bluuebunny/crossref_metadata_2025 huggingface dataset:
Subthalamic and nigral neurons are differentially modulated during parkinsonian gait
Authors: Gulberti Alessandro , Wagner Jonas R , Horn Martin A , Reuss Jacob H , Heise Miriam , Koeppen Johannes A , Pinnschmidt Hans O , Westphal Manfred , Engel Andreas K , Gerloff Christian , Sharott Andrew , Hamel Wolfgang , Moll Christian K E , Pötter-Nerger Monika
Published: February 2023

The parkinsonian gait disorder and freezing of gait are therapeutically demanding symptoms with considerable impact on quality of life. The aim of this study was to assess the role of subthalamic and nigral neurons in the parkinsonian gait control using intraoperative microelectrode recordings of basal ganglia neurons during a supine stepping task.

Twelve male patients (56 ± 7 years) suffering from moderate idiopathic Parkinson’s disease (disease duration 10 ± 3 years, Hoehn and Yahr stage 2), undergoing awake neurosurgery for deep brain stimulation, participated in the study. After 10 s resting, stepping at self-paced speed for 35 s was followed by short intervals of stepping in response to random ‘start’ and ‘stop’ cues. Single- and multi-unit activity was analysed offline in relation to different aspects of the stepping task (attentional ‘start’ and ‘stop’ cues, heel strikes, stepping irregularities) in terms of firing frequency, firing pattern and oscillatory activity.

Subthalamic nucleus and substantia nigra neurons responded to different aspects of the stepping task. Of the subthalamic nucleus neurons, 24% exhibited movement-related activity modulation as an increase of the firing rate, suggesting a predominant role of the subthalamic nucleus in motor aspects of the task, while 8% of subthalamic nucleus neurons showed a modulation in response to the attentional cues. In contrast, responsive substantia nigra neurons showed activity changes exclusively associated with attentional aspects of the stepping task (15%). The firing pattern of subthalamic nucleus neurons revealed gait-related firing regularization and a drop of beta oscillations during the stepping performance. During freezing episodes instead, there was a rise of beta oscillatory activity.

This study shows for the first time specific, task-related subthalamic nucleus and substantia nigra single-unit activity changes during gait-like movements in humans with differential roles in motor and attentional control of gait. The emergence of perturbed firing patterns in the subthalamic nucleus indicates a disrupted information transfer within the gait network, resulting in freezing of gait.
Multifaceted nanoparticles: emerging mechanisms and therapies in neurodegenerative diseases
Authors: Mistretta Miriam , Farini Andrea , Torrente Yvan , Villa Chiara
Published: February 2023

Neurodegenerative diseases are a major global health burden particularly with the increasing ageing population. Hereditary predisposition and environmental risk factors contribute to the heterogeneity of existing pathological phenotypes. Traditional clinical interventions focused on the use of small drugs have often led to failures due to the difficulties in crossing the blood–brain barrier and reaching the brain. In this regard, nanosystems can specifically deliver drugs and improve their bioavailability, overcoming some of the major challenges in neurodegenerative disease treatment.

This review focuses on the use of nanosystems as an encouraging therapeutic approach targeting molecular pathways involved in localized and systematic neurodegenerative diseases. Among the latter, Friedreich’s ataxia is an untreatable complex multisystemic disorder and the most widespread type of ataxia; it represents a test case to validate the clinical potential of therapeutic strategies based on nanoparticles with pleiotropic effects.
Integrative miRNA–mRNA profiling of human epidermis: unique signature of SCN9A painful neuropathy
Authors: Andelic Mirna , Salvi Erika , Marcuzzo Stefania , Marchi Margherita , Lombardi Raffaella , Cartelli Daniele , Cazzato Daniele , Mehmeti Elkadia , Gelemanovic Andrea , Paolini Matilde , Pardo Carlotta , D’Amato Ilaria , Hoeijmakers Janneke G J , Dib-Hajj Sulayman , Waxman Stephen G , Faber Catharina G , Lauria Giuseppe
Published: February 2023

Personalized management of neuropathic pain is an unmet clinical need due to heterogeneity of the underlying aetiologies, incompletely understood pathophysiological mechanisms and limited efficacy of existing treatments. Recent studies on microRNA in pain preclinical models have begun to yield insights into pain-related mechanisms, identifying nociception-related species differences and pinpointing potential drug candidates.

With the aim of bridging the translational gap towards the clinic, we generated a human pain-related integrative miRNA and mRNA molecular profile of the epidermis, the tissue hosting small nerve fibres, in a deeply phenotyped cohort of patients with sodium channel-related painful neuropathy not responding to currently available therapies.

We identified four miRNAs strongly discriminating patients from healthy individuals, confirming their effect on differentially expressed gene targets driving peripheral sensory transduction, transmission, modulation and post-transcriptional modifications, with strong effects on gene targets including NEDD4. We identified a complex epidermal miRNA–mRNA network based on tissue-specific experimental data suggesting a cross-talk between epidermal cells and axons in neuropathy pain. Using immunofluorescence assay and confocal microscopy, we observed that Nav1.7 signal intensity in keratinocytes strongly inversely correlated with NEDD4 expression that was downregulated by miR-30 family, suggesting post-transcriptional fine tuning of pain-related protein expression. Our targeted molecular profiling advances the understanding of specific neuropathic pain fine signatures and may accelerate process towards personalized medicine in patients with neuropathic pain.
Media populism and the metanarrative of God in the Philippines
Authors: Ragragio Jefferson Lyndon D
Published: February 2023

This article uses the concept of media populism to analyze the sophisticated role of networked platforms in organizing political discourses. Building on the scholarship on mediatization and mediated populism, it examines the mediated appeal of the God metanarrative—Religious Duterte, Catholic Church, Apollo Quiboloy, and Daily Prayer—and shows how God-related posts amplify the communicative style of populism in the Philippines. The God metanarrative on Facebook inspires communal engagement much as it polarizes the civil consensus on free expression and inclusive nationalism. The embedding of non-conflictual sentiments in the digital sphere blurs the precarious line between free expression of religious views and of political support, enabling political entrepreneurs to exploit the former as a way to consolidate the latter.
Forward perspective on the development and strategic pathway of green hydrogen in China
Authors: Liu Guoyue
Published: February 2023

Fundamental transformations are taking place in the areas of energy structure on the supply side and on the energy-consumption side towards clean, low-carbon and safe energy. Furthermore, a new energy system is being constructed with renewable energy as its core in China with energy transition and ‘carbon peak and carbon neutral’ as the overall goal. China’s hydrogen-industry plan, ‘Mid-to-long term hydrogen industry development plan (2021–2035)’, has an emphasis on hydrogen generation by using renewable energies as the centre piece, which points in the right direction for hydrogen’s green development. In this paper, the current status of China’s hydrogen industry is analysed; strategic needs for green hydrogen’s development and its hurdles in its paths are sorted out. Integrated demonstration at provincial levels, development of a ‘great hydrogen base’ and the green-hydrogen development path by gradual substitution with renewable hydrogen are proposed. Scaled-up hydrogen production, expanded consumer hydrogen usage and established hydrogen commodity exchange are recommended to safeguard its development and promote its high-quality development in China.
Activating words without language: beta and theta oscillations reflect lexical access and control processes during verbal and non-verbal object recognition tasks
Authors: Branzi Francesca M , Martin Clara D , Biau Emmanuel
Published: February 2023

The intention to name an object modulates neural responses during object recognition tasks. However, the nature of this modulation is still unclear. We established whether a core operation in language, i.e. lexical access, can be observed even when the task does not require language (size-judgment task), and whether response selection in verbal versus non-verbal semantic tasks relies on similar neuronal processes. We measured and compared neuronal oscillatory activities and behavioral responses to the same set of pictures of meaningful objects, while the type of task participants had to perform (picture-naming versus size-judgment) and the type of stimuli to measure lexical access (cognate versus non-cognate) were manipulated. Despite activation of words was facilitated when the task required explicit word-retrieval (picture-naming task), lexical access occurred even without the intention to name the object (non-verbal size-judgment task). Activation of words and response selection were accompanied by beta (25–35 Hz) desynchronization and theta (3–7 Hz) synchronization, respectively. These effects were observed in both picture-naming and size-judgment tasks, suggesting that words became activated via similar mechanisms, irrespective of whether the task involves language explicitly. This finding has important implications to understand the link between core linguistic operations and performance in verbal and non-verbal semantic tasks.
Mild hypothermia attenuates ischaemia/reperfusion injury: insights from serial non-invasive pressure–volume loops
Authors: Berg Jonathan , Jablonowski Robert , Nordlund David , Ryd Daniel , Heiberg Einar , Carlsson Marcus , Arheden Håkan
Published: February 2023

Aims

Mild hypothermia, 32–35°C, reduces infarct size in experimental studies, potentially mediating reperfusion injuries, but human trials have been ambiguous. To elucidate the cardioprotective mechanisms of mild hypothermia, we analysed cardiac performance in a porcine model of ischaemia/reperfusion, with serial cardiovascular magnetic resonance (CMR) imaging throughout 1 week using non-invasive pressure–volume (PV) loops.

Methods and results

Normothermia and Hypothermia group sessions (n = 7 + 7 pigs, non-random allocation) were imaged with Cardiovascular magnetic resonance (CMR) at baseline and subjected to 40 min of normothermic ischaemia by catheter intervention. Thereafter, the Hypothermia group was rapidly cooled (mean 34.5°C) for 5 min before reperfusion. Additional CMR sessions at 2 h, 24 h, and 7 days acquired ventricular volumes and ischaemic injuries (unblinded analysis). Stroke volume (SV: −24%; P = 0.029; Friedmans test) and ejection fraction (EF: −20%; P = 0.068) were notably reduced at 24 h in the Normothermia group compared with baseline. In contrast, the decreases were ameliorated in the Hypothermia group (SV: −6%; P = 0.77; EF: −6%; P = 0.13). Mean arterial pressure remained stable in Normothermic animals (−3%, P = 0.77) but dropped 2 h post-reperfusion in hypothermic animals (−18%, P = 0.007). Both groups experienced a decrease and partial recovery pattern for PV loop-derived variables over 1 week, but the adverse effects tended to attenuate in the Hypothermia group. Infarct sizes were 10 ± 8% in Hypothermic and 15 ± 8% in Normothermic animals (P = 0.32). Analysis of covariance at 24 h indicated that hypothermia has cardioprotective properties incremental to reducing infarct size, such as higher external power (P = 0.061) and lower arterial elastance (P = 0.015).

Conclusion

Using non-invasive PV loops by CMR, we observed that mild hypothermia at reperfusion alleviates the heart’s work after ischaemia/reperfusion injuries during the first week and preserves short-term cardiac performance. This hypothesis-generating study suggests hypothermia to have cardioprotective properties, incremental to reducing infarct size. The primary cardioprotective mechanism was likely an afterload reduction acutely unloading the left ventricle.
Declining Enrolment and Other Challenges in IBD Clinical Trials: Causes and Potential Solutions
Authors: Uzzan Mathieu , Bouhnik Yoram , Abreu Maria , Ahmad Harris A , Adsul Shashi , Carlier Hilde , Dubinsky Marla , Germinaro Matthew , Jairath Vipul , Modesto Irene , Mortensen Eric , Narula Neeraj , Neimark Ezequiel , Oortwijn Alessandra , Protic Marijana , Rubin David T , Oh Young S , Wichary Jolanta , Peyrin-Biroulet Laurent , Reinisch Walter
Published: February 2023

Background

Rates of enrolment in clinical trials in inflammatory bowel disease [IBD] have decreased dramatically in recent years. This has led to delays, increased costs and failures to develop novel treatments.

Aims

The aim of this work is to describe the current bottlenecks of IBD clinical trial enrolment and propose solutions.

Methods

A taskforce comprising experienced IBD clinical trialists from academic centres and pharmaceutical companies involved in IBD clinical research predefined the four following levels: [1] study design, [2] investigative centre, [3] physician and [4] patient. At each level, the taskforce collectively explored the reasons for declining enrolment rates and generated an inventory of potential solutions.

Results

The main reasons identified included the overall increased demands for trials, the high screen failure rates, particularly in Crohn’s disease, partly due to the lack of correlation between clinical and endoscopic activity, and the use of complicated endoscopic scoring systems not reflective of the totality of inflammation. In addition, complex trial protocols with restrictive eligibility criteria, increasing burden of procedures and administrative tasks enhance the need for qualified resources in study coordination. At the physician level, lack of dedicated time and training is crucial. From the patients’ perspective, long washout periods from previous medications and protocol requirements not reflecting clinical practice, such as prolonged steroid management and placebo exposures, limit their participation in clinical trials.

Conclusion

This joint effort is proposed as the basis for profound clinical trial transformation triggered by investigative centres, contract research organizations, sponsors and regulatory agencies.
Web Vibrations in Intraspecific Contests of Female Black Widow Spiders,Latrodectus hesperus
Authors: Krugner Rodrigo , Espindola Crystal , Justus Nathan , Hatton Ross L
Published: February 2023

Female black widow spiders, Latrodectus hesperus Chamberlin and Ivie (Araneae: Theridiidae), are solitary predators of arthropods with no tolerance for intruders on the webs. In California, L. hesperus are found in urban and agricultural settings and can be a phytosanitary pest in fresh produce. Spatial separation of L. hesperus webs could be determined by seasonal population densities, with territorial competition expected under high densities in the environment. However, little is known about female-female communication behaviors in this species. In 1-hr laboratory observations, displays of female-female rivalry included production of vibrational signals in a majority (20 of 30) of trials. The number of signals produced by both females was highest during the initial 10 min of trials, with signaling rate (time interval between signals) peaking during the 40–50 min observation period. The overall ratio of signals produced by the resident female and the introduced female was about 5:1, with the number of signals produced by the resident female higher than the number of signals produced by the introduced female. Analysis of rivalry signals showed a peak in magnitude (about 0.4 m/s) ranging from 6 to 23 Hz and smaller peaks at about 29, 38, and 47 Hz. Collectively, these results demonstrate that female L. hesperus exhibit territorial rivalry and that female-female rivalry is mediated by emission of vibrational signals through the web. Understanding the mechanisms of intraspecific competition in L. hesperus is required for elucidating interspecific interactions in the environment and may lead to development of novel methods to prevent spiders from colonizing crops.
Deep learning estimation of three-dimensional left atrial shape from two-chamber and four-chamber cardiac long axis views
Authors: Xu Hao , Williams Steven E , Williams Michelle C , Newby David E , Taylor Jonathan , Neji Radhouene , Kunze Karl P , Niederer Steven A , Young Alistair A
Published: February 2023

Aims

Left atrial volume is commonly estimated using the bi-plane area-length method from two-chamber (2CH) and four-chamber (4CH) long axes views. However, this can be inaccurate due to a violation of geometric assumptions. We aimed to develop a deep learning neural network to infer 3D left atrial shape, volume and surface area from 2CH and 4CH views.

Methods and results

A 3D UNet was trained and tested using 2CH and 4CH segmentations generated from 3D coronary computed tomography angiography (CCTA) segmentations (n = 1700, with 1400/100/200 cases for training/validating/testing). An independent test dataset from another institution was also evaluated, using cardiac magnetic resonance (CMR) 2CH and 4CH segmentations as input and 3D CCTA segmentations as the ground truth (n = 20). For the 200 test cases generated from CCTA, the network achieved a mean Dice score value of 93.7%, showing excellent 3D shape reconstruction from two views compared with the 3D segmentation Dice of 97.4%. The network also showed significantly lower mean absolute error values of 3.5 mL/4.9 cm2 for LA volume/surface area respectively compared to the area-length method errors of 13.0 mL/34.1 cm2 respectively (P < 0.05 for both). For the independent CMR test set, the network achieved accurate 3D shape estimation (mean Dice score value of 87.4%), and a mean absolute error values of 6.0 mL/5.7 cm2 for left atrial volume/surface area respectively, significantly less than the area-length method errors of 14.2 mL/19.3 cm2 respectively (P < 0.05 for both).

Conclusions

Compared to the bi-plane area-length method, the network showed higher accuracy and robustness for both volume and surface area.
Israeli Courts and the Paradox of International Human Rights Law
Authors: Davidson Natalie R , Hostovsky Brandes Tamar
Published: February 2023

This article offers the first comprehensive mapping of the place of international human rights law (IHRL) in Israeli case law. It explores how Israeli courts use IHRL, based on quantitative and qualitative content analysis of all decisions, in all courts, referring to IHRL between 1990 and 2019. It reveals that Israeli courts mobilize IHRL predominantly with respect to children’s rights and due process, seldom invoking IHRL in relation to ethnic and gender equality. It further shows that a significant portion of references to IHRL serve to justify state action. We discuss possible explanations for these patterns of use of IHRL and argue that, overall, these findings illustrate the paradox of IHRL being amenable to uses that are both emancipatory and protective of power.
Women in European academia before 1800—religion, marriage, and human capital
Authors: de la Croix David , Vitale Mara
Published: February 2023

We document the participation of women in European academia from the first universities to the eve of the Industrial Revolution. A total of 108 women taught at universities or were members of academies of arts and sciences. Most of them were active in Catholic southern Europe—an unexpected result. We conjecture that Protestantism left less room for women at the top of the distribution of human capital to exercise their talent. The percentage of ever-married female scholars is 79%, but a large fraction of them remained childless. Comparing them with 58,995 male scholars, we find that they were on average better.
Signals, educational decision-making, and inequality: a comment on the formal model by Holm, Hjorth-Trolle, and Jæger
Authors: Yastrebov Gordey
Published: February 2023

In this comment, I explore the assumptions and the implications of the formal (mathematical) model proposed by Holm, Hjorth-Trolle, and Jæger (HHJ) in their article in European Sociological Review, 35(4) (2019). The model links educational decision-making to social background inequality and academic ability and is said to conform to the key propositions of the Relative-Risk-Aversion theory and the Compensatory-Advantage-Model. Its most original component is that it allows for the error in estimating one’s ability, which, once known, impacts on the decision to (dis)continue education. The error is said to have a differential impact on students of different social backgrounds, whereby social inequality in educational decisions is effectively maintained. The model also deserves attention and praise as one of the few attempts in our field to reason formally and provide a mathematical formulation of theoretical arguments. However, I scrutinize the model and show that (i) some of its assumptions may not be defensible; that (ii) the most interesting and original hypothesis proposed by HHJ does not follow from the model; and that (iii) the empirical implications of the model are wrongly interpreted in terms of probability differences. I then show which particular assumption is required for HHJ’s most original hypothesis to hold. The assumption is non-intuitive, and I conclude that the hypothesis, as formulated by HHJ, does not have a sound theoretical basis.
Outcomes in novel hospital-at-home model for patients with COVID-19: a multicentre retrospective cohort study
Authors: Tsujimoto Yasushi , Kobayashi Masanori , Oku Tomohisa , Ogawa Takahisa , Yamadera Shinichi , Tsukamoto Masako , Matsuda Noriya , Nishihira Morikazu , Terauchi Yu , Tanaka Takahiro , Kawabata Yoshitaka , Miyamoto Yuki , Morikami Yoshiki ,   KISA2-Tai Osaka
Published: February 2023

Background

Hospital-at-home (HaH) care has been proposed as an alternative to inpatient care for patients with coronavirus disease (COVID-19). Previous reports were hospital-led and involved patients triaged at the hospitals. To reduce the burden on hospitals, we constructed a novel HaH care model organized by a team of local primary care clinics.

Methods

We conducted a multicentre retrospective cohort study of the COVID-19 patients who received our HaH care from 1 January to 31 March 2022. Patients who were not able to be triaged for the need for hospitalization by the Health Center solely responsible for the management of COVID-19 patients in Osaka city were included. The primary outcome was receiving medical care beyond the HaH care defined as a composite outcome of any medical consultation, hospitalization, or death within 30 days from the initial treatment.

Results

Of 382 eligible patients, 34 (9%) were triaged for hospitalization immediately after the initial visit. Of the remaining 348 patients followed up, 37 (11%) developed the primary outcome, while none died. Obesity, fever, and gastrointestinal symptoms at baseline were independently associated with an increased risk of needing medical care beyond the HaH care. A further 129 (37%) patients were managed online alone without home visit, and 170 (50%) required only 1 home visit in addition to online treatment.

Conclusions

The HaH care model with a team of primary care clinics was able to triage patients with COVID-19 who needed immediate hospitalization without involving hospitals, and treated most of the remaining patients at home.
Perceived importance and interest in research by Chilean primary care providers
Authors: García-Huidobro Diego , Aracena Marcela , Bravo Paulina , González Karla , Soto Mauricio , von Borries Pamela , Sapag Jaime C
Published: February 2023

Background

Primary care providers (PCPs) are relevant stakeholders for primary care research (PCR).

Objective

We report the perceived importance and interest in PCR of a national sample of Chilean PCPs.

Methods

We conducted a cross-sectional study targeting Chilean PCPs. An electronic survey assessing perceived relevance of PCR, research training and experience, training interests, and demographics was disseminated through emails and WhatsApp messages. Descriptive statistics were used to summarize data. Logistic regression models were used to estimate adjusted probabilities and 95% confidence intervals for high interest in PCR, high interest in using research methods, and high interest in receiving research training, and predictors of these outcomes.

Results

A total of 387 providers completed the online survey. Only 26.4% of PCPs had research experience as a principal or co-investigator. However, most clinicians perceived PCR as very important (92.5%) and were interested in using research methods (90.7%) and receiving training (94.3%). There were no statistically significant differences in these perceptions between provider’s discipline, role, sex, age, and geographical location after adjusting for covariates.

Conclusions

Despite few Chilean PCPs have research training, a large majority perceive it as important, are interested in using it in their practice and would like to receive training.
Impacts of coniferous bark-derived organic soil amendments on microbial communities in arable soil – a microcosm study
Authors: Peltoniemi Krista , Velmala Sannakajsa , Fritze Hannu , Jyske Tuula , Rasi Saija , Pennanen Taina
Published: February 2023

A decline in the carbon content of agricultural soils has been reported globally. Amendments of forest industry side-streams might counteract this. We tested the effects of industrial conifer bark and its cascade process materials on the soil microbiome under barley (Hordeum vulgare L.) in clay and silt soil microcosms for 10 months, simulating the seasonal temperature changes of the boreal region. Microbial gene copy numbers were higher in clay soils than in silt. All amendments except unextracted bark increased bacterial gene copies in both soils. In turn, all other amendments, but not unextracted bark from an anaerobic digestion process, increased fungal gene copy numbers in silt soil. In clay soil, fungal increase occurred only with unextracted bark and hot water extracted bark. Soil, amendment type and simulated season affected both the bacterial and fungal community composition. Amendments increased bacteria originating from the anaerobic digestion process, as well as dinitrogen fixers and decomposers of plant cells. In turn, unextracted and hot water extracted bark determined the fungal community composition in silt. As fungal abundance increase and community diversification are related to soil carbon acquisition, bark-based amendments to soils can thus contribute to sustainable agriculture.
From the organismal to biosphere levels: environmental impacts on the amphibian microbiota
Authors: Hernández-Gómez Obed , Hua Jessica
Published: February 2023

This review summarizes the role of environmental factors on amphibian microbiotas at the organismal, population, community, ecosystem, and biosphere levels. At the organismal-level, tissue source, disease status, and experimental manipulations were the strongest predictors of variation in amphibian microbiotas. At the population-level, habitat quality, disease status, and ancestry were commonly documented as drivers of microbiota turnover. At the community-level, studies focused on how species’ niche influence microbiota structure and function. At the ecosystem-level, abiotic and biotic reservoirs were important contributors to microbiota structure. At the biosphere-level, databases, sample banks, and seminatural experiments were commonly used to describe microbiota assembly mechanisms among temperate and tropical amphibians. Collectively, our review demonstrates that environmental factors can influence microbiotas through diverse mechanisms at all biological scales. Importantly, while environmental mechanisms occurring at each of the different scales can interact to shape microbiotas, the past 10 years of research have mostly been characterized by targeted approaches at individual scales. Looking forward, efforts considering how environmental factors at multiple organizational levels interact to shape microbiota diversity and function are paramount. Generating opportunities for meaningful cross-disciplinary interactions and supporting infrastructure for research that spans biological scales are imperative to addressing this gap.
Effects of providing tailored information about e-cigarettes in a digital smoking cessation intervention: randomized controlled trial
Authors: Elling J M , Crutzen R , Talhout R , de Vries H
Published: February 2023

The effectiveness of e-cigarettes in smoking cessation is under debate. Informing smokers who are motivated to quit smoking about e-cigarettes may help them to make an informed decision about their use for smoking cessation, which, however, may also lead to unintended effects such as less quitting. This experimental study assessed the influence of providing tailored information about e-cigarettes in a web-based tailored smoking cessation intervention on participants’ decision-making and smoking behavior. Adult smokers (N = 331) were randomized into a personalized eHealth intervention on (i) smoking cessation (control condition) or (ii) smoking cessation and information about e-cigarettes (intervention condition). Directly postintervention, participants in the intervention condition had more knowledge about e-cigarettes than participants in the control condition. Attitudes toward e-cigarettes were more positive among intervention participants than control participants, but the differences in attitude were less pronounced than the differences in knowledge and not consistent across items. At a 6-month follow-up, no between-condition differences were observed in the use of e-cigarettes as a smoking cessation method, the number of tobacco cigarettes smoked in the past 7 days, or other smoking outcomes.
Human DUX4 and porcine DUXC activate similar early embryonic programs in pig muscle cells: implications for preclinical models of FSHD
Authors: Nip Yee , Bennett Sean R , Smith Andrew A , Jones Takako I , Jones Peter L , Tapscott Stephen J
Published: February 2023

Human DUX4 and its mouse ortholog Dux are normally expressed in the early embryo—the 4-cell or 2-cell cleavage stage embryo, respectively—and activate a portion of the first wave of zygotic gene expression. DUX4 is epigenetically suppressed in nearly all somatic tissue, whereas facioscapulohumeral dystrophy (FSHD)-causing mutations result in its aberrant expression in skeletal muscle, transcriptional activation of the early embryonic program and subsequent muscle pathology. Although DUX4 and Dux both activate an early totipotent transcriptional program, divergence of their DNA binding domains limits the use of DUX4 expressed in mice as a preclinical model for FSHD. In this study, we identify the porcine DUXC messenger ribonucleic acid expressed in early development and show that both pig DUXC and human DUX4 robustly activate a highly similar early embryonic program in pig muscle cells. These results support further investigation of pig preclinical models for FSHD.
Interaction of methionine sulfoxide reductase B5 with SlMYC2 stimulates the transcription of MeJA-mediated autophagy-related genes in tomato fruit
Authors: Min Dedong , Li Fujun , Ali Maratab , Liu Jiong , Fu Xiaodong , Song Yanan , Ding Jun , Li Xiaoan , Ji Nana , Zhang Xinhua
Published: February 2023

Methyl jasmonate (MeJA) has been shown to induce autophagy in various plant stress responses and metabolic pathways. MYC2 is involved in MeJA-mediated postharvest fruit biological metabolism, but it is unclear how it affects MeJA-induced fruit autophagy. In this study, we noticed that silencing SlMYC2 significantly reduced the increase in autophagy-related genes (SlATGs) expression induced by MeJA. SlMYC2 could also bind to the promoters of several SlATGs, including SlATG13a, SlATG13b, SlATG18a, and SlATG18h, and activate their transcript levels. Moreover, SlMsrB5, a methionine sulfoxide reductase, could interact with SlMYC2. Methionine oxidation in SlMYC2 and mimicking sulfoxidation in SlMYC2 by mutation of methionine-542 to glutamine reduced the DNA-binding ability and transcriptional activity of SlMYC2, respectively. SlMsrB5 partially repaired oxidized SlMYC2 and restored its DNA-binding ability. On the other hand, silencing SlMsrB5 inhibited the transcript levels of SlMYC2-targeted genes (SlATG13a, SlATG13b, SlATG18a, and SlATG18h). Similarly, dual-luciferase reporter (DLR) analysis revealed that SlMsrB5–SlMYC2 interaction significantly increased the ability of SlMYC2-mediated transcriptional activation of SlATG13a, SlATG13b, SlATG18a, and SlATG18h. These findings demonstrate that SlMsrB5-mediated cyclic oxidation/reduction of methionine in SlMYC2 influences SlATGs expression. Collectively, these findings reveal the mechanism of SlMYC2 in SlATGs transcriptional regulation, providing insight into the mechanism of MeJA-mediated postharvest fruit quality regulation.
RsERF40contributes to cold stress tolerance and cell expansion of taproot in radish (Raphanus sativusL.)
Authors: Li Cui , Mao Baozhen , Wang Kai , Xu Liang , Fan Lianxue , Wang Yan , Li Ying , Ma Yinbo , Wang Lun , Liu Liwang
Published: February 2023

The growth and development of taproots are inhibited by cold stress in radish (Raphanus sativus L.). Ethylene-responsive element binding factors (ERF) are key participators in the cold stress response and growth regulation of plants. However, the function of ERF genes in cold tolerance and root development in radish remains elusive. Here, we showed that the secondary growth of radish taproots was inhibited by cold stress. Comparative transcriptome analysis demonstrated that the RsERF40 gene is an important regulator of the cold stress response and root growth regulation. The cold tolerance of transgenic Arabidopsis plants overexpressing the RsERF40 gene was significantly improved. Overexpressing RsERF40 in the cold-sensitive radish genotype and silencing RsERF40 in the cold-tolerant radish genotype indicated that RsERF40 was beneficial for alleviating oxidative damage under cold stress in radish. Transgenic Arabidopsis seedlings showed an increase in the elongation and radial growth of dark-grown roots. RT-qPCR analysis showed that the expression of the cold-related genes (CORs) RsCOR78 and RsCOR413PM1 and the cell wall strengthening-related genes RsCESA6 and RsEXPB3 was upregulated in transgenic Arabidopsis seedlings. Yeast one-hybrid (Y1H) and dual-luciferase reporter assays (DLA) revealed that RsERF40 directly regulates RsCOR78, RsCOR413PM1, RsCESA6 and RsEXPB3 expression, illustrating that RsERF40 enhances cold tolerance and taproot growth by modulating osmotic adjustment and cell wall mechanical strength in radish. In this study, the RsERF40-regulon was firstly found to be a new cold response pathway independent of the CBF-COR pathway conferring cold stress tolerance with increasing radish taproot growth. These results provided novel insight into the molecular mechanism underlying cold stress response and would facilitate the genetic improvement of cold tolerance in radish and other root vegetable crops.
Simulation-based educational approach toward improving thermal outdoor comfort for pedestrians in semi-arid climate
Authors: Sayad Bouthaina , Alkama Djamel , Ibrahim Hossam Samir , Hegazy Ibrahim Rizk , Imam Ayman Amin , Abed Ahmed Mohammed , Alhubashi Haytham Hussain
Published: February 2023

The urban cooling is the most effective strategy to fight the urban climate change effects in summertime. Thus, searching urban cool islands can remedy the rise of urban temperatures. This study aims to consider cool urban pathways offering optimal levels of thermal comfort in downtown Guelma during summer overheating. This involves researching the appropriate tree ratio and typology, tree layout and suitable configurations of water bodies of outdoor spaces. The scientific methodology is made through either straightforward step included on-site measurements and calculating the difference of urban temperatures to select five outdoor spaces with maximum heat stress. As our study also aims to improve the outdoor thermal comfort by natural elements, it simulates different scenarios of the selected stations using ENVI-Met model and exploiting the real field measurement of the urban microclimate. The most significant reductions in thermal comfort levels (UTCI) over three thermal phases identify the coolest urban pathways. Consequently, we confirmed that considering cool pathways spanning from station S2 to station S8 is possible with optimal thermal comfort levels over the day; 0.46–6.9°C in the morning phase, 0.94–3.87°C in the hot thermal phase and 1.42–3.54°C in the thermal relief phase. The findings indicate three main effects of microclimatic regulation underlie the improvement of the thermal comfort levels: tree cooling effect with (Ta ≤ 1.1°C), cooling effect of water bodies (Ta ≤ 0.3°C) and cooling effect of trees in combination with water bodies (Ta ≤ 1.9°C).
Identification and characterization of plasmids carrying the mobile colistin resistance gene mcr-1 using optical DNA mapping
Authors: KK Sriram , Wranne Moa S , Sewunet Tsegaye , Ekedahl Elina , Coorens Maarten , Tangkoskul Teerawit , Thamlikitkul Visanu , Giske Christian G , Westerlund Fredrik
Published: February 2023

Objectives

Colistin is a last-resort antibiotic, but there has been a rapid increase in colistin resistance, threatening its use in the treatment of infections with carbapenem-resistant Enterobacterales (CRE). Plasmid-mediated colistin resistance, in particular the mcr-1 gene, has been identified and WGS is the go-to method in identifying plasmids carrying mcr-1 genes. The goal of this study is to demonstrate the use of optical DNA mapping (ODM), a fast, efficient and amplification-free technique, to characterize plasmids carrying mcr-1.

Methods

ODM is a single-molecule technique, which we have demonstrated can be used for identifying plasmids harbouring antibiotic resistance genes. We here applied the technique to plasmids isolated from 12 clinical Enterobacterales isolates from patients at a major hospital in Thailand and verified our results using Nanopore long-read sequencing.

Results

We successfully identified plasmids encoding the mcr-1 gene and, for the first time, demonstrated the ability of ODM to identify resistance gene sites in small (∼30 kb) plasmids. We further identified blaCTX-M genes in different plasmids than the ones encoding mcr-1 in three of the isolates studied. Finally, we propose a cut-and-stretch assay, based on similar principles, but performed using surface-functionalized cover slips for DNA immobilization and an inexpensive microscope with basic functionalities, to identify the mcr-1 gene in a plasmid sample.

Conclusions

Both ODM and the cut-and-stretch assay developed could be very useful in identifying plasmids encoding antibiotic resistance in hospitals and healthcare facilities. The cut-and-stretch assay is particularly useful in low- and middle-income countries, where existing techniques are limited.
Flies (Insecta, Diptera) collected in the environment of dairy farms as carriers of Rotavirus A and betacoronavirus
Authors: Bertolini Amanda Bezerra , Thyssen Patrícia Jacqueline , Brandão Paulo Eduardo , Prado Aline Marrara , Silva Sheila Oliveira de Souza , Mioni Mateus de Souza Ribeiro , de Gouvea Fábio Lucas Rezende , Pantoja José Carlos de Figueiredo , Langoni Helio , Guimarães Felipe Freitas , Joaquim Sâmea Fernandes , Guerra Simony Trevizan , Leite Domingos da Silva , Rall Vera Mores , Hernandes Rodrigo Tavanelli , Lucheis Simone Baldini , Rossi Gabriel Augusto Marques , Ribeiro Márcio Garcia
Published: February 2023

Aims

We aimed to investigate the prevalence of rotavirus and coronavirus in dipterans that commonly inhabit the environment of dairy farms.

Methods and Results

We collected 217 insect specimens from nine dairy farms, which were examined through hemi-nested RT-PCR followed by Sanger sequencing in search of VP1 and N genes for rotavirus and bovine coronavirus-BCoV, respectively. With a predominance of Muscidae (152/217 = 70%) 11 families of Diptera were identified. Rotavirus A (RVA) and betacoronavirus (BCoV) were detected in 14.7% (32/217) and 4.6% (10/217) of the dipterans, respectively. Sequencing of the amplicons was possible for 11.5% (25/217) of RVA and 0.5% (1/217) of BCoV, confirming the presence of these pathogens.

Conclusions

Our findings highlight the role of dipterans as carriers of RVA and BCoV of great relevance for public and animal health.
Lacticaseibacillus caseiCNRZ1874 supplementation promotes M1 alveolar macrophage activation and attenuatesMycoplasma pneumoniaepneumonia
Authors: Zhang Naiyu , Zeng Wuwei , Du Tingfeng , Wei Hongjiang , Tian Wei , Meng Yan , He Guiting , Lei Aihua , Zhu Cuiming
Published: February 2023

Aims

To evaluate the protective effect of intestinal supplementation with Lacticaseibacillus casei CNRZ1874 on the inflammatory response induced by Mycoplasma pneumoniae in C57BL/6 J mice, and provide a potential strategy for alleviating M. pneumoniae pneumonia.

Methods and results

C57BL/6 J mice were gavaged with L. casei CNRZ1874 or PBS for 7 consecutive days, and then infected with M. pneumoniae on day 8. Treatment with L. casei CNRZ1874 significantly reduced M. pneumoniae loads in the lungs and alleviated the lung inflammation on day 3 and 10 after pathogen infection. Importantly, oral administration with L. casei CNRZ1874 promoted M1 alveolar macrophages activation as evidenced by increased expression of iNOS, TNF-α, and CXCL1, while inhibited M2 alveolar macrophages activation as the expression of Arg1 and Chi3l3 were significantly decreased. In consistent with the M1 alveolar macrophages activation and enhanced mycoplasma clearance, the level of TNF-α was increased while the level of IL-4 was decreased in lung tissue from the L. casei CNRZ1874 group compared with the control group. However, oral administration with L. casei CNRZ1874 may not influence adaptive immunity induced by M. pneumoniae as evaluated by M. pneumoniae specific antibodies and T cells responses in spleen.

Conclusions

Intestinal supplementation with L. casei CNRZ1874 can promote M1 alveolar macrophages activation, which contributes to the clearance of M. pneumoniae and attenuation of M.pneumoniae pneumonia.
Plant Gall Diversity in Burned Semi-natural Grasslands in Japan
Authors: Koyama Asuka , Ide Tatsuya
Published: February 2023

We surveyed woody plants, including oaks and chestnuts (Quercus L. and Castanea Mill.), and recorded the inhabiting galls induced by oak gall wasps (Hymenoptera: Cynipidae: Cynipini) at seven Japanese semi-natural grassland sites maintained by traditional regular burning with two of the seven abandoned grassland areas. Woody plants were established in all burned and abandoned grasslands. Oak species were found at four of the seven sites. In total, 15 types of cynipid galls were recorded at all four sites where oak species were found. However, the occurrence of species was site-specific for host trees and cynipid galls. Although a few ecological studies of oak gall wasps inhabiting grassland environments, which have rapidly decreased in recent decades, have been conducted, this study suggests that semi-natural grasslands may be potential habitats for oak gall wasps and their host trees, and we provide a checklist of oak gall wasps with host oak records in semi-natural grasslands throughout Japan.
KAT7 promotes radioresistance through upregulating PI3K/AKT signaling in breast cancer
Authors: Ma Yan , Chen Xiaohua , Ding Ting , Zhang Hanqun , Zhang Qiuning , Dai Huanyu , Zhang Haibo , Tang Jianming , Wang Xiaohu
Published: February 2023

Chromatin-modifying enzymes are commonly altered in cancers, but the molecular mechanism by which they regulate cancers remains poorly understood. Herein, we demonstrated that Lysine acetyltransferase 7 (KAT7) was upregulated in breast cancer. KAT7 expression negatively correlated with the survival of breast cancer patients, and KAT7 silencing suppressed breast cancer radioresistance in vitro. Mechanistically, KAT7 activated Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) transcription, leading to enhanced PI3K/AKT signaling and radioresistance. Overexpression of AKT or PIK3CA restored radioresistance suppression induced by KAT7 inhibition. Moreover, overexpression of KAT7, but not KAT7 acetyltransferase activity-deficient mutants promoted AKT phosphorylation at the Ser473 site, PIK3CA expression and radioresistance suppression due to KAT7 inhibition. In conclusion, KAT7 has huge prospects for clinical application as a new target for predicting radioresistance in breast cancer patients.
Group- and individual-based approaches to health inequality: towards an integration
Authors: Permanyer Iñaki , Sasson Isaac , Villavicencio Francisco
Published: February 2023

When assessing health inequalities, should one compare health outcomes across predetermined groups (e.g., race, ethnicity, socioeconomic status), or across individuals? Group-based approaches comparing group-specific means do not account for intra-group heterogeneity. Yet, traditional approaches based on additive decompositions splitting total inequality in its within- and between-group components fail to elucidate the groups’ relative performance. Here, we develop a third approach based on pairwise comparisons to evaluatenot only the variability that might exist across individuals within and between groups, but also the relative performance of the different groups vis-a-vis each other—thus integrating both perspectives into a coherent framework.
Experimental evaluation of algorithm-assisted human decision-making: application to pretrial public safety assessment*
Authors: Imai Kosuke , Jiang Zhichao , Greiner D James , Halen Ryan , Shin Sooahn
Published: February 2023

Despite an increasing reliance on fully-automated algorithmic decision-making in our day-to-day lives, humans still make consequential decisions. While the existing literature focuses on the bias and fairness of algorithmic recommendations, an overlooked question is whether they improve human decisions. We develop a general statistical methodology for experimentally evaluating the causal impacts of algorithmic recommendations on human decisions. We also examine whether algorithmic recommendations improve the fairness of human decisions and derive the optimal decision rules under various settings. We apply the proposed methodology to the first-ever randomized controlled trial that evaluates the pretrial Public Safety Assessment in the United States criminal justice system. Our analysis of the preliminary data shows that providing the PSA to the judge has little overall impact on the judge’s decisions and subsequent arrestee behaviour.
Haemorrhagic mesenteric abscess in infective endocarditis: a unique cause of spontaneous haemoperitoneum
Authors: Read Phillipa , Walker Patrick , Menon Tulsi
Published: February 2023

Spontaneous haemoperitoneum (SH) is a rare but life-threatening condition with several well-recognized causes. SH often occurs in anticoagulated patients and requires urgent treatment to prevent mortality. SH is rarely associated with infective endocarditis (IE). To date, there are no reported cases of a haemorrhagic mesenteric abscess causing haemoperitoneum. We present the case of a warfarinized 30-year-old intravenous drug user with IE 2 weeks post-revision of a metallic valve who reported abdominal pain and subsequently suffered haemodynamic collapse. Abdominal computed tomography and damage-control laparotomy revealed haemoperitoneum secondary to an actively bleeding mesenteric nodule which was resected. Histopathology confirmed a haemorrhagic mesenteric abscess representing a rare sequela of IE and a novel cause of SH. Given that the incidence of IE appears to be increasing in people who inject drugs in Australia, the general surgeon should be aware of this clinical entity and the need for urgent intervention to prevent catastrophic sequelae.