bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutritional screening and nutritional interventions in patients following gastrointestinal surgery in a general surgical ward: a best practice implementation project
Authors: Zhang Qi , Yu Zhenghong , Qi Birong , Ni Xiaohong , Moola Sandeep
Published: November 2021

Objectives:

The aim of this implementation project was to improve nutritional screening and nutritional interventions for patients scheduled for gastrointestinal surgery in a general surgical ward.

Introduction:

Malnutrition is common in hospitalized surgical patients and has many adverse outcomes affecting the patients’ quality of life. Improving nutritional risk screening and nutritional support could reduce the incidence of malnutrition and its adverse outcomes.

Methods:

The project used the JBI audit and feedback method to implement evidence into practice. JBI Practical Application of Clinical Evidence System and Getting Research into Practice audit tools were used for promoting change in general surgical wards. Six audit criteria were created based on an evidence summary, including using screening tool, patients’ and caregivers’ education, nurses’ education on nutritional screening and support, preoperative nutrition support and postoperative early food intake. A baseline audit was conducted, followed by nursing information system improvement, education, multidisciplinary meetings targeted at clinicians and two cycles of follow-up audits.

Results:

Results from the baseline and follow-up audits showed improvement for all the criteria. Compliance for criteria 1–3 increased from 0 to 100%, and that for criterion 4 increased from 32 to 100%. These four criteria sustained 100% in follow-up cycle 2. Compliance for criterion 5 increased from 8 to 50% in follow-up cycle 1 audit, but decreased to 0% in follow-up cycle 2 audit, and similarly for criterion 6, compliance increased from 45 to 56% in follow-up cycle 1 audit, but decreased to 48% in follow-up cycle 2 audit.

Conclusion:

The objectives related to nutritional risk screening, nurse knowledge, patients and families were successfully realized and sustained positive results. This project demonstrated that a nursing information system and long-term patient education are essential strategies to achieve and sustain positive results. The objectives related to preoperative nutritional support and postoperative early enteral food intake were challenges and represented barriers. In future, a multiple-pronged strategy will be implemented to achieve overall success and change according to best practice.
Perioperative diabetes management of adult patients with diabetes: a best practice implementation project
Authors: Chen Tanghua , Kumaran Suji , Vigh Gia , Astorga Cecilia , Beehan Sean , Burrell Maria , Deakin Gail , Kernahan Carmen , Lambrakis Paul , Loader Joanne , Ly Nakim , Nguyen Mark , Pasco Kristofer , Perry Mary , Richter Matthew , Russell Hamish , Smith Frances , Venzon Raquel , Vernon Amanda
Published: November 2021

Objectives:

The objectives of this project were to conduct a retrospective healthcare records audit to determine the current compliance with evidence-based criteria regarding perioperative management of patients with diabetes; to identify barriers and facilitators to achieve compliance and develop strategies to address areas of non-compliance, and to implement evidence-based best practice recommendations for perioperative diabetic management and to assess the effectiveness of these strategies in improving compliance of perioperative diabetic management across five participating clinical areas in a large tertiary referral hospital.

Introduction:

Type 2 diabetes is a frequent co-morbidity among inpatients. It affects up to 20% of the general surgical population. Patients with diabetes undergoing surgery have a greater complication rate and length of hospital stay. Optimization of diabetes management of hospitalized patients will improve quality of care delivery, prevent postoperative complications and reduce length of stay and costs. However, there is limited knowledge and understanding of whether the current nursing practices concerning perioperative diabetic management meet the best practice recommendations outlined by JBI best practice criteria.

Methods:

A pre-post intervention healthcare record audit was conducted to examine compliance with nine best practice recommendations for perioperative diabetic management across five clinical areas. Following pre-intervention data analysis along with two focus group discussions, barriers to compliance with best practice criteria were identified and targeted strategies were used to address the issues. This project used the JBI Practice Application of Clinical Evidence System (PACES) and Getting Research into Practice (GRiP) tools.

Results:

Face to face education sessions and educational resources relating to perioperative diabetic management were delivered to nursing staff, which resulted in improved compliance for most of the audit criteria, with significant improvement in the areas of regular blood glucose level monitoring and nursing staff receiving education and training in the post-implementation analysis.
Maintaining oral hydration in older adults in surgical wards: a best practice implementation project
Authors: Seah Kwang Hui , Low Amanda Pei Shan , Low Jian Ying , Luk Grace Kar Sin , Chia Hui Xian , Goh Mien Li
Published: November 2021

Introduction and aim:

Oral hydration is essential in older adults as poor hydration can complicate existing medical conditions and increase morbidity. Older adults in surgical wards are at risk of dehydration due to insufficient fluid consumption. The aim of this project is to ensure patients aged 65 years and above are adequately hydrated.

Methods:

The current project was conducted over 7 months from February to August 2019 and involved pre and postimplementation audits to ensure compliance with best practice. The Joanna Briggs Institute Practical Application of Clinical Evidence System and the Getting Research into Practice tools were used as a guide. Audits were conducted at four surgical wards with a sample of 42 patients at each audit. The measures implemented include educating nurses on the importance of oral hydration in older adult patients and labelling water jugs to encourage fluid intake among these patients.

Results:

Nurses’ compliance in monitoring older adult patients’ daily fluid intake increased from 5 to 76% at follow-up audit (P < 0.05). In addition, the average amount of fluid consumed over 3 days increased from 858.23 to 1037.50 ml.

Conclusion:

This project demonstrated a significant increase in oral fluid intake among older adult patients during hospitalization and their understanding of adequate fluid intake. Nurses play an important role in ensuring adequate amounts of daily fluid intake by these patients.
The incorporation of body composition assessments as part of routine clinical care in a tertiary hospital's dietetic department: a best practice implementation project
Authors: Wilkinson Shelley A. , Jobber Chloe J.D. , Nave Fiona , van der Meij Barbara S.
Published: November 2021

Objectives:

Our aim was to incorporate body composition assessment (BCA) into dietetic department procedures using interventions tailored to previously identified barriers and enablers.

Introduction:

BCA is recommended as part of routine malnutrition assessment and follow-up but is not yet part of usual care.

Methods:

Evidence-informed strategies to overcome barriers and enablers were operationalized and delivered as three overarching interventions: upskilling (professional development strategy), modelling and reducing fear of change (Clinical Champion project), and embedding as usual practice (departmental integration). Process evaluation assessed intervention fidelity. A survey assessed utilization of BCA devices, (perceived) competency, and attitudes of clinical dietitians towards BCA before and after interventions.

Results:

Two of the three elements were incorporated as planned (upskilling and embedding as usual practice), with one element (modelling and reducing fear of change) modified through iterative processes. The Clinical Champion project ran for 12 rather than 6 months, and resulted in the majority of champions confident with their skills, completing BCA within their daily clinical workload and feeling BCA was useful. Pre-surveys and post-surveys within the department of 26 dietitians showed a marked reduction in most perceived barriers and improved recognition of enablers across all theoretical framework domains; with a large proportion of ‘not applicable’ responses given for many barriers at follow-up.

Conclusion:

This evidence-informed implementation strategy successfully integrated BCA into dietitians’ practice and departmental processes highlighting direction for future service changes. Continual assessment of barriers and success of integration into routine workloads is required to facilitate this.
Improvement in use of best practice in the care of patients with oral mucositis in a comprehensive cancer center in Iran: a best practice implementation case study
Authors: Alizadeh Mahasti , Moradi Siavash , Zaboli Ehsan , Emadian Seyedeh Fatemeh , Ghorbani Anahita , Hedayatizadeh Omran Akbar , Alizadeh Navaei Reza
Published: November 2021

Introduction:

Oral mucositis is a common debilitating complication of cancer treatments, particularly chemotherapy and radiation.

Objectives:

The purpose of this study was to improve oral mucositis prevention and control among cancer patients through the implementation of best practice guidelines in a tertiary referral center in Northern Iran.

Methods:

A clinical audit design was utilized in this implementation project. A preimplementation audit was conducted against nine best practice criteria for the prevention and treatment of oral mucositis among new cases of cancer patients in November and December 2019. Fifty cancer patients and 20 nurses participated in this phase of the clinical audit. The next step included a facilitated multidisciplinary focus group identifying targeted strategies and implementing them, completed in late December 2019. A postimplementation audit was then conducted on another 50 cancer patients and the same 20 nurses in January and early February 2020. The project utilized the Joanna Briggs Institute Practical Application of Clinical Evidence System and Getting Research into Practice software.

Results:

The preimplementation audit revealed gaps between the current practice and best practice across eight of the nine criteria. After implementing the targeted strategies, the outcomes improved across most of the criteria in the follow-up audit: 80% increase was observed in compliance of staff education, 100% increase in providing standard oral hygiene protocol in place, 64% increase in carrying out a dental examination and conducting initial oral cavity examination, and also 34% increase in conducting of ongoing oral cavity examination by a dentist, and finally 100% increase in providing preventive and therapeutic oral care regimens in place and oral pain assessment using a validated tool.

Conclusion:

The results of this project indicate that clinical auditing is an effective approach to the assessment of evidence-based care practices for oral mucositis among new cancer patients. Evidence-based oral mucositis management among cancer patients can be achieved by educating the patients and nursing staff using the newest guidelines and dentists’ comprehensive dental and oral hygiene examinations.
Ancestral sequences of a large promiscuous enzyme family correspond to bridges in sequence space in a network representation
Authors: Buchholz Patrick C. F. , van Loo Bert , Eenink Bernard D. G. , Bornberg-Bauer Erich , Pleiss Jürgen
Published: November 2021

Evolutionary relationships of protein families can be characterized either by networks or by trees. Whereas trees allow for hierarchical grouping and reconstruction of the most likely ancestral sequences, networks lack a time axis but allow for thresholds of pairwise sequence identity to be chosen and, therefore, the clustering of family members with presumably more similar functions. Here, we use the large family of arylsulfatases and phosphonate monoester hydrolases to investigate similarities, strengths and weaknesses in tree and network representations. For varying thresholds of pairwise sequence identity, values of betweenness centrality and clustering coefficients were derived for nodes of the reconstructed ancestors to measure the propensity to act as a bridge in a network. Based on these properties, ancestral protein sequences emerge as bridges in protein sequence networks. Interestingly, many ancestral protein sequences appear close to extant sequences. Therefore, reconstructed ancestor sequences might also be interpreted as yet-to-be-identified homologues. The concept of ancestor reconstruction is compared to consensus sequences, too. It was found that hub sequences in a network, e.g. reconstructed ancestral sequences that are connected to many neighbouring sequences, share closer similarity with derived consensus sequences. Therefore, some reconstructed ancestor sequences can also be interpreted as consensus sequences.
Early-Stage Identification and Avoidance of Antisense Oligonucleotides Causing Species-Specific Inflammatory Responses in Human Volunteers Peripheral Blood Mononuclear Cells
Authors: Burel Sebastien A. , Machemer Todd , Baker Brenda F. , Kwoh T. Jesse , Paz Suzanne , Younis Husam , Henry Scott P.
Published: November 2021

A human peripheral blood mononuclear cell (PBMC)-based assay was developed to identify antisense oligonucleotide (ASO) with the potential to activate a cellular innate immune response outside of an acceptable level. The development of this assay was initiated when ISIS 353512 targeting the mRNA for human C-reactive protein was tested in a phase I clinical trial in which healthy human volunteers unexpectedly experienced increases in interleukin-6 (IL-6) and C-reactive protein. This level of immune stimulation was not anticipated following rodent and non-human primate safety studies in which no evidence of exaggerated proinflammatory effects were observed. The IL-6 increase induced by ISIS 353512 was caused by activation of B-cells. The IL-6 induction was inhibited by chloroquine pretreatment of the PBMC and the nature of the ASOs suggested that the response is mediated by a toll like receptor, in all likelihood TLR9. While assessing the inter PBMC donor variability, two class of responders to ISIS 353512 were identified (discriminator and non-discriminators). The discriminator source of PBMC was shown to produce low level of IL-6 after 24 hours in culture in absence of ASO treatment. The PBMC assay using discriminator donors was shown to be reproducible allowing to assess reliably the immune potential of ASOs via comparison to known benchmark ASO controls that were previously shown to be either safe or inflammatory in clinical trials.
Overlapping Representation of Basic Tastes in the Human Gustatory Cortex
Authors: Zhang Du , Wang Xiaoxiao , Wang Yanming , Nguchu Benedictor Alexander , Jiang Zhoufang , Shi Chenwei , Qiu Bensheng
Published: November 2021

The topological representation is a fundamental property of human primary sensory cortices. The human gustatory cortex (GC) responds to the five basic tastes: bitter, salty, sweet, umami, and sour. However, the topological representation of the human gustatory cortex remains controversial. Through functional magnetic resonance imaging(fMRI) measurements of human responses to the five basic tastes, the current study aimed to delineate the taste representations within the GC. During the scanning, the volunteers tasted solutions of the five basic tastes, then washed their mouths with the tasteless solution. The solutions were then sucked from the volunteers’ mouths, eliminating the action of swallowing. The results showed that the bilateral mid-insula activated most during the taste task, and the active areas were mainly in the precentral and central insular sulcus. However, the regions responding to the five basic tastes are substantially overlapped, and the analysis of contrasts between each taste response and the averaged response to the remaining tastes does not report any significant results. Furthermore, in the gustatory insular cortex, the multivariate pattern analysis (MVPA) was unable to distinguish the activation patterns of the basic tastes, suggesting the possibility of weakly clustered distribution of the taste-preference neural activities in the human insular cortex. In conclusion, the presented results suggest overlapping representations of the basic tastes in the human gustatory insular cortex.
Evaluation of machine learning models for proteoform retention and migration time prediction in top-down mass spectrometry
Authors: Chen Wenrong , McCool Elijah N. , Sun Liangliang , Zang Yong , Ning Xia , Liu Xiaowen
Published: November 2021

Reversed-phase liquid chromatography (RPLC) and capillary zone electrophoresis (CZE) are two popular proteoform separation methods in mass spectrometry (MS)-based top-down proteomics. The prediction of proteoform retention time in RPLC and migration time in CZE provides additional information that can increase the accuracy of proteoform identification and quantification. Whereas existing methods for retention and migration time prediction are mainly focused on peptides in bottom-up MS, there is still a lack of methods for the problem in top-down MS. We systematically evaluated 6 models for proteoform retention and/or migration time prediction in top-down MS and showed that the Prosit model achieved a high accuracy (R2> 0.91) for proteoform retention time prediction and that the Prosit model and a fully connected neural network model obtained a high accuracy (R2> 0.94) for proteoform migration time prediction.
dynaPhenoM: Dynamic Phenotype Modeling from Longitudinal Patient Records Using Machine Learning
Authors: Zhang Hao , Zang Chengxi , Xu Jie , Zhang Hansi , Fouladvand Sajjad , Havaldar Shreyas , Su Chang , Cheng Feixiong , Glicksberg Benjamin S. , Chen Jin , Bian Jiang , Wang Fei
Published: November 2021

Identification of clinically meaningful subphenotypes of disease progression can facilitate better understanding of disease heterogeneity and underlying pathophysiology. We propose a machine learning algorithm, termed dynaPhenoM, to achieve this goal based on longitudinal patient records such as electronic health records (EHR) or insurance claims. Specifically, dynaPhenoM first learns a set of coherent clinical topics from the events across different patient visits within the records along with the topic transition probability matrix, and then employs the time-aware latent class analysis (T-LCA) procedure to characterize each subphenotype as the evolution of these learned topics over time. The patients in the same subphenotype have similar such topic evolution patterns. We demonstrate the effectiveness and robustness of dynaPhenoM on the case of mild cognitive impairment (MCI) to Alzheimer’s disease (AD) progression on three patient cohorts, and five informative subphenotypes were identified which suggest the different clinical trajectories for disease progression from MCI to AD.
Removing unwanted variation from large-scale cancer RNA-sequencing data
Authors: Molania Ramyar , Foroutan Momeneh , Gagnon-Bartsch Johann A. , Gandolfo Luke , Olshansky Gavriel , Dobrovic Alexander , Papenfuss Anthony T , Speed Terence P
Published: November 2021

The accurate identification and effective removal of unwanted variation are essential to derive meaningful biological results from RNA-seq data, especially when the data come from large and complex studies. We have used The Cancer Genome Atlas (TCGA) RNA-seq data to show that library size, batch effects, and tumor purity are major sources of unwanted variation across all TCGA RNA-seq datasets and that existing gold standard approaches to normalizations fail to remove this unwanted variation. Additionally, we illustrate how different sources of unwanted variation can compromise downstream analyses, including gene co-expression, association between gene expression and survival outcomes, and cancer subtype identifications. Here, we propose the use of a novel strategy, pseudo-replicates of pseudo-samples (PRPS), to deploy the Removing Unwanted Variation III (RUV-III) method to remove different sources of unwanted variation from large and complex gene expression studies. Our approach requires at least one roughly known biologically homogenous subclass of samples shared across sources of unwanted variation. To create PRPS, we first need to identify the sources of unwanted variation, which we will call batches in the data. Then the gene expression measurements of biologically homogeneous sets of samples are averaged within batches, and the results called pseudo-samples. Pseudo-samples with the same biology and different batches are then defined to be pseudo-replicates and used in RUV-III as replicates. The variation between pseudo-samples of a set pseudo-replicates is mainly unwanted variation. We illustrate the value of our approach by comparing it to the TCGA normalizations on several TCGA RNA-seq datasets. RUV-III with PRPS can be used for any large genomics project involving multiple labs, technicians, or platforms.
Comparative genomics among three cyst nematode species reveals distinct evolutionary histories among effector families and an irregular distribution of effector-associated promoter motifs
Authors: van Steenbrugge Joris J.M. , van den Elsen Sven , Holterman Martijn , Lozano-Torres Jose L. , Putker Vera , Thorpe Peter , Goverse Aska , Sterken Mark G. , Smant Geert , Helder Johannes
Published: November 2021

Potato cyst nematodes (PCNs), an umbrella term used for two species, Globodera pallida and G. rostochiensis, belong worldwide to the most harmful pathogens of potato. Pathotype-specific host plant resistances are an essential handle for PCN control. However, the poor delineation of G. pallida pathotypes hampers the efficient use of available host plant resistances. Long-read sequencing technology allowed us to generate a new reference genome of G. pallida population D383 and, as compared to the current reference, the new genome assembly is 42 times less fragmented. For comparison of diversification patterns of six effector families between G. pallida and G. rostochiensis, an additional reference genome was generated for an outgroup, the beet cyst nematode Heterodera schachtii (IRS population). Large evolutionary contrasts in effector family topologies were observed. While VAPs diversified before the split between the three cyst nematode species, the families GLAND5 and GLAND13 only expanded in PCN after their separation from the genus Heterodera. Although DNA motifs in the promoter regions thought to be involved in the orchestration of effector expression (‘DOG boxes’) were present in all three cyst nematode species, their presence is not a necessity for dorsal gland-produced effectors. Notably, DOG box dosage was only loosely correlated with expression level of individual effector variants. Comparison of the G. pallida genome with those of two other cyst nematodes underlined the fundamental differences in evolutionary history between effector families. Re-sequencing of PCN populations with deviant virulence characteristics will allow for the linking of these characteristics with the composition of the effector repertoire as well as for the mapping of PCN diversification patterns resulting from extreme anthropogenic range expansion.
Garlic-derived organosulfur compounds regulate metabolic and immune pathways in macrophages and attenuate intestinal inflammation in mice
Authors: Zhu Ling , Myhill Laura J. , Andersen-Civil Audrey I.S. , Thamsborg Stig M. , Blanchard Alexandra , Williams Andrew R.
Published: November 2021

Scope

Garlic is a source of bioactive phytonutrients that may have anti-inflammatory or immunomodulatory properties. The mechanism(s) underlying the bioactivity of these compounds and their ability to regulate responses to enteric infections remains unclear.

Methods and Results

We investigated if a garlic-derived preparation (PTSO-PTS) containing two organosulfur metabolites, propyl-propane thiosulfonate (PTSO) and propyl-propane thiosulfinate (PTS), regulated inflammatory responses in murine macrophages and intestinal epithelial cells (IEC)in vitro,as well as in a model of enteric parasite-induced inflammation. PTSO-PTS decreased lipopolysaccharide-induced secretion of TNFα, IL-6 and IL-27 in macrophages. RNA-sequencing demonstrated that PTSO-PTS strongly suppressed pathways related to immune and inflammatory signaling. PTSO-PTS induced the expression of a number of genes involved in antioxidant responses in IEC during exposure to antigens from the parasiteTrichuris muris. In vivo,PTSO-PTS did not affectT. murisestablishment or intestinal T-cell responses but significantly altered caecal transcriptomic responses. Notably, a reduction inT. muris-induced expression ofTnf, Saa2andNos2was observed.

Conclusion

Garlic-derived organosulfur compounds exert anti-inflammatory effects in macrophages and IEC, and regulate gene expression during intestinal infection. These compounds and related organic molecules may thus hold potential as functional food components to improve gut health in humans and animals.
Annexin A4 senses membrane curvature in a density dependent manner
Authors: Florentsen Christoffer D. , Daniels Joshua A. , Moreno-Pescador Guillermo , Qoqaj Iliriana , Nylandsted Jesper , Bendix Poul Martin
Published: November 2021

Annexins (ANXs) are a family of peripheral membrane binding proteins which play a vital role in the maintenance and function of cellular membranes. These proteins are known to be part of the plasma membrane repair machinery where they are known to bind to negatively charged lipids in the cell membrane in a calcium dependent manner. The shape of the plasma membrane is known to be a regulator of protein density and thereby affects several biological functions of the cell such as exo-and endocytosis, cell motility, immune responses and also membrane repair. Membrane deformation and curvature sensing by proteins is a well described phenomenon which can assist in recruitment of specific proteins to certain regions in the cell and facilitate membrane bending. Following ruptures in the plasma membrane, calcium influx assist in the association of ANXs with the membrane around the ruptured area. Due to the expected increase in curvature at the damaged membrane site, it has been suggested that both membrane curvature and Ca2+ participate in the recruitment of ANXs. We have investigated the curvature sensing of ANXA4 in giant unilamellar vesicles (GUVs) by pulling high curvature membrane tethers from the vesicle surface using optical tweezers showing that ANXA4 recruitment increases with higher membrane curvature. We also describe an assay for determining protein density on the plasma membrane by utilizing ANXA4’s property as a calcium dependent membrane binding protein. This new assay allows us to investigate the effect of protein density on curvature sensing.
ParS-independent recruitment of the bacterial chromosome-partitioning protein ParB
Authors: Tišma Miloš , Panoukidou Maria , Antar Hammam , Soh Young-Min , Barth Roman , Pradhan Biswajit , van der Torre Jaco , Michieletto Davide , Gruber Stephan , Dekker Cees
Published: November 2021

The ParABS system plays an essential role in prokaryotic chromosome segregation. After loading at the parS site on the genome, ParB proteins rapidly redistribute to distances of ~15 kb away from the loading site. It has remained puzzling how this large-distance spreading can occur along DNA that is loaded with hundreds of proteins. Using single-molecule in vitro visualization, we here show that, unexpectedly, ParB can load onto DNA independently and distantly of parS, whereby loaded ParB molecules are themselves able to recruit additional ParB proteins from bulk. Strikingly, this recruitment can occur in-cis but also in-trans whereby, at low tensions within the DNA, newly recruited ParB can bypass roadblocks as it gets loaded to spatially proximal but genomically distant DNA regions. The data are supported by Molecular Dynamics simulations which also show that cooperative ParB-ParB recruitment enhances spreading. ParS-independent recruitment explains how ParB can cover substantial genomic distance during chromosome segregation which is vital for the bacterial cell cycle.
Inhibitory Cerebellar Stimulation Increases Cortical Activation: Evidence for Cerebellar Scaffolding of Cortical Processing
Authors: Maldonado Ted , Jackson T. Bryan , Bernard Jessica A.
Published: November 2021

While the cerebellum makes known contributions to non-motor task performance, the role of the structure remains unknown. One possibility is that the cerebellum allows for the offloading of cortical processing, providing support during task performance, using internal models. The current work used transcranial direct current stimulation to modulate cerebellar function and investigate the impact on cortical activation patterns. Participants received stimulation over the right cerebellum before a functional magnetic resonance imaging scan where participants completed a sequence learning and a working memory task. We predicted that cathodal stimulation would improve, and anodal stimulation would hinder task performance and cortical activation. We found that anodal cerebellar stimulation resulted in increased bilateral cortical activation, particularly in parietal and frontal regions known to be involved in cognitive processing. This suggests that if the cerebellum is not functioning optimally, there is a greater need for cortical resources.
Microglia ferroptosis is prevalent in neurodegenerative disease and regulated by SEC24B
Authors: Ryan Sean K. , Zelic Matija , Han Yingnan , Teeple Erin , Chen Luoman , Sadeghi Mahdiar , Shankara Srinivas , Guo Lilu , Li Cong , Pontarelli Fabrizio , Jensen Elizabeth H. , Kumar Dinesh , Zhang Mindy , Gans Joseph , Zhang Bailin , Proto Jonathan , Saleh Jacqueline , Dodge James C. , Rajpal Deepak , Ofengeim Dimitry , Hammond Timothy R.
Published: November 2021

Iron dysregulation has been implicated in multiple neurodegenerative diseases, including Parkinson’s Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS). One prominent feature of affected brain regions are iron-loaded microglia, but how iron overload influences microglia physiology and disease response is poorly understood. Here we show that microglia are highly susceptible to ferroptosis, an iron-dependent form of cell death. In a tri-culture of human iPSC-derived neurons, astrocytes, and microglia, under ferroptosis-inducing conditions, microglia undergo a drastic shift in cell state, with increased ferritin levels, disrupted glutathione homeostasis, and altered cytokine signaling. Similar ferroptosis-associated signature (FAS) microglia were uncovered in PD, and the signature was also found in a large cohort of PD patient blood samples, raising the possibility that ferroptosis can be identified clinically. We performed a genome-wide CRISPR screen which revealed a novel regulator of ferroptosis, the vesicle trafficking gene SEC24B. A small molecule screen also nominated several candidates which blocked ferroptosis, some of which are already in clinical use. These data suggest that ferroptosis sits at the interface of cell death and inflammation, and inhibition of this process in microglia and other brain cells may provide new ways for treating neurodegenerative disease.
Unpacking strategic corporate social responsibility in the time of crisis: a critical review
Authors: Ashraf Zubaida , Afshan Gul , Sahibzada Umar Farooq
Published: November 2021

Purpose

An increasing number of organizations focus on creating value in economics and growing their aspect, encompassing human, social and environmental perspectives. Traditionally, organizations mostly contained corporate social responsibility (CSR) as their actions only in an economically favorable situation. However, CSR can also be used in an unfavorable time as a strategic process to recover and sustain the organization during a crisis. The purpose of this study is to review six years (2015-2021) articles published on strategic CSR.

Design/methodology/approach

The literature review of the current study examines through source data and combination findings the role of strategic CSR during a time of crisis. The search was conducted using Google Scholars, Psych Info, Emerald Insight, Science Direct and ProQuest. The study reviewed six years of articles on strategic CSR (2015–2021).

Findings

The paper concludes by suggesting propositions and a model that indicated that effective communication encourages employees and external stakeholders to participate and enhance their contribution during the crisis and help gain a competitive advantage.

Research limitations/implications

The present review demonstrated managing crisis by incorporating strategic CSR initiatives. The role of communication is important for understanding the crisis, which builds a trust-based relationship with employees and external stakeholders and enhances their participation and engagement that can help sustain during the crisis. This study will help the organizations during the time of crisis because strategic CSR initiatives reduce the negative effect of the crisis and help achieve organizational competitive advantages.

Originality/value

The present review bridges the gap in strategic CSR during the COVID-19 crisis interface. This review aims to understand the role of strategic CSR during the time COVID-19 of crisis. This study contributes to the strategic CSR research by giving clarity regarding the managing crises of organizations.
Exploring a natural baseline for large‐herbivore biomass in ecological restoration
Authors: Fløjgaard Camilla , Pedersen Pil Birkefeldt Møller , Sandom Christopher J. , Svenning Jens‐Christian , Ejrnæs Rasmus
Published: November 2021

Large herbivores provide key ecosystem processes, but have experienced massive historical losses and are under intense pressure, leaving current ecosystems with dramatically simplified faunas relative to the long‐term evolutionary norm. Hampered by a shifting baseline, natural levels of large‐herbivore biomass are poorly understood and seldom targeted. This ‘Decade of ecosystem restoration’ calls for evidence‐based targets for restoring the natural diversity and biomass of large herbivores.

We apply the scaling of the consumer–producer relationship to a global dataset of large‐herbivore density in natural areas. The analyses reveal that African ecosystems generally have much higher large‐herbivore biomass and also the strongest consumer–producer relationship. For Europe, Asia and South America, there are no significant relationships with primary productivity indicative of impoverished faunas. Compared to expectations from the African scaling relation, large‐herbivore biomass in ecosystems outside Africa is considerably lower than expected.

Synthesis and applications. Ecological restoration and rewilding entail restoration of a natural grazing process. Our findings indicate that many nature reserves are depleted in large‐herbivore biomass, judged from their primary productivity. Meanwhile, overexploitation by seasonal livestock grazing takes place in other areas. It is thus difficult, but urgent, to reach scientific consensus regarding a natural baseline for large‐herbivore biomass. Until such agreement has been reached, we recommend to manage, or rewild, large herbivores in year‐round near‐natural grazing and without predefined density targets, but following natural and fluctuating resource availability with minimal management intervention. The establishment of experimental rewilding sites with reactive herbivore management is needed to further advance our understanding of natural grazing density.
Human Trafficking, SM v Croatia and the Conceptual Evolution of Article 4 ECHR
Authors: Hughes Kirsty
Published: November 2021

Over the last decade the European Court of Human Rights has sought to reinterpret Article 4 ECHR in ways that render it applicable to human trafficking and modern slavery. Yet whilst this accorded Article 4 ECHR a vital role, ambiguity pervaded the question of what constitutes ‘human trafficking’; an issue that came to the fore in SM v Croatia, ultimately culminating in the first Grand Chamber human trafficking judgment. This analysis piece responds to these developments by drawing out and reflecting upon the conceptual framework for human trafficking and Article 4 ECHR, identifying what we now know, and equally what remains unknown, about this important right. In this regard it highlights significant differences of opinion within the Court. Underpinning those differences are diverging views as to both the scope of Article 4 ECHR, and the role of the Court, such that radically different future directions remain both possible and contested.
Design and engineering of whole‐cell biocatalyst for efficient synthesis of (R)‐citronellal
Authors: Zhang Baoqi , Du Han , Zheng Yanqiu , Sun Jiale , Shen Yu , Lin Jinping , Wei Dongzhi
Published: November 2021

Bioproduction of optical pure (R)‐citronellal from (E/Z)‐citral at high substrate loading remains challenging. Low catalytic efficiency of (R)‐stereoselective ene reductases towards crude citral mixture is one of the major bottlenecks. Herein, a structure‐based engineering strategy was adopted to enhance the catalytic efficiency and stereoselectivity of an ene reductase (OYE2p) from Saccharomyces cerevisiae YJM1341 towards (E/Z)‐citral. On basis of homologous modelling, molecular docking analysis and alanine scanning at the binding pocket of OYE2p, a mutant Y84A was obtained with simultaneous increase in catalytic efficiency and stereoselectivity. Furthermore, site‐saturation mutagenesis of Y84 yielded seven mutants with improved activity and stereoselectivity in the (E/Z)‐citral reduction. Among them, the variant Y84V exhibited an 18.3% and 71.3% rise in catalytic efficiency (kcat/Km) for (Z)‐citral and (E)‐citral respectively. Meanwhile, the stereoselectivity of Y84V was improved from 89.2% to 98.0% in the reduction in (E/Z)‐citral. The docking analysis and molecular dynamics simulation of OYE2p and its variants revealed that the substitution Y84V enabled (E)‐citral and (Z)‐citral to bind with a smaller distance to the key hydrogen donors at a modified (R)‐selective binding mode. The variant Y84V was then co‐expressed with glucose dehydrogenase from Bacillus megaterium in E. coli D4, in which competing prim‐alcohol dehydrogenase genes were deleted to prevent the undesired reduction in the aldehyde moiety of citral and citronellal. Employing this biocatalyst, 106 g l−1 (E/Z)‐citral was completely converted into (R)‐citronellal with 95.4% ee value and a high space‐time yield of 121.6 g l−1 day−1. The work highlights the synthetic potential of Y84V, which enabled the highest productivity of (R)‐citronellal from (E/Z)‐citral in high enantiopurity so far.
Impact of COVID vaccination rollout on the use of computed tomography venography for the assessment of cerebral venous sinus thrombosis
Authors: Thompson Corey , Karunadasa Hirannya , Varma Dinesh , Schoenwaelder Mark , Clements Warren
Published: November 2021

Introduction

Cerebral venous sinus thrombosis (CVST) is rare; however, it has been observed in patients with vaccine‐induced immune thrombotic thrombocytopaenia syndrome (VITT) following the use of adenovirus vector vaccines against COVID‐19. Adverse vaccine effects have been heavily addressed in mainstream media, likely contributing to vaccination anxiety. This study aimed to assess how the vaccine rollout and media coverage has influenced the use of computed tomography venography (CTV) in an acute care setting of a tertiary hospital.

Method

Single‐centre retrospective cohort study from 30 March 2021 to 13 June 2021. Direct comparison to same calendar dates in the preceding 3 years.

Results

In 2021, 57 patients received CTV with headache being the reason in 48 (84%) and 40 (70%) had received ChAdOx1 nCov‐19 (AstraZeneca COVID‐19 vaccination). Only 20 of these patients received CTV after platelets and D‐Dimer had returned, and only three patients met existing guidelines for imaging. Zero cases were positive. The number of CTV studies was 5.2 times than in 2020 and 2.7 times the mean number for the 3 preceding years.

Conclusion

The use of CTV in patients with headache has markedly increased at our centre since negatively biased vaccination influence of mainstream media. Headache is a common vaccine‐related side effect and VITT is exceptionably rare. With the rates of vaccination increasing in the community, these results highlight the importance of strict adherence to established evidence‐based guidelines. Otherwise, critical care capacity, and in particular imaging resources already under pressure will be strained further.
Drug checking services for people who use drugs: a systematic review
Authors: Maghsoudi Nazlee , Tanguay Justine , Scarfone Kristy , Rammohan Indhu , Ziegler Carolyn , Werb Dan , Scheim Ayden I.
Published: November 2021

Background and Aims

Drug checking services provide people who use drugs with chemical analysis results of their drug samples while simultaneously monitoring the unregulated drug market. We sought to identify and synthesize literature on the following domains: (a) the influence of drug checking services on the behaviour of people who use drugs; (b) monitoring of drug markets by drug checking services; and (c) outcomes related to models of drug checking services.

Methods

Systematic review. A systematic literature search was conducted in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PsycINFO, Scopus, Web of Science and Dissertations and Theses Global. Eligible studies were peer‐reviewed articles and conference abstracts or grey literature, published in any language since 1990 and including original data on the domains. We assessed risk of bias for quantitative peer‐reviewed articles reporting on behaviour or models of drug checking services using National Institutes of Health tools.

Results

We screened 2463 titles and abstracts and 156 full texts, with 90 studies meeting inclusion criteria. Most (n = 65, 72.2%) were from Europe and used cross‐sectional designs (n = 79, 87.7%). Monitoring of drug markets by drug checking services (n = 63, 70%) was the most reported domain, followed by the influence of drug checking services on behaviour (n = 31, 34.4%), including intent to use, actual use and disposal of the drug, and outcomes related to models of drug checking services (n = 17, 18.9%). The most common outcome measures were detection of unexpected substances (n = 50, 55.6%), expected substances (n = 44, 48.9%), new psychoactive substances (n = 40, 44.4%) and drugs of concern (n = 32, 36.5%) by drug checking services.

Conclusions

Drug checking services appear to influence behavioural intentions and the behaviour of people who use drugs, particularly when results from drug checking services are unexpected or drugs of concern. Monitoring of drug markets by drug checking services is well established in Europe, and increasingly in North America. Concerns about drug contents and negative health consequences facilitate the use of drug checking services; lack of concern; trust in drug sellers; lack of accessibility of drug checking services; and legal and privacy concerns are barriers to use.
Opioid agonist treatment uptake within provincial correctional facilities in British Columbia, Canada
Authors: Kurz Megan , Dale Laura M. , Min Jeong Eun , Hongdilokkul Natt , Greiner Leigh , Olley Maureen , McLeod Katherine E. , Slaunwhite Amanda , Nosyk Bohdan
Published: November 2021

Background and Aims

Multiple interventions and policy changes related to opioid agonist treatment (OAT) have been introduced in British Columbia, Canada to increase engagement and retention in OAT. We aimed to estimate the impact of policy changes and the announcement of the opioid overdose‐related public health emergency on the use of OAT for incarcerated individuals with opioid use disorder.

Design

Interrupted time‐series analysis. Events of interest included the expansion of buprenorphine/naloxone into provincial health‐care insurance coverage in October 2015 and the public health emergency declared in April 2016.

Setting and Participants

Our study included 9220 incarcerated individuals from 12 provincial corrections facilities in British Columbia, Canada for a total of 75 649 calendar months of incarceration.

Measurements

Monthly measures of OAT use during incarceration from 1 January 2013 to 30 September 2017. We estimated changes in OAT use, controlling for individual and facility‐level factors, using a general estimating equation, specified with a logit link and an autoregressive correlation matrix.

Findings

After the provincial health insurance coverage expansion, a sharp increase in OAT use during incarceration was observed [adjusted odds ratio (aOR) = 1.16, 95% confidence interval (CI) = 1.13, 1.19]. The public health emergency coincided with an immediate but temporary increase in OAT receipt (aOR = 1.34, 95% CI = 1.22, 1.47). During the entire study period, we estimated a 10‐fold increase in the adjusted odds of OAT use during incarceration (aOR = 10.10, 95% CI = 8.98, 11.37).

Conclusion

Following an expansion of health‐care insurance coverage to include buprenorphine/naloxone, receipt of opioid agonist treatment (OAT) within correctional facilities in British Columbia, Canada increased, largely driven by an increase in buprenorphine/naloxone prescriptions among individuals without recent OAT experience.
Axonal injury following mild traumatic brain injury is exacerbated by repetitive insult and is linked to the delayed attenuation of NeuN expression without concomitant neuronal death in the mouse
Authors: Ogino Yasuaki , Bernas Tytus , Greer John E. , Povlishock John T.
Published: November 2021

Mild traumatic brain injury (mTBI) affects brain structure and function and can lead to persistent abnormalities. Repetitive mTBI exacerbates the acute phase response to injury. Nonetheless, its long‐term implications remain poorly understood, particularly in the context of traumatic axonal injury (TAI), a player in TBI morbidity via axonal disconnection, synaptic loss and retrograde neuronal perturbation. In contrast to the examination of these processes in the acute phase of injury, the chronic‐phase burden of TAI and/or its implications for retrograde neuronal perturbation or death have received little consideration. To critically assess this issue, murine neocortical tissue was investigated at acute (24‐h postinjury, 24hpi) and chronic time points (28‐days postinjury, 28dpi) after singular or repetitive mTBI induced by central fluid percussion injury (cFPI). Neurons were immunofluorescently labeled for NeuroTrace and NeuN (all neurons), p‐c‐Jun (axotomized neurons) and DRAQ5 (cell nuclei), imaged in 3D and quantified in automated manner. Single mTBI produced axotomy in 10% of neurons at 24hpi and the percentage increased after repetitive injury. The fraction of p‐c‐Jun+ neurons decreased at 28dpi but without neuronal loss (NeuroTrace), suggesting their reorganization and/or repair following TAI. In contrast, NeuN+ neurons decreased with repetitive injury at 24hpi while the corresponding fraction of NeuroTrace+ neurons decreased over 28dpi. Attenuated NeuN expression was linked exclusively to non‐axotomized neurons at 24hpi which extended to the axotomized at 28dpi, revealing a delayed response of the axotomized neurons. Collectively, we demonstrate an increased burden of TAI after repetitive mTBI, which is most striking in the acute phase response to the injury. Our finding of widespread axotomy in large fields of intact neurons contradicts the notion that repetitive mTBI elicits progressive neuronal death, rather, emphasizing the importance of axotomy‐mediated change.