bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol milestones and internalizing, externalizing, and executive function: longitudinal and polygenic score associations
Authors: Paul Sarah E. , Baranger David A.A. , Johnson Emma C. , Jackson Joshua J. , Gorelik Aaron J. , Miller Alex P. , Hatoum Alexander S. , Thompson Wesley K. , Strube Michael , Dick Danielle M. , Kamarajan Chella , Kramer John R. , Plawecki Martin H. , Chan Grace , Anokhin Andrey P. , Chorlian David B. , Kinreich Sivan , Meyers Jacquelyn L. , Porjesz Bernice , Edenberg Howard J. , Agrawal Arpana , Bucholz Kathleen K. , Bogdan Ryan
Published: May 2024

Background

Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.

Methods

Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.

Results

Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).

Conclusions

Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.
The contribution of cannabis use to the increased psychosis risk among minority ethnic groups in Europe
Authors: Selten J. P. , Di Forti M. , Quattrone D. , Jones P. B. , Jongsma H. E. , Gayer-Anderson C. , Szöke A. , Llorca P. M. , Arango C. , Bernardo M. , Sanjuan J. , Santos J. L. , Arrojo M. , Tarricone I. , Berardi D. , Lasalvia A. , Tosato S. , la Cascia C. , Velthorst E. , van der Ven E. M. A. , de Haan L. , Rutten B. P. , van Os J. , Kirkbride J. B. , Morgan C. M. , Murray R. M. , Termorshuizen F.
Published: May 2024

Background

We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe.

Methods

We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use.

Results

The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39–2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38–2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25–4.79) to 1.61 (95% CI 0.74–3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07–6.15) to 1.67 (95% CI 0.62–4.53).

Conclusions

The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.
The impact of health impairments on employment entry and the quality of employment among basic income support recipients in Germany
Authors: Zabel Cordula
Published: May 2024

Policies for recipients of basic income support for jobseekers in Germany focus on activation and quick labour market integration. Yet, the majority of benefit recipients report severe health impairments. Against this background, the article investigates implications of health impairments for benefit recipients’ jobcentre relationship and employment opportunities. The analyses show that 63 per cent of non-employed benefit recipients report health restrictions on their employment capabilities, 51 per cent report severe health impairments, and 25 per cent that they cannot work at all. The most frequent types of health impairments are musculoskeletal and mental health impairments. Health impairments significantly reduce entry rates into socially insured employment, but do not seem to inhibit taking up uninsured minijobs. Counselling frequency increases job entry rates for benefit recipients without health impairments in the short-term. For those with health impairments, no short-term effects are found over a one-year follow-up period. Policy responses could include a more explicit acknowledgement of health impairments as a central issue for benefit recipients. Greater investments in rehabilitation and subsidised employment could be part of a strategy to improve opportunities for benefit recipients with health impairments to find better-quality (part-time) employment instead of uninsured minijobs. The analyses are based on linked longitudinal PASS survey and administrative data.
Re Holy Rood, Edwalton
Authors: Willink David
Published: May 2024

Adjacent to, and connected to, the churchyard was an area known as the ‘church garden’. The land had been given to the church in 1960 for the purpose of adding to the churchyard, the deed of gift conforming with the formula set out in section 5 of the Consecration of Churchyards Act 1867. After a long period of disuse, the land was used to create a garden, separated from the churchyard by a hedge. The garden was never consecrated. As well as containing amenities such as a lawn, trees, flower beds, benches and a ‘fairy grotto’, the garden had been the site of various scatterings and interments of cremated remains. No authority had ever been sought for such interments.
Re Removal of a Commemorative Plaque for Safeguarding Reasons
Authors: Gyane Naomi
Published: May 2024

This unopposed petition was for the removal of a commemorative plaque, installed without a faculty, on the windowsill of the south wall of the nave of the Grade II* listed church. In order to protect the privacy of any person affected by the judgment, the names of the church and the people involved were anonymised.
Re St James, Piccadilly
Authors: Gyane Naomi
Published: May 2024

The petitioners sought permission to carry out major re-ordering works including the erection of a new thatched pavilion building. Many aspects of the works, including the creation of the single storey thatched building, had also been the subject of a successful planning application to the local planning authority.
Does checking-in help? Understanding L2 learners’ autonomous check-in behavior in an English-language MOOC through learning analytics
Authors: Zhang Yining , Yang Fang , Yang Haolin , Han Shuyuan
Published: May 2024

Concerns over the quality of teaching in massive open online courses devoted to language learning (LMOOCs) have prompted extensive research on learning behavior in such courses. The purpose of this study is to gain a better understanding of autonomous learning check-ins – that is, individuals sharing their own learning records and/or other information about their learning-related experience – a novel behavior that has not been studied in previous LMOOC research. Using learning analytics, we found that just 6.2% (n = 699) of a sample of 11,293 learners autonomously engaged in check-in behavior, and that the content of these learners’ check-ins varied considerably according to their contexts and the language skills they were seeking to acquire. We further found (1) a positive association between check-in behavior and LMOOC completion; (2) that students who chose to check in earned relatively low grades on unit quizzes, especially in their early stage of learning, but outperformed the non-check-in group significantly in final exam scores; and (3) that those who checked in engaged with a significantly wider array of in-LMOOC learning components than those who did not, and thus accessed a wider system of language-learning experiences. Taken together, these results confirm that check-in behavior can aid the process of learning in an LMOOC and further highlight this behavior’s wider potential to aid self-directed autonomous online learning.
Assessment of normal tissue objectives in RapidArc treatment for cervical cancer
Authors: P. Athulya , Manna Sumanta , Singh Sharad
Published: May 2024

Purpose:

The normal tissue objective (NTO) is a tool used in inverse-planned intensity-modulated radiation therapy (IMRT) to minimize dose dispersion to surrounding tissues. The current study focuses on the NTO’s impact on RapidArc treatment plans for cervical cancer patients or its role in reducing doses to healthy surrounding tissues.

Material and methods:

This study included 11 cervical cancer patients who underwent RapidArc treatment. We assessed plans both with and without the NTO objective by evaluating parameters such as homogeneity, conformity, gradient index (GI), IMRT factor, integral dose and the volume of normal tissues receiving low doses of 40, 30, 20 and 10 Gy. Further, differences between automatic NTO and manual NTO were evaluated using Wilcoxon signed-rank test.

Results:

There were no significant differences in the conformity index, homogeneity index, IMRT factor and integral dose between plans with automatic NTO and those with manual NTO RapidArc plans. However, we did observe a clear advantage in using manual NTO for controlling low-dose exposure to normal tissues. The comparisons between automatic and manual NTO resulted in a GI of 3·1 ± 0·3 versus 2·7 ± 0·68 (p = 0·008). Furthermore, we noticed a significant reduction in the volumes receiving low doses (V10, V20, V30 and V40) with the manual NTO settings.

Conclusion:

The NTO plays a crucial role in optimizing RapidArc plans for treating cervical cancer. Based on the findings of this study, manual NTO settings of distance from PTV border xstart = 0·5 mm, start dose f0 = 105%, end dose f∞ = an average of 40%, dose fall-off 0·2 mm–1 were optimal. Further research involving a larger sample size and exploration of various NTO parameters is necessary to validate our results.
Conceptualizing National Advisory Boards in primary care research: application to the Two in One HIV and COVID screening and testing model
Authors: Ward Maranda C. , Delgado Setien Paloma , Konopasky Abigail , Conserve Donaldson F.
Published: May 2024

The authors report on their development of a National Advisory Board (NAB) to guide a funded project: Two in One: HIV + COVID-19 Screening and Testing Model. This project aimed to improve primary care practitioners’ capacity to routinize HIV, PrEP/PEP, and COVID-19 vaccine screenings for all their patients while relying on culturally responsive communication with their minoritized patients. To approach their monumental research and education tasks, they created a NAB, drawing from the literature on advisory boards to (a) promote board member engagement and (b) progress successfully through the six stages suggested for successful advisory boards. A midpoint survey and final focus groups with NAB members indicated mixed levels of engagement, a sense of time and work being valued, and pride in the media and academic reach of the project. The authors offer considerations for others considering forming a NAB to guide primary care research and interventions.
Patients’ experiences of and roles in interprofessional collaborative practice in primary care: a constructivist grounded theory study
Authors: Davidson Alexandra R. , Morgan Mark , Ball Lauren , Reidlinger Dianne P.
Published: May 2024

Aim:

This constructivist grounded theory study aimed to (1) explore patients’ experiences of and roles in interprofessional collaborative practice for chronic conditions in primary care and (2) consider the relevance and alignment of an existing theoretical framework on patients’ roles and based on the experiences of patient advocates.

Background:

High-quality management of chronic conditions requires an interprofessional collaborative practice model of care considering an individual’s mental, physical, and social health situation. Patients’ experiences of this model in the primary care setting are relatively unknown.

Methods:

A constructivist grounded theory approach was taken. Interview data were collected from primary care patients with chronic conditions across Australia in August 2020 – February 2022. Interviews were recorded, transcribed verbatim, and thematically analysed by (1) initial line-by-line coding, (2) focused coding, (3) memo writing, (4) categorisation, and (5) theme and sub-theme development. Themes and sub-themes were mapped against an existing theoretical framework to expand and confirm the results from a previous study with a similar research aim.

Findings:

Twenty adults with chronic conditions spanning physical disability, diabetes, heart disease, cancer, autoimmune, and mental health conditions participated. Two themes were developed: (1) Adapting to Change with two sub-themes describing how patients adapt to interprofessional team care and (2) Shifting across the spectrum of roles, with five sub-themes outlining the roles patients enact while receiving care. The findings suggest that patients’ roles are highly variable and fluid in interprofessional collaborative practice, and further work is recommended to develop a resource to support greater patient engagement in interprofessional collaborative practice.
Mother, child and adolescent health outcomes in two long-term refugee camp settings at the Thai-Myanmar border 2000–2018: a retrospective analysis
Authors: Benner Marie T. , Mohr Oliver , Kaloy Wiphan , Sansoenboon Ammarat , Moungsookjarean Aree , Kaiser Peter , Carrara Verena I. , McGready Rose
Published: May 2024

Aim:

The study assessed mothers, children and adolescents’ health (MCAH) outcomes in the context of a Primary Health Care (PHC) project and associated costs in two protracted long-term refugee camps, along the Thai-Myanmar border.

Background:

Myanmar refugees settled in Thailand nearly 40 years ago, in a string of camps along the border, where they fully depend on external support for health and social services. Between 2000 and 2018, a single international NGO has been implementing an integrated PHC project.

Methods:

This retrospective study looked at the trends of MCAH indicators of mortality and morbidity and compared them to the sustainable development goals (SDGs) indicators. A review of programme documents explored and triangulated the evolution and changing context of the PHC services, and associated project costs were analysed. To verify changes over time, interviews with 12 key informants were conducted.

Findings:

While maternal mortality (SDG3.1) remained high at 126.5/100,000 live births, child mortality (SDG 3.2) and infectious diseases in children under 5 (SDG 3.3) fell by 69% and by up to 92%, respectively. Maternal anaemia decreased by 30%; and more than 90% of pregnant women attended four or more antenatal care visits, whereas 80% delivered by a skilled birth attendant; caesarean section rates rose but remained low at an average of 3.7%; the adolescent (15–19 years) birth rate peaked at 188 per 1000 in 2015 but declined to 89/1000 in 2018 (SDG 3.7).

Conclusion:

Comprehensive PHC delivery, with improved health provider competence in MCAH care, together with secured funding is an appropriate strategy to bring MCAH indicators to acceptable levels. However, inequities due to confinement in camps, fragmentation of specific health services, prevent fulfilment of the 2030 SDG Agenda to ‘Leave no one behind’. Costs per birth was 115 EURO in 2018; however, MCAH expenditure requires further exploration over a longer period.
Assessment of Nocturnal NOx Heterogeneous Reaction Mechanisms in the Community Multiscale Air Quality (CMAQ) Model
Authors: Hoffman Alicia , Bertram Timothy H. , Holloway Tracey , Harkey Monica
Published: May 2024

Nitrogen oxides (NOx) have adverse human health impacts and play a central role in the production of ozone and PM2.5. Nighttime heterogeneous chemistry regulates the nocturnal reservoirs and sinks of NOx such as N2O5 removal and ClNO2 production. However, existing parameterizations of nocturnal NOx heterogeneous chemistry in air quality models do not capture the variability in observations. Here, we implemented for the first time in the Community Multiscale Air Quality (CMAQ) model the Gaston N2O5 uptake (γ(N2O5)) mechanism that accounts for the role of particulate organic matter in regulating N2O5 uptake and the Staudt ClNO2 yield (Φ(ClNO2)) mechanism that includes the role of reactive solutes in suppressing ClNO2 production. With the Gaston and Staudt parameterizations, the coarse mode contributed modestly to N2O5 loss (17.2%) but significantly to ClNO2 production (60.3%), highlighting the impact of coarse mode chemistry. The Gaston γ(N2O5) parameterization in the fine mode increased agreement between modeled N2O5 concentration and observations (RMSEnew = 0.37ppb) compared to the model default (RMSEdefault = 0.43ppb). The Gaston γ(N2O5) parameterization was overall biased low due to underestimates in modeled particle oxygen to carbon ratio (O:C). The Staudt Φ(ClNO2) parameterization resulted in further underestimation (NMBnew = −73.7%) compared to the model default (NMBdefault = −37.9%) because of underestimation of fine mode particle chloride concentration. We expect that the updated parameterizations may more accurately capture the mean state and variability in γ(N2O5) and Φ(ClNO2) under conditions where model particulate O:C and chloride are better represented.
Introducing the New Editor-in-Chief of JGR: Planets
Authors: Hendrix Amanda
Published: May 2024

Learn about the person taking the helm of JGR: Planets and their vision for the coming years.
Global Ocean Cooling of 2.3°C During the Last Glacial Maximum
Authors: Seltzer A. M. , Davidson P. W. , Shackleton S. A. , Nicholson D. P. , Khatiwala S.
Published: May 2024

Quantitative constraints on past mean ocean temperature (MOT) critically inform our historical understanding of Earth's energy balance. A recently developed MOT proxy based on paleoatmospheric Xe, Kr, and N2 ratios in ice core air bubbles is a promising tool rooted in the temperature dependences of gas solubilities. However, these inert gases are systematically undersaturated in the modern ocean interior, and it remains unclear how air‐sea disequilibrium may have changed in the past. Here, we carry out 30 tracer‐enabled model simulations under varying circulation, sea ice cover, and wind stress regimes to evaluate air‐sea disequilibrium in the Last Glacial Maximum (LGM) ocean. We find that undersaturation of all three gases was likely reduced, primarily due to strengthened high‐latitude winds, biasing reconstructed MOT by −0.38 ± 0.37°C (1σ). Accounting for air‐sea disequilibrium, paleoatmospheric inert gases indicate that LGM MOT was 2.27 ± 0.46°C (1σ) colder than the pre‐industrial era.
Decreased apoptotic priming and loss of BCL-2 dependence are functional hallmarks of Richter’s syndrome
Authors: Rigo Antonella , Vaisitti Tiziana , Laudanna Carlo , Terrabuio Eleonora , Micillo Matilde , Frusteri Cristina , D’Ulivo Beatrice , Merigo Flavia , Sbarbati Andrea , Mellert Kevin , Möeller Peter , Montresor Alessio , Di Napoli Arianna , Cirombella Roberto , Butturini Elena , Massaia Massimo , Constantin Gabriela , Vinante Fabrizio , Deaglio Silvia , Ferrarini Isacco
Published: May 2024

Richter’s syndrome (RS) is the transformation of chronic lymphocytic leukemia (CLL) into a high-grade B-cell malignancy. Molecular and functional studies have pointed out that CLL cells are close to the apoptotic threshold and dependent on BCL-2 for survival. However, it remains undefined how evasion from apoptosis evolves during disease transformation. Here, we employed functional and static approaches to compare the regulation of mitochondrial apoptosis in CLL and RS. BH3 profiling of 17 CLL and 9 RS samples demonstrated that RS cells had reduced apoptotic priming and lower BCL-2 dependence than CLL cells. While a subset of RS was dependent on alternative anti-apoptotic proteins and was sensitive to specific BH3 mimetics, other RS cases harbored no specific anti-apoptotic addiction. Transcriptomics of paired CLL/RS samples revealed downregulation of pro-apoptotic sensitizers during disease transformation. Albeit expressed, effector and activator members were less likely to colocalize with mitochondria in RS compared to CLL. Electron microscopy highlighted reduced cristae width in RS mitochondria, a condition further promoting apoptosis resistance. Collectively, our data suggest that RS cells evolve multiple mechanisms that lower the apoptotic priming and shift the anti-apoptotic dependencies away from BCL-2, making direct targeting of mitochondrial apoptosis more challenging after disease transformation.
SOAT1 regulates cholesterol metabolism to induce EMT in hepatocellular carcinoma
Authors: Fu Rongrong , Xue Wenqing , Liang Jingjie , Li Xinran , Zheng Juan , Wang Lechen , Zhang Min , Meng Jing
Published: May 2024

Cholesterol metabolism reprogramming is one of the significant characteristics of hepatocellular carcinoma (HCC). Cholesterol increases the risk of epithelial–mesenchymal transition (EMT) in cancer. Sterol O-acyltransferases 1 (SOAT1) maintains the cholesterol homeostasis. However, the exact mechanistic contribution of SOAT1 to EMT in HCC remains unclear. Here we demonstrated that SOAT1 positively related to poor prognosis of HCC, EMT markers and promoted cell migration and invasion in vitro, which was mediated by the increased cholesterol in plasmalemma and cholesterol esters accumulation. Furthermore, we reported that SOAT1 disrupted cholesterol metabolism homeostasis to accelerate tumorigenesis and development in HCC xenograft and NAFLD-HCC. Also, we detected that nootkatone, a sesquiterpene ketone, inhibited EMT by targeting SOAT1 in vitro and in vivo. Collectively, our finding indicated that SOAT1 promotes EMT and contributes to hepatocarcinogenesis by increasing cholesterol esterification, which is suppressed efficiently by nootkatone. This study demonstrated that SOAT1 is a potential biomarker and therapeutic target in NAFLD-HCC and SOAT1-targeting inhibitors are expected to be the potential new therapeutic treatment for HCC.
Phase-separated droplets swim to their dissolution
Authors: Jambon-Puillet Etienne , Testa Andrea , Lorenz Charlotta , Style Robert W. , Rebane Aleksander A. , Dufresne Eric R.
Published: May 2024

Biological macromolecules can condense into liquid domains. In cells, these condensates form membraneless organelles that can organize chemical reactions. However, little is known about the physical consequences of chemical activity in and around condensates. Working with model bovine serum albumin (BSA) condensates, we show that droplets swim along chemical gradients. Active BSA droplets loaded with urease swim toward each other. Passive BSA droplets show diverse responses to externally applied gradients of the enzyme’s substrate and products. In all these cases, droplets swim toward solvent conditions that favor their dissolution. We call this behavior “dialytaxis”, and expect it to be generic, as conditions which favor dissolution typically reduce interfacial tension, whose gradients are well-known to drive droplet motion through the Marangoni effect. These results could potentially suggest alternative physical mechanisms for active transport in living cells, and may enable the design of fluid micro-robots.
Pervasive structural heterogeneity rewires glioblastoma chromosomes to sustain patient-specific transcriptional programs
Authors: Xie Ting , Danieli-Mackay Adi , Buccarelli Mariachiara , Barbieri Mariano , Papadionysiou Ioanna , D’Alessandris Q. Giorgio , Robens Claudia , Übelmesser Nadine , Vinchure Omkar Suhas , Lauretti Liverana , Fotia Giorgio , Schwarz Roland F. , Wang Xiaotao , Ricci-Vitiani Lucia , Gopalakrishnan Jay , Pallini Roberto , Papantonis Argyris
Published: May 2024

Glioblastoma multiforme (GBM) encompasses brain malignancies marked by phenotypic and transcriptional heterogeneity thought to render these tumors aggressive, resistant to therapy, and inevitably recurrent. However, little is known about how the spatial organization of GBM genomes underlies this heterogeneity and its effects. Here, we compile a cohort of 28 patient-derived glioblastoma stem cell-like lines (GSCs) known to reflect the properties of their tumor-of-origin; six of these were primary-relapse tumor pairs from the same patient. We generate and analyze 5 kbp-resolution chromosome conformation capture (Hi-C) data from all GSCs to systematically map thousands of standalone and complex structural variants (SVs) and the multitude of neoloops arising as a result. By combining Hi-C, histone modification, and gene expression data with chromatin folding simulations, we explain how the pervasive, uneven, and idiosyncratic occurrence of neoloops sustains tumor-specific transcriptional programs via the formation of new enhancer-promoter contacts. We also show how even moderately recurrent neoloops can relate to patient-specific vulnerabilities. Together, our data provide a resource for dissecting GBM biology and heterogeneity, as well as for informing therapeutic approaches.
CLK2 mediates IκBα-independent early termination of NF-κB activation by inducing cytoplasmic redistribution and degradation
Authors: Li Shang-Ze , Shu Qi-Peng , Zhou Hai-Meng , Liu Yu-Ying , Fan Meng-Qi , Liang Xin-Yi , Qi Lin-Zhi , He Ya-Nan , Liu Xue-Yi , Du Xue-Hua , Huang Xi-Chen , Chen Yu-Zhen , Du Run-Lei , Liang Yue-Xiu , Zhang Xiao-Dong
Published: May 2024

Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.
Shared EEG correlates between non-REM parasomnia experiences and dreams
Authors: Cataldi Jacinthe , Stephan Aurélie M. , Haba-Rubio José , Siclari Francesca
Published: May 2024

Sleepwalking and related parasomnias result from incomplete awakenings out of non-rapid eye movement sleep. Behavioral episodes can occur without consciousness or recollection, or in relation to dream-like experiences. To understand what accounts for these differences in consciousness and recall, here we recorded parasomnia episodes with high-density electroencephalography (EEG) and interviewed participants immediately afterward about their experiences. Compared to reports of no experience (19%), reports of conscious experience (56%) were preceded by high-amplitude EEG slow waves in anterior cortical regions and activation of posterior cortical regions, similar to previously described EEG correlates of dreaming. Recall of the content of the experience (56%), compared to no recall (25%), was associated with higher EEG activation in the right medial temporal region before movement onset. Our work suggests that the EEG correlates of parasomnia experiences are similar to those reported for dreams and may thus reflect core physiological processes involved in sleep consciousness.
Fourier Quantum Process Tomography
Authors: Di Colandrea Francesco , Dehghan Nazanin , D’Errico Alessio , Karimi Ebrahim
Published: May 2024

The characterization of a quantum device is a crucial step in the development of quantum experiments. This is accomplished via Quantum Process Tomography, which combines the outcomes of different projective measurements to deliver a possible reconstruction of the underlying process. The tomography is typically performed by processing an overcomplete set of measurements and extracting the process matrix from maximum-likelihood estimation. Here, we introduce Fourier Quantum Process Tomography, a technique which requires a reduced number of measurements, and benchmark its performance against the standard maximum-likelihood approach. Fourier Quantum Process Tomography is based on measuring probability distributions in two conjugate spaces for different state preparations and projections. Exploiting the concept of phase retrieval, our scheme achieves a complete and robust characterization of the setup by processing a near-minimal set of measurements. We experimentally test the technique on different space-dependent polarization transformations, reporting average fidelities higher than 90% and significant computational advantage.
Alzheimer’s disease rewires gene coexpression networks coupling different brain regions
Authors: Mitra Sanga , BP Kailash , C R Srivatsan , Saikumar Naga Venkata , Philip Philge , Narayanan Manikandan
Published: May 2024

Connectome studies have shown how Alzheimer’s disease (AD) disrupts functional and structural connectivity among brain regions. But the molecular basis of such disruptions is less studied, with most genomic/transcriptomic studies performing within-brain-region analyses. To inspect how AD rewires the correlation structure among genes in different brain regions, we performed an Inter-brain-region Differential Correlation (Inter-DC) analysis of RNA-seq data from Mount Sinai Brain Bank on four brain regions (frontal pole, superior temporal gyrus, parahippocampal gyrus and inferior frontal gyrus, comprising 264 AD and 372 control human post-mortem samples). An Inter-DC network was assembled from all pairs of genes across two brain regions that gained (or lost) correlation strength in the AD group relative to controls at FDR 1%. The differentially correlated (DC) genes in this network complemented known differentially expressed genes in AD, and likely reflects cell-intrinsic changes since we adjusted for cell compositional effects. Each brain region used a distinctive set of DC genes when coupling with other regions, with parahippocampal gyrus showing the most rewiring, consistent with its known vulnerability to AD. The Inter-DC network revealed master dysregulation hubs in AD (at genes ZKSCAN1, SLC5A3, RCC1, IL17RB, PLK4, etc.), inter-region gene modules enriched for known AD pathways (synaptic signaling, endocytosis, etc.), and candidate signaling molecules that could mediate region-region communication. The Inter-DC network generated in this study is a valuable resource of gene pairs, pathways and signaling molecules whose inter-brain-region functional coupling is disrupted in AD, thereby offering a new perspective of AD etiology.
The metal-poor atmosphere of a potential sub-Neptune progenitor
Authors: Barat Saugata , Désert Jean-Michel , Vazan Allona , Baeyens Robin , Line Michael R. , Fortney Jonathan J. , David Trevor J. , Livingston John H. , Jacobs Bob , Panwar Vatsal , Shivkumar Hinna , Todorov Kamen O. , Pino Lorenzo , Mraz Georgia , Petigura Erik A.
Published: May 2024

Young transiting exoplanets offer a unique opportunity to characterize the atmospheres of freshly formed and evolving planets. We present the transmission spectrum of V1298 Tau b, a 23-Myr-old warm Jupiter-sized (0.91 ± 0.05 RJ, where RJ is the radius of Jupiter) planet orbiting a pre-main-sequence star. We detect a mostly clear primordial atmosphere with an exceptionally large atmospheric scale height, and a water vapour absorption at a 5σ level of significance, from which we estimate a planetary mass upper limit (23 Earth masses, 0.12 g cm−3 at a 3σ level). This is one of the lowest-density planets discovered so far. We retrieve a low atmospheric metallicity ($$\log{Z}=-0.{7}_{-0.7}^{+0.8}\,{\mathrm{solar}}$$

log
Z
=
−
0
.

7

−
0.7

+
0.8

solar

), consistent with solar/sub-solar values. Our findings challenge the expected mass–metallicity relation from core-accretion theory. Our observations can instead be explained by in situ formation via pebble accretion together with ongoing evolutionary mechanisms. We do not detect methane, which hints at a hotter-than-expected interior from just the formation entropy of this planet. Our observations suggest that V1298 Tau b is likely to evolve into a sub-Neptune.
Computational design of non-porous pH-responsive antibody nanoparticles
Authors: Yang Erin C. , Divine Robby , Miranda Marcos C. , Borst Andrew J. , Sheffler Will , Zhang Jason Z. , Decarreau Justin , Saragovi Amijai , Abedi Mohamad , Goldbach Nicolas , Ahlrichs Maggie , Dobbins Craig , Hand Alexis , Cheng Suna , Lamb Mila , Levine Paul M. , Chan Sidney , Skotheim Rebecca , Fallas Jorge , Ueda George , Lubner Joshua , Somiya Masaharu , Khmelinskaia Alena , King Neil P. , Baker David
Published: May 2024

Programming protein nanomaterials to respond to changes in environmental conditions is a current challenge for protein design and is important for targeted delivery of biologics. Here we describe the design of octahedral non-porous nanoparticles with a targeting antibody on the two-fold symmetry axis, a designed trimer programmed to disassemble below a tunable pH transition point on the three-fold axis, and a designed tetramer on the four-fold symmetry axis. Designed non-covalent interfaces guide cooperative nanoparticle assembly from independently purified components, and a cryo-EM density map closely matches the computational design model. The designed nanoparticles can package protein and nucleic acid payloads, are endocytosed following antibody-mediated targeting of cell surface receptors, and undergo tunable pH-dependent disassembly at pH values ranging between 5.9 and 6.7. The ability to incorporate almost any antibody into a non-porous pH-dependent nanoparticle opens up new routes to antibody-directed targeted delivery.
Multispectral analysis-ready satellite data for three East African mountain ecosystems
Authors: Bhandari Netra , Bald Lisa , Wraase Luise , Zeuss Dirk
Published: May 2024

The East African mountain ecosystems are facing increasing threats due to global change, putting their unique socio-ecological systems at risk. To monitor and understand these changes, researchers and stakeholders require accessible analysis-ready remote sensing data. Although satellite data is available for many applications, it often lacks accurate geometric orientation and has extensive cloud cover. This can generate misleading results and make it unreliable for time-series analysis. Therefore, it needs comprehensive processing before usage, which encompasses multi-step operations, requiring large computational and storage capacities, as well as expert knowledge. Here, we provide high-quality, atmospherically corrected, and cloud-free analysis-ready Sentinel-2 imagery for the Bale Mountains (Ethiopia), Mounts Kilimanjaro and Meru (Tanzania) ecosystems in East Africa. Our dataset ranges from 2017 to 2021 and is provided as monthly and annual aggregated products together with 24 spectral indices. Our dataset enables researchers and stakeholders to conduct immediate and impactful analyses. These applications can include vegetation mapping, wildlife habitat assessment, land cover change detection, ecosystem monitoring, and climate change research.
Global WaterPack - The development of global surface water over the past 20 years at daily temporal resolution
Authors: Klein Igor , Uereyen Soner , Sogno Patrick , Twele André , Hirner Andreas , Kuenzer Claudia
Published: May 2024

Open surface water across the globe is essential for many life forms and is an important source for human settlements, agriculture, and industry. The presence and variation in time and space is influenced by different natural conditions (e.g. climate, topography, geology) and human use (e.g. irrigation, flood protection). The information on the spatial and temporal distribution of open surface water is fundamental for many disciplines and is also required as an essential parameter for hydrological and climatological modelling. Here, we present a dataset derived from satellite earth observation, which is based on more than 6.3 million single MODIS products with a volume of approx. 300 TB. The resulting dataset reflects the situation of open surface water on a global scale for each day over the time period from 2003 to 2022 at a spatial resolution of 250 m. The dataset enables the analysis of the development of lake and reservoir surface areas, freezing cycles, and inundation areas.
Transcriptome dynamics of Gossypium purpurascens in response to abiotic stresses by Iso-seq and RNA-seq data
Authors: Rehman Abdul , Tian Chunyan , He Shoupu , Li Hongge , Lu Shuai , Du Xiongming , Peng Zhen
Published: May 2024

Gossypium purpurascens is a member of the Malvaceae family, holds immense economic significance as a fiber crop worldwide. Abiotic stresses harm cotton crops, reduce yields, and cause economic losses. Generating high-quality reference genomes and large-scale transcriptomic datasets across diverse conditions can offer valuable insights into identifying preferred agronomic traits for crop breeding. The present research used leaf tissues to conduct PacBio Iso-seq and RNA-seq analysis. We carried out an in-depth analysis of DEGs using both correlations with cluster analysis and principal component analysis. Additionally, the study also involved the identification of both lncRNAs and CDS. We have prepared RNA-seq libraries from 75 RNA samples to study the effects of drought, salinity, alkali, and saline-alkali stress, as well as control conditions. A total of 454.06 Gigabytes of transcriptome data were effectively validated through the identification of differentially expressed genes and KEGG and GO analysis. Overwhelmingly, gene expression profiles and full-length transcripts from cotton tissues will aid in understanding the genetic mechanism of abiotic stress tolerance in G. purpurascens.
Evaluation of the feeding safety of Moringa (Moringa oleifera L.) in the Sprague Dawley rat
Authors: Zhang Yu-Wen , Wang Fu-Jun , Cai Ming , Liu Yan-Pei , Liu Jian-Yong , Huang Bi-Zhi
Published: May 2024

This study aimed to evaluate the safety of Moringa by comparing the effects of different gavage doses of Moringa. The general behavior, body weight, food intake, blood indexes, serum biochemical indexes, and histopathology of rats were used to determine the safety threshold and to provide a reference for the further development and use of Moringa as animal feed. 40 Sprague Dawley rats were selected and given transoral gavage for 28 consecutive days. The T1, T2 and T3 groups were observed for general behavior, body weight, and food intake. Blood and serum biochemical indices were quantified, and histopathology was performed to evaluate the effect and safety of Moringa. The results of the toxicological test showed that (1) Only T1 groups experienced diarrhea. (2) The body weight and food intake of rats in each group were normal compared with the control group. (3) The hematological and serum biochemical indices of rats in the T1 group were significantly different from those of CK but were in the normal range; (4) The results of microscopic examination of the heart, liver, spleen, lung, and kidney of rats in each group were normal, but inflammation occurred in stomach and jejunum of rats in the T1 group, but not in the ileum. The gastrointestinal tract of rats in the T2 and T3 groups were normal. (5) No abnormal death occurred in any of the treatment groups.The results of this study revealed that gavage of Moringa homogenate at a dose of 6 g/kg BW can cause diarrhea in rats. Although there is no pathological effect on weight, food intake, blood and serum biochemical indicators in rats, there are pathological textures in the gastrointestinal tissue caused by diarrhea. Therefore, the safety threshold of Moringa homogenate should be ≤ 3 g/kg BW.
Multi-scene application of intelligent inspection robot based on computer vision in power plant
Authors: Lin Lulu , Guo Jianxian , Liu Lincheng
Published: May 2024

As industries develop, the automation and intelligence level of power plants is constantly improving, and the application of patrol robots is also increasingly widespread. This research combines computer vision technology and particle swarm optimization algorithm to build an obstacle recognition model and obstacle avoidance model of an intelligent patrol robot in a power plant respectively. Firstly, the traditional convolutional recurrent neural network is optimized, and the obstacle recognition model of an intelligent patrol robot is built by combining the connection timing classification algorithm. Then, the artificial potential field method optimizes the traditional particle swarm optimization algorithm, and an obstacle avoidance model of an intelligent patrol robot is built. The performance of the two models was tested, and it was found that the highest precision, recall, and F1 values of the identification model were 0.978, 0.974, and 0.975. The highest precision, recall, and F1 values of the obstacle avoidance model were 0.97, 0.96, and 0.96 respectively. The two optimization models designed in this research have better performance. In conclusion, the two models in this study are superior to the traditional methods in recognition effect and obstacle avoidance efficiency, providing an effective technical scheme for intelligent patrol inspection of power plants.
Cetuximab inhibits colorectal cancer development through inactivating the Wnt/β-catenin pathway and modulating PLCB3 expression
Authors: Zhang Xiaohong , Zhou Wenming , Wu Chenqu , Jiang Jun , Guo Qianqian , Feng Li , Cheng Xun , Zhang Xingxing
Published: May 2024

Colorectal cancer (CRC) often necessitates cetuximab (an EGFR-targeting monoclonal antibody) for treatment. Despite its clinical utility, the specific operative mechanism of cetuximab remains elusive. This research investigated the influence of PLCB3, a potential CRC oncogene, on cetuximab treatment. We extracted differentially expressed genes from the GSE140973, the overlapping genes combined with 151 Wnt/β-Catenin signaling pathway-related genes were identified. Then, we conducted bioinformatics analysis to pinpoint the hub gene. Subsequently, we investigated the clinical expression characteristics of this hub gene, through cell experimental, scrutinized the impact of cetuximab and PLCB3 on CRC cellular progression. The study identified 26 overlapping genes. High expression of PLCB3, correlated with poorer prognosis. PLCB3 emerged as a significant oncogene associated with patient prognosis. In vitro tests revealed that cetuximab exerted a cytotoxic effect on CRC cells, with PLCB3 knockdown inhibiting CRC cell progression. Furthermore, cetuximab treatment led to a reduction in both β-catenin and PLCB3 expression, while simultaneously augmenting E-cadherin expression. These findings revealed PLCB3 promoted cetuximab inhibition on Wnt/β-catenin signaling. Finally, simultaneous application of cetuximab with a Wnt activator (IM12) and PLCB3 demonstrated inhibited CRC proliferation, migration, and invasion. The study emphasized the pivotal role of PLCB3 in CRC and its potential to enhance the efficacy of cetuximab treatment. Furthermore, cetuximab suppressed Wnt/β-catenin pathway to modulate PLCB3 expression, thus inhibiting colorectal cancer progression. This study offered fresh perspectives on cetuximab mechanism in CRC.
Multifractal analysis of maize and soybean DNA
Authors: Correia J. P.
Published: May 2024

This paper investigates the complexity of DNA sequences in maize and soybean using the multifractal detrended fluctuation analysis (MF-DFA) method, chaos game representation (CGR), and the complexity-entropy plane approach. The study aims to understand the patterns and structures of these DNA sequences, which can provide insights into their genetic makeup and improve crop yield and quality. The results show that maize and soybean DNA sequences exhibit fractal properties, indicating a complex and self-organizing structure. We observe the persistence trend between sequences of base pairs, which indicates long-range correlations between base pairs. We also identified the stochastic nature of the DNA sequences of both species.
Chaga mushroom extract suppresses oral cancer cell growth via inhibition of energy metabolism
Authors: Yeo Donghyeon , Yun Yeo Gyun , Shin Seong-Jin , Dashnyam Khandmaa , Khurelbaatar Anand , Lee Jun Hee , Kim Hae-Won
Published: May 2024

Oral cancer stands as a prevalent maligancy worldwide; however, its therapeutic potential is limited by undesired effects and complications. As a medicinal edible fungus, Chaga mushroom (Inonotus obliquus) exhibits anticancer effects across diverse cancers. Yet, the precise mechanisms underlying its efficacy remain unclear. We explored the detailed mechanisms underlying the anticancer action of Chaga mushroom extract in oral cancer cells (HSC-4). Following treatment with Chaga mushroom extracts, we analyzed cell viability, proliferation capacity, glycolysis, mitochondrial respiration, and apoptosis. Our findings revealed that the extract reduced cell viability and proliferation of HSC-4 cells while arresting their cell cycle via suppression of STAT3 activity. Regarding energy metabolism, Chaga mushroom extract inhibited glycolysis and mitochondrial membrane potential in HSC-4 cells, thereby triggering autophagy-mediated apoptotic cell death through activation of the p38 MAPK and NF-κB signaling pathways. Our results indicate that Chaga mushroom extract impedes oral cancer cell progression, by inhibiting cell cycle and proliferation, suppressing cancer cell energy metabolism, and promoting autophagy-mediated apoptotic cell death. These findings suggest that this extract is a promising supplementary medicine for the treatment of patients with oral cancer.