bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between intravenous fluid resuscitation and outcome among patients with suspected infection and sepsis: A retrospective cohort study
Authors: Kabil Gladis , Liang Sophie , Delaney Anthony , Macdonald Stephen , Thompson Kelly , Saavedra Aldo , Suster Carl , Moscova Michelle , McNally Stephen , Frost Steven , Hatcher Deborah , Shetty Amith
Published: November 2021

Objective

To investigate the association between timing and volume of intravenous fluids administered to ED patients with suspected infection and all‐cause in‐hospital mortality.

Methods

Retrospective cohort study of ED presentations at four metropolitan hospitals in Sydney, Australia, between October 2018 and May 2019. Patients over 16 years of age with suspected infection who received intravenous fluids within 24 h of presentation were included.

Results

During the study period, 7533 patients with suspected infection received intravenous fluids. Of these, 1996 (26.5%) and 231 (3.1%) had suspected sepsis and septic shock, respectively. Each 1000 mL increase in intravenous fluids administered was associated with a reduction in risk of in‐hospital mortality (adjusted odds ratio [AOR] 0.87, 95% confidence interval [CI] 0.76–0.99). This association was stronger in patients with septic shock (AOR 0.66, 95% CI 0.49–0.89), and those admitted to intensive care unit (ICU) (AOR 0.74, 95% CI 0.56–0.96). Patients with suspected sepsis and septic shock who received a total volume of >3600 mL had lower in‐hospital mortality (AOR 0.44, 95% CI 0.22–0.91; AOR 0.16, 95% CI 0.05–0.57) compared to those administered <3600 mL within the first 24 h of presenting to the ED. There was no association between the time of initiation of fluids and in‐hospital mortality among survivors and non‐survivors (2.3 vs 2.5 h, P = 0.50).

Conclusion

We observed a reduction in risk of in‐hospital mortality for each 1000 mL increase in intravenous fluids administered in patients with septic shock or admitted to ICU suggesting illness severity to be a likely effect modifier.
Antibiofilm and repair activity of ozonated oil in liposome
Authors: Zerillo Lucrezia , Polvere Immacolata , Varricchio Romualdo , Madera Jessica Raffaella , D’Andrea Silvia , Voccola Serena , Franchini Iacopo , Stilo Romania , Vito Pasquale , Zotti Tiziana
Published: November 2021

The use of medical devices, such as contact lenses, represents a substantial risk of infection, as they can act as scaffolds for formation of microbial biofilms. Recently, the increasing emergency of antibiotic resistance has prompted the development of novel and effective antimicrobial drugs for biofilm treatment, such as oxidizing agents. The purpose of this study is to investigate the effects of Ozodrop® and Ozodrop® gel, commercial names of ozonated oil in liposomes plus hypromellose, on eradication and de novo formation of biofilms on different supports, such as plastic plates and contact lens. Our results demonstrate that ozonated liposomal sunflower oil plus hypromellose have an excellent inhibitory effect on bacterial viability and on both de novo formation and eradication of biofilms produced on plates and contact lens by Pseudomonas aeruginosa and Staphylococcus aureus. Moreover, we show that Ozodrop® formulations stimulate expression of antimicrobial peptides and that Ozodrop® gel has a strong repair activity on human epithelial cells, suggesting further applications for the treatment of non‐healing infected wounds.
Active cycle of breathing technique may reduce pulmonary complications after esophagectomy: A randomized clinical trial
Authors: Zhong Jiudi , Zhang Siwen , Li Chuangzhen , Hu Yi , Wei Weijin , Liu Li , Wang Ming , Hong Zhangxian , Long Hao , Rong Tiehua , Yang Hong , Su Xiaodong
Published: November 2021

Background

The purpose of the study was to determine whether the active cycle of breathing technique (ACBT) has an impact on postoperative pulmonary complication (PPC) after esophagectomy.

Methods

In this prospective randomized trial, patients who were candidates for esophagectomy were randomized into groups, wherein they received either ACBT (n = 146) or conventional chest physiotherapy (control group, n = 145) on postoperative days (POD) 1–3. The primary outcome was PPC. The secondary outcomes included the incidence of anastomotic leakage (AL), efficacy of airway clearance, and postoperative hospital length of stay (LOS).

Results

After esophagectomy, the PPC rate was significantly lower in the ACBT group (15.2%) than in the control group (31.0%) (p = 0.001). The incidences of AL were 5.5% and 12.4% in the ACBT and control groups, respectively (p = 0.042). Mean hospital LOS was 12.3 days for the ACBT group and 16.8 days for the control group (p = 0.008). ACBT significantly increased the mean sputum wet weight (g) on POD 1–3 when compared with conventional therapy (POD 1 9.08 vs. 6.47, POD 2 16.86 vs. 10.92, POD 3 24.65 vs. 13.52, all p < 0.001). Multivariable analysis revealed that ACBT decreased the rates of PPC (odds ratio [OR] 0.403, p = 0.003), AL (OR 0.379，p = 0.038)，arrhythmia (OR 0.397, p = 0.028), and bronchoscopy aspiration (OR 0.362, p = 0.016).

Conclusion

ACBT is an effective airway clearance technique that significantly reduces the incidence of PPC after esophagectomy. ACBT could also significantly reduce both AL and LOS.
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

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

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

Background

Negative 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.

Methods

We 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.

Results

Wheel 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.

Conclusions

This 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.
Indian caste names and cooperation in the Prisoner’s Dilemma
Authors: Tiwari Shambhavi , Ścigała Karolina Aleksandra , Schild Christoph , Zettler Ingo
Published: November 2021

Ingroup/outgroup categorisation is a repeatedly found phenomenon. Given the long‐standing caste system, the Indian societal structure provides a unique perspective on such social categorisation. The Indian caste system contains hereditarily inherited identity roles defining profession and status‐based hierarchies. In this preregistered experiment, we investigate the influence of caste‐based identity on cooperation using a (hypothetical) Prisoner’s Dilemma. Specifically, Indian participants (N = 685) were paired with a (hypothetical) other in a Prisoner’s Dilemma, whose last name reflected either a general caste (i.e., a “high” caste) or a backward (“lower”) caste including the scheduled caste, scheduled tribe, and other backward classes. Because participants indicated belonging to a general or a backward caste themselves, they thus played the (hypothetical) Prisoner’s Dilemma with either a member of the same or a different caste group. We did not find that the partner’s caste group membership in terms of stemming from an ingroup (same caste) or outgroup (different caste) influenced participants’ cooperation. Further, we found participants from the general caste to be more cooperative when paired with (hypothetical) backward caste others (outgroup), compared to backward caste participants when paired with (hypothetical) general caste participants (outgroup); however, this difference disappeared once controlling for other demographic characteristics.
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

In 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

Aim

To 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.

Methods

We 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.

Results

Sputum 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.

Conclusion

Mediator 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

Within 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

Human 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

Objective

To 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 Methods

A 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.

Results

A 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).

Conclusions

This 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

Objectives

To describe clinical, imaging, and histopathological characteristics of inflammatory myofibroblastic tumour (IMT) of the urinary bladder and provide initial management and surveillance recommendations.

Patients and Methods

We 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.

Results

IMT 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.

Conclusions

No 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 Purpose

Analogues 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 Approach

Efruxifermin 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 Results

Efruxifermin 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 Implications

Efruxifermin 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

Lung 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

A 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.
Care in COVID: A qualitative analysis of the impact of COVID‐19 on the health and care of children and young people with severe physical neurodisability and their families
Authors: Cadwgan Jill , Goodwin Jane , Arichi Tomoki , Patel Anita , Turner Susie , Barkey Sinead , McDonald Aoife , Lumsden Daniel E. , Fairhurst Charlie
Published: November 2021

Aim

To evaluate clinicians' perspectives on the impact of ‘lockdown’ during the COVID‐19 pandemic for children and young people with severe physical neurodisability and their families.

Method

Framework analysis of comments from families during a recent service review was used to code the themes discussed according to the World Health Organization International Classification of Functioning, Disability and Health (ICF) and interpreted into emergent themes to summarize the impact of lockdown (Stage 1). They were presented to a clinician focus group for discussion (consultants and physiotherapists working in a specialist motor disorders service, [Stage 2]).

Results

Three overarching themes ‘Uncertainty and Anxiety’, ‘Exacerbation of Existing Inequalities’ and ‘Care Provision: Reaction, Adaptation, and Innovation’ summed up the impact of the COVID‐19 pandemic on health and well‐being in children and young people with neurodisability and their families. All themes were influenced by time.

Interpretation

This study reflects clinician's perceptions of family experiences of the pandemic and lockdown. Significant impact is apparent in the entire U.K. population, but the complexity of care needs for children with physical neurodisability exacerbates this. Lobbying for government policy is vital to ensure that all children, and in particular those with significant health and social care needs, are protected and continue to access services. During the restoration and recovery phase of the pandemic, there is a need for service reconfiguration that utilizes what we have learned and is adaptive to individual family circumstances.
Lipid transfer protein allergy: A review of current controversies
Authors: Asero Riccardo , Pravettoni Valerio , Scala Enrico , Villalta Danilo
Published: November 2021

Sensitization to lipid transfer protein (LTP), the most frequent cause of food allergy in southern Europe, still shows several controversial, but also intriguing, aspects. Some of these include the degree of cross‐reactivity between LTPs from botanically distant sources, the definition of risk factors, the role of some cofactors, clinical outcomes, geographical differences and the identification of the primary sensitizer in different areas. This review article tries to analyse and comment on these aspects point by point suggesting some explanatory hypotheses with the final scope to stimulate critical thoughts and elicit the scientific discussion about this issue in the readership.
The effects of a resilience programme on social skills, bullying, and victimisation among eight to thirteen‐year‐old students
Authors: Bain Brian J. , Lunde Rebecca M.
Published: November 2021

The continued problem of bullying merits prevention. The resilience programme studied in this research teaches victimisation avoidance skills. The purpose of this study was to determine the effects of a resilience programme on social skills, victimisation, and bullying among eight to thirteen‐year‐old students. This quantitative, quasi‐experimental design sampled students’ self‐reported social skills (n = 72), bullying (n = 67), and victimisation (n = 67) in two, Northeastern U.S. schools. Paired samples t‐test analyses showed that the programme had positive effects on social skills, no effects on bullying, and negative effects on victimisation. Recommendations were made regarding bullying prevention and future research.
Characteristics of hand eczema in final‐year apprentice nurses during the COVID‐19 pandemic
Authors: Šakić Franka , Babić Željka , Franić Zrinka , Macan Jelena
Published: November 2021

Background

Apprentice nurses are considered at high risk to developing occupational skin diseases.

Objectives

This study assessed the frequency and origin of hand eczema, and work‐related risk factors in apprentice nurses.

Methods

The study involved 240 final‐year apprentice nurses (females 75%, median age 19 years) from vocational schools in Zagreb, Croatia. The study was performed in 2020/2021 and included a questionnaire and clinical examination by means of the Osnabrück Hand Eczema Severity Index (OHSI). Skin prick test (SPT) with natural rubber latex (NRL) allergen, and patch test with the basic series of allergens, and disinfectants, were performed in 42 apprentice nurses with hand eczema that lasted more than 3 months.

Results

Clinically observed and self‐reported hand eczema were found in 49% and 46% of apprentice nurses, respectively. Those with observed changes were older and reported more days per month spent on practical work than those with healthy skin (P = .001). Median OHSI was 4 (interquartile range 2‐6). There were no positive SPTs to latex, and 11 (26%) apprentice nurses had positive patch test reactions to one or more tested allergens, mostly nickel.

Conclusions

Hand eczema was common in final‐year apprentice nurses during the COVID‐19 pandemic. It was mostly of irritative origin, associated with the duration of practical training, confirming cumulative effect of hazards on skin barrier.
Characterizing demographics and cost of care for dyshidrotic eczema
Authors: Gladys Taylor E. , Maczuga Steven , Flamm Alexandra
Published: November 2021

Background

Dyshidrotic eczema (DE) is a common form of eczema affecting the hands, feet, or both areas. To date, there has been little research examining demographics and cost burden associated with this disease.

Objective

This study seeks to characterize the demographics of patients affected and the direct costs of care associated with DE.

Methods

This is a retrospective analysis utilizing insurance claim information from IBM MarketScan. Pertinent data including demographic information, healthcare provider type, medications prescribed, and average cost of care were identified using the ICD 10 code L30.1 for DE for the year 2018.

Results

In 2018, 34 932 patients filed claims for DE, with 61% female and an average age of 37 years at first diagnosis. DE was mostly seen in employees from the service industry and the manufacturing of durable goods. The total annual direct cost was US $11 738 985. Average annual costs, however, did vary based on type of treating healthcare provider, level of care, and medications prescribed.

Conclusions

Patients with DE can face an economic burden due to their disease and providers should aim to recognize this disease and its treatments to minimize healthcare costs for patients and improve quality of life.
Human retinal pigment epithelial cells
Authors: Wang Lei , Cao Jiani , Peng Yaojin , Fu Boqiang , Jin Zibing , Hu Yuntao , Wu Wei , Xiang Andy peng , Hu Shijun , Yu Junying , Zhang Yu , Wei Jun , Zhang Yong , Li Qiyuan , Zhou Jiaxi , Zhai Peijun , Zhu Huanxin , Liang Lingmin , Ma Aijin , Stacey Glyn , Zhao Tongbiao , Hao Jie
Published: November 2021

'Human retinal pigment epithelial cells' is the first set of guidelines on human retinal pigment epithelial cells in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies technical requirements, test methods, inspection rules, instructions for usage, labelling requirements, packaging requirements, storage requirements and transportation requirements and waste disposal requirements for human retinal pigment epithelial cells, which is applicable to quality control during the process of manufacturing and testing of human retinal pigment epithelial cells. It was originally released by the Chinese Society for Cell Biology on 9 January 2021. We hope that publication of these guidelines will promote institutional establishment, acceptance and execution of proper protocols and accelerate the international standardization of human retinal pigment epithelial cells for applications.
Ethical issues of organ donation after circulatory death: Considerations for a successful implementation in Chile
Authors: Pérez Castro Pablo , Salas Sofía P.
Published: November 2021

Organ transplantation is a lifesaving procedure for end‐organ damage and remains up to today as the most cost‐effective alternative to treat these conditions. However, the main limitation to performing organ transplants is the availability of donor organs suitable for transplantation. To increase the donor pool, expanding organ donation from the conventional neurologic determination of death (NDD) to include circulatory determination of death (DCD) has been a well‐established method of increasing donors in other countries. In this article, we discuss the clinical and ethical considerations for introducing DCD in Chile. The concepts we have used could very well be translatable to other similar countries which have not implemented this donation system yet. The most relevant issue to date is that DCD needs to alter the care of dying patients to obtain quality donor organs. In some countries, including Chile, there are some cultural barriers regarding withdrawal‐of‐care. These barriers include confusing withdrawal of care with acceleration of death, which leads to many practitioners refusing to remove artificial life support, and in turn only minimize ventilatory support or switch to a T‐tube (without extubation). This cultural barrier could be overcome with careful consideration of the opinions of healthcare workers, family members, community and policy‐based stakeholders. We also identified ethical issues related to informed consent of both donor and recipients, among other relevant ethical considerations. In conclusion, DCD donation in Chile can increase organ donation numbers in one of Latin America's countries with the lowest effective donor rate. However, this opportunity must be taken with caution to avoid the opposite effect if this policy is not well implemented, respecting the sound ethical principles mentioned in this paper.
Real‐world evidence on clinical outcomes of people with type 1 diabetes using open‐source and commercial automated insulin dosing systems: A systematic review
Authors: Knoll Christine , Peacock Sofia , Wäldchen Mandy , Cooper Drew , Aulakh Simran Kaur , Raile Klemens , Hussain Sufyan , Braune Katarina
Published: November 2021

Aims

Several commercial and open‐source automated insulin dosing (AID) systems have recently been developed and are now used by an increasing number of people with diabetes (PwD). This systematic review explored the current status of real‐world evidence on the latest available AID systems in helping to understand their safety and effectiveness.

Methods

A systematic review of real‐world studies on the effect of commercial and open‐source AID system use on clinical outcomes was conducted employing a devised protocol (PROSPERO ID 257354).

Results

Of 441 initially identified studies, 21 published 2018–2021 were included: 12 for Medtronic 670G; one for Tandem Control‐IQ; one for Diabeloop DBLG1; two for AndroidAPS; one for OpenAPS; one for Loop; three comparing various types of AID systems. These studies found that several types of AID systems improve Time‐in‐Range and haemoglobin A1c (HbA1c) with minimal concerns around severe hypoglycaemia. These improvements were observed in open‐source and commercially developed AID systems alike.

Conclusions

Commercially developed and open‐source AID systems represent effective and safe treatment options for PwD of several age groups and genders. Alongside evidence from randomized clinical trials, real‐world studies on AID systems and their effects on glycaemic outcomes are a helpful method for evaluating their safety and effectiveness.
Diabetes management in the face of adversity: Experiences of asylum‐seekers in Belgian reception centres
Authors: Van Hemelrijck Wanda Monika Johanna , Vandenheede Hadewijch , Argeseanu Cunningham Solveig
Published: November 2021

Background

Diabetes poses a heavy burden on patients due to its progressive and chronic nature; it requires continuous management to promote a high‐quality and long life. Disease management is especially challenging in emergency settings. We examined how displaced people with diabetes experienced managing their illness before and throughout the process of fleeing their home communities and seeking resettlement in Europe.

Design

We designed an interview instrument with closed‐ and open‐ended questions about diabetes diagnosis and management before fleeing the home country, during migration, stays in transit countries and reception in the European Union. We interviewed 20 asylum‐seekers living in Belgian reception centres with diagnosed diabetes mellitus.

Results

Primary topics emerging from interviews were availability, accessibility, and quality. Belgium was described as a setting with high availability, accessibility and quality of diabetes management components (medication, tools, care) compared with other settings before and during migration. Even in Belgium, maintaining a healthy diet as an asylum‐seeker was difficult. Other concerns such as safety, other health issues and the asylum request itself often outweighed diabetes management.

Conclusions

Displaced people in non‐Western countries need attention for nutrition and diabetes medicine, so aid agencies should consider providing for those needs. For people seeking asylum in the West and living in temporary facilities, care should be paid to the dietary options available for those with diabetes. For irregular migrants, diabetes can be deadly, and resources should be made available for their basic diabetes needs, even if they are not eligible for regular health services.
Acoustic telemetry predation sensors reveal the tribulations of Atlantic salmon (Salmo salar) smolts migrating through lakes
Authors: Hanssen Erlend M. , Vollset Knut Wiik , Salvanes Anne Gro Vea , Barlaup Bjørn , Whoriskey Kim , Isaksen Trond Einar , Normann Eirik Straume , Hulbak Magnus , Lennox Robert J.
Published: November 2021

Smolt migration through lakes is hazardous, as the predation pressure can be extreme and the hydrology a great contrast to that of a riverine area. However, the mechanisms yielding these challenges have been scarcely investigated. We conducted an acoustic telemetry field study in Lake Evangervatnet, Voss, Norway, utilising Vemco V5 predation tags. Atlantic salmon (Salmo salar) smolts (N = 20) were tagged with the novel predation sensor tag to investigate mortality, the lacustrine migration behaviour of smolts, and the applicability of these tags for smolt studies. A total of 60% of tagged Atlantic salmon (Salmo salar) smolts perished in the lake. Half of the mortalities (30% of tagged fish) were directly attributed to predation by brown trout (Salmo trutta) based on predation sensors. The surviving smolts were slow to traverse the 6.5 km lake, with progression rate between lake inlet and outlet on average 0.016 m/s over a mean of 7.9 ± 6.2 (SD) days. Acoustic detections revealed a consistent pattern of nocturnal migration and multidirectional movements within the lake. By running a series of correlated random walks under varying parameters and comparing the simulated travel times to the observed travel time used by the tagged smolts, we emulated the observed behaviour of the smolts. These simulations suggested that smolts lacked the ability to efficiently navigate through the lake, instead swimming in random directions until they reached the lake outlet. Predation sensors can offer improved resolution when tracking the behaviour and fate of smolts and can facilitate better mitigation efforts by identifying survival bottlenecks and separating predation from non‐predatory mortality.
Landscape genomics of the streamside salamander: Implications for species management in the face of environmental change
Authors: Beer Marc A. , Kane Rachael A. , Micheletti Steven J. , Kozakiewicz Christopher P. , Storfer Andrew
Published: November 2021

Understanding spatial patterns of genetic differentiation and local adaptation is critical in a period of rapid environmental change. Climate change and anthropogenic development have led to population declines and shifting geographic distributions in numerous species. The streamside salamander, Ambystoma barbouri, is an endemic amphibian with a small geographic range that predominantly inhabits small, ephemeral streams. As A. barbouri is listed as near‐threatened by the IUCN, we describe range‐wide patterns of genetic differentiation and adaptation to assess the species’ potential to respond to environmental change. We use outlier scans and genetic‐environment association analyses to identify genomic variation putatively underlying local adaptation across the species’ geographic range. We find evidence for adaptation with a polygenic architecture and a set of candidate SNPs that identify genes putatively contributing to local adaptation. Our results build on earlier work that suggests that some A. barbouri populations are locally adapted despite evidence for asymmetric gene flow between the range core and periphery. Taken together, the body of work describing the evolutionary genetics of range limits in A. barbouri suggests that the species may be unlikely to respond naturally to environmental challenges through a range shift or in situ adaptation. We suggest that management efforts such as assisted migration may be necessary in future.