bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent advancement of decellularization extracellular matrix for tissue engineering and biomedical application
Authors: Yang Jiamin , Dang Hangyu , Xu Yi
Published: December 2021

Background

Decellularized extracellular matrixs (dECMs) derived from organs and tissues have emerged as a promising tool, as they encompass the characteristics of an ideal tissue scaffold: complex composition, vascular networks and unique tissue‐specific architecture. Consequently, their use has propagated throughout tissue engineering and regenerative medicine. dECM can be easily obtained from various tissues/organs by appropriate decellularization protocolsand is entitled to provide necessary cues to cells homing.

Methods

In this review, we describe the decellularization and sterilization methods that are commonly used in recent research, the effects of these methods upon biologic scaffold material are discussed. Also, we summarize the recent developments of recellularization and vascularization techniques in regeneration medicine. Additionally, dECM preservation methods is mentioned, which provides the basis for the establishment of organ bank.

Results

Biomedical applications and the status of current research developments relating to dECM biomaterials are outlined, including transplantation in vivo, disease models and drug screening, organoid, 3D bioprinting, tissue reconstruction and rehabilitation and cell transplantation and culture. Finally, critical challenges and future developing technologies are discussed.

Conclusions

With the development of tissue engineering and regenerative medicine, dECM will have broader applications in the field of biomedicine in the near future.
In silico design, chemical synthesis and biological screening of novel 4‐(1H)‐pyridone‐based antimalarial agents
Authors: Audu Oluwatosin , Stander Andre , Ajani Olayinka , Egieyeh Samuel , October Natasha
Published: December 2021

Identifying novel lead compounds in drug discovery has been challenging because of the rapid rise of drug resistance to the existing chemotherapeutics and a lack of understanding of complex metabolic pathways in the parasite. Integrating computational and experimental approaches has shown to be of great worth in identifying and developing novel promising pharmacophore hybrids. In this present research, a series of new 4‐(1H)‐pyridone‐derived antimalarial agents were designed based on recent reports and our preliminary findings through in silico studies. Two of the 4‐(1H)‐Pyridone derivatives showed potential to bind to the Q0 site of the cytochrome bc1 complex and disrupt the mitochondrial electron transport chain. These compounds, along with previously synthesized compounds, exhibited significant inhibitory activities against the malaria parasite. Presently, seven compounds were successfully synthesized, characterized and these novel compounds have shown promise as antimalarial agents.
Chronic sublethal pesticide exposure affects brood production, morphology and endosymbionts, but not immunity in the ant, Cardiocondyla obscurior
Authors: Leponiemi Matti , Schultner Eva , Dickel Franziska , Freitak Dalial
Published: December 2021

Insect diversity and biomass have been declining around the world. This might have severe consequences on the environment since insects provide many crucial ecosystem services. One major driver behind the decline is continuous pesticide use which also affects nontarget organisms. Even at low doses, chronic exposure to pesticides may have negative long‐term effects. Ants have not received much attention in this context, despite their importance in terrestrial ecosystems.

A full factorial experimental design was used to test how ingestion of two widely used pesticides influence colonies of the ant Cardiocondyla obscurior. Colonies were exposed for 12 weeks to the herbicide glyphosate and the neonicotinoid insecticide thiacloprid, separately and in combination. Brood production and the size of new workers and queens produced in these colonies were measured. In addition, the relative densities of two endosymbionts were quantified and immunocompetence tested by measuring survival after fungal infection.

The two pesticides in combination decreased brood production, which was measured as the number of produced eggs and pupae. Workers and queens produced in pesticide‐exposed colonies differed in body size from individuals produced in control colonies. Furthermore, endosymbiont densities decreased after glyphosate exposure. Neither pesticide influenced survival after fungal infection.

The results show that chronic exposure to two widely used pesticides causes apparent trade‐offs in reproduction and other physiological traits of ants, potentially decreasing fitness. Even low levels of pesticides in the environment may therefore have negative effects on ant colonies, contributing to the worldwide insect decline.
Combining Process Information and Item Response Modeling to Estimate Problem‐Solving Ability
Authors: Xiao Yue , Veldkamp Bernard , Liu Hongyun
Published: December 2021

The action sequences of respondents in problem‐solving tasks reflect rich and detailed information about their performance, including differences in problem‐solving ability, even if item scores are equal. It is therefore not sufficient to infer individual problem‐solving skills based solely on item scores. This study is a preliminary attempt to incorporate process data analysis into the measurement of problem‐solving ability. The entire procedure consists of using information from process data as prior information for the estimation of problem‐solving proficiency in an item response model. The purpose of this study is twofold: (1) to investigate the impact of adding process information on the estimation of latent ability; (2) to examine the extent to which the ability estimates obtained from the combination model can reflect the information of the problem‐solving process. Seven problem‐solving items from the Programme for International Assessment of Adult Competencies were used. Results indicate that the inclusion of process priors enhances the correlation between proficiency estimates and process information related to the problem‐solving strategies adopted by respondents, as well as to their solution efficiency. The inclusion of process priors further reveals differences in the problem‐solving performance of respondents exhibiting the same score pattern and increases precision of latent ability estimation.
Energy‐efficient routing paradigm for resource‐constrained Internet of Things‐based cognitive smart city
Authors: Verma Sandeep
Published: December 2021

The exponential growth in the smart cities and the massive deployment of wireless sensor network‐based Internet of Things (IoT) has resulted in generating the humongous data, which needs to be orchestrated. Further, it is observed that the resource‐constrained IoT devices act as stumbling block in the successful realization of cognitive smart cities. Hence, there is a high need to manage the data transmission from massive IoT devices and also to enhance the productivity of such devices. To address this issue, in this article, we present energy‐efficient routing paradigm for resource‐constrained IoT‐based cognitive smart city (EI‐CSC). We adapt Sooty tern optimization algorithm (STOA) due to its faster convergence and high ‘exploration and exploitation’ capabilities to perform energy efficient cluster‐based routing. We focus primarily on rendering the optimized solution to the cluster head selection problem through STOA. The outcomes of simulation analysis of EI‐CSC promises enhanced performance in the context of stability period and network lifetime by 83.4% and 107.7%, ‘respectively’ as compared to recently proposed ‘genetic algorithm and PSO based hybrid clustering algorithm’.
Recognition of potential therapeutic role of 2‐hydroxy‐3‐methylanthraquinones in the treatment of gallbladder carcinoma: A proteomics analysis
Authors: Jin Hao , Cui Min
Published: December 2021

Gallbladder carcinoma (GBC), with early metastasis and high recurrence rates, is an enormous threat to health. As an anthraquinones monomer of traditional Chinese medicineHedyotis diffusa, 2‐hydroxy‐3‐methylanthraquinone (HMA) has been reported to inhibit the growth of several cancers. But in our preliminary study, HMA could only weakly induce GBC cell apoptosis. To explore other possible mechanism underlying the inhibition effect of HMA on GBC, this proteomics analysis was performed. A proteomics analysis was performed on one GBC cell line bought from the China Life Science Cell Bank. Several computational techniques were merged to develop analysis for those differently expressed proteins. A comparative protein–protein interaction network analysis was carried out among the differently expressed proteins to identify the proteins potentially inhibiting GBC. Thus, a GO and KEGG analysis was performed to identify the signaling pathways underlying a potential therapeutic role for HMA. A total of 285 proteins were affected by HMA, including 187 upregulated and 98 downregulated. The subcellular localization of differently expressed proteins were identified, including 142 in nuclear, 67 in cytoplasm, 67 in extracellular matrix, 46 in plasma membrane, 13 in mitochondrion, 3 in lysosome, and 1 in cytoskeleton. HMA could regulate EGFR, FN1, PLG, PLAUR, LAMA3, HRG, THBS1, PLAT, KNG1, ENAM, SERPINE1, ECM1, interleukin‐8, and trypsin in GBC. Most of the regulated proteins involve in cell migration. Pathways including PI3K–Akt, Wnt, HIF‐1, focal adhesion, microRNAs were regulated by HMA. HMA was shown to be an inhibition agent for GBC development, and this analysis would contribute to the development of new anti‐GBC drugs.
Literature searching methods or guidance and their application to public health topics: A narrative review
Authors: Heath Andrea , Levay Paul , Tuvey Daniel
Published: December 2021

Background

Information specialists conducting searches for systematic reviews need to consider key questions around which and how many sources to search. This is particularly important for public health topics where evidence may be found in diverse sources.

Objectives

The objective of this review is to give an overview of recent studies on information retrieval guidance and methods that could be applied to public health evidence and used to guide future searches.

Methods

A literature search was performed in core databases and supplemented by browsing health information journals and citation searching. Results were sifted and reviewed.

Results

Seventy‐two papers were found and grouped into themes covering sources and search techniques. Public health topics were poorly covered in this literature.

Discussion

Many researchers follow the recommendations to search multiple databases. The review topic influences decisions about sources. Additional sources covering grey literature eliminate bias but are time‐consuming and difficult to search systematically. Public health searching is complex, often requiring searches in multidisciplinary sources and using additional methods.

Conclusions

Search planning is advisable to enable decisions about which and how many sources to search. This could improve with more work on modelling search scenarios, particularly in public health topics, to examine where publications were found and guide future research.
Purification and identification of novel antibacterial peptides isolated from Tualang honey
Authors: Aween Mohamed Mustafa , Hassan Zaiton , Muhialdin Belal J.
Published: December 2021

This study aimed to determine the role of bioactive peptides in the antibacterial activity of honey. The peptides were extracted, and the concentration was determined. The peptides were fractionated and evaluated for their antibacterial activity towards selected bacteria. The results showed high peptide content in Tualang honey 1.01 mg g−1. A total of seven essential amino acids were present in Tualang honey. The peptide mixture extracted from Tualang honey showed high antibacterial activity towards Staphylococcus aureus, Salmonella enterica serovar Typhimurium, Escherichia coli and Pseudomonas aeruginosa. A total of 33 peptides were identified in the fractions 9 and 10 obtained from RP‐HPLC. The identified peptides belonged to different sources including novel peptides that have no match to the protein database. The results of this first study revealed the role of the peptides generated by honeybees, nectar and pollen, and novel peptides of the natural microflora in the antibacterial activity of honey.
Low clinical utility of testing for anti‐platelet factor 4 in asymptomatic individuals after ChAdOx1 nCoV‐19 vaccine
Authors: Barefah Ahmed S. , Radhwi Osman O. , Alamri Sawsan S. , Alahwal Hatem M. , Denetiu Iuliana , Almohammadi Abdullah T. , Bahashwan Salem M. , Qari Mohamad H. , Algaissi Abdullah , Alamer Edrous , Alhazmi Abdulaziz , Abuzenadah Adel M. , Nasraldeen Walleed H. , Alzahrani Sami H. , Hashem Anwar M.
Published: December 2021

Introduction

The development of anti‐platelet factor 4 (PF4) antibodies is linked to a rare thrombotic complication described now as vaccine‐induced immune thrombotic thrombocytopenia (VITT). This clinical syndrome with thrombosis and thrombocytopenia was reported after exposure to the Oxford‐AstraZeneca COVID‐19 vaccine, ChAdOx1 nCoV‐19 vaccine (AZD1222), and Ad26.COV2.S vaccine (Janssen/Johnson & Johnson). In the absence of the clinical features, the incidence of positive anti‐PF4 antibodies in asymptomatic individuals post‐vaccination is unclear.

Methods

The aim of this study was to evaluate the development of anti‐PF4 antibodies in asymptomatic individuals 14–21 days after receiving the first dose of ChAdOx1 nCoV‐19 vaccine (AZD1222) and BNT162b2 vaccine. Prospectively, we collected serum from individuals before and after ChAdOx1 nCoV‐19 vaccine and BNT162b2 vaccine and measured anti‐PF4 antibodies using the Asserachrom HPIA IgG ELISA (Stago, Asnieres, France).

Results

We detected positive anti‐PF4 antibodies in 5 of 94 asymptomatic individuals post‐vaccine with a rate of 5.3% with low titers (OD 0.3–0.7). Four of 5 individuals who tested positive after the vaccine had also positive anti‐PF4 antibodies before the vaccine, which indicates that a majority of the positive results are due to preexisting anti‐PF4 antibodies. We did not find a relation between the development of anti‐PF4 antibodies and the immune response to the vaccine, status of prior COVID‐19 infection, and baseline characteristics of participants. None of the participants developed thrombosis nor thrombocytopenia.

Conclusion

Our results provide new evidence to guide the diagnostic algorithm of suspected cases of VITT. In the absence of thrombosis and thrombocytopenia, there is a low utility of testing for anti‐PF4 antibodies.
Negative aging perceptions and cognitive and functional decline: Are you as old as you feel?
Authors: McGarrigle Christine A. , Ward Mark , Kenny Rose Anne
Published: December 2021

Background

Research has shown the associations between negative aging perceptions and cognitive and physical decline may be mediated through behavioral and psychological pathways, but they are rarely examined simultaneously. We aimed at assessing the difference in the probability of following a high‐, mid‐, or low‐performing cognitive trajectory, and a high‐ or low‐performing physical function trajectory by negative aging perceptions. We sought to test two competing pathway mechanisms for the associations.

Methods

This longitudinal study used data from the Irish Longitudinal Study on Ageing (TILDA), a nationally representative study of community‐dwelling adults in Ireland. Adults aged ≥50 years who participated in two or more waves of TILDA (n = 6121) were included. An analysis of the population aged 65 years and above was also conducted (n = 2359). We identified latent class trajectories of Mini‐Mental State Examination (MMSE), Instrumental Activities of Daily Living (IADL), ADL, and Timed‐Up‐and‐Go (TUG) performance using Latent Growth Class Analysis (LGCA) on data collected every 2 years over 5 waves. Multinomial logistic regression was used to estimate the likelihood of membership to each trajectory class by negative aging perceptions (APQ). Finally, we tested possible behavioral, psychological, and social mechanisms.

Results

LCGA identified three trajectory classes in cognitive and two in each physical function measure. People with the highest tertile of negative APQ were more likely to be in the declining MMSE class and the increasing IADL, ADL, and TUG classes. These associations for cognitive function were partially mediated by psychosocial pathways and for physical function were fully mediated by both psychosocial and health behavior pathways.

Conclusions

Negative aging perceptions were associated with cognitive and physical function declines. Poor self‐rated health, depressive symptoms, loneliness, and low exercise seem to explain the relationships; however, the possibility of reverse causation remains.
Caring for patients with eating deficiencies in palliative care—Registered nurses’ experiences: A qualitative study
Authors: Wallin Viktoria , Mattsson Elisabet , Omerov Pernilla , Klarare Anna
Published: December 2021

Aims and Objectives

The aim was to explore RNs’ experiences of caring for patients with eating deficiencies in palliative care.

Background

Food and mealtimes are fundamental aspects for wellbeing and social interactions. The worldwide trajectory of ageing populations may result in increased need for palliative care. Everyday life with chronic life limiting illness and eating deficiencies is challenging for patients and families. RNs are key care providers at end‐of‐life.

Design

A qualitative study with an inductive approach was used.

Methods

Nineteen experienced RNs in palliative care were interviewed through telephone; interviews were audio recorded and transcribed verbatim. Inductive qualitative content analysis was performed, and the COREQ checklist was used to guide proceedings.

Results

The overarching theme, Supporting persons with eating deficiencies in‐between palliative care and end‐of‐life care, is represented by three sub‐themes: Easy to stick with doing, Just being, without doing, is hard and Letting go. Near end‐of‐life, eating symbolized social belonging and quality of life for RNs, whereas for patients and families, eating symbolized life. RNs tried practical solutions, however, not always according to patients’ and families’ preferences.

Conclusions

RNs were well prepared to tackle physical inconveniences and provide support, however, less prepared to encounter existential, psychological and social issues in relation to eating deficiencies. Although RNs stated that human beings stop eating when they are about to die, letting nature run its’ course and facilitating patients’ transition to end‐of‐life care was challenging.

Relevance to clinical practice

Food and mealtimes represent fundamental aspects of human life and denote central parts in RNs clinical practice in palliative care. The findings can inspire development of a comprehensive palliative care approach to support patients and families. Structured reflection in relation to clinical practice may support and encourage RNs, caring for patients with eating deficiencies, in mastering both doing and being.
Canopy damage during a natural drought depends on species identity, physiology and stand composition
Authors: Britton Travis G. , Brodribb Timothy J. , Richards Shane A. , Ridley Chantelle , Hovenden Mark J.
Published: December 2021

Vulnerability to xylem cavitation is a strong predictor of drought‐induced damage in forest communities. However, biotic features of the community itself can influence water availability at the individual tree‐level, thereby modifying patterns of drought damage.

Using an experimental forest in Tasmania, Australia, we determined the vulnerability to cavitation (leaf P50) of four tree species and assessed the drought‐induced canopy damage of 2944 6‐yr‐old trees after an extreme natural drought episode. We examined how individual damage was related to their size and the density and species identity of neighbouring trees.

The two co‐occurring dominant tree species, Eucalyptus delegatensis and Eucalyptus regnans, were the most vulnerable to drought‐induced xylem cavitation and both species suffered significantly greater damage than neighbouring, subdominant species Pomaderris apetala and Acacia dealbata. While the two eucalypts had similar leaf P50 values, E. delegatensis suffered significantly greater damage, which was strongly related to the density of neighbouring P. apetala. Damage in E. regnans was less impacted by neighbouring plants and smaller trees of both eucalypts sustained significantly more damage than larger trees.

Our findings demonstrate that natural drought damage is influenced by individual plant physiology as well as the composition, physiology and density of the surrounding stand.
Leadless pacemaker implant guided by intracardiac echocardiography in a patient after Mustard repair
Authors: Kautzner Josef , Wunschova Hanka , Haskova Jana
Published: December 2021

This case report describes a successful leadless pacemaker implant (Micra VR Medtronic, Inc, Minneapolis, MN) in a 48‐year‐old patient with a history of Mustard repair. Twenty‐one years after dual‐chamber pacemaker implant, both conventional leads became dysfunctional. Lead extraction was refused by the patient and the subclavian vein was obstructed. A leadless pacemaker was selected as an alternative. Intracardiac echocardiography allowed the safe introduction of the delivery system into the nonsystemic left ventricle. Four months after implant, the pacing parameters are stable and the patient is without new complaints. A leadless pacemaker could be considered in patients with complex grown‐up congenital heart disease (GUCH).
COVID‐19 implications for pediatric anesthesia: Lessons learnt and how to prepare for the next pandemic
Authors: Afshari Arash , Disma Nicola , von Ungern‐Sternberg Britta S. , Matava Clyde
Published: December 2021

COVID‐19 is mainly considered an “adult pandemic,” but it also has strong implications for children and consequently for pediatric anesthesia. Despite the lethality of SARS‐CoV‐2 infection being directly correlated with age, children have equally experienced the negative impacts of this pandemic. In fact, the spectrum of COVID‐19 symptoms among children ranges from very mild to those resembling adults, but may also present as a multisystemic inflammatory syndrome. Moreover, the vast majority of children might be affected by asymptomatic or pauci‐symptomatic infection making them the “perfect” carriers for spreading the disease in the community. Beyond the clinical manifestations of SARS‐CoV‐2 infection, the COVID‐19 pandemic may ultimately have catastrophic health and socioeconomic consequences for children and adolescents, which are yet to be defined. The aim of this narrative review is to highlight how COVID‐19 pandemic has affected and changed the pediatric anesthesia practice and which lessons are to be learned in case of a future “pandemic.” In particular, the rapid evolution and dissemination of research and clinical findings have forced the scientific community to adapt and alter clinical practice on an unseen and pragmatic manner. Equally, implementation of new platforms, techniques, and devices together with artificial intelligence and large‐scale collaborative efforts may present a giant step for mankind. The valuable lessons of this pandemic will ultimately translate into new treatments modalities for various diseases but will also have the potential for safety improvement and better quality of care. However, this pandemic has revealed the vulnerability and deficiencies of our health‐care system. If not addressed properly, we may end up with a tsunami of burnout and compassionate fatigue among health‐care professionals. Pediatric anesthesia and critical care staff are no exceptions.
Sense perception in theZhuangzi莊子
Authors: Lacertosa Massimiliano
Published: December 2021

In this essay I explore the controversial issue of sense perception in theZhuangzi莊子. Although scholars have not explicitly addressed this aspect of the Chinese text, a common assumption is that theZhuangziproposes a mysticism that undermines sense perception in favour of a transcendent self. After an overview of this interpretation, and after analysing some key passages of the text that deal with heart fasting (xinzhai心齋), sitting and forgetting (zuowang坐忘) and skill mastery, I demonstrate that some interpreters of theZhuangziread the text as if it has a metaphysical bent, recommending that sense perception be transcended as a prerequisite to perfection. In contrast, my thesis is that the text does not propose a withdrawal from the senses and from the world, but rather warns about the danger of abiding to doctrinal knowledge, which has the consequence of a person losing their responsive awareness. Indeed, in theZhuangzi, sense perception is not an impediment on the way to a supersensible reality, but an integral part of one's own being in the world. Through my analysis, I object to the idea that theZhuangziproposes a mystical union with something not immediately available, which moreover needs to be achieved by transcending the lived world that is encountered through sense perception. My view is that such a move not only postulates union with a transcendent entity, it also forces a dualism between a person's capacities. This is problematic because theZhuangzidoes not point to another world–in a two worlds theory–where one must ideally attain the condition of a transcendent self. On the contrary, in rejecting a univocalethos, the text suggests one should keep responding to changing circumstances without turning one's perceptual awareness into entrenched habits. Thus, theZhuangzishows how sense perception should be seen, not as a “problem” but as an ethical possibility through which the univocity of doctrinal knowledge can be undermined.
Many‐objective land use planning using a hypercube‐based NSGA‐III algorithm
Authors: Maleki Jamshid , Masoumi Zohreh , Hakimpour Farshad , Coello Coello Carlos A.
Published: December 2021

Due to the many objectives and constraints involved in urban land use planning (ULUP), this is considered as a many‐objective and complex optimization problem that needs a variety of geographical analyses. In this article, the main target is improving NSGA‐III as an advanced many‐objective optimization algorithm for solving the ULUP problem. In this study, five objective functions (i.e., consistency, dependency, compactness, suitability, and per capita violation of land uses) are considered for their simultaneous optimization for allocation. The proposed algorithm is tested using the spatial data of region 7, district 1 of Tehran using a vector format. To evaluate the results, two more real datasets were implemented. The performance of the improved algorithm is compared concerning NSGA‐II and NSGA‐III in the main case study area and two other instances. The comparison results show that the improved algorithm increases the convergence and diversity of the generated solutions in ULUP concerning the results obtained by these two other algorithms. The results of the optimization with these methods can help decision‐makers toward sustainable development in the construction of new cities, new towns, and smart cities.
Calculation of reflection and transmission coefficients for waves in multilayered piezoelectric structures using the mixed variable method
Authors: Zhang Yanhui , Gao Qiang
Published: December 2021

The reflection and transmission (R/T) behavior of elastic waves in an anisotropic multilayered piezoelectric structure bounded by two homogeneous half-spaces is studied using the mixed variable method. The mixed variable method, which is based on the mixed energy matrix, takes the displacement vector at one end of the structure and the stress vector at other end of the structure as the basic variables. The wave equation for a homogeneous piezoelectric layer is transformed into a first-order state equation in the Hamiltonian system by introducing a dual vector. The general solution of the state equation can be expressed in terms of the eigenvalues and eigenvectors of the complex Hamiltonian matrix. A mixed energy matrix is applied to establish the relationship between the generalized displacement and stress vectors on the upper and lower interfaces of a layer. By an efficient recursive algorithm, the global mixed energy matrix is formed for an arbitrarily anisotropic multilayered piezoelectric structure. The R/T coefficients of the waves in an anisotropic multilayered piezoelectric structure are derived by the global mixed energy matrix. Numerical examples are provided to show the robustness of the mixed variable method. The effects of the incident angles, wavenumbers, and critical angles on the R/T coefficients are discussed.
Energy Cost of Running in Well-Trained Athletes: Toward Slope-Dependent Factors
Authors: Lemire Marcel , Remetter Romain , Hureau Thomas J. , Geny Bernard , Lonsdorfer Evelyne , Favret Fabrice , Dufour Stéphane P.
Published: December 2021

Purpose: This study aimed to determine the contribution of metabolic, cardiopulmonary, neuromuscular, and biomechanical factors to the energy cost (ECR) of graded running in well-trained runners. Methods: Eight men who were well-trained trail runners (age: 29 [10] y, mean [SD]; maximum oxygen consumption: 68.0 [6.4] mL·min−1·kg−1) completed maximal isometric evaluations of lower limb extensor muscles and 3 randomized trials on a treadmill to determine their metabolic and cardiovascular responses and running gait kinematics during downhill (DR: −15% slope), level (0%), and uphill running (UR: 15%) performed at similar O2 uptake (approximately 60% maximum oxygen consumption). Results: Despite similar O2 demand, ECR was lower in DR versus level running versus UR (2.5 [0.2] vs 3.6 [0.2] vs 7.9 [0.5] J·kg−1·m−1, respectively; all P < .001). Energy cost of running was correlated between DR and level running conditions only (r2 = .63; P = .018). Importantly, while ECR was correlated with heart rate, cardiac output, and arteriovenous O2 difference in UR (all r2 > .50; P < .05), ECR was correlated with lower limb vertical stiffness, ground contact time, stride length, and step frequency in DR (all r2 > .58; P < .05). Lower limb isometric extension torques were not related to ECR whatever the slope. Conclusion: The determining physiological factors of ECR might be slope specific, mainly metabolic and cardiovascular in UR versus mainly neuromuscular and mechanical in DR. This possible slope specificity of ECR during incline running opens the way for the implementation of differentiated physiological evaluations and training strategies to optimize performance in well-trained trail runners.
De novo macrocyclic peptides for inhibiting, stabilizing, and probing the function of the retromer endosomal trafficking complex
Authors: Chen Kai-En , Guo Qian , Hill Timothy A. , Cui Yi , Kendall Amy K. , Yang Zhe , Hall Ryan J. , Healy Michael D. , Sacharz Joanna , Norwood Suzanne J. , Fonseka Sachini , Xie Boyang , Reid Robert C. , Leneva Natalya , Parton Robert G. , Ghai Rajesh , Stroud David A. , Fairlie David P. , Suga Hiroaki , Jackson Lauren P. , Teasdale Rohan D. , Passioura Toby , Collins Brett M.
Published: December 2021

Novel macrocyclic peptides are found that bind and modulate the function of the retromer membrane trafficking complex.
Observing 0D subwavelength-localized modes at ~100 THz protected by weak topology
Authors: Lu Jinlong , Wirth Konstantin G. , Gao Wenlong , Heßler Andreas , Sain Basudeb , Taubner Thomas , Zentgraf Thomas
Published: December 2021

Strongly confined zero-dimensional localization with weak topological design is verified by near-field optical microscopy.
Repeated
Plasmodium falciparum
infection in humans drives the clonal expansion of an adaptive γδ T cell repertoire
Authors: von Borstel Anouk , Chevour Priyanka , Arsovski Daniel , Krol Jelte M. M. , Howson Lauren J. , Berry Andrea A. , Day Cheryl L. , Ogongo Paul , Ernst Joel D. , Nomicos Effie Y. H. , Boddey Justin A. , Giles Edward M. , Rossjohn Jamie , Traore Boubacar , Lyke Kirsten E. , Williamson Kim C. , Crompton Peter D. , Davey Martin S.
Published: December 2021

Malaria drives the adaptive differentiation of the human γδ T cell repertoire.
Discovery of an Antarctic Ascidian-Associated Uncultivated
Verrucomicrobia
with Antimelanoma Palmerolide Biosynthetic Potential
Authors: Murray Alison E. , Lo Chien-Chi , Daligault Hajnalka E. , Avalon Nicole E. , Read Robert W. , Davenport Karen W. , Higham Mary L. , Kunde Yuliya , Dichosa Armand E. K. , Baker Bill J. , Chain Patrick S. G.
Published: December 2021

Palmerolide A has potential as a chemotherapeutic agent to target melanoma. We interrogated the microbiome of the Antarctic ascidian,
Synoicum adareanum
, using a cultivation-independent high-throughput sequencing and bioinformatic strategy.
Lessons Learned from Implementation of an Interferon Gamma Release Assay to Screen for Latent Tuberculosis Infection in a Large Multicenter Observational Cohort Study in Brazil
Authors: Costa Allyson G. , Carvalho Brenda K. S. , Araújo-Pereira Mariana , Ibiapina Hiochelson N. S. , Spener-Gomes Renata , Souza Alexandra B. , Gomes-Silva Adriano , Andrade Alice M. S. , Silva Elisangela C. , Arriaga María B. , Benjamin Aline , Rocha Michael S. , Moreira Adriana S. R. , Oliveira Jamile G. , Figueiredo Marina C. , Turner Megan M. , Durovni Betina , Cavalcante Solange , Kritski Afranio L. , Rolla Valeria C. , Sterling Timothy R. , Andrade Bruno B. , Cordeiro-Santos Marcelo ,   RePORT-Brazil Consortium
Published: December 2021

The IGRA has emerged as a useful tool for identifying persons with LTBI. Although the implementation of IGRAs is of utmost importance, to our knowledge there is scarce information on the identification of logistical and technical challenges for systematic screening for LTBI on a large scale.
A Systematic Investigation Unveils High Coinfection Status of Porcine Parvovirus Types 1 through 7 in China from 2016 to 2020
Authors: Li Jixiang , Xiao Yanzhao , Qiu Ming , Li Xinshuai , Li Shubin , Lin Hong , Li Xiangdong , Zhu Jianzhong , Chen Nanhua
Published: December 2021

Porcine parvoviruses (PPVs) are prevalent in China associating with reproductive failure in swine. The coinfection of seven genotypes of PPVs (PPV1-7) might have synergistic effects on PPV1 associated SMEDI syndrome.
Differences in Fecal Microbiome and Antimicrobial Resistance between Captive and Free-Range Sika Deer under the Same Exposure of Antibiotic Anthelmintics
Authors: Wu Kangqi , Xu Yongtao , Zhang Weiwei , Mao Huirong , Chen Biao , Zheng Yunlin , Hu Xiaolong
Published: December 2021

We used a metagenomic approach to investigate whether and how captive and free-range impact the microbial communities and antimicrobial resistance in sika deer. The results provide solid evidence of the significant impacts on the microbial composition and function in captive and free-range sika deer. Interestingly, although the sika deer had the same exposure to antibiotic anthelmintics, the antimicrobial resistances were affected by the breeding environment.
Appearance and disappearance rates of Phanerozoic marine animal paleocommunities
Authors: Muscente A.D. , Martindale Rowan C. , Prabhu Anirudh , Ma Xiaogang , Fox Peter , Hazen Robert M. , Knoll Andrew H.
Published: December 2021

Ecological observations and paleontological data show that communities of organisms recur in space and time. Various observations suggest that communities largely disappear in extinction events and appear during radiations. This hypothesis, however, has not been tested on a large scale due to a lack of methods for analyzing fossil data, identifying communities, and quantifying their turnover. We demonstrate an approach for quantifying turnover of communities over the Phanerozoic Eon. Using network analysis of fossil occurrence data, we provide the first estimates of appearance and disappearance rates for marine animal paleocommunities in the 100 stages of the Phanerozoic record. Our analysis of 124,605 fossil collections (representing 25,749 living and extinct marine animal genera) shows that paleocommunity disappearance and appearance rates are generally highest in mass extinctions and recovery intervals, respectively, with rates three times greater than background levels. Although taxonomic change is, in general, a fair predictor of ecologic reorganization, the variance is high, and ecologic and taxonomic changes were episodically decoupled at times in the past. Extinction rate, therefore, is an imperfect proxy for ecologic change. The paleocommunity turnover rates suggest that efforts to assess the ecological consequences of the present-day biodiversity crisis should focus on the selectivity of extinctions and changes in the prevalence of biological interactions.
Post-traumatic temporal bone pneumatocele presenting after aggressive Valsalva
Authors: Seicshnaydre Jacob , Erbele Isaac , Hernandez Stephen , Arriaga Moisés
Published: December 2021

We report a case of a temporal bone pneumatocele with full-thickness erosion of the cranium associated with aggressive nose blowing. This condition presented 9 years after traumatic fracture of the temporal bone. There are 17 reported cases of mastoid sinus hyperpneumatisation in the literature. Eleven of the 17 are associated with Valsalva manoeuvres or elevated middle ear pressure. However, no other cases of full-thickness erosion at the site of a former fracture have been reported. We propose that the fracture, in combination with elevated mastoid sinus pressure from aggressive nose blowing, led to escape and trapping of pressurised air in the epidural and subcutaneous spaces, which resulted in bone erosion.
Failure of dual plating in a complex open distal femur fracture as the result of major trauma
Authors: Ward Thomas Robert William , Garala Kanai , Riemer Bryan
Published: December 2021

A 61-year-old polytrauma patient was admitted with a right distal comminuted metaphyseal femoral fracture with intra-articular extension (Orthopaedic Trauma Association 33C2.3 classification) among other injuries. Due to the high degree of comminution and massive bone loss, this was initially managed with a dual plating open reduction internal fixation. Dual plating has shown to be a superior fixation method than single variable angle locking compression plate (VA-LCP) plating providing greater fixation in metaphyseal bone. Our case reports the failure of dual plating which required removal of metalwork and subsequent fixation using intramedullary nail and plate technique. Failure of dual plating is not well documented in the literature. The most recent radiographs taken 15 months postrevision surgery show that the bone has started to heal with evidence of callus formation.
Para-aortic lymphadenopathy associated with adult COVID-19 multisystem inflammatory syndrome
Authors: Carvalho Victor , Damasco Paula H , Mello Thiago S , Gonçalves Bruno
Published: December 2021

A 21-year-old woman arrived at the emergency department with dyspnoea, arterial hypotension and abdominal pain after 5 days with a influenza-like syndrome. SARS-CoV-2 was detected by reverse transcription PCR in a nasopharyngeal swab specimen. CT of the chest and abdomen with contrast demonstrated a minimal amount of free intraperitoneal fluid, gallbladder with wall oedema, multiple para-aortic lymph node and interlobular septal thickening with ground glass opacities on the lungs. No pleural effusion or thromboembolism. Early broad-spectrum antibiotics, high-flow nasal cannula and norepinephrine were started. She was successfully treated with intravenous immunoglobulin and pulse corticosteroid therapy with methylprednisolone. The patient was discharged home with complete resolution of her symptoms and returned to her previous health status.
ARCADIA study protocol: a phase II, randomised, double-blind, placebo-controlled clinical trial to assess the safety and efficacy of AZD1656 in patients with diabetes hospitalised with suspected or confirmed COVID-19
Authors: McCafferty Kieran , Hollowood Zoe , Allan Michelle , Lockhart Donna , Chorlton Jamie , Martin John
Published: December 2021

Introduction

COVID-19, caused by SARS-CoV-2, remains a global pandemic that has affected more than 100 million people worldwide with over 4.8 million deaths as of October 2021. Patients with diabetes have both an increased susceptibility to SARS-CoV-2 infection, enhanced disease severity and increased risk of mortality. The challenge presented in these patients is both to improve glycaemic control—which itself may confer a survival advantage—and to help maintain or restore immunological homeostasis. The specific glucokinase activator AZD1656 may address both of these challenges via its glucose-lowering effect and its immunological mechanism of action. The aim of theAlleviation of cardioRespiratory complications in patients withCOVID-19AndDIAbetes (ARCADIA) trial is to investigate this hypothesis and determine whether AZD1656 can improve clinical outcomes for these patients.

Methods and analysis

ARCADIA is a double-blind, placebo-controlled, interventional study of AZD1656 in 150 patients with either type 1 or type 2 diabetes who have been admitted to hospital with COVID-19. Eligible, consented patients will be randomised in a 1:1 manner to receive either active drug or matched placebo tablets while they are in hospital. All patients will receive the usual and current standard of care for patients with COVID-19 in that hospital. Clinical and laboratory data will be collected and assessed at baseline and throughout their participation in the study. Data will be captured in the case report form, which will be electronically archived at the end of the trial in the trial master file. The WHO 8-point Ordinal Scale for Clinical Improvement will be used to measure clinical outcome for the primary endpoint of the trial.

Ethics and dissemination

Ethical approval has been obtained from the East Midlands-Leicester South Ethics Committee (REC 20/EM/0198) in the UK, from the National Bioethics Committee of Medicines and Medical Devices in Bucharest, Romania, and from the Ethics Committee IKEM a TN in Prague, Czech Republic. All study-related data will be used by the sponsor in accordance with local data protection law. In the UK, all patient identifiable data will be stored on a password-protected National Health Service N3 network with full audit trail. Anonymised data will be stored in an ISO27001 certificated data warehouse.

Trial registration number

EudraCT 2020-002211-21,NCT04516759.
Risk of infections and mortality in Danish patients with cancer diagnosed with bone metastases: a population-based cohort study
Authors: Hjelholt Thomas Johannesson , Rasmussen Thomas Bøjer , Seesaghur Anouchka , Hernandez Rohini K , Marongiu Andrea , Obel Niels , Sørensen Henrik Toft , Pedersen A B
Published: December 2021

Objectives

Risk of infections in patients with solid cancers and bone metastases (BM) and the subsequent impact on prognosis is unclear. We examined the risk of infections among patients with cancer diagnosed with BM and the subsequent impact of infections on mortality.

Design

Population-based cohort study.

Setting

Danish medical databases holding information on all hospital contacts in Denmark.

Participants

Adult patients with solid cancers and BM between 1 January 1994 and 30 November 2013.

Outcome measures

In the risk analyses, the outcome was time to hospitalisation for common severe infections, pneumonia, sepsis and urinary tract infections. In the mortality analysis, we used Cox regression to compute HRs of death, modelling infection as time-varying exposure, stratifying for primary cancer type and adjusting for age, sex and comorbidities.

Results

Among 23 336 patients with cancer and BM, cumulative incidences of common severe infections were 4.6%, 14.0% and 20.0% during 1 month, 1 year and 10 years follow-up. The highest incidence was observed for pneumonia, followed by urinary tract infections and sepsis. Infection was a strong predictor of 1 month mortality (adjusted HR: 2.1 (95% CI 1.8 to 2.3)) and HRs increased after 1 and 10 years: 2.4 (95% CI 2.3 to 2.6) and 2.4 (95% CI 2.4 to 2.6). Sepsis and pneumonia were the strongest predictors of death. Results were consistent across cancer types.

Conclusion

Patients with cancer and BM were at high risk of infections, which was associated with a more than twofold increased risk of death for up to 10 years of follow-up. The findings underscore the importance of preventing infections in patients with cancer and BM.
Odds of return: a prospective study using provider assessment to predict short-term patient return visits to the emergency department
Authors: Fruhan Scott , Bills Corey B
Published: December 2021

Objective

Previous studies have assessed patient-level characteristics associated with emergency department (ED) return visits, but none have used provider assessment. We prospectively investigate whether clinical providers could accurately predict ED return visits.

Methods

Prospective cohort study.

Setting

Single academically affiliated urban county hospital.

Participants

Discharged ED patients over a 14-month period with a provider assessment of the likelihood of patient return within 7 days of ED discharge.

Main outcome measures

The primary outcome of interest was a return visit to the ED within 7 days. Additional outcome measures included a return visit within 72 hours and a return visit resulting in admission. We also measured the accuracy of provider gestalt, and provide measures of sensitivity, specificity, predictive values, and likelihood ratios.

Results

Of the 11 922 ED discharges included in this study, providers expected 2116 (17.7%) to result in a return visit within 7 days. Providers were much more likely to perceive a return visit if the patient left against medical advice (OR: 5.97, 95% CI: 4.67 to 7.62), or was homeless (OR: 5.69, 95% CI: 5.14 to 6.29). Patients who actually returned were also more likely to be homeless, English speaking and to have left the ED against medical advice on the initial encounter. The strongest predictor of a return visit at both 72 hours and 7 days in multivariable modelling was provider assessment (OR: 3.77, 95% CI: 3.25 to 4.37; OR: 3.72, 95% CI: 3.29 to 4.21, respectively). Overall sensitivity and specificity of provider gestalt as a measure of patient return within 7 days were 47% and 87%, respectively. The positive and negative likelihood ratios were 3.51 and 0.61, respectively.

Conclusions

Clinician assessment was the strongest predictor of a return visit in this dataset. Clinician assessment may be used as a way to screen patients during the index visit and enrol them in efforts to decrease return visits.