bluuebunny/crossref_metadata_2025 huggingface dataset:
DegCre: Probabilistic association of differential gene expression with regulatory regions
Authors: Roberts Brian S. , Cooper Gregory M. , Myers Richard M.
Published: October 2023

Differential gene expression in response to perturbations is mediated at least in part by changes in binding of transcription factors (TFs) and other proteins at specific genomic regions. Association of these cis-regulatory elements (CREs) with their target genes is a challenging task that is essential to address many biological and mechanistic questions. Many current approaches rely on chromatin conformation capture techniques that identify spatial proximity between genomic sites to establish CRE-to-gene associations. These methods can be effective but have limitations, including resolution, minimal detectable interaction distance, and cost. As an alternative, we have developed DegCre, a non-parametric method that evaluates correlations between measurements of perturbation-induced differential gene expression and differential regulatory signal at CREs to score possible CRE-to-gene associations. It has several unique features, including the ability to: use any type of CRE activity measurement; yield probabilistic scores for CRE-to-gene pairs; and assess CRE-to-gene pairings across a wide range of sequence distances. We apply DegCre to three data sets, each employing different perturbations and containing a variety of regulatory signal measurements, including chromatin openness, histone modifications, and TF occupancy. To test their efficacy, we compare DegCre associations to HiC loop calls and to CRISPR validated interactions, with both yielding good agreement. We demonstrate the identification of perturbation direct target genes with DegCre confirm the results with previous reports. DegCre is a novel approach to the association of CREs to genes from a perturbation-differential perspective, with strengths that are complementary to existing approaches and allow for new insights into gene regulation.
An anthropology of impossible futures
Authors: Goodale Mark
Published: October 2023

This guest editorial explores the intricate relationship between anthropology and the concept of impossible futures, focusing on the global push towards electric vehicles (EVs) and the lithium energy assemblage. Drawing inspiration from a lecture by palaeobiologist Mark Williams, a member of the Anthropocene Working Group (AWG), the author reflects on the Anthropocene epoch and the human‐caused transformations of the earth. It examines the European Green Deal's impact on the automotive industry, the global struggle for lithium and the paradoxes of green technology investments. It questions the feasibility of the envisioned future, emphasizing the contradictions within global capitalism and the potential futility of climate change mitigation efforts. The author calls for a reorientation in anthropological research, focusing on novel forms of unity, solidarity, justice and interspecies bonds in the face of seemingly impossible conditions. It concludes with a contemplation of anthropology's role in translating and understanding social life in the context of unattainable futures without losing sight of the discipline's contested past and inherent hope.
Waste and its masquerades: On the production of urban natures in Kochi, India
Authors: Barlow Matt
Published: October 2023

Waste management has been a focal point in ethnographic research, yet its aesthetic and ideological facets in shaping ‘urban nature’ have been largely overlooked. The article delves into a comparative study of two parks in Kochi, a South Indian city, examining the intersection of environmental aesthetics, infrastructural visibility, and the conceptualization of urban nature. Through this juxtaposition, the study elucidates how divergent waste management strategies reflect broader ideologies concerning urban environments and their role in urban development initiatives. The article posits that waste and its management are not peripheral elements in the urban experience of nature; rather, they are integral components that shape it.
A prospective comparison of a modified miniaturised hand‐held epifluorescence microscope and touch imprint cytology for evaluation of axillary sentinel lymph nodes intraoperatively in breast cancer patients
Authors: Chen Jia‐jian , Yu Bao‐hua , Shen Ti‐jing , Wang Ying , Ren Fei , Yang Li‐rui , Dong Yuan , Zheng Ming‐jie , Hao Shuang , Yang Wen‐tao , Wu Jiong
Published: October 2023

Background

The management of axillary lymph nodes in early‐stage breast cancer patients has changed considerably, with the primary focus shifting from the examination of sentinel lymph nodes (SLNs) to toward the detection of all macro‐metastases. However, current methods, such as touch imprint cytology (TIC) and frozen sections, are inadequate for clinical needs. To address this issue, we proposed a novel miniaturised epifluorescence widefield microscope (MEW‐M) to assess SLN status intraoperatively for improved diagnostic efficiency.

Methods

A prospective, side‐by‐side comparison of intraoperative SLN evaluation between MEW‐M and TIC was performed.

Results

A total of 73 patients with 319 SLNs consecutive enrolled in this study. MEW‐M showed significantly superior image quality compared to TIC (median score 3.1 vs 2.1, p < 0.0001) and had a shorter time to issue results (10.3 vs 19.4 min, p < 0.0001). Likelihood ratio analysis illustrated that the positive likelihood ratio value of MEW‐M compared with TIC was infinitely great vs 52.37 (95% CI, 21.96‐124.90) in model 1 (classifying results into negative/positive), infinitely great vs 52.37 (95% CI, 21.96‐124.90) in model 2 (classifying results into macro‐metastasis/others, and TIC results followed the same classification as model 1), respectively. Similarly, the negative likelihood ratio values of MEW‐M compared with TIC were 0.055 (95% CI, 0.018‐0.160) and 0.074 (95% CI, 0.029‐0.190) in model 1; and 0.019 (95% CI, 0.003‐0.130) vs 0.020 (95% CI, 0.003‐0.140) in model 2, respectively.

Conclusions

MEW‐M is a promising technique that can be utilised to provide a rapid and accurate intraoperative assessment of SLN in a clinical setting to help improve decision‐making in axillary surgery.
Understanding how self‐management education and support programmes for type 2 diabetes are expected to change behaviour: A document analysis of two programmes
Authors: Carvalho Márcia , Byrne Molly , Kenny Eanna , Caba Molly , Hadjiconstantinou Michelle , Dunbar Jenny , Powell Sinéad , McSharry Jenny
Published: October 2023

Aims

Attendance at diabetes self‐management education and support (DSMES) programmes for type 2 diabetes is associated with positive outcomes, but the impact on some outcomes is inconsistent and tends to decline over time. Understanding the active ingredients of effective programmes is essential to optimise their effectiveness. This study aimed to (1) retrospectively identify behaviour change techniques (BCTs), mechanisms of action (MoAs) and intervention functions in two DSMES programmes, the Community‐Oriented Diabetes Education and the Diabetes Education and Self‐Management for Ongoing and Newly Diagnosed and (2) examine variation in content between programmes.

Methods

A multiple case study approach, including a documentary analysis of the programme materials, was conducted. Materials were coded using the BCT Taxonomy v1, the Mode of Delivery Ontology v1 and the Intervention Source Ontology v1. The Behaviour Change Wheel guidance and the Theory and Techniques tool were used to identify intervention functions and MoAs. Programme stakeholders provided feedback on the findings.

Results

Thirty‐four BCTs were identified across the programmes, with 22 common to both. The identified BCTs were frequently related to ‘goals and planning’, ‘feedback and monitoring’ and ‘natural consequences’. BCTs were linked with 15 MoAs, predominantly related to reflective motivation (‘beliefs about capabilities’ and ‘beliefs about consequences’) and psychological capability (‘knowledge’). BCTs served six intervention functions, most frequently ‘education’, ‘enablement’ and ‘persuasion’.

Conclusions

Although both programmes included several BCTs, some BCTs were rarely or never used. Additional BCTs could be considered to potentially enhance effectiveness by addressing a wider range of barriers.
Use of the synergist piperonyl butoxide can slow the development of alpha‐cypermethrin resistance in the whitefly Bemisia tabaci
Authors: Zimmer C. T. , Panini M. , Singh K. S. , Randall E. L. , Field L. M. , Roditakis E. , Mazzoni E. , Bass C.
Published: October 2023

The development of insecticide resistance in insect pests of crops is a growing threat to sustainable food production, and strategies that slow the development of resistance are therefore urgently required. The insecticide synergist piperonyl butoxide (PBO) inhibits certain insect detoxification systems and so may delay the evolution of metabolic resistance. In the current study we characterized resistance development in the silverleaf whitefly, Bemisia tabaci, after selection with either a neonicotinoid (thiacloprid) or pyrethroid (alpha‐cypermethrin) insecticide alone or in combination with PBO. Resistance development was significantly suppressed (> 60%) in the line selected with alpha‐cypermethrin + PBO compared to the line selected with alpha‐cypermethrin alone. RNA sequencing (RNAseq) analyses revealed an increase in frequency of a knock‐down resistance mutation but no differentially expressed genes were identified that could explain the sensitivity shift. No significant difference was observed in the level of resistance between the thiacloprid and thiacloprid + PBO selected lines, and RNA sequencing (RNAseq) analyses revealed that the cytochrome P450 monooxygenase CYP6CM1, known to metabolize neonicotinoids, was significantly upregulated (>10‐fold) in both lines. The findings of this study demonstrate that PBO used in combination with certain insecticides can suppress the development of resistance in a laboratory setting; however, the mechanism by which PBO supresses resistance development remains unclear.
Corporate Governance in China
Authors: Morck Randall , Yeung Bernard
Published: October 2023

Since the death of Mao Tse Tung in 1976, China has achieved unprecedented economic growth. Per capita GDP has increased from one of the lowest in the world to a level that is firmly in the middle of the international ranks. But can China continue on the growth path of the last four decades? The question arises because of the tendency of developing economies, having achieved periods of “catch‐up” growth, to become mired in a “middle‐income trap” that appears to stem from a variety of factors, including the tendency for elites and oligarchs to protect their own interests by blocking competition.

China's success to date has come without many of the key institutions—notably, private property rights, shareholder‐centered corporate governance, and a well‐functioning impartial legal system—that most Western economists believe essential to long‐term success. China's description of its system as “market socialism with Chinese characteristics” is an accurate one. Markets, not decrees, set most prices, while the state, in the form of the Communist Party, continues to control the careers of SOEs' senior executives, regulators, and government officials, and retains “options” to intervene in a large variety of financial and corporate affairs as well as judicial processes and decisions.

Chinese history underpins the system in the sense that the Party is, at least in some respects, a genuine meritocracy reminiscent of the imperial civil service of past eras. And the authors raise the possibility that the Party's Leading Role has actually contributed to China's extraordinary growth not only by fostering such a meritocracy, but by initiating and presiding over what development economists describe as a “Big Push,” a coordinated simultaneous development of many firms in multiple industries that was necessary to transform a subsistence agricultural economy into a modern industrial one.

But for all the effectiveness of China's “Big Push,” the authors close by expressing doubt that China can continue to rise into the world's economic upper ranks until it adopts the substance as well as the form of those missing institutions that, they argue, are the only well‐marked path to high‐income status.
CARE Conference Hong Kong Polytechnic University, June 9, 2014: Equity Financing for Early‐Stage Companies in China
Authors: Jia Ning
Published: October 2023

Many of the smaller private‐sector Chinese companies in their entrepreneurial growth stage are now being funded by Chinese venture capital (VC) and private equity (PE) firms. In contrast to western VC markets, where institutional investors such as pension funds and endowments have been the main providers of capital, in China most capital for domestic funds has come from private business owners and high net worth individuals. As relatively new players in the market who are less accustomed to entrusting their capital to fund managers for a lengthy period of time, Chinese VCs and their investors have shown a shorter investment horizon and demanded a faster return of capital and profits.

In an attempt to explain this behavior, Paul Gompers and Josh Lerner of Harvard Business School have offered a “grandstanding hypothesis” that focuses on the incentives of younger, less established VCs to push their portfolio companies out into the IPO market as early as they can—and thus possibly prematurely—to establish a track record and facilitate future fundraising. This explanation is supported by the under‐performance of Chinese VC‐backed IPOs that has been documented by the author's recent research.

Although they continue to offer significant opportunities for global investors, China's VC and PE markets still face many challenges. The supervisory system and legal environment need further improvement, and Chinese funds need to find a way to attract more institutional investors—a goal that can and likely will be promoted through government inducements.
Research Reviews: Advances in methods for evaluating child and adolescent mental health interventions
Authors: Pickles Andrew , Edwards Danielle , Horvath Levente , Emsley Richard
Published: October 2023

Backround

The evidence base for interventions for child mental health and neurodevelopment is weak and the current capacity for rigorous evaluation limited. We describe some of the challenges that make this field particularly difficult and expensive for evaluation studies.

Methods

We describe and review the use of novel study designs and analysis methodology for their potential to improve this situation.

Results

While several novel designs appeared ill‐suited to our field, systematic review found others that offered potential but had yet to be widely adopted, some not at all.

Conclusions

While funding is inevitably a constraint, we argue that improvements in the evidence base of both current and new treatments will only be achieved by the adoption of a number of these new technologies and study designs, the consistent application of rigorous constructive but demanding standards, and the engagement of the public, patients, clinical and research services to build a design, recruitment, and analysis infrastructure.
Acne microbiome: From phyla to phylotypes
Authors: Dreno Brigitte , Dekio Itaru , Baldwin Hilary , Demessant Anne Laure , Dagnelie Marie‐Ange , Khammari Amir , Corvec Stephane
Published: October 2023

Acne vulgaris is a chronic inflammatory skin disease with a complex pathogenesis. Traditionally, the primary pathophysiologic factors in acne have been thought to be: (1) altered sebum production, (2) inflammation, (3) excess keratinization and (4) colonization with the commensal Cutibacterium acnes. However, the role of C. acnes has been unclear, since virtually all adults have C. acnes on their skin yet not all develop acne. In recent years, understanding of the role of C. acnes has expanded. It is still acknowledged to have an important place in acne pathogenesis, but evidence suggests that an imbalance of individual C. acnes phylotypes and an alteration of the skin microbiome trigger acne. In addition, it is now believed that Staphylococcus epidermidis is also an actor in acne development. Together, C. acnes and S. epidermidis maintain and regulate homeostasis of the skin microbiota. Antibiotics, which have long been a staple of acne therapy, induce cutaneous dysbiosis. This finding, together with the long‐standing public health edict to spare antibiotic use when possible, highlights the need for a change in acne management strategies. One fertile direction of study for new approaches involves dermocosmetic products that can support epidermal barrier function and have a positive effect on the skin microbiome.
Superheated steam treatment of soft wheat on the physicochemical properties and structure of wheat starch
Authors: Liu Yuanxiao , Li Mengmeng , Guan Erqi , Liu Yuanfang , Bian Ke , Zhang Yingquan
Published: October 2023

Soft wheat grains were treated with superheated steam (SS) at 165 and 190°C, respectively for 1–5 min to understand the changes in the structures and properties of wheat starch following SS treatment. The damaged starch contents, amylose ratio, gelatinization properties, surface morphology, viscosity, and crystalline structure of the starch in wheat flour were determined. Damaged starch content, amylose ratio, and starch viscosity significantly increased after SS treatment. The onset temperature (To) and peak temperature (Tp) of wheat starch increased with the extending of treatment time, while an opposite variation trend was observed for (Tc − To). Additionally, the gelatinization enthalpy (ΔH) decreased after 3–5 min of SS treatment. Starch aggregation was observed in scanning electron microscopy (SEM) graphs. Compared to traditional heat treatment methods, SS treatment of wheat grains may be preferable for modifying the starch properties of soft wheat since much time and energy could be saved.

Practical Application

The physicochemical properties and structure of soft wheat starch significantly affect the quality of cakes made with soft wheat flour. After SS treatment of wheat kernels, the amylose ratio and damaged starch content in wheat starch significantly increased. Moreover, gelatinization properties and starch viscosity of wheat starch were also significantly affected. The changes in physicochemical properties were mainly due to the changes in the structure of starch granules and starch molecules. The above results in the physicochemical properties and structure of starch led to the increase in the viscosity and gas retention capacity of cake batter, which might be the reason why the specific volumes and texture of cakes could be improved after SS treatment of wheat. This research verified SS treatment may be preferable for improving cake quality compared to traditional heat treatment methods, which promotes the application of SS in wheat process engineering.
Dendrimer nanotherapy targeting of glial dysfunction improves inflammation and neurobehavioral phenotype in adult female Mecp2‐heterozygous mouse model of Rett syndrome
Authors: Khoury Elizabeth Smith , Patel Ruchit V. , O'Ferrall Caroline , Fowler Amanda , Sah Nirnath , Sharma Anjali , Gupta Siddharth , Scafidi Susanna , Kurtz Joshua S. , Olmstead Sarah J. , Kudchadkar Sapna R. , Kannan Rangaramanujam M. , Blue Mary E. , Kannan Sujatha
Published: October 2023

Rett syndrome is an X‐linked neurodevelopmental disorder caused by mutation of Mecp2 gene and primarily affects females. Glial cell dysfunction has been implicated in in Rett syndrome (RTT) both in patients and in mouse models of this disorder and can affect synaptogenesis, glial metabolism and inflammation. Here we assessed whether treatment of adult (5–6 months old) symptomatic Mecp2‐heterozygous female mice with N‐acetyl cysteine conjugated to dendrimer (D‐NAC), which is known to target glia and modulate inflammation and oxidative injury, results in improved behavioral phenotype, sleep and glial inflammatory profile. We show that unbiased global metabolomic analysis of the hippocampus and striatum in adult Mecp2‐heterozygous mice demonstrates significant differences in lipid metabolism associated with neuroinflammation, providing the rationale for targeting glial inflammation in this model. Our results demonstrate that treatment with D‐NAC (10 mg/kg NAC) once weekly is more efficacious than equivalently dosed free NAC in improving the gross neurobehavioral phenotype in symptomatic Mecp2‐heterozygous female mice. We also show that D‐NAC therapy is significantly better than saline in ameliorating several aspects of the abnormal phenotype including paw clench, mobility, fear memory, REM sleep and epileptiform activity burden. Systemic D‐NAC significantly improves microglial proinflammatory cytokine production and is associated with improvements in several aspects of the phenotype including paw clench, mobility, fear memory, and REM sleep, and epileptiform activity burden in comparison to saline‐treated Mecp2‐hetereozygous mice. Systemic glial‐targeted delivery of D‐NAC after symptom onset in an older clinically relevant Rett syndrome model shows promise in improving neurobehavioral impairments along with sleep pattern and epileptiform activity burden. These findings argue for the translational value of this approach for treatment of patients with Rett Syndrome.

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Romantic Planet: Science and Literature within the Anthropocene
Authors: Griffiths Devin
Published: October 2023

This article surveys recent scholarship in Romantic science and literature, exploring what such studies may offer the recent “planetary turn” in ecocriticism and postcolonial research on the Anthropocene. Situating these studies in a longer critical history, it explores their implications for how we engage modern climate science. The “Romantic century” 1750–1850 marks both the dawn of the Anthropocene and a formative stage in its sciences and technologies, from the industrial revolution to modern theories of climate change and ecology. Because ecocritical writing, including green Romanticism and ecofeminism, as well as research into colonialism, empire, and global capitalism were traditionally skeptical of Western science, their recent theorizations of “planetarity” do not adequately confront a new investment in the empirical claims of global warming. Positing that the traffic between science and social forms is asymmetric – two‐way but uneven – the author argues that Romantic science and literature both furnishes a sophisticated historical epistemology for planetary studies and, in its concern for the technologies, genres, and social forms that produced the Anthropocene, an epistemology of the climate that may help us dig our way out.
Co‐evolution at protein–protein interfaces guides inference of stoichiometry of oligomeric protein complexes by de novo structure prediction
Authors: Kilian Max , Bischofs Ilka B.
Published: October 2023

The quaternary structure with specific stoichiometry is pivotal to the specific function of protein complexes. However, determining the structure of many protein complexes experimentally remains a major bottleneck. Structural bioinformatics approaches, such as the deep learning algorithm Alphafold2‐multimer (AF2‐multimer), leverage the co‐evolution of amino acids and sequence‐structure relationships for accurate de novo structure and contact prediction. Pseudo‐likelihood maximization direct coupling analysis (plmDCA) has been used to detect co‐evolving residue pairs by statistical modeling. Here, we provide evidence that combining both methods can be used for de novo prediction of the quaternary structure and stoichiometry of a protein complex. We achieve this by augmenting the existing AF2‐multimer confidence metrics with an interpretable score to identify the complex with an optimal fraction of native contacts of co‐evolving residue pairs at intermolecular interfaces. We use this strategy to predict the quaternary structure and non‐trivial stoichiometries of Bacillus subtilis spore germination protein complexes with unknown structures. Co‐evolution at intermolecular interfaces may therefore synergize with AI‐based de novo quaternary structure prediction of structurally uncharacterized bacterial protein complexes.
Electron microscopy: The key to resolve RNA viruses replication organelles
Authors: Stelitano Debora , Cortese Mirko
Published: October 2023

Positive‐sense single‐stranded RNA viruses significantly reshape intracellular membranes to generate viral replication organelles that form a controlled niche in which nucleic acids, enzymes, and cofactors accumulate to assure an efficient replication of the viral genome. In recent years, advancements in electron microscopy (EM) techniques have enabled imaging of these viral factories in a near‐native state providing significantly higher molecular details that have led to progress in our general understanding of virus biology. In this review, we describe the contribution of the cutting‐edge EM approaches to the current knowledge of replication organelles biogenesis, structure, and functions.
Nrf2 protein in melanoma progression, as a new means of treatment
Authors: Feng Qun , Xu Xiaolin , Zhang Shoulin
Published: October 2023

Melanoma is a potentially lethal form of skin cancer resulting from the unlimited proliferation of melanocytes. Melanocytic lineage appears to have a greater rate of reactive oxygen species (ROS) production, possibly as a result of exposure to ultraviolet (UV) light and the production of melanin. It has been established that nuclear factor erythroid 2‐related factor 2 (Nrf2) serves as a master regulator of the cellular response to oxidative stresses. Recent research has shown that the Nrf2 and its critical negative regulator Kelch‐like ECH‐associated protein 1 (Keap1) are misregulated in melanoma, and the Keap1‐Nrf2 pathway has emerged as a promising new target for treating and preventing melanoma. In melanoma, Nrf2 may either limit tumor growth or promote its development. This review covers a wide range of topics, including the dual functions played by the Keap1‐Nrf2 signaling pathway in melanoma and the most recent targeting techniques of the Nrf2.
On subgroup separability of free‐by‐cyclic and deficiency 1 groups
Authors: Kudlinska Monika
Published: October 2023

We show that a free‐by‐cyclic group with a polynomially growing monodromy is subgroup separable exactly when it is virtually . We also prove that random deficiency 1 groups are not subgroup separable with positive asymptotic probability.
The creativity of cells: aneural irrational cognition
Authors: Alexander Victoria N.
Published: October 2023

Evidence of cognition in aneural cells is well‐establish in the literature. This paper extends the exploration of the mechanisms of cognition by considering whether or not aneural cells may be capable of irrational cognition, making associations based on coincidental similarities and circumstantial factors. If aneural cells do harness such semiosic qualities, as with higher‐level creativity, this might be how they are able to overcome old algorithms and invent tools for new situations. I will look at three examples of irrational learning in aneural systems in terms of semiotics: (1) generalisation in the immune system, based on viral molecular mimicry, whereby immune cells attack the self, which seems to be an overgeneralisation of an icon sign based on mere similarity, not identity, (2) the classical conditioning of pea plants to trope toward wind as a sign of light, which seems to be an association of an index sign based on mere temporal proximity, and (3) a pharmaceutical intervention to prevent pregnancy, using a conjugate to encrypt self with non‐self, which seems to be an example of symbol use. We identify irrational cognition easily when it leads to ‘wrong’ outcomes, but, if it occurs, it may also lead to favourable outcomes and ‘creative’ solutions.

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The mouse suprachiasmatic nucleus encodes irradiance via a diverse population of neurons monotonically tuned to different ranges of intensity
Authors: Orlowska‐Feuer Patrycja , Bano‐Otalora Beatriz , Rodgers Jessica , Martial Franck P. , Storchi Riccardo , Lucas Robert James
Published: October 2023

Many neurons of the mammalian master circadian oscillator in the suprachiasmatic nuclei (SCN) respond to light pulses with irradiance‐dependent changes in firing. Here, we set out to better understand this irradiance coding ability by considering how the SCN tracks more continuous changes in irradiance at both population and single unit level. To this end, we recorded extracellular activity in the SCN of anaesthetised mice presented with up + down irradiance staircase stimuli covering moonlight to daylight conditions and incorporating epochs with steady light or superimposed higher frequency modulations (temporal white noise (WN) and frequency/contrast chirps). Single unit activity was extracted by spike sorting. The population response of SCN units to this stimulus was a progressive increase in firing rate at higher irradiances. This relationship was symmetrical for up vs. down phases of the ramp in the presence of white noise or chirps but exhibited hysteresis for steady light, with firing systematically higher during increasing irradiance. Single units also showed a monotonic relationship between firing and irradiance but exhibited diversity not only in response polarity (increases vs. decreases in firing), but also in the sensitivity (EC50) and slope of fitted functions. These data show that individual SCN neurons exhibit monotonic relationships between irradiance and firing rate but differ in the irradiance range over which they respond. This property may help the SCN to encode the large differences in irradiance found in nature using neurons with a constrained range of firing rates.

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Key points

Daily changes in environmental light (irradiance) entrain the suprachiasmatic nucleus (SCN) circadian clock. The mouse SCN shows graded increases in neurophysiological activity with light pulses of increasing irradiance.

We show that this monotonic relationship between firing rate and irradiance is retained at population and single unit level when probed with more naturalistic staircase increases and decreases in irradiance.

The irradiance response is more reliable in the presence of ongoing higher temporal frequency modulations in light intensity than under steady light.

Single units varied in sensitivity allowing the population to cover a wide range of irradiances.

Irradiance coding in the SCN has characteristics of a sparse code with individual neurons tracking different portions of the natural irradiance range. This property may address the challenge of encoding a 109‐fold day:night difference in irradiance within the constrained range of firing rates available to individual neurons.
A comparative examination of morphine and fentanyl: unravelling the differential impacts on breathing and airway stability
Authors: Burgraff Nicholas J. , Baertsch Nathan A. , Ramirez Jan‐Marino
Published: October 2023

This study provides an in‐depth analysis of the distinct consequences of the opioid drugs morphine and fentanyl during opioid‐induced respiratory depression (OIRD). We explored the physiological implications of both drugs on ventilation and airway patency in anaesthetized mice. Our results revealed a similar reduction in respiratory frequency with equivalent scaled dosages of fentanyl and morphine, though the onset of suppression was more rapid with fentanyl. Additionally, fentanyl resulted in transient airflow obstructions during the inspiratory cycle, which were absent following morphine administration. Notably, these fentanyl‐specific obstructions were eliminated with tracheostomy, implicating the upper airways as a major factor contributing to fentanyl‐induced respiratory depression. We further demonstrate that bronchodilators salbutamol and adrenaline effectively reversed these obstructions, highlighting the bronchi's contribution to fentanyl‐induced airflow obstruction. Our study also uncovered a significant reduction in sighs during OIRD, which were eliminated by fentanyl and markedly reduced by morphine. Finally, we found that fentanyl‐exposed mice had reduced survival under hypoxic conditions compared to mice given morphine, demonstrating that fentanyl becomes more lethal in the context of hypoxaemia. Our findings shed light on the distinct and profound impacts of these opioids on respiration and airway stability and lay the foundation for improved opioid use guidelines and more effective OIRD prevention strategies.

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Key points

Both morphine and fentanyl significantly suppressed respiratory frequency, but the onset of suppression was faster with fentanyl. Also, while both drugs increased tidal volume, this effect was more pronounced with fentanyl.

Fentanyl administration resulted in transient obstructions during the inspiratory phase, suggesting its unique impact on airway stability. This obstruction was not observed with morphine.

The fentanyl‐induced obstructions were reversed by administering bronchodilators such as salbutamol and adrenaline. This suggests a possible therapeutic strategy for mitigating the adverse airway effects of fentanyl.

Both drugs reduced the frequency of physiological sighs, a key mechanism to prevent alveolar collapse. However, fentanyl administration led to a complete cessation of sighs, while morphine only reduced their occurrence.

Fentanyl‐treated mice showed a significantly reduced ability to survive under hypoxic conditions compared to those administered morphine. This indicates that the impacts of hypoxaemia during opioid‐induced respiratory depression can vary based on the opioid used.
Effect of research participation versus usual clinical care in patients with rheumatic and musculoskeletal disorders: a prospective cohort study
Authors: Ginnerup-Nielsen Elisabeth , Christensen Robin , Bliddal Henning , Henriksen Marius
Published: October 2023

Objective

To compare illness perception (IP), pain, functional level and health-related quality of life (HR-QoL) between patients with musculoskeletal pain who participate versus those who do not participate in clinical research projects.

Methods

Data were collected between 1 January 2019 and 31 December 2021 in patients visiting the Outpatient Osteoarthritis Clinic at Frederiksberg Hospital, Copenhagen, as part of either clinical research or regular treatment. Questionnaires were collected at baseline and after 10–18 months. Major outcome measure was the change from baseline to follow-up in the Brief Pain Inventory - Short Form (BPI-SF) item ‘Average pain’. Secondary outcome measures included The Brief Illness Perception Questionnaire (B-IPQ), measured only at baseline, the EuroQol (EQ-5D-3L), the Health Assessment Questionnaire Disability Index and PainDETECT.

Results

1495 patients were included with 358 (24%) categorised as research participants (exposed) and 1137 (76%) being non-participants (unexposed). The baseline B-IPQ item scores were generally more favourable in the exposed group with statistically significant standardised differences (SD) of 0.2–0.3. Similarly, an SD of 0.3 on the EQ-5D-3L score indicated a better HR-QoL in the exposed group. At follow-up, 24% in the exposed group and 27% in the unexposed group, completed the questionnaires. The mean BPI-sf Average pain between-group difference was: −0.01 points (95% CI: −0.6 to 0.6). Similar clinically irrelevant differences were seen in the other outcomes.

Conclusions

Among musculoskeletal pain patients, research participants report more positive IP and better HR-QoL than non-participants. No additional effect of research participation was found in any outcome over time.

Trial registration number

NCT03785561.
Structural reliability assessment of steel bridges using OSIM visual inspection data and Bayesian updating
Authors: Salaheddine Mohamad , Arjomandi Kaveh
Published: October 2023

Structural reliability theories are used in the calibration of load and resistance factor design (LRFD) in the Canadian Highway Bridge Design Code (CHBDC). The LRFD approach contains certain assumptions about uncertainties in the load and capacity estimation that prevent it from fully exploiting the information gathered during visual inspections. This paper presents a reliability-based framework for analyzing the visual inspection data obtained according to the Ontario structure inspection manual (OSIM). Existing deterioration models are adapted. The Bayesian interference is utilized to estimate the updated structural properties according to the prior information from the bridge maintenance and deterioration models and the new information collected from visual inspections. The criteria set by the CHBDC are used to analyze components and systems reliability. The value of the proposed framework for bridge evaluation and optimizing maintenance is demonstrated through the full implementation of a case-study bridge in the Canadian Province of NB.
Exploring the Associations between Chronotype, Night Shift Work Schedule, Quality of Work Life, and Sleep Quality among Maternal and Child Health Nurses: A Multicentre Cross-Sectional Study
Authors: Li Jia-Ning , Chen Xiao-Qian , Jiang Xiu-Min , Zheng Qing-Xiang , Pan Yu-Qing , Zhu Yu , Huang Ling , Liu Ru-Lin
Published: October 2023

Aim. To examine the state of sleep quality among maternal and child health (MCH) nurses and explore the associations between chronotype, night shift work schedule, quality of work life, and sleep quality among MCH nurses. Background. MCH nurses, who play an important role in protecting the health of women and children, often experience poor sleep quality. However, research on the sleep quality of MCH nurses has been scarce following implementation of the three-child policy in China. Methods. A multicentre cross-sectional study was conducted with 1426 MCH nurses. Data were collected using a demographic questionnaire, participants’ self-reported chronotype, the Pittsburgh Sleep Quality Index, and the Work-Related Quality of Life-2 scale. A chi-squared test, independent samples t-test, Pearson correlation test, and binary logistic regression analysis were used to analyse the data. Results. Of the 1426 respondents, 57.9% reported poor sleep quality. Binary logistic regression analysis indicated that chronotype, including intermediate-morning, intermediate-evening, and evening (reference: morning), and quality of work life, including stress at work, control at work, and general well-being, had effects on sleep quality among MCH nurses. Older age, frequent caffeine intake, and irregular meals were also associated with poor sleep quality. However, night shift work schedule did not affect sleep quality in the adjusted model. Conclusions. Poor sleep quality was common among MCH nurses. The findings of this study also illustrate that chronotype and quality of work life are closely related to sleep quality. Implications for Nursing Management. Nursing managers should be aware of MCH nurses’ chronotype and quality of work life and tailor interventions to address both modifiable and nonmodifiable factors associated with sleep to improve MCH nurses’ sleep quality.
School-Issued Devices for Home Use in Kindergarten through 5th Grade and Parent Perceptions of Child Learning, Behavior, and Conflict
Authors: McDaniel Brandon T. , Gullo Nathalie , Kaiser Zachary , Reining Lauren , Chang I. Joyce , Drouin Michelle
Published: October 2023

With many U.S. schools adopting 1-to-1 school device programs, research on the potential impacts of this device usage at home is critical. In this study, we examined elementary school parents’ perceptions of their child’s use of their school-issued device for academic skill-building and entertainment at home. We then examined the associations between these different types of use and children’s learning, behavior, and parent-child conflict over the device use. Overall, we found that children’s use of school devices at home for building academic skills was predictive of positive impacts on learning and child behaviors and less frequent parent-child conflict over use. In contrast, children’s use of school devices for entertainment purposes was associated with negative impacts on learning and child behaviors and more frequent parent-child conflict over use. Additionally, although most parents received some training or resources, many parents felt that device training from schools was insufficient, and parent perceptions of insufficient training were related to less use of the device for academic purposes and greater parent-child conflict. Considering this duality, we offer suggestions for training by schools, which training emphasizes effective child use of school-issued devices within the home.
Performance Analysis of Bus Voltage in Distribution Network with High Penetration of PV Controlled via Data-Driven Approach
Authors: Yadav Anju , Kishor Nand , Negi Richa , Opas Mikael , Raussi Petra
Published: October 2023

Integration of large-scale distributed photovoltaic (PV) generation resources can lead to technical challenges, particularly voltage rise caused by PVs power injection at the time of high solar radiation profile and low load demand. Reactive power control of PV inverters can help mitigate the voltage rise, which arises just for a short duration due to high incident solar radiation. There is a possibility to control functions on these PV inverters based on the rating of the PV inverter. For one-second resolution, local data-driven voltage sensitivity estimation is applied to update the control functions such as volt-var and volt-watt on the PV inverters so as to regulate the bus voltage. Different forms of solar radiation profiles, transient varying, smooth varying, and worst operating scenario corresponding to the minimum load at the time of high PV generation, are included. The study is demonstrated for different PV penetration levels. The voltage analysis on buses is performed using power hardware (PV emulator) in the loop simulation, at one of the buses in the network, while the remaining PVs are being controlled using volt-var control (VVC)/volt-watt control (VWC) methods. The applied approach confirms to maintaining bus voltage within limits even against a very short transient time instant of solar radiation profile.
The PTP1B Inhibitor Trodusquemine (MSI-1436) Improves Glucose Uptake in Equine Metabolic Syndrome Affected Liver through Anti-Inflammatory and Antifibrotic Activity
Authors: Bourebaba Lynda , Serwotka-Suszczak Anna , Bourebaba Nabila , Zyzak Magdalena , Marycz Krzysztof
Published: October 2023

Background. Hyperactivation of protein tyrosine phosphatase (PTP1B) has been associated with several metabolic malfunctions ranging from insulin resistance, metaflammation, lipotoxicity, and hyperglycaemia. Liver metabolism failure has been proposed as a core element in underlying endocrine disorders through persistent inflammation and highly fibrotic phenotype. Methods. In this study, the outcomes of PTP1B inhibition using trodusquemine (MSI-1436) on key equine metabolic syndrome (EMS)-related alterations including inflammation, fibrosis, and glucose uptake have been analyzed in liver explants collected from EMS-affected horses using various analytical techniques, namely, flow cytometry, RT-qPCR, and Western blot. Results. PTP1B inhibition using trodusquemine resulted in decreased proinflammatory cytokines (IL-1β, TNF-α, and IL-6) release from liver and PBMC affected by EMS and regulated expression of major proinflammatory microRNAs such as miR-802 and miR-211. Moreover, MSI-1436 enhanced the anti-inflammatory profile of livers by elevating the expression of IL-10 and IL-4 and activating CD4+CD25+Foxp3+ regulatory T cells in treated PBMC. Similarly, the inhibitor attenuated fibrogenic pathways in the liver by downregulating TGF-β/NOX1/4 axis and associated MMP-2/9 overactivation. Interestingly, PTP1B inhibition ameliorated the expression of TIMP-1 and Smad7, both important antifibrotic mediators. Furthermore, application of MSI-1436 was found to augment the abundance of glycosylated Glut-2, which subsequently expanded the glucose absorption in the EMS liver, probably due to an enhanced Glut-2 stability and half-life onto the plasma cell membranes. Conclusion. Taken together, the presented data suggest that the PTP1B inhibition strategy and the use of its specific inhibitor MSI-1436 represents a promising option for the improvement of liver tissue integrity and homeostasis in the course of EMS and adds more insights for ongoing clinical trials for human MetS management.
Serum Galectin-3 Predicts Mortality in Venoarterial Extracorporeal Membrane Oxygenation Patients
Authors: Zhu Jianlong , Guo Dehui , Liu Liying , Zhong Jing
Published: October 2023

Objective. We investigated the potential use of galectin-3 (Gal-3) as a prognostic indicator for patients with cardiogenic shock and developed a predictive mortality model for venoarterial extracorporeal membrane oxygenation (VA-ECMO). Methods. We prospectively studied patients (survivors and nonsurvivors) who received VA-ECMO for cardiogenic shock from 2019 to 2021. We recorded baseline data, Gal-3, and B-type natriuretic peptide (BNP) before ECMO and 24–72 h after ECMO. We used multivariable logistic regression to analyze significant risk factors and construct a VA-ECMO death prediction model. Receiver operating characteristic (ROC) curves were plotted to assess the predictive efficacy of the model. Results. We enrolled 73 patients with cardiogenic shock who received VA-ECMO support; 38 (52.05%) died in hospital. The median age was 57 years (interquartile range (IQR): 48–67 years); the median duration of ECMO therapy was 5.8 days (IQR: 4.62–7.57 days); and the median intensive care unit stay was 19.04 days (IQR: 13.92–26.15 days). Compared with the nonsurvivors, survivors had lower acute physiology and chronic health evaluation (APACHE) II scores (

p

 < 0.001), increased left ventricular ejection fraction (

p

 < 0.05), lower Gal-3 levels at 24 and 72 h (both

p

 = 0.001), lower BNP levels at 24 and 72 h (both

p

 = 0.001), and higher platelet counts (

p

 = 0.009). Further multivariable analysis showed that APACHE II score, BNP-T72, and Gal-3-T72 were independent risk factors for death in VA-ECMO patients. Gal-3 and BNP were positively correlated (

p

 < 0.05) and decreased significantly during ECMO treatment. The areas under the ROC curve (AUC) for APACHE II score, Gal-3-T72, and BNP-T72 were 0.687, 0.799, and 0.723, respectively. We constructed a combined prediction model with an AUC of 0.884 (

p

 < 0.01). Conclusion. Gal-3 may serve as a prognostic indicator for patients receiving VA-ECMO for cardiogenic shock. The combined early warning score is a simple and effective tool for predicting mortality in VA-ECMO patients.