bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychological aspects of vestibular disorders: a national survey of clinical practice
Authors: Smith Laura J , Pyke Wesley , Wilkinson David , Travers-Hill Emma , Surenthiran SS
Published: April 2024

Objective

This study examines how psychological aspects of vestibular disorders are currently addressed highlighting any national variation.

Method

An online survey was completed by 101 UK healthcare professionals treating vestibular disorders. The survey covered service configurations, attitudes towards psychological aspects and current clinical practice.

Results

Ninety-six per cent of respondents thought there was a psychological component to vestibular disorders. There was a discrepancy between perceived importance of addressing psychological aspects and low confidence to undertake this. Those with more experience felt more confident addressing psychological aspects. History taking and questionnaires containing one or two psychological items were the most common assessment approaches. Discussing symptoms and signposting were the most frequent management approaches. Qualitative responses highlighted the interdependence of psychological and vestibular disorders which require timely intervention. Barriers included limited referral pathways, resources and interdisciplinary expertise.

Conclusion

Although psychological distress is frequently identified, suitable psychological treatment is not routinely offered in the UK.
Diagnostic criteria and core outcome set development for necrotising otitis externa: the COSNOE Delphi consensus study
Authors: Lodhi Sirat , Dodgson Kirsty , Dykes Michael , Vishwanath Veena , Bazaz Rohit , Mathur Sachin , Watson Glen , Cartwright Katherine , Pearson Amy , Wearmouth Deborah , List Richard , Yates Phillip , Dixon Joanna , Puveendran Arullendran , Wilson Margarita , Watson Katherine , Cullinan Milo , Mentias Youssef , Capper Ruth , Jewes Linda , Wallis Sebastian , Hamilton David , Adams Brook , Khalid-Raja Mamoona , Faris Barzo , Khan Maha , Linton Stefan , Abrar Rohma , Owen Eloise , Bisbinas Vasiliki , Ijaz Ali , Lau Kimberley , Timms Sara , Bruce Jack , Stapleton Emma
Published: April 2024

Objective

Evidence for necrotising otitis externa (NOE) diagnosis and management is limited, and outcome reporting is heterogeneous. International best practice guidelines were used to develop consensus diagnostic criteria and a core outcome set (COS).

Methods

The study was pre-registered on the Core Outcome Measures in Effectiveness Trials (COMET) database. Systematic literature review identified candidate items. Patient-centred items were identified via a qualitative study. Items and their definitions were refined by multidisciplinary stakeholders in a two-round Delphi exercise and subsequent consensus meeting.

Results

The final COS incorporates 36 items within 12 themes: Signs and symptoms; Pain; Advanced Disease Indicators; Complications; Survival; Antibiotic regimes and side effects; Patient comorbidities; Non-antibiotic treatments; Patient compliance; Duration and cessation of treatment; Relapse and readmission; Multidisciplinary team management.

Consensus diagnostic criteria include 12 items within 6 themes: Signs and symptoms (oedema, otorrhoea, granulation); Pain (otalgia, nocturnal otalgia); Investigations (microbiology [does not have to be positive], histology [malignancy excluded], positive CT and MRI); Persistent symptoms despite local and/or systemic treatment for at least two weeks; At least one risk factor for impaired immune response; Indicators of advanced disease (not obligatory but mut be reported when present at diagnosis). Stakeholders were unanimous that there is no role for secondary, graded, or optional diagnostic items. The consensus meeting identified themes for future research.

Conclusion

The adoption of consensus-defined diagnostic criteria and COS facilitates standardised research reporting and robust data synthesis. Inclusion of patient and professional perspectives ensures best practice stakeholder engagement.
Developing an accurately sized tonsil tie simulator: a prospective, observational study to measure the anatomical distance from the incisor teeth to the inferior tonsillar pole in a paediatric population
Authors: Eleftheriadou Aikaterini , Taylor Addison , Krishnan Madhankumar , Street Ian
Published: April 2024

Objective

The aim of this study is to measure the distance from the midline of the upper incisors to the lower pole of the tonsils in paediatric patients of varying ages. This will enable the design of accurately sized tonsil tie simulators.

Methods

Two hundred patients between 1 year and 16 years old were recruited in this prospective observational study. The patient's age and the mean distance from the midline of the upper incisors to the lower pole of the tonsils were plotted into a scatter plot and the line of best fit was calculated.

Results

The equation for the line of best fit was: distance (mm) = 1.9604 × age (digitalised years) + 72.436.

Conclusion

This is the first study to measure the anatomical distance from the upper incisor teeth to the inferior tonsillar pole in a paediatric population. This can be used to accurately size tonsil tie simulators and enhance their fidelity.
Nutritional vulnerability of early zoeal stages of the ornamental shrimp Lysmata ankeri (Decapoda: Caridea)
Authors: Barros-Alves Samara de P. , de Almeida Ariádine Cristine , Negreiros-Fransozo Maria Lucia , Alves Douglas Fernandes Rodrigues
Published: April 2024

The evaluation of the effects of early starvation and feeding on survival and growth in the early stages of the life cycle of ornamental marine caridean shrimp species is fundamental to establish adequate feeding protocols in their culture. In this study, we determine the nutritional vulnerability in the early larval stages of ornamental shrimp Lysmata ankeri exposed to different periods of starvation or feeding. The larvae were separated into three groups (zoea I-ZI, zoea II with ZI fed, and zoea II with ZI unfed) and subjected to two experiments: (1) point-of-no-return (PNR), comprising one or two days of initial starvation followed by feeding; and (2) point-of-reserve-saturation (PRS), comprising one or two days of initial feeding followed by starvation. Each experiment was still composed of two control groups: continuous feeding and continuous starvation. Larvae tolerated some periods of starvation, with a high PNR value (2.00) and low PRS (0.50). Longer periods of starvation influenced both growth and survival rates in zoea II stages. The nutritional vulnerability index for zoea I was 0.25, which represents a low dependence on food supply. In this study, it was observed that ornamental shrimp L. ankeri larvae hatch with energy reserves, presenting facultative primary lecithotrophy, in which they are able to moult from zoea I to zoea II using such reserves in the absence of food. In this sense, the early larvae stages (zoeas I and II) can tolerate a certain period of starvation, indicating the great potential of this species for aquaculture.
To what extent do children’s expressions of time actually refer to time? An investigation into the temporal and discursive usages of temporal adverbs in family interaction
Authors: Surakka Maija , Kirjavainen Minna
Published: April 2024

Many studies have explored children’s acquisition of temporal adverbs. However, the extent to which children’s early temporal language has discursive instead of solely temporal meanings has been largely ignored. We report two corpus-based studies that investigated temporal adverbs in Finnish child-parent interaction between the children’s ages of 1;7 and 4;11. Study 1 shows that the two corpus children used temporal adverbs to construe both temporal and discursive meanings from their early adverb production and that the children’s usage syntactically broadly reflected the input received. Study 2 shows that the discursive uses of adverbs appeared to be learned from contextually anchored caregiver constructions that convey discourse functions like urging and reassuring, and that the usage is related to the children’s and caregivers’ interactional roles. Our study adds to the literature on the acquisition of temporal adverbs by demonstrating that these items are learned also with additional discursive meanings in family interaction.
Insights into child abuse and neglect: Findings from the Minnesota Longitudinal Study of Risk and Adaptation
Authors: Nivison Marissa D. , Labella Madelyn H. , Raby K. Lee , Doom Jenalee R. , Martin Jodi , Johnson William F. , Zamir Osnat , Englund Michelle M. , Simpson Jeffry A. , Carlson Elizabeth A. , Roisman Glenn I.
Published: April 2024

The Minnesota Longitudinal Study of Risk and Adaptation (MLSRA) is a landmark prospective, longitudinal study of human development focused on a sample of mothers experiencing poverty and their firstborn children. Although the MLSRA pioneered a number of important topics in the area of social and emotional development, it began with the more specific goal of examining the antecedents of child maltreatment. From that foundation and for more than 40 years, the study has produced a significant body of research on the origins, sequelae, and measurement of childhood abuse and neglect. The principal objectives of this report are to document the early history of the MLSRA and its contributions to the study of child maltreatment and to review and summarize results from the recently updated childhood abuse and neglect coding of the cohort, with particular emphasis on findings related to adult adjustment. While doing so, we highlight key themes and contributions from Dr Dante Cicchetti’s body of research and developmental psychopathology perspective to the MLSRA, a project launched during his tenure as a graduate student at the University of Minnesota.
Paediatric resident identification of cardiac emergencies
Authors: Hills Brittney K. , Gal Dana B. , Zackoff Matthew , Williams Brenda , Marcuccio Elisa , Klein Melissa , Unaka Ndidi
Published: April 2024

Objectives:

Critical CHD is associated with morbidity and mortality, worsened by delayed diagnosis. Paediatric residents are front-line clinicians, yet identification of congenital CHD remains challenging. Current exposure to cardiology is limited in paediatric resident education. We evaluated the impact of rapid cycle deliberate practice simulation on paediatric residents’ skills, knowledge, and perceived competence to recognise and manage infants with congenital CHD.

Methods:

We conducted a 6-month pilot study. Interns rotating in paediatric cardiology completed a case scenario assessment during weeks 1 and 4 and participated in paired simulations (traditional debrief and rapid cycle deliberate practice) in weeks 2–4. We assessed interns’ skills during the simulation using a checklist of “cannot miss” tasks. In week 4, they completed a retrospective pre-post knowledge-based survey. We analysed the data using summary statistics and mixed effect linear regression.

Results:

A total of 26 interns participated. There was a significant increase in case scenario assessment scores between weeks 1 and 4 (4, interquartile range 3–6 versus 8, interquartile range 6–10; p-value < 0.0001). The percentage of “cannot miss” tasks on the simulation checklist increased from weeks 2 to 3 (73% versus 83%, p-value 0.0263) and from weeks 2–4 (73% versus 92%, p-value 0.0025). The retrospective pre-post survey scores also increased (1.67, interquartile range 1.33–2.17 versus 3.83, interquartile range 3.17–4; p-value < 0.0001).

Conclusion:

Rapid cycle deliberate practice simulations resulted in improved recognition and initiation of treatment of simulated infants with congenital CHD among paediatric interns. Future studies will include full implementation of the curriculum and knowledge retention work.
The political economy of foreign fighter death in the Russo-Ukrainian War: the role of institutions, politics, and international trade
Authors: Mixon Franklin G. , Cebula Richard J.
Published: April 2024

This empirical study extends the public choice literature on the allocation of death during war by examining the political economy of foreign fighter deaths in the Russo-Ukrainian War since the 24 February 2022 invasion. The study explores the roles played by various demographic factors, military institutions, and international trade relations in determining the number of foreign fighters from a variety of countries who have died in support of either Ukraine or Russia during the Russo-Ukrainian War. Unlike other related studies, this study also investigates the importance of, and finds evidence in support of, both economic freedom and a robust democracy in shaping the choices made by individuals around the globe to venture to, and die fighting on, the battlefields of Ukraine.
De-risking in multi-state life and health insurance
Authors: Levantesi Susanna , Menzietti Massimiliano , Nyegaard Anna Kamille
Published: April 2024

The calculation of life and health insurance liabilities is based on assumptions about mortality and disability rates, and insurance companies face systematic insurance risks if assumptions about these rates change. In this paper, we study how to manage systematic insurance risks in a multi-state setup by considering securities linked to the transition intensities of the model. We assume there exists a market for trading two securities linked to, for instance, mortality and disability rates, the de-risking option and the de-risking swap, and we describe the optimization problem to find the de-risking strategy that minimizes systematic insurance risks in a multi-state setup. We develop a numerical example based on the disability model, and the results imply that systematic insurance risks significantly decrease when implementing de-risking strategies.
Estimating the Ionospheric Induction Electric Field Using Ground Magnetometers
Authors: Madelaire Michael , Laundal Karl , Hatch Spencer , Vanhamäki Heikki , Reistad Jone , Ohma Anders , Merkin Viacheslav , Lin Dong
Published: April 2024

The ionospheric convection electric field is often assumed to be a potential field. This assumption is not always valid, especially when the ionosphere changes on short time scales min. We present a technique for estimating the induction electric field using ground magnetometer measurements. The technique is demonstrated on real and simulated data for sudden increases in solar wind dynamic pressure of 1 and 10 nPa, respectively. For the real data, the ionospheric induction electric field is 0.15 0.015 mV/m, and the corresponding compressional flow is 2.5 0.3 m/s. For the simulated data, the induction electric field and compressional flow reach 3 mV/m and 50 m/s, respectively. The induction electric field can locally constitute tens of percent of the total electric field. Inclusion of the induction electric field increased the total Joule heating by 2.4%. Locally the Joule heating changed by tens of percent. This corresponds to energy dissipation that is not accounted for in existing models.
Improving Global Barotropic Tides With Sub‐Grid Scale Topography
Authors: Wang He , Hallberg Robert , Wallcraft Alan J. , Arbic Brian K. , Chassignet Eric P.
Published: April 2024

In recent years, efforts have been made to include tides in both operational ocean models as well as climate and earth system models. The accuracy of the barotropic tides is often limited by the model topography, which is in turn limited by model horizontal resolution. In this work, we explore the reduction of barotropic tidal errors in an ocean general circulation model (Modular Ocean Model version 6; MOM6) using sub‐grid scale topography representation. We follow the methodology from Adcroft (2013, https://doi.org/10.1016/j.ocemod.2013.03.002), which utilizes statistics from finer resolution topographic data sets to represent sub‐grid scale features with a light computational cost in a structured finite volume formulation. The geometric effect from sub‐grid scale topography can be introduced to the model with only a few parameters at each grid cell. The porous barriers, which are implemented at the walls of the grid cells, are used to modify transport between grid cells. Our results show that the globally averaged tidal error in lower‐resolution simulations is significantly reduced with the use of porous barriers. We argue this method is a potentially useful tool to improve simulations of tides (and other flows) in low‐resolution simulations.
Soil Moisture Profiles of Ecosystem Water Use Revealed With ECOSTRESS
Authors: Feldman Andrew F. , Koster Randal D. , Cawse‐Nicholson Kerry , Crow Wade T. , Holmes Thomas R. H. , Poulter Benjamin
Published: April 2024

While remote sensing has provided extensive insights into the global terrestrial water, carbon, and energy cycles, space‐based retrievals remain limited in observing the belowground influence of the full soil moisture (SM) profile on ecosystem function. We show that this gap can be addressed when coupling 70 m resolution ECOsystem Spaceborne Thermal Radiometer Experiment on Space Station retrievals of land surface temperature (LST) with in‐situ SM profile measurements. These data sets together reveal that ecosystem water use decreases with depth with 93% of sites showing significant LST coupling with SM shallower than 20 cm while 34% of sites have interactions with SM deeper than 50 cm. Furthermore, the median depth of peak ecosystem water use is estimated to be 10 cm, though forests have more common peak interactions with deeper soil layers (50–100 cm) in 37% of cases. High spatial resolution remote sensing coupled with field‐level data can thus elucidate the role of belowground processes on land surface behavior.
Missed diagnosis—a major barrier to patient access to obesity healthcare in the primary care setting
Authors: Kasher Meron Michal , Eizenstein Sapir , Cukierman-Yaffe Tali , Oieru Dan
Published: April 2024

Objective

To investigate whether individuals with an elevated BMI measurement, for whom a diagnosis of overweight or obesity (OW/OB) is not recorded, are less likely to be offered clinical care for obesity compared to those with a recorded diagnosis.

Subjects

A retrospective cohort study using the electronic medical record database of Maccabi Healthcare Services (MHS) in Israel. Included were 200,000 adults with BMI ≥ 25 kg/m2 measurement recorded during a primary care visit between 2014 and 2020, and no prior diagnosis of OW/OB or related co-morbidities.

Methods

The relationships between a recorded diagnosis of OW/OB and two composite outcomes: 1. A composite of referrals to screening tests for metabolic complications; 2. A composite of weight loss intervention and follow up, were analyzed using multivariate logistic regression models.

Results

In only 18% of individuals, a diagnosis of OW/OB was recorded. After adjusting for multiple potential confounding factors, individuals who received a recorded diagnosis were 18% more likely to be offered an evaluation for obesity-related metabolic complication, (OR 1.18, 95% CI 1.15–1.21, p < 0.001), and almost twice as likely to be offered intervention and follow up for their excess body weight (OR 1.84, 95% CI 1.76–1.94, p < 0.001) compared to individuals with missed diagnosis. These results persisted after adjusting for inter-physician variability. In addition, male sex, older age, and Arab sector were all associated with lower rates of weight loss intervention and follow up, while young individuals were less likely to be screened for metabolic complications.

Conclusion

Beyond BMI measurement, a recorded diagnosis of OW/OB is associated with statistically and clinically significant higher rates of performance of obesity care and intervention. Undiagnosed OW/OB presents a significant clinical opportunity, as recording a diagnosis of OW/OB would predict improved patient access to obesity healthcare and improved clinical outcomes.
Characterization of transcriptional profiles associated with stress-induced neuronal activation in Arc-GFP mice
Authors: Butto Tamer , Chongtham Monika Chanu , Mungikar Kanak , Hartwich Dewi , Linke Matthias , Ruffini Nicolas , Radyushkin Konstantin , Schweiger Susann , Winter Jennifer , Gerber Susanne
Published: April 2024

Chronic stress has become a predominant factor associated with a variety of psychiatric disorders, such as depression and anxiety, in both human and animal models. Although multiple studies have looked at transcriptional changes after social defeat stress, these studies primarily focus on bulk tissues, which might dilute important molecular signatures of social interaction in activated cells. In this study, we employed the Arc-GFP mouse model in conjunction with chronic social defeat (CSD) to selectively isolate activated nuclei (AN) populations in the ventral hippocampus (vHIP) and prefrontal cortex (PFC) of resilient and susceptible animals. Nuclear RNA-seq of susceptible vs. resilient populations revealed distinct transcriptional profiles linked predominantly with neuronal and synaptic regulation mechanisms. In the vHIP, susceptible AN exhibited increased expression of genes related to the cytoskeleton and synaptic organization. At the same time, resilient AN showed upregulation of cell adhesion genes and differential expression of major glutamatergic subunits. In the PFC, susceptible mice exhibited upregulation of synaptotagmins and immediate early genes (IEGs), suggesting a potentially over-amplified neuronal activity state. Our findings provide a novel view of stress-exposed neuronal activation and the molecular response mechanisms in stress-susceptible vs. resilient animals, which may have important implications for understanding mental resilience.
Efficacy and safety of aticaprant, a kappa receptor antagonist, adjunctive to oral SSRI/SNRI antidepressant in major depressive disorder: results of a phase 2 randomized, double-blind, placebo-controlled study
Authors: Schmidt Mark E. , Kezic Iva , Popova Vanina , Melkote Rama , Van Der Ark Peter , Pemberton Darrel J. , Mareels Guy , Canuso Carla M. , Fava Maurizio , Drevets Wayne C.
Published: April 2024

This was a double-blind, randomized, phase 2 study of adults (18–64 years) with DSM−5 diagnosis of major depressive disorder (MDD), with moderate-to-severe episode severity (Montgomery–Åsberg Depression Rating Scale [MADRS] ≥25) despite an adequate course with ongoing antidepressant for ≥6 weeks to ≤12 months. Following a double-blind placebo lead-in period (up to 3 weeks), participants were randomized to receive once daily aticaprant 10 mg or continue placebo, added to their ongoing treatment, for 6 weeks. Of 184 participants enrolled, 169 were included in safety analyses (aticaprant n = 85, placebo n = 84) and 166 in full intent-to-treat (fITT) efficacy analyses; 121 placebo lead-in non-responders (<30% reduction in MADRS total score) in fITT were included in enriched ITT (eITT) analyses. Improvement (least squares mean difference [upper limit 1-sided 80% CI] versus placebo) in MADRS total score at week 6 for aticaprant was significant versus placebo (eITT: −2.1 [−1.09], 1-sided p = 0.044; effect size (ES) 0.23; fITT −3.1 [2.21], 1-sided p = 0.002; ES 0.36). The between-group difference was larger among participants with Snaith–Hamilton Pleasure Scale (SHAPS) score greater/equal to versus less than baseline median SHAPS. The most common treatment-emergent adverse events reported for aticaprant (versus placebo) were headache (11.8% versus 7.1%), diarrhea (8.2% versus 2.4%), nasopharyngitis (5.9% versus 2.4%), and pruritus (5.9% versus 0%). One participant (1.2%) in each arm discontinued treatment due to an adverse event. In this study of participants with MDD and inadequate response to SSRI/SNRI, adjunctive treatment with aticaprant significantly reduced depressive symptoms versus placebo, without resulting in significant safety signals, supporting further investigation in larger trials.
Regional variability in therapeutic hypothermia eligibility criteria for neonatal hypoxic-ischemic encephalopathy
Authors: Proietti Jacopo , Boylan Geraldine B. , Walsh Brian H.
Published: April 2024

Early induced therapeutic hypothermia represents the cornerstone treatment in neonates with probable hypoxic-ischemic encephalopathy. The selection of patients for treatment usually involves meeting criteria indicating evidence of perinatal hypoxia-ischemia and the presence of moderate or severe encephalopathy. In this review, we highlight the variability that exists between some of the different regional and national eligibility guidelines. Determining the potential presence of perinatal hypoxia-ischemia may require either one, two or three signs amongst history of acute perinatal event, prolonged resuscitation at delivery, abnormal blood gases and low Apgar score, with a range of cutoff values. Clinical neurological exams often define the severity of encephalopathy differently, with varying number of domains required for determining eligibility and blurred interpretation of findings assigned to different severity grades in different systems. The role of early electrophysiological assessment is weighted differently. A clinical implication is that infants may receive different care depending on the location in which they are born. This could also impact epidemiological data, as inference of rates of moderate-severe encephalopathy based on therapeutic hypothermia rates are misleading and influenced by different eligibility methods used. We would advocate that a universally endorsed single severity staging of encephalopathy is vital for standardizing management and neonatal outcome.

Impact

Variability exists between regional and national therapeutic hypothermia eligibility guidelines for neonates with probable hypoxic-ischemic encephalopathy.

Differences are common in both criteria indicating perinatal hypoxia-ischemia and criteria defining moderate or severe encephalopathy. The role of early electrophysiological assessment is also weighted unequally.

This reflects in different individual care and impacts research data. A universally endorsed single severity staging of encephalopathy would be crucial for standardizing management.
T cells in testicular germ cell tumors: new evidence of fundamental contributions by rare subsets
Authors: Islam Rashidul , Heyer Jannis , Figura Miriam , Wang Xiaoyan , Nie Xichen , Nathaniel Benedict , Indumathy Sivanjah , Hartmann Katja , Pleuger Christiane , Fijak Monika , Kliesch Sabine , Dittmar Florian , Pilatz Adrian , Wagenlehner Florian , Hedger Mark , Loveland Bruce , Hotaling James H. , Guo Jingtao , Loveland Kate L. , Schuppe Hans-Christian , Fietz Daniela
Published: April 2024

Background

Immune cell infiltration is heterogeneous but common in testicular germ cell tumors (TGCT) and pre-invasive germ cell neoplasia in situ (GCNIS). Tumor-infiltrating T cells including regulatory T (Treg) and follicular helper T (Tfh) cells are found in other cancer entities, but their contributions to TGCT are unknown.

Methods

Human testis specimens from independent patient cohorts were analyzed using immunohistochemistry, flow cytometry and single-cell RNA sequencing (scRNA-seq) with special emphasis on delineating T cell subtypes.

Results

Profound changes in immune cell composition within TGCT, shifting from macrophages in normal testes to T cells plus B and dendritic cells in TGCT, were documented. In most samples (96%), the CD4+ T cell frequency exceeded that of CD8+ cells, with decreasing numbers from central to peripheral tumor areas, and to tumor-free, contralateral testes. T cells including Treg and Tfh were most abundant in seminoma compared to mixed tumors and embryonal carcinoma.

Conclusion

Despite considerable heterogeneity between patients, T cell subtypes form a key part of the TGCT microenvironment. The novel finding of rare Treg and Tfh cells in human testis suggests their involvement in TGCT pathobiology, with implications for understanding tumor progression, to assess patients’ prognosis, and as putative targets for personalized immunotherapy.
Hepatic Sirt6 activation abrogates acute liver failure
Authors: Luo Jinque , Liu Huan , Xu Yanni , Yu Nanhui , Steiner Rebbeca A. , Wu Xiaoqian , Si Shuyi , Jin Zheng Gen
Published: April 2024

Acute liver failure (ALF) is a deadly illness due to insufficient detoxification in liver induced by drugs, toxins, and other etiologies, and the effective treatment for ALF is very limited. Among the drug-induced ALF, acetaminophen (APAP) overdose is the most common cause. However, the molecular mechanisms underlying APAP hepatoxicity remain incompletely understood. Sirtuin 6 (Sirt6) is a stress responsive protein deacetylase and plays an important role in regulation of DNA repair, genomic stability, oxidative stress, and inflammation. Here, we report that genetic and pharmacological activation of Sirt6 protects against ALF in mice. We first observed that Sirt6 expression was significantly reduced in the liver tissues of human patients with ALF and mice treated with an overdose of APAP. Then we developed an inducible Sirt6 transgenic mice for Cre-mediated overexpression of the human Sirt6 gene in systemic (Sirt6-Tg) and hepatic-specific (Sirt6-HepTg) manners. Both Sirt6-Tg mice and Sirt6-HepTg mice exhibited the significant protection against APAP hepatoxicity. In contrast, hepatic-specific Sirt6 knockout mice exaggerated APAP-induced liver damages. Mechanistically, Sirt6 attenuated APAP-induced hepatocyte necrosis and apoptosis through downregulation of oxidative stress, inflammation, the stress-activated kinase JNK activation, and apoptotic caspase activation. Moreover, Sirt6 negatively modulated the level and activity of poly (ADP-ribose) polymerase 1 (PARP1) in APAP-treated mouse liver tissues. Importantly, the specific Sirt6 activator MDL-800 exhibited better therapeutic potential for APAP hepatoxicity than the current drug acetylcysteine. Furthermore, in the model of bile duct ligation induced ALF, hepatic Sirt6-KO exacerbated, but Sirt6-HepTg mitigated liver damage. Collectively, our results demonstrate that Sirt6 protects against ALF and suggest that targeting Sirt6 activation could be a new therapeutic strategy to alleviate ALF.
An ultra energy-efficient hardware platform for neuromorphic computing enabled by 2D-TMD tunnel-FETs
Authors: Pal Arnab , Chai Zichun , Jiang Junkai , Cao Wei , Davies Mike , De Vivek , Banerjee Kaustav
Published: April 2024

Brain-like energy-efficient computing has remained elusive for neuromorphic (NM) circuits and hardware platform implementations despite decades of research. In this work we reveal the opportunity to significantly improve the energy efficiency of digital neuromorphic hardware by introducing NM circuits employing two-dimensional (2D) transition metal dichalcogenide (TMD) layered channel material-based tunnel-field-effect transistors (TFETs). Our novel leaky-integrate-fire (LIF) based digital NM circuit along with its Hebbian learning circuitry operates at a wide range of supply voltages, frequencies, and activity factors, enabling two orders of magnitude higher energy-efficient computing that is difficult to achieve with conventional material and/or device platforms, specifically the silicon-based 7 nm low-standby-power FinFET technology. Our innovative 2D-TFET based NM circuit paves the way toward brain-like energy-efficient computing that can unleash major transformations in future AI and data analytics platforms.
Estimating the effects of temperature on transmission of the human malaria parasite, Plasmodium falciparum
Authors: Suh Eunho , Stopard Isaac J. , Lambert Ben , Waite Jessica L. , Dennington Nina L. , Churcher Thomas S. , Thomas Matthew B.
Published: April 2024

Despite concern that climate change could increase the human risk to malaria in certain areas, the temperature dependency of malaria transmission is poorly characterized. Here, we use a mechanistic model fitted to experimental data to describe how Plasmodium falciparum infection of the African malaria vector, Anopheles gambiae, is modulated by temperature, including its influences on parasite establishment, conversion efficiency through parasite developmental stages, parasite development rate, and overall vector competence. We use these data, together with estimates of the survival of infected blood-fed mosquitoes, to explore the theoretical influence of temperature on transmission in four locations in Kenya, considering recent conditions and future climate change. Results provide insights into factors limiting transmission in cooler environments and indicate that increases in malaria transmission due to climate warming in areas like the Kenyan Highlands, might be less than previously predicted.
Local CO2 reservoir layer promotes rapid and selective electrochemical CO2 reduction
Authors: Mukhopadhyay Subhabrata , Naeem Muhammad Saad , Shiva Shanker G. , Ghatak Arnab , Kottaichamy Alagar R. , Shimoni Ran , Avram Liat , Liberman Itamar , Balilty Rotem , Ifraemov Raya , Rozenberg Illya , Shalom Menny , López Núria , Hod Idan
Published: April 2024

Electrochemical CO2 reduction reaction in aqueous electrolytes is a promising route to produce added-value chemicals and decrease carbon emissions. However, even in Gas-Diffusion Electrode devices, low aqueous CO2 solubility limits catalysis rate and selectivity. Here, we demonstrate that when assembled over a heterogeneous electrocatalyst, a film of nitrile-modified Metal-Organic Framework (MOF) acts as a remarkable CO2-solvation layer that increases its local concentration by ~27-fold compared to bulk electrolyte, reaching 0.82 M. When mounted on a Bi catalyst in a Gas Diffusion Electrode, the MOF drastically improves CO2-to-HCOOH conversion, reaching above 90% selectivity and partial HCOOH currents of 166 mA/cm2 (at −0.9 V vs RHE). The MOF also facilitates catalysis through stabilization of reaction intermediates, as identified by operando infrared spectroscopy and Density Functional Theory. Hence, the presented strategy provides new molecular means to enhance heterogeneous electrochemical CO2 reduction reaction, leading it closer to the requirements for practical implementation.
PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus
Authors: TCHEN John , SIMON Quentin , CHAPART Léa , THAMINY Morgane K. , VIBHUSHAN Shamila , SAVEANU Loredana , LAMRI Yasmine , SAIDOUNE Fanny , PACREAU Emeline , PELLEFIGUES Christophe , BEX-COUDRAT Julie , KARASUYAMA Hajime , MIYAKE Kensuke , HIDALGO Juan , FALLON Padraic G. , PAPO Thomas , BLANK Ulrich , BENHAMOU Marc , HANOUNA Guillaume , SACRE Karim , DAUGAS Eric , CHARLES Nicolas
Published: April 2024

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by anti-nuclear autoantibodies whose production is promoted by autoreactive T follicular helper (TFH) cells. During SLE pathogenesis, basophils accumulate in secondary lymphoid organs (SLO), amplify autoantibody production and disease progression through mechanisms that remain to be defined. Here, we provide evidence for a direct functional relationship between TFH cells and basophils during lupus pathogenesis, both in humans and mice. PD-L1 upregulation on basophils and IL-4 production are associated with TFH and TFH2 cell expansions and with disease activity. Pathogenic TFH cell accumulation, maintenance, and function in SLO were dependent on PD-L1 and IL-4 in basophils, which induced a transcriptional program allowing TFH2 cell differentiation and function. Our study establishes a direct mechanistic link between basophils and TFH cells in SLE that promotes autoantibody production and lupus nephritis.
Diverse and asymmetric patterns of single-neuron projectome in regulating interhemispheric connectivity
Authors: Fei Yao , Wu Qihang , Zhao Shijie , Song Kun , Han Junwei , Liu Cirong
Published: April 2024

The corpus callosum, historically considered primarily for homotopic connections, supports many heterotopic connections, indicating complex interhemispheric connectivity. Understanding this complexity is crucial yet challenging due to diverse cell-specific wiring patterns. Here, we utilized public AAV bulk tracing and single-neuron tracing data to delineate the anatomical connection patterns of mouse brains and conducted wide-field calcium imaging to assess functional connectivity across various brain states in male mice. The single-neuron data uncovered complex and dense interconnected patterns, particularly for interhemispheric-heterotopic connections. We proposed a metric “heterogeneity” to quantify the complexity of the connection patterns. Computational modeling of these patterns suggested that the heterogeneity of upstream projections impacted downstream homotopic functional connectivity. Furthermore, higher heterogeneity observed in interhemispheric-heterotopic projections would cause lower strength but higher stability in functional connectivity than their intrahemispheric counterparts. These findings were corroborated by our wide-field functional imaging data, underscoring the important role of heterotopic-projection heterogeneity in interhemispheric communication.
Mechanical scission of a knotted polymer
Authors: Zhang Min , Nixon Robert , Schaufelberger Fredrik , Pirvu Lucian , De Bo Guillaume , Leigh David A.
Published: April 2024

Molecular knots and entanglements form randomly and spontaneously in both biological and synthetic polymer chains. It is known that macroscopic materials, such as ropes, are substantially weakened by the presence of knots, but until now it has been unclear whether similar behaviour occurs on a molecular level. Here we show that the presence of a well-defined overhand knot in a polymer chain substantially increases the rate of scission of the polymer under tension (≥2.6× faster) in solution, because deformation of the polymer backbone induced by the tightening knot activates otherwise unreactive covalent bonds. The fragments formed upon severing of the knotted chain differ from those that arise from cleavage of a similar, but unknotted, polymer. Our solution studies provide experimental evidence that knotting can contribute to higher mechanical scission rates of polymers. It also demonstrates that entanglement design can be used to generate mechanophores that are among the most reactive described to date, providing opportunities to increase the reactivity of otherwise inert functional groups.
Star formation shut down by multiphase gas outflow in a galaxy at a redshift of 2.45
Authors: Belli Sirio , Park Minjung , Davies Rebecca L. , Mendel J. Trevor , Johnson Benjamin D. , Conroy Charlie , Benton Chloë , Bugiani Letizia , Emami Razieh , Leja Joel , Li Yijia , Maheson Gabriel , Mathews Elijah P. , Naidu Rohan P. , Nelson Erica J. , Tacchella Sandro , Terrazas Bryan A. , Weinberger Rainer
Published: April 2024

Large-scale outflows driven by supermassive black holes are thought to have a fundamental role in suppressing star formation in massive galaxies. However, direct observational evidence for this hypothesis is still lacking, particularly in the young universe where star-formation quenching is remarkably rapid1–3, thus requiring effective removal of gas4 as opposed to slow gas heating5,6. Although outflows of ionized gas are frequently detected in massive distant galaxies7, the amount of ejected mass is too small to be able to suppress star formation8,9. Gas ejection is expected to be more efficient in the neutral and molecular phases10, but at high redshift these have only been observed in starbursts and quasars11,12. Here we report JWST spectroscopy of a massive galaxy experiencing rapid quenching at a redshift of 2.445. We detect a weak outflow of ionized gas and a powerful outflow of neutral gas, with a mass outflow rate that is sufficient to quench the star formation. Neither X-ray nor radio activity is detected; however, the presence of a supermassive black hole is suggested by the properties of the ionized gas emission lines. We thus conclude that supermassive black holes are able to rapidly suppress star formation in massive galaxies by efficiently ejecting neutral gas.
Large-scale uterine myoma MRI dataset covering all FIGO types with pixel-level annotations
Authors: Pan Haixia , Chen Minghuang , Bai Wenpei , Li Bin , Zhao Xiaoran , Zhang Meng , Zhang Dongdong , Li Yanan , Wang Hongqiang , Geng Haotian , Kong Weiya , Yin Cong , Han Linfeng , Lan Jiahua , Zhao Tian
Published: April 2024

Uterine myomas are the most common pelvic tumors in women, which can lead to abnormal uterine bleeding, abdominal pain, pelvic compression symptoms, infertility, or adverse pregnancy. In this article, we provide a dataset named uterine myoma MRI dataset (UMD), which can be used for clinical research on uterine myoma imaging. The UMD is the largest publicly available uterine MRI dataset to date including 300 cases of uterine myoma T2-weighted imaging (T2WI) sagittal patient images and their corresponding annotation files. The UMD covers 9 types of uterine myomas classified by the International Federation of Obstetrics and Gynecology (FIGO), which were annotated and reviewed by 11 experienced doctors to ensure the authority of the annotated data. The UMD is helpful for uterine myomas classification and uterine 3D reconstruction tasks, which has important implications for clinical research on uterine myomas.
Evaluation of recoverable potential of deep coalbed methane in the Linxing Block, Eastern Margin of the Ordos Basin
Authors: Chen Bo , Li Song , Tang Dazhen , Pu Yifan , Zhong Guanghao
Published: April 2024

The deep coalbed methane (CBM) resources are widely developed in the Linxing Block. However, the evaluation of CBM geological areas suitable for CBM exploitation remains unexplored, hindering further development. This research optimizes the key geological parameters that influence the development of deep CBM from the perspectives of resource and development conditions. The evaluation system for deep CBM recoverability has been established, and the multi-fuzzy evaluation method has been used to perform the quantitative evaluation of recoverability. The results indicate that the resource conditions of No.8 + 9 coal seam are superior to those of No.4 + 5 coal seam. Favorable resource conditions are predominantly concentrated in the northeast and specific southern portions of the research area. Favorable development conditions for both coal seams are mostly concentrated in the northeastern area. Based on the classification standard of recoverable favorable areas, the Level II area is crucial for the development of No.4 + 5 coal seam. This area is primarily distributed in the northeast of the research area., Both Level I and Level II areas for the No. 8 + 9 coal seam are situated in the northeast. The Level III area is earmarked for deep CBM production and shows potential for exploration. Further analysis reveals that the resource conditions in the favorable area are generally superior to the development conditions. These areas are classified as Class A, including categories such as I-A, II-A, and III-A, indicating relatively complex reservoir transformation.
Evaluating the potential and eligibility of conservation agriculture practices for carbon credits
Authors: Cariappa Adeeth A. G. , Konath Noufa C. , Sapkota Tek B. , Krishna Vijesh V.
Published: April 2024

Carbon credits, a voluntary market mechanism to reduce greenhouse gas (GHG) emissions, can incentivize climate action. We evaluate the potential and eligibility of Conservation Agriculture (CA) practices for carbon credit generation in India under Verra's VM0042 methodology. Using farmer surveys and remote sensing data, we assess the eligibility based on the following conditions: Additionality Condition (GHG emission reductions to exceed legal requirements and the weighted mean adoption rate to be < 20% of area in the baseline), Yield Penalty Condition (no > 5% decrease in crop yields), and Quantitative Adjustment Condition (reduction in chemical fertilizer use by > 5%). Our analysis shows that CA has the potential to increase farmers’ carbon credit earnings by USD 18/ha and USD 30/ha in Bihar and Punjab, respectively. Punjab's ban on crop residue burning and the fact that > 20% of the area unburned limits the full economic realization of CA through carbon markets, decreasing potential income to USD 16/ha. A 60% increase in carbon prices from the current norm (USD 25) is required to encourage wider adoption of CA. Zero tillage of wheat in both Punjab and Bihar and reduction of nitrogen fertilizer overuse in Punjab fulfil all the conditions and are eligible for carbon farming projects.
Multimodal decoding of error processing in a virtual reality flight simulation
Authors: Wimmer Michael , Weidinger Nicole , Veas Eduardo , Müller-Putz Gernot R.
Published: April 2024

Technological advances in head-mounted displays (HMDs) facilitate the acquisition of physiological data of the user, such as gaze, pupil size, or heart rate. Still, interactions with such systems can be prone to errors, including unintended behavior or unexpected changes in the presented virtual environments. In this study, we investigated if multimodal physiological data can be used to decode error processing, which has been studied, to date, with brain signals only. We examined the feasibility of decoding errors solely with pupil size data and proposed a hybrid decoding approach combining electroencephalographic (EEG) and pupillometric signals. Moreover, we analyzed if hybrid approaches can improve existing EEG-based classification approaches and focused on setups that offer increased usability for practical applications, such as the presented game-like virtual reality flight simulation. Our results indicate that classifiers trained with pupil size data can decode errors above chance. Moreover, hybrid approaches yielded improved performance compared to EEG-based decoders in setups with a reduced number of channels, which is crucial for many out-of-the-lab scenarios. These findings contribute to the development of hybrid brain-computer interfaces, particularly in combination with wearable devices, which allow for easy acquisition of additional physiological data.
A dynamic prediction model of landslide displacement based on VMD–SSO–LSTM approach
Authors: Wang Haiying , Ao Yang , Wang Chenguang , Zhang Yingzhi , Zhang Xiaofeng
Published: April 2024

Addressing the limitations of existing landslide displacement prediction models in capturing the dynamic characteristics of data changes, this study introduces a novel dynamic displacement prediction model for landslides. The proposed method combines Variational Mode Decomposition (VMD) with Sparrow Search Optimization (SSO) and Long Short-Term Memory (LSTM) techniques to formulate a comprehensive VMD–SSO–LSTM model. Through the application of VMD, the method dissects cumulative displacement and rainfall data, thereby extracting distinct components such as trend, periodicity, and fluctuation components for displacement, as well as low-frequency and high-frequency components for rainfall. Furthermore, leveraging Gray Correlational Analysis, the interrelationships between the periodic component of displacement and the low-frequency component of rainfall, as well as the fluctuation component of displacement and the high-frequency component of rainfall, are established. Building upon this foundation, the SSO–LSTM model dynamically predicts the interrelated displacement components, synthesizing the predicted values of each component to generate real-time dynamic forecasts. Simulation results underscore the effectiveness of the proposed VMD–SSO–LSTM model, indicating root-mean-square error (RMSE) and mean absolute percentage error (MAPE) values of 1.2329 mm and 0.1624%, respectively, along with a goodness of fit (R2) of 0.9969. In comparison to both back propagation (BP) prediction model and LSTM prediction model, the VMD–SSO–LSTM model exhibits heightened predictive accuracy.