampling) samples detected 45/79 cases (57%). mpMRI‐targeted samples alone detected 7/79 (9%) csPCa cases which were missed by micro‐US‐targeted and non‐targeted samples. Three of these seven were anterior lesions with 2/7 in the transition zone. Micro‐US‐targeted samples alone detected 5/79 (6%) and completion sampling alone detected 4/79 cases (5%). Micro‐US was non‐inferior to mpMRI and detected 97% of the csPCa cases detected by mpMRI‐targeted biopsy (95% CI 80–116%; P = 0.023).ConclusionsThis is the first multicentre prospective study comparing micro‐US‐targeted biopsy with mpMRI‐targeted biopsy. The study provides further evidence that micro‐US can reliably detect cancer lesions and suggests that micro‐US biopsy might be as effective as mpMRI for detection of csPCA. This result has significant implications for increasing accessibility, reducing costs and expediting diagnosis.
Clinicopathological analysis and outcomes of inflammatory myofibroblastic tumours of the urinary bladder
Authors: Hensley Patrick J. , Bree Kelly K. , Guo Charles C. , Lobo Niyati , Campbell Matthew T. , Pettaway Curtis A. , Kamat Ashish M. 
Published: November 2021

ObjectivesTo describe clinical, imaging, and histopathological characteristics of inflammatory myofibroblastic tumour (IMT) of the urinary bladder and provide initial management and surveillance recommendations.Patients and MethodsWe identified patients with IMT of the bladder treated at our facility from 1998 to 2020. Categorical variables were analysed with chi‐square and Fisher’s exact tests and continuous variables with the Mann–Whitney U‐test. Kaplan–Meier analysis was performed for recurrence‐free survival.ResultsIMT was diagnosed in 35 patients with median (interquartile range [IQR]) follow‐up of 20 (11.5–68.5) months. At initial diagnosis 86% were clinically organ‐confined, 9% locally advanced, and 5% metastatic. Majority of patients (92%) had residual disease on re‐staging transurethral resection (TUR). Of the 15 patients with organ‐confined disease managed initially with TUR alone, five (33%) recurred at a median (IQR) of 5 (3.0–5.5) months from initial diagnosis. Presentation with visible haematuria was associated with recurrence (100% in recurrence vs 40% in non‐recurrence groups, P = 0.044). There were no patients who developed a recurrence beyond 6 months after diagnosis. Partial or radical cystectomy was required in 23% and 9% of patients, respectively. One patient presented with metastatic disease associated with anaplastic lymphoma kinase (ALK) translocation and achieved a durable complete remission with 7 months of crizotinib therapy.ConclusionsNo patient with IMT treated with aggressive endoscopic management developed recurrences beyond 6 months. There were additionally no recurrences noted after definitive radical or partial cystectomy. These data support organ sparing therapy with aggressive endoscopic management and short‐term surveillance in patients with localised IMT, with extirpative surgery reserved for refractory cases.
Efruxifermin, a long‐acting Fc‐fusion FGF21 analogue, reduces body weight gain but does not increase sympathetic tone or urine volume in Sprague Dawley rats
Authors: Tillman Erik J. , Brock William J. , Rolph Tim 
Published: November 2021

Background and PurposeAnalogues of fibroblast growth factor 21 (FGF21) demonstrate diverse metabolic benefits in preclinical models of type 2 diabetes, dyslipidaemia and non‐alcoholic steatohepatitis (NASH), but clinical responses with different analogues are inconsistent. Efruxifermin is an Fc‐FGF21 fusion protein with prolonged half‐life and enhanced receptor affinity compared with native human FGF21. Efruxifermin is in clinical trials for the treatment of non‐alcoholic steatohepatitis.Experimental ApproachEfruxifermin was administered weekly to male and female Sprague Dawley rats for 4 or 26 weeks. Body and organ weights, macroscopic and microscopic pathology, clinical chemistry, blood cytology and serum and urine biomarkers were analysed to characterize the pharmacodynamics of efruxifermin and to investigate potential non‐clinical toxicities following chronic administration of supra‐pharmacological doses of efruxifermin.Key ResultsEfruxifermin significantly reduced body weight gain after 4 and 26 weeks, despite increasing food intake. Changes in tissue pathology, clinical chemistry and serum biomarkers generally appeared to be associated with weight loss, except for a significant decrease in urine volume in both males and females without perturbed electrolyte balance. Markers of sympathetic activation, urinary corticosterone and ratio of adrenal‐to‐body weight were unchanged.Conclusion and ImplicationsEfruxifermin attenuated body weight gain, consistent with other FGF21 analogues. In contrast to at least one other FGF21 analogue, efruxifermin decreased rather than increased urine volume. The absence of an increase in sympathetic tone in rats mirrors the unchanged salivary cortisol and systemic blood pressure following efruxifermin treatment in humans.
Nuclear accumulation of KPNA2 impacts radioresistance through positive regulation of the PLSCR1‐STAT1 loop in lung adenocarcinoma
Authors: Liao Wei‐Chao , Lin Tsung‐Jen , Liu Yu‐Chin , Wei Yu‐Shan , Chen Guan‐Ying , Feng Hsiang‐Pu , Chang Yi‐Feng , Chang Hsin‐Tzu , Wang Chih‐Liang , Chi Hsinag‐Cheng , Wang Chun‐I , Lin Kwang‐Huei , Ou Yang Wei‐Ting , Yu Chia‐Jung 
Published: November 2021

AbstractLung adenocarcinoma (ADC) is the predominant histological type of lung cancer, and radiotherapy is one of the current therapeutic strategies for lung cancer treatment. Unfortunately, biological complexity and cancer heterogeneity contribute to radioresistance development. Karyopherin α2 (KPNA2) is a member of the importin α family that mediates the nucleocytoplasmic transport of cargo proteins. KPNA2 overexpression is observed across cancer tissues of diverse origins. However, the role of KPNA2 in lung cancer radioresistance is unclear. Herein, we demonstrated that high expression of KPNA2 is positively correlated with radioresistance and cancer stem cell (CSC) properties in lung ADC cells. Radioresistant cells exhibited nuclear accumulation of KPNA2 and its cargos (OCT4 and c‐MYC). Additionally, KPNA2 knockdown regulated CSC‐related gene expression in radioresistant cells. Next‐generation sequencing and bioinformatic analysis revealed that STAT1 activation and nuclear phospholipid scramblase 1 (PLSCR1) are involved in KPNA2‐mediated radioresistance. Endogenous PLSCR1 interacting with KPNA2 and PLSCR1 knockdown suppressed the radioresistance induced by KPNA2 expression. Both STAT1 and PLSCR1 were found to be positively correlated with dysregulated KPNA2 in radioresistant cells and ADC tissues. We further demonstrated a potential positive feedback loop between PLSCR1 and STAT1 in radioresistant cells, and this PLSCR1‐STAT1 loop modulates CSC characteristics. In addition, AKT1 knockdown attenuated the nuclear accumulation of KPNA2 in radioresistant lung cancer cells. Our results collectively support a mechanistic understanding of a novel role for KPNA2 in promoting radioresistance in lung ADC cells.
Synthesis, biological evaluation, and molecular modeling studies of acetophenones‐tethered 1,2,4‐triazoles and their oximes as epidermal growth factor receptor inhibitors
Authors: El‐Wahab Hend A. A. Abd , Ali Ahmed M. , Abdel‐Rahman Hamdy M. , Qayed Wesam S. 
Published: November 2021

AbstractA series of 5‐(4‐pyridyl)‐1,2,4‐triazoles hybrids with acetophenones and their oxime derivatives was rationally designed and synthesized as epidermal growth factor receptor (EGFR) kinase inhibitors. Initially, drug Likeness and pharmacokinetics properties of the prepared compounds were evaluated. Afterward, the prepared compounds were in vitro screened for their ability to inhibit the growth of the NCI‐60 human cancer cell lines where certain compounds showed moderate activity. Compounds 4e and 5b emerged as the most potent compounds in this series were further tested for their EGFR enzyme inhibition activity. They showed IC50 values of 0.14 and 0.18 µM, respectively, in comparison with Gefitinib as a reference with an IC50 value of 0.06 µM. Docking of compounds 4e and 5b into the binding site of EGFR tyrosine kinase was performed to explains their possible binding mode and to compare it with known inhibitors. Moreover, molecular dynamic simulations were estimated for deeper understanding of the binding mode of compounds 4e and 5b at the binding site of EGFR tyrosine kinase. The findings indicated that the novel ligands 4e and 5b were stable in the EGFR tyrosine kinase active site.