bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell DNA methylome and 3D multi-omic atlas of the adult mouse brain
Authors: Liu Hanqing , Zeng Qiurui , Zhou Jingtian , Bartlett Anna , Wang Bang-An , Berube Peter , Tian Wei , Kenworthy Mia , Altshul Jordan , Nery Joseph R. , Chen Huaming , Castanon Rosa G. , Zu Songpeng , Li Yang Eric , Lucero Jacinta , Osteen Julia K. , Pinto-Duarte Antonio , Lee Jasper , Rink Jon , Cho Silvia , Emerson Nora , Nunn Michael , O’Connor Carolyn , Wu Zhanghao , Stoica Ion , Yao Zizhen , Smith Kimberly A. , Tasic Bosiljka , Luo Chongyuan , Dixon Jesse R. , Zeng Hongkui , Ren Bing , Behrens M. Margarita , Ecker Joseph R.
Published: December 2023

Cytosine DNA methylation is essential in brain development and is implicated in various neurological disorders. Understanding DNA methylation diversity across the entire brain in a spatial context is fundamental for a complete molecular atlas of brain cell types and their gene regulatory landscapes. Here we used single-nucleus methylome sequencing (snmC-seq3) and multi-omic sequencing (snm3C-seq)1technologies to generate 301,626 methylomes and 176,003 chromatin conformation–methylome joint profiles from 117 dissected regions throughout the adult mouse brain. Using iterative clustering and integrating with companion whole-brain transcriptome and chromatin accessibility datasets, we constructed a methylation-based cell taxonomy with 4,673 cell groups and 274 cross-modality-annotated subclasses. We identified 2.6 million differentially methylated regions across the genome that represent potential gene regulation elements. Notably, we observed spatial cytosine methylation patterns on both genes and regulatory elements in cell types within and across brain regions. Brain-wide spatial transcriptomics data validated the association of spatial epigenetic diversity with transcription and improved the anatomical mapping of our epigenetic datasets. Furthermore, chromatin conformation diversities occurred in important neuronal genes and were highly associated with DNA methylation and transcription changes. Brain-wide cell-type comparisons enabled the construction of regulatory networks that incorporate transcription factors, regulatory elements and their potential downstream gene targets. Finally, intragenic DNA methylation and chromatin conformation patterns predicted alternative gene isoform expression observed in a whole-brain SMART-seq2dataset. Our study establishes a brain-wide, single-cell DNA methylome and 3D multi-omic atlas and provides a valuable resource for comprehending the cellular–spatial and regulatory genome diversity of the mouse brain.
Molecularly defined and spatially resolved cell atlas of the whole mouse brain
Authors: Zhang Meng , Pan Xingjie , Jung Won , Halpern Aaron R. , Eichhorn Stephen W. , Lei Zhiyun , Cohen Limor , Smith Kimberly A. , Tasic Bosiljka , Yao Zizhen , Zeng Hongkui , Zhuang Xiaowei
Published: December 2023

In mammalian brains, millions to billions of cells form complex interaction networks to enable a wide range of functions. The enormous diversity and intricate organization of cells have impeded our understanding of the molecular and cellular basis of brain function. Recent advances in spatially resolved single-cell transcriptomics have enabled systematic mapping of the spatial organization of molecularly defined cell types in complex tissues1–3, including several brain regions (for example, refs. 1–11). However, a comprehensive cell atlas of the whole brain is still missing. Here we imaged a panel of more than 1,100 genes in approximately 10 million cells across the entire adult mouse brains using multiplexed error-robust fluorescence in situ hybridization12 and performed spatially resolved, single-cell expression profiling at the whole-transcriptome scale by integrating multiplexed error-robust fluorescence in situ hybridization and single-cell RNA sequencing data. Using this approach, we generated a comprehensive cell atlas of more than 5,000 transcriptionally distinct cell clusters, belonging to more than 300 major cell types, in the whole mouse brain with high molecular and spatial resolution. Registration of this atlas to the mouse brain common coordinate framework allowed systematic quantifications of the cell-type composition and organization in individual brain regions. We further identified spatial modules characterized by distinct cell-type compositions and spatial gradients featuring gradual changes of cells. Finally, this high-resolution spatial map of cells, each with a transcriptome-wide expression profile, allowed us to infer cell-type-specific interactions between hundreds of cell-type pairs and predict molecular (ligand–receptor) basis and functional implications of these cell–cell interactions. These results provide rich insights into the molecular and cellular architecture of the brain and a foundation for functional investigations of neural circuits and their dysfunction in health and disease.
The molecular cytoarchitecture of the adult mouse brain
Authors: Langlieb Jonah , Sachdev Nina S. , Balderrama Karol S. , Nadaf Naeem M. , Raj Mukund , Murray Evan , Webber James T. , Vanderburg Charles , Gazestani Vahid , Tward Daniel , Mezias Chris , Li Xu , Flowers Katelyn , Cable Dylan M. , Norton Tabitha , Mitra Partha , Chen Fei , Macosko Evan Z.
Published: December 2023

The function of the mammalian brain relies upon the specification and spatial positioning of diversely specialized cell types. Yet, the molecular identities of the cell types and their positions within individual anatomical structures remain incompletely known. To construct a comprehensive atlas of cell types in each brain structure, we paired high-throughput single-nucleus RNA sequencing with Slide-seq1,2—a recently developed spatial transcriptomics method with near-cellular resolution—across the entire mouse brain. Integration of these datasets revealed the cell type composition of each neuroanatomical structure. Cell type diversity was found to be remarkably high in the midbrain, hindbrain and hypothalamus, with most clusters requiring a combination of at least three discrete gene expression markers to uniquely define them. Using these data, we developed a framework for genetically accessing each cell type, comprehensively characterized neuropeptide and neurotransmitter signalling, elucidated region-specific specializations in activity-regulated gene expression and ascertained the heritability enrichment of neurological and psychiatric phenotypes. These data, available as an online resource (www.BrainCellData.org), should find diverse applications across neuroscience, including the construction of new genetic tools and the prioritization of specific cell types and circuits in the study of brain diseases.
Conserved and divergent gene regulatory programs of the mammalian neocortex
Authors: Zemke Nathan R. , Armand Ethan J. , Wang Wenliang , Lee Seoyeon , Zhou Jingtian , Li Yang Eric , Liu Hanqing , Tian Wei , Nery Joseph R. , Castanon Rosa G. , Bartlett Anna , Osteen Julia K. , Li Daofeng , Zhuo Xiaoyu , Xu Vincent , Chang Lei , Dong Keyi , Indralingam Hannah S. , Rink Jonathan A. , Xie Yang , Miller Michael , Krienen Fenna M. , Zhang Qiangge , Taskin Naz , Ting Jonathan , Feng Guoping , McCarroll Steven A. , Callaway Edward M. , Wang Ting , Lein Ed S. , Behrens M. Margarita , Ecker Joseph R. , Ren Bing
Published: December 2023

Divergence of cis-regulatory elements drives species-specific traits1, but how this manifests in the evolution of the neocortex at the molecular and cellular level remains unclear. Here we investigated the gene regulatory programs in the primary motor cortex of human, macaque, marmoset and mouse using single-cell multiomics assays, generating gene expression, chromatin accessibility, DNA methylome and chromosomal conformation profiles from a total of over 200,000 cells. From these data, we show evidence that divergence of transcription factor expression corresponds to species-specific epigenome landscapes. We find that conserved and divergent gene regulatory features are reflected in the evolution of the three-dimensional genome. Transposable elements contribute to nearly 80% of the human-specific candidate cis-regulatory elements in cortical cells. Through machine learning, we develop sequence-based predictors of candidate cis-regulatory elements in different species and demonstrate that the genomic regulatory syntax is highly preserved from rodents to primates. Finally, we show that epigenetic conservation combined with sequence similarity helps to uncover functional cis-regulatory elements and enhances our ability to interpret genetic variants contributing to neurological disease and traits.
Slide-tags enables single-nucleus barcoding for multimodal spatial genomics
Authors: Russell Andrew J. C. , Weir Jackson A. , Nadaf Naeem M. , Shabet Matthew , Kumar Vipin , Kambhampati Sandeep , Raichur Ruth , Marrero Giovanni J. , Liu Sophia , Balderrama Karol S. , Vanderburg Charles R. , Shanmugam Vignesh , Tian Luyi , Iorgulescu J. Bryan , Yoon Charles H. , Wu Catherine J. , Macosko Evan Z. , Chen Fei
Published: December 2023

Recent technological innovations have enabled the high-throughput quantification of gene expression and epigenetic regulation within individual cells, transforming our understanding of how complex tissues are constructed1–6. However, missing from these measurements is the ability to routinely and easily spatially localize these profiled cells. We developed a strategy, Slide-tags, in which single nuclei within an intact tissue section are tagged with spatial barcode oligonucleotides derived from DNA-barcoded beads with known positions. These tagged nuclei can then be used as an input into a wide variety of single-nucleus profiling assays. Application of Slide-tags to the mouse hippocampus positioned nuclei at less than 10 μm spatial resolution and delivered whole-transcriptome data that are indistinguishable in quality from ordinary single-nucleus RNA-sequencing data. To demonstrate that Slide-tags can be applied to a wide variety of human tissues, we performed the assay on brain, tonsil and melanoma. We revealed cell-type-specific spatially varying gene expression across cortical layers and spatially contextualized receptor–ligand interactions driving B cell maturation in lymphoid tissue. A major benefit of Slide-tags is that it is easily adaptable to almost any single-cell measurement technology. As a proof of principle, we performed multiomic measurements of open chromatin, RNA and T cell receptor (TCR) sequences in the same cells from metastatic melanoma, identifying transcription factor motifs driving cancer cell state transitions in spatially distinct microenvironments. Slide-tags offers a universal platform for importing the compendium of established single-cell measurements into the spatial genomics repertoire.
Bioactive glycans in a microbiome-directed food for children with malnutrition
Authors: Hibberd Matthew C. , Webber Daniel M. , Rodionov Dmitry A. , Henrissat Suzanne , Chen Robert Y. , Zhou Cyrus , Lynn Hannah M. , Wang Yi , Chang Hao-Wei , Lee Evan M. , Lelwala-Guruge Janaki , Kazanov Marat D. , Arzamasov Aleksandr A. , Leyn Semen A. , Lombard Vincent , Terrapon Nicolas , Henrissat Bernard , Castillo Juan J. , Couture Garret , Bacalzo Nikita P. , Chen Ye , Lebrilla Carlito B. , Mostafa Ishita , Das Subhasish , Mahfuz Mustafa , Barratt Michael J. , Osterman Andrei L. , Ahmed Tahmeed , Gordon Jeffrey I.
Published: December 2023

Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition1–4. Here we analyse biospecimens from a randomized, controlled trial of a microbiome-directed complementary food (MDCF-2) that produced superior rates of weight gain compared with a calorically more dense conventional ready-to-use supplementary food in 12–18-month-old Bangladeshi children with moderate acute malnutrition4. We reconstructed 1,000 bacterial genomes (metagenome-assembled genomes (MAGs)) from the faecal microbiomes of trial participants, identified 75 MAGs of which the abundances were positively associated with ponderal growth (change in weight-for-length Z score (WLZ)), characterized changes in MAG gene expression as a function of treatment type and WLZ response, and quantified carbohydrate structures in MDCF-2 and faeces. The results reveal that two Prevotella copri MAGs that are positively associated with WLZ are the principal contributors to MDCF-2-induced expression of metabolic pathways involved in utilizing the component glycans of MDCF-2. The predicted specificities of carbohydrate-active enzymes expressed by their polysaccharide-utilization loci are correlated with (1) the in vitro growth of Bangladeshi P. copri strains, possessing varying degrees of polysaccharide-utilization loci and genomic conservation with these MAGs, in defined medium containing different purified glycans representative of those in MDCF-2, and (2) the levels of faecal carbohydrate structures in the trial participants. These associations suggest that identifying bioactive glycan structures in MDCFs metabolized by growth-associated bacterial taxa will help to guide recommendations about their use in children with acute malnutrition and enable the development of additional formulations.
Large-scale single-neuron speech sound encoding across the depth of human cortex
Authors: Leonard Matthew K. , Gwilliams Laura , Sellers Kristin K. , Chung Jason E. , Xu Duo , Mischler Gavin , Mesgarani Nima , Welkenhuysen Marleen , Dutta Barundeb , Chang Edward F.
Published: December 2023

Understanding the neural basis of speech perception requires that we study the human brain both at the scale of the fundamental computational unit of neurons and in their organization across the depth of cortex. Here we used high-density Neuropixels arrays1–3 to record from 685 neurons across cortical layers at nine sites in a high-level auditory region that is critical for speech, the superior temporal gyrus4,5, while participants listened to spoken sentences. Single neurons encoded a wide range of speech sound cues, including features of consonants and vowels, relative vocal pitch, onsets, amplitude envelope and sequence statistics. Neurons at each cross-laminar recording exhibited dominant tuning to a primary speech feature while also containing a substantial proportion of neurons that encoded other features contributing to heterogeneous selectivity. Spatially, neurons at similar cortical depths tended to encode similar speech features. Activity across all cortical layers was predictive of high-frequency field potentials (electrocorticography), providing a neuronal origin for macroelectrode recordings from the cortical surface. Together, these results establish single-neuron tuning across the cortical laminae as an important dimension of speech encoding in human superior temporal gyrus.
The landscape of genomic structural variation in Indigenous Australians
Authors: Reis Andre L. M. , Rapadas Melissa , Hammond Jillian M. , Gamaarachchi Hasindu , Stevanovski Igor , Ayuputeri Kumaheri Meutia , Chintalaphani Sanjog R. , Dissanayake Duminda S. B. , Siggs Owen M. , Hewitt Alex W. , Llamas Bastien , Brown Alex , Baynam Gareth , Mann Graham J. , McMorran Brendan J. , Easteal Simon , Hermes Azure , Jenkins Misty R. ,   The National Centre for Indigenous Genomics, Pearson Glen , Roe Yvette , Mohamed Janine , Murray Ben , Ormond-Parker Lyndon , Kneipp Erica , Nugent Keith , Mann Graham , Patel Hardip R. , Deveson Ira W.
Published: December 2023

Indigenous Australians harbour rich and unique genomic diversity. However, Aboriginal and Torres Strait Islander ancestries are historically under-represented in genomics research and almost completely missing from reference datasets1–3. Addressing this representation gap is critical, both to advance our understanding of global human genomic diversity and as a prerequisite for ensuring equitable outcomes in genomic medicine. Here we apply population-scale whole-genome long-read sequencing4 to profile genomic structural variation across four remote Indigenous communities. We uncover an abundance of large insertion–deletion variants (20–49 bp; n = 136,797), structural variants (50  b–50 kb; n = 159,912) and regions of variable copy number (>50 kb; n = 156). The majority of variants are composed of tandem repeat or interspersed mobile element sequences (up to 90%) and have not been previously annotated (up to 62%). A large fraction of structural variants appear to be exclusive to Indigenous Australians (12% lower-bound estimate) and most of these are found in only a single community, underscoring the need for broad and deep sampling to achieve a comprehensive catalogue of genomic structural variation across the Australian continent. Finally, we explore short tandem repeats throughout the genome to characterize allelic diversity at 50 known disease loci5, uncover hundreds of novel repeat expansion sites within protein-coding genes, and identify unique patterns of diversity and constraint among short tandem repeat sequences. Our study sheds new light on the dimensions and dynamics of genomic structural variation within and beyond Australia.
Modelling post-implantation human development to yolk sac blood emergence
Authors: Hislop Joshua , Song Qi , Keshavarz F. Kamyar , Alavi Amir , Schoenberger Rayna , LeGraw Ryan , Velazquez Jeremy J. , Mokhtari Tahere , Taheri Mohammad Naser , Rytel Matthew , Chuva de Sousa Lopes Susana M. , Watkins Simon , Stolz Donna , Kiani Samira , Sozen Berna , Bar-Joseph Ziv , Ebrahimkhani Mo R.
Published: December 2023

Implantation of the human embryo begins a critical developmental stage that comprises profound events including axis formation, gastrulation and the emergence of haematopoietic system1,2. Our mechanistic knowledge of this window of human life remains limited due to restricted access to in vivo samples for both technical and ethical reasons3–5. Stem cell models of human embryo have emerged to help unlock the mysteries of this stage6–16. Here we present a genetically inducible stem cell-derived embryoid model of early post-implantation human embryogenesis that captures the reciprocal codevelopment of embryonic tissue and the extra-embryonic endoderm and mesoderm niche with early haematopoiesis. This model is produced from induced pluripotent stem cells and shows unanticipated self-organizing cellular programmes similar to those that occur in embryogenesis, including the formation of amniotic cavity and bilaminar disc morphologies as well as the generation of an anterior hypoblast pole and posterior domain. The extra-embryonic layer in these embryoids lacks trophoblast and shows advanced multilineage yolk sac tissue-like morphogenesis that harbours a process similar to distinct waves of haematopoiesis, including the emergence of erythroid-, megakaryocyte-, myeloid- and lymphoid-like cells. This model presents an easy-to-use, high-throughput, reproducible and scalable platform to probe multifaceted aspects of human development and blood formation at the early post-implantation stage. It will provide a tractable human-based model for drug testing and disease modelling.
GDF15 linked to maternal risk of nausea and vomiting during pregnancy
Authors: Fejzo M. , Rocha N. , Cimino I. , Lockhart S. M. , Petry C. J. , Kay R. G. , Burling K. , Barker P. , George A. L. , Yasara N. , Premawardhena A. , Gong S. , Cook E. , Rimmington D. , Rainbow K. , Withers D. J. , Cortessis V. , Mullin P. M. , MacGibbon K. W. , Jin E. , Kam A. , Campbell A. , Polasek O. , Tzoneva G. , Gribble F. M. , Yeo G. S. H. , Lam B. Y. H. , Saudek V. , Hughes I. A. , Ong K. K. , Perry J. R. B. , Sutton Cole A. , Baumgarten M. , Welsh P. , Sattar N. , Smith G. C. S. , Charnock-Jones D. S. , Coll A. P. , Meek C. L. , Mettananda S. , Hayward C. , Mancuso N. , O’Rahilly S.
Published: December 2023

GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but a full mechanistic understanding is lacking1–4. Here we report that fetal production of GDF15 and maternal sensitivity to it both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally labelled GDF15 variant, we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants, we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with β-thalassaemia, a condition in which GDF15 levels are chronically high5, report very low levels of nausea and vomiting of pregnancy. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by prepregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.
Response of Arctic benthic foraminiferal traits to past environmental changes
Authors: Hansen Katrine Elnegaard , Pearce Christof , Seidenkrantz Marit-Solveig
Published: December 2023

The Arctic is subjected to all-encompassing disruptions in marine ecosystems caused by anthropogenic warming. To provide reliable estimates of how future changes will affect the ecosystems, knowledge of Arctic marine ecosystem responses to past environmental variability beyond the instrumental era is essential. Here, we present a novel approach on how to evaluate the state of benthic marine biotic conditions during the deglacial and Holocene period on the Northeast Greenland shelf. Benthic foraminiferal species were assigned traits (e.g., oxygen tolerance, food preferences) aiming to identify past faunal changes as a response to external forcing mechanisms. This approach was applied on sediment cores from offshore Northeast Greenland. We performed numerical rate-of-change detection to determine significant changes in the benthic foraminiferal traits. That way, the significant abrupt trait changes can be assessed across sites, providing a better understanding of the impact of climate drivers on the traits. Our results demonstrate that during the last ~ 14,000 years, bottom water oxygen is the main factor affecting the variability in the benthic foraminiferal faunas in this area. Our results show that significant changes in the traits correspond to drastic climate perturbations. Specifically, the deglacial-Holocene transition and mid-Holocene warm period exhibited significant change, with several trait turnovers.
Molecular assessment of drug-phospholipid interactions consequent to cancer treatment: a study of anthracycline-induced cardiotoxicity
Authors: Ahmed Yara , Elkhodary Khalil I. , Youssef Mostafa
Published: December 2023

Cardiotoxicity limits the use of anthracyclines as potent chemotherapeutics. We employ classical molecular dynamics to explore anthracycline interactions with a realistic myocardial membrane and compare to an ideal membrane widely used in literature. The interaction of these two membranes with four anthracyclines; doxorubicin, epirubicin, daunorubicin, and idarubicin are studied. Careful analysis was conducted on three forms of each drug; pristine, primary metabolite, and cationic salt. By examining the molecular residence time near the membrane’s surface, the average number of molecule/membrane hydrogen bonds, the immobilization of the molecules near the membrane, and the location of those molecules relative to the mid-plane of the membrane we found out that salt forms exhibit the highest cardiotoxic probability, followed by the metabolites and pristine forms. Additionally, all forms have more affinity to the upper layer of the realistic myocardial membrane. Meanwhile, an ideal membrane consisting of a single type of phospholipids is not capable of capturing the specific interactions of each drug form. These findings confirm that cardiotoxic mechanisms are membrane-layer and drug-form dependent.
Pupil responses to colorfulness are selectively reduced in healthy older adults
Authors: van Leeuwen Janneke E. P. , McDougall Amy , Mylonas Dimitris , Suárez-González Aida , Crutch Sebastian J. , Warren Jason D.
Published: December 2023

The alignment between visual pathway signaling and pupil dynamics offers a promising non-invasive method to further illuminate the mechanisms of human color perception. However, only limited research has been done in this area and the effects of healthy aging on pupil responses to the different color components have not been studied yet. Here we aim to address this by modelling the effects of color lightness and chroma (colorfulness) on pupil responses in young and older adults, in a closely controlled passive viewing experiment with 26 broad-spectrum digital color fields. We show that pupil responses to color lightness and chroma are independent from each other in both young and older adults. Pupil responses to color lightness levels are unaffected by healthy aging, when correcting for smaller baseline pupil sizes in older adults. Older adults exhibit weaker pupil responses to chroma increases, predominantly along the Green–Magenta axis, while relatively sparing the Blue–Yellow axis. Our findings complement behavioral studies in providing physiological evidence that colors fade with age, with implications for color-based applications and interventions both in healthy aging and later-life neurodegenerative disorders.
surviveR: a flexible shiny application for patient survival analysis
Authors: Sessler Tamas , Quinn Gerard P. , Wappett Mark , Rogan Emily , Sharkey David , Ahmaderaghi Baharak , Lawler Mark , Longley Daniel B. , McDade Simon S.
Published: December 2023

Kaplan–Meier (KM) survival analyses based on complex patient categorization due to the burgeoning volumes of genomic, molecular and phenotypic data, are an increasingly important aspect of the biomedical researcher’s toolkit. Commercial statistics and graphing packages for such analyses are functionally limited, whereas open-source tools have a high barrier-to-entry in terms of understanding of methodologies and computational expertise. We developed surviveR to address this unmet need for a survival analysis tool that can enable users with limited computational expertise to conduct routine but complex analyses. surviveR is a cloud-based Shiny application, that addresses our identified unmet need for an easy-to-use web-based tool that can plot and analyse survival based datasets. Integrated customization options allows a user with limited computational expertise to easily filter patients to enable custom cohort generation, automatically calculate log-rank test and Cox hazard ratios. Continuous datasets can be integrated, such as RNA or protein expression measurements which can be then used as categories for survival plotting. We further demonstrate the utility through exemplifying its application to a clinically relevant colorectal cancer patient dataset. surviveR is a cloud-based web application available at https://generatr.qub.ac.uk/app/surviveR, that can be used by non-experts users to perform complex custom survival analysis.
Ultrasound performance in pediatric deep soft-tissue tumor characterization
Authors: Li Cong , Chen Wenyi , Jin Ya , Xu Hong , Luo Hong
Published: December 2023

This study investigated the performance of ultrasonography in diagnosing deep soft-tissue tumors and tumor-like lesions in children with histological results. Demographic information and ultrasound characteristics of benign and malignant masses were statistically analyzed. Three radiologists (Radiologists 1, 2, and 3) independently reviewed the ultrasonography studies while being blinded to the medical history and other imaging findings. The 82 lesions included in the study were histopathologically classified as malignant (n = 25) or benign (n = 57). No statistically significant differences were observed between the benign and malignant subgroups regarding age (p = 0.059), sex (p = 1.0), disease course (p = 0.812), presence or absence of symptoms (p = 0.534), maximum diameter (p = 0.359), margin (p = 1.0), calcification (p = 0.057), or blood Adler type (p = 0.563). However, statistically significant differences were observed between the benign and malignant subgroups in terms of isolated or Multiple occurrences (p < 0.001), history of malignancy (p < 0.001), shape (p < 0.001), and echogenicity (p < 0.001). Parameters such as tumor shape (p = 0.042, OR = 6.222), single or multiple occurrences (p = 0.008, OR = 17.000), and history of malignancy (p = 0.038, OR = 13.962) were identified as independent predictors of benign and malignant tumors. The diagnostic sensitivities evaluated by the three radiologists were 68.0%, 72.0%, 96.0%, respectively, while the specificities were 77.2%, 82.5%, 77.2%, respectively. Ultrasound demonstrates good performance in the diagnosis of benign deep lesions such as hemangiomas/venous malformation and adipocytic tumors. Multiple irregular morphologies and a history of malignancy were identified as independent risk factors for malignant masses. The experience of radiologists in recognizing specific tumors is important. Careful attention should be paid to masses with ambiguous ultrasound features, as well as small lesions.
Longing for touch post-COVID-19: current observations and future directions
Authors: Hasenack Birgit , Meijer Larissa L. , van Harmelen Anna , Overvliet Krista E. , Keizer Anouk
Published: December 2023

Previous studies have reported an association between the COVID-19 pandemic, social distancing regulations and longing for touch (LFT; i.e., a discrepancy between actual touch frequency and one’s desire to be touched). However, less is known about the prevalence and severity of LFT in the general population in the absence of social distancing regulations. The aim of this study was therefore to exploratively compare data collected during and after the pandemic. Pandemic data was collected online in an international sample (n = 1982), of which a matched subsample (n = 115) was used in the reported analyses. Post-pandemic data was collected one week after social distancing regulations restrictions were lifted in the Netherlands (n = 60) and when virtually no restrictions were in place (n = 55). The severity of LFT was significantly higher during the pandemic than afterwards. Although there were no significant differences in the general prevalence of LFT, significantly more participants reported high levels of LFT (score of 75–100) during the pandemic. We cautiously conclude that, although LFT may have peaked during the pandemic, a large portion of the general population desires to experience more interpersonal touch, even in the absence of social distancing regulations.
Combination of melt-electrospun poly-ε-caprolactone scaffolds and hepatocyte-like cells from footprint-free hiPSCs to create 3D biohybrid constructs for liver tissue engineering
Authors: Weber Josefin , Linti Carsten , Lörch Christiane , Weber Marbod , Andt Madelene , Schlensak Christian , Wendel Hans Peter , Doser Michael , Avci-Adali Meltem
Published: December 2023

The liver is a vital organ with numerous functions, including metabolic functions, detoxification, and the synthesis of secretory proteins. The increasing prevalence of liver diseases requires the development of effective treatments, models, and regenerative approaches. The field of liver tissue engineering represents a significant advance in overcoming these challenges. In this study, 3D biohybrid constructs were created by combining hepatocyte-like cells (HLCs) derived from patient-specific footprint-free human induced pluripotent stem cells (hiPSCs) and 3D melt-electrospun poly-ε-caprolactone (PCL) scaffolds. First, a differentiation procedure was established to obtain autologous HCLs from hiPSCs reprogrammed from renal epithelial cells using self-replicating mRNA. The obtained cells expressed hepatocyte-specific markers and exhibited important hepatocyte functions, such as albumin synthesis, cytochrome P450 activity, glycogen storage, and indocyanine green metabolism. Biocompatible PCL scaffolds were fabricated by melt-electrospinning and seeded with pre-differentiated hepatoblasts, which uniformly attached to the fibers of the scaffolds and successfully matured into HLCs. The use of patient-specific, footprint-free hiPSC-derived HLCs represents a promising cell source for personalized liver regeneration strategies. In combination with biocompatible 3D scaffolds, this innovative approach has a broader range of applications spanning liver tissue engineering, drug testing and discovery, and disease modeling.
Human iPSC-derived microglia carrying the LRRK2-G2019S mutation show a Parkinson’s disease related transcriptional profile and function
Authors: Ohtonen Sohvi , Giudice Luca , Jäntti Henna , Fazaludeen Mohammad Feroze , Shakirzyanova Anastasia , Gómez-Budia Mireia , Välimäki Nelli-Noora , Niskanen Jonna , Korvenlaita Nea , Fagerlund Ilkka , Koistinaho Jari , Amiry-Moghaddam Mahmood , Savchenko Ekaterina , Roybon Laurent , Lehtonen Šárka , Korhonen Paula , Malm Tarja
Published: December 2023

LRRK2-G2019S is one of the most common Parkinson’s disease (PD)-associated mutations and has been shown to alter microglial functionality. However, the impact of LRRK2-G2019S on transcriptional profile of human induced pluripotent stem cell-derived microglia-like cells (iMGLs) and how it corresponds to microglia in idiopathic PD brain is not known. Here we demonstrate that LRRK2-G2019S carrying iMGL recapitulate aspects of the transcriptional signature of human idiopathic PD midbrain microglia. LRRK2-G2019S induced subtle and donor-dependent alterations in iMGL mitochondrial respiration, phagocytosis and cytokine secretion. Investigation of microglial transcriptional state in the midbrains of PD patients revealed a subset of microglia with a transcriptional overlap between the in vitro PD-iMGL and human midbrain PD microglia. We conclude that LRRK2-G2019S iMGL serve as a model to study PD-related effects in human microglia.
Discrimination of finger movements by magnetomyography with optically pumped magnetometers
Authors: Greco Antonino , Baek Sangyeob , Middelmann Thomas , Mehring Carsten , Braun Christoph , Marquetand Justus , Siegel Markus
Published: December 2023

Optically pumped magnetometers (OPM) are quantum sensors that offer new possibilities to measure biomagnetic signals. Compared to the current standard surface electromyography (EMG), in magnetomyography (MMG), OPM sensors offer the advantage of contactless measurements of muscle activity. However, little is known about the relative performance of OPM-MMG and EMG, e.g. in their ability to detect and classify finger movements. To address this in a proof-of-principle study, we recorded simultaneous OPM-MMG and EMG of finger flexor muscles for the discrimination of individual finger movements on a single human participant. Using a deep learning model for movement classification, we found that both sensor modalities were able to discriminate finger movements with above 89% accuracy. Furthermore, model predictions for the two sensor modalities showed high agreement in movement detection (85% agreement; Cohen’s kappa: 0.45). Our findings show that OPM sensors can be employed for contactless discrimination of finger movements and incentivize future applications of OPM in magnetomyography.
The role of captopril in leukotriene deficient type 1 diabetic mice
Authors: Guimarães João Pedro Tôrres , Queiroz Luiz A. D. , Menikdiwela Kalhara R. , Pereira Nayara , Ramalho Theresa , Jancar Sonia , Moustaid-Moussa Naima , Martins Joilson O.
Published: December 2023

T1D can be associated with metabolic disorders and several impaired pathways, including insulin signaling, and development of insulin resistance through the renin-angiotensin system (RAS). The main precursor of RAS is angiotensinogen (Agt) and this system is often linked to autophagy dysregulation. Dysregulated autophagy has been described in T1D and linked to impairments in both glucose metabolism, and leukotrienes (LTs) production. Here, we have investigated the role of RAS and LTs in both muscle and liver from T1D mice, and its effects on insulin and autophagy pathways. We have chemically induced T1D in 129sve and 129sve 5LO−/− mice (lacking LTs) with streptozotocin (STZ). To further inhibit ACE activity, mice were treated with captopril (Cap). In muscle of T1D mice, treatment with Cap increased the expression of RAS (angiotensinogen and angiotensin II receptor), insulin signaling, and autophagy markers, regardless of the genotype. In the liver of T1D mice, the treatment with Cap increased the expression of RAS and insulin signaling markers, mostly when LTs were absent. 5LO−/− T1D mice showed increased insulin sensitivity, and decreased NEFA, after the Cap treatment. Cap treatment impacted both insulin signaling and autophagy pathways at the mRNA levels in muscle and liver, indicating the potential role of ACE inhibition on insulin sensitivity and autophagy in T1D.
Combined clinical and ultrasound criteria could accurately predict the Y chromosome in primary amenorrhea patient
Authors: Sumapraja Kanadi , Pangastuti Niken Pudji , Ikhsan Muhammad , Harzif Achmad Kemal , Maidarti Mila
Published: December 2023

This study aimed to assess the combined clinical and ultrasound criteria as a diagnostic tool for screening the Y chromosome related to primary amenorrhea. This cross-sectional study involving 59 subjects was taken from medical records at the Reproductive Immunoendocrinology Polyclinic of Cipto Mangunkusumo General Hospital, Jakarta, Indonesia. The medical records of subjects were then cross-checked with karyotyping analysis results. Sensitivity, specificity, and predictive values were analyzed to assess the criteria. Two subjects were presented with a Y chromosome, and one without a Y chromosome was misclassified into another group. After analysis, we found that combined clinical and ultrasound criteria could predict the Y chromosome related to primary amenorrhea with 95.9% accuracy, with sensitivity and specificity of 80% and 97.96%, respectively. Combined clinical and ultrasound criteria (introduced as Kanadi Sumapraja Criteria) could be used as a diagnostic tool for screening a Y chromosome related to primary amenorrhea.
On enhancing the noise-reduction performance of the acoustic lined duct utilizing the phase-modulating metasurface
Authors: Ou Yang , Zhao Yonghui
Published: December 2023

This work proposes a noise-reduction structure that integrates phase-modulating metasurface (PMM) with acoustic liners (ALs) to enhance the narrow band absorption performance of a duct with relatively small length-diameter ratio. The PMM manipulates the wavefront by introducing different transmission phase shifts based on an array of Helmholtz resonators, so that the spinning wave within the duct can be generated. Compared with the plane wave, the generated spinning wave has a lower group velocity, which results in a greater traveling distance over the ALs in the duct. The optimization design is performed to determine the final structural parameters of the PMM, which is based on the predictions of the amplitude and phase shift of the acoustic wave at the outlet of the PMM using the theory of passive phased array. With the manipulation of the PMM, the incident plane wave is modulated into a spinning wave, and then enters into the acoustic liner duct (ALD), whose structural parameters are optimized by maximizing the transmission loss using the mode-matching technique. Finally, the noise-reduction performance of this combined structure is evaluated by numerical simulations in the presence of grazing flow. The results demonstrate that, compared with the traditional ALD, the proposed structure exhibits a significant increase in transmission loss within the considered frequency band, especially near the peak frequency of the narrow band noise.
Spatio-temporal analysis of land use land cover change and its impact on land surface temperature of Sialkot City, Pakistan
Authors: Javaid Kainat , Ghafoor Gul Zareen , Sharif Faiza , Shahid Memuna Ghafoor , Shahzad Laila , Ghafoor Naghmana , Hayyat Muhammad Umar , Farhan Muhammad
Published: December 2023

The dynamic interplay between urbanization and its impacts on climate is a subject of recent concern, particularly in rapidly urbanizing cities of Pakistan. This research investigated the spatio-temporal effects of urban growth in terms of Land Use Land Cover changes on the thermal environment (Land Surface Temperature) of the Sialkot city, Pakistan using satellite data spanning four distinct time periods (1989, 2000, 2009 and 2020) and predicted changes for year 2030 by employing Cellular Automata Markov Chain Model. Satellite imagery (Landsat 5, 7 and 8) was processed, and maximum likelihood supervised classification was done to generate LULC maps for each of the aforementioned years. In addition to LULC classification, thermal bands of satellite data (for summer and winter) were processed to compute Land Surface Temperature (LST) of the city. The prediction of LULC changes and LST was done for year 2030 using Cellular Automata Markov Chain Model. The accuracy of classified and prediction maps was checked using Kappa Index. The LULC analysis revealed 4.14% increase in the built-up area and 3.43% decrease in vegetation cover of the city during 1989 to 2020. Both land covers are expected to change in the future (year 2030) by + 1.31% (built-up) and − 1.1% (vegetation). Furthermore, a declining trend in the barren land and water bodies was also observed over time. These LULC changes were found affecting the LST of study area. The transformation of vegetation cover into built-up area resulted in an increase in LST over time. A notable rise of 4.5 °C (summer) and 5.7 °C (winter) in the mean LST of Sialkot was observed during 1989 to 2020 and further increases are anticipated in year 2030. This study calls for attention of the policy makers to reduce human impact on the local climate of the city. The study will also help city developers in analyzing the urban population growth trend, finding suitable location to built new infrastructure by governmental authorities and how the rising temperature can affect energy demand and agriculture production of the city in future.
Environmental uncertainty and digital technologies corporate in shaping corporate green behavior and tax avoidance
Authors: Ao Xiang-Yuan , Ong Tze San , Aprile Roberto , Di Vaio Assunta
Published: December 2023

This study contributes to the field of sustainability by analyzing changes in firms following the adoption of new environmental protection laws to meet community sustainability needs. Focusing on the Chinese context, it examined the relationship between firms' environmental protection measures (i.e., corporate green behavior) and profitability (i.e., corporate tax avoidance). The moderating roles of environmental uncertainty and digital technology application in this relationship were also investigated. The findings offer insights into the complex dynamics linking firms’ environmental initiatives to their business outcomes and financial decisions within the framework of a sustainable community. Ultimately, this study highlights the importance and implications of sustainable practices for both the environment and corporate financial performance. Firms’ environmental behaviors are enablers of sustainable communities by deploying natural resources and creating a more resilient economy through active community participation in green production models.
Effect of freeze–thaw manipulation on phytostabilization of industrially contaminated soil with halloysite nanotubes
Authors: Radziemska Maja , Gusiatin Mariusz Z. , Cydzik-Kwiatkowska Agnieszka , Blazejczyk Aurelia , Majewski Grzegorz , Jaskulska Iwona , Brtnicky Martin
Published: December 2023

The latest trends in improving the performance properties of soils contaminated with potentially toxic elements (PTEs) relate to the possibility of using raw additives, including halloysite nanotubes (HNTs) due to eco-friendliness, and inexpensiveness. Lolium perenne L. was cultivated for 52 days in a greenhouse and then moved to a freezing–thawing chamber for 64 days. HNT addition into PTE-contaminated soil cultivated with grass under freezing–thawing conditions (FTC) was tested to demonstrate PTE immobilization during phytostabilization. The relative yields increased by 47% in HNT-enriched soil in a greenhouse, while under FTC decreased by 17% compared to the adequate greenhouse series. The higher PTE accumulation in roots in HNT presence was evident both in greenhouse and chamber conditions. (Cr/Cd and Cu)-relative contents were reduced in soil HNT-enriched-not-FTC-exposed, while (Cr and Cu) in HNT-enriched-FTC-exposed. PTE-immobilization was discernible by (Cd/Cr/Pb and Zn)-redistribution into the reducible fraction and (Cu/Ni and Zn) into the residual fraction in soil HNT-enriched-not-FTC-exposed. FTC and HNT facilitated transformation to the residual fraction mainly for Pb. Based on PTE-distribution patterns and redistribution indexes, HNT’s role in increasing PTE stability in soils not-FTC-exposed is more pronounced than in FTC-exposed compared to the adequate series. Sphingomonas, Acidobacterium, and Mycobacterium appeared in all soils. HNTs mitigated FTC’s negative effect on microbial diversity and increased Planctomycetia abundance.
Efficient agricultural practices in Africa reduce crop water footprint despite climate change, but rely on blue water resources
Authors: Giordano Vittorio , Tuninetti Marta , Laio Francesco
Published: December 2023

Alarming projections of climate change, decline in crop yields, and increased food demand constitute daunting threats to African food production and sustainable water management. Here, we map this complex water-food nexus by combining gridded climate data and process-based crop modelling to quantify scenarios of crop water footprint under Representative Concentration Pathway 2.6 and Representative Concentration Pathway 6.0 for time horizons 2040, 2070 and 2100. We show that high-input agricultural management coupled with the expansion of irrigation infrastructure could generate an average reduction of water use intensity up to 64% for staple crops, but only 5% for cash crops, by 2040. Notwithstanding the positive effect of intensification, between 82 Km3 (2040) and 102 Km3 (2100) of additional blue water will be required to sustain the increased yields. Our scenarios are suited for identifying locations where crops are subject to high climate impacts and where crop production shows trade-offs between high-input management and irrigation demand.
Substantial blue carbon sequestration in the world’s largest seagrass meadow
Authors: Fu Chuancheng , Frappi Sofia , Havlik Michelle Nicole , Howe Wells , Harris S. David , Laiolo Elisa , Gallagher Austin J. , Masqué Pere , Duarte Carlos M.
Published: December 2023

Seagrass meadows are important sinks for organic carbon and provide co-benefits. However, data on the organic carbon stock in seagrass sediments are scarce for many regions, particularly The Bahamas, which accounts for up to 40.7% of the documented global seagrass area, limiting formulation of blue carbon strategies. Here, we sampled 10 seagrass meadows across an extensive island chain in The Bahamas. We estimate that Bahamas seagrass meadows store 0.42–0.59 Pg organic carbon in the top-meter sediments with an accumulation rate of 2.1–2.9 Tg annually, representing a substantial global blue carbon hotspot. Autochthonous organic carbon in sediments decreased from ~1980 onwards, with concomitant increases in cyanobacterial and mangrove contributions, suggesting disturbance of seagrass ecosystems, likely caused by tourism and maritime traffic activities. This study provides seagrass blue carbon data from a vast, understudied region and contributes to improving climate action for The Bahamas and the Greater Caribbean region.