bluuebunny/crossref_metadata_2025 huggingface dataset:
The 3-T Model of Informed Consent for Nonstandard Risk Donors: A Proposal for Transplant Clinical Practice
Authors: Grossi Alessandra Agnese , Nicoli Federico , De Feo Tullia Maria , Cardillo Massimo , Biffa Gabriella , Pegoraro Renzo , Petrini Carlo , Torelli Rosanna , Puoti Francesca , Rossini Giuseppe , Piccolo Giuseppe , Vesconi Sergio , Minetti Enrico , Pozzo Barbara , Vanacore Giuseppe , Paredes David , Grossi Paolo Antonio , Picozzi Mario
Published: October 2021

Background.

The risk of disease transmission from nonstandard risk donors (NSRDs) is low, and outcomes are similar or better relative to transplants performed with standard criteria donors. However, NSRDs have posed new ethical challenges to the informed consent (IC) process. Based on the shared decision-making model, coinciding with the 3 main timings of the IC process ([1] pretransplant assessments and waiting list registration, [2] time on the waiting list, and [3] time of the organ offer), we put forward a model (3-T Model) to summarize the knowledge on IC for NSRDs and to deliver conceptual and practical support to transplant providers on this emergent issue.

Methods.

We searched PubMed and analyzed data from our area to provide evidence and ethical arguments to promote standardization of the timing of patient information, degree of patient participation, and disclosure of donor risk factors throughout the 3 stages of the time continuum leading to the potential acceptance of NSRDs.

Results.

Each of the 3 timings carries special ethical significance and entails well-defined duties for transplant providers relative to patient involvement and information of the benefits and risks associated with NSRDs. Based on our framework, experience, and interpretation of the literature, we put forward a list of recommendations to combine standardization (ie, timing, content, and degree of patient participation) and individualization of IC.

Conclusions.

The 3-T Model may enable the prevention of physicians’ arbitrariness and the promotion of patient-centered care. Future studies will assess the effectiveness of the 3-T Model in transplant clinical practice.
Towards Optimum Reporting of Pulmonary Effectiveness Databases and Outcomes (TORPEDO): identifying a core dataset for asthma and COPD studies
Authors: van Boven Job FM , Lucas Sarah J , Parker Gary , Kaplan Alan , Trofor Antigona , Bonevski Billie , Kirenga Bruce J , Ryan Dermot , Pizzichini Emilio , van Ganse Eric , Huang Erick Wan-Chun , Brakema Evelyn , Gould Gillian , Kocks Janwillem , Alison Jennifer , Quint Jennifer K , Soriano Joan B , Hurst John , Siddiqi Kamran , Boydell Katherine , Miravitlles Marc , Flores-Valdez Mario Alberto , Kasteleyn Marise , FitzGerald Mark , Boeckmann Melanie , Chaiton Michael , Rodriguez Miguel Roman , Kulkarni Muralidhar , Roche Nicolas , Chavannes Niels , Papadopoulos Nikolaos G , Behrakis Panagiotis , Dennis Sarah , Bassi Shalini , Williams Siân , Maher Toby M , Siddharthan Trishul , Kamath Veena , Verhamme Katia MC
Published: October 2021

Purpose

There remains a need for a standardized dataset for respiratory studies to accelerate data collection, improve research efficiency and aid the sharing, merging and comparison of datasets. This TORPEDO (Towards Optimum Reporting of Pulmonary Effectiveness Databases and Outcomes) project aimed to develop a checklist of optimum and minimum variables for asthma and chronic obstructive pulmonary disease (COPD) research.

Methods

A 3-phase modified Delphi survey was conducted: in phase 1, an expert panel generated a list of variables, in phase 2 a Delphi panel selected the minimum variables (>66% agreement) for any design and in phase 3 they were asked to select a minimum set for specific study designs.

Results

In phase 1 the expert panel (n=22) proposed 224 variables. In phase 2, voting by 64 participants resulted in consensus (>66% agreement) for 18 variables and partial agreement (50-66%) for 44 variables, following this, 5 technical variables (e.g. date of test) were removed. In phase 3, 34 members of the Delphi panel completed voting; consensus was reached for 13 variables for retrospective asthma studies and 34 for prospective asthma studies. For COPD, there were 16 variables for retrospective studies and 37 for prospective studies. Gender, asthma/COPD exacerbations and patient-reported outcomes were the only variables with 100% agreement for both asthma and COPD studies.

Conclusion

The proposed list of minimally required variables will allow the assessment of current data sources for their utility in asthma and COPD studies, facilitate the merging of datasets, aid standardization of data collection and improve research efficiency.
Immunogenicity and reactogenicity of booster vaccinations after Ad26.COV2.S priming
Authors: Sablerolles R.S.G. , Rietdijk W.J.R. , Goorhuis A. , Postma D.F. , Visser L.G. , Geers D. , Schmitz K.S. , Garrido H.M. Garcia , Koopmans M.P.G. , Dalm V.A.S.H. , Kootstra N.A. , Huckriede A.L.W. , Lafeber M. , van Baarle D. , GeurtsvanKessel C.H. , de Vries R.D. , van der Kuy P.H.M.
Published: October 2021

Background

In face of the developing COVID-19 pandemic with a need for rapid and practical vaccination strategies, Ad26.COV2.S was approved as single shot immunization regimen. While effective against severe COVID-19, Ad26.COV2.S vaccination induces lower SARS-CoV-2-specific antibody levels compared to its mRNA-based counterparts. To support decision making on the need for booster vaccinations in Ad26.COV2.S-primed individuals, we assessed the immunogenicity and reactogenicity of homologous and heterologous booster vaccinations in Ad26.COV2.S-primed health care workers (HCWs).

Methods

The SWITCH trial is a single-(participant)-blinded, multi-center, randomized controlled trial among 434 HCWs who received a single Ad26.COV2.S vaccination. HCWs were randomized to no boost, Ad26.COV2.S boost, mRNA-1273 boost, or BNT162b2 boost. We assessed the level of SARS-CoV-2-specific binding antibodies, neutralizing antibodies against infectious virus, SARS-CoV-2-specific T-cell responses, and reactogenicity.

Results

Homologous and heterologous booster vaccinations resulted in an increase in SARS-CoV-2-specific binding antibodies, neutralizing antibodies and T-cell responses when compared to single Ad26.COV.2.S vaccination. In comparison with the homologous boost, the increase was significantly larger in heterologous regimens with the mRNA-based vaccines. mRNA-1273 boosting was most immunogenic, associated with higher reactogenicity. Only mild to moderate local and systemic reactions were observed on the first two days following booster.

Conclusions

Boosting of Ad26.COV2.S-primed HCWs was well-tolerated and immunogenic. Strongest responses were detected after boosting with mRNA-based vaccines. Based on our data, efficacy on infection and transmission of boosters is expected. In addition to efficacy, decision making on boost vaccinations should include timing, target population, level of SARS CoV-2 circulation, and the global inequity in vaccine access.

Trial registration

Funded by ZonMW (10430072110001);ClinicalTrials.govnumber,NCT04927936.
Who has long-COVID? A big data approach
Authors: Pfaff Emily R. , Girvin Andrew T , Bennett Tellen D. , Bhatia Abhishek , Brooks Ian M. , Deer Rachel R , Dekermanjian Jonathan P , Jolley Sarah Elizabeth , Kahn Michael G. , Kostka Kristin , McMurry Julie A , Moffitt Richard , Walden Anita , Chute Christopher G , Haendel Melissa A
Published: October 2021

Background

Post-acute sequelae of SARS-CoV-2 infection (PASC), otherwise known as long-COVID, have severely impacted recovery from the pandemic for patients and society alike. This new disease is characterized by evolving, heterogeneous symptoms, making it challenging to derive an unambiguous long-COVID definition. Electronic health record (EHR) studies are a critical element of the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative, which is addressing the urgent need to understand PASC, accurately identify who has PASC, and identify treatments.

Methods

Using the National COVID Cohort Collaborative’s (N3C) EHR repository, we developed XGBoost machine learning (ML) models to identify potential long-COVID patients. We examined demographics, healthcare utilization, diagnoses, and medications for 97,995 adult COVID-19 patients. We used these features and 597 long-COVID clinic patients to train three ML models to identify potential long-COVID patients among (1) all COVID-19 patients, (2) patients hospitalized with COVID-19, and (3) patients who had COVID-19 but were not hospitalized.

Findings

Our models identified potential long-COVID patients with high accuracy, achieving areas under the receiver operator characteristic curve of 0.91 (all patients), 0.90 (hospitalized); and 0.85 (non-hospitalized). Important features include rate of healthcare utilization, patient age, dyspnea, and other diagnosis and medication information available within the EHR. Applying the “all patients” model to the larger N3C cohort identified 100,263 potential long-COVID patients.

Interpretation

Patients flagged by our models can be interpreted as “patients likely to be referred to or seek care at a long-COVID specialty clinic,” an essential proxy for long-COVID diagnosis in the current absence of a definition. We also achieve the urgent goal of identifying potential long-COVID patients for clinical trials. As more data sources are identified, the models can be retrained and tuned based on study needs.

Funding

This study was funded by NCATS and NIH through the RECOVER Initiative.
Use and impact of virtual primary care on quality and safety: the public’s perspectives during the COVID-19 pandemic
Authors: Neves Ana Luisa , van Dael Jackie , O’Brien Niki , Flott Kelsey , Ghafur Saira , Darzi Ara , Mayer Erik
Published: October 2021

Background

With the onset of COVID-19, primary care has swiftly transitioned from face-to-face to virtual care, yet it remains largely unknown how this has impacted on the quality and safety of care.

Aim

To evaluate patient use of virtual primary care models during COVID-19 in terms of change in uptake, perceived impact on the quality and safety of care, and willingness of future use.

Design and setting

An online cross-sectional survey was administered to the public across the United Kingdom, Sweden, Italy and Germany.

Methods

McNemar tests were conducted to test pre- and post pandemic differences in uptake for each technology. One-way analysis of variance was conducted to examine patient experience ratings and perceived impacts on healthcare quality and safety across demographic characteristics.

Results

Respondents (N=6,326) reported an increased use of telephone consultations (+6.3%, P<.001), patient-initiated services (+1.5%, n=98, p<0.001), video consultations (+1.4%, P<.001), remote triage (+1.3, p<0.001), and secure messaging systems (+0.9%, P=.019). Experience rates using virtual care technologies were higher for men (2.39±0.96 vs 2.29±0.92, P<.001), those with higher literacy (2.75±1.02 vs 2.29±0.92, P<.001), and participants from Germany (2.54±0.91, P<.001). Healthcare timeliness and efficiency were the quality dimensions most often reported as being positively impacted by virtual technologies (60.2%, n=2,793 and 55.7%, n=2,401, respectively), followed by effectiveness (46.5%, n=1,802), safety (45.5%, n=1,822), patient-centredness (45.2%, n=45.2) and equity (42.9%, n=1,726). Interest in future use was highest for telephone consultations (55.9%), followed by patient-initiated digital services (56.1%), secure messaging systems (43.4%), online triage (35.1%), video consultations (37.0%), and chat consultations (30.1%), although significant variation was observed between countries and patient characteristics.

Conclusion

Future work must examine the drivers and determinants of positive experiences using remote care to co-create a supportive environment that ensures equitable adoption and use across different patient groups. Comparative analysis between countries and health systems offers the opportunity for policymakers to learn from best practices internationally.
PyDesigner: A Pythonic Implementation of the DESIGNER Pipeline for Diffusion Tensor and Diffusional Kurtosis Imaging
Authors: Dhiman Siddhartha , Teves Joshua B , Thorn Kathryn E , McKinnon Emilie T , Moss Hunter G , Adisetiyo Vitria , Ades-Aron Benjamin , Veraart Jelle , Chen Jenny , Fieremans Els , Benitez Andreana , Helpern Joseph A , Jensen Jens H
Published: October 2021

PyDesigner is an open-source and containerized Python software package, adapted from the DESIGNER pipeline, for diffusion weighted magnetic resonance imaging preprocessing and tensor estimation. PyDesigner combines tools from FSL and MRtrix3 to reduce the effects of signal noise and imaging artifacts on multiple diffusion measures that can be derived from the diffusion and kurtosis tensors. This publication describes the main features of PyDesigner and highlights its ease of use across platforms, while examining its accuracy and robustness in deriving commonly used diffusion and kurtosis metrics.
Severe fever with thrombocytopenia syndrome virus and parthenogenetic Asian longhorned tick Haemaphysalis longicornis (Acari: Ixodidae)
Authors: Zhang Xing , Zhao Chaoyue , Cheng Chaoyuan , Li Hongyue , Yu Tao , Lawrence Kevin , Sun Jimin , Yang Zeyu , Ye Ling , Chu Hongliang , Wang Ying , Han Xiaohu , Jia Yongchao , Fan Shuozhang , Kanuka Hirotaka , Tanaka Tetsuya , Jenkins Cheryl , Gedye Kristene , Chandra Shona , Price Dana C. , Liu Qiyong , Choi Young Ki , Zhan Xiangjiang , Zhang Guogang , Zhang Zhibin , Zheng Aihua
Published: October 2021

Severe fever with thrombocytopenia syndrome virus (SFTSV) is spreading rapidly in Asia. It is transmitted by Haemaphysalis longicornis (Asian longhorned tick, ALT), which has both parthenogenetically and sexually reproducing populations. Parthenogenetic populations were found in at least 15 provinces in China and strongly correlated with the distribution of SFTS. The distribution of SFTS cases was however poorly correlated with the distribution of populations of bisexual ALTs. Phylogeographic analysis suggested that the parthenogenetic population spread much faster than bisexual population because colonization is independent of sexual reproduction. A higher proportion of parthenogenetic ALTs were collected from migratory birds captured at an SFTS endemic area, implicating the contribution to the long-range movement of ALTs in China. The SFTSV susceptibility of parthenogenetic females was like that of bisexual females under laboratory conditions. These results suggest that parthenogenetic ALT, probably transported by migratory birds, play a major role in the rapid spread of SFTSV.

Article Summary Line

The parthenogenetic population of Asian longhorned tick is broadly distributed in China and plays a major role in the long-distance spread of SFTSV and perhaps future invasion of countries outside of Asia.
The basolateral amygdala to lateral septum circuit is critical for regulating sociability in mice
Authors: Rodriguez Lionel A. , Kim Sun-Hong , Page Stephanie C. , Nguyen Claudia V. , Pattie Elizabeth A. , Hallock Henry L. , Valerino Jessica , Maynard Kristen R. , Jaffe Andrew E. , Martinowich Keri
Published: October 2021

The lateral septum (LS) is a GABAergic region in the basal forebrain that is implicated in sociability. However, the neural circuits and cell signaling pathways that converge on the LS to mediate social behaviors aren’t well understood. Multiple lines of evidence suggest that brain-derived neurotrophic factor (BDNF) signaling through its receptor TrkB plays important roles in social behavior. While BDNF is not locally produced in LS, we demonstrate that nearly all GABAergic neurons in LS express TrkB. Local knock-down of TrkB expression from LS neurons decreased sociability and reduced recruitment of social novelty-induced neural activity. Since BDNF is not synthesized in LS, we evaluated which inputs to the LS could serve as potential BDNF sources for controlling sociability. By selectively ablating inputs to LS, we demonstrated that inputs from the basolateral amygdala (BLA), but not ventral CA1 (vCA1), regulate sociability. Moreover, depleting BDNF selectively in BLA-LS projection neurons phenocopied the decreased sociability observed following either local LS TrkB knockdown or ablation of BLA-LS inputs. These data support the hypothesis that BLA-LS projection neurons could serve as a critical source of BDNF for activating TrkB signaling in LS neurons to control sociability.
Commensal bacteria promote type I interferon signaling to maintain immune tolerance
Authors: Ayala Adriana Vasquez , Hsu Chia-Yun , Matsuo Kazuhiko , Buzun Ekaterina , Terrazas Marvic Carrillo , Loomis Luke R. , Lu Hsueh-Han , Park Jong Hwee , Rivaud Paul , Thomson Matt , Chu Hiutung
Published: October 2021

Type I interferons (IFN) exert a broad range of biological effects important in coordinating immune responses. Host and microbial factors regulate IFN production, triggering a signaling cascade that has classically been studied in the context of pathogen clearance. In particular, commensal bacteria have been shown to induce IFN to protect against viral infections. Yet, whether immunomodulatory bacteria operate through IFN pathways to support immune tolerance remains elusive. Here, we demonstrate microbiota-dependent IFN signaling is required for priming tolerogenic T regulatory cells (Tregs) by intestinal dendritic cells (DCs). DCs deficient in IFN signaling through deletion of IFNAR-1 display dysregulated cytokine production in response to the commensal bacteria Bacteroides fragilis, resulting in blunted downstream Treg responses. Single cell RNA sequencing of gut tissues demonstrated that colonization with B. fragilis promotes a distinct type I IFN gene signature in Tregs during homeostasis and intestinal inflammation. Moreover, B. fragilis-mediated protection during experimental colitis was abrogated in IFNAR1-deficient mice. Altogether, our findings demonstrate an important role of microbiota-mediated immune tolerance via tonic type I IFN signaling.
Automated and parallelized spike collision tests to identify spike signal projections
Authors: Mitani Keita , Kawabata Masanori , Isomura Yoshikazu , Sakai Yutaka
Published: October 2021

The spike collision test is a highly reliable technique to identify axonal projection of a neuron recorded electrophysiologically for investigating functional spike information among brain areas. It is potentially applicable to more neuronal projections by combining multi-channel recording with optogenetic stimulation. Yet, it remains inefficient and laborious because an experimenter must visually select spikes in every channel and manually repeat spike collision tests for each neuron serially. Here, we established a novel technique to automatically perform spike collision tests for all channels in parallel (Multi-Linc analysis), employing two distinct protocols implemented in a multi-channel real-time processing system. The rat cortical neurons identified with this technique displayed physiological spike features consistent with excitatory projection neurons. Their antidromic spikes were similar in shape but slightly larger in amplitude compared with spontaneous spikes. In addition, we demonstrated simultaneous identification of reciprocal or bifurcating projections among cortical areas. Thus, our Multi-Linc analysis will be a powerful research approach to elucidate interareal spike communication.
Proteomic analysis of mouse kidney tissue associates peroxisomal dysfunction with early diabetic kidney disease
Authors: Tserga Aggeliki , Pouloudi Despoina , Saulnier-Blache Jean Sébastien , Stroggilos Rafael , Theochari Irene , Gakiopoulou Harikleia , Mischak Harald , Zoidakis Jerome , Schanstra Joost Peter , Vlahou Antonia , Makridakis Manousos
Published: October 2021

Background

The absence of efficient inhibitors for DKD progression reflects the gaps in our understanding of DKD molecular pathogenesis. A comprehensive proteomic analysis was performed on glomeruli and kidney cortex of diabetic mice with subsequent validation of findings in human biopsies and - omics datasets aiming to better understand the underlying molecular biology of early DKD development and progression.

Methods

LC–MS/MS was employed to analyze the kidney proteome of DKD mouse models: Glomeruli of Ins2Akita mice 2 month and 4 month old, and cortex of db/db mice 6 month old. Following label-free quantification, the abundance of detected proteins were correlated with existing kidney datasets and functionally annotated. Tissue sections from 16 DKD patients were analyzed by IHC.

Results

Pathway analysis of differentially expressed proteins in the early and late DKD versus controls predicted dysregulation in DKD hallmarks (such as peroxisomal lipid metabolism, β-oxidation and TCA cycle) supporting the functional relevance of the findings. Comparing the observed protein changes in early and late DKD, consistent upregulation of 21 and downregulation of 18 proteins was detected. Among these were downregulated peroxisomal proteins such as NUDT19, ACOX1, and AMACR and upregulated mitochondrial proteins related to aminoacid metabolism including GLS, GLDC, and GCAT. Several of these changes were also observed in the kidney cortex proteome of db/db mice. IHC of human kidney further confirmed the differential expression of NUDT19, AGPS, AMACR and CAT proteins in DKD.

Conclusions

Our study shows an extensive differential expression of peroxisomal proteins in the early stages of DKD that persists regardless of the disease severity. These proteins therefore represent potential markers of early DKD pathogenesis. Collectively, essential pathways associated with peroxisomes such as lipid β-oxidation, plasmalogen synthesis, aminoacid metabolism and response to oxidative stress are downregulated in early DKD, providing new perspectives and potential markers of diabetic kidney dysfunction.
Colour Vision in Stomatopod Crustaceans: more questions than answers
Authors: Streets Amy , England Hayley , Marshall Justin
Published: October 2021

Stomatopod crustaceans, or mantis shrimps, are known for their extensive range of spectral sensitivities but relatively poor spectral discrimination. Instead of the colour-opponent mechanism of other colour vision systems, the 12 narrow-band colour channels they possess may underlie a different method of colour processing. We investigated one hypothesis, in which the photoreceptors are proposed to act as individual wave-band detectors, interpreting colour as a parallel pattern of photoreceptor activation, rather than a ratiometric comparison of individual signals. This different form of colour detection has been used to explain previous behavioural tests in which low saturation blue was not discriminated from grey potentially because of similar activation patterns. Results here, however, indicate that the stomatopod, Haptosquilla trispinosa was able to easily distinguish several colours, including blue of both high and low saturation, from greys. The animals did show a decrease in performance over time in an artificially lit environment, indicating plasticity in colour discrimination ability. This rapid plasticity, most likely the result of a change in opsin (visual pigment) expression, has now been noted in several animal lineages (both invertebrate and vertebrate) and is a factor we suggest needing care and potential re-examination in any colour-based behavioural tests. As for stomatopods, it remains unclear why they achieve poor colour discrimination using the most comprehensive set of spectral sensitivities in the animal kingdom and also what form of colour processing they may utilise.
The HIV-1 Integrase C-Terminal domain induces TAR RNA structural changes promoting Tat binding
Authors: Rocchi Cecilia , Louvat Camille , Miele Adriana , Batisse Julien , Guillon Christophe , Ballut Lionel , Lener Daniela , Negroni Matteo , Ruff Marc , Gouet Patrice , Fiorini Francesca
Published: October 2021

Recent evidence indicated that HIV-1 Integrase (IN) binds genomic viral RNA (gRNA) playing a critical role in viral particle morphogenesis and gRNA stability in host cells. Combining biophysical and biochemical approaches we show that the C-terminal flexible 18-residues tail of IN acts as a sensor of the peculiar apical structure of trans-activation response element RNA (TAR), directly interacting with its hexaloop. We highlighted how the whole IN C-terminal domain, once bound to TAR, can change its structure assisting the binding of Tat, the HIV trans-activator protein, which finally displaces IN from TAR. Our results are consistent with the emerging role of IN in early stage of proviral transcription and suggest new steps of HIV-1 life cycle that can be considered as therapeutic targets.
Learning the statistics of pain: computational and neural mechanisms
Authors: Mancini Flavia , Zhang Suyi , Seymour Ben
Published: October 2021

Pain invariably changes over time, and these temporal fluctuations are riddled with uncertainty about body safety. In theory, statistical regularities of pain through time contain useful information that can be learned, allowing the brain to generate expectations and inform behaviour. To investigate this, we exposed healthy participants to probabilistic sequences of low and high-intensity electrical stimuli to the left hand, containing sudden changes in stimulus frequencies. We demonstrate that humans can learn to extract these regularities, and explicitly predict the likelihood of forthcoming pain intensities in a manner consistent with optimal Bayesian models with dynamic update of beliefs. We studied brain activity using functional MRI whilst subjects performed the task, which allowed us to dissect the underlying neural correlates of these statistical inferences from their uncertainty and update. We found that the inferred frequency (posterior probability) of high intensity pain correlated with activity in bilateral sensorimotor cortex, secondary somatosensory cortex and right caudate. The uncertainty of statistical inferences of pain was encoded in the right superior parietal cortex. An intrinsic part of this hierarchical Bayesian model is the way that unexpected changes in frequency lead to shift beliefs and update the internal model. This is reflected by the KL divergence between consecutive posterior distributions and associated with brain responses in the premotor cortex, dorsolateral prefrontal cortex, and posterior parietal cortex. In conclusion, this study extends what is conventionally considered a sensory pain pathway dedicated to process pain intensity, to include the generation of Bayesian internal models of temporal statistics of pain intensity levels in sensorimotor regions, which are updated dynamically through the engagement of premotor, prefrontal and parietal regions.
A holistic insight of mycobacteriophage induced changes in mycobacterial cells
Authors: Calcuttawala Fatema , Shaw Rahul , Sarbajna Arpita , Dutta Moumita , Sinha Saptarshi , Das Gupta Sujoy K.
Published: October 2021

Mycobacteriophages are phages that interact with mycobacteria resulting in their killing. Although lysis is the major mechanism by which mycobacteriophages cause cell death, other mechanisms may also be involved. The present study was initiated with the objective of investigating the changes that take place at the cellular level following the infection of mycobacterial cells by phage D29. To investigate this issue, we took recourse to performing immunofluorescence and electron microscopic studies. Transmission electron microscopic examination revealed the adsorption of phages on to the surface of mycobacteria, following which penetration of the tail through the thick mycoloic acid layer was seen. At later time points discrete populations of cells at different stages of lysis were observed, which comprised of completely lysed cells, in which the cells were fragmented and those at the early onset stage exhibited formation of membrane pores through which the phages and intracellular contents were released. SEM results also indicated that phages may come out through the entire surface of the cell, or alternatively through gaps in the surface. In some of the images we observed structures that apparently resembled membrane blebs which are normally encountered when cells undergo programmed cell death (PCD). In addition, we observed significant increase in DNA fragmentation as well as membrane depolarization, which are also indicative of occurrence of PCD. As several bacterial PCD pathways are mediated by the toxin-antitoxin (TA) modules, the expression profile of all the TA systems was examined before and after phage infection. Apart from specifically addressing the issue of PCD in mycobacteriophage infected cells, this investigation has led to the development of facile tools necessary for investigating mycobacteriophage-mycobacteria interactions by means of microscopic methods.
Neuropeptide Neuromedin B does not alter body weight and glucose homeostasis nor does it act as an insulin-releasing peptide
Authors: Cikes Domagoj , Atanes Patricio , Huang Guo-Cai , Persaud Shanta J. , Penninger Josef M.
Published: October 2021

Neuromedin B (NMB) is a member of the neuromedin family of neuropeptides with a high level of region-specific expression in the brain. Several GWAS studies on non-obese and obese patients suggested that polymorphisms in NMB predispose to obesity by affecting appetite control and feeding preference. Furthermore, several studies proposed that NMB can act as an insulin releasing peptide. Since the functional study has never been done, the in vivo role of NMB as modulator of weight gain or glucose metabolism remains unclear. Here, we generated Nmb conditional mice and nervous system deficient NmB mice. We then performed olfactory and food preference analysis, as well as metabolic analysis under standard and high fat diet. Additionally, in direct islet studies we evaluated the role of NMB on basal and glucose-stimulated insulin secretion in mouse and humans.
Cooperative Effects of RIG-I-like Receptor Signaling and IRF1 on DNA Damage-Induced Cell Death
Authors: Zander David Y. , Burkart Sandy S. , Wüst Sandra , Magalhães Vladimir G. , Binder Marco
Published: October 2021

Properly responding to DNA damage is vital for eukaryotic cells, including the induction of DNA repair, growth arrest and, as a last resort to prevent neoplastic transformation, cell death. Besides being crucial for ensuring homeostasis, the same pathways and mechanisms are at the basis of chemoradiotherapy in cancer treatment, which involves therapeutic induction of DNA damage by chemical or physical (radiological) measures. Apart from typical DNA damage response mediators, the relevance of cell-intrinsic antiviral signaling pathways in response to DNA breaks has recently emerged. Originally known for combatting viruses via expression of antiviral factors including IFNs and establishing of an antiviral state, RIG-I-like receptors (RLRs) were found to be critical for adequate induction of cell death upon the introduction of DNA double-strand breaks. We here show that presence of IRF3 is crucial in this process, most likely through direct activation of pro-apoptotic factors rather than transcriptional induction of canonical downstream components, such as IFNs. Investigating genes reported to be involved in both DNA damage response and antiviral signaling, we demonstrate that IRF1 is an obligatory factor for DNA damage-induced cell death. Interestingly, its regulation doesnotrequire activation of RLR signaling, but rather sensing of DNA double strand breaks by ATM and ATR. Hence, even though independently regulated, both RLR signaling and IRF1 are essential for proper induction/execution of intrinsic apoptosis. Our results not only support more broadly developing IRF1 as a biomarker predictive for the effectiveness of chemoradiotherapy, but also suggest investigating a combined pharmacological stimulation of RLR and IRF1 signaling as a potential adjuvant regimen in tumor therapy.
Contribution of cytoplasm viscoelastic properties to mitotic spindle positioning
Authors: Xie Jing , Najafi Javad , Borgne Rémi Le , Verbavatz Jean-Marc , Durieu Catherine , Sallé Jeremy , Minc Nicolas
Published: October 2021

Cells are filled with macromolecules and polymer networks that set scale-dependent viscous and elastic properties to the cytoplasm. Although the role of these parameters in molecular diffusion, reaction kinetics and cellular biochemistry is being increasingly recognized, their contributions to the motion and positioning of larger organelles, such as mitotic spindles for cell division remain unknown. Here, using magnetic tweezers to displace and rotate mitotic spindles in living embryos, we uncovered that the cytoplasm can impart viscoelastic reactive forces that move spindles, or passive objects with similar size, back to their original position. These forces are independent of cytoskeletal force generators, yet reach hundreds of piconewtons and scale with cytoplasm crowding. Spindle motion shears and fluidizes the cytoplasm, dissipating elastic energy and limiting spindle recoils with functional implications for asymmetric and oriented divisions. These findings suggest that bulk cytoplasm material properties may constitute important control elements for the regulation of division positioning and cellular organization.

Significance Statement

The regulation of mitotic spindle positioning is a key process for tissue architecture, embryo development and stem cells. To date, most models have assumed that spindles are positioned by forces exerted by polar cytoskeleton networks, like microtubule asters or acto-myosin bundles. Here, usingin situmagnetic tweezers to apply calibrated forces and torques to mitotic spindles in live dividing sea urchin cells, we found that the viscoelastic properties of the cytoplasm medium in which spindles are embedded can hold spindles in place, and move them back if their original position is perturbed. These viscoelastic forces are large and may significantly participate in the force balance that position and orient mitotic spindles in many cell types.
Actin filaments act as a size-dependent diffusion barrier around centrosomes
Authors: Cheng Hsuan , Kao Yu-Lin , Sharma Lohitaksh , Yang Wen-Ting , Huang Shih-Han , Lin Hong-Rui , Huang Yao-Shen , Kao Chi-Ling , Yang Lee-Wei , Bearon Rachel , Lin Yu-Chun
Published: October 2021

The centrosome, a non-membranous organelle, constrains various soluble molecules locally to execute its functions. As the centrosome is surrounded by various dense components, we hypothesized that the centrosome may be bordered by a putative diffusion barrier. After quantitatively measuring the trapping kinetics of soluble proteins of varying size at centrosomes by a chemically inducible diffusion trapping assay, we found that centrosomes were highly accessible to soluble molecules with a Stokes radius of ≤ 5.1 nm, whereas larger molecules rarely reach centrosomes, indicating the existence of a size-dependent diffusion barrier at centrosomes. The permeability of barriers was tightly regulated by branched actin filaments outside of centrosomes. Such barrier gated the microtubule nucleation. We propose that actin filaments spatiotemporally constrain the distribution of molecules at centrosomes in a size-dependent manner.

Significance Statement

Centrosome maintains its microenvironment without membrane. Whether the dense protein complexes outside centrosomes including pericentriolar matrix, microtubules, and branched actin filaments provide physical obstruction is unclear yet. We here established a series of new tools for quantitative evaluation of the diffusion rates of varisized soluble proteins in different sub-compartments of centrosomes. Our results demonstrated that branched actin filaments, but not pericentriolar matrix or microtubules, around centrosome have acted as a size-dependent diffusion barrier and physically constrain centrosome microtubule nucleation.
Hyperphosphatemia increases inflammation to exacerbate anemia and skeletal muscle wasting independently of FGF23-FGFR4 signaling
Authors: Czaya Brian , Heitman Kylie , Campos Isaac , Yanucil Christopher , Kentrup Dominik , Westbrook David , Gutierrez Orlando , Babitt Jodie L. , Jung Grace , Salusky Isidro B. , Hanudel Mark R. , Faul Christian
Published: October 2021

Elevations in plasma phosphate concentrations (hyperphosphatemia) occur in chronic kidney disease (CKD), in certain genetic disorders, and following the intake of a phosphate-rich diet. Whether hyperphosphatemia and/or associated changes in metabolic regulators, including elevations of fibroblast growth factor 23 (FGF23) directly contribute to specific complications of CKD is uncertain. Here we report that similar to patients with CKD, mice with adenine-induced CKD develop inflammation, anemia and skeletal muscle wasting. These complications are also observed in mice fed high phosphate diet even without CKD. Ablation of pathologic FGF23- FGFR4 signaling did not protect mice on an increased phosphate diet or mice with adenine- induced CKD from these sequelae. However, low phosphate diet ameliorated anemia and skeletal muscle wasting in a genetic mouse model of CKD. Our mechanistic in vitro studies indicate that phosphate elevations induce inflammatory signaling and increase hepcidin expression in hepatocytes, a potential causative link between hyperphosphatemia, anemia and skeletal muscle dysfunction. Our study suggests that high phosphate intake, as caused by the consumption of processed food, may have harmful effects irrespective of pre-existing kidney injury, supporting not only the clinical utility of treating hyperphosphatemia in CKD patients but also arguing for limiting phosphate intake in healthy individuals.
Active disturbance rejection attitude control of unmanned quadrotor via paired coevolution pigeon-inspired optimization
Authors: Yuan Yang , Duan Haibin
Published: October 2021

Purpose

The purpose of this paper is to develop a novel active disturbance rejection attitude controller for quadrotors and propose a controller parameters identification approach to obtain better control results.

Design/methodology/approach

Aiming at the problem that quadrotor is susceptible to disturbance in outdoor flight, the improved active disturbance rejection control (IADRC) is applied to design attitude controller. To overcome the difficulty that adjusting the parameters of IADRC controller manually is complex, paired coevolution pigeon-inspired optimization (PCPIO) algorithm is used to optimize the control parameters.

Findings

The IADRC, where nonlinear state error feedback control law is replaced by non-singular fast terminal sliding mode control law and a third-order tracking differentiator is designed for second derivative of the state, has higher control accuracy and better robustness than ADRC. The improved PIO algorithm based on evolutionary mechanism, named PCPIO, is proposed. The optimal parameters of ADRC controller are found by PCPIO with the optimization criterion of integral of time-weighted absolute value of the error. The effectiveness of the proposed method is verified by a series of simulation experiments.

Practical implications

IADRC can improve the accuracy of attitude control of quadrotor and resist external interference more effectively. The proposed PCPIO algorithm can be easily applied to practice and can help the design of the quadrotor control system.

Originality/value

An improved active disturbance rejection controller is designed for quadrotor attitude control, and a hybrid model of PIO and evolution mechanism is proposed for parameters identification of the controller.
Content requirements for narrative reporting in the public sector: a contextual perspective
Authors: Igboke Benson , Raj Razaq
Published: October 2021

Purpose

Accounting literature is definite about the content and presentation of traditional financial statements, but the basic information to be provided in the narrative reports of public sector entities remains unsettled. This paper aims to investigate the needs and expectations of stakeholders (primary users and preparers) regarding the content and presentation of narrative reports in the public sector of Nigeria.

Design/methodology/approach

The research used a qualitative approach that draws on stakeholder and contingency theories to collect primary data through in-depth individual interviews using semi-structured questionnaires. Data were analysed by a thematic method using the NVivo 11 Pro software package.

Findings

The study reveals that financial statements constitute the statutory financial reports of public sector entities in Nigeria as narrative reporting is undeveloped, both as a concept and in practice. Stakeholders believe that narrative reporting is required to enhance the accountability usefulness of the annual financial reports published by the government and public agencies. Data analysis further reveals that public perception about the management of government financial resources influences the information needs of stakeholders regarding financial reporting. In addition, stakeholders consider the approved budget as the cornerstone of public financial reporting. Accordingly, users and other stakeholders expect public sector narrative reports to provide budget-based performance information that relates the accounting data presented in the financial statements to the key budgetary provisions, in both financial outlays and service delivery achievements. Stakeholders also expect narrative reports to be presented in plain language and provide information about the impact of financial decisions and actions on the basic socioeconomic variables that signpost citizens’ well-being, such as education, health care, employment and security.

Practical implications

The study suggests that the inclusion of narrative information in the statutory financial reports of public entities in Nigeria is imperative and should engage the attention of policymakers and relevant regulatory authorities. In addition, a more elaborate systematic investigation of the information needs of stakeholders in Nigeria should be undertaken by relevant units of government.

Originality/value

To the best of the authors’ knowledge, this is the first documented research on narrative reporting and the information needs of a broad range of stakeholders in the public sector of Nigeria. The paper identifies the approved budget as the focal point of governmental financial reporting, and a clear linkage between budget provisions, accounting results and service delivery achievements as the basic content of a narrative report in developing countries.
Active personalized construction safety training using run-time data collection in physical and virtual reality work environments
Authors: Jacobsen Emil L. , Solberg Alex , Golovina Olga , Teizer Jochen
Published: October 2021

Purpose

Accidents resulting from poorly planned or setup work environments are a major concern within the construction industry. While traditional education and training of personnel offer well-known approaches for establishing safe work practices, serious games in virtual reality (VR) are increasingly being used as a complementary approach for active learning experiences. By taking full advantage of data collection and the interactions possible in the virtual environment, the education and training of construction personnel improves by using non-biased feedback and immersion.

Design/methodology/approach

This research presents a framework for the generation and automated assessment of VR data. The proposed approach is tested and evaluated in a virtual work environment consisting of multiple hazards. VR requires expensive hardware, technical knowledge and user acceptance to run the games effectively. An effort has been made to transfer the advantages VR gives to a physical setup. This is done using a light detection and ranging sensing system, which collects similar data and enables the same learning experiences.

Findings

Encouraging results on the participants’ experiences are presented and discussed based on actual needs in the Danish construction industry. An outlook presents future avenues towards enhancing existing learning methods.

Practical implications

The proposed method will help develop active learning environments, which could lead to safer construction work stations in the future, either through VR or physical simulations.

Originality/value

The utilization of run-time data collection and automatic analysis allows for better personalized feedback in the construction safety training. Furthermore, this study investigates the possibility of transferring the benefits of this system to a physical setup that is easier to use on construction sites without investing in a full VR setup.
Status demotion in hierarchical loyalty programs and customers’ revenge and avoidance intentions
Authors: Banik Shanta , Gao Yongqiang , Rabbanee Fazlul K.
Published: October 2021

Purpose

Status demotion in hierarchical loyalty programs (HLPs) has received considerable academic attention. However, little is known about whether status demotion engenders two widely recognised behavioural intentions: revenge and avoidance. This study aims to make up this gap by examining the effects of status demotion on customers’ revenge and avoidance intentions. The underlying mechanism and boundary conditions of these effects are also explored.

Design/methodology/approach

Two studies were conducted to test the hypotheses. Study 1 was conducted using a structured survey from 347 active HLP members/customers of Chinese airlines. Study 2 used an online experiment amongst 268 active HLP airline customers in Australia. Partial least squares-based structural equation modelling and Hayes’ (2013) PROCESS macro were used for data analysis.

Findings

The results of Study 1 show that status demotion increases customers’ revenge and avoidance intentions simultaneously. Meanwhile, these effects are more significant for demoted customers with an external locus of causality than those with an internal locus of causality and demoted customers with higher entitlement tend to possess more revenge intentions than avoidance intentions. Study 2 further identified perceived inequity as a mechanism, which links status demotion to revenge and avoidance intentions of demoted customers.

Research limitations/implications

This study examines demoted customers’ revenge and avoidance intentions amongst Chinese and Australian airline travellers. Future research may focus on actual behaviour and test the current study’s model in cross-cultural and cross-industry settings.

Practical implications

Managers should deal with demotion decisions carefully as the failure to manage outraged customers may weaken customer-company relationships.

Originality/value

This study extends the existing literature on relationship marketing and HLPs by offering a better understanding of how and under what conditions status demotion elicits customers’ intentions for revenge and avoidance.