bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal brain structure changes in Parkinson’s disease: a replication study
Authors: Sokołowski Andrzej , Bhagwat Nikhil , Chatelain Yohan , Dugré Mathieu , Hanganu Alexandru , Monchi Oury , McPherson Brent , Wang Michelle , Poline Jean-Baptiste , Sharp Madeleine , Glatard Tristan
Published: April 2023

Context

An existing major challenge in Parkinson’s disease (PD) research is the identification of biomarkers of disease progression. While Magnetic Resonance Imaging (MRI) is a potential source of PD biomarkers, none of the MRI measures of PD are robust enough to warrant their adoption in clinical research. This study is part of a project that aims to replicate 11 PD studies reviewed in a recent survey (JAMA neurology, 78(10) 2021) to investigate the robustness of PD neuroimaging findings to data and analytical variations.

Objective

This study attempts to replicate the results in Hanganu et al. (Brain, 137(4) 2014) using data from the Parkinson’s Progression Markers Initiative (PPMI).

Methods

Using 25 PD subjects and 18 healthy controls, we analyzed the rate of change of cortical thickness and of the volume of subcortical structures, and we measured the relationship between MRI structural changes and cognitive decline. We compared our findings to the results in the original study.

Results

Similarly to the original study, PD patients with mild cognitive impairment (MCI) exhibited increased cortical thinning over time compared to patients without MCI in the right middle temporal gyrus, insula, and precuneus. (2) The rate of cortical thinning in the left inferior temporal and precentral gyri in PD patients correlated with the change in cognitive performance. (3) There were no group differences in the change of subcortical volumes. (4) We did not find a relationship between the change in subcortical volumes and the change in cognitive performance.

Conclusion

Despite important differences in the dataset used in this replication study, and despite differences in sample size, we were able to partially replicate the original results. We produced a publicly available reproducible notebook allowing researchers to further investigate the reproducibility of the results in Hanganu et al. (2014) when more data becomes available in PPMI.
Translation in a Box: Orthogonal Evolution in theSaccharomyces cerevisiaeMitochondrion
Authors: Rothschild-Mancinelli Brooke , Alvarez-Carreño Claudia , Guo Wenying , Ito Chieri , Costa Alex , Petrov Anton S. , Lobachev Kirill , Williams Loren Dean
Published: April 2023

The ability to re-engineer and creatively evolve the translation system (TS) would allow invention of new coded polymers by altering the amino acid sidechain inventory and by shifting the polypeptide backbone into new chemical spaces. Unfortunately, the TS is difficult to manipulate and is more constrained over evolution than any other biological system. An orthogonal TS, running in parallel to the primary TS within a given host cell, would release constraints and allow TS manipulation. A fully orthogonal TS requires dedicated rRNAs, rProteins, aminoacyl-tRNA synthetases, and initiation and termination factors, none of which interact with the primary TS. TheS. cerevisiaemitochondrial TS is fully orthogonal to the cytosolic TS. Mito-rRNAs, mito- rProteins, mito-tRNAs, mito-aminoacyl tRNA synthetases, and mito-translation factors are distinct from, physically separated from, and functionally independent of their cytosolic counterparts. Here, theS. cerevisiaemitochondrial translation system was subjected to various stresses including antibiotics, mutagenesis and truncation of mito-rProteins, or wholesale replacement of mito-rProteins. Directed evolution of these stressed systems was facilitated by controlled transitions between fermentation and respiration, by changing the carbon source in the growth medium; the dependence ofS. cerevisiaesurvival on mitochondrial translation can be toggled on and off. Specific recreation of the resulting mutations recapitulate the evolved phenotypes. The method developed here appears to be a general approach for discovering functional dependencies. Suppressor mutations reveal functional dependencies within theS. cerevisiaemitochondrial TS. For example proteins Rrg9 or Mrx1 interact with the mito-TS and have critical role in its function. The combined results indicate that theS. cerevisiaemitochondrial TS can be engineered and evolved in isolation of the cytosolic TS.

Significance

The Central Dogma of Molecular Biology rules life on Earth. Information flows from DNA to mRNA to protein. In the last step of the Central Dogma, the translation system decodes mRNA and produces coded proteins by linking amino acids into polymers. Engineering and evolving the translation system could permits full technical control over this process and could lead to the generation of novel polymers. Here, we use the mitochondrial translation system in the budding yeastSaccharomyces cerevisiaefor directed evolution of translation. We modify and evolve the translation system both directly and indirectly using antibiotics and gene editing tools and then measure resulting functionality. Our results show this secondary translation system insideS. cerevisiaemitochondria can be used as an approach for translation engineering.
Hippocampal neural fluctuation between memory encoding and retrieval states during a working memory task in humans
Authors: Watanabe Yusuke , Ikegaya Yuji , Yanagisawa Takufumi
Published: April 2023

Background

Working memory (WM) is essential for everyday life, yet its neural mechanism remains unclear. Although the hippocampus plays a critical role in memory consolidation and retrieval, its role in WM tasks has yet to be fully elucidated. We hypothesized that multiunit activities in the hippocampus alter their representations depending on the memory load and phase of a WM task, particularly in relation to sharp-wave ripple complexes (SWRs), which are known as various cognitive biomarkers.

Methods

We used an open dataset of intracranial electroencephalogram (iEEG) data and multiunit activity recorded from the medial temporal lobe (MTL) of nine patients with epilepsy. The MTL includes the hippocampus, entorhinal cortex, and amygdala. During the recording, all subjects performed an eight-second Sternberg test, in which they memorized sets of four, six, or eight letters (encoding phase), waited for three seconds (maintenance phase), and recalled whether a probe letter was included (Match IN task) or not (Mismatch OUT task) (retrieval phase). We used Gaussian-process factor analysis to visualize the neural trajectories of multiunit activity in MTL regions during the task. We also detected SWRs from the iEEG data in the hippocampus.

Findings

We found that the trajectory distance between phases of the Sternberg task was larger in the hippocampus compared to the entorhinal cortex and amygdala. Additionally, the trajectory distance between the encoding and retrieval phases was memory load dependent. Moreover, a transient trajectory increase was detected during SWRs. Finally, the trajectory direction of the hippocampus fluctuated between the encoding and retrieval states, and the balance of the fluctuation was shifted to the retrieval state during SWR periods.

Interpretation

Our results demonstrate the involvement of the hippocampus during a WM task. Furthermore, it is suggested that SWR in the retrieval phase plays a role in memory retrieval for a WM task. Our results provide new insight into the two-stage model of memory formation.
Plasticity of host cell organelles in response to Pb infection
Authors: Djavaheri Mohammad , Clothier Leah , Kindrachuk Colin , Borhan M. Hossein
Published: April 2023

Plasmodiophora brassicae(Pb) is the most important member of the plant pathogenic protist subgroup, Rhizaria.Pbis an obligate soil-borne plant root pathogen which makes the study ofPbbiology and its interaction with its host challenging. To overcome this challenge, we adopted an axenic cell culture method to study the interaction ofPbwith its host plantBrassica spp. at the cellular and molecular levels.Pb, during its life cycle within the host, was confined to the cytoplasm of the infected cells. Our results showed that upon Pb infection, the dynamics of the plant cell organelles including mitochondria, plastids, nuclei, vacuoles, vesicles were altered. Both Plant’s and parasite’sdiacylglycerol acyltransferases(DGAT) genes were highly expressed in the calli, which indicated a need for the oil accumulation at the switch between replication and growth stages of the pathogen. This notion was supported by the accumulation of oil bodies that were only observed inside the pathogen cells. Our results also indicated that starch was utilized by thePbin infected cells, an indication thatPbinduces cell viability by altering the host carbon metabolism. The ongoing dynamic changes in the infected plant cell organelles suggest that plant responds toPbinfection, through the induction of organellar plasticity.
Single-cell profiling reveals immune aberrations in progressive idiopathic pulmonary fibrosis
Authors: Unterman Avraham , Zhao Amy Y. , Neumark Nir , Schupp Jonas C. , Ahangari Farida , Cosme Carlos , Sharma Prapti , Flint Jasper , Stein Yan , Ryu Changwan , Ishikawa Genta , Sumida Tomokazu S. , Gomez Jose L. , Herazo-Maya Jose , Cruz Charles S. Dela , Herzog Erica L. , Kaminski Naftali
Published: April 2023

Rationale

Changes in peripheral blood cell populations have been observed but not detailed at single-cell resolution in idiopathic pulmonary fibrosis (IPF).

Objectives

To provide an atlas of the changes in the peripheral immune system in stable and progressive IPF.

Methods

Peripheral blood mononuclear cells (PBMCs) from IPF patients and controls were profiled using 10x Chromium 5’ single-cell RNA sequencing (scRNA-seq). Flow cytometry was used for validation. Protein concentrations of Regulatory T-cells (Tregs) and Monocytes chemoattractants were measured in plasma and lung homogenates from patients and controls.

Measurements and Main Results

Thirty-eight PBMC samples from 25 patients with IPF and 13 matched controls yielded 149,564 cells that segregated into 23 subpopulations, corresponding to all expected peripheral blood cell populations. Classical monocytes were increased in progressive and stable IPF compared to controls (32.1%, 25.2%, 17.9%, respectively, p<0.05). Total lymphocytes were decreased in IPF vs controls, and in progressive vs stable IPF (52.6% vs 62.6%, p=0.035). Tregs were increased in progressive IPF (1.8% vs 1.1%, p=0.007), and were associated with decreased survival (P=0.009 in Kaplan-Meier analysis). Flow cytometry analysis confirmed this finding in an independent cohort of IPF patients. Tregs were also increased in two cohorts of lung scRNA-seq. CCL22 and CCL18, ligands for CCR4 and CCR8 Treg chemotaxis receptors, were increased in IPF.

Conclusions

The single-cell atlas of the peripheral immune system in IPF, reveals an outcome-predictive increase in classical monocytes and Tregs, as well as evidence for a lung-blood immune recruitment axis involving CCL7 (for classical monocytes) and CCL18/CCL22 (for Tregs).
Migrant healthcare workers’ experiences and mobility patterns in a global health crisis: a qualitative study with Romania physicians working in Germany
Authors: Kuhlmann Ellen , Ungureanu Marius-Ionuț , Thilo Nancy , Fehr Leonie Mac , Cosma Nicoleta-Carmen , Brînzac Monica Georgina , Dopfer-Jablonka Alexandra
Published: April 2023

Introduction

Attention to the healthcare workforce has increased, yet comprehensive information on migrant healthcare workers is missing. This study focuses on migrant healthcare workers’ experiences and explores mobility patterns in the middle of a global health crisis, aiming to explore the capacity for circular migration and support effective equitable healthcare workforce policy.

Methods

Romanian physicians in Germany served as an empirical case study. We applied a qualitative explorative approach; interviews (n=21) were collected from mid of September to early November 2022 and content analysis was performed.

Results

Migrant physicians showed strong resilience during the COVID-19 crisis and rarely complained. Commitment to high professional standards and career development were major pull factors towards Germany, while perceptions of limited career choices, nepotism and corruption in Romania caused strong push mechanisms. We identified two major mobility patterns that may support circular migration policies: well-integrated physicians with a wish to give something back to their home country, and mobile cosmopolitan physicians who flexibly balance career opportunities and personal/family interests.

Conclusions

Health policy must establish systematic monitoring of the migrant HCWF including actor-centred approaches, support integration in destination countries as well as health system development in sending countries, and invest in evidence-based circular migration policy.
Do try this at home: Age prediction from sleep and meditation with large-scale low-cost mobile EEG
Authors: Banville Hubert , Jaoude Maurice Abou , Wood Sean U.N. , Aimone Chris , Holst Sebastian C. , Gramfort Alexandre , Engemann Denis-Alexander
Published: April 2023

EEG is an established method for quantifying large-scale neuronal dynamics which enables diverse real-world biomedical applications including brain-computer interfaces, epilepsy monitoring and sleep staging. Advances in sensor technology have freed EEG from traditional laboratory settings, making low-cost ambulatory or at-home assessments of brain function possible. While ecologically valid brain assessments are becoming more practical, the impact of their reduced spatial resolution and susceptibility to noise remain to be investigated. This study set out to explore the potential of at-home EEG assessments for biomarker discovery using the brain age framework and four-channel consumer EEG data. We analyzed recordings from more than 5200 human subjects (18-81 years) during meditation and sleep, focusing on the age prediction task. With cross-validatedR2scores between 0.3 - 0.5, prediction performance was within the range of results obtained by recent benchmarks focused on laboratory-grade EEG. While age prediction was successful from both meditation and sleep recordings, the latter led to higher performance. Analysis by sleep stage uncovered that N2-N3 stages contained most of the signal. When combined, EEG features extracted from all sleep stages gave the best performance, suggesting that the entire night of sleep contains valuable age-related information. Furthermore, model comparisons suggested that information was spread out across electrodes and frequencies, supporting the use of multivariate modeling approaches. Thanks to our unique dataset of longitudinal repeat sessions spanning 153 to 529 days from eight subjects, we finally evaluated the variability of EEG-based age predictions, showing that they reflect both trait- and state-like information. Overall, our results demonstrate that state-of-the-art machine learning approaches based on age prediction can be readily applied to real-world EEG recordings obtained during at-home sleep and meditation practice.
WITHDRAWN: The adhesion GPCR Adgrd1 is a prion protein receptor and a mediator of prion cytotoxicity
Authors: Lakkaraju Asvin KK , Tejero Oliver , Guixà-González Ramon , Cecco Elena De , Jungo Martina , Tsai Ching-Ju , Mastromartino Rocco , Marino Jacopo , Deupi Xavier , Hornemann Simone , Schertler Gebhard FX , Aguzzi Adriano
Published: April 2023

Withdrawal Statement

The authors have withdrawn their manuscript owing to several irregularities that have recently come to light. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Beyond resilience: towards antifragility?
Authors: Hillson David
Published: April 2023

Purpose

This opinion piece draws on the author's experience as a thought leader and expert practitioner in risk management to explore possible routes to applying antifragility in the organisational context, drawing on three metaphors from outside the business domain. Organisational responses to stressors have focused on the development of robustness and resilience. Recent global events have highlighted weaknesses in both these approaches. Antifragility might prove to be a valuable addition to the organisational armoury, but little progress has been made in finding practical implementations of the concept since it was first proposed over 10 years ago (Taleb, 2012).

Design/methodology/approach

Distinctions between robustness, resilience and antifragility are clarified. Descriptive analogy is used to expose ways in which antifragility might be implemented in practice, by comparison with three disparate metaphors.

Findings

Antifragility is currently not well understood or implemented, but it offers a potentially powerful additional organisational strategy in response to stress, to complement more traditional robustness and resilience approaches. Drawing on the three metaphors, four distinct types of antifragility are outlined which suggest how organisations might begin to develop antifragility in practice: innate antifragility, adaptive antifragility, rheopectic antifragility and emergent antifragility. These are presented as an organisational antifragility taxonomy that can support further research and practice.

Originality/value

The use of metaphor to explore antifragility is unique, providing insights into ways it might be applied.
Improving supply chain resilience from the perspective of information processing theory
Authors: Lu Qiang , Jiang Yu , Wang Yu
Published: April 2023

Purpose

Supply chain resilience (SCR) has attracted much attention in the context of the high uncertainty caused by the coronavirus disease 2019 (COVID-19), local regional conflicts and natural disasters. Based on information processing theory (IPT), this study investigates the role of supply chain information processing capability in enhancing SCR through supply chain governance (SCG), under different conditions of environmental uncertainty.

Design/methodology/approach

The hypothetical model is tested by using hierarchical regression on the primary samples collected from the Chinese manufacturing industry.

Findings

The results indicate that supply chain information processing capability has a significant positive effect on SCR. Also, SCG plays a mediating role between supply chain information processing capability and SCR. Furthermore, environmental uncertainty positively moderates the effect of supply chain information acquisition and supply chain information analysis on relational governance. However, environmental uncertainty only positively moderates the effect of supply chain information analysis on contractual governance.

Originality/value

This is the first study to explain the effect of information processing capability on SCR from the supply chain perspective, while also exploring the mediating role of SCG between SCR and supply chain information processing capacity, based on IPT.
Exploring drivers of business performance in web-enabled supply chains: the role of web technology training and supply chain integration
Authors: Mora-Monge Carlo A. , Fatoki Jimoh , Arslan Faruk , Rauniar Rupak
Published: April 2023

Purpose

Grounded on the resource-based and dynamic capability views and the contingency theories, this study examines the direct and indirect effects of web technology training (WTT) and web-enabled transaction use (WTU) on business performance (BPE) through internal supply chain integration (ISCI) and supplier supply chain integration (SSCI).

Design/methodology/approach

Based on survey data collected from a sample of 175 respondents in the USA, the authors used structural equation modeling with AMOS 24.0 to test the measurement model for validity, reliability and the conceptual model for hypothesized structural relationships.

Findings

The results reveal that WTT significantly impacts WTU, which, in turn, has a significant direct relationship with BPE. Further, WTU indirectly affects BPE through SSCI. Additionally, ISCI has a significant direct effect on SSCI.

Practical implications

The findings support the relationship between WTT and BPE via WTU SCI. Managers are advised to develop ongoing capabilities in WTT to maximize the value of WTU to enhance the ISCI and SSCI operations, thus leading to improvements in BPE.

Originality/value

The research contributes to the supply chain literature by empirically demonstrating the usefulness of WTT in improving WTU use and BPE through effective ISCI and SSCI.
Robotising, but how? Evidence from the automotive sector in South Africa
Authors: Anzolin Guendalina , Andreoni Antonio
Published: April 2023

Purpose

This paper focuses on understanding firm-level determinants of industrial robots' adoption and how these determinants result in heterogenous processes of robotisation across firms within the same sector. The paper presents results from in-depth case studies of final assemblers in the South African automotive sector.

Design/methodology/approach

The research has been conducted through multiple case studies with a focus on final assemblers. During the case studies, as well as before and after it, data coming from in-depth semi-structured interviews were triangulated with secondary data available from the international database on industrial robots' adoption and documents provided by firms and institutions.

Findings

This paper identifies three firm-level determinants of robotisation – i.e. modularity of the production process, flexibility in the use of technology and stability in product design. The results also showed that firms' robotisation depend on each of these determinants as well as their interdependence. The authors introduce a framework to study interdependence between these technology–organisational choices, which reveals heterogenous patterns of technology deployment and related managerial implications.

Originality/value

This research introduces a new framework on factors driving industrial robotisation – a key digital production technology – and offers empirical evidence of the heterogenous deployment of this technology. The authors identify two main manufacturing approaches to robotisation in the automotive sector: one in which the firm designs a robotised process around a certain product design – i.e. the German/American way and one in which the firm designs its product based on certain robotised processes – i.e. the Japanese way. These findings are valuable for both industry, operational research and the scientific community as they reveal heterogeneity on the “how” of robotisation and implications for manufacturing technology management.
Microfoundations of dynamic capabilities: a systematic review and a multilevel framework
Authors: Chen Yantai , Liu Lu , Li Weiwen , Xie Zaiyang , Wei Chenchen
Published: April 2023

Purpose

Microfoundations have become an effective approach for capability scholars to explore the heterogeneity of organizational results. Since the early pioneering work of scholars such as Felin and Foss, the microfoundations of strategic organization had not been extensively studied until 2010. The theoretical and empirical literature associated with the microfoundations of dynamic capabilities has developed rapidly. However, the diversity and fragmentation of micro-elements lead to a lack of a relatively consistent understanding of microfoundations, the study purpose is to aggregate the associated scattered terminology into a cohesive discussion.

Design/methodology/approach

A systematic literature review was conducted on research papers published between 2000 and 2022 using a hybrid methodology that included bibliometric and content analysis.

Findings

The authors suggest that this line of research can be divided into three stages. The study further develop a framework delineating the main components and mechanism involved in the microfoundations of dynamic capabilities, which in turn help us distill research gaps and opportunities for future work.

Originality/value

The authors construct a framework that can serve as a coherent research platform for further knowledge development. In the framework, the authors highlight that the research of group constructs, culture and leadership, data-driven topics are valuable for our understanding of the microfoundations of dynamics capabilities.
Bringing the Emigration State Back In
Authors: Foks Freddy
Published: April 2023

The decades between 1948 and 1980 are often remembered as a time of mass immigration, yet almost 2 million more people left Britain than arrived in those years. Mass emigration has been an enduring part of Britain's modern history and this article explores its effects on British politics. The two world wars, the turn to tariffs, joining the EEC and leaving the EU: at these critical junctures, Britain's overseas diaspora was mobilised to reshape domestic politics and to transform the UK's global political economy. Charting the rise, fall and afterlife of Britain's ‘emigration state’ can contribute to our understanding of these events and help researchers analyse the effects of racism and empire on modern British politics.
Interactional power and support in digital inclusion of an adult with intellectual disabilities: a case study analysis
Authors: Chadwick Darren D. , Buell Susan
Published: April 2023

Digital inclusion of people with intellectual disabilities is not commensurate with those without disabilities. Societal, political, financial, individual and interpersonal barriers help explain this disparity. Caregivers can act as both support and gatekeeper to internet access and use by adults with intellectual disabilities. This study investigated micro‐level interpersonal factors influencing access and use of the internet by an adult with intellectual disabilities to explore the balance and interplay of power and support around the processes of digital inclusion and online risk taking. Taking a case study approach, perspectives of three key stakeholders were gathered via interviews: the person with intellectual disabilities, his mother and a paid support worker. Perspectives and experiences were contrasted using systemic functional linguistic analysis of discourse to explore the ways power and support were represented in the language of negotiated digital inclusion. Dynamics between the parent and person with intellectual disabilities and between the parent and paid staff clearly influenced processes of digital inclusion and were affected by varying priorities, positions and perceptions of power to allow, disallow and monitor access and use of the internet. These had the power to shape and drive internet access. Language choices by the person with intellectual disabilities showed that he was not fully aware of the risks involved in engaging with certain aspects of digital inclusion but how he spoke about the internet indicated some autonomy in technology use. Supporting the development of digital competence, confidence and resilience in people with learning disabilities should be combined with support to increase self‐awareness regarding digital risk. Those supporting people with intellectual disabilities towards digital inclusion need additional guidance on how to do this effectively for the people they support.
The emerging role of auxins as bacterial signal molecules: Potential biotechnological applications
Authors: Krell Tino , Gavira José A. , Roca Amalia , Matilla Miguel A.
Published: April 2023

Microorganisms are exposed in their natural niches to a wide diversity of signal molecules. Specific detection of these signals results in alterations in microbial metabolism and physiology. Auxins like indole‐3‐acetic acid are key phytohormones that regulate plant growth and development. Nonetheless, auxin biosynthesis is not restricted to plants but is ubiquitous in all kingdoms of life. This wide phylogenetic distribution of auxins production, together with the diversity of regulated cellular processes, have made auxins key intra‐ and inter‐kingdom signal molecules in life modulating, for example microbial physiology, metabolism and virulence. Despite their increasing importance as global signal molecules, the mechanisms by which auxins perform their regulatory functions in microorganisms are largely unknown. In this article, we outline recent research that has advanced our knowledge of the mechanisms of bacterial auxin perception. We also highlight the potential applications of this research in aspects such as antibiotic production, biosensor design, plant microbiome engineering and antivirulence therapies.
Robust rhythm reporting will advance ecological and evolutionary research
Authors: Hersh Taylor A. , Ravignani Andrea , Burchardt Lara S.
Published: April 2023

Rhythmicity in the millisecond to second range is a fundamental building block of communication and coordinated movement. But how widespread are rhythmic capacities across species, and how did they evolve under different environmental pressures? Comparative research is necessary to answer these questions but has been hindered by limited crosstalk and comparability among results from different study species.

Most acoustics studies do not explicitly focus on characterising or quantifying rhythm, but many are just a few scrapes away from contributing to and advancing the field of comparative rhythm research. Here, we present an eight‐level rhythm reporting framework which details actionable steps researchers can take to report rhythm‐relevant metrics. Levels fall into two categories: metric reporting and data sharing. Metric reporting levels include defining rhythm‐relevant metrics, providing point estimates of temporal interval variability, reporting interval distributions, and conducting rhythm analyses. Data sharing levels are: sharing audio recordings, sharing interval durations, sharing sound element start and end times, and sharing audio recordings with sound element start/end times.

Using sounds recorded from a sperm whale as a case study, we demonstrate how each reporting framework level can be implemented on real data. We also highlight existing best practice examples from recent research spanning multiple species. We clearly detail how engagement with our framework can be tailored case‐by‐case based on how much time and effort researchers are willing to contribute. Finally, we illustrate how reporting at any of the suggested levels will help advance comparative rhythm research.

This framework will actively facilitate a comparative approach to acoustic rhythms while also promoting cooperation and data sustainability. By quantifying and reporting rhythm metrics more consistently and broadly, new avenues of inquiry and several long‐standing, big picture research questions become more tractable. These lines of research can inform not only about the behavioural ecology of animals but also about the evolution of rhythm‐relevant phenomena and the behavioural neuroscience of rhythm production and perception. Rhythm is clearly an emergent feature of life; adopting our framework, researchers from different fields and with different study species can help understand why.
Ubiquitin C‐terminal hydrolase L1 after out‐of‐hospital cardiac arrest
Authors: Wihersaari Lauri , Reinikainen Matti , Tiainen Marjaana , Bendel Stepani , Kaukonen Kirsi‐Maija , Vaahersalo Jukka , Romppanen Jarkko , Pettilä Ville , Skrifvars Markus B. ,   The FINNRESUSCI Study Group
Published: April 2023

Background

We studied the prognostic ability of serum ubiquitin C‐terminal hydrolase L1 (UCH‐L1) after out‐of‐hospital cardiac arrest (OHCA), compared to that of neuron‐specific enolase (NSE).

Methods

In this post‐hoc analysis of the FINNRESUSCI study, we measured serum concentrations of UCH‐L1 in 249 OHCA patients treated in 21 Finnish intensive care units in 2010–2011. We evaluated the ability of UCH‐L1 to predict unfavourable outcome at 12 months (defined as cerebral performance category 3–5) by assessing the area under the receiver operating characteristic curve (AUROC), in comparison with NSE.

Results

The concentrations of UCH‐L1 were higher in patients with unfavourable outcome than for those with favourable outcome: median concentration 10.8 ng/mL (interquartile range, 7.5–18.5 ng/mL) versus 7.8 ng/mL (5.9–11.8 ng/mL) at 24 h (p < .001), and 16.2 ng/mL (12.2–27.7 ng/mL) versus 11.5 ng/mL (9.0–17.2 ng/mL) (p < .001) at 48 h after OHCA. For UCH‐L1 as a 12‐month outcome predictor, the AUROC was 0.66 (95% confidence interval, 0.60–0.73) at 24 h and 0.66 (0.59–0.74) at 48 h. For NSE, the AUROC was 0.66 (0.59–0.73) at 24 h and 0.72 (0.65–0.80) at 48 h. The prognostic ability of UCH‐L1 was not different from that of NSE at 24 h (p = .82) and at 48 h (p = .23).

Conclusion

Concentrations of UCH‐L1 in serum were higher in patients with unfavourable outcome than in those with favourable outcome. However, the ability of UCH‐L1 to predict unfavourable outcome after OHCA was only moderate and not superior to that of NSE.
Buildup from birth onward of short telomeres in human hematopoietic cells
Authors: Lai Tsung‐Po , Verhulst Simon , Savage Sharon A. , Gadalla Shahinaz M. , Benetos Athanase , Toupance Simon , Factor‐Litvak Pam , Susser Ezra , Aviv Abraham
Published: April 2023

Telomere length (TL) limits somatic cell replication. However, the shortest among the telomeres in each nucleus, not mean TL, is thought to induce replicative senescence. Researchers have relied on Southern blotting (SB), and techniques calibrated by SB, for precise measurements of TL in epidemiological studies. However, SB provides little information on the shortest telomeres among the 92 telomeres in the nucleus of human somatic cells. Therefore, little is known about the accumulation of short telomeres with age, or whether it limits the human lifespan. To fill this knowledge void, we used the Telomere‐Shortest‐Length‐Assay (TeSLA), a method that tallies and measures single telomeres of all chromosomes. We charted the age‐dependent buildup of short telomeres (<3 kb) in human hematopoietic cells from 334 individuals (birth‐89 years) from the general population, and 18 patients with dyskeratosis congenita‐telomere biology disorders (DC/TBDs), whose hematopoietic cells have presumably reached or are close to their replicative limit. For comparison, we also measured TL with SB. We found that in hematopoietic cells, the buildup of short telomeres occurs in parallel with the shortening with age of mean TL. However, the proportion of short telomeres was lower in octogenarians from the general population than in patients with DC/TBDs. At any age, mean TL was longer and the proportion of short telomeres lower in females than in males. We conclude that though converging to the TL‐mediated replicative limit, hematopoietic cell telomeres are unlikely to reach this limit during the lifespan of most contemporary humans.
The One Health approach for allergic diseases and asthma
Authors: Jutel Marek , Mosnaim Giselle S. , Bernstein Jonathan A. , del Giacco Stefano , Khan David A. , Nadeau Kari C. , Pali‐Schöll Isabella , Torres Maria J. , Zemelka‐Wiacek Magdalena , Agache Ioana
Published: April 2023

The One Health approach is a collaborative and interdisciplinary strategy with focal point on human, animal, and environmental health interconnections. One Health can support the advanced management of allergic diseases and asthma, as complex, multifactorial diseases driven by interactions between the resilience response to the exposome. According to the One Health concept allergic diseases and asthma arising from exposures to a wide range of allergens, infectious agents and irritants (such as pollutants) occurring indoors and outdoors can be heavily influenced by environmental health (air, water, and soil quality) intermingled with animal health. These are currently heavily impacted by climate change, land use, urbanization, migration, overpopulation, and many more. Thus, a coordinated response to address the underlying factors that contribute to the development of allergic diseases and asthma needs to focus on the environment, human, and animal health altogether. Collaborative efforts across multiple sectors, including public health, veterinary medicine, environmental science, and community engagement are thus needed. A wide range of activities, including monitoring and surveillance of environmental and health data, targeted interventions to reduce exposures to allergens and irritants, and research on the underlying mechanisms that drive the development of allergic diseases and asthma are needed to move the field forward. In this consensus document elaborated by the European Academy of Allergy and Clinical Immunology (EAACI) and American Academy of Allergy, Asthma, and Immunology (AAAAI) under the practical allergy (PRACTALL) series, we provide insights into the One Heath approach aiming to provide a framework for addressing the complex and multifactorial nature of allergic diseases and asthma.
The environmental impact of pharmaceuticals in Italy: Integrating healthcare and eco‐toxicological data to assess and potentially mitigate their diffusion to water supplies
Authors: Giunchi Valentina , Fusaroli Michele , Linder Elkanah , Villén Johanna , Wettermark Björn , Nekoro Marmar , Raschi Emanuel , Lunghi Carlotta , Poluzzi Elisabetta
Published: April 2023

Pharmaceuticals can reach the environment at all stages of their lifecycle and accumulate in the ecosystem, potentially reaching toxic levels for animals and plants. In recent years, efforts have been made to map and control this hazard. Assessing country‐specific environmental risks could drive regulatory actions towards eco‐friendlier drug utilization and disposal practices. By starting from a list of 25 environmentally hazardous pharmaceuticals developed by Region Stockholm, we integrated eco‐toxicological and 2019–2021 Italian drug utilization data to estimate the environmental impact of pharmaceuticals in Italy. We calculated the risk as the ratio between the predicted environmental concentration (PEC) and the predicted no‐effect concentration (PNEC). We found a high risk for levonorgestrel, ciprofloxacin, amoxicillin, azithromycin, venlafaxine, sertraline and diclofenac and a moderate risk for ethinyloestradiol, oestradiol and clarithromycin. This analysis can be periodically performed to identify the pharmaceuticals with the highest risk for the environment and ascertain if containment measures should be implemented.
Ethicizing history. Bioethical representations of Nazi medicine
Authors: Schütz Mathias , Braswell Harold
Published: April 2023

The article presents and analyzes different approaches of U.S. bioethicists in comprehending the Nazi medical crimes after 1945. The account is divided into two sections: one dealing with discussions on research ethics and the Nuremberg Code up until the 1970s and the other ranging from the 1970s to the present and highlighting bioethics' engagement with Nazi analogies. The portrayal of different bioethical scholars, institutions, and documents—most notably Henry K. Beecher, Jay Katz, the Belmont Report, the Hastings Center, Arthur L. Caplan, and Robert M. Veatch—provides a nuanced interpretation of the motives that bioethicists held and the strategies that they applied to establish an understanding of the Nazi medical crimes and their relation to contemporary bioethical issues. In this, the different approaches shared a common goal: To integrate the Nazi medical crimes into an ethical framework by means of selective acknowledgments and representation of their history.
Ethics of live uterus donor compensation
Authors: Lee Ji‐Young
Published: April 2023

In this paper, I claim that live uterus donors ought to be considered for the possibility of compensation. I support my claim on the basis of comparable arguments which have already been applied to gamete donation, surrogacy, and other kinds of organ donation. However, I acknowledge that there are specificities associated with uterus donation, which make the issue of incentive and reward a harder ethical case relative to gamete donation, surrogacy, and other kinds of organ donation. Ultimately, I contend that while reimbursement for the costs incurred by live uterus donors should be treated as a necessary ethical minimum, how much further we ought to remunerate uterus donations remains an open question.
The effects of MYC on exosomes derived from cancer cells in the context of breast cancer
Authors: Celikkaya Busra , Durak Taner , Farooqi Ammad Ahmad , Inci Kubilay , Tokgun Pervin Elvan , Tokgun Onur
Published: April 2023

MYC amplification and overexpression in breast cancer occur 16% and 22%, respectively, and MYC has a linchpin role in breast carcinogenesis. Emerging evidence has started to shed light on central role of MYC in breast cancer progression. On the contrary, tumor‐derived exosomes and their cargo molecules are required for the modulation of the tumor environment and to promote carcinogenesis. Still, how MYC regulates tumor‐derived exosomes is still a matter of investigation in the context of breast cancer. Here, we investigated for the first time how MYC affects the biological functions of normal breast cells cocultured with exosomes derived from MYC‐expression manipulated breast cancer cells. Accordingly, exosomes were isolated from MCF‐7 and MDA‐MB‐231 cells that MYC expression was manipulated through siRNAs or lentiviral vectors by using exosome isolation reagent. Then, normal breast epithelial MCF‐10A cells were treated with breast cancer cell‐derived exosomes. The cellular activity of MCF‐10A was investigated by cell growth assay, wound healing assay, and transwell assay. Our results suggested that MCF‐10A cells treated with exosomes derived from MYC‐overexpressing breast cancer cells demonstrated higher proliferation and migration capability compared with nontreated cells. Likewise, MCF‐10A cells treated with exosomes derived from MYC‐silenced cancer cells did not show high proliferation and invasive capacity. Overall, MYC can drive the functions of exosomes secreted from breast cancer cells. This may allow exploring a new mechanism how tumor cells regulate cancer progression and modulate tumor environment. The present study clears the way for further researches as in vivo studies and multi‐omics that clarify exosomal content in an MYC‐dependent manner.
Post‐COVID‐19 vaccination Guillain–Barré syndrome with sensory ataxia, gaze‐evoked nystagmus, mental‐status change and positive pathological reflex
Authors: Saso Nanami , Toru Shuta , Iwasaru Keiichi , Yokote Hiroaki , Uchihara Toshiki
Published: April 2023

Background

Various neurological disorders have been reported after vaccination against coronavirus disease 2019, one of which is Guillain–Barré Syndrome (GBS).

Case Presentation

We report a case of a 73‐year‐old woman who developed GBS and extra‐GBS manifestations 19 days after the second dose of BNT162b2 mRNA vaccine. She presented lower limb predominant muscle weakness and loss of tendon reflexes. Nerve conduction study showed acute motor and sensory axonal neuropathy. In addition, she developed notable deep sensory ataxia, and showed positive pathological reflex, gaze‐evoked nystagmus and altered consciousness, which suggested brainstem involvement.

Conclusions

This is the first coronavirus disease 2019 vaccine‐related GBS complicated with such central nervous system manifestations.
Electromyography in the prognostication of recovery in patients with acute peripheral facial nerve palsy: A systematic review
Authors: Petrides George Andrew , Hayler Raymond , Lee Jennifer W. , Jankelowitz Stacey , Low Tsu‐Hui
Published: April 2023

Objectives

Needle electromyography (EMG) may be used to characterise the severity of the injury in acute peripheral facial nerve palsy (FNP) to predict recovery and guide management, but its prognostic value and clinical utility remain controversial. The aim of this systematic review was to evaluate the role of EMG to prognosticate the recovery of facial motor function in patients with acute peripheral FNP.

Design

A comprehensive search strategy was applied in PubMed, Embase, and Web of Science based on Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. The main outcome measure was the accuracy of EMG in predicting long‐term facial function at least 6 months following symptom onset.

Results

Eleven studies were included comprising 3837 participants, with 91.6% of these diagnosed with Bell's palsy (BP). In BP patients, the positive predictive value and negative predictive value for a good outcome based on EMG findings ranged from 82.1% to 100% and 66.7% to 80.5%, respectively, with two out of three studies finding that EMG remained a significant predictor of the outcome on multivariate analysis. Three studies addressed the role of EMG in non‐idiopathic FNP with two of these studies supporting EMG to predict prognosis.

Conclusions

EMG is a useful tool to gain insight into the likely outcome to guide management decisions and counsel patients on their expectations, particularly in BP. However, given inconsistencies in its application and lack of evidence around non‐idiopathic FNP, it should not currently be relied on to predict recovery. Ultimately, its prognostic value and widespread adoption are dependent on the implementation of a clear and standardised protocol in future high‐quality studies and routine clinical settings.
Digital health technology derived measures: Biomarkers or clinical outcome assessments?
Authors: Izmailova Elena S. , Demanuele Charmaine , McCarthy Marie
Published: April 2023

Digital health technologies (DHTs) present unique opportunities for clinical evidence generation but pose certain challenges. These challenges stem, in part, from existing definitions of drug development tools, which were not created with DHT‐derived measures in mind. DHT‐derived measures can be leveraged as either clinical outcome assessments (COAs) or as biomarkers since they share properties with both categories of drug development tools. Examples from the literature indicate a variety of applications for DHT‐derived data, including capturing disease physiology, symptom tracking, or response to therapies. The distinction between the categorization of DHT‐derived measures as COAs or as biomarkers can be very fine, with terminology variability among regulatory authorities. This has significant implications for integration of DHT‐derived measures in clinical trials, leading to confusion regarding the evidence required to support these tools' use in drug development. There is a need to amend definitions and create clear evidentiary requirements to support broad adoption of these new and innovative tools. The biopharma industry, the technology sector, consulting businesses, academic researchers, and regulators need a dialogue via multi‐stakeholder collaborations to clarify questions around DHT‐derived measures, to unify definitions, and to create the foundations for evidentiary package requirements, providing a path forward to predictable results.