bluuebunny/crossref_metadata_2025 huggingface dataset:
Piplartine eliminates CD34 + AML stem/progenitor cells by inducing oxidative stress and suppressing NF-κB signalling
Authors: Rodrigues Ana Carolina B. da C. , Silva Suellen L. R. , Dias Ingrid R. S. B. , Costa Rafaela G. A. , Oliveira Maiara de S. , Soares Milena B. P. , Dias Rosane B. , Valverde Ludmila F. , Rocha Clarissa A. G. , Johnson Emily M. , Pina Cristina , Bezerra Daniel P.
Published: March 2024

Acute myeloid leukaemia (AML) is a haematological malignancy characterised by the accumulation of transformed myeloid progenitors in the bone marrow. Piplartine (PL), also known as piperlongumine, is a pro-oxidant small molecule extracted from peppers that has demonstrated antineoplastic potential in solid tumours and other haematological malignancies. In this work, we explored the potential of PL to treat AML through the use of a combination of cellular and molecular analyses of primary and cultured leukaemia cells in vitro and in vivo. We showed that PL exhibits in vitro cytotoxicity against AML cells, including CD34+ leukaemia-propagating cells, but not healthy haematopoietic progenitors, suggesting anti-leukaemia selectivity. Mechanistically, PL treatment increased reactive oxygen species (ROS) levels and induced ROS-mediated apoptosis in AML cells, which could be prevented by treatment with the antioxidant scavenger N-acetyl-cysteine and the pancaspase inhibitor Z-VAD(OMe)-FMK. PL treatment reduced NFKB1 gene transcription and the level of NF-κB p65 (pS536), which was depleted from the nucleus of AML cells, indicating suppression of NF-κB p65 signalling. Significantly, PL suppressed AML development in a mouse xenograft model, and its combination with current AML treatments (cytarabine, daunorubicin and azacytidine) had synergistic effects, indicating translational therapeutic potential. Taken together, these data position PL as a novel anti-AML candidate drug that can target leukaemia stem/progenitors and is amenable to combinatorial therapeutic strategies.
Structure of prolylrapamycin: confirmation through a revised and detailed NMR assignment study
Authors: Mortoni Annalisa , Castelli Eugenio , Recca Teresa , Quadrelli Paolo
Published: March 2024

A complete and detailed characterization of Rapamycin (1) and Prolylrapamycin (2) has been conducted by homo- and hetero-nuclear NMR experiments in DMSO-d6 along with HRMS and FT-IR spectra and DSCs analyses. The NMR experiments allowed the assignment of every single proton and carbon atom belonging to the two structures and the definitive confirm of the presence of a pyrrolidine ring in Prolylrapamycin (2) in place of the piperidine ring that characterizes the structure of Sirolimus.
Single cell atlas of Xenoturbella bocki highlights limited cell-type complexity
Authors: Robertson Helen E. , Sebé-Pedrós Arnau , Saudemont Baptiste , Loe-Mie Yann , Zakrzewski Anne-C. , Grau-Bové Xavier , Mailhe Marie-Pierre , Schiffer Philipp , Telford Maximilian J. , Marlow Heather
Published: March 2024

Phylogenetic analyses over the last two decades have united a few small, and previously orphan clades, the nematodermatids, acoels and xenoturbelids, into the phylum Xenacoelomorpha. Some phylogenetic analyses support a sister relationship between Xenacoelomorpha and Ambulacraria (Xenambulacraria), while others suggest that Xenacoelomorpha may be sister to the rest of the Bilateria (Nephrozoa). An understanding of the cell type complements of Xenacoelomorphs is essential to assessing these alternatives as well as to our broader understanding of bilaterian cell type evolution. Employing whole organism single-cell RNA-seq in the marine xenacoelomorph worm Xenoturbella bocki, we show that Xenambulacrarian nerve nets share regulatory features and a peptidergic identity with those found in cnidarians and protostomes and more broadly share muscle and gland cell similarities with other metazoans. Taken together, these data are consistent with broad homologies of animal gland, muscle, and neurons as well as more specific affinities between Xenoturbella and acoel gut and epidermal tissues, consistent with the monophyly of Xenacoelomorpha.
SCGB1D2 inhibits growth of Borrelia burgdorferi and affects susceptibility to Lyme disease
Authors: Strausz Satu , Abner Erik , Blacker Grace , Galloway Sarah , Hansen Paige , Feng Qingying , Lee Brandon T. , Jones Samuel E. , Haapaniemi Hele , Raak Sten , Nahass George Ronald , Sanders Erin ,   FinnGen,   Estonian Genome Centre,   Estonian Biobank Research Team, Soodla Pilleriin , Võsa Urmo , Esko Tõnu , Sinnott-Armstrong Nasa , Weissman Irving L. , Daly Mark , Aivelo Tuomas , Tal Michal Caspi , Ollila Hanna M.
Published: March 2024

Lyme disease is a tick-borne disease caused by bacteria of the genus Borrelia. The host factors that modulate susceptibility for Lyme disease have remained mostly unknown. Using epidemiological and genetic data from FinnGen and Estonian Biobank, we identify two previously known variants and an unknown common missense variant at the gene encoding for Secretoglobin family 1D member 2 (SCGB1D2) protein that increases the susceptibility for Lyme disease. Using live Borrelia burgdorferi (Bb) we find that recombinant reference SCGB1D2 protein inhibits the growth of Bb in vitro more efficiently than the recombinant protein with SCGB1D2 P53L deleterious missense variant. Finally, using an in vivo murine infection model we show that recombinant SCGB1D2 prevents infection by Borrelia in vivo. Together, these data suggest that SCGB1D2 is a host defense factor present in the skin, sweat, and other secretions which protects against Bb infection and opens an exciting therapeutic avenue for Lyme disease.
Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates new blood pressure and hypertension targets
Authors: Xu Xiaoguang , Khunsriraksakul Chachrit , Eales James M. , Rubin Sebastien , Scannali David , Saluja Sushant , Talavera David , Markus Havell , Wang Lida , Drzal Maciej , Maan Akhlaq , Lay Abigail C. , Prestes Priscilla R. , Regan Jeniece , Diwadkar Avantika R. , Denniff Matthew , Rempega Grzegorz , Ryszawy Jakub , Król Robert , Dormer John P. , Szulinska Monika , Walczak Marta , Antczak Andrzej , Matías-García Pamela R. , Waldenberger Melanie , Woolf Adrian S. , Keavney Bernard , Zukowska-Szczechowska Ewa , Wystrychowski Wojciech , Zywiec Joanna , Bogdanski Pawel , Danser A. H. Jan , Samani Nilesh J. , Guzik Tomasz J. , Morris Andrew P. , Liu Dajiang J. , Charchar Fadi J. ,   Human Kidney Tissue Resource Study Group, Tomaszewski Maciej
Published: March 2024

Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation. Imputation of kidney proteome and microRNAome uncovered 97 renal proteins and 11 miRNAs associated with BP. Integration with plasma proteomics and metabolomics illuminated circulating levels of myo-inositol, 4-guanidinobutanoate and angiotensinogen as downstream effectors of several kidney BP genes (SLC5A11,AGMAT,AGT, respectively). We showed that genetically determined reduction in renal expression may mimic the effects of rare loss-of-function variants on kidney mRNA/protein and lead to an increase in BP (e.g.,ENPEP). We demonstrated a strong correlation (r = 0.81) in expression of protein-coding genes between cells harvested from urine and the kidney highlighting a diagnostic potential of urinary cell transcriptomics. We uncovered adenylyl cyclase activators as a repurposing opportunity for hypertension and illustrated examples of BP-elevating effects of anticancer drugs (e.g. tubulin polymerisation inhibitors). Collectively, our studies provide new biological insights into genetic regulation of BP with potential to drive clinical translation in hypertension.
Genetic gains underpinning a little-known strawberry Green Revolution
Authors: Feldmann Mitchell J. , Pincot Dominique D. A. , Cole Glenn S. , Knapp Steven J.
Published: March 2024

The annual production of strawberry has increased by one million tonnes in the US and 8.4 million tonnes worldwide since 1960. Here we show that the US expansion was driven by genetic gains from Green Revolution breeding and production advances that increased yields by 2,755%. Using a California population with a century-long breeding history and phenotypes of hybrids observed in coastal California environments, we estimate that breeding has increased fruit yields by 2,974-6,636%, counts by 1,454-3,940%, weights by 228-504%, and firmness by 239-769%. Using genomic prediction approaches, we pinpoint the origin of the Green Revolution to the early 1950s and uncover significant increases in additive genetic variation caused by transgressive segregation and phenotypic diversification. Lastly, we show that the most consequential Green Revolution breeding breakthrough was the introduction of photoperiod-insensitive, PERPETUAL FLOWERING hybrids in the 1970s that doubled yields and drove the dramatic expansion of strawberry production in California.
Face and context integration in emotion inference is limited and variable across categories and individuals
Authors: Goel Srishti , Jara-Ettinger Julian , Ong Desmond C. , Gendron Maria
Published: March 2024

The ability to make nuanced inferences about other people’s emotional states is central to social functioning. While emotion inferences can be sensitive to both facial movements and the situational context that they occur in, relatively little is understood about when these two sources of information are integrated across emotion categories and individuals. In a series of studies, we use one archival and five empirical datasets to demonstrate that people could be integrating, but that emotion inferences are just as well (and sometimes better) captured by knowledge of the situation alone, while isolated facial cues are insufficient. Further, people integrate facial cues more for categories for which they most frequently encounter facial expressions in everyday life (e.g.,happiness). People are also moderately stable over time in their reliance on situational cues and integration of cues and those who reliably utilize situation cues more also have better situated emotion knowledge. These findings underscore the importance of studying variability in reliance on and integration of cues.
Fibroblast-specific PRMT5 deficiency suppresses cardiac fibrosis and left ventricular dysfunction in male mice
Authors: Katanasaka Yasufumi , Yabe Harumi , Murata Noriyuki , Sobukawa Minori , Sugiyama Yuga , Sato Hikaru , Honda Hiroki , Sunagawa Yoichi , Funamoto Masafumi , Shimizu Satoshi , Shimizu Kana , Hamabe-Horiike Toshihide , Hawke Philip , Komiyama Maki , Mori Kiyoshi , Hasegawa Koji , Morimoto Tatsuya
Published: March 2024

Protein arginine methyltransferase 5 (PRMT5) is a well-known epigenetic regulatory enzyme. However, the role of PRMT5-mediated arginine methylation in gene transcription related to cardiac fibrosis is unknown. Here we show that fibroblast-specific deletion of PRMT5 significantly reduces pressure overload-induced cardiac fibrosis and improves cardiac dysfunction in male mice. Both the PRMT5-selective inhibitor EPZ015666 and knockdown of PRMT5 suppress α-smooth muscle actin (α-SMA) expression induced by transforming growth factor-β (TGF-β) in cultured cardiac fibroblasts. TGF-β stimulation promotes the recruitment of the PRMT5/Smad3 complex to the promoter site of α-SMA. It also increases PRMT5-mediated H3R2 symmetric dimethylation, and this increase is inhibited by Smad3 knockdown. TGF-β stimulation increases H3K4 tri-methylation mediated by the WDR5/MLL1 methyltransferase complex, which recognizes H3R2 dimethylation. Finally, treatment with EPZ015666 significantly improves pressure overload-induced cardiac fibrosis and dysfunction. These findings suggest that PRMT5 regulates TGF-β/Smad3-dependent fibrotic gene transcription, possibly through histone methylation crosstalk, and plays a critical role in cardiac fibrosis and dysfunction.
VCF1 is a p97/VCP cofactor promoting recognition of ubiquitylated p97-UFD1-NPL4 substrates
Authors: Mirsanaye Ann Schirin , Hoffmann Saskia , Weisser Melanie , Mund Andreas , Lopez Mendez Blanca , Typas Dimitris , van den Boom Johannes , Benedict Bente , Hendriks Ivo A. , Nielsen Michael Lund , Meyer Hemmo , Duxin Julien P. , Montoya Guillermo , Mailand Niels
Published: March 2024

The hexameric AAA+ ATPase p97/VCP functions as an essential mediator of ubiquitin-dependent cellular processes, extracting ubiquitylated proteins from macromolecular complexes or membranes by catalyzing their unfolding. p97 is directed to ubiquitylated client proteins via multiple cofactors, most of which interact with the p97 N-domain. Here, we discover that FAM104A, a protein of unknown function also named VCF1 (VCP/p97 nuclear Cofactor Family member 1), acts as a p97 cofactor in human cells. Detailed structure-function studies reveal that VCF1 directly binds p97 via a conserved α-helical motif that recognizes the p97 N-domain with unusually high affinity, exceeding that of other cofactors. We show that VCF1 engages in joint p97 complex formation with the heterodimeric primary p97 cofactor UFD1-NPL4 and promotes p97-UFD1-NPL4-dependent proteasomal degradation of ubiquitylated substrates in cells. Mechanistically, VCF1 indirectly stimulates UFD1-NPL4 interactions with ubiquitin conjugates via its binding to p97 but has no intrinsic affinity for ubiquitin. Collectively, our findings establish VCF1 as an unconventional p97 cofactor that promotes p97-dependent protein turnover by facilitating p97-UFD1-NPL4 recruitment to ubiquitylated targets.
Prediction of glycopeptide fragment mass spectra by deep learning
Authors: Yang Yi , Fang Qun
Published: March 2024

Deep learning has achieved a notable success in mass spectrometry-based proteomics and is now emerging in glycoproteomics. While various deep learning models can predict fragment mass spectra of peptides with good accuracy, they cannot cope with the non-linear glycan structure in an intact glycopeptide. Herein, we present DeepGlyco, a deep learning-based approach for the prediction of fragment spectra of intact glycopeptides. Our model adopts tree-structured long-short term memory networks to process the glycan moiety and a graph neural network architecture to incorporate potential fragmentation pathways of a specific glycan structure. This feature is beneficial to model explainability and differentiation ability of glycan structural isomers. We further demonstrate that predicted spectral libraries can be used for data-independent acquisition glycoproteomics as a supplement for library completeness. We expect that this work will provide a valuable deep learning resource for glycoproteomics.
High hydrostatic pressure stimulates microbial nitrate reduction in hadal trench sediments under oxic conditions
Authors: Yang Na , Lv Yongxin , Ji Mukan , Wu Shiguo , Zhang Yu
Published: March 2024

Hadal trenches are extreme environments situated over 6000 m below sea surface, where enormous hydrostatic pressure affects the biochemical cycling of elements. Recent studies have indicated that hadal trenches may represent a previously overlooked source of fixed nitrogen loss; however, the mechanisms and role of hydrostatic pressure in this process are still being debated. To this end, we investigate the effects of hydrostatic pressure (0.1 to 115 MPa) on the chemical profile, microbial community structure and functions of surface sediments from the Mariana Trench using a Deep Ocean Experimental Simulator supplied with nitrate and oxygen. We observe enhanced denitrification activity at high hydrostatic pressure under oxic conditions, while the anaerobic ammonium oxidation – a previously recognized dominant nitrogen loss pathway – is not detected. Additionally, we further confirm the simultaneous occurrence of nitrate reduction and aerobic respiration using a metatranscriptomic dataset from in situ RNA-fixed sediments in the Mariana Trench. Taken together, our findings demonstrate that hydrostatic pressure can influence microbial contributions to nitrogen cycling and that the hadal trenches are a potential nitrogen loss hotspot. Knowledge of the influence of hydrostatic pressure on anaerobic processes in oxygenated surface sediments can greatly broaden our understanding of element cycling in hadal trenches.
Corrosion behavior and cellular automata simulation of carbon steel in salt-spray environment
Authors: Qin Hong , Liu Jin , Shao Qianxi , Zhang Xiqing , Teng Yingxue , Chen Shuweng , Zhang Dazhen , Bao Shuo
Published: March 2024

Scanning electron microscope (SEM) and X-ray diffraction (XRD) were used to discuss the corrosion loss and morphology of the pit and rust layer of carbon steel. It was found that the corrosion process is largely influenced by the cyclic shedding of surface corrosion products, in addition to being controlled by the mechanism of oxide film shedding and pit evolution. A corrosion mechanism (the mechanism of rust layer shedding) is proposed. As a result, in this paper, the corrosion process of the test steel is simulated by the cellular automata. It was set up that the mechanism of oxide film shedding, the mechanism of pit evolution, and the mechanism of rust layer shedding in Cellular Automata Simulation. The optimal time ratio and simulation parameters were found, and a predictable cellular automata corrosion simulation model was built, providing a solution for carbon steel’s service life prediction.
Comparative statistical analysis of pitting in Two 2205 duplex stainless steel variants
Authors: Ran Guoyong , Tu Wenrui , Dong Haopeng , Jiang Yiming , Li Jin , Liu Kezhao , Sun Yangting
Published: March 2024

The inherent variability of pitting poses challenges in accurately evaluating the pitting resistance due to potential disparities in test results. This study compares the pitting resistance of two commercial 2205 duplex stainless steels. Counterintuitively, the variant with higher Pitting Resistance Equivalent Number, exhibits a lower Critical Pitting Temperature. Through the potentiostatic pulse test and potentiostatic polarization, this variant is observed to have a greater number of pitting initiation sites. Further investigation, using SEM inclusion statistics, reveals an increased presence of inclusions rich in calcium oxides as the underlying cause of this unexpected phenomenon.
Distinguishing features of Parkinson’s disease fallers based on wireless insole plantar pressure monitoring
Authors: Herbers Cara , Zhang Raymond , Erdman Arthur , Johnson Matthew D.
Published: March 2024

Postural instability is one of the most disabling motor signs of Parkinson’s disease (PD) and often underlies an increased likelihood of falling and loss of independence. Current clinical assessments of PD-related postural instability are based on a retropulsion test, which introduces human error and only evaluates reactive balance. There is an unmet need for objective, multi-dimensional assessments of postural instability that directly reflect activities of daily living in which individuals may experience postural instability. In this study, we trained machine-learning models on insole plantar pressure data from 111 participants (44 with PD and 67 controls) as they performed simulated static and active postural tasks of activities that often occur during daily living. Models accurately classified PD from young controls (area under the curve (AUC) 0.99+/− 0.00), PD from age-matched controls (AUC 0.99+/− 0.01), and PD fallers from PD non-fallers (AUC 0.91+/− 0.08). Utilizing features from both static and active postural tasks significantly improved classification performances, and all tasks were useful for separating PD from controls; however, tasks with higher postural threats were preferred for separating PD fallers from PD non-fallers.
Critical enhancement of the spin Hall effect by spin fluctuations
Authors: Okamoto Satoshi , Nagaosa Naoto
Published: March 2024

The spin Hall (SH) effect, the conversion of the electric current to the spin current along the transverse direction, relies on the relativistic spin-orbit coupling (SOC). Here, we develop a microscopic theory on the mechanisms of the SH effect in magnetic metals, where itinerant electrons are coupled with localized magnetic moments via the Hund exchange interaction and the SOC. Both antiferromagnetic metals and ferromagnetic metals are considered. It is shown that the SH conductivity can be significantly enhanced by the spin fluctuation when approaching the magnetic transition temperature of both cases. For antiferromagnetic metals, the pure SH effect appears in the entire temperature range, while for ferromagnetic metals, the pure SH effect is expected to be replaced by the anomalous Hall effect below the transition temperature. We discuss possible experimental realizations and the effect of the quantum criticality when the antiferromagnetic transition temperature is tuned to zero temperature.
Design of hepadnavirus core protein-based chimeric virus-like particles carrying epitopes from respiratory syncytial virus
Authors: Shao Shuai , Zhang Xue Feng , Hou Jun Wei , Yang Sen Sen , Han Zi Bo , Wu Hai Lan , Tang Fang , Li Xin Yu , Lei Ze Hua , Zhao Zi Xin , Li Shu Xiang , Liu Zhao Ming , Shan Pu , Jin Yu Qin , Su Ji Guo , Liang Yu , Zhang Jing , Li Qi Ming
Published: March 2024

Respiratory syncytial virus (RSV) is one of the most important pathogens causing respiratory tract infection in humans, especially in infants and the elderly. The identification and structural resolution of the potent neutralizing epitopes on RSV fusion (F) protein enable an “epitope-focused” vaccine design. However, the display of RSV F epitope II on the surface of the widely-used human hepatitis B virus core antigen (HBcAg) has failed to induce neutralizing antibody response in mice. Here, we used the hepadnavirus core protein (HcAg) from different mammalian hosts as scaffolds to construct chimeric virus-like particles (VLPs) presenting the RSV F epitope II. Mouse immunization showed that different HcAg-based chimeric VLPs elicited significantly different neutralizing antibody responses, among which the HcAg derived from roundleaf bat (RBHcAg) is the most immunogenic. Furthermore, RBHcAg was used as the scaffold platform to present multiple RSV F epitopes, and the immunogenicity was further improved in comparison to that displaying a single epitope II. The designed RBHcAg-based multiple-epitope-presenting VLP formulated with MF59-like adjuvant elicited a potent and balanced Th1/Th2 immune response, and offered substantial protection in mice against the challenge of live RSV A2 virus. The designed chimeric VLPs may serve as the potential starting point for developing epitope-focused vaccines against RSV. Our study also demonstrated that RBHcAg is an effective VLP carrier for presenting foreign epitopes, providing a promising platform for epitope-focused vaccine design.
Chromosomal barcodes for simultaneous tracking of near-isogenic bacterial strains in plant microbiota
Authors: Ordon Jana , Thouin Julien , Nakano Ryohei Thomas , Ma Ka-Wai , Zhang Pengfan , Huettel Bruno , Garrido-Oter Ruben , Schulze-Lefert Paul
Published: March 2024

DNA-amplicon-based microbiota profiling can estimate species diversity and abundance but cannot resolve genetic differences within individuals of the same species. Here we report the development of modular bacterial tags (MoBacTags) encoding DNA barcodes that enable tracking of near-isogenic bacterial commensals in an array of complex microbiome communities. Chromosomally integrated DNA barcodes are then co-amplified with endogenous marker genes of the community by integrating corresponding primer binding sites into the barcode. We use this approach to assess the contributions of individual bacterial genes to Arabidopsis thaliana root microbiota establishment with synthetic communities that include MoBacTag-labelled strains of Pseudomonas capeferrum. Results show reduced root colonization for certain mutant strains with defects in gluconic-acid-mediated host immunosuppression, which would not be detected with traditional amplicon sequencing. Our work illustrates how MoBacTags can be applied to assess scaling of individual bacterial genetic determinants in the plant microbiota.
Design of amyloidogenic peptide traps
Authors: Sahtoe Danny D. , Andrzejewska Ewa A. , Han Hannah L. , Rennella Enrico , Schneider Matthias M. , Meisl Georg , Ahlrichs Maggie , Decarreau Justin , Nguyen Hannah , Kang Alex , Levine Paul , Lamb Mila , Li Xinting , Bera Asim K. , Kay Lewis E. , Knowles Tuomas P. J. , Baker David
Published: March 2024

Segments of proteins with high β-strand propensity can self-associate to form amyloid fibrils implicated in many diseases. We describe a general approach to bind such segments in β-strand and β-hairpin conformations using de novo designed scaffolds that contain deep peptide-binding clefts. The designs bind their cognate peptides in vitro with nanomolar affinities. The crystal structure of a designed protein−peptide complex is close to the design model, and NMR characterization reveals how the peptide-binding cleft is protected in the apo state. We use the approach to design binders to the amyloid-forming proteins transthyretin, tau, serum amyloid A1 and amyloid β1−42 (Aβ42). The Aβ binders block the assembly of Aβ fibrils as effectively as the most potent of the clinically tested antibodies to date and protect cells from toxic Aβ42 species.
Dataset on the effects of psychological care on depression and suicide ideation in underrepresented children
Authors: Liu Xuerong , Li Wei , Gong Jie , Zhang Qianyu , Tian Xiaobing , Ren Ji-Dong , Xia Lei , Li Yanyan , Zhan Yu , Zhang Jing-Xuan , Chuan-Peng Hu , Chen Ji , Feng Zhengzhi ,   The Psychological Health Guard for Children and Adolescents Project of China (CPHG) Group, Liu Yue-Guang , An Xian-Yong , Yuan Xiang , Zhang Yi , Yang Jian , Li Wan-Xia , Peng Yao , Liao Yu-Jia , Cheng Si-Yu , Liu Lu , Yu Hong-Jiang , Liu Tian-Tian , Liang Li-Jun , Cheng Meng-Zhu , Zhao Xi , Deng Xiang-Yu , Xu Hui-Lei , Li Xue-Hua , Wen Yi-Han , Lei Jun , He Xiao , Liu Hong-Ying , Zhang Lei , Liu Zhen-Mi , Meng Xiandong , Jiang Xia , Li Yuan-Yuan , Xu Jiajun , Chen Zhiyi
Published: March 2024

Massive increases in the risks of depressive disorders and the ensuing suicide have become the overarching menace for children/adolescents. Despite global consensus to instigate psychological healthcare policy for these children/adolescents, their effects remain largely unclear neither from a small amount of official data nor from small-scale scientific studies. More importantly, in underprivileged children/adolescents in lower-middle-economic-status countries/areas, the data collection may not be as equally accessible as in developed countries/areas, thus resulting in underrepresented observations. To address these challenges, we released a large-scale and multi-center cohort dataset (n = 249,772) showing the effects of primary psychological healthcare on decreasing depression and suicidal ideation in these children/adolescents who were underrepresented in previous studies or current healthcare systems, including unattended children/adolescents, orphans, children/adolescents in especially difficult circumstances, and “left-behind” and “single-parenting” children/adolescents. We provided all individual data recording the depressive symptoms and suicide ideation that had been collected at baseline (Oct 2022) and half-year follow-up (May 2023) from practicing this psychological healthcare system.
Novel epoxy-bPBD-BisMSB composite plastic scintillator for alpha, beta and gamma radiation detection
Authors: Sahani R. M. , Pandya Arun
Published: March 2024

A composite plastic scintillator is prepared by uniform dispersion of organic fluorophores 2-(4-Biphenylyl)-5-(4-tert-butylphenyl)-1,3,4-oxadiazole (b-PBD) and 1,4-bis(2-methylstyryl) benzene (Bis-MSB) in epoxy resin followed by curing at room temperature. The developed scintillator is strong blue emitter (425 nm), confirmed by 365 nm UV excited Photo luminescence and beta particle (90Sr-90Y) excited Radio-luminescence characterizations. The developed scintillator is highly transparent (~ 70%) to emitted light wavelength. Moreover, the scintillator’s blue emission is appropriate for photomultiplier tube (PMT) based scintillation measurement due to its maximum peak spectral response in blue region. Alpha, beta and gamma radiation detection were performed on PMT coupled scintillators of sizes Ø50 mm × 1 mm, Ø50 mm × 5 mm and Ø50 mm × 25 mm respectively. Pulse height spectra were recorded using 1 k Multichannel analyser (MCA) using various reference radiation sources. All scintillators demonstrated promising response to the respective radiations. Absolute detection efficiency of alpha scintillator is obtained as 32% (241Am), 86% of that of standard plastic scintillator EJ-212. Beta endpoint energy and gamma Compton edges showed linear variation w.r.t. corresponding channel numbers. Detection efficiency of beta and gamma scintillator is found to be 35.7% (90Sr-90Y) and 6.7% (136Cs) respectively. The developed scintillator has potential to be used for radioactivity contamination & gamma dose rate measurement applications.
Development of a predictive model for risk stratification of acute kidney injury in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy
Authors: Krause Martin , Mehdipour Soraya , Veerapong Jula , Baumgartner Joel M. , Lowy Andrew M. , Gabriel Rodney A.
Published: March 2024

Acute kidney injury (AKI) following hyperthermic intraperitoneal chemotherapy (HIPEC) is common. Identifying patients at risk could have implications for surgical and anesthetic management. We aimed to develop a predictive model that could predict AKI based on patients’ preoperative characteristics and intraperitoneal chemotherapy regimen. We retrospectively gathered data of adult patients undergoing HIPEC at our health system between November 2013 and April 2022. Next, we developed a model predicting postoperative AKI using multivariable logistic regression and calculated the performance of the model (area under the receiver operating characteristics curve [AUC]) via tenfold cross-validation. A total of 412 patients were included, of which 36 (8.7%) developed postoperative AKI. Based on our multivariable logistic regression model, multiple preoperative and intraoperative characteristics were associated with AKI. We included the total intraoperative cisplatin dose, body mass index, male sex, and preoperative hemoglobin level in the final model. The mean area under the receiver operating characteristics curve value was 0.82 (95% confidence interval 0.71–0.93). Our risk model predicted AKI with high accuracy in patients undergoing HIPEC in our institution. The external validity of our model should now be tested in independent and prospective patient cohorts.
Variation in social media sensitivity across people and contexts
Authors: Vaid Sumer S. , Kroencke Lara , Roshanaei Mahnaz , Talaifar Sanaz , Hancock Jeffrey T. , Back Mitja D. , Gosling Samuel D. , Ram Nilam , Harari Gabriella M.
Published: March 2024

Social media impacts people’s wellbeing in different ways, but relatively little is known about why this is the case. Here we introduce the construct of “social media sensitivity” to understand how social media and wellbeing associations differ across people and the contexts in which these platforms are used. In a month-long large-scale intensive longitudinal study (total n = 1632; total number of observations = 120,599), we examined for whom and under which circumstances social media was associated with positive and negative changes in social and affective wellbeing. Applying a combination of frequentist and Bayesian multilevel models, we found a small negative average association between social media use AND subsequent wellbeing, but the associations were heterogenous across people. People with psychologically vulnerable dispositions (e.g., those who were depressed, lonely, not satisfied with life) tended to experience heightened negative social media sensitivity in comparison to people who were not psychologically vulnerable. People also experienced heightened negative social media sensitivity when in certain types of places (e.g., in social places, in nature) and while around certain types of people (e.g., around family members, close ties), as compared to using social media in other contexts. Our results suggest that an understanding of the effects of social media on wellbeing should account for the psychological dispositions of social media users, and the physical and social contexts surrounding their use. We discuss theoretical and practical implications of social media sensitivity for scholars, policymakers, and those in the technology industry.
Thought habits and processing modes among Japanese university students do not influence dynamic associations between rumination and negative affect
Authors: Kambara Kohei , Namba Shushi , Yokoyama Satoshi , Ogata Akiko
Published: March 2024

The integrated model of rumination argues that two trait factors—negative thinking habits and processing modes—get people stuck in maladaptive rumination. There is little evidence showing whether these factors influence the daily dynamic associations between rumination and negative moods. To address this, in this study, we conducted an experience-sampling method on Japanese university students. We recruited 92 Japanese university students and assessed their daily rumination and negative affect (NA) eight times a day for seven days. We examined the effects of habits and processing modes on the dynamic associations between rumination and negative moods using dynamic structural equation modeling. We found that individuals were more likely to ruminate when they experienced NA. However, contrary to previous findings, this study’s participants did not experience NA after engaging in rumination. Moreover, we did not detect any significant trait factor effect on these dynamic associations. Our findings imply that individuals are more likely to engage in rumination after experiencing NA, but the reverse association, particularly the autoregression of rumination, may not be maintained in natural daily life. Furthermore, negative thinking habits and processing modes may not influence the daily dynamic associations between rumination and NA among Japanese university students.
Biochar influences nitrogen and phosphorus dynamics in two texturally different soils
Authors: Gupta Rajeev Kumar , Vashisht Monika , Naresh R. K. , Dhingra Nitish , Sidhu Mehra S. , Singh P. K. , Rani Neeraj , Al-Ansari Nadhir , Alataway Abed , Dewidar Ahmed Z. , Mattar Mohamed A.
Published: March 2024

Nitrogen (N) and phosphorus (P) are vital for crop growth. However, most agricultural systems have limited inherent ability to supply N and P to crops. Biochars (BCs) are strongly advocated in agrosystems and are known to improve the availability of N and P in crops through different chemical transformations. Herein, a soil-biochar incubation experiment was carried out to investigate the transformations of N and P in two different textured soils, namely clay loam and loamy sand, on mixing with rice straw biochar (RSB) and acacia wood biochar (ACB) at each level (0, 0.5, and 1.0% w/w). Ammonium N (NH4-N) decreased continuously with the increasing incubation period. The ammonium N content disappeared rapidly in both the soils incubated with biochars compared to the unamended soil. RSB increased the nitrate N (NO3–N) content significantly compared to ACB for the entire study period in both texturally divergent soils. The nitrate N content increased with the enhanced biochar addition rate in clay loam soil until 15 days after incubation; however, it was reduced for the biochar addition rate of 1% compared to 0.5% at 30 and 60 days after incubation in loamy sand soil. With ACB, the net increase in nitrate N content with the biochar addition rate of 1% remained higher than the 0.5% rate for 60 days in clay loam and 30 days in loamy sand soil. The phosphorus content remained consistently higher in both the soils amended with two types of biochars till the completion of the experiment.
Exploring the personality and relationship factors that mediate the connection between differentiation of self and phubbing
Authors: Peleg Ora , Boniel-Nissim Meyran
Published: March 2024

One of the family patterns crucial for mental and physical well-being is differentiation of self. In this study, our aim was to investigate its impact on the phenomenon of phubbing—where individuals prioritize smartphones over in-person interactions. The prevalence of phubbing behavior has risen substantially in tandem with the increased adoption of smartphones. The study investigated familial, interpersonal, and personal factors that could potentially contribute to the escalation of phubbing behaviors. It was hypothesized that differentiation of self would be associated with phubbing through the mediation of fear of missing out, romantic relationship satisfaction, and loneliness in intimate relationships. We also expected gender differences in the study variables. A sample of 431 young adults, with an average age of 29 (M = 29.05, SD = 9.14), completed the DSI-R, Phubbing, FoMO, ENRICH, and LIRS questionnaires online. Results indicated that fear of missing out mediated the relationship between three dimensions of differentiation of self—emotional reactivity, emotional cutoff, and fusion with others—and phubbing behavior. However, the expected mediation by romantic relationship satisfaction and loneliness in intimate relationships did not reach significance, although these variables were found to be associated with differentiation of self. Women reported higher levels of phubbing behavior, emotional reactivity, and fusion with others, whereas men reported higher levels of I-position. We conclude that fear of missing out may serve as a catalyst, triggering anxiety in individuals, which in turn drives them to adopt phubbing as a coping mechanism. Moreover, individuals with lower levels of differentiation of self appear to be at increased risk of engaging in phubbing behaviors through the mediation of fear of missing out.
Short turnaround time of seven to nine hours from sample collection until informed decision for sepsis treatment using nanopore sequencing
Authors: Ali Jawad , Johansen Wenche , Ahmad Rafi
Published: March 2024

Bloodstream infections (BSIs) and sepsis are major health problems, annually claiming millions of lives. Traditional blood culture techniques, employed to identify sepsis-causing pathogens and assess antibiotic susceptibility, usually take 2–4 days. Early and accurate antibiotic prescription is vital in sepsis to mitigate mortality and antibiotic resistance. This study aimed to reduce the wait time for sepsis diagnosis by employing shorter blood culture incubation times for BD BACTEC™ bottles using standard laboratory incubators, followed by real-time nanopore sequencing and data analysis. The method was tested on nine blood samples spiked with clinical isolates from the six most prevalent sepsis-causing pathogens. The results showed that pathogen identification was possible at as low as 102–104 CFU/mL, achieved after just 2 h of incubation and within 40 min of nanopore sequencing. Moreover, all the antimicrobial resistance genes were identified at 103–107 CFU/mL, achieved after incubation for 5 h and only 10 min to 3 h of sequencing. Therefore, the total turnaround time from sample collection to the information required for an informed decision on the right antibiotic treatment was between 7 and 9 h. These results hold significant promise for better clinical management of sepsis compared with current culture-based methods.
Uncovering the molecular mechanisms of russet skin formation in Niagara grapevine (Vitis vinifera × Vitis labrusca)
Authors: Niederauer Guilherme Francio , de Oliveira Geovani Luciano , Aono Alexandre Hild , da Silva Graciano Diego , Carmello-Guerreiro Sandra Maria , Moura Mara Fernandes , de Souza Anete Pereira
Published: March 2024

Grape breeding programs are mostly focused on developing new varieties with high production volume, sugar contents, and phenolic compound diversity combined with resistance and tolerance to the main pathogens under culture and adverse environmental conditions. The ‘Niagara’ variety (Vitis labrusca$$\times$$
×
Vitis vinifera) is one of the most widely produced and commercialized table grapes in Brazil. In this work, we selected three Niagara somatic variants with contrasting berry phenotypes and performed morphological and transcriptomic analyses of their berries. Histological sections of the berries were also performed to understand anatomical and chemical composition differences of the berry skin between the genotypes. An RNA-Seq pipeline was implemented, followed by global coexpression network modeling. ‘Niagara Steck’, an intensified russet mutant with the most extreme phenotype, showed the largest difference in expression and showed selection of coexpressed network modules involved in the development of its russet-like characteristics. Enrichment analysis of differently expressed genes and hub network modules revealed differences in transcription regulation, auxin signaling and cell wall and plasmatic membrane biogenesis. Cutin- and suberin-related genes were also differently expressed, supporting the anatomical differences observed with microscopy.
Close negative correlation of local and circulating Dickkopf-1 and Sclerostin levels during human fracture healing
Authors: Starlinger Julia , Santol Jonas , Kaiser Georg , Sarahrudi Kambiz
Published: March 2024

Wnt signaling is critically involved in fracture healing. Existing data predominantly relies on rodent models. Here, we explored local and circulating Dickkopf-1 (DKK1) levels in patients with respect to fracture healing and explore its association to sclerostin (SOST). 69 patients after surgical stabilization of long bone fractures of which six patients had impaired fracture healing were included in this study. Life-style and patient related factors with a known effect on DKK1 and SOST were recorded. DKK1 and SOST concentrations were measured using enzyme-linked immunosorbent assay (ELISA) at the fracture site and in circulation. DKK1 and SOST showed a close inverse correlation. In fracture hematoma and immediately after trauma DKK1 levels were significantly reduced while SOST levels were significantly increased, compared to healthy control. Postoperatively, DKK1 peaked at week 2 and SOST at week 8, again demonstrating a close negative correlation. Age and smoking status affected the balance of DKK1 and SOST, while type 2 diabetes and sex did not demonstrate a significant influence. Early postoperative elevation of SOST without compensatory DKK1 decrease was associated with fracture non-union in younger patients (< 50a). The close inverse correlation and very rapid dynamics of DKK1 and SOST locally as well as systemically suggest their critical involvement during human fracture healing. Importantly, as immediate compensatory feedback mechanism are apparent, we provide evidence that dual-blockade of DKK1 and SOST could be critical to allow for therapeutic efficiency of Wnt targeted therapies for fracture healing.
Lightweight federated learning for STIs/HIV prediction
Authors: Nguyen Thi Phuoc Van , Yang Wencheng , Tang Zhaohui , Xia Xiaoyu , Mullens Amy B. , Dean Judith A. , Li Yan
Published: March 2024

This paper presents a solution that prioritises high privacy protection and improves communication throughput for predicting the risk of sexually transmissible infections/human immunodeficiency virus (STIs/HIV). The approach utilised Federated Learning (FL) to construct a model from multiple clinics and key stakeholders. FL ensured that only models were shared between clinics, minimising the risk of personal information leakage. Additionally, an algorithm was explored on the FL manager side to construct a global model that aligns with the communication status of the system. Our proposed method introduced Random Forest Federated Learning for assessing the risk of STIs/HIV, incorporating a flexible aggregation process that can be adjusted to accommodate the capacious communication system. Experimental results demonstrated the significant potential of a solution for estimating STIs/HIV risk. In comparison with recent studies, our approach yielded superior results in terms of AUC (0.97) and accuracy ($$93\%$$93%). Despite these promising findings, a limitation of the study lies in the experiment for man’s data, due to the self-reported nature of the data and sensitive content. which may be subject to participant bias. Future research could check the performance of the proposed framework in partnership with high-risk populations (e.g., men who have sex with men) to provide a more comprehensive understanding of the proposed framework’s impact and ultimately aim to improve health outcomes/health service optimisation.
Data-driven simulations for training AI-based segmentation of neutron images
Authors: Sathe Pushkar S. , Wolf Caitlyn M. , Kim Youngju , Robinson Sarah M. , Daugherty M. Cyrus , Murphy Ryan P. , LaManna Jacob M. , Huber Michael G. , Jacobson David L. , Kienzle Paul A. , Weigandt Katie M. , Klimov Nikolai N. , Hussey Daniel S. , Bajcsy Peter
Published: March 2024

Neutron interferometry uniquely combines neutron imaging and scattering methods to enable characterization of multiple length scales from 1 nm to 10 µm. However, building, operating, and using such neutron imaging instruments poses constraints on the acquisition time and on the number of measured images per sample. Experiment time-constraints yield small quantities of measured images that are insufficient for automating image analyses using supervised artificial intelligence (AI) models. One approach alleviates this problem by supplementing annotated measured images with synthetic images. To this end, we create a data-driven simulation framework that supplements training data beyond typical data-driven augmentations by leveraging statistical intensity models, such as the Johnson family of probability density functions (PDFs). We follow the simulation framework steps for an image segmentation task including Estimate PDFs $$\,\rightarrow \,$$

→

Validate PDFs $$\,\rightarrow \,$$

→

Design Image Masks $$\,\rightarrow \,$$

→

Generate Intensities $$\,\rightarrow \,$$

→

Train AI Model for Segmentation. Our goal is to minimize the manual labor needed to execute the steps and maximize our confidence in simulations and segmentation accuracy. We report results for a set of nine known materials (calibration phantoms) that were imaged using a neutron interferometer acquiring four-dimensional images and segmented by AI models trained with synthetic and measured images and their masks.