bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactive Oxygen Species Generation by Reverse Electron Transfer at Mitochondrial Complex I Under Simulated Early Reperfusion Conditions
Authors: Fukushima Caio Tabata , Dancil Ian-Shika , Clary Hannah , Shah Nidhi , Nadtochiy Sergiy M. , Brookes Paul S.
Published: November 2023

Ischemic tissues accumulate succinate, which is rapidly oxidized upon reperfusion, driving a burst of mitochondrial reactive oxygen species (ROS) generation that triggers cell death. In isolated mitochondria with succinate as the sole metabolic substrate under non-phosphorylating conditions, 90% of ROS generation is from reverse electron transfer (RET) at the Q site of respiratory complex I (Cx-I). Together, these observations suggest Cx-I RET is the source of pathologic ROS in reperfusion injury. However, numerous factors present in early reperfusion may impact Cx-I RET, including: (i) High [NADH]; (ii) High [lactate]; (iii) Mildly acidic pH; (iv) Defined ATP/ADP ratios; (v) Presence of the nucleosides adenosine and inosine; and (vi) Defined free [Ca2+]. Herein, experiments with mouse cardiac mitochondria revealed that under simulated early reperfusion conditions including these factors, overall mitochondrial ROS generation was only 56% of that seen with succinate alone, and only 52% of this ROS was assignable to Cx-I RET. The residual non-RET ROS could be partially assigned to complex III (Cx-III) with the remainder likely originating from other ROS sources upstream of the Cx-I Q site. Together, these data suggest the relative contribution of Cx-I RET ROS to reperfusion injury may be overestimated, and other ROS sources may contribute a significant fraction of ROS in early reperfusion.
Multi-Scale Geometric Network Analysis Identifies Melanoma Immunotherapy Response Gene Modules
Authors: Murgas Kevin A. , Elkin Rena , Riaz Nadeem , Saucan Emil , Deasy Joseph O. , Tannenbaum Allen R.
Published: November 2023

Melanoma response to immune-modulating therapy remains incompletely characterized at the molecular level. In this study, we assess melanoma immunotherapy response using a multi-scale network approach to identify gene modules with coordinated gene expression in response to treatment. Using gene expression data of melanoma before and after treatment with nivolumab, we modeled gene expression changes in a correlation network and measured a key network geometric property, dynamic Ollivier-Ricci curvature, to distinguish critical edges within the network and reveal multi-scale treatment-response gene communities. Analysis identified six distinct gene modules corresponding to sets of genes interacting in response to immunotherapy. One module alone, overlapping with the nuclear factor kappa-B pathway (NFKB), was associated with improved patient survival and a positive clinical response to immunotherapy. This analysis demonstrates the usefulness of dynamic Ollivier-Ricci curvature as a general method for identifying information-sharing gene modules in cancer.
Asgard archaea modulate potential methanogenesis substrates in wetland soil
Authors: Valentin-Alvarado Luis E. , Appler Kathryn E. , De Anda Valerie , Schoelmerich Marie C. , West-Roberts Jacob , Kivenson Veronika , Crits-Christoph Alexander , Ly Lynn , Sachdeva Rohan , Savage David F. , Baker Brett J. , Banfield Jillian F.
Published: November 2023

The roles of Asgard archaea in eukaryogenesis and marine biogeochemical cycles are well studied, yet their contributions in soil ecosystems are unknown. Of particular interest are Asgard archaeal contributions to methane cycling in wetland soils. To investigate this, we reconstructed two complete genomes for soil-associated Atabeyarchaeia, a new Asgard lineage, and the first complete genome of Freyarchaeia, and defined their metabolismin situ. Metatranscriptomics highlights high expression of [NiFe]-hydrogenases, pyruvate oxidation and carbon fixation via the Wood-Ljungdahl pathway genes. Also highly expressed are genes encoding enzymes for amino acid metabolism, anaerobic aldehyde oxidation, hydrogen peroxide detoxification and glycerol and carbohydrate breakdown to acetate and formate. Overall, soil-associated Asgard archaea are predicted to be non-methanogenic acetogens, likely impacting reservoirs of substrates for methane production in terrestrial ecosystems.

One-Sentence Summary

Complete genomes of Asgard archaea, coupled with metatranscriptomic data, indicate roles in production and consumption of carbon compounds that are known to serve as substrates for methane production in wetlands.
EMO: Predicting Non-coding Mutation-induced Up- and Down-regulation of Risk Gene Expression using Deep Learning
Authors: Liu Zhe , Bao Yihang , Song Weichen , Lin Guan Ning
Published: November 2023

The challenge of understanding how alterations in non-coding DNA regulate gene expression is substantial, with far-reaching consequences for the advancement of human genetics and disease research. Accurately predicting the up- and down-regulation of gene expression quantitative trait loci (eQTLs) offers a potential avenue to accelerate the identification of associations between non-coding variants and phenotypic traits. However, current methods for predicting the impact of non-coding mutations on gene expression changes fail to predict the sign of eQTLs accurately. Additionally, the requirement for tissue-specific training models within these methods restricts their applicability, especially when extending predictive abilities to single-cell resolution. In this study, we present EMO, an innovative transformer-based pre-trained method, designed to predict the up- and down-regulation of gene expression caused by single non-coding mutations using DNA sequences and ATAC-seq data. EMO extends the effective prediction range up to 1Mbp between the non-coding mutation and the transcription start site (TSS) of the target gene. It demonstrates competitive prediction performance across various variant TSS distances and surpasses the state-of-the-art structure. To assess its effectiveness, EMO was fine-tuned using eQTLs from two brain tissues for external validation. We also evaluated EMO's transferability to single-cell resolution by fine-tuning it on eQTLs from six types of immune cells, achieving satisfactory results in each cell type (AUC > 0.860). Furthermore, EMO displayed promising potential in analyzing disease-associated eQTLs.
Cohesin composition and dosage independently affect early development in zebrafish
Authors: Labudina Anastasia A. , Meier Michael , Gimenez Gregory , Tatarakis David , Ketharnathan Sarada , Mackie Bridget , Schilling Thomas F. , Antony Jisha , Horsfield Julia A.
Published: November 2023

Cohesin, a chromatin-associated protein complex with four core subunits (Smc1a, Smc3, Rad21 and either Stag1 or 2), has a central role in cell proliferation and gene expression in metazoans. Human developmental disorders termed “cohesinopathies” are characterised by germline mutations in cohesin or its regulators that do not entirely eliminate cohesin function. However, it is not clear if mutations in individual cohesin subunits have independent developmental consequences. Here we show that zebrafishrad21orstag2bmutants independently influence embryonic tailbud development. Both mutants have altered mesoderm induction, but only homozygous or heterozygousrad21mutation affects cell cycle gene expression.stag2bmutants have narrower notochords and reduced Wnt signaling in neuromesodermal progenitors as revealed by single cell RNA-sequencing. Stimulation of Wnt signaling rescues transcription and morphology instag2b, but notrad21mutants. Our results suggest that mutations altering the quantity versus composition of cohesin have independent developmental consequences, with implications for the understanding and management of cohesinopathies.

Summary Statement

Viable zebrafish mutants show that cohesin complex quantity versus composition lead to different transcriptional and developmental outcomes in the early embryo.
The androgen receptor in mesenchymal progenitors regulates skeletal muscle mass via Igf1 expression in male mice.
Authors: Sakai Hiroshi , Uno Hideaki , Yamakawa Harumi , Tanaka Kaori , Ikedo Aoi , Uezumi Akiyoshi , Ohkawa Yasuyuki , Imai Yuuki
Published: November 2023

Androgens exert their effects primarily by binding to the androgen receptor (AR), a ligand-dependent nuclear receptor. While androgens have anabolic effects on skeletal muscle, previous studies reported that AR functions in myofibers to regulate skeletal muscle quality, rather than skeletal muscle mass. Therefore, the anabolic effects of androgens are exerted via extra-myofiber cells or tissues. In this context, the cellular and molecular mechanisms of AR in mesenchymal progenitors, which play a crucial role in maintaining skeletal muscle homeostasis, remain largely unknown. In this study, we demonstrated expression of AR in mesenchymal progenitors and found that targeted AR ablation in mesenchymal progenitors reduced limb muscle mass in mature adult, but not young or aged, male mice, although fatty infiltration of muscle was not affected. The absence of AR in mesenchymal progenitors led to remarkable perineal muscle hypotrophy, regardless of age, due to abnormal regulation of transcripts associated with cell death and extracellular matrix organization. Additionally, we revealed that AR in mesenchymal progenitors regulates the expression of insulin-like growth factor 1 (Igf1), and that IGF1 administration prevents perineal muscles atrophy in a paracrine manner. These findings indicate that the anabolic effects of androgens regulate skeletal muscle mass via, at least in part, AR signaling in mesenchymal progenitors.
A within-person randomised trial to investigate the effects of a rigid cervical collar on three-dimensional angular movement and angular acceleration during emergency spinal immobilisation and extrication procedures in elite football (soccer) players: The RESTRICT study
Authors: Callaghan Michael J , Hughes Tom , Davin John , Hayes Russell , Hough Neil , Torpey Dan , Perry David , Dawson Sam , Murray Eoghan , Lancett Matthew , Liu Anmin , Jones Richard K
Published: November 2023

Objective

To determine the effects of rigid collars on cervical movement and acceleration during triple spinal immobilisation and extrication.

Methods

Procedures were performed on 15 non-injured volunteers in random order of collar and no-collar. Primary outcomes were angular movements and angular accelerations of the head relative to the thorax. Secondary outcome was the total procedure time.

Results

Between collar and no-collar, small but significant differences were found for mean angular movements during 15°tilt tasks for lateral flexion (3.4°: 95%CI: 1.4°, 5.4°), flexion-extension (2.4°95%CI: 0.4°, 4.4°), rotation (–3.7°: 95%CI: –7.2°, –0.2°) and total rotation (6°: 95%CI; 2.9°, 9.1°). For the lift and lower task there was a significant difference in total lateral flexion of only 0.3°(95%CI: 0.1°, 0.5°). Total movement during the procedure was significantly more for rotation without the collar (6.6°: 95% CI: 1.9°, 11.3°). Small but significant differences were found for angular acceleration only during the lift and lower task for maximum lateral flexion (–6.5 rads/s2, 95%CI: –12, –1 rads/s2), maximum rotation (–2.8 rads/s2, 95% CI: –5.2, –0.4 rads/s2) and minimum rotation (–3.5 rads/s2, 95%CI: –5.9, –0.1 rads/s2). The procedure was significantly longer with the collar (257.5s [95%CI: 245.3, 269.7s}versus230.9s [95%CI: 215, 246.8s].

Conclusion

There were statistically significant but clinically negligible differences between a rigid cervical collar and no-collar in some parameters for the triple immobilisation and extrication procedure in the sporting context. These novel results provide highlight important clinical considerations when immobilising and extricating players after a head or cervical injury.
Motor unit firing rate modulation is more impaired during flexion synergy-driven contractions of the biceps brachii in chronic stroke
Authors: Beauchamp James A. , Hassan Altamash S. , McPherson Laura M. , Negro Francesco , Pearcey Gregory E. P. , Cummings Mark , Heckman CJ , Dewald Julius P. A.
Published: November 2023

Following a hemiparetic stroke, individuals exhibit altered motor unit firing patterns during voluntary muscle contractions, including impairments in firing rate modulation and recruitment. These individuals also exhibit abnormal muscle coactivation through multi-joint synergies (e.g., flexion synergy). Here, we investigate whether motor unit firing activity during flexion synergy-driven contractions of the paretic biceps brachii differs from that of voluntary contractions and use these differences to predict changes in descending motor commands. To accomplish this, we characterized motor unit firing patterns of the biceps brachii in individuals with chronic hemiparetic stroke during voluntary isometric elbow flexion contractions in the paretic and non-paretic limbs, as well as during contractions driven by voluntary effort and by flexion synergy expression in the paretic limb. We observed significant reductions in motor unit firing rate modulation from the non-paretic to paretic limb (non-paretic – paretic: 0.14 pps/%MVT, 95% CI: [0.09 0.19]) that were further reduced during synergy-driven contractions (voluntary paretic – synergy driven: 0.19 pps/%MVT, 95% CI: [0.14 0.25]). Moreover, using recently developed metrics, we evaluated how a stroke-induced reliance on indirect motor pathways alters the inputs that motor units receive and revealed progressive increases in neuromodulatory and inhibitory drive to the motor pool in the paretic limb, with the changes greatest during synergy-driven contractions. These findings suggest that an interplay between heightened neuromodulatory drive and alterations in inhibitory command structure may account for the observed motor unit impairments, further illuminating underlying neural mechanisms involved in the flexion synergy and its impact on motor unit firing patterns post-stroke.
Convolutional neural networks can identify brain interactions involved in decoding spatial auditory attention
Authors: Mahjoory Keyvan , Bahmer Andreas , Henry Molly J.
Published: November 2023

Human listeners have the ability to direct their attention to a single speaker in a multi-talker environment. The neural correlates of selective attention can be decoded from a single trial of electroencephalography (EEG) data. In this study, leveraging the source-reconstructed and anatomically-resolved EEG data as inputs, we sought to employ CNN as an interpretable model to uncover task-specific interactions between brain regions, rather than simply to utilize it as a black box decoder. To this end, our CNN model was specifically designed to learn pairwise interaction representations for 10 cortical regions from five-second input trials. By exclusively utilizing these features for decoding, our model was able to attain a median accuracy of 77.56% for within-participant and 65.14% for cross-participant classification. Through ablation analysis together with dissecting the features of the models and applying cluster analysis, we were able to discern the presence of alpha-band-dominated inter-hemisphere interactions, as well as alpha-and beta-band dominant interactions that were either hemisphere-specific or were characterized by a contrasting pattern between the right and left hemispheres. These interactions were more pronounced in parietal and central regions for within-participant decoding, but in parietal, central, and partly frontal regions for cross-participant decoding. These findings demonstrate that our CNN model can effectively utilize features known to be important in auditory attention tasks and suggest that the application of domain knowledge inspired CNNs on source-reconstructed EEG data can offer a novel computational framework for studying task-relevant brain interactions.
ThePgb1locus controls glycogen aggregation in astrocytes of the aged hippocampus without impacting cognitive function
Authors: Gómez-Pascual A. , Glikman D. M. , Ng H. X. , Tomkins J. E. , Lu L. , Xu Y. , Ashbrook D. G. , Kaczorowski C. , Kempermann G. , Killmar J. , Mozhui K. , Ohlenschläger O. , Aebersold R. , Ingram D.K. , Williams E. G. , Williams R. W. , Overall R. W. , Jucker M. , de Bakker D. E. M.
Published: November 2023

In aged humans and mice, aggregates of hypobranched glycogen molecules called polyglucosan bodies (PGBs) accumulate in hippocampal astrocytes. PGBs are known to drive cognitive decline in neurological diseases but remain largely unstudied in the context of typical brain aging. Here, we show that PGBs arise in autophagy-dysregulated astrocytes of the aged C57BL/6J mouse hippocampus. To map the genetic cause of age-related PGB accumulation, we quantified PGB burden in 32 fully sequenced BXD-recombinant inbred mouse strains, which display a 400-fold variation in hippocampal PGB burden at 16-18 months of age. A major modifier locus was mapped to chromosome 1 at 72–75 Mb, which we defined as thePgb1locus. To evaluate candidate genes and downstream mechanisms by whichPgb1controls the aggregation of glycogen, extensive hippocampal transcriptomic and proteomic datasets were produced for aged mice of the BXD family. We utilized these datasets to identifySmarcal1andUsp37as potential regulators of PGB accumulation. To assess the effect of PGB burden on age-related cognitive decline, we performed phenome-wide association scans, transcriptomic analyses as well as conditioned fear memory and Y-maze testing. Importantly, we did not find any evidence suggesting a negative impact of PGBs on cognition. Taken together, our study demonstrates that thePgb1locus controls glycogen aggregation in astrocytes of the aged hippocampus without affecting age-related cognitive decline.
DRA Global: implementing digital transformation through change management in a project consultancy firm
Authors: Ramiah Krishnaveni , Moore Amy Fisher
Published: November 2023

Learning outcomes

After reading and discussing the case study, students should be able to identify the reasons why the company needed to digitise and how this links to the company’s strategy around technology and innovation, analyse the digitalisation implementation process followed in the case study by using an organisational change management model and make recommendations and propose a solution for the protagonist to consider for the successful roll-out of the digitalisation project.

Case overview/synopsis

DRA Projects is part of the DRA Global business based in South Africa. The company is known locally in the mining and engineering industry for its project development, delivery, execution and operations capabilities. Digital transformation is a key strategic focus in the industry, as clients seek digitised integrated systems. For this client offering, J.C. Heslinga, managing director of DRA Projects, was tasked with leading the digitalisation of the project delivery system. From July 2020 until July 2022, Heslinga led the implementation team through different organisational change stages. As the next phase included rolling out digitalisation to pilot projects and engaging employees and clients in the new process, Heslinga wondered if enough was done to ready the business for this change. The end users would be executing the changes, so their adoption will be imperative for successfully rolling out digitalisation. The case study concludes with Heslinga pondering the approach needed for the next phase. The case study focuses on the digitalisation implementation process through the lens of organisational change. The case study presents an opportunity to analyse and identify the theories and models used in organisational change within a real-life business context. The organisational change learnings can be adapted to help students with any transformation changes in similar business scenarios.

Complexity academic level

Postgraduate- and master’s-level students and business executives attending short courses will benefit from the learnings. The learnings can be applied to improve decision-making, organisational behaviour and strategic implementation using the fundamental principles of organisational change.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 6: Human resource management
The effect of COVID-19 containment measures on fresh food market vendors in Uganda
Authors: Nakazi Florence , Nasirumbi Sanya Losira , Mugisha Johnny
Published: November 2023

Purpose

The coronavirus disease (COVID-19) pandemic continues to impact economic systems, with devastating consequences on livelihoods. Anecdotal evidence has predicted the adverse effects of COVID-19 on the livelihood of food system actors. Uganda experienced two lockdowns in March 2020 and June 2021 with varying government containment measures. During the first lockdown, fresh food market vending was deemed essential to meet urban food demand, and was consequently exempted from a total shutdown despite the ban on public and private transport. Thus, this study sought to examine the effect of COVID-19 containment measures on fresh food market vending businesses in Uganda.

Design/methodology/approach

Using primary data collected from fresh food market vendors, this study applied a pooled time-series estimation to examine the effect of the first lockdown COVID-19 containment measures on fresh food vendors' welfare.

Findings

The study revealed that COVID-19 had a significant negative impact on the income of fresh food vendors, with female vendors being the most affected. COVID-19 containment measures reduced the diversity of buyers, individual customers and the number of commodities traded in causing a greater impact on vendors' income.

Research limitations/implications

The unavailability of data for vendors who did not return to the market at the time of data collection limits the scope of the study. Additionally, the absence of data for the second lockdown limited the analysis to only March 2020 lockdown period.

Originality/value

The empirical analysis highlights how vulnerabilities of different gender categories could be exacerbated by crises. The study provides empirical evidence of various market distortions caused by the COVID-19 pandemic and the disproportionate impact on women and men market vendors which calls for the need to integrate women's perspectives in future planning for market systems as well as advocating for gender-sensitive recovery responses.
Letter: Abdominal pain in inflammatory bowel disease patients in remission—A look beyond psychosocial factors
Authors: Bassotti Gabrio , Villanacci Vincenzo , Maconi Giovanni
Published: November 2023

LINKED CONTENT

This article is linked to Janssen et al papers. To view these articles, visit https://doi.org/10.1111/apt.17718 and https://doi.org/10.1111/apt.17775
Letter: Tofacitinib, vedolizumab and ustekinumab in patients with ulcerative colitis—Authors' reply
Authors: Desai Aakash , Regueiro Miguel , Kochhar Gursimran S.
Published: November 2023

LINKED CONTENT

This article is linked to Kochhar et al papers. To view these articles, visit https://doi.org/10.1111/apt.17570 and https://doi.org/10.1111/apt.17697
DMI: Social Innovation Case One: The Healthy Laddoo Project
Authors: Ford Ramsey , Hanisian Kate
Published: November 2023

A lot of local knowledge and a bit of design thinking combined to convert a popular dessert item into a weapon against malnutrition.

Design Impact connects design with low‐income communities in India and the US. This initiative, which fights malnutrition, is typical—and likely to become widespread.
“Heroic” medicine in neurology: A historical perspective
Authors: Sakalauskaitė‐Juodeikienė Eglė
Published: November 2023

Background and purpose

Repetitive bloodletting, promoting profuse diarrhoea and vomiting, the formation of artificial ulcers, and other aggressive treatment methods based on humoral theory and Brunonian medicine were used for patients with nervous system (NS) diseases until the end of the 19th century. These methods are also termed “heroic” medicine by modern medical historians.

Methods

I analysed doctoral dissertations on the subject of NS diseases, clinical reports from 1806 to 1842 from the Vilnius University clinics, and other primary sources. This study was conducted in the vein of a historical–medical analysis and synthesis of primary sources, using comparative analysis, analogy, descriptive methods, and the method of retrospective diagnosis.

Results

Copious bloodletting, purgatives, leeches, cupping therapy, and other potentially harmful methods were frequently employed as habitual treatments for patients with NS diseases. Calomel was used as a purgative and an anti‐inflammatory drug, and acidum borussicum was prescribed for patients with hydrophobia. After analysing three clinical cases, I revealed how principles of desperate, “heroic” medicine were applied to treat severe NS diseases with the “strongest” drugs, described in the scientific literature of the time.

Conclusions

My work was not intended to judge or criticize historical treatment methods but to demonstrate on what contemporary scientific theories they were based. We should not rule out the idea that some aggressive treatment methods used nowadays, although they eradicate or reduce the burden of a NS disease, or even prolong patients' lives, may offer exceptional examples of 21st century “heroic” medicine for future generations.
Text classification based on PEGCN: Graph convolution classification using location information and edge features
Authors: Zhang Ruidong , Guo Zelin , Huan Hai
Published: November 2023

The purpose of text classification is to label the text with known labels. In recent years, the method based on graph neural network (GNN) has achieved good results. However, the existing methods based on GNN only regard the text as the set of co‐occurring words, without considering the position information of each word in the statement. At the same time, the method mainly extracts the node features in the graph, and the edge features between the nodes are not used enough. To solve these problems, a new text classification method, graph convolutional network using positions and edges, is proposed. In the word embedding section, a positional encoding input representation is employed to enable the neural network to learn the relative positional information among words. Meanwhile, the dimension of the adjacency matrix is increased to extract the multi‐dimensional edge features. Through experiments on multiple text classification datasets, the proposed method is shown to be superior to the traditional text classification method, and has achieved a maximum improvement of more than 4%.
High‐throughput determination of grain size distributions by EBSD with low‐discrepancy sampling
Authors: Long Timothy J. H. , Holbrook William , Hufnagel Todd C. , Mueller Tim
Published: November 2023

Because microstructure plays an important role in the mechanical properties of structural materials, developing the capability to quantify microstructures rapidly is important to enabling high‐throughput screening of structural materials. Electron backscatter diffraction (EBSD) is a common method for studying microstructures and extracting information such as grain size distributions (GSDs), but is not particularly fast and thus could be a bottleneck in high‐throughput systems. One approach to accelerating EBSD is to reduce the number of points that must be scanned. In this work, we describe an iterative method for reducing the number of scan points needed to measure GSDs using incremental low‐discrepancy sampling, including on‐the‐fly grain size calculations and a convergence test for the resulting GSD based on the Kolmogorov–Smirnov test. We demonstrate this method on five real EBSD maps collected from magnesium AZ31B specimens and compare the effectiveness of sampling according to two different low discrepancy sequences, the Sobol and R2sequences, and random sampling. We find that R2sampling is able to produce GSDs that are statistically very similar to the GSDs of the full density grids using, on average, only 52% of the total scan points. For EBSD maps that contained monodisperse GSDs and over 1000 grains, R2sampling only required an average of 39% of the total EBSD points.
Peacemaking through the lens of participation: Revisiting the 2016 Colombian peace accord
Authors: Lara‐Rodríguez Juan Sebastián , Rodríguez‐Romero Carlos Alberto
Published: November 2023

How should we analyze democratic participation mechanisms created to end a civil war? This article examines participation in the design and ratification of Colombia's 2016 peace settlement. By analyzing theoretical participation approaches and reviewing official reports, proceedings, and formal rules engendered by the peacemaking, we consider the ways in which the stakeholders participated to formalize the agreement between the government and rebels in the Revolutionary Armed Forced of Colombia–People's Army. The case argues that inclusion does not necessarily mean control of civil society over the peacemaking process; the participation of the political society and insurgency groups is a precondition.
An emergent plant‐parasitic nematode in Brazil: Aphelenchoides besseyi. Current status and research perspectives
Authors: de Souza Victor Hugo Moura , Philadelphi Sophia Moracchioli , Galbieri Rafael , Sonawala Unnati , Eves‐van den Akker Sebastian
Published: November 2023

Aphelenchoides besseyi is an emerging and yet overlooked plant parasite of many economically important crops, including cotton, soybean and common bean. It presents an economic risk to these crops in several countries, notably in Brazil. Although first reported infecting strawberries in the United States as early as 1942, it was only identified to be the causal agent of green stem and foliar retention (GSFR) disease in Brazil in 2017. Currently, there are no chemical nematicides registered in Brazil against A. besseyi, and no known sources of genetic resistance. Here, we review the biology of A. besseyi, its spread across Brazil, its relevance to the country's current and future agriculture and the limited control measures. We describe control measures that have been successfully used to manage infestations of other plant‐parasitic nematodes and could potentially be extended to use in the control of A. besseyi. We also review and discuss potential future control measures, such as RNA interference and genome editing, for the development of crops with enhanced resistance to A. besseyi.
Emotional competencies and psychological distress: Is loneliness a mediating factor?
Authors: Ghiggia Ada , Castelli Lorys , Adenzato Mauro , Di Tella Marialaura
Published: November 2023

Emotional competencies, such as emotion regulation and empathy, are essential for social interaction. Impairment of these skills has been associated with increased rates of anxiety/depressive symptoms and loneliness, which has been defined as the discrepancy between the desired and actual quality and quantity of social relationships a person maintains. The aim of the present study was to shed light on the associations between these constructs and to examine the possible mediating role of loneliness in the relationship between emotional competencies and anxiety/depressive symptoms in a sample of non‐clinical individuals. A total of 298 participants were recruited for this study and were asked to complete a series of measures assessing difficulties in emotion regulation, empathy, loneliness, and anxiety/depressive symptoms. Regression and mediation models were tested to analyze the associations between these variables. Results showed that reduced emotional competencies in emotion regulation and empathy were both directly and indirectly associated with increased anxiety/depressive symptoms and emotional loneliness, which in turn was related to higher levels of psychological distress (with a partial mediation of loneliness). Overall, the present findings seem to indicate that emotional competencies play a key role in the experience of loneliness and psychological distress. Therefore, individuals reporting high levels of loneliness in combination with anxious/depressive symptoms should receive appropriate assessment and treatment of emotion regulation and empathic skills.
A framework for robotic excavation and dry stone construction using on-site materials
Authors: Johns Ryan Luke , Wermelinger Martin , Mascaro Ruben , Jud Dominic , Hurkxkens Ilmar , Vasey Lauren , Chli Margarita , Gramazio Fabio , Kohler Matthias , Hutter Marco
Published: November 2023

Automated building processes that enable efficient in situ resource utilization can facilitate construction in remote locations while simultaneously offering a carbon-reducing alternative to commonplace building practices. Toward these ends, we present a robotic construction pipeline that is capable of planning and building freeform stone walls and landscapes from highly heterogeneous local materials using a robotic excavator equipped with a shovel and gripper. Our system learns from real and simulated data to facilitate the online detection and segmentation of stone instances in spatial maps, enabling robotic grasping and textured 3D scanning of individual stones and rubble elements. Given a limited inventory of these digitized stones, our geometric planning algorithm uses a combination of constrained registration and signed-distance-field classification to determine how these should be positioned toward the formation of stable and explicitly shaped structures. We present a holistic approach for the robotic manipulation of complex objects toward dry stone construction and use the same hardware and mapping to facilitate autonomous terrain-shaping on a single construction site. Our process is demonstrated with the construction of a freestanding stone wall (10 meters by 1.7 meters by 4 meters) and a permanent retaining wall (65.5 meters by 1.8 meters by 6 meters) that is integrated with robotically contoured terraces (665 square meters). The work illustrates the potential of autonomous heavy construction vehicles to build adaptively with highly irregular, abundant, and sustainable materials that require little to no transportation and preprocessing.
REC protein family expansion by the emergence of a new signaling pathway
Authors: Garber Megan E. , Frank Vered , Kazakov Alexey E. , Incha Matthew R. , Nava Alberto A. , Zhang Hanqiao , Valencia Luis E. , Keasling Jay D. , Rajeev Lara , Mukhopadhyay Aindrila
Published: November 2023

This report presents multi-genome evidence that REC protein family expansion occurs when the emergence of new pathways gives rise to functional discordance. Specificity between residues in REC domain containing response regulators with paired histidine kinases is under negative purifying selection, constrained by the presence of other bacterial two-component systems signaling cascades that share sequence and structural identity. Presuming that the two-component systems can evolve by neutral amino acid changes (neutral drift) when purifying evolutionary constraints are relaxed, how might the REC protein family expand by amino acid changes when these constraints remain intact? Using an unsupervised machine learning approach to observe the sequence landscape of REC domains across long phylogenetic distances, we find that within-gene recombination, a subcategory of gene conversion, switched the effector domain and, consequently, the regulatory context of a duplicated response regulator from transcriptional regulation by σ54 to that by σ70. We determined that the recombined response regulator diverged from its parent by episodic diversifying selection and neutral drift. Functional experiments of the parent of recombined response regulators in a model
Pseudomonas putida
KT2440 model system revealed that the parent and recombined response regulators sense and respond to different carboxylic acids. Finally, a residue-switching experiment using structural predictions and functional characterization suggests that the new residues in the recombined regulator could form a new interaction interface and mediate condition-specific phosphotransfer. Overall, our study finds that genetic perturbations can create conditions of functional discordance, whereby the REC protein family can evolve by episodic diversifying selection.

IMPORTANCE

We explore when and why large classes of proteins expand into new sequence space. We used an unsupervised machine learning approach to observe the sequence landscape of REC domains of bacterial response regulator proteins. We find that within-gene recombination can switch effector domains and, consequently, change the regulatory context of the duplicated protein.
Pilot study to test the safety, tolerability and feasibility of dulaglutide during a low-energy diet for weight loss and improved glycaemic control
Authors: Shand James Allan Douglas , Young Simon , Verster Francois , Peters Carl
Published: November 2023

Introduction

Diabetes and obesity are significant public health concerns. Previous studies have demonstrated that low energy diets are effective in promoting weight loss and inducing diabetes remission. However, hunger is a potential barrier to adherence for such diets.

Dulaglutide is a glucagon-like peptide receptor agonist used in diabetes treatment. Its use is associated with weight loss, partly through increased satiety. The use of dulaglutide may improve adherence to a low energy diet through a reduction in hunger. We undertook a pilot study to assess the safety, tolerability and feasibility of this combination in individuals with obesity and type 2 diabetes.

Research design and methods

We enrolled individuals with type 2 diabetes and obesity from a tertiary diabetes service in Auckland, New Zealand. Owing to their higher rates of diabetes and poorer diabetes-related health outcomes, we preferentially enrolled Māori and Pacific individuals.

Participants underwent 2 weeks of dulaglutide run-in followed by 12 weeks of the combination of dulaglutide and low energy diet. The primary endpoints were the proportion of people successfully completing the dietary intervention and the rates and types of adverse events. Secondary outcomes were changes in weight, glycaemic control, quality of life and biochemical parameters.

Results

The intervention was well tolerated. Mild side effects were common during the first 2 weeks of the intervention but generally improved over the study period. Eighty-nine per cent of participants completed the 12-week dietary intervention. Participants achieved an average weight loss of 9.5 kg and a mean reduction in haemoglobin A1cof 15.8 mmol/mol. Quality of life metrics were unchanged.

Conclusions

We conclude that the combination of dulaglutide and a low energy diet is a feasible and well-tolerated intervention for individuals with diabetes and increased body weight. Future studies could be performed assessing this combination against a low energy diet alone.

Trial registration number

This study was registered with the Australia New Zealand Clinical Trials Registry (ACTRN1262200015279p).
Why do some people with stroke not receive the recommended 45 min of occupational therapy and physiotherapy after stroke? A qualitative study using focus groups
Authors: Clark Beth , Burridge Jane , Whitall Jill , Turk Ruth , Hughes Ann-Marie , Truman Juliette
Published: November 2023

Objectives

To generate qualitative data on the views of Occupational Therapists and Physiotherapists about why people do not receive the Royal College of Physicians’ recommended minimum of 45 minutes (min) of daily therapy after stroke, in order to inform a Delphi study.

Design

Focus group study.

Setting

Stroke services in the South of England.

Participants

A total of nine participants, in two groups, including therapists covering inpatient and Early Supported Discharge (ESD) services with awareness of the 45 min guideline.

Results

Thematic analysis of focus group data identified five factors that influence the amount of therapy a person receives: The Person (with stroke), Individual Therapist, Stroke Multidisciplinary Team, the Organisation and the Guideline. Study findings suggest that the reasons why a person does not receive the therapy recommendation in inpatient and ESD services relate to either the suitability of the guideline for the person with stroke, or the ability of the service to deliver the guideline.

Conclusion

This study provides evidence for possible reasons why some people do not receive a minimum of 45 minutes of therapy, 5 days per week, related to (1) the suitability of the guideline for people with stroke and (2) services’ ability to deliver this amount of intervention. These two factors are related; therapists decide who should receive therapy and how much in the context of (a) resource availability and (b) people’s need and the benefit they will experience. The study findings, combined with the findings from other studies, will be used to initiate a Delphi study, which will establish consensus among therapists regarding the reasons why some people do not receive the guideline amount of therapy.
Qualitative exploration of the constraints on mothers’ and pregnant women’s ability to turn available services into nutrition benefits in a low-resource urban setting, South Africa
Authors: Erzse Agnes , Desmond Chris , Hofman Karen , Barker Mary , Christofides Nicola Joan
Published: November 2023

Objectives

Despite free primary healthcare services and social protection system for mothers and children, significant nutrition inequalities occur across the globe, including in South Africa. This study aimed to explore what determines mothers’ ability to access and turn available services into nutrition benefits.

Design

An exploratory qualitative study was conducted including semistructured interviews with employees from community-based organisations and focus groups with pregnant women and mothers. Discussions focused on existing services perceived as important to nutrition, differences in mothers’ ability to benefit from these services, and the underlying unmet needs contributing to these disparities. Data were analysed thematically using a novel social needs framework developed for this study where social needs are defined as the requisites that can magnify (if unmet) or reduce (if met) variation in the degree to which individuals can benefit from existing services.

Setting

A resource-constrained urban township, Soweto in Johannesburg.

Participants

Thirty mothers of infants (<1 year old) and 21 pregnant women attending 5 primary healthcare facilities participated in 7 focus groups, and 18 interviews were conducted with employees from 10 community-based organisations.

Results

Mothers identified social needs related to financial planning, personal income stability, appropriate and affordable housing, access to government services, social support and affordable healthier foods. The degree to which these needs were met determined mothers’ capabilities to benefit from eight services. These were clinic-based services including nutrition advice and social work support, social grants, food aid, community savings groups, poverty alleviation projects, skills training workshops, formal employment opportunities and crèches/school feeding schemes.

Conclusion

Findings demonstrate that while current social protection mechanisms and free health services are necessary, they are not sufficient to address nutrition inequalities. Women’s social needs must also be met to ensure that services are accessed and used to improve the nutrition of all mothers and their children.
Human responses in adolescents with oncological disease: a scoping review protocol
Authors: Guerreiro Gonçalo Miguel , Deodato Sérgio , Graça Daniela , Fernandes Catarina
Published: November 2023

Introduction

The classification of human responses to health conditions or life processes, assuming that human responses are the way that a person responds, referring to the individual’s experiences, feelings, perceptions, behaviours and physical reactions, can be an exercise that, although challenging, is central to nursing diagnoses and, consequently, to nursing practice. It is necessary to gather and organise the existing knowledge about the human responses in adolescents with cancer, starting from the moment of diagnosis, due to the specificities inherent to this stage of human development. A scoping review is an appropriate method to use in order to map the existing knowledge on human responses in adolescents with oncological diseases experienced since the diagnosis.

Inclusion criteria

Will encompass all types of studies, including ‘grey literature’ that centres on human responses related to adolescents aged 10–19 years with oncological diseases. There will be no restrictions based on the type of cancer, disease stage or other contextual factors, whether in home or healthcare settings.

Methods and analysis

The review will be conducted following the guidelines outlined by the Joanna Briggs Institute for scoping reviews. The search will encompass the following databases: CINAHL Complete (EBSCOhost), Cochrane Database of Systematic Reviews (EBSCOhost), MEDLINE Complete (EBSCOhost), Nursing and Allied Health Collection: Comprehensive (EBSCOhost), Cochrane Clinical Answers (EBSCOhost Answers), Latin American and Caribbean Literature on Health Sciences (LILACS) and ‘grey literature’ sources accessible through the Scientific Open Access Repositories of Portugal (RCAAP). A three-step search strategy will be implemented. Titles and abstracts will undergo analysis by two independent reviewers. Articles selected for a full-text review will be organised. The results will be presented in tables and narratively summarised.

Ethics and dissemination

Ethics approval and patient consent for publication are not necessary. Findings will be disseminated through publication in scientific journals and through conference presentations.

Review registration number

EXUB4. Registration was made in the Open Science Framework (OSF).
Rates and risk factors for anastomotic leak following blunt trauma-associated bucket handle intestinal injuries: a multicenter study
Authors: Grossman Holly , Dhanasekara Chathurka Samudani , Shrestha Kripa , Marschke Brianna , Morris Erin , Richmond Robyn , Ko Ara , Tennakoon Lakshika , Campion Eric M , Wood Frank C , Brandt Maggie , Ng Grace , Regner Justin L , Keith Stacey L , McNutt Michelle K , Kregel Heather , Gandhi Rajesh R , Schroeppel Thomas J , Margulies Daniel R , Hashim Yassar M , Herrold Joseph , Goetz Mallory , Simpson LeRone , Doan Xuan-Lan , Dissanaike Sharmila
Published: November 2023

Objectives

The risk factors for anastomotic leak (AL) after resection and primary anastomosis for traumatic bucket handle injury (BHI) have not been previously defined. This multicenter study was conducted to address this knowledge gap.

Methods

This is a multicenter retrospective study on small intestine and colonic BHIs from blunt trauma between 2010 and 2021. Baseline patient characteristics, risk factors, presence of shock and transfusion, operative details, and clinical outcomes were compared using R.

Results

Data on 395 subjects were submitted by 12 trauma centers, of whom 33 (8.1%) patients developed AL. Baseline details were similar, except for a higher proportion of patients in the AL group who had medical comorbidities such as diabetes, hypertension, and obesity (60.6% vs. 37.3%, p=0.015). AL had higher rates of surgical site infections (13.4% vs. 5.3%, p=0.004) and organ space infections (65.2% vs. 11.7%, p<0.001), along with higher readmission and reoperation rates (48.4% vs. 9.1%, p<0.001, and 39.4% vs. 11.6%, p<0.001, respectively). There was no difference in intensive care unit length of stay or mortality (p>0.05). More patients with AL were discharged with an ostomy (69.7% vs. 7.3%, p<0.001), and the mean duration until ostomy reversal was 5.85±3 months (range 2–12.4 months). The risk of AL significantly increased when the initial operation was a damage control procedure, after adjusting for age, sex, injury severity, presence of one or more comorbidities, shock, transfusion of >6 units of packed red blood cells, and site of injury (adjusted RR=2.32 (1.13, 5.17)), none of which were independent risk factors in themselves.

Conclusion

Damage control surgery performed as the initial operation appears to double the risk of AL after intestinal BHI, even after controlling for other markers of injury severity.

Level of evidence

III.