bluuebunny/crossref_metadata_2025 huggingface dataset:
Ocean Heat Content Responses to Changing Anthropogenic Aerosol Forcing Strength: Regional and Multi‐Decadal Variability
Authors: Boland Emma J. D. , Dittus Andrea J. , Jones Daniel C. , Josey Simon A. , Sinha Bablu
Published: June 2023

The causes of decadal variations in global warming are poorly understood, however it is widely understood that variations in ocean heat content (OHC) are linked with variations in surface warming. To investigate the forced response of OHC to anthropogenic aerosols (AA), we use an ensemble of historical simulations, which were carried out using a range of anthropogenic aerosol forcing magnitudes in a CMIP6‐era global circulation model. We find that the centennial scale linear trends in historical OHC are significantly sensitive to AA forcing magnitude (−3.0 ± 0.1 × 105 (J m−3 century−1)/(W m−2), R2 = 0.99), but interannual to multi‐decadal variability in global OHC appear largely independent of AA forcing magnitude. Comparison with observations find consistencies in different depth ranges and at different time scales with all but the strongest aerosol forcing magnitude, at least partly due to limited observational accuracy. We find that OHC is sensitive to aerosol forcing magnitude across much of the tropics and sub‐tropics, and stronger negative forcing induces more ocean cooling. The polar regions and North Atlantic show the strongest heat content trends, and also show the strongest dependence on aerosol forcing magnitude. However, the OHC response to increasing aerosol forcing magnitude in the North Atlantic and Southern Ocean is either dominated by internal variability, or strongly state dependent, showing different behavior in different time periods. Our results suggest the response to aerosols in these regions is a complex combination of influences from ocean transport, atmospheric forcings, and sea ice.
Long‐Term Offshore Borehole Fluid‐Pressure Monitoring at the Northern Cascadia Subduction Zone and Inferences Regarding the State of Megathrust Locking
Authors: Davis Earl E. , Sun Tianhaozhe , Heesemann Martin , Becker Keir , Schlesinger Angela
Published: June 2023

The Cascadia subduction megathrust off the Pacific Northwest follows an “end member” seismogenic behavior, producing large (up to moment magnitude 9) but infrequent (every several hundred years) earthquakes and tsunamis. Crustal deformation associated with the ongoing plate convergence has been characterized by land‐based geodetic observations, but the state of locking across the full breadth of the seismogenic fault is poorly constrained. We report results of offshore monitoring of borehole fluid pressure, as a proxy for formation volumetric strain, at a site ∼20 km landward of the Cascadia subduction deformation front since 2010. The multi‐depth pressure records were plagued by hydrologic noise, but noise at the deepest monitoring level (303 m sub‐seafloor) abated in 2015. Subsequently, including at the times of regional large earthquakes that caused significant dynamic stressing, no persistent pressure transients are present above a threshold of 0.08 kPa imposed by unremovable oceanographic signals, corresponding to a strain detection limit of ∼16 nanostrain. Simple dislocation models using local megathrust geometry suggest a resolvable slip of <1 cm along a trench‐normal corridor beneath the borehole for a range of slip‐patch dimensions. A large slip patch can be well resolved even at considerable along‐strike distances from the borehole; for instance, ∼10 cm slip is detectable over a 200‐km strike range for a slip‐patch radius of ∼50 km. This high sensitivity for detecting slip, along with the lack of observed events, stands in stark contrast to observations at other subduction zones, and suggests that the Northern Cascadia megathrust is most likely fully locked.
Hybrid Simulation of Proton Cyclotron Waves Upstream of Mars Generated by Pickup Ion Beam Distribution
Authors: Cheng Kun , Liu Kaijun , Mousavi Ameneh , Cowee Misa , Liu Yuqi , Wang Yan , Wang Mengmeng , Zheng Xianming , Zhou Jingyi
Published: June 2023

Linear instability analysis as well as a corresponding two‐dimensional hybrid simulation are performed to examine the excitation of the proton cyclotron waves observed upstream of Mars. The waves are believed to be excited by the pickup ions produced from the ionization of the Martian hydrogen exosphere. And previous statistical analysis of wave observations suggested that the waves are mostly related to pickup ion beam velocity distributions. While earlier linear instability analysis of pickup ion beam distributions has mainly been focused on the parallel unstable modes, our analysis reveals that the maximum growth rate occurs at very oblique propagation. The corresponding hybrid simulation confirms the linear analysis results and further demonstrates that the pickup ions are scattered toward an isotropic shell velocity distribution by the waves excited. Interestingly, the waves at oblique propagation gradually damp out and the system is eventually dominated by waves of quasi‐parallel propagation.
Dissecting the causal association between social or physical inactivity and depression: a bidirectional two-sample Mendelian Randomization study
Authors: Zhao Guorui , Lu Zhe , Sun Yaoyao , Kang Zhewei , Feng Xiaoyang , Liao Yundan , Sun Junyuan , Zhang Yuyanan , Huang Yu , Yue Weihua
Published: June 2023

A growing body of research suggests that social or physical activity can affect the risk of Major depressive disorder (MDD). However, the bidirectional relationship between them remains to be clarified further, especially between inactivity and MDD. Here, we performed a two-sample Mendelian Randomization analysis using genetic variants associated with social/physical activities and MDD, and assessed the mediating effect of obesity-related measures and brain imaging phenotypes. The dataset on MDD, social activities, and physical activities included 500,199; 461,369; 460,376 individuals, respectively. Information regarding body mass index (BMI), body fat percentage (BFP), IDPs for 454,633; 461,460; 8,428 participants, respectively. We identified bidirectional causal relationships between sport clubs or gyms, strenuous sports, heavy do-it-youself, other exercises and MDD. We also observed that leisure/social inactivity (odds ratio [OR] = 1.64; P = 5.14 × 10−5) or physical inactivity (OR = 3.67; P = 1.99 × 10−5) caused an increased risk of MDD, which were partially mediated by BMI or BFP and masked by the weighted-mean orientation dispersion index of left acoustic radiation or volume of right caudate. Furthermore, we discovered that MDD increased the risk of leisure/social inactivity (OR = 1.03; P = 9.89 × 10−4) or physical inactivity (OR = 1.01; P = 7.96 × 10−4). In conclusions, we found that social/physical activities reduced the risk of MDD, while MDD in turn hindered social/physical activities. Inactivity may increase the risk of MDD, which was mediated or masked by brain imaging phenotypes. These results help to understand the manifestations of MDD and provide evidence and direction for the advancement of intervention and prevention.
The dental management of patients irradiated for head and neck cancer
Authors: Goh Elizabeth Z. , Beech Nicholas , Johnson Nigel R. , Batstone Martin
Published: June 2023

Patients undergoing radiotherapy for head and neck cancers are prone to a range of dental complications, including mucositis, trismus, xerostomia, radiation caries and osteoradionecrosis. Specific considerations include the preventive, restorative and rehabilitative management of such patients, and the prevention and treatment of complications. This article aims to highlight the current understanding and management of dental needs for patients who have had or will undergo radiotherapy.
Targeting pathogenic macrophages by the application of SHP-1 agonists reduces inflammation and alleviates pulmonary fibrosis
Authors: Hong Shiao-Ya , Lu Ya-Ting , Chen Shih-Yu , Hsu Chiung-Fang , Lu Yi-Chun , Wang Cheng-Yi , Huang Kun-Lun
Published: June 2023

Idiopathic pulmonary fibrosis is a progressive fibrotic disorder with no cure that is characterized by deterioration of lung function. Current FDA-approved drugs for IPF delay the decline in lung function, but neither reverse fibrosis nor significantly improve overall survival. SHP-1 deficiency results in hyperactive alveolar macrophages accumulating in the lung, which contribute to the induction of pulmonary fibrosis. Herein, we investigated whether employing a SHP-1 agonist ameliorates pulmonary fibrosis in a bleomycin-induced pulmonary fibrosis murine model. Histological examination and micro-computed tomography images showed that SHP-1 agonist treatment alleviates bleomycin-induced pulmonary fibrosis. Reduced alveolar hemorrhage, lung inflammation, and collagen deposition, as well as enhanced alveolar space, lung capacity, and improved overall survival were observed in mice administered the SHP-1 agonist. The percentage of macrophages collected from bronchoalveolar lavage fluid and circulating monocytes in bleomycin-instilled mice were also significantly reduced by SHP-1 agonist treatment, suggesting that the SHP-1 agonist may alleviate pulmonary fibrosis by targeting macrophages and reshaping the immunofibrotic niche. In human monocyte-derived macrophages, SHP-1 agonist treatment downregulated CSF1R expression and inactivated STAT3/NFκB signaling, culminating in inhibited macrophage survival and perturbed macrophage polarization. The expression of pro-fibrotic markers (e.g., MRC1, CD200R1, and FN1) by IL4/IL13-induced M2 macrophages that rely on CSF1R signaling for their fate-determination was restricted by SHP-1 agonist treatment. While M2-derived medium promoted the expression of fibroblast-to-myofibroblast transition markers (e.g., ACTA2 and COL3A1), the application of SHP-1 agonist reversed the transition in a dose-dependent manner. Our report indicates that pharmacological activation of SHP-1 ameliorates pulmonary fibrosis via suppression of CSF1R signaling in macrophages, reduction of pathogenic macrophages, and the inhibition of fibroblast-to-myofibroblast transition. Our study thus identifies SHP-1 as a druggable target for the treatment of IPF, and suggests that the SHP-1 agonist may be developed as an anti-pulmonary fibrosis medication that both suppresses inflammation and restrains fibroblast-to-myofibroblast transition.
Data fusion and multivariate analysis for food authenticity analysis
Authors: Hong Yunhe , Birse Nicholas , Quinn Brian , Li Yicong , Jia Wenyang , McCarron Philip , Wu Di , da Silva Gonçalo Rosas , Vanhaecke Lynn , van Ruth Saskia , Elliott Christopher T.
Published: June 2023

A mid-level data fusion coupled with multivariate analysis approach is applied to dual-platform mass spectrometry data sets using Rapid Evaporative Ionization Mass Spectrometry and Inductively Coupled Plasma Mass Spectrometry to determine the correct classification of salmon origin and production methods. Salmon (n = 522) from five different regions and two production methods are used in the study. The method achieves a cross-validation classification accuracy of 100% and all test samples (n = 17) have their origins correctly determined, which is not possible with single-platform methods. Eighteen robust lipid markers and nine elemental markers are found, which provide robust evidence of the provenance of the salmon. Thus, we demonstrate that our mid-level data fusion - multivariate analysis strategy greatly improves the ability to correctly identify the geographical origin and production method of salmon, and this innovative approach can be applied to many other food authenticity applications.
High-efficiency bio-inspired hybrid multi-generation photovoltaic leaf
Authors: Huang Gan , Xu Jingyuan , Markides Christos N.
Published: June 2023

Most solar energy incident (>70%) upon commercial photovoltaic panels is dissipated as heat, increasing their operating temperature, and leading to significant deterioration in electrical performance. The solar utilisation efficiency of commercial photovoltaic panels is typically below 25%. Here, we demonstrate a hybrid multi-generation photovoltaic leaf concept that employs a biomimetic transpiration structure made of eco-friendly, low-cost and widely-available materials for effective passive thermal management and multi-generation. We demonstrate experimentally that bio-inspired transpiration can remove ~590 W/m2 of heat from a photovoltaic cell, reducing the cell temperature by ~26 °C under an irradiance of 1000 W/m2, and resulting in a relatively 13.6% increase in electrical efficiency. Furthermore, the photovoltaic leaf is capable of synergistically utilising the recovered heat to co-generate additional thermal energy and freshwater simultaneously within the same component, significantly elevating the overall solar utilisation efficiency from 13.2% to over 74.5%, along with over 1.1 L/h/m2 of clean water.
SERCA2 phosphorylation at serine 663 is a key regulator of Ca2+ homeostasis in heart diseases
Authors: Gonnot Fabrice , Boulogne Laura , Brun Camille , Dia Maya , Gouriou Yves , Bidaux Gabriel , Chouabe Christophe , Crola Da Silva Claire , Ducreux Sylvie , Pillot Bruno , Kaczmarczyk Andrea , Leon Christelle , Chanon Stephanie , Perret Coralie , Sciandra Franck , Dargar Tanushri , Gache Vincent , Farhat Fadi , Sebbag Laurent , Bochaton Thomas , Thibault Helene , Ovize Michel , Paillard Melanie , Gomez Ludovic
Published: June 2023

Despite advances in cardioprotection, new therapeutic strategies capable of preventing ischemia-reperfusion injury of patients are still needed. Here, we discover that sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA2) phosphorylation at serine 663 is a clinical and pathophysiological event of cardiac function. Indeed, the phosphorylation level of SERCA2 at serine 663 is increased in ischemic hearts of patients and mouse. Analyses on different human cell lines indicate that preventing serine 663 phosphorylation significantly increases SERCA2 activity and protects against cell death, by counteracting cytosolic and mitochondrial Ca2+ overload. By identifying the phosphorylation level of SERCA2 at serine 663 as an essential regulator of SERCA2 activity, Ca2+ homeostasis and infarct size, these data contribute to a more comprehensive understanding of the excitation/contraction coupling of cardiomyocytes and establish the pathophysiological role and the therapeutic potential of SERCA2 modulation in acute myocardial infarction, based on the hotspot phosphorylation level of SERCA2 at serine 663 residue.
MG1 interacts with a protease inhibitor and confers resistance to rice root-knot nematode
Authors: Wang Xiaomin , Cheng Rui , Xu Daochao , Huang Renliang , Li Haoxing , Jin Liang , Wu Yufeng , Tang Jiuyou , Sun Changhui , Peng Deliang , Chu Chengcai , Guo Xiaoli
Published: June 2023

The rice root-knot nematode (Meloidogyne graminicola) is one of the most destructive pests threatening rice (Oryza sativa L.) production in Asia; however, no rice resistance genes have been cloned. Here, we demonstrate that M. GRAMINICOLA-RESISTANCE GENE 1 (MG1), an R gene highly expressed at the site of nematode invasion, determines resistance against the nematode in several rice varieties. Introgressing MG1 into susceptible varieties increases resistance comparable to resistant varieties, for which the leucine-rich repeat domain is critical for recognizing root-knot nematode invasion. We also report transcriptome and cytological changes that are correlated with a rapid and robust response during the incompatible interaction that occurs in resistant rice upon nematode invasion. Furthermore, we identified a putative protease inhibitor that directly interacts with MG1 during MG1-mediated resistance. Our findings provide insight into the molecular basis of nematode resistance as well as valuable resources for developing rice varieties with improved nematode resistance.
Origin of minicircular mitochondrial genomes in red algae
Authors: Lee Yongsung , Cho Chung Hyun , Noh Chanyoung , Yang Ji Hyun , Park Seung In , Lee Yu Min , West John A. , Bhattacharya Debashish , Jo Kyubong , Yoon Hwan Su
Published: June 2023

Eukaryotic organelle genomes are generally of conserved size and gene content within phylogenetic groups. However, significant variation in genome structure may occur. Here, we report that the Stylonematophyceae red algae contain multipartite circular mitochondrial genomes (i.e., minicircles) which encode one or two genes bounded by a specific cassette and a conserved constant region. These minicircles are visualized using fluorescence microscope and scanning electron microscope, proving the circularity. Mitochondrial gene sets are reduced in these highly divergent mitogenomes. Newly generated chromosome-level nuclear genome assembly of Rhodosorus marinus reveals that most mitochondrial ribosomal subunit genes are transferred to the nuclear genome. Hetero-concatemers that resulted from recombination between minicircles and unique gene inventory that is responsible for mitochondrial genome stability may explain how the transition from typical mitochondrial genome to minicircles occurs. Our results offer inspiration on minicircular organelle genome formation and highlight an extreme case of mitochondrial gene inventory reduction.
Single-electron charge transfer into putative Majorana and trivial modes in individual vortices
Authors: Ge Jian-Feng , Bastiaans Koen M. , Chatzopoulos Damianos , Cho Doohee , Tromp Willem O. , Benschop Tjerk , Niu Jiasen , Gu Genda , Allan Milan P.
Published: June 2023

Majorana bound states are putative collective excitations in solids that exhibit the self-conjugate property of Majorana fermions—they are their own antiparticles. In iron-based superconductors, zero-energy states in vortices have been reported as potential Majorana bound states, but the evidence remains controversial. Here, we use scanning tunneling noise spectroscopy to study the tunneling process into vortex bound states in the conventional superconductor NbSe2, and in the putative Majorana platform FeTe0.55Se0.45. We find that tunneling into vortex bound states in both cases exhibits charge transfer of a single electron charge. Our data for the zero-energy bound states in FeTe0.55Se0.45 exclude the possibility of Yu–Shiba–Rusinov states and are consistent with both Majorana bound states and trivial vortex bound states. Our results open an avenue for investigating the exotic states in vortex cores and for future Majorana devices, although further theoretical investigations involving charge dynamics and superconducting tips are necessary.
Tumour mutations in long noncoding RNAs enhance cell fitness
Authors: Esposito Roberta , Lanzós Andrés , Uroda Tina , Ramnarayanan Sunandini , Büchi Isabel , Polidori Taisia , Guillen-Ramirez Hugo , Mihaljevic Ante , Merlin Bernard Mefi , Mela Lia , Zoni Eugenio , Hovhannisyan Lusine , McCluggage Finn , Medo Matúš , Basile Giulia , Meise Dominik F. , Zwyssig Sandra , Wenger Corina , Schwarz Kyriakos , Vancura Adrienne , Bosch-Guiteras Núria , Andrades Álvaro , Tham Ai Ming , Roemmele Michaela , Medina Pedro P. , Ochsenbein Adrian F. , Riether Carsten , Kruithof-de Julio Marianna , Zimmer Yitzhak , Medová Michaela , Stroka Deborah , Fox Archa , Johnson Rory
Published: June 2023

Long noncoding RNAs (lncRNAs) are linked to cancer via pathogenic changes in their expression levels. Yet, it remains unclear whether lncRNAs can also impact tumour cell fitness via function-altering somatic “driver” mutations. To search for such driver-lncRNAs, we here perform a genome-wide analysis of fitness-altering single nucleotide variants (SNVs) across a cohort of 2583 primary and 3527 metastatic tumours. The resulting 54 mutated and positively-selected lncRNAs are significantly enriched for previously-reported cancer genes and a range of clinical and genomic features. A number of these lncRNAs promote tumour cell proliferation when overexpressed in in vitro models. Our results also highlight a dense SNV hotspot in the widely-studied NEAT1 oncogene. To directly evaluate the functional significance of NEAT1 SNVs, we use in cellulo mutagenesis to introduce tumour-like mutations in the gene and observe a significant and reproducible increase in cell fitness, both in vitro and in a mouse model. Mechanistic studies reveal that SNVs remodel the NEAT1 ribonucleoprotein and boost subnuclear paraspeckles. In summary, this work demonstrates the utility of driver analysis for mapping cancer-promoting lncRNAs, and provides experimental evidence that somatic mutations can act through lncRNAs to enhance pathological cancer cell fitness.
A multicentre study on grey matter morphometric biomarkers for classifying early schizophrenia and parkinson’s disease psychosis
Authors: Knolle Franziska , Arumugham Shyam S. , Barker Roger A. , Chee Michael W. L. , Justicia Azucena , Kamble Nitish , Lee Jimmy , Liu Siwei , Lenka Abhishek , Lewis Simon J. G. , Murray Graham K. , Pal Pramod Kumar , Saini Jitender , Szeto Jennifer , Yadav Ravi , Zhou Juan H. , Koch Kathrin
Published: June 2023

Psychotic symptoms occur in a majority of schizophrenia patients and in ~50% of all Parkinson’s disease (PD) patients. Altered grey matter (GM) structure within several brain areas and networks may contribute to their pathogenesis. Little is known, however, about transdiagnostic similarities when psychotic symptoms occur in different disorders, such as in schizophrenia and PD. The present study investigated a large, multicenter sample containing 722 participants: 146 patients with first episode psychosis, FEP; 106 individuals in at-risk mental state for developing psychosis, ARMS; 145 healthy controls matching FEP and ARMS, Con-Psy; 92 PD patients with psychotic symptoms, PDP; 145 PD patients without psychotic symptoms, PDN; 88 healthy controls matching PDN and PDP, Con-PD. We applied source-based morphometry in association with receiver operating curves (ROC) analyses to identify common GM structural covariance networks (SCN) and investigated their accuracy in identifying the different patient groups. We assessed group-specific homogeneity and variability across the different networks and potential associations with clinical symptoms. SCN-extracted GM values differed significantly between FEP and Con-Psy, PDP and Con-PD, PDN and Con-PD, as well as PDN and PDP, indicating significant overall grey matter reductions in PD and early schizophrenia. ROC analyses showed that SCN-based classification algorithms allow good classification (AUC ~0.80) of FEP and Con-Psy, and fair performance (AUC ~0.72) when differentiating PDP from Con-PD. Importantly, the best performance was found in partly the same networks, including the thalamus. Alterations within selected SCNs may be related to the presence of psychotic symptoms in both early schizophrenia and PD psychosis, indicating some commonality of underlying mechanisms. Furthermore, results provide evidence that GM volume within specific SCNs may serve as a biomarker for identifying FEP and PDP.
Nonlinear nanomechanical resonators approaching the quantum ground state
Authors: Samanta C. , De Bonis S. L. , Møller C. B. , Tormo-Queralt R. , Yang W. , Urgell C. , Stamenic B. , Thibeault B. , Jin Y. , Czaplewski D. A. , Pistolesi F. , Bachtold A.
Published: June 2023

It is an open question whether mechanical resonators can be made nonlinear with vibrations approaching the quantum ground state. This requires the engineering of a mechanical nonlinearity far beyond what has been realized so far. Here we discover a mechanism to boost the Duffing nonlinearity by coupling the vibrations of a nanotube resonator to single-electron tunnelling and by operating the system in the ultrastrong-coupling regime. We find that thermal vibrations become highly nonlinear when lowering the temperature. The average vibration amplitude at the lowest temperature is 13 times the zero-point motion, with approximately 42% of the thermal energy stored in the anharmonic part of the potential. Our work may enable the realization of mechanical Schrödinger cat states, mechanical qubits and quantum simulators emulating the electron–phonon coupling.
Hardwiring tissue-specific AAV transduction in mice through engineered receptor expression
Authors: Zengel James , Wang Yu Xin , Seo Jai Woong , Ning Ke , Hamilton James N. , Wu Bo , Raie Marina , Holbrook Colin , Su Shiqi , Clements Derek R. , Pillay Sirika , Puschnik Andreas S. , Winslow Monte M. , Idoyaga Juliana , Nagamine Claude M. , Sun Yang , Mahajan Vinit B. , Ferrara Katherine W. , Blau Helen M. , Carette Jan E.
Published: June 2023

The development of transgenic mouse models that express genes of interest in specific cell types has transformed our understanding of basic biology and disease. However, generating these models is time- and resource-intensive. Here we describe a model system, SELective Expression and Controlled Transduction In Vivo (SELECTIV), that enables efficient and specific expression of transgenes by coupling adeno-associated virus (AAV) vectors with Cre-inducible overexpression of the multi-serotype AAV receptor, AAVR. We demonstrate that transgenic AAVR overexpression greatly increases the efficiency of transduction of many diverse cell types, including muscle stem cells, which are normally refractory to AAV transduction. Superior specificity is achieved by combining Cre-mediated AAVR overexpression with whole-body knockout of endogenous Aavr, which is demonstrated in heart cardiomyocytes, liver hepatocytes and cholinergic neurons. The enhanced efficacy and exquisite specificity of SELECTIV has broad utility in development of new mouse model systems and expands the use of AAV for gene delivery in vivo.
RNA polymerase II depletion from the inactive X chromosome territory is not mediated by physical compartmentalization
Authors: Collombet Samuel , Rall Isabell , Dugast-Darzacq Claire , Heckert Alec , Halavatyi Aliaksandr , Le Saux Agnes , Dailey Gina , Darzacq Xavier , Heard Edith
Published: June 2023

Subnuclear compartmentalization has been proposed to play an important role in gene regulation by segregating active and inactive parts of the genome in distinct physical and biochemical environments. During X chromosome inactivation (XCI), the noncoding Xist RNA coats the X chromosome, triggers gene silencing and forms a dense body of heterochromatin from which the transcription machinery appears to be excluded. Phase separation has been proposed to be involved in XCI, and might explain the exclusion of the transcription machinery by preventing its diffusion into the Xist-coated territory. Here, using quantitative fluorescence microscopy and single-particle tracking, we show that RNA polymerase II (RNAPII) freely accesses the Xist territory during the initiation of XCI. Instead, the apparent depletion of RNAPII is due to the loss of its chromatin stably bound fraction. These findings indicate that initial exclusion of RNAPII from the inactive X reflects the absence of actively transcribing RNAPII, rather than a consequence of putative physical compartmentalization of the inactive X heterochromatin domain.
A Bos taurus sequencing methods benchmark for assembly, haplotyping, and variant calling
Authors: Eché Camille , Iampietro Carole , Birbes Clément , Dréau Andreea , Kuchly Claire , Di Franco Arnaud , Klopp Christophe , Faraut Thomas , Djebali Sarah , Castinel Adrien , Zytnicki Matthias , Denis Erwan , Boussaha Mekki , Grohs Cécile , Boichard Didier , Gaspin Christine , Milan Denis , Donnadieu Cécile
Published: June 2023

Inspired by the production of reference data sets in the Genome in a Bottle project, we sequenced one Charolais heifer with different technologies: Illumina paired-end, Oxford Nanopore, Pacific Biosciences (HiFi and CLR), 10X Genomics linked-reads, and Hi-C. In order to generate haplotypic assemblies, we also sequenced both parents with short reads. From these data, we built two haplotyped trio high quality reference genomes and a consensus assembly, using up-to-date software packages. The assemblies obtained using PacBio HiFi reaches a size of 3.2 Gb, which is significantly larger than the 2.7 Gb ARS-UCD1.2 reference. The BUSCO score of the consensus assembly reaches a completeness of 95.8%, among highly conserved mammal genes. We also identified 35,866 structural variants larger than 50 base pairs. This assembly is a contribution to the bovine pangenome for the “Charolais” breed. These datasets will prove to be useful resources enabling the community to gain additional insight on sequencing technologies for applications such as SNP, indel or structural variant calling, and de novo assembly.
MER and increased operative time are not risk factors for the formation of pneumocephalus during DBS
Authors: Iess Guglielmo , Bonomo Giulio , Levi Vincenzo , Aquino Domenico , Zekaj Edvin , Mezza Federica , Servello Domenico
Published: June 2023

Although only recently directional leads have proven their potential to compensate for sub-optimally placed electrodes, optimal lead positioning remains the most critical factor in determining Deep Brain Stimulation (DBS) outcome. Pneumocephalus is a recognized source of error, but the factors that contribute to its formation are still a matter of debate. Among these, operative time is one of the most controversial. Because cases of DBS performed with Microelectrode Recordings (MER) are affected by an increase in surgical length, it is useful to analyze whether MER places patients at risk for increased intracranial air entry. Data of 94 patients from two different institutes who underwent DBS for different neurologic and psychiatric conditions were analyzed for the presence of postoperative pneumocephalus. Operative time and use of MER, as well as other potential risk factors for pneumocephalus (age, awake vs. asleep surgery, number of MER passages, burr hole size, target and unilateral vs. bilateral implants) were examined. Mann-Whitney U and Kruskal-Wallis tests were utilized to compare intracranial air distributions across groups of categorical variables. Partial correlations were used to assess the association between time and volume. A generalized linear model was created to predict the effects of time and MER on the volume of intracranial air, controlling for other potential risk factors identified: age, number of MER passages, awake vs. asleep surgery, burr hole size, target, unilateral vs. bilateral surgery. Significantly different distributions of air volume were noted between different targets, unilateral vs. bilateral implants, and number of MER trajectories. Patients undergoing DBS with MER did not present a significant increase in pneumocephalus compared to patients operated without (p = 0.067). No significant correlation was found between pneumocephalus and time. Using multivariate analysis, unilateral implants exhibited lower volumes of pneumocephalus (p = 0.002). Two specific targets exhibited significantly different volumes of pneumocephalus: the bed nucleus of the stria terminalis with lower volumes (p < 0.001) and the posterior hypothalamus with higher volumes (p = 0.011). MER, time, and other parameters analyzed failed to reach statistical significance. Operative time and use of intraoperative MER are not significant predictors of pneumocephalus during DBS. Air entry is greater for bilateral surgeries and may be also influenced by the specific stimulated target.
Impact of the COVID-19 pandemic on liver transplant waitlist outcome in France
Authors: Legeai Camille , Antoine Corinne , Jasseron Carine , Kerbaul François , Dumortier Jérôme
Published: June 2023

The objective of this study was to investigate the impact of the COVID-19 pandemic on the outcome of patients on the liver transplantation (LT) waitlist in 2020 in France, in particular, the incidence of deaths and delisting for worsening condition, depending on the allocation score component. The 2020 cohort of patients on the waiting list was compared with the 2018/2019 cohorts. 2020 saw fewer LTs than in either 2019 or 2018 (1128, 1356, and 1325, respectively), together with fewer actual brain dead donors (1355, 1729, and 1743). In 2020, deaths or delisting for worsening condition increased significantly versus 2018/2019 (subdistribution hazard ratio 1.4, 95% confidence interval [CI] 1.2–1.7), after adjustment for age, place of care, diabetes, blood type, and score component, although COVID-19-related mortality was low. This increased risk mainly concerned patients with hepatocellular carcinoma (1.52, 95% CI 1.22–1.90), with 650 MELD exception points (2.19, 95% CI 1.08–4.43), and especially those without HCC and MELD scores from 25 to 30 (3.36 [95% CI 1.82–6.18]). In conclusion, by significantly decreasing LT activity in 2020, the COVID-19 pandemic increased the number of waitlist deaths and delisting for worsening condition, and significantly more for particular components of the score, including intermediate severity cirrhosis.
Tailoring recommendation algorithms to ideal preferences makes users better off
Authors: Khambatta Poruz , Mariadassou Shwetha , Morris Joshua , Wheeler S. Christian
Published: June 2023

People often struggle to do what they ideally want because of a conflict between their actual and ideal preferences. ​​​By focusing on maximizing engagement, recommendation algorithms appear to be exacerbating this struggle. However, this need not be the case. Here we show that tailoring recommendation algorithms to ideal (vs. actual) preferences would provide meaningful benefits to both users and companies. To examine this, we built algorithmic recommendation systems that generated real-time, personalized recommendations tailored to either a person’s actual or ideal preferences. Then, in a high-powered, pre-registered experiment (n = 6488), we measured the effects of these recommendation algorithms. We found that targeting ideal rather than actual preferences resulted in somewhat fewer clicks, but it also increased the extent to which people felt better off and that their time was well spent. Moreover, of note to companies, targeting ideal preferences increased users' willingness to pay for the service, the extent to which they felt the company had their best interest at heart, and their likelihood of using the service again. Our results suggest that users and companies would be better off if recommendation algorithms learned what each person was striving for and nudged individuals toward their own unique ideals.
Assessing the cytotoxicity of aerosolized carbon black and benzo[a]pyrene with controlled physical and chemical properties on human lung epithelial cells
Authors: Ryu Youngri , Roh Soonjong , Joung Young Soo
Published: June 2023

Atmospheric particulate matter (PM) is a complex mixture of hazardous particles containing hundreds of inorganic and organic species. Organic components, such as carbon black (CB) and benzo[a]pyrene (BaP), are known to exhibit diverse genotoxic and carcinogenic effects. The toxicity of CB and polycyclic aromatic hydrocarbons has been well studied, however the combined toxicity is much less understood. A spray-drying system was used to control the size and chemical composition of PMs. PMs were prepared by loading BaP on three different sized CBs (0.1 μm, 2.5 μm, and 10 μm) to obtain BaP-unloaded CB (CB0.1, CB2.5, and CB10) and BaP-loaded CB (CB0.1–BaP, CB2.5–BaP, and CB10–BaP). We analyzed cell viability, levels of oxidative stress, and pro-inflammatory cytokines using human lung cells (A549 epithelial cells). Cell viability decreased when exposed to all PMs (PM0.1, PM2.5, and PM10), regardless of the presence of BaP. The increase in PM size due to BaP-adsorption to CB resulted in insufficient toxic effects on human lung cells compared to CB alone. Smaller CBs reduced cell viability, leading to reactive oxygen species formation, which can cause damage to cellular structures deliver more harmful substances. Additionally, small CBs were predominant in inducing the expression of pro-inflammatory cytokines in A549 epithelial cells. These results indicate that the size of CB is a key factor that immediately affects the inflammation of lung cells, compared to the presence of BaP.
Biomechanical performance of a novel light-curable bone fixation technique
Authors: Schwarzenberg Peter , Colding-Rasmussen Thomas , Hutchinson Daniel J. , Mischler Dominic , Horstmann Peter , Petersen Michael Mørk , Jacobsen Stine , Pastor Tatjana , Malkoch Michael , Wong Christian , Varga Peter
Published: June 2023

Traumatic bone fractures are often debilitating injuries that may require surgical fixation to ensure sufficient healing. Currently, the most frequently used osteosynthesis materials are metal-based; however, in certain cases, such as complex comminuted osteoporotic fractures, they may not provide the best solution due to their rigid and non-customizable nature. In phalanx fractures in particular, metal plates have been shown to induce joint stiffness and soft tissue adhesions. A new osteosynthesis method using a light curable polymer composite has been developed. This method has demonstrated itself to be a versatile solution that can be shaped by surgeons in situ and has been shown to induce no soft tissue adhesions. In this study, the biomechanical performance of AdhFix was compared to conventional metal plates. The osteosyntheses were tested in seven different groups with varying loading modality (bending and torsion), osteotomy gap size, and fixation type and size in a sheep phalanx model. AdhFix demonstrated statistically higher stiffnesses in torsion (64.64 ± 9.27 and 114.08 ± 20.98 Nmm/° vs. 33.88 ± 3.10 Nmm/°) and in reduced fractures in bending (13.70 ± 2.75 Nm/mm vs. 8.69 ± 1.16 Nmm/°), while the metal plates were stiffer in unreduced fractures (7.44 ± 1.75 Nm/mm vs. 2.70 ± 0.72 Nmm/°). The metal plates withstood equivalent or significantly higher torques in torsion (534.28 ± 25.74 Nmm vs. 614.10 ± 118.44 and 414.82 ± 70.98 Nmm) and significantly higher bending moments (19.51 ± 2.24 and 22.72 ± 2.68 Nm vs. 5.38 ± 0.73 and 1.22 ± 0.30 Nm). This study illustrated that the AdhFix platform is a viable, customizable solution that is comparable to the mechanical properties of traditional metal plates within the range of physiological loading values reported in literature.
Tumor-educated platelet blood tests for Non-Small Cell Lung Cancer detection and management
Authors: Antunes-Ferreira Mafalda , D’Ambrosi Silvia , Arkani Mohammad , Post Edward , In ‘t Veld Sjors G. J. G. , Ramaker Jip , Zwaan Kenn , Kucukguzel Ece Demirel , Wedekind Laurine E. , Griffioen Arjan W. , Oude Egbrink Mirjam , Kuijpers Marijke J. E. , van den Broek Daan , Noske David P. , Hartemink Koen J. , Sabrkhany Siamack , Bahce Idris , Sol Nik , Bogaard Harm-Jan , Koppers-Lalic Danijela , Best Myron G. , Wurdinger Thomas
Published: June 2023

Liquid biopsy approaches offer a promising technology for early and minimally invasive cancer detection. Tumor-educated platelets (TEPs) have emerged as a promising liquid biopsy biosource for the detection of various cancer types. In this study, we processed and analyzed the TEPs collected from 466 Non-small Cell Lung Carcinoma (NSCLC) patients and 410 asymptomatic individuals (controls) using the previously established thromboSeq protocol. We developed a novel particle-swarm optimization machine learning algorithm which enabled the selection of an 881 RNA biomarker panel (AUC 0.88). Herein we propose and validate in an independent cohort of samples (n = 558) two approaches for blood samples testing: one with high sensitivity (95% NSCLC detected) and another with high specificity (94% controls detected). Our data explain how TEP-derived spliced RNAs may serve as a biomarker for minimally-invasive clinical blood tests, complement existing imaging tests, and assist the detection and management of lung cancer patients.
Study on the driving mechanism of lagged effects based on different time scales in a karst drainage basin in South China
Authors: He Zhonghua , Pan Shan , Gu Xiaolin , Xu Mingjin , Wang Maoqiang
Published: June 2023

Compared to earthquakes and volcanoes, drought is one of the most damaging natural disasters and is mainly affected by rainfall losses, especially by the runoff regulation ability of the underlying watershed surface. Based on monthly rainfall runoff data recorded from 1980 to 2020, in this study, the distributed lag regression model is used to simulate the rainfall-runoff process in the karst distribution region of South China, and a time series of watershed lagged-flow volumes is calculated. The watershed lagged effect is analyzed by four distribution models, and the joint probability between the lagged intensity and frequency is simulated by the copula function family. The results show that (1) the watershed lagged effects simulated by the normal, log-normal, P-III and log-logistic distribution models in the karst drainage basin are particularly significant, with small mean square errors (MSEs) and significant time-scale characteristics. (2) Affected by spatiotemporal distribution differences in rainfall and the impacts of different basin media and structures, the lag response of runoff to rainfall differs significantly among different time scales. Especially at the 1-, 3- and 12-month scales, the coefficient of variation (Cv) of the watershed lagged intensity is greater than 1, while it is less than 1 at the 6- and 9-month scales. (3) The lagged frequencies simulated by the log-normal, P-III and log-logistic distribution models are relatively high (with medium, medium–high and high frequencies, respectively), while that simulated by the normal distribution is relatively low (medium–low and low frequencies). (4) There is a significant negative correlation (R < − 0.8, Sig. < 0.01) between the watershed lagged intensity and frequency. For the joint probability simulation, the fitting effect of the gumbel Copula is the best, followed by the Clayton and Frank-1 copulas, and while that of the Frank-2 copula is relatively weak. Consequently, the propagation mechanism from meteorological drought to agricultural or hydrological drought and the conversion mechanism between agricultural and hydrological drought are effectively revealed in this study, thereby providing a scientific basis for the rational utilization of water resources and drought resistance and disaster relief in karst areas.
Impact of the South Atlantic Anomaly on radiation exposure at flight altitudes during solar minimum
Authors: Meier Matthias M. , Berger Thomas , Jahn Thomas , Matthiä Daniel , Plettenberg Mona C. , Scheibinger Markus , Schennetten Kai , Wirtz Michael
Published: June 2023

The South Atlantic Anomaly (SAA) is a geographical region over the South Atlantic Ocean where the inner Van Allen radiation belt extends down particularly close to Earth. This leads to highly increased levels of ionizing radiation and related impacts on spacecraft in Low Earth Orbits, e.g., correspondingly increased radiation exposure of astronauts and electronic components on the International Space Station. According to an urban legend, the SAA is also supposed to affect the radiation field in the atmosphere even down to the altitudes of civil aviation. In order to identify and quantify any additional contributions to the omnipresent radiation exposure due to the Galactic Cosmic Radiation at flight altitudes, comprehensive measurements were performed crossing the geographical region of the SAA at an altitude of 13 km in a unique flight mission—Atlantic Kiss. No indication of increased radiation exposure was found.
Foot morphology as a predictor of hallux valgus development in children
Authors: Martín-Casado Laura , Aldana-Caballero Alberto , Barquín Christian , Criado-Álvarez Juan José , Polonio-López Begoña , Marcos-Tejedor Félix
Published: June 2023

An excess of body weight can produce morphological changes in the feet of children. The aim of this study was to assess the morphological differences of the foot in children based on their body mass index and to determine the risk factors for the development of a hallux valgus in childhood and adolescence. One Thousand Six Hundred Seventy-Eight children (5–17 years) were classified as group with obesity, overweight, and normal weight. Lengths, widths, heights and angles of both feet was measured with a 3D scanner. The risk of developing hallux valgus was calculated. Group with overweight and obesity presented longer feet (p = 0.00), wider metatarsals (p = 0.00) and wider heels (p = 0.00). Arch height was lower (p > 0.01) in the group with obesity, and the hallux angle was greater in the group with normal weight (p < 0.05). The relative risk of a lateral hallux deviation increases with age, foot length and heel width (Exp (B) > 1). Children with overweight and obesity had longer and wider feet. The arch height was higher in children with overweight, and lower in children with obesity. Age, foot length, and heel width could be risk factors for the development of hallux valgus, while metatarsal width and arch height could be protective factors. Monitorization of the development and characterization of the foot in childhood as a clinical tool could help professionals to early identify the patients presenting risk factors and prevent future deformities and other biomechanical conditions in adulthood by implementing protecting measures.
Temperature contributes to host specialization of coffee wilt disease (Fusarium xylarioides) on arabica and robusta coffee crops
Authors: Zhang Xiuhan , Peck Lily D. , Flood Julie , Ryan Matthew J. , Barraclough Timothy G.
Published: June 2023

Coffee wilt disease, caused by the fungusFusarium xylarioides, is a vascular wilt disease that has affected coffee production in sub-Saharan Africa over the past century. Today, the disease has two host-specific populations specialising on arabica and robusta coffee crops, which grow at high and low altitude, respectively. Here we test whether adaptation to different temperatures contributes to specialisation of the fungi on each crop. Firstly, climate models show that the severity of the arabica and robusta populations of coffee wilt disease correlates with temperature. The robusta population shows higher peak severity than the arabica population overall, but the latter has greater cold tolerance. Secondly, growth assays of thermal performance of fungal strains in vitro show that, while robusta strains grow faster than arabicas at intermediate temperatures, the arabica strains have higher sporulation and spore germination rates at temperatures below 15ºC. The match between environmental patterns of severity in nature with thermal performance of fungal cultures in the laboratory supports a role for temperature adaptation in specialisation on arabica and robusta coffee. Extrapolating our temperature-models to future climate change predicts that disease severity could decline on average due to increased temperature but could increase in some coffee-growing regions.