bluuebunny/crossref_metadata_2025 huggingface dataset:
Dental treatment of children with special healthcare needs: A retrospective study of 10 years of treatment
Authors: Hieronymus Hanna , Aydin Selin , Frese Cornelia , Huck Matthias , Wolff Diana , Sekundo Caroline
Published: April 2024

Background/Aim

Children with special healthcare needs (CSHCN) often face oral health challenges. This retrospective cross‐sectional study at a university hospital aimed to determine CSHCN's medical spectrum, dental treatment needs, and mode of treatment: general anesthesia (GA) or outpatient dental care (ODC).

Design

Data from the Department of Conservative Dentistry, Heidelberg University Hospital, 2012–2022, were reviewed, considering age, gender, International Classification of Diseases‐10 diagnoses, caries experience (dmft/DMFT), restorative parameters, and treatment under GA/ODC. For patients under GA, their American Society of Anesthesiologists (ASA) classification was considered. Descriptive statistics, Kruskal–Wallis test, Mann–Whitney U‐test and logistic regression were utilized.

Results

Of 669 patients, congenital and chromosomal malformations (34.7%), diseases of the nervous system (19.1%), and mental and behavioral disorders (16.0%) were mainly diagnosed. Dentin caries prevalence was high at 79.1%, with treatments performed mainly under GA (51.4%). The odds of receiving treatment under GA decreased with patient age and increased with higher dmft/DMFT scores. Most under GA were classified as ASA 3 (51.7%), indicating high anesthesia risks.

Conclusion

Children with special healthcare needs often have diseases that can lead to higher challenges related to cooperation. The high prevalence of dentin caries underscores the substantial need for dental treatments, which were consequently often performed under GA, despite the associated risks. These findings stress the need for trained dental professionals.
Contextually balanced engagement: Navigating paradoxes of localisation and cultural embedding in rural health information systems implementation
Authors: Qureshi Israr , Shukla Dhirendra Mani , Bhatt Babita , Hota Pradeep , Sun Ruonan
Published: April 2024

Although health information systems (HIS) play an important role in elevating health standards, a comprehensive understanding of how to effectively implement HIS in rural areas is lacking. This issue becomes more significant when considering that globally a majority of the approximately 1.5 million deaths of children under the age of five in 2019 that were attributable to vaccine‐preventable diseases occurred in rural areas. Accordingly, we ask two questions. How does rurality influence the implementation of information and communication technology for development (ICT4D) projects? How do organisations navigate challenges associated with rurality during the implementation of these projects? Our findings, derived from an in‐depth case study of a social enterprise in rural India, reveal two paradoxes that pose challenges to the effective implementation of HIS in rural settings: the localisation paradox and the cultural embedding paradox. We found that contextually balanced engagement was comprised of four organisational responses—prioritising; localising; cultural adjustment; and engaging stakeholders—that help navigate the challenges posed by the localisation and cultural embedding paradoxes. Synthesising these findings, we develop a process model that shows how the implementation of HIS in rural areas is shaped by the descriptive and sociocultural characteristics of rurality. Further, organisations require a dynamic approach, engaging in multiple responses over time to navigate the paradoxes inherent in HIS implementation. We suggest that organisational responses to paradoxical tensions stemming from the descriptive and sociocultural characteristics of rurality lead to the development of HIS enabled for rurality. Our findings contribute the understanding of ICT4D projects implementation.
Nurse leaders' interpersonal communication competence: A mixed‐method systematic review
Authors: Kämäräinen Petra , Mikkola Leena , Nurmeksela Anu , Wright Mea , Kvist Tarja
Published: April 2024

Aim(s)

To identify and synthesize evidence available on nurse leaders' interpersonal communication competence.

Design

Systematic mixed‐methods review according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis checklist.

Methods

The data were collected following predefined inclusion criteria. Two authors independently performed the study selection using Covidence software. Three authors assessed the quality using Joanna Briggs' Institute's critical appraisal tool and the mixed‐methods appraisal tool. The data‐based convergent synthesis design and narrative synthesis were used.

Data Sources

CINAHL, PubMed, Scopus, Business Source Elite, Academic Search Premier, Communication & Mass Media Complete, PsycInfo, Web of Sciences, Medic and Finna.fi were searched and the screening of citations in relevant articles. The final searches were performed on 17 October 2022.

Results

A total of 26 studies—15 quantitative, 9 qualitative and 1 of both mixed‐method and multi‐method—met the inclusion criteria. The nurse leaders' interpersonal communication competences described in the extant literature were categorized into three themes: message competence, relational competence and task competence. There were considerable differences in the levels of competence, as some competences were considered basic communication skills, while others required more advanced level competences. Furthermore, three competence levels were identified: novice, competent and expert.

Conclusions

This study unravels a unique hierarchical description of communication skills across competence categories, supported by the assumption that communication skills are structured hierarchically. The studies reviewed herein had a narrow perception of nurse leaders' interpersonal communication competence and indicated a transmissional understanding of communication.

Impact

This is the first mixed‐methods systematic review that describes and synthesizes the evidence on nurse leaders' communication competencies hierarchically and across competence levels. The study suggests that further research should focus on a broader and more analytical understanding of the cognitive and affective aspects of interpersonal communication competence.

PROSPERO ID

CRD42023385058.

Patient or Public Contribution

No patient or public contribution.
Improving the effectiveness of financial education programs. A targeting approach
Authors: Buratti Ginevra , D'Ignazio Alessio
Published: April 2024

We investigate whether targeting algorithms can improve the effectiveness of financial education programs by identifying ex‐ante the most appropriate recipients. To this end, we use micro‐data from around 3800 individuals who participated in a financial education campaign conducted in Italy in late 2021. First, we employ machine learning (ML) tools to devise a targeting rule that identifies individuals who should be primarily targeted by a financial education campaign based on easily observable characteristics. Second, we simulate a policy scenario, using a random sample of individuals who took part in the campaign but were not employed to devise the targeting rule. We find that pairing a financial education campaign with an ML‐based targeting rule leads to greater effectiveness. Finally, we discuss the policy implications of our findings, and the conditions that must be met for ML‐based targeting to be effectively implemented.
A Portfolio Approach to Global Imbalances
Authors: JIANG ZHENGYANG , RICHMOND ROBERT J. , ZHANG TONY
Published: April 2024

We use a portfolio‐based framework to understand what drives the decline of the U.S. net foreign asset (NFA) position and the reversal in returns earned on the U.S. NFA (exorbitant privilege). We show that global savings gluts and monetary policies widened the U.S. NFA position, while investor demand shifts partially offset this widening. Moreover, U.S. privilege declined after 2010, in line with increasing foreign demand for U.S. equity. We also highlight a quantity dimension of the U.S. privilege: The U.S. can issue substantially more debt than other countries for a given yield increase.
Loss of GCN5L1 exacerbates damage in alcoholic liver disease through ferroptosis activation
Authors: Yang Chenxi , Yang Ye , Hu Xiuya , Tang Qiqi , Zhang Jiaqi , Zhang Peiyu , Lu Xin , Xu Juan , Li Sai , Dong Zhengni , Zhu Lu , Wang Lingdi
Published: April 2024

Background and Aims

Iron overload, oxidative stress and ferroptosis are associated with liver injury in alcohol‐associated liver disease (ALD), however, the crosstalk among these regulatory pathways in ALD development is unclear.

Methods

ALD mouse model and general control of amino acid synthesis 5 like 1 (GCN5L1) liver knockout mice were generated to investigate the role of GCN5L1 in ALD development. Proteomic screening tests were performed to identify the key factors mediating GCN5L1 loss‐induced ALD.

Results

Gene Expression Omnibus data set analysis indicates that GCN5L1 expression is negatively associated with ALD progression. GCN5L1 hepatic knockout mice develop severe liver injury and lipid accumulation when fed an alcohol diet. Screening tests identified that GCN5L1 targeted the mitochondrial iron transporter CISD1 to regulate mitochondrial iron homeostasis in ethanol‐induced ferroptosis. GCN5L1‐modulated CISD1 acetylation and activity were crucial for iron accumulation and ferroptosis in response to alcohol exposure.

Conclusion

Pharmaceutical modulation of CISD1 activity is critical for cellular iron homeostasis and ethanol‐induced ferroptosis. The GCN5L1/CISD1 axis is crucial for oxidative stress and ethanol‐induced ferroptosis in ALD and is a promising avenue for novel therapeutic strategies.
Sonata Form as Temporal Process: the First Movement of Bruckner's Sixth symphony
Authors: KIM SUNBIN
Published: April 2024

The timeworn view that Bruckner's sonata form is a motionless architecture devoid of dynamic processes has long contributed his isolation from the mainstream post‐Beethovenian tradition. Taking inspiration from August Halm's (1914) and Ernst Kurth's (1925) approaches, which were aimed at overcoming this view, this article seeks to elucidate the processual aspects of Bruckner's symphonic form in light of recent theoretical developments in musical form. Specifically, it combines William Caplin's form‐functional theory (1998), especially its beginning–middle–end paradigm, with Matthew Arndt's (2018) reconception of formal functionality to construct a new framework for the analysis of Bruckner's symphonic forms.

By way of an analytical case study of the first movement of Bruckner's Sixth Symphony, the article reveals that the expression of continuous motion occurring across discrete formal entities, often further dramatised by ‘wave dynamics’ (Kurth 1925), is fundamental to Bruckner's reinvigoration of sonata form's inherent temporal process in a post‐Romantic context. In the exposition, the inter‐thematic beginning, middle and end paradigms are redistributed to the three thematic groups, which express their unique temporal domain while delineating a continuous tonal journey from the home key to the subordinate key. The remainder of the movement articulates a gradual journey of homecoming, with each subsequent large‐scale part addressing previously suggested tonal implications. Ultimately, the modified form‐functional approach adopted in this study sheds light on Bruckner's exceptional care for formal syntax on various levels of structure, and its close association with an overarching, though unconventional, tonal plot.
Prairie voles as a model for adaptive reward remodeling following loss of a bonded partner
Authors: Sadino Julie M. , Donaldson Zoe R.
Published: April 2024

Loss of a loved one is a painful event that substantially elevates the risk for physical and mental illness and impaired daily function. Socially monogamous prairie voles are laboratory‐amenable rodents that form life‐long pair bonds and exhibit distress upon partner separation, mirroring phenotypes seen in humans. These attributes make voles an excellent model for studying the biology of loss. In this review, we highlight parallels between humans and prairie voles, focusing on reward system engagement during pair bonding and loss. As yearning is a unique feature that differentiates loss from other negative mental states, we posit a model in which the homeostatic reward mechanisms that help to maintain bonds are disrupted upon loss, resulting in yearning and other negative impacts. Finally, we synthesize studies in humans and voles that delineate the remodeling of reward systems during loss adaptation. The stalling of these processes likely contributes to prolonged grief disorder, a diagnosis recently added to the Diagnostic and Statistical Manual for Psychiatry.
Efficient chemiluminescence of luminol in the presence of hemin without added hydrogen peroxide†
Authors: Tsaplev Yurii B. , Trofimov Aleksei V.
Published: April 2024

The results reported herein demonstrate for the first time that typical reducing agents in an alkaline medium initiate chemiluminescence of luminol in the presence of hemin, and the efficiency of their action is comparable to that of hydrogen peroxide and exceeds it in the case of the superoxide anion. The pertinent implications of these findings refer to new possibilities for developing chemiluminescence assays and biosensors and to precautions for determining hydrogen peroxide using luminol and hemin in samples of unknown composition, most prominently, of biological origin.
Social functioning predicts individual changes in EEG microstates following intranasal oxytocin administration: A double‐blind, cross‐over randomized clinical trial
Authors: Tomescu Miralena I. , Van der Donck Stephanie , Perisanu Emanuela M. , Berceanu Alexandru I. , Alaerts Kaat , Boets Bart , Carcea Ioana
Published: April 2024

Oxytocin (OXT) modulates social behaviors. However, the administration of exogenous OXT in humans produces inconsistent behavioral changes, affecting future consideration of OXT as a treatment for autism and other disorders with social symptoms. Inter‐individual variability in social functioning traits might play a key role in how OXT changes brain activity and, therefore, behavior. Here, we investigated if inter‐individual variability might dictate how single‐dose intranasal OXT administration (IN‐OXT) changes spontaneous neural activity during the eyes‐open resting state. We used a double‐blinded, randomized, placebo‐controlled, cross‐over design on 30 typically developing young adult men to investigate the dynamics of EEG microstates corresponding to activity in defined neural networks. We confirmed previous reports that, at the group level, IN‐OXT increases the representation of the attention and salience microstates. Furthermore, we identified a decreased representation of microstates associated with the default mode network. Using multivariate partial least square statistical analysis, we found that social functioning traits associated with IN‐OXT‐induced changes in microstate dynamics in specific spectral bands. Correlation analysis further revealed that the higher the social functioning, the more IN‐OXT increased the appearance of the visual network‐associated microstate, and suppressed the appearance of a default mode network‐related microstate. The lower the social functioning, the more IN‐OXT increases the appearance of the salience microstate. The effects we report on the salience microstate support the hypothesis that OXT regulates behavior by enhancing social salience. Moreover, our findings indicate that social functioning traits modulate responses to IN‐OXT and could partially explain the inconsistent reports on IN‐OXT effects.
Blocked versus interleaved: How range contexts modulate time perception and its EEG signatures
Authors: Baykan Cemre , Zhu Xiuna , Zinchenko Artyom , Shi Zhuanghua
Published: April 2024

Accurate time perception is a crucial element in a wide range of cognitive tasks, including decision‐making, memory, and motor control. One commonly observed phenomenon is that when given a range of time intervals to consider, people's estimates often cluster around the midpoint of those intervals. Previous studies have suggested that the range of these intervals can also influence our judgments, but the neural mechanisms behind this “range effect” are not yet understood. We used both behavioral tests and electroencephalographic (EEG) measures to understand how the range of sample time intervals affects the accuracy of people's subsequent time estimates. Study participants were exposed to two different setups: In the “blocked‐range” (BR) session, short and long intervals were presented in separate blocks, whereas in the “interleaved‐range” (IR) session, intervals of various lengths were presented randomly. Our findings indicated that the BR context led to more accurate time estimates compared to the IR context. In terms of EEG data, the BR context resulted in quicker buildup of contingent negative variation (CNV), which also reached higher amplitude levels and dissolved more rapidly during the encoding stage. We also observed an enhanced amplitude in the offset P2 component of the EEG signal. Overall, our results suggest that the variability in time intervals, as defined by their range, influences the neural processes that underlie time estimation.
The concept of unlivability: A reading of Frantz Fanon's “The North African Syndrome” (1952)
Authors: Dhanvantari Sujaya
Published: April 2024

From a close reading of Frantz Fanon's “The North African Syndrome” (1952), this article draws out Fanon's understanding of “death in life” to suggest that a concept of unlivability in the present must account for the temporal duration of racialized and colonized experiences of pain and trauma. It is thus critical of Judith Butler's and Frédéric Worms's discussion of unlivability in The Livable and The Unlivable (2023) for not centering a phenomenological study of the testimonies of the oppressed. I argue for a greater engagement with Fanon on the longue durée of racial and colonial violence enacted on the bodies, psyches, and histories of racialized and colonized peoples. This article concludes by pointing to possibilities for a shared unlivability in a shared temporality, with potential to move beyond refusal and toward resistance to the colonial control over time.
Picturing self‐harm: Investigating flash‐forward mental imagery as a proximal and modifiable driver of non‐suicidal self‐injury
Authors: Ji Julie L. , Kyron Michael , Saulsman Lisa , Becerra Rodrigo , Lin Ashleigh , Hasking Penelope , Holmes Emily A.
Published: April 2024

Objectives

Non‐suicidal self‐injury (NSSI) is theorized to be reinforced by its emotional consequences. Mental images of NSSI are commonly reported as occurring prior to NSSI. Based on the known functional properties of anticipatory mental imagery as an emotional and motivational amplifier, this study investigated whether NSSI mental imagery constitutes a proximal and dynamic mechanism underpinning NSSI risk.

Method

An intensive ecological momentary assessment (EMA) study was conducted to track the occurrence and characteristics of NSSI mental imagery alongside NSSI urge and behavior in naturalistic settings. A sample of N = 43 individuals aged 17 to 24 with a history of repetitive NSSI completed EMA surveys seven times a day for 14 days.

Results

Mental preoccupation in the form of NSSI mental imagery‐based flash‐forwards to the actions, bodily sensations, and emotional benefits of NSSI was found to occur when NSSI urge was high but not when urge was low. Critically, objective cross‐panel analyses showed that higher frequencies of NSSI imagery occurrence predicted greater future NSSI urge and increased likelihood of acting on urge, over and above current urge.

Conclusions

Mental imagery of NSSI is not simply an epiphenomenal by‐product of NSSI urge and may constitute a dynamic and proximal novel intervention target.
Identity and standards for English as a European Union lingua franca
Authors: Modiano Marko
Published: April 2024

This article addresses, from an applied linguistics perspective, the position English maintains among the myriad of languages spoken in the European Union (EU). The linguistic make‐up of EU society, as well as the language policy of the Union, is scrutinised. The role English is playing in European unification is also important for the discussion, as is the call for a re‐evaluation of the norms deployed in English language teaching. The linguistic nativisation currently taking place in mainland Europe, which indicates that English is functioning more as an Outer Circle rather than as an Expanding Circle language, is juxtaposed with these developments.
English in Dutch‐speaking Europe: Features, competence, domains and status
Authors: Gerritsen Marinel
Published: April 2024

After a description of the area in Europe where Dutch is an official language, the historical developments are discussed that resulted in differences between the Netherlands and Dutch‐speaking Belgium (Flanders) in attitude towards Dutch and foreign languages. Next, features of English in these areas, its effects on Inner Circle and other speakers of English and norms strived for are dealt with. English competence is described on the basis of learning objectives for English and results of large‐scale studies. Subsequently, domains where English is used are described: education, scientific research, business, songs. Finally, the attitude of the Dutch and Flemish towards English is outlined. These data are considered in the perspective of the Outer or Expanding Circle status of English. In both the Netherlands and Flanders English does not have second language status, but is the first foreign language, although French has that status by law in Flanders.
Auckland Council Food Scraps Project
Authors: Doyle Max
Published: April 2024

This research project delves into the complexities of Auckland City Council's food scraps collection rollout, spanning from kerbside collection to the Anaerobic Digestion Facility in Reporoa, Rotorua; where collected food scraps are transformed into environmentally friendly fertilisers and renewable gases. The project comprises two key components: assisting in the creation of a dashboard to display weekly and monthly collection and disposal data to monitor ongoing participation rates and collected tonnage requirements are met; and assisting with the continuation of the food scraps rollout initiative in wider Auckland regions and help increase consumer knowledge and involvement. This is in conjunction of aligning with Auckland Council's aim for zero waste by 2040. The initiative aims to keep food scraps out of landfills, minimising harmful greenhouse gas emissions and return valuable nutrients to the land through biofertiliser production. This project required me to learn about Auckland's circular economy solution which emphasises prevention of food waste, supporting redistribution initiatives, and promoting home and community composting. As part of helping with the rollout and helping create an easy way for residents to separate their food scraps from general rubbish, individuals have gained a raised awareness of wastage, leading to considered meal planning and cost savings. The government's commitment to nationwide food scraps services by 2030 underscores the urgency of sustainable waste management practices which it why it was crucial for me to be familiar with the whole process and sectors within the rollout to assist Auckland Council to meet this commitment. This project has also meant that I was able to understand the whole process of the Anaerobic Digestion Facility's innovative technology which processes organic material into biogas and nutrient-liquid fertiliser, contributing to New Zealand's sustainability goals. Through comprehensive monitoring and filtration systems, the facilities uphold environmental standards while pioneering large-scale food scraps processing in the country.

Supervised by: Sarah Nicholls

Scholarship Project Funded by: Auckland City Council
Over 6 MV/cm operation in β-Ga2O3 Schottky barrier diodes with IrO2 and RuO2 anodes deposited by molecular beam epitaxy
Authors: Cromer B. , Saraswat D. , Pieczulewski N. , Li W. , Nomoto K. , Hensling F. V. E. , Azizie K. , Nair H. P. , Schlom D. G. , Muller D. A. , Jena D. , Xing H. G.
Published: April 2024

β -Ga2O3 is actively touted as the next ultrawide bandgap material for power electronics. To fully utilize its high intrinsic critical electric field, development of high-quality robust large-barrier height junctions is essential. To this end, various high-work function metals, metal oxides, and hole-conducting oxides have been deposited on Ga2O3, primarily formed by sputter deposition. Unfortunately, reports to date indicate that measured barrier heights often deviate from the Schottky–Mott model as well as x-ray photoelectron spectroscopy (XPS) extractions of conduction band offsets, suggesting significant densities of electrically active defects at these junctions. We report Schottky diodes made from noble metal oxides, IrO2 and RuO2, deposited by ozone molecular beam epitaxy (ozone MBE) with barrier heights near 1.8 eV. These barriers show close agreement across extraction methods and robust to high surface electric fields upward of 6 MV/cm and 60 A/cm2 reverse current without degradation.
Remote inductively coupled plasmas in Ar/N2 mixtures and implications for plasma enhanced ALD
Authors: Boris David R. , Johnson Michael J. , Woodward Jeffrey M. , Wheeler Virginia D. , Walton Scott G.
Published: April 2024

Plasma enhanced atomic layer deposition (PEALD) is a cyclic atomic layer deposition (ALD) process that incorporates plasma-generated species into one of the cycle substeps. The addition of plasma is advantageous as it generally provides unique reactants and a substantially reduced growth temperature compared to thermal approaches. However, the inclusion of plasma, coupled with the increasing variety of plasma sources used in PEALD, can make these systems challenging to understand and control. This work focuses on the use of plasma diagnostics to examine the plasma characteristics of a remote inductively coupled plasma (ICP) source, a type of plasma source that is commonly used for PEALD. Ultraviolet to near-infrared spectroscopy and spatially resolved Langmuir probe measurements are employed to characterize a remote ICP system using nitrogen-based gas chemistries typical for III-nitride growth processes. Spectroscopy is used to characterize the relative concentrations of important reactive and energetic neutral species generated in the remote ICP as a function of gas flow rate, Ar/N2 flow fraction, and gas pressure. In addition, the plasma potential and plasma density for the same process parameters are examined using an RF compensated Langmuir probe downstream from the ICP source. The results are also discussed in terms of their impact on materials growth.
Combinatorially restricted computational design of protein-protein interfaces to produce IgG heterodimers
Authors: Azzam Tala , Du Jonathan J. , Flowers Maria W. , Ali Adeela V. , Hunn Jeremy C. , Vijayvargiya Nina , Knagaram Rushil , Bogacz Marek , Maravillas Kino E. , Sastre Diego E. , Fields James K. , Mirzaei Ardalan , Pierce Brian G. , Sundberg Eric J.
Published: April 2024

Redesigning protein-protein interfaces is an important tool for developing therapeutic strategies. Interfaces can be redesigned by in silico screening, which allows for efficient sampling of a large protein space before experimental validation. However, computational costs limit the number of combinations that can be reasonably sampled. Here, we present combinatorial tyrosine (Y)/serine (S) selection (combYSelect), a computational approach combining in silico determination of the change in binding free energy (ΔΔ
G
) of an interface with a highly restricted library composed of just two amino acids, tyrosine and serine. We used combYSelect to design two immunoglobulin G (IgG) heterodimers—combYSelect1 (L368S/D399Y-K409S/T411Y) and combYSelect2 (D399Y/K447S-K409S/T411Y)—that exhibit near-optimal heterodimerization, without affecting IgG stability or function. We solved the crystal structures of these heterodimers and found that dynamic π-stacking interactions and polar contacts drive preferential heterodimeric interactions. Finally, we demonstrated the utility of our combYSelect heterodimers by engineering both a bispecific antibody and a cytokine trap for two unique therapeutic applications.
The scales, mechanisms, and dynamics of the genome architecture
Authors: Lizana Ludvig , Schwartz Yuri B.
Published: April 2024

Even when split into several chromosomes, DNA molecules that make up our genome are too long to fit into the cell nuclei unless massively folded. Such folding must accommodate the need for timely access to selected parts of the genome by transcription factors, RNA polymerases, and DNA replication machinery. Here, we review our current understanding of the genome folding inside the interphase nuclei. We consider the resulting genome architecture at three scales with a particular focus on the intermediate (meso) scale and summarize the insights gained from recent experimental observations and diverse computational models.
Learning agile soccer skills for a bipedal robot with deep reinforcement learning
Authors: Haarnoja Tuomas , Moran Ben , Lever Guy , Huang Sandy H. , Tirumala Dhruva , Humplik Jan , Wulfmeier Markus , Tunyasuvunakool Saran , Siegel Noah Y. , Hafner Roland , Bloesch Michael , Hartikainen Kristian , Byravan Arunkumar , Hasenclever Leonard , Tassa Yuval , Sadeghi Fereshteh , Batchelor Nathan , Casarini Federico , Saliceti Stefano , Game Charles , Sreendra Neil , Patel Kushal , Gwira Marlon , Huber Andrea , Hurley Nicole , Nori Francesco , Hadsell Raia , Heess Nicolas
Published: April 2024

We investigated whether deep reinforcement learning (deep RL) is able to synthesize sophisticated and safe movement skills for a low-cost, miniature humanoid robot that can be composed into complex behavioral strategies. We used deep RL to train a humanoid robot to play a simplified one-versus-one soccer game. The resulting agent exhibits robust and dynamic movement skills, such as rapid fall recovery, walking, turning, and kicking, and it transitions between them in a smooth and efficient manner. It also learned to anticipate ball movements and block opponent shots. The agent’s tactical behavior adapts to specific game contexts in a way that would be impractical to manually design. Our agent was trained in simulation and transferred to real robots zero-shot. A combination of sufficiently high-frequency control, targeted dynamics randomization, and perturbations during training enabled good-quality transfer. In experiments, the agent walked 181% faster, turned 302% faster, took 63% less time to get up, and kicked a ball 34% faster than a scripted baseline.
An autonomous plasmid as an inovirus phage satellite
Authors: Schmid Nicole , Brandt David , Walasek Claudia , Rolland Clara , Wittmann Johannes , Fischer Dorian , Müsken Mathias , Kalinowski Jörn , Thormann Kai
Published: April 2024

Bacterial viruses (phages) are potent agents of lateral gene transfer and thus are important drivers of evolution. A group of mobile genetic elements, referred to as phage satellites, exploits phages to disseminate their own genetic material. Here, we isolated a novel member of the family Inoviridae,
Shewanella
phage Dolos, along with an autonomously replicating plasmid, pDolos. Dolos causes a chronic infection in its host
Shewanella oneidensis
by phage production with only minor effects on the host cell proliferation. When present, plasmid pDolos hijacks Dolos functions to be predominantly packaged into phage virions and released into the environment and, thus, acts as a phage satellite. pDolos can disseminate further genetic material encoding, e.g., resistances or fluorophores to host cells sensitive to Dolos infection. Given the rather simple requirements of a plasmid for takeover of an inovirus and the wide distribution of phages of this group, we speculate that similar phage-satellite systems are common among bacteria.

IMPORTANCE

Phage satellites are mobile genetic elements, which hijack phages to be transferred to other host cells. The vast majority of these phage satellites integrate within the host’s chromosome, and they all carry remaining phage genes. Here, we identified a novel phage satellite, pDolos, which uses an inovirus for dissemination. pDolos (i) remains as an autonomously replicating plasmid within its host, (ii) does not carry recognizable phage genes, and (iii) is smaller than any other phage satellites identified so far. Thus, pDolos is the first member of a new class of phage satellites, which resemble natural versions of phagemids.
Evidence for intracellular
Pseudomonas aeruginosa
Authors: Resko Zachary J. , Suhi Rachel F. , Thota Adam V. , Kroken Abby R.
Published: April 2024

Pseudomonas aeruginosa
is a significant cause of global morbidity and mortality. Although it is often regarded as an extracellular pathogen toward human cells, numerous investigations report its ability to survive and replicate within host cells, and additional studies demonstrate specific mechanisms enabling it to adopt an intracellular lifestyle. This ability of
P. aeruginosa
remains less well-investigated than that of other intracellular bacteria, although it is currently gaining attention. If intracellular bacteria are not killed after entering host cells, they may instead receive protection from immune recognition and experience reduced exposure to antibiotic therapy, among additional potential advantages shared with other facultative intracellular pathogens. For this review, we compiled studies that observe intracellular
P. aeruginosa
across strains, cell types, and experimental systems
in vitro
, as well as contextualize these findings with the few studies that report similar observations
in vivo
. We also seek to address key findings that drove the perception that
P. aeruginosa
remains extracellular in order to reconcile what is currently understood about intracellular pathogenesis and highlight open questions regarding its contribution to disease.
Mesozoic intra-arc basin records the tectonic transition from the Paleo-Asian Ocean to the Paleo-Pacific Ocean in northeastern Eurasia
Authors: Wang Hong-Yan , Zhou Jian-Bo , Wilde Simon A. , Li Gong-Yu , Fu Bin
Published: April 2024

Since the Paleozoic, the tectonic evolution of northeastern Eurasia has been dominated by the Paleo-Asian Ocean and the Paleo-Pacific Ocean tectonic domains. However, the spatiotemporal framework and the timing of tectonic transition between these two oceanic domains remain enigmatic. To address this issue, we report petrological, geochronological, and geochemical data for eight sandstone samples deposited along the convergent margin between the Northeast China terranes and the North China craton in central Jilin Province, China. The results show that these sandstones are immature graywackes with a maximum depositional age of Early Triassic (248 ± 1 Ma), and their sediments were largely derived from coeval magmatic rocks in a juvenile continental arc. According to our new results and previous studies, we identified a sedimentary basin (most likely an intra-arc or forearc basin) intimately associated with one or more continental arcs along the northeastern edge of the North China craton, and we suggest that the southwestward subduction of the Jilin-Heilongjiang Ocean in the early Mesozoic accounts for this continental arc setting. There is a distinct temporal gap between the closure of the Paleo-Asian Ocean (ca. 260 Ma) and the onset of Paleo-Pacific plate subduction (234–220 Ma), which is essentially coeval with the southwestward subduction of the Jilin-Heilongjiang Ocean between 256 Ma and 239 Ma, meaning the latter is a key link that marks the transition between these two tectonic domains.
Supplemental Material: Scoria cone erosional degradation by incision: Different behaviors in three volcanic fields reflect environmental conditions
Authors: Zarazúa-Carbajal Maria C. , al. et
Published: April 2024

Table S1: Results from the 20 analyzed scoria cones within the Lunar Crater Volcanic Field.  
Strength, power and aerobic capacity of transgender athletes: a cross-sectional study
Authors: Hamilton Blair , Brown Andrew , Montagner-Moraes Stephanie , Comeras-Chueca Cristina , Bush Peter G , Guppy Fergus M , Pitsiladis Yannis P
Published: April 2024

Objective

The primary objective of this cross-sectional study was to compare standard laboratory performance metrics of transgender athletes to cisgender athletes.

Methods

19 cisgender men (CM) (mean±SD, age: 37±9 years), 12 transgender men (TM) (age: 34±7 years), 23 transgender women (TW) (age: 34±10 years) and 21 cisgender women (CW) (age: 30±9 years) underwent a series of standard laboratory performance tests, including body composition, lung function, cardiopulmonary exercise testing, strength and lower body power. Haemoglobin concentration in capillary blood and testosterone and oestradiol in serum were also measured.

Results

In this cohort of athletes, TW had similar testosterone concentration (TW 0.7±0.5 nmol/L, CW 0.9±0.4 nmol/), higher oestrogen (TW 742.4±801.9 pmol/L, CW 336.0±266.3 pmol/L, p=0.045), higher absolute handgrip strength (TW 40.7±6.8 kg, CW 34.2±3.7 kg, p=0.01), lower forced expiratory volume in 1 s:forced vital capacity ratio (TW 0.83±0.07, CW 0.88±0.04, p=0.04), lower relative jump height (TW 0.7±0.2 cm/kg; CW 1.0±0.2 cm/kg, p<0.001) and lower relative V̇O2max (TW 45.1±13.3 mL/kg/min/, CW 54.1±6.0 mL/kg/min, p<0.001) compared with CW athletes. TM had similar testosterone concentration (TM 20.5±5.8 nmol/L, CM 24.8±12.3 nmol/L), lower absolute hand grip strength (TM 38.8±7.5 kg, CM 45.7±6.9 kg, p=0.03) and lower absolute V̇O2max (TM 3635±644 mL/min, CM 4467±641 mL/min p=0.002) than CM.

Conclusion

While longitudinal transitioning studies of transgender athletes are urgently needed, these results should caution against precautionary bans and sport eligibility exclusions that are not based on sport-specific (or sport-relevant) research.
Advances in management of heart failure
Authors: Heidenreich Paul , Sandhu Alexander
Published: April 2024

Heart failure is increasing in prevalence in many countries with aging populations. Fortunately, remarkable scientific advances have been made in the past few years that have led to new treatments and improved prognosis for patients with heart failure. This review examines these changes with a focus on the diagnosis and medical management of heart failure. The changes include the increase to four foundational drug classes (pillars of therapy) now recommended for patients with heart failure and reduced left ventricular ejection fraction, use of sodium-glucose cotransporter-2 inhibitors for those with a higher ejection fraction, and the importance of rapid initiation of life prolonging therapies once a diagnosis of heart failure has been made. Device management and other non-drug management have also evolved with the publication of new clinical trials. The review emphasizes evidence published since the recent heart failure guidelines of the European Society of Cardiology and American College of Cardiology/American Heart Association/Heart Failure Society of America in 2021 and 2022. Additional studies are needed to determine how best to implement these new interventions in clinical practice.
Efficacy of a digital lifestyle intervention on health-related QUAlity of life in non-small cell LUng CAncer survivors following inpatient rehabilitation: protocol of the QUALUCA Swiss multicentre randomised controlled trial
Authors: Weber Manuel , Raab Anja Maria , Schmitt Kai-Uwe , Büsching Gilbert , Marcin Thimo , Spielmanns Marc , Puhan Milo Alan , Frei Anja
Published: April 2024

Introduction

Non-small cell lung cancer (NSCLC) survivors suffer from impaired physical and psychological functioning and reduced health-related quality of life (HRQoL) that persist after active treatment ends. Sustaining rehabilitation benefits, promoting a healthy lifestyle and facilitating self-management at home require a multifaceted aftercare programme. We aim to investigate the effect of a 12-week digital lifestyle intervention on HRQoL and lifestyle-related outcomes in NSCLC survivors after completion of inpatient rehabilitation.

Methods and analysis

QUAlity of life in LUng CAncer Survivors (QUALUCA) is a multicentre randomised controlled trial that follows a hybrid type 1 design. We randomly allocate participants in a 1:1 ratio to the intervention group (digital lifestyle intervention) or the control group (standard care) using block randomisation stratified by tumour stage and study site. Four accredited Swiss inpatient rehabilitation centres recruit participants. Key inclusion criteria are a diagnosis of NSCLC, an estimated life expectancy of ≥6 months and access to a smartphone or tablet. The 12-week intervention comprises physical activity, nutrition and breathing/relaxation, delivered through a mobile application (app). The primary outcome is the change in HRQoL from baseline (1 week after rehabilitation) to follow-up (3 months after baseline), assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Secondary outcomes include body mass index, self-reported physical activity, exercise capacity, risk of low protein intake, appetite, psychological distress, cancer-related fatigue, enablement and self-rated health. Explanatory outcomes in the intervention group include app usability, acceptability, appropriateness, and feasibility of the intervention, experiences and satisfaction with the intervention, and app usage data. We aim to enrol 88 participants. For the main statistical analysis, we will use analysis of covariance, adjusted for baseline measures, stratification variables, age and sex.

Ethics and dissemination

The Ethics Committees of the Canton of Zurich (lead), the Canton of Bern and Northwest and Central Switzerland approved the study (2023-00245). We will disseminate study results to researchers, health professionals, study participants and relevant organisations, and through publications in international peer-reviewed journals.

Trial registration number

NCT05819346
.
Novel potential lncRNA biomarker in B cells indicates essential pathogenic pathway activation in patients with SLE
Authors: Zhu Xinyi , Chen Yashuo , Yin Zhihua , Zhang Yutong , Shen Yiwei , Dai Dai , Lin Xiaojing , Zou Ling-Hua , Shen Nan , Ye Zhizhong , Ding Huihua , Hou Guojun
Published: April 2024

Objectives

Systemic lupus erythematosus (SLE) is a highly heterogeneous disease, and B cell abnormalities play a central role in the pathogenesis of SLE. Long non-coding RNAs (lncRNAs) have also been implicated in the pathogenesis of SLE. The expression of lncRNAs is finely regulated and cell-type dependent, so we aimed to identify B cell-expressing lncRNAs as biomarkers for SLE, and to explore their ability to reflect the status of SLE critical pathway and disease activity.

Methods

Weighted gene coexpression network analysis (WGCNA) was used to cluster B cell-expressing genes of patients with SLE into different gene modules and relate them to clinical features. Based on the results of WGCNA, candidate lncRNA levels were further explored in public bulk and single-cell RNA-sequencing data. In another independent cohort, the levels of the candidate were detected by RT-qPCR and the correlation with disease activity was analysed.

Results

WGCNA analysis revealed one gene module significantly correlated with clinical features, which was enriched in type I interferon (IFN) pathway. Among non-coding genes in this module, lncRNA RP11-273G15.2 was differentially expressed in all five subsets of B cells from patients with SLE compared with healthy controls and other autoimmune diseases. RT-qPCR validated that RP11-273G15.2 was highly expressed in SLE B cells and positively correlated with IFN scores (r=0.7329, p<0.0001) and disease activity (r=0.4710, p=0.0005).

Conclusion

RP11-273G15.2 could act as a diagnostic and disease activity monitoring biomarker for SLE, which might have the potential to guide clinical management.
Incidence and outcome of COVID-19 following vaccine and hybrid immunity in patients on immunosuppressive therapy: identification of protective post-immunisation anti-RBD antibody levels in a prospective cohort study
Authors: Ørbo Hilde S , Bjørlykke Kristin H , Sexton Joseph , Jyssum Ingrid , Tveter Anne T , Christensen Ingrid E , Mjaaland Siri , Kvien Tore K , Grødeland Gunnveig , Kro Grete B , Jahnsen Jørgen , Haavardsholm Espen A , Munthe Ludvig A , Provan Sella A , Vaage John T , Goll Guro Løvik , Jørgensen Kristin Kaasen , Syversen Silje Watterdal
Published: April 2024

Objectives

To assess incidence, severity and predictors of COVID-19, including protective post-vaccination levels of antibodies to the receptor-binding domain of SARS-CoV-2 spike protein (anti-RBD), informing further vaccine strategies for patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive medication.

Methods

IMIDs on immunosuppressives and healthy controls (HC) receiving SARS-CoV-2 vaccines were included in this prospective observational study. COVID-19 and outcome were registered and anti-RBD antibodies measured 2–5 weeks post-immunisation.

Results

Between 15 February 2021 and 15 February 2023, 1729 IMIDs and 350 HC provided blood samples and self-reported COVID-19. The incidence of COVID-19 was 66% in patients and 67% in HC, with re-infection occurring in 12% of patients. Severe COVID-19 was recorded in 22 (2%) patients and no HC. No COVID-19-related deaths occurred. Vaccine-induced immunity gave higher risk of COVID-19 (HR 5.89 (95% CI 4.45 to 7.80)) than hybrid immunity. Post-immunisation anti-RBD levels <6000 binding antibody units/mL were associated with an increased risk of COVID-19 following three (HR 1.37 (95% CI 1.08 to 1.74)) and four doses (HR 1.28 (95% CI 1.02 to 1.62)), and of COVID-19 re-infection (HR 4.47 (95% CI 1.87 to 10.67)).

Conclusion

Vaccinated patients with IMID have a low risk of severe COVID-19. Hybrid immunity lowers the risk of infection. High post-immunisation anti-RBD levels protect against COVID-19. These results suggest that knowledge on COVID-19 history, and assessment of antibody levels post-immunisation can help individualise vaccination programme series in high-risk individuals.

Trial registration number

NCT04798625.
Distinctive profile of monomeric and polymeric anti-SSA/Ro52 immunoglobulin A1 isoforms in saliva of patients with primary Sjögren’s syndrome and Sicca
Authors: Chiang Samantha , Grogan Tristan , Kamounah Sarah , Wei Fang , Tayob Nabihah , Kim Ju Yeon , Kyun Park Jin , Akin David , Elashoff David A , Pedersen Anne Marie Lynge , Song Yeong Wook , Wong David T W , Chia David
Published: April 2024

Objective

Primary Sjögren’s syndrome (pSS) is the second most common chronic autoimmune connective tissue disease. Autoantibodies, immunoglobulin (IgG) anti-SSA/Ro, in serum is a key diagnostic feature of pSS. Since pSS is a disease of the salivary gland, we investigated anti-SSA/Ro52 in saliva.

Methods

Using a novel electrochemical detection platform, Electric Field-Induced Release and Measurement, we measured IgG/M/A, IgG, IgA, IgA isotypes (IgA1 and IgA2) and IgA1 subclasses (polymeric and monomeric IgA1) to anti-SSA/Ro52 in saliva supernatant of 34 pSS, 35 dry eyes and dry mouth (patients with Sicca) and 41 health controls.

Results

Saliva IgG/M/A, IgG, IgA, IgA isotypes and IgA1 subclasses to anti-SSA/Ro52 differed significantly between pSS, non-pSS Sicca and healthy subjects. Elevated monomeric IgA1 was observed in patients with non-pSS Sicca while elevated polymeric IgA1 (pIgA1) was observed in patients with pSS. Salivary polymeric but not monomeric IgA1 (mIgA1) isoform correlated with focus score (r2=0.467, p=0.001)

Conclusions

Salivary anti-Ro52 polymeric IgA1 isoform is associated with glandular inflammation in pSS, while salivary monomeric IgA1 is associated with Sicca. Whether IgA1 isotope switching plays a role in the progression of the Sicca to pSS warrants further investigation.