bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanoscale Spectroscopic Identification and Characterization of Minerals and Organic Matter in Ryugu Particles
Authors: Yesiltas Mehmet , Glotch Timothy D. , Kebukawa Yoko , Sava Bogdan , Durmaz Yasin C. , Northrup Paul
Published: April 2024

Carbonaceous asteroids are leftover materials from the early solar system. They did not undergo planetary differentiation processes and thus still retained signatures and clues of the origin and evolution of the solar system. Thus, samples of carbonaceous asteroids provide significant potential for deciphering the origin of the solar system. The Hayabusa2 spacecraft returned the first samples of a carbonaceous asteroid (162173) Ryugu. In this work, we report the nanoscale mineralogy and organic matter content of two Ryugu particles, A0030 and C0034. These were analyzed by highly novel scattering‐type scanning near‐field optical microscopy (s‐SNOM)‐based nanoscale‐Fourier transform infrared (nano‐FTIR) spectroscopy with ∼20 nm spatial resolution. The nano‐FTIR measurements were supported by confocal micro‐Raman imaging and spectroscopy (∼500 nm/pixel spatial sampling). Our investigations show that the two Ryugu particles (a) contain different silicate mineralogies, indicating heterogeneous and incomplete aqueous alteration and (b) are highly rich in organic matter, consisting a variety of molecular functional groups. The spatial distributions of chemical functional groups and their associations based on pseudo‐heterodyne (PsHet) SNOM imaging show that the organic matter is distributed as either diffused or discrete grains. Micro‐Raman spectra show that the Ryugu particles experienced minimal thermal metamorphism, although A0030 was slightly more heated than C0034. The identification of abundant nanoscale organic molecules within the Ryugu grains that could not be identified via micrometer‐scale investigations emphasizes the importance of using nanoscale nondestructive methods for studying primitive solar system materials, such as Ryugu and OSIRIS‐Rex particles and those that will be returned in the future (such as MMX samples).
Depositional Facies and Sequence Stratigraphy of Kodiak Butte, Western Delta of Jezero Crater, Mars
Authors: Caravaca G. , Dromart G. , Mangold N. , Gupta S. , Kah L. C. , Tate C. , Williams R. M. E. , Le Mouélic S. , Gasnault O. , Bell J. , Beyssac O. , Nuñez J. I. , Randazzo N. , Rice J. , Crumpler L. S. , Williams A. , Russel P. , Stack K. M. , Farley K. A. , Maurice S. , Wiens R. C.
Published: April 2024

High‐resolution 2D and 3D data remotely acquired by SuperCam's Remote Micro‐Imager and Mastcam‐Z aboard the Perseverance rover enabled us to characterize the stratigraphic architecture and sedimentary record of the Kodiak butte, an isolated remnant of the western delta fan of Jezero crater. Using these data, we build up on previous interpretations of the butte interpreted as a prograding Gilbert‐type deltaic series. We characterize three individual stratigraphic Units 0 to 2 on the eastern and northern faces of the butte. Each Unit displays the same vertical succession of prodeltaic/lacustrine bottomsets, delta slope toesets and foresets, and fluvially influenced topsets of a deltaic plain with a braided river pattern, shown by 11 individual sedimentary facies. We infer that these individual Units record the formation of three distinct deltaic mouth bars successively across time and space. For the first time on another planet than Earth, we are able to construct a precise sequence stratigraphic framework to highlight lake‐level fluctuations at the time the Kodiak butte was emplaced, during the latest stages of deltaic activity. We identify four hydrogeological cycles indicated by alternating rises and falls of the lake‐level on the order of 5–10 m. These were most probably linked to climatic events and variations controlling lake water inputs in probable relation to an astronomical control.
Rock Glacier Movement and Debris Transport Over Annual to Multi‐Millennial Timescales
Authors: Munroe Jeffrey S. , Laabs Benjamin J. C. , Corbett Lee B. , Bierman Paul R. , Handwerger Alexander L.
Published: April 2024

Rock glaciers are common in alpine landscapes, but their evolution over time and their significance as agents of debris transport are not well‐understood. Here, we assess the movement of an ice‐cemented rock glacier over a range of timescales using GPS surveying, satellite‐based radar, and cosmogenic 10Be surface‐exposure dating. GPS and InSAR measurements indicate that the rock glacier moved at an average rate of ∼10 cm yr−1 in recent years. Sampled boulders on the rock glacier have cosmogenic surface‐exposure ages from 1.2 to 10 ka, indicating that they have been exposed since the beginning of the Holocene. Exposure ages increase linearly with distance downslope, suggesting a slower long‐term mean surface velocity of 3 ± 0.3 cm yr−1. Our findings suggest that the behavior of this rock glacier may be dominated by episodes of dormancy punctuated by intervals of relatively rapid movement over both short and long timescales. Our findings also show that the volume of the rock glacier corresponds to ∼10 m of material stripped from the headwall during the Holocene. These are the first cosmogenic surface‐exposure ages to constrain movement of a North American rock glacier, and together with the GPS and satellite radar measurements, they reveal that rock glaciers are effective geomorphic agents with dynamic multi‐millennial histories.
Consequences of Continental Core Complexes on Rifting Patterns: Insights From Multichannel Seismic Data From the Northern Margin of the South China Sea
Authors: Xu Yancheng , Ren Jianye , Zhao Yanghui , Zheng Jinyun , Lei Chao , Zhu Dingwei
Published: April 2024

Core complex type structures are common in continental margins. Recent studies have proposed exhumation of deeper crustal and mantle levels during extension of the continental margin along the Northern South China Sea (NSCS) in a core complex mode. Here, we present high‐resolution seismic profiles across different sections of the NSCS that allow us to observe two types of core complex systems. The Kaiping Rift and eastern Baiyun Rift are characterized by a sub‐horizontal Moho and exhumation of ductile deeper crust beneath an extremely thinned brittle upper crust. The central Baiyun Rift in contrast is marked by homogeneous thinning of the entire crust that is floored by mantle unroofing with a concave‐down Moho geometry. While the former type, referred to as crustal core complexes, coincides with relatively intense syn‐rift magmatism, the latter, referred to as mantle core complexes, is marked by limited magmatism. Consistently, basin subsidence rates are lower over crustal core complexes than mantle core complexes. Compared to mantle core complexes at the magma‐poor Iberian margin, the widely distributed crustal core complexes in the NSCS indicate higher geotherms and more intense magmatism during extension of the continental lithosphere. We propose that the continental core complexes observed at the NSCS represent a typical outcome of extension of a gravitationally unstable lithosphere.
Glacier Retreat in Eastern Himalaya Drives Catastrophic Glacier Hazard Chain
Authors: Li Yao , Cui Yifei , Hu Xie , Lu Zhong , Guo Jian , Wang Yu , Wang Hao , Wang Shuofan , Zhou Xinzhi
Published: April 2024

Cryospheric responses to climate warming include glacier retreat, altitude‐dependent thermal instability, and abundant meltwater, which increase the frequency of catastrophic glacier hazard chain (CGHC) events. Here we investigated the formation mechanism of a special CGHC event in 2018, in the Sedongpu Glacier, Eastern Himalayas, China. Based on the multi‐source remote sensing, seismic signal analysis, and numerical simulation, we conducted long‐term retrospective analysis and co‐event process reconstruction. The results show that the event could be divided into two phases. First, the hanging glacier with a volume of 8.5 × 106 m3 collapsed onto the downstream trunk glacier. Next, ∼1.17 × 108 m3 eroded materials from the impacted glacier transformed into debris flow and traveled downstream 8 km. During the cascading process, ice‐rock avalanche momentum and glacier velocity are key factors in determining CGHC formation and eventual volume. Our study helps better understand the domino effects of the CGHC disaster.
Continental Crust Rejuvenation Across the Paleo‐Mesoarchean Transition Resulted From Elevated Mantle Geotherms
Authors: Lu Gui‐Mei , Xu Yi‐Gang , Wang Wei , Spencer Christopher J. , Huang Guangyu , Roberts Nick M. W.
Published: April 2024

The increase in initial Hf isotopes identified in early Mesoarchean detrital zircon is commonly interpreted as a reflection of the geodynamic transition from stagnant‐lid to mobile‐lid tectonics. However, given the lack of petrogenetic context, interpreting detrital zircon may lead to spurious conclusions. In this contribution, we use zircon U‐Pb‐Hf‐O isotopic and bulk rock compositions of newly identified 3.05–2.9 Ga granitoids from the SW Yangtze Block to posit petrogenesis within an isotopically juvenile magmatic system. A statistical analysis of these data with a global igneous zircon Lu‐Hf isotopic compilation reveals an increase in average initial radiogenic Hf isotopes during the Paleoarchean to Mesoarchean transition. We posit that the Earth's continental crust underwent a global rejuvenation across the Paleo‐Mesoarchean transition. This rejuvenation can be explained by an independently observed increase in mantle temperatures resulting from mantle thermal evolution and does not require a change in tectonic style.
Genome-wide DNA methylation-analysis of blastic plasmacytoid dendritic cell neoplasm identifies distinct molecular features
Authors: Künstner Axel , Schwarting Julian , Witte Hanno M. , Xing Pengwei , Bernard Veronica , Stölting Stephanie , Lohneis Philipp , Janke Florian , Salehi Maede , Chen Xingqi , Kusch Kathrin , Sültmann Holger , Chteinberg Emil , Fischer Anja , Siebert Reiner , von Bubnoff Nikolas , Merz Hartmut , Busch Hauke , Feller Alfred C. , Gebauer Niklas
Published: April 2024

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) constitutes a rare and aggressive malignancy originating from plasmacytoid dendritic cells (pDCs) with a primarily cutaneous tropism followed by dissemination to the bone marrow and other organs. We conducted a genome-wide analysis of the tumor methylome in an extended cohort of 45 BPDCN patients supplemented by WES and RNA-seq as well as ATAC-seq on selected cases. We determined the BPDCN DNA methylation profile and observed a dramatic loss of DNA methylation during malignant transformation from early and mature DCs towards BPDCN. DNA methylation profiles further differentiate between BPDCN, AML, CMML, and T-ALL exhibiting the most striking global demethylation, mitotic stress, and merely localized DNA hypermethylation in BPDCN resulting in pronounced inactivation of tumor suppressor genes by comparison. DNA methylation-based analysis of the tumor microenvironment by MethylCIBERSORT yielded two, prognostically relevant clusters (IC1 and IC2) with specific cellular composition and mutational spectra. Further, the transcriptional subgroups of BPDCN (C1 and C2) differ by DNA methylation signatures in interleukin/inflammatory signaling genes but also by higher transcription factor activity of JAK-STAT and NFkB signaling in C2 in contrast to an EZH2 dependence in C1-BPDCN. Our integrative characterization of BPDCN offers novel molecular insights and potential diagnostic applications.
Combination p53 activation and BCL-xL/BCL-2 inhibition as a therapeutic strategy in high-risk and relapsed acute lymphoblastic leukemia
Authors: Bell Hayden L. , Blair Helen J. , Jepson Gosling Samantha J. , Galler Martin , Astley Daniel , Moorman Anthony V. , Heidenreich Olaf , Veal Gareth J. , van Delft Frederik W. , Lunec John , Irving Julie A. E.
Published: April 2024

Due to the rarity of TP53 mutations in acute lymphoblastic leukemia (ALL), p53 re-activation by antagonism of the p53-MDM2 interaction represents a potential therapeutic strategy for the majority of ALL. Here, we demonstrate the potent antileukemic activity of the MDM2 antagonist idasanutlin in high-risk and relapsed ex vivo coculture models of TP53 wildtype ALL (n = 40). Insufficient clinical responses to monotherapy MDM2 inhibitors in other cancers prompted us to explore optimal drugs for combination therapy. Utilizing high-throughput combination screening of 1971 FDA-approved and clinically advanced compounds, we identified BCL-xL/BCL-2 inhibitor navitoclax as the most promising idasanutlin combination partner. The idasanutlin-navitoclax combination was synergistically lethal to prognostically-poor, primary-derived and primary patient blasts in ex vivo coculture, and reduced leukemia burden in two very high-risk ALL xenograft models at drug concentrations safely attained in patients; in fact, the navitoclax plasma concentrations were equivalent to those attained in contemporary “low-dose” navitoclax clinical trials. We demonstrate a preferential engagement of cell death over G1 cell cycle arrest, mechanistically implicating MCL-1-binding pro-apoptotic sensitizer NOXA. The proposed combination of two clinical-stage compounds independently under clinical evaluation for ALL is of high clinical relevance and warrants consideration for the treatment of patients with high-risk and relapsed ALL.
AM6527, a neutral CB1 receptor antagonist, suppresses opioid taking and seeking, as well as cocaine seeking in rodents without aversive effects
Authors: Soler-Cedeño Omar , Alton Hannah , Bi Guo-Hua , Linz Emily , Ji Lipin , Makriyannis Alexandros , Xi Zheng-Xiong
Published: April 2024

Preclinical research has demonstrated the efficacy of CB1 receptor (CB1R) antagonists in reducing drug-taking behavior. However, clinical trials with rimonabant, a CB1R antagonist with inverse agonist profile, failed due to severe adverse effects, such as depression and suicidality. As a result, efforts have shifted towards developing novel neutral CB1R antagonists without an inverse agonist profile for treating substance use disorders. Here, we assessed AM6527, a CB1R neutral antagonist, in addiction animal models. Our findings revealed that AM6527 did not affect cocaine self-administration under fixed-ratio reinforcement schedules but dose-dependently inhibited it under progressive-ratio reinforcement schedules. Additionally, AM6527 dose-dependently inhibited heroin self-administration under both fixed-ratio and progressive-ratio reinforcement schedules and oral sucrose self-administration under a fixed-ratio reinforcement schedule, as well as cocaine- or heroin-triggered reinstatement of drug-seeking behavior in rats. However, chronic AM6527 administration for five consecutive days significantly inhibited heroin self-administration only during the initial two days, indicating tolerance development. Notably, AM6527 did not produce rewarding or aversive effects by itself in classical electrical intracranial self-stimulation and conditioned place preference tests. However, in optical intracranial self-stimulation (oICSS) maintained by optogenetic stimulation of midbrain dopamine neurons in DAT-cre mice, both AM6527 and rimonabant dose-dependently inhibited dopamine-dependent oICSS behavior. Together, these findings suggest that AM6527 effectively reduces drug-taking and seeking behaviors without rimonabant-like adverse effects. Thus, AM6527 warrants further investigation as a potential pharmacotherapy for opioid and cocaine use disorders.
NRF2 activation by cysteine as a survival mechanism for triple-negative breast cancer cells
Authors: Bottoni Laura , Minetti Alberto , Realini Giulia , Pio Elena , Giustarini Daniela , Rossi Ranieri , Rocchio Chiara , Franci Lorenzo , Salvini Laura , Catona Orazio , D’Aurizio Romina , Rasa Mahdi , Giurisato Emanuele , Neri Francesco , Orlandini Maurizio , Chiariello Mario , Galvagni Federico
Published: April 2024

Triple-negative breast cancer (TNBC) is a very aggressive and heterogeneous group of tumors. In order to develop effective therapeutic strategies, it is therefore essential to identify the subtype-specific molecular mechanisms underlying disease progression and resistance to chemotherapy. TNBC cells are highly dependent on exogenous cystine, provided by overexpression of the cystine/glutamate antiporter SLC7A11/xCT, to fuel glutathione synthesis and promote an oxidative stress response consistent with their high metabolic demands. Here we show that TNBC cells of the mesenchymal stem-like subtype (MSL) utilize forced cystine uptake to induce activation of the transcription factor NRF2 and promote a glutathione-independent mechanism to defend against oxidative stress. Mechanistically, we demonstrate that NRF2 activation is mediated by direct cysteinylation of the inhibitor KEAP1. Furthermore, we show that cystine-mediated NRF2 activation induces the expression of important genes involved in oxidative stress response, but also in epithelial-to-mesenchymal transition and stem-like phenotype. Remarkably, in survival analysis, four upregulated genes (OSGIN1, RGS17, SRXN1, AKR1B10) are negative prognostic markers for TNBC. Finally, expression of exogenous OSGIN1, similarly to expression of exogenous NRF2, can prevent cystine depletion-dependent death of MSL TNBC cells. The results suggest that the cystine/NRF2/OSGIN1 axis is a potential target for effective treatment of MSL TNBCs.
Robotic technology (ROBERT®) to enhance muscle strength in the hip flexor muscles following spinal cord injury: a feasibility study
Authors: Sørensen S. L. , Poulsen I. , Harvey L. A. , Biering-Sørensen F. , Nielsen J. F.
Published: April 2024

Study design

Feasibility study.

Objective

To determine the feasibility of conducting a large trial designed to determine whether the ROBERT® can be used to increase the strength of the hip flexor muscles after spinal cord injury (SCI). The ROBERT® is a robotic device that provides assisted active movement while supporting the weight of the leg. Focus was on recruitment capability, suitability, and acceptability of the intervention and outcome measure.

Setting

Specialised SCI centre in Denmark.

Methods

All first-time admitted patients were screened to assess participant recruitment capability. Four people with SCI < 3 months tested a protocol consisting of 60 repetitions of hip flexion in supine conducted with the assistance of the ROBERT® three times a week for 4 weeks. Feasibility was assessed based on adherence to the protocol and completion rate and from the participants’ perspectives. Maximal voluntary contraction (MVC) was accessed at baseline and four weeks.

Results

The recruitment rate was 8% (7 months). The four participants completed 44 out of 48 sessions (92%). No adverse events occurred. One physiotherapist was required to set-up and supervise each session. The active exercise time varied from 7.5 to 17 min. The participants found the ROBERT® a good supplement to their usual rehabilitation. We were able to measure MVC in even very weak hip flexor muscles with a dynamometer MicroFET2 fixed to a frame.

Conclusion

The ROBERT® was feasible and acceptable. The participants perceived it as a supplement, not a replacement to usual physiotherapy. However, recruitment to the study was slow.

Trial registration

ClinicalTrials.gov NCT05558254. Registered 28th September 2022.
Higher-order functional brain networks and anterior cingulate glutamate + glutamine (Glx) in antipsychotic-naïve first episode psychosis patients
Authors: Maximo Jose O. , Briend Frederic , Armstrong William P. , Kraguljac Nina V. , Lahti Adrienne C.
Published: April 2024

Human connectome studies have provided abundant data consistent with the hypothesis that functional dysconnectivity is predominant in psychosis spectrum disorders. Converging lines of evidence also suggest an interaction between dorsal anterior cingulate cortex (dACC) cortical glutamate with higher-order functional brain networks (FC) such as the default mode (DMN), dorsal attention (DAN), and executive control networks (ECN) in healthy controls (HC) and this mechanism may be impaired in psychosis. Data from 70 antipsychotic-medication naïve first-episode psychosis (FEP) and 52 HC were analyzed. 3T Proton magnetic resonance spectroscopy (1H-MRS) data were acquired from a voxel in the dACC and assessed correlations (positive FC) and anticorrelations (negative FC) of the DMN, DAN, and ECN. We then performed regressions to assess associations between glutamate + glutamine (Glx) with positive and negative FC of these same networks and compared them between groups. We found alterations in positive and negative FC in all networks (HC > FEP). A relationship between dACC Glx and positive and negative FC was found in both groups, but when comparing these relationships between groups, we found contrasting associations between these variables in FEP patients compared to HC. We demonstrated that both positive and negative FC in three higher-order resting state networks are already altered in antipsychotic-naïve FEP, underscoring the importance of also considering anticorrelations for optimal characterization of large-scale functional brain networks as these represent biological processes as well. Our data also adds to the growing body of evidence supporting the role of dACC cortical Glx as a mechanism underlying alterations in functional brain network connectivity. Overall, the implications for these findings are imperative as this particular mechanism may differ in untreated or chronic psychotic patients; therefore, understanding this mechanism prior to treatment could better inform clinicians.

Clinical trial registration: Trajectories of Treatment Response as Window into the Heterogeneity of Psychosis: A Longitudinal Multimodal Imaging Study, NCT03442101. Glutamate, Brain Connectivity and Duration of Untreated Psychosis (DUP), NCT02034253.
Neratinib could be effective as monotherapy or in combination with trastuzumab in HER2-low breast cancer cells and organoid models
Authors: Arshad Maryam , Azad Abul , Chan Phoebe Yuen Ka , Vigneswara Vasanthy , Feldinger Katharina , Nafi Siti Norasikin Mohd , Laporte-Maguire Eloise , De Santo Carmela , Zuo Jianmin , Shaaban Abeer M. , Kong Anthony
Published: April 2024

Background

Previous studies have suggested that patients with HER2-low breast cancers do not benefit from trastuzumab treatment although the reasons remain unclear.

Methods

We investigated the effect of trastuzumab monotherapy and its combination with different HER2 targeting treatments in a panel of breast cancer cell lines and patient-derived organoids (PDOs) using biochemical methods and cell viability assays.

Results

Compared to sensitive HER2 over-expressing (IHC3 + ) breast cancer cells, increasing doses of trastuzumab could not achieve IC50 in MDA-MB-361 (IHC 2 + FISH + ) and MDA-MB-453 (IHC 2 + FISH-) cells which showed an intermediate response to trastuzumab. Trastuzumab treatment induced upregulation of HER ligand release, resulting in the activation of HER receptors in these cells, which could account for their trastuzumab insensitivity. Adding a dual ADAM10/17 inhibitor to inhibit the shedding of HER ligands in combination with trastuzumab only showed a modest decrease in the cell viability of HER2-low breast cancer cells and PDOs. However, the panHER inhibitor neratinib was an effective monotherapy in HER2-low breast cancer cells and PDOs, and showed additive effects when combined with trastuzumab.

Conclusion

This study demonstrates that neratinib in combination with trastuzumab may be effective in a subset of HER2-low breast cancers although further validation is required in a larger panel of PDOs and in future clinical studies.
Increased miR-3074-5p expression promotes M1 polarization and pyroptosis of macrophages via ERα/NLRP3 pathway and induces adverse pregnancy outcomes in mice
Authors: Yang Long , Xu Hao-Ran , Zhang Xuan , Shi Yan , Shi Jia-Xin , Chen Qian-Qian , Shen Xiao-Rong , He Ya-Ping , Tang Jia-Nan , Gu Wen-Wen , Wang Jian
Published: April 2024

Decidual macrophages (dMϕs) play critical roles in regulation of immune-microhomeostasis at maternal-fetal interface during pregnancy, but the underlying molecular mechanisms are still unclear. In this study, it was found that litter size and fetal weight were significantly reduced, whereas the rate of embryo resorption was increased in miR-3074-5p knock-in (3074-KI) pregnant mice, compared to that of wild-type (WT) pregnant mice. Plasma levels of pro-inflammatory cytokines in 3074-KI pregnant mice were also significantly elevated compared to WT pregnant mice at GD7.5. The quantity of M1-Mϕs in uterine tissues of 3074-KI pregnant mice was significantly increased compared to WT pregnant mice at GD13.5. Estrogen receptor-α (ERα) was validated to be a target of miR-3074-5p. Either miR-3074-5p overexpression or ERα knockdown promoted transcriptional activity of NF-κB/p65, induced M1-polarization and pyroptosis of THP1-derived Mϕs, accompanied with increased intracellular levels of cleaved Caspase-1, cleaved IL-1β, NLRP3, cleaved GSDMD and ASC aggregation. Furthermore, ERα could not only bind to NLRP3 or ASC directly, but also inhibit the interaction between NLRP3 and ASC. The endometrial miR-3074-5p expression level at the middle secretory stage of repeated implantation failure (RIF) patients was significantly decreased compared to that of control fertile women. These data indicated that miR-3074-5p could promote M1 polarization and pyroptosis of Mϕs via activation of NLRP3 inflammasome by targeting ERα, and the dysregulation of miR-3074-5p expression in dMϕs might damage the embryo implantation and placentation by interfering with inflammatory microenvironment at the maternal-fetal interface during early pregnancy.
Prevalence of presenting bilateral visual impairment associated with refractive error – findings from the See4School, pre-school vision screening programme in NHS Scotland
Authors: Pentland Lee , Conway Miriam Louise
Published: April 2024

Background/objectives

The See4School programme in Scotland is a pre-school vision screening initiative delivered by orthoptists on a national scale. The primary objective of any vision screening programme is to identify amblyopia, given the common understanding that this condition is unlikely to be detected either at home or through conventional healthcare channels. The target condition is not bilateral visual impairment, as it is believed that most children will be identified within the first year of life either through observations at home or as part of the diagnosis of another related disorder. This belief persists even though bilateral visual impairment is likely to have a more detrimental impact on a child’s day-to-day life, including their education. If this hypothesis were accurate, the occurrence of bilateral visual impairment detected through the Scottish vision screening programme would be minimal as children already under the hospital eye service are not invited for testing. The overarching aim of this study was therefore to determine the prevalence of presenting bilateral visual impairment associated with refractive error detected via the Scottish preschool screening programme.

Subjects/methods

Retrospective anonymised data from vision screening referrals in Scotland from 2013–2016 were collected. Children underwent an assessment using a crowded logMAR vision test and a small number of orthoptic tests.

Results

During the 3-year period, out of 165,489 eligible children, 141,237 (85.35%) received the vision screening assessment. Among them, 27,010 (19.12%) failed at least one part of the screening and were subsequently referred into the diagnostic pathway, where they received a full sight test. The prevalence of bilateral visual impairment associated with refractive error and detected via the vision screening programme (≥ 0.3LogMAR) was reported to range between 1.47% (1.37–1.59) and 2.42% (2.29–2.57).

Conclusions

It is estimated that up to 2.42% (2.29–2.57) of children living Scotland have poorer than driving standard of vision (6/12) in their pre-school year, primarily due to undetected refractive error. Reduced vision has the potential to impact a child’s their day-to-day life including their future educational, health and social outcomes.
Transcription-coupled DNA–protein crosslink repair by CSB and CRL4CSA-mediated degradation
Authors: van Sluis Marjolein , Yu Qing , van der Woude Melanie , Gonzalo-Hansen Camila , Dealy Shannon C. , Janssens Roel C. , Somsen Hedda B. , Ramadhin Anisha R. , Dekkers Dick H. W. , Wienecke Hannah Lena , Demmers Joris J. P. G. , Raams Anja , Davó-Martínez Carlota , Llerena Schiffmacher Diana A. , van Toorn Marvin , Häckes David , Thijssen Karen L. , Zhou Di , Lammers Judith G. , Pines Alex , Vermeulen Wim , Pothof Joris , Demmers Jeroen A. A. , van den Berg Debbie L. C. , Lans Hannes , Marteijn Jurgen A.
Published: April 2024

DNA–protein crosslinks (DPCs) arise from enzymatic intermediates, metabolism or chemicals like chemotherapeutics. DPCs are highly cytotoxic as they impede DNA-based processes such as replication, which is counteracted through proteolysis-mediated DPC removal by spartan (SPRTN) or the proteasome. However, whether DPCs affect transcription and how transcription-blocking DPCs are repaired remains largely unknown. Here we show that DPCs severely impede RNA polymerase II-mediated transcription and are preferentially repaired in active genes by transcription-coupled DPC (TC-DPC) repair. TC-DPC repair is initiated by recruiting the transcription-coupled nucleotide excision repair (TC-NER) factors CSB and CSA to DPC-stalled RNA polymerase II. CSA and CSB are indispensable for TC-DPC repair; however, the downstream TC-NER factors UVSSA and XPA are not, a result indicative of a non-canonical TC-NER mechanism. TC-DPC repair functions independently of SPRTN but is mediated by the ubiquitin ligase CRL4CSA and the proteasome. Thus, DPCs in genes are preferentially repaired in a transcription-coupled manner to facilitate unperturbed transcription.
Endogenous aldehyde-induced DNA–protein crosslinks are resolved by transcription-coupled repair
Authors: Oka Yasuyoshi , Nakazawa Yuka , Shimada Mayuko , Ogi Tomoo
Published: April 2024

DNA–protein crosslinks (DPCs) induced by aldehydes interfere with replication and transcription. Hereditary deficiencies in DPC repair and aldehyde clearance processes cause progeria, including Ruijs–Aalfs syndrome (RJALS) and AMeD syndrome (AMeDS) in humans. Although the elimination of DPC during replication has been well established, how cells overcome DPC lesions in transcription remains elusive. Here we show that endogenous aldehyde-induced DPC roadblocks are efficiently resolved by transcription-coupled repair (TCR). We develop a high-throughput sequencing technique to measure the genome-wide distribution of DPCs (DPC-seq). Using proteomics and DPC-seq, we demonstrate that the conventional TCR complex as well as VCP/p97 and the proteasome are required for the removal of formaldehyde-induced DPCs. TFIIS-dependent cleavage of RNAPII transcripts protects against transcription obstacles. Finally, a mouse model lacking both aldehyde clearance and TCR confirms endogenous DPC accumulation in actively transcribed regions. Collectively, our data provide evidence that transcription-coupled DPC repair (TC-DPCR) as well as aldehyde clearance are crucial for protecting against metabolic genotoxin, thus explaining the molecular pathogenesis of AMeDS and other disorders associated with defects in TCR, such as Cockayne syndrome.
Emergence of fractal geometries in the evolution of a metabolic enzyme
Authors: Sendker Franziska L. , Lo Yat Kei , Heimerl Thomas , Bohn Stefan , Persson Louise J. , Mais Christopher-Nils , Sadowska Wiktoria , Paczia Nicole , Nußbaum Eva , del Carmen Sánchez Olmos María , Forchhammer Karl , Schindler Daniel , Erb Tobias J. , Benesch Justin L. P. , Marklund Erik G. , Bange Gert , Schuller Jan M. , Hochberg Georg K. A.
Published: April 2024

Fractals are patterns that are self-similar across multiple length-scales1. Macroscopic fractals are common in nature2–4; however, so far, molecular assembly into fractals is restricted to synthetic systems5–12. Here we report the discovery of a natural protein, citrate synthase from the cyanobacterium Synechococcus elongatus, which self-assembles into Sierpiński triangles. Using cryo-electron microscopy, we reveal how the fractal assembles from a hexameric building block. Although different stimuli modulate the formation of fractal complexes and these complexes can regulate the enzymatic activity of citrate synthase in vitro, the fractal may not serve a physiological function in vivo. We use ancestral sequence reconstruction to retrace how the citrate synthase fractal evolved from non-fractal precursors, and the results suggest it may have emerged as a harmless evolutionary accident. Our findings expand the space of possible protein complexes and demonstrate that intricate and regulatable assemblies can evolve in a single substitution.
Generative models improve fairness of medical classifiers under distribution shifts
Authors: Ktena Ira , Wiles Olivia , Albuquerque Isabela , Rebuffi Sylvestre-Alvise , Tanno Ryutaro , Roy Abhijit Guha , Azizi Shekoofeh , Belgrave Danielle , Kohli Pushmeet , Cemgil Taylan , Karthikesalingam Alan , Gowal Sven
Published: April 2024

Domain generalization is a ubiquitous challenge for machine learning in healthcare. Model performance in real-world conditions might be lower than expected because of discrepancies between the data encountered during deployment and development. Underrepresentation of some groups or conditions during model development is a common cause of this phenomenon. This challenge is often not readily addressed by targeted data acquisition and ‘labeling’ by expert clinicians, which can be prohibitively expensive or practically impossible because of the rarity of conditions or the available clinical expertise. We hypothesize that advances in generative artificial intelligence can help mitigate this unmet need in a steerable fashion, enriching our training dataset with synthetic examples that address shortfalls of underrepresented conditions or subgroups. We show that diffusion models can automatically learn realistic augmentations from data in a label-efficient manner. We demonstrate that learned augmentations make models more robust and statistically fair in-distribution and out of distribution. To evaluate the generality of our approach, we studied three distinct medical imaging contexts of varying difficulty: (1) histopathology, (2) chest X-ray and (3) dermatology images. Complementing real samples with synthetic ones improved the robustness of models in all three medical tasks and increased fairness by improving the accuracy of clinical diagnosis within underrepresented groups, especially out of distribution.
High resolution optical and acoustic remote sensing datasets of the Puck Lagoon
Authors: Janowski Łukasz , Skarlatos Dimitrios , Agrafiotis Panagiotis , Tysiąc Paweł , Pydyn Andrzej , Popek Mateusz , Kotarba-Morley Anna M. , Mandlburger Gottfried , Gajewski Łukasz , Kołakowski Mateusz , Papadaki Alexandra , Gajewski Juliusz
Published: April 2024

The very shallow marine basin of Puck Lagoon in the southern Baltic Sea, on the Northern coast of Poland, hosts valuable benthic habitats and cultural heritage sites. These include, among others, protected Zostera marina meadows, one of the Baltic’s major medieval harbours, a ship graveyard, and likely other submerged features that are yet to be discovered. Prior to this project, no comprehensive high-resolution remote sensing data were available for this area. This article describes the first Digital Elevation Models (DEMs) derived from a combination of airborne bathymetric LiDAR, multibeam echosounder, airborne photogrammetry and satellite imagery. These datasets also include multibeam echosounder backscatter and LiDAR intensity, allowing determination of the character and properties of the seafloor. Combined, these datasets are a vital resource for assessing and understanding seafloor morphology, benthic habitats, cultural heritage, and submerged landscapes. Given the significance of Puck Lagoon’s hydrographical, ecological, geological, and archaeological environs, the high-resolution bathymetry, acquired by our project, can provide the foundation for sustainable management and informed decision-making for this area of interest.
Fabrication of glass/madar fibers reinforced hybrid epoxy composite: a comprehensive study on the material stability
Authors: Raja Thandavamoorthy , Yuvarajan D. , Ali Saheb , Dhanraj G. , Kaliappan Nandagopal
Published: April 2024

The present study aims to examine the characteristics of a composite material composed of glass/madar fibers and porcelain particles, which are reinforced with epoxy. A compression molding technique achieves the fabrication of this composite. A comprehensive characterization was conducted by employing a mixture of analytical techniques, including X-ray Diffraction (XRD), mechanical testing, Scanning Electron Microscopy (SEM), Dynamic Mechanical Analysis (DMA), and Thermogravimetric Analysis (TGA). The composition of the composite was determined using X-ray diffraction (XRD) analysis, which demonstrated the successful integration of porcelain fillers. The material exhibited notable mechanical properties, rendering it appropriate for utilization in structural applications. The utilization of SEM facilitated the examination of the microstructure of the composite material, thereby providing a deeper understanding of the interactions between the fibers and the matrix. DMA results revealed the glass/madar composite contained 4.2% higher viscoelastic properties when the addition of porcelain filler, thermal stability was improved up to the maximum temperature of 357 °C. This study provided significant insights into the properties of a hybrid epoxy composite consisting of glass/madar fibers reinforced porcelain particles.
RETRACTED ARTICLE: Break oily water emulsion during petroleum enhancing production processes using green approach for the synthesis of SnCuO@FeO nanocomposite from microorganisms
Authors: Hosny M. , Mubarak Mahmoud F. , El-Sheshtawy H. S. , Hosny R.
Published: April 2024

The aim of this work was to synthesize a green nanoparticle SnCuO@FeO nanocomposite core–shell to break oily water emulsions during petroleum-enhancing production processes as an alternative to chemical and physical processes. In this study, eight bacterial isolates (MHB1–MHB8) have been isolated from tree leaves, giant reeds, and soil samples. The investigation involved testing bacterial isolates for their ability to make FeO nanoparticles and choosing the best producers. The selected isolate (MHB5) was identified by amplification and sequencing of the 16S rRNA gene as Bacillus paramycoides strain OQ878685. MHB5 produced the FeO nanoparticles with the smallest particle size (78.7 nm) using DLS. XRD, FTIR, and TEM were used to characterize the biosynthesized nanoparticles. The jar experiment used SnCuO@FeO with different ratios of Sn to CuO (1:1, 2:1, and 3:1) to study the effect of oil concentration, retention time, and temperature. The most effective performance was observed with a 1:1 ratio of Sn to CuO, achieving an 85% separation efficiency at a concentration of 5 mg/L, for a duration of 5 min, and at a temperature of 373 K. Analysis using kinetic models indicates that the adsorption process can be accurately described by both the pseudo-first-order and pseudo-second-order models. This suggests that the adsorption mechanism likely involves a combination of film diffusion and intraparticle diffusion. Regarding the adsorption isotherm, the Langmuir model provides a strong fit for the data, while the D-R model indicates that physical interactions primarily govern the adsorption mechanism. Thermodynamic analysis reveals a ∆H value of 18.62 kJ/mol, indicating an exothermic adsorption process. This suggests that the adsorption is a favorable process, as energy is released during the process. Finally, the synthesized green SnCuO@FeO nanocomposite has potential for use in advanced applications in the oil and gas industry to help the industry meet regulatory compliance, lower operation costs, reduce environmental impact, and enhance production efficiency.
Cervicocephalic kinaesthesia reveals novel subgroups of motor control impairments in patients with neck pain
Authors: Majcen Rosker Ziva , Rosker Jernej
Published: April 2024

Cervical-spine sensorimotor control is associated with chronicity and recurrence of neck pain (NP). Tests used to measure sensorimotor impairments lack consistency in studied parameters. Interpretation is often based on either a handful or numerous parameters, without considering their possible interrelation. Different aspects of motor-control could be studied with different parameters, but this has not yet been addressed. The aim of this study was to determine if different parameters of cervical position (JPE) and movement (Butterfly) sense tests represent distinct components of motor-control strategies in patients with chronic NP. Principal component analysis performed on 135 patients revealed three direction-specific (repositioning from flexion, extension or rotations) and one parameter-specific (variability of repositioning) component for JPE, two difficulty-specific (easy or medium and difficult trajectory) and one movement-specific (undershooting a target) component for Butterfly test. Here we report that these components could be related to central (neck repositioning and control of cervical movement) and peripheral sensorimotor adaptations (variability of repositioning) present in NP. New technologies allow extraction of greater number of parameters of which hand-picking could lead to information loss. This study adds towards better identification of diverse groups of parameters offering potentially clinically relevant information and improved functional diagnostics for patients with NP.
Numerical study of transient absorption saturation in single-layer graphene for optical nanoscopy applications
Authors: Kariman Behjat S. , Diaspro Alberto , Bianchini Paolo
Published: April 2024

Transient absorption, or pump–probe microscopy is an absorption-based technique that can explore samples ultrafast dynamic properties and provide fluorescence-free contrast mechanisms. When applied to graphene and its derivatives, this technique exploits the graphene transient response caused by the ultrafast interband transition as the imaging contrast mechanism. The saturation of this transition is fundamental to allow for super-resolution optical far-field imaging, following the reversible saturable optical fluorescence transitions (RESOLFT) concept, although not involving fluorescence. With this aim, we propose a model to numerically compute the temporal evolution under saturation conditions of the single-layer graphene molecular states, which are involved in the transient absorption. Exploiting an algorithm based on the fourth order Runge–Kutta (RK4) method, and the density matrix approach, we numerically demonstrate that the transient absorption signal of single-layer graphene varies linearly as a function of excitation intensity until it reaches saturation. We experimentally verify this model using a custom pump–probe super-resolution microscope. The results define the intensities necessary to achieve super-resolution in a pump–probe nanoscope while studying graphene-based materials and open the possibility of predicting such a saturation process in other light-matter interactions that undergo the same transition.
Genomic wide association study and selective sweep analysis identify genes associated with improved yield under drought in Turkish winter wheat germplasm
Authors: Sehgal Deepmala , Rathan Nagenahalli Dharmegowda , Özdemir Fatih , Keser Mesut , Akin Beyhan , Dababat Abdelfattah A. , Koc Emrah , Dreisigacker Susanne , Morgounov Alexey
Published: April 2024

A panel comprising of 84 Turkish winter wheat landraces (LR) and 73 modern varieties (MV) was analyzed with genome wide association study (GWAS) to identify genes/genomic regions associated with increased yield under favorable and drought conditions. In addition, selective sweep analysis was conducted to detect signatures of selection in the winter wheat genome driving the differentiation between LR and MV, to gather an understanding of genomic regions linked to adaptation and yield improvement. The panel was genotyped with 25 K wheat SNP array and phenotyped for agronomic traits for two growing seasons (2018 and 2019) in Konya, Turkey. Year 2018 was treated as drought environment due to very low precipitation prior to heading whereas year 2019 was considered as a favorable season. GWAS conducted with SNPs and haplotype blocks using mixed linear model identified 18 genomic regions in the vicinities of known genes i.e., TaERF3-3A, TaERF3-3B, DEP1-5A, FRIZZY PANICLE-2D, TaSnRK23-1A, TaAGL6-A, TaARF12-2A, TaARF12-2B, WAPO1, TaSPL16-7D, TaTGW6-A1, KAT-2B, TaOGT1, TaSPL21-6B, TaSBEIb, trs1/WFZP-A, TaCwi-A1-2A and TaPIN1-7A associated with grain yield (GY) and yield related traits. Haplotype-based GWAS identified five haplotype blocks (H1A-42, H2A-71, H4A-48, H7B-123 and H7B-124), with the favorable haplotypes showing a yield increase of > 700 kg/ha in the drought season. SNP-based GWAS, detected only one larger effect genomic region on chromosome 7B, in common with haplotype-based GWAS. On an average, the percentage variation (PV) explained by haplotypes was 8.0% higher than PV explained by SNPs for all the investigated traits. Selective sweep analysis detected 39 signatures of selection between LR and MV of which 15 were within proximity of known functional genes controlling flowering (PRR-A1, PPR-D1, TaHd1-6B), GY and GY components (TaSus2-2B, TaGS2-B1, AG1-1A/WAG1-1A, DUO-A1, DUO-B1, AG2-3A/WAG2-3A, TaLAX1, TaSnRK210-4A, FBP, TaLAX1, TaPIL1 and AP3-1-7A/WPA3-7A) and 10 regions underlying various transcription factors and regulatory genes. The study outcomes contribute to utilization of LR in breeding winter wheat.