bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermospheric Temperature and ΣO/N2 Variations as Observed by GOLD and Compared to MSIS and WACCM‐X Simulations During 2019–2020 at Deep Solar Minimum
Authors: Liu Guiping , Rowland Douglas E. , Gan Quan , Liu Han‐Li , Klenzing Jeffrey H. , England Scott L. , Eastes Richard W.
Published: May 2023

The ultraviolet‐imaging spectrograph that comprises Global‐scale Observations of the Limb and Disk (GOLD) mission in geostationary orbit at 47.5°W longitude has taken full disk images at high cadence throughout the deep solar minimum period of 2019–2020. Synoptic (i.e., concurrent and spatially unified and resolved) observations of thermospheric temperature and composition at ∼150 km altitude are made for the first time, allowing GOLD to disambiguate temporal and spatial variations. Here we analyze the daytime effective temperature and column integrated O and N2 density ratio (ΣO/N2) data simultaneously observed by GOLD over 120°W–20°E longitude and 60°S–60°N latitude from 13 October 2019 to 12 October 2020. Daily zonal mean values are calculated for each latitude and compared with NRLMSIS 2.0 and simulations from the Whole Atmosphere Community Climate Model with thermosphere and ionosphere extension (WACCM‐X). On average, the GOLD observations show higher temperatures than Mass Spectrometer Incoherent Scatter radar (MSIS) and WACCM‐X by ∼20–60 K (5%–10%) and 80–120 K (12%–18%), respectively. The ΣO/N2 ratios observed by GOLD are larger than the MSIS results by ∼0.4 (40%) but smaller than the WACCM‐X simulations by ∼0.3 (30%). The observed and modeled results are correlated at most latitudes (r = 0.4–0.8), and GOLD, MSIS, and WACCM‐X all display a similar seasonal variation and change with latitude. WACCM‐X simulates a larger annual variation in ΣO/N2, suggesting that the thermospheric circulation is overestimated and atmospheric waves and turbulence transport are not properly represented in the model.
Macrophages in immunoregulation and therapeutics
Authors: Chen Shanze , Saeed Abdullah F.U.H. , Liu Quan , Jiang Qiong , Xu Haizhao , Xiao Gary Guishan , Rao Lang , Duo Yanhong
Published: May 2023

Macrophages exist in various tissues, several body cavities, and around mucosal surfaces and are a vital part of the innate immune system for host defense against many pathogens and cancers. Macrophages possess binary M1/M2 macrophage polarization settings, which perform a central role in an array of immune tasks via intrinsic signal cascades and, therefore, must be precisely regulated. Many crucial questions about macrophage signaling and immune modulation are yet to be uncovered. In addition, the clinical importance of tumor-associated macrophages is becoming more widely recognized as significant progress has been made in understanding their biology. Moreover, they are an integral part of the tumor microenvironment, playing a part in the regulation of a wide variety of processes including angiogenesis, extracellular matrix transformation, cancer cell proliferation, metastasis, immunosuppression, and resistance to chemotherapeutic and checkpoint blockade immunotherapies. Herein, we discuss immune regulation in macrophage polarization and signaling, mechanical stresses and modulation, metabolic signaling pathways, mitochondrial and transcriptional, and epigenetic regulation. Furthermore, we have broadly extended the understanding of macrophages in extracellular traps and the essential roles of autophagy and aging in regulating macrophage functions. Moreover, we discussed recent advances in macrophages-mediated immune regulation of autoimmune diseases and tumorigenesis. Lastly, we discussed targeted macrophage therapy to portray prospective targets for therapeutic strategies in health and diseases.
Accelerated aging in articular cartilage by ZMPSTE24 deficiency leads to osteoarthritis with impaired metabolic signaling and epigenetic regulation
Authors: Suo Jinlong , Shao Rui , Yang Ruici , Wang Jinghui , Zhang Zhong , Wang Duo , Niu Ningning , Zheng Xianyou , Zou Weiguo
Published: May 2023

Osteoarthritis (OA) is an age-related degenerative disease without disease-modifying therapy. The lack of aging-induced osteoarthritis models makes the discovery of therapeutic drugs more challenging. The deficiency of ZMPSTE24 could induce Hutchinson–Gilford progeria syndrome (HGPS), a genetic disorder of rapid aging. However, the relationship between HGPS and OA remains unclear. Our results found that the expression of Zmpste24 was decreased in the articular cartilage during the aging process. Zmpste24 knockout mice, Prx1-Cre; Zmpste24fl/fl mice and Col2-CreERT2; Zmpste24fl/fl mice displayed OA phenotype. Loss of Zmpste24 in articular cartilage could exacerbate the occurrence and development of osteoarthritis. Transcriptome sequencing revealed that deletion of Zmpste24 or accumulation of progerin affects chondrocyte metabolism, inhibits cell proliferation and promotes cell senescence. Using this animal model, we elucidate the upregulation of H3K27me3 during chondrocyte senescence and discover the molecular mechanism by which lamin A mutant stabilizes EZH2 expression. The construction of aging-induced osteoarthritis models and the elucidation of the signaling pathways and molecular mechanisms of articular chondrocyte senescence would benefit the discovery and development of new drugs for OA.
The deleted in oral cancer (DOC1 aka CDK2AP1) tumor suppressor gene is downregulated in oral squamous cell carcinoma by multiple microRNAs
Authors: Stabile Roberto , Cabezas Mario Román , Verhagen Mathijs P. , Tucci Francesco A. , van den Bosch Thierry P. P. , De Herdt Maria J. , van der Steen Berdine , Nigg Alex L. , Chen Meng , Ivan Cristina , Shimizu Masayoshi , Koljenović Senada , Hardillo Jose A. , Verrijzer C. Peter , Baatenburg de Jong Robert J. , Calin George A. , Fodde Riccardo
Published: May 2023

Cyclin-dependent kinase 2-associated protein 1 (CDK2AP1; also known as deleted in oral cancer or DOC1) is a tumor suppressor gene known to play functional roles in both cell cycle regulation and in the epigenetic control of embryonic stem cell differentiation, the latter as a core subunit of the nucleosome remodeling and histone deacetylation (NuRD) complex. In the vast majority of oral squamous cell carcinomas (OSCC), expression of the CDK2AP1 protein is reduced or lost. Notwithstanding the latter (and the DOC1 acronym), mutations or deletions in its coding sequence are extremely rare. Accordingly, CDK2AP1 protein-deficient oral cancer cell lines express as much CDK2AP1 mRNA as proficient cell lines. Here, by combining in silico and in vitro approaches, and by taking advantage of patient-derived data and tumor material in the analysis of loss of CDK2AP1 expression, we identified a set of microRNAs, namely miR-21-5p, miR-23b-3p, miR-26b-5p, miR-93-5p, and miR-155-5p, which inhibit its translation in both cell lines and patient-derived OSCCs. Of note, no synergistic effects were observed of the different miRs on the CDK2AP1–3-UTR common target. We also developed a novel approach to the combined ISH/IF tissue microarray analysis to study the expression patterns of miRs and their target genes in the context of tumor architecture. Last, we show that CDK2AP1 loss, as the result of miRNA expression, correlates with overall survival, thus highlighting the clinical relevance of these processes for carcinomas of the oral cavity.
Clinical diagnosis of genetic disorders at both single-nucleotide and chromosomal levels based on BGISEQ-500 platform
Authors: Liu Yanqiu , Mao Liangwei , Huang Hui , Li Wei , Man Jianfen , Zhang Wenqian , Wang Lina , Li Long , Sun Yan , Zhai Teng , Guo Xueqin , Du Lique , Huang Jin , Li Hao , Wan Yang , Wei Xiaoming
Published: May 2023

Most variations in the human genome refer to single-nucleotide variation (SNV), small fragment insertions and deletions, and genomic copy number variation (CNV). Many human diseases including genetic disorders are associated with variations in the genome. These disorders are often difficult to be diagnosed because of their complex clinical conditions, therefore, an effective detection method is needed to facilitate clinical diagnosis and prevent birth defects. With the development of high-throughput sequencing technology, the method of targeted sequence capture chip has been extensively used owing to its high throughput, high accuracy, fast speed, and low cost. In this study, we designed a chip that potentially captured the coding region of 3043 genes associated with 4013 monogenic diseases, with an addition of 148 chromosomal abnormalities that can be identified by targeting specific regions. To assess the efficiency, a strategy of combining the BGISEQ500 sequencing platform with the designed chip was utilized to screen variants in 63 patients. Eventually, 67 disease-associated variants were found, 31 of which were novel. The results of the evaluation test also show that this combined strategy complies with the requirements of clinical testing and has proper clinical application value.
Accuracy of cuff blood pressure and systolic blood pressure amplification
Authors: Bui Tan V. , Picone Dean S. , Schultz Martin G. , Peng Xiaoqing , Black J. Andrew , Dwyer Nathan , Roberts-Thomson Philip , Adams Heath , Chen Chen-Huan , Cheng Hao-min , Pucci Giacomo , Wang Jiguang , Goupil Remi , Sharman James E.
Published: May 2023

Automated cuff measured blood pressure (BP) is the global standard used for diagnosing hypertension, but there are concerns regarding the accuracy of the method. Individual variability in systolic BP (SBP) amplification from central (aorta) to peripheral (brachial) arteries could be related to the accuracy of cuff BP, but this has never been determined and was the aim of this study. Automated cuff BP and invasive brachial BP were recorded in 795 participants (74% male, aged 64 ± 11 years) receiving coronary angiography at five independent research sites (using seven different automated cuff BP devices). SBP amplification was recorded invasively by catheter and defined as brachial SBP minus aortic SBP. Compared with invasive brachial SBP, cuff SBP was significantly underestimated (130 ± 18 mmHg vs. 138 ± 22 mmHg, p < 0.001). The level of SBP amplification varied significantly among individuals (mean ± SD, 7.3 ± 9.1 mmHg) and was similar to level of difference between cuff and invasive brachial SBP (mean difference –7.6 ± 11.9 mmHg). SBP amplification explained most of the variance in accuracy of cuff SBP (R2 = 19%). The accuracy of cuff SBP was greatest among participants with the lowest SBP amplification (ptrend < 0.001). After cuff BP values were corrected for SBP amplification, there was a significant improvement in the mean difference from the intra-arterial standard (p < 0.0001) and in the accuracy of hypertension classification according to 2017 ACC/AHA guideline thresholds (p = 0.005). The level of SBP amplification is a critical factor associated with the accuracy of conventional automated cuff measured BP.
Neural-network decoders for measurement induced phase transitions
Authors: Dehghani Hossein , Lavasani Ali , Hafezi Mohammad , Gullans Michael J.
Published: May 2023

Open quantum systems have been shown to host a plethora of exotic dynamical phases. Measurement-induced entanglement phase transitions in monitored quantum systems are a striking example of this phenomena. However, naive realizations of such phase transitions requires an exponential number of repetitions of the experiment which is practically unfeasible on large systems. Recently, it has been proposed that these phase transitions can be probed locally via entangling reference qubits and studying their purification dynamics. In this work, we leverage modern machine learning tools to devise a neural network decoder to determine the state of the reference qubits conditioned on the measurement outcomes. We show that the entanglement phase transition manifests itself as a stark change in the learnability of the decoder function. We study the complexity and scalability of this approach in both Clifford and Haar random circuits and discuss how it can be utilized to detect entanglement phase transitions in generic experiments.
Reference-free assembly of long-read transcriptome sequencing data with RNA-Bloom2
Authors: Nip Ka Ming , Hafezqorani Saber , Gagalova Kristina K. , Chiu Readman , Yang Chen , Warren René L. , Birol Inanc
Published: May 2023

Long-read sequencing technologies have improved significantly since their emergence. Their read lengths, potentially spanning entire transcripts, is advantageous for reconstructing transcriptomes. Existing long-read transcriptome assembly methods are primarily reference-based and to date, there is little focus on reference-free transcriptome assembly. We introduce “RNA-Bloom2 [https://github.com/bcgsc/RNA-Bloom]”, a reference-free assembly method for long-read transcriptome sequencing data. Using simulated datasets and spike-in control data, we show that the transcriptome assembly quality of RNA-Bloom2 is competitive to those of reference-based methods. Furthermore, we find that RNA-Bloom2 requires 27.0 to 80.6% of the peak memory and 3.6 to 10.8% of the total wall-clock runtime of a competing reference-free method. Finally, we showcase RNA-Bloom2 in assembling a transcriptome sample of Picea sitchensis (Sitka spruce). Since our method does not rely on a reference, it further sets the groundwork for large-scale comparative transcriptomics where high-quality draft genome assemblies are not readily available.
Decentralized federated learning through proxy model sharing
Authors: Kalra Shivam , Wen Junfeng , Cresswell Jesse C. , Volkovs Maksims , Tizhoosh H. R.
Published: May 2023

Institutions in highly regulated domains such as finance and healthcare often have restrictive rules around data sharing. Federated learning is a distributed learning framework that enables multi-institutional collaborations on decentralized data with improved protection for each collaborator’s data privacy. In this paper, we propose a communication-efficient scheme for decentralized federated learning called ProxyFL, or proxy-based federated learning. Each participant in ProxyFL maintains two models, a private model, and a publicly shared proxy model designed to protect the participant’s privacy. Proxy models allow efficient information exchange among participants without the need of a centralized server. The proposed method eliminates a significant limitation of canonical federated learning by allowing model heterogeneity; each participant can have a private model with any architecture. Furthermore, our protocol for communication by proxy leads to stronger privacy guarantees using differential privacy analysis. Experiments on popular image datasets, and a cancer diagnostic problem using high-quality gigapixel histology whole slide images, show that ProxyFL can outperform existing alternatives with much less communication overhead and stronger privacy.
Upregulation of breathing rate during running exercise by central locomotor circuits in mice
Authors: Hérent Coralie , Diem Séverine , Usseglio Giovanni , Fortin Gilles , Bouvier Julien
Published: May 2023

While respiratory adaptation to exercise is compulsory to cope with the increased metabolic demand, the neural signals at stake remain poorly identified. Using neural circuit tracing and activity interference strategies in mice, we uncover here two systems by which the central locomotor network can enable respiratory augmentation in relation to running activity. One originates in the mesencephalic locomotor region (MLR), a conserved locomotor controller. Through direct projections onto the neurons of the preBötzinger complex that generate the inspiratory rhythm, the MLR can trigger a moderate increase of respiratory frequency, prior to, or even in the absence of, locomotion. The other is the lumbar enlargement of the spinal cord containing the hindlimb motor circuits. When activated, and through projections onto the retrotrapezoid nucleus (RTN), it also potently upregulates breathing rate. On top of identifying critical underpinnings for respiratory hyperpnea, these data also expand the functional implication of cell types and pathways that are typically regarded as “locomotor” or “respiratory” related.
Spectroscopic signature of obstructed surface states in SrIn2P2
Authors: Liu Xiang-Rui , Deng Hanbin , Liu Yuntian , Yin Zhouyi , Chen Congrun , Zhu Yu-Peng , Yang Yichen , Jiang Zhicheng , Liu Zhengtai , Ye Mao , Shen Dawei , Yin Jia-Xin , Wang Kedong , Liu Qihang , Zhao Yue , Liu Chang
Published: May 2023

The century-long development of surface sciences has witnessed the discoveries of a variety of quantum states. In the recently proposed “obstructed atomic insulators”, symmetric charges are pinned at virtual sites where no real atoms reside. The cleavage through these sites could lead to a set of obstructed surface states with partial electronic occupation. Here, utilizing scanning tunneling microscopy, angle-resolved photoemission spectroscopy and first-principles calculations, we observe spectroscopic signature of obstructed surface states in SrIn2P2. We find that a pair of surface states that are originated from the pristine obstructed surface states split in energy by a unique surface reconstruction. The upper branch is marked with a striking differential conductance peak followed by negative differential conductance, signaling its localized nature, while the lower branch is found to be highly dispersive. This pair of surface states is in consistency with our calculational results. Our finding not only demonstrates a surface quantum state induced by a new type of bulk-boundary correspondence, but also provides a platform for exploring efficient catalysts and related surface engineering.
Chemo-mechanical diffusion waves explain collective dynamics of immune cell podosomes
Authors: Gong Ze , van den Dries Koen , Migueles-Ramírez Rodrigo A. , Wiseman Paul W. , Cambi Alessandra , Shenoy Vivek B.
Published: May 2023

Immune cells, such as macrophages and dendritic cells, can utilize podosomes, mechanosensitive actin-rich protrusions, to generate forces, migrate, and patrol for foreign antigens. Individual podosomes probe their microenvironment through periodic protrusion and retraction cycles (height oscillations), while oscillations of multiple podosomes in a cluster are coordinated in a wave-like fashion. However, the mechanisms governing both the individual oscillations and the collective wave-like dynamics remain unclear. Here, by integrating actin polymerization, myosin contractility, actin diffusion, and mechanosensitive signaling, we develop a chemo-mechanical model for podosome dynamics in clusters. Our model reveals that podosomes show oscillatory growth when actin polymerization-driven protrusion and signaling-associated myosin contraction occur at similar rates, while the diffusion of actin monomers drives wave-like coordination of podosome oscillations. Our theoretical predictions are validated by different pharmacological treatments and the impact of microenvironment stiffness on chemo-mechanical waves. Our proposed framework can shed light on the role of podosomes in immune cell mechanosensing within the context of wound healing and cancer immunotherapy.
Platelet-derived chemokines promote skeletal muscle regeneration by guiding neutrophil recruitment to injured muscles
Authors: Graca Flavia A. , Stephan Anna , Minden-Birkenmaier Benjamin A. , Shirinifard Abbas , Wang Yong-Dong , Demontis Fabio , Labelle Myriam
Published: May 2023

Skeletal muscle regeneration involves coordinated interactions between different cell types. Injection of platelet-rich plasma is circumstantially considered an aid to muscle repair but whether platelets promote regeneration beyond their role in hemostasis remains unexplored. Here, we find that signaling via platelet-released chemokines is an early event necessary for muscle repair in mice. Platelet depletion reduces the levels of the platelet-secreted neutrophil chemoattractants CXCL5 and CXCL7/PPBP. Consequently, early-phase neutrophil infiltration to injured muscles is impaired whereas later inflammation is exacerbated. Consistent with this model, neutrophil infiltration to injured muscles is compromised in male mice with Cxcl7-knockout platelets. Moreover, neo-angiogenesis and the re-establishment of myofiber size and muscle strength occurs optimally in control mice post-injury but not in Cxcl7ko mice and in neutrophil-depleted mice. Altogether, these findings indicate that platelet-secreted CXCL7 promotes regeneration by recruiting neutrophils to injured muscles, and that this signaling axis could be utilized therapeutically to boost muscle regeneration.
Data-driven prediction of complex crystal structures of dense lithium
Authors: Wang Xiaoyang , Wang Zhenyu , Gao Pengyue , Zhang Chengqian , Lv Jian , Wang Han , Liu Haifeng , Wang Yanchao , Ma Yanming
Published: May 2023

Lithium (Li) is a prototypical simple metal at ambient conditions, but exhibits remarkable changes in structural and electronic properties under compression. There has been intense debate about the structure of dense Li, and recent experiments offered fresh evidence for yet undetermined crystalline phases near the enigmatic melting minimum region in the pressure-temperature phase diagram of Li. Here, we report on an extensive exploration of the energy landscape of Li using an advanced crystal structure search method combined with a machine-learning approach, which greatly expands the scale of structure search, leading to the prediction of four complex Li crystal structures containing up to 192 atoms in the unit cell that are energetically competitive with known Li structures. These findings provide a viable solution to the observed yet unidentified crystalline phases of Li, and showcase the predictive power of the global structure search method for discovering complex crystal structures in conjunction with accurate machine learning potentials.
Engineered bacterial outer membrane vesicles encapsulating oncolytic adenoviruses enhance the efficacy of cancer virotherapy by augmenting tumor cell autophagy
Authors: Ban Weiyue , Sun Mengchi , Huang Hanwei , Huang Wanxu , Pan Siwei , Liu Pengfei , Li Bingwu , Cheng Zhenguo , He Zhonggui , Liu Funan , Sun Jin
Published: May 2023

Oncolytic adenovirus (Ad) infection promotes intracellular autophagy in tumors. This could kill cancer cells and contribute to Ads-mediated anticancer immunity. However, the low intratumoral content of intravenously delivered Ads could be insufficient to efficiently activate tumor over-autophagy. Herein, we report bacterial outer membrane vesicles (OMVs)-encapsulating Ads as microbial nanocomposites that are engineered for autophagy-cascade-augmented immunotherapy. Biomineral shells cover the surface antigens of OMVs to slow their clearance during in vivo circulation, enhancing intratumoral accumulation. After entering tumor cells, there is excessive H2O2 accumulation through the catalytic effect of overexpressed pyranose oxidase (P2O) from microbial nanocomposite. This increases oxidative stress levels and triggers tumor autophagy. The autophagy-induced autophagosomes further promote Ads replication in infected tumor cells, leading to Ads-overactivated autophagy. Moreover, OMVs are powerful immunostimulants for remolding the immunosuppressive tumor microenvironment, facilitating antitumor immune response in preclinical cancer models in female mice. Therefore, the present autophagy-cascade-boosted immunotherapeutic method can expand OVs-based immunotherapy.
Ligand-enabled Ni-catalysed enantioconvergent intermolecular Alkyl-Alkyl cross-coupling between distinct Alkyl halides
Authors: Zhao Wen-Tao , Zhang Jian-Xin , Chen Bi-Hong , Shu Wei
Published: May 2023

α-Tertiary aliphatic amides are key elements in organic molecules, which are abundantly present in natural products, pharmaceuticals, agrochemicals, and functional organic materials. Enantioconvergent alkyl-alkyl bond-forming process is one of the most straightforward and efficient, yet highly challenging ways to build such stereogenic carbon centers. Herein, we report an enantioselective alkyl-alkyl cross-coupling between two different alkyl electrophiles to access α-tertiary aliphatic amides. With a newly-developed chiral tridentate ligand, two distinct alkyl halides were successfully cross-coupled together to forge an alkyl-alkyl bond enantioselectively under reductive conditions. Mechanistic investigations reveal that one alkyl halides exclusively undergo oxidative addition with nickel versus in-situ formation of alkyl zinc reagents from the other alkyl halides, rendering formal reductive alkyl-alkyl cross-coupling from easily available alkyl electrophiles without preformation of organometallic reagents.
A smart pathogen detector engineered from intracellular hydrogelation of DNA-decorated macrophages
Authors: Gui Yueyue , Zeng Yujing , Chen Binrui , Yang Yueping , Ma Jiehua , Li Chao
Published: May 2023

Bacterial infection is a major threat to global public health, which urgently requires useful tools to rapidly analyze pathogens in the early stages of infection. Herein, we develop a smart macrophage (Mø)-based bacteria detector, which can recognize, capture, enrich and detect different bacteria and their secreted exotoxins. We transform the fragile native Møs into robust gelated cell particles (GMøs) using photo-activated crosslinking chemistry, which retains membrane integrity and recognition capacity for different microbes. Meanwhile, these GMøs equipped with magnetic nanoparticles and DNA sensing elements can not only respond to an external magnet for facile bacteria collection, but allow the detection of multiple types of bacteria in a single assay. Additionally, we design a propidium iodide-based staining assay to rapidly detect pathogen-associated exotoxins at ultralow concentrations. Overall, these nanoengineered cell particles have broad applicability in the analysis of bacteria, and could potentially be used for the management and diagnosis of infectious diseases.
Senotherapeutic peptide treatment reduces biological age and senescence burden in human skin models
Authors: Zonari Alessandra , Brace Lear E. , Al-Katib Kallie , Porto William F. , Foyt Daniel , Guiang Mylieneth , Cruz Edgar Andres Ochoa , Marshall Bailey , Gentz Melissa , Guimarães Gabriela Rapozo , Franco Octavio L. , Oliveira Carolina R. , Boroni Mariana , Carvalho Juliana L.
Published: May 2023

Cellular senescence is known to play a role in age-related skin function deterioration which potentially influences longevity. Here, a two-step phenotypic screening was performed to identify senotherapeutic peptides, leading to the identification of Peptide (Pep) 14. Pep 14 effectively decreased human dermal fibroblast senescence burden induced by Hutchinson-Gilford Progeria Syndrome (HGPS), chronological aging, ultraviolet-B radiation (UVB), and etoposide treatment, without inducing significant toxicity. Pep 14 functions via modulation of PP2A, an understudied holoenzyme that promotes genomic stability and is involved in DNA repair and senescence pathways. At the single-cell level, Pep 14 modulates genes that prevent senescence progression by arresting the cell cycle and enhancing DNA repair, which consequently reduce the number of cells progressing to late senescence. When applied on aged ex vivo skin, Pep 14 promoted a healthy skin phenotype with structural and molecular resemblance to young ex vivo skin, decreased the expression of senescence markers, including SASP, and reduced the DNA methylation age. In summary, this work shows the safe reduction of the biological age of ex vivo human skins by a senomorphic peptide.
Nationwide genetic analysis of more than 600 families with inherited eye diseases in Argentina
Authors: Schlottmann Patricio G. , Luna José D. , Labat Natalia , Yadarola María Belén , Bainttein Silvina , Esposito Evangelina , Ibañez Agustina , Barbaro Evangelina Ivón , Álvarez Mendiara Alejandro , Picotti Carolina P. , Chirino Misisian Andrea , Andreussi Luciana , Gras Julieta , Capalbo Luciana , Visotto Mauro , Dipierri José E. , Alcoba Emilio , Fernández Gabrielli Laura , Ávila Silvia , Aucar María Emilia , Martin Daniel M. , Ormaechea Gerardo Juan , Inga M. Eugenia , Francone Aníbal A. , Charles Martin , Zompa Tamara , Pérez Pablo Javier , Lotersztein Vanesa , Nuova Pedro J. , Canonero Ivana B. , Mahroo Omar A. , Michaelides Michel , Arno Gavin , Daich Varela Malena
Published: May 2023

This study corresponds to the first large-scale genetic analysis of inherited eye diseases (IED) in Argentina and describes the comprehensive genetic profile of a large cohort of patients. Medical records of 22 ophthalmology and genetics services throughout 13 Argentinian provinces were analyzed retrospectively. Patients with a clinical diagnosis of an ophthalmic genetic disease and a history of genetic testing were included. Medical, ophthalmological and family history was collected. A total of 773 patients from 637 families were included, with 98% having inherited retinal disease. The most common phenotype was retinitis pigmentosa (RP, 62%). Causative variants were detected in 379 (59%) patients.USH2A,RPGR, andABCA4were the most common disease-associated genes.USH2Awas the most frequent gene associated with RP,RDH12early-onset severe retinal dystrophy,ABCA4Stargardt disease,PROM1cone-rod dystrophy, andBEST1macular dystrophy. The most frequent variants wereRPGRc.1345 C > T, p.(Arg449*) andUSH2Ac.15089 C > A, p.(Ser5030*). The study revealed 156/448 (35%) previously unreported pathogenic/likely pathogenic variants and 8 possible founder mutations. We present the genetic landscape of IED in Argentina and the largest cohort in South America. This data will serve as a reference for future genetic studies, aid diagnosis, inform counseling, and assist in addressing the largely unmet need for clinical trials to be conducted in the region.
A systematic review of psychosocial functioning changes after gender-affirming hormone therapy among transgender people
Authors: Doyle David Matthew , Lewis Tom O. G. , Barreto Manuela
Published: May 2023

This systematic review assessed the state and quality of evidence for effects of gender-affirming hormone therapy on psychosocial functioning. Forty-six relevant journal articles (six qualitative, 21 cross-sectional, 19 prospective cohort) were identified. Gender-affirming hormone therapy was consistently found to reduce depressive symptoms and psychological distress. Evidence for quality of life was inconsistent, with some trends suggesting improvements. There was some evidence of affective changes differing for those on masculinizing versus feminizing hormone therapy. Results for self-mastery effects were ambiguous, with some studies suggesting greater anger expression, particularly among those on masculinizing hormone therapy, but no increase in anger intensity. There were some trends toward positive change in interpersonal functioning. Overall, risk of bias was highly variable between studies. Small samples and lack of adjustment for key confounders limited causal inferences. More high-quality evidence for psychosocial effects of gender-affirming hormone therapy is vital for ensuring health equity for transgender people.
A massive quiescent galaxy at redshift 4.658
Authors: Carnall Adam C. , McLure Ross J. , Dunlop James S. , McLeod Derek J. , Wild Vivienne , Cullen Fergus , Magee Dan , Begley Ryan , Cimatti Andrea , Donnan Callum T. , Hamadouche Massissilia L. , Jewell Sophie M. , Walker Sam
Published: May 2023

The extremely rapid assembly of the earliest galaxies during the first billion years of cosmic history is a major challenge for our understanding of galaxy formation physics1–5. The advent of the James Webb Space Telescope (JWST) has exacerbated this issue by confirming the existence of galaxies in substantial numbers as early as the first few hundred million years6–8. Perhaps even more surprisingly, in some galaxies, this initial highly efficient star formation rapidly shuts down, or quenches, giving rise to massive quiescent galaxies as little as 1.5 billion years after the Big Bang9,10. However, due to their faintness and red colour, it has proven extremely challenging to learn about these extreme quiescent galaxies, or to confirm whether any existed at earlier times. Here we report the spectroscopic confirmation of a massive quiescent galaxy, GS-9209, at redshift, z = 4.658, just 1.25 billion years after the Big Bang, using the JWST Near-Infrared Spectrograph (NIRSpec). From these data we infer a stellar mass of M* = 3.8 ± 0.2 × 1010 M⊙, which formed over a roughly 200 Myr period before this galaxy quenched its star-formation activity at $$z={6.5}_{-0.5}^{+0.2}$$

z
=

6.5

−
0.5

+
0.2

, when the Universe was approximately 800 Myr old. This galaxy is both a likely descendent of the highest-redshift submillimetre galaxies and quasars, and a likely progenitor for the dense, ancient cores of the most massive local galaxies.
Strand-selective base editing of human mitochondrial DNA using mitoBEs
Authors: Yi Zongyi , Zhang Xiaoxue , Tang Wei , Yu Ying , Wei Xiaoxu , Zhang Xue , Wei Wensheng
Published: May 2023

A number of mitochondrial diseases in humans are caused by point mutations that could be corrected by base editors, but delivery of CRISPR guide RNAs into the mitochondria is difficult. In this study, we present mitochondrial DNA base editors (mitoBEs), which combine a transcription activator-like effector (TALE)-fused nickase and a deaminase for precise base editing in mitochondrial DNA. Combining mitochondria-localized, programmable TALE binding proteins with the nickase MutH or Nt.BspD6I(C) and either the single-stranded DNA-specific adenine deaminase TadA8e or the cytosine deaminase ABOBEC1 and UGI, we achieve A-to-G or C-to-T base editing with up to 77% efficiency and high specificity. We find that mitoBEs are DNA strand-selective mitochondrial base editors, with editing results more likely to be retained on the nonnicked DNA strand. Furthermore, we correct pathogenic mitochondrial DNA mutations in patient-derived cells by delivering mitoBEs encoded in circular RNAs. mitoBEs offer a precise, efficient DNA editing tool with broad applicability for therapy in mitochondrial genetic diseases.
The wheat stem rust resistance gene Sr43 encodes an unusual protein kinase
Authors: Yu Guotai , Matny Oadi , Gourdoupis Spyridon , Rayapuram Naganand , Aljedaani Fatimah R. , Wang Yan L. , Nürnberger Thorsten , Johnson Ryan , Crean Emma E. , Saur Isabel M.-L. , Gardener Catherine , Yue Yajuan , Kangara Ngonidzashe , Steuernagel Burkhard , Hayta Sadiye , Smedley Mark , Harwood Wendy , Patpour Mehran , Wu Shuangye , Poland Jesse , Jones Jonathan D. G. , Reuber T. Lynne , Ronen Moshe , Sharon Amir , Rouse Matthew N. , Xu Steven , Holušová Kateřina , Bartoš Jan , Molnár István , Karafiátová Miroslava , Hirt Heribert , Blilou Ikram , Jaremko Łukasz , Doležel Jaroslav , Steffenson Brian J. , Wulff Brande B. H.
Published: May 2023

To safeguard bread wheat against pests and diseases, breeders have introduced over 200 resistance genes into its genome, thus nearly doubling the number of designated resistance genes in the wheat gene pool1. Isolating these genes facilitates their fast-tracking in breeding programs and incorporation into polygene stacks for more durable resistance. We cloned the stem rust resistance gene Sr43, which was crossed into bread wheat from the wild grass Thinopyrum elongatum2,3. Sr43 encodes an active protein kinase fused to two domains of unknown function. The gene, which is unique to the Triticeae, appears to have arisen through a gene fusion event 6.7 to 11.6 million years ago. Transgenic expression of Sr43 in wheat conferred high levels of resistance to a wide range of isolates of the pathogen causing stem rust, highlighting the potential value of Sr43 in resistance breeding and engineering.
Flexible neural control of transition points within the egg-laying behavioral sequence in Drosophila
Authors: Cury Kevin M. , Axel Richard
Published: May 2023

Innate behaviors are frequently comprised of ordered sequences of component actions that progress to satisfy essential drives. Progression is governed by specialized sensory cues that induce transitions between components within the appropriate context. Here we have characterized the structure of the egg-laying behavioral sequence in Drosophila and found significant variability in the transitions between component actions that affords the organism an adaptive flexibility. We identified distinct classes of interoceptive and exteroceptive sensory neurons that control the timing and direction of transitions between the terminal components of the sequence. We also identified a pair of motor neurons that enact the final transition to egg expulsion. These results provide a logic for the organization of innate behavior in which sensory information processed at critical junctures allows for flexible adjustments in component actions to satisfy drives across varied internal and external environments.
Adding tactile feedback increases avatar ownership and makes virtual reality more effective at reducing pain in a randomized crossover study
Authors: Hoffman Hunter G. , Fontenot Miles R. , Garcia-Palacios Azucena , Greenleaf Walter J. , Alhalabi Wadee , Curatolo Michele , Flor Herta
Published: May 2023

Severe pain is a widespread health problem in need of novel treatment approaches. In the current study we used real water to give virtual objects (i.e., animated virtual water) more realistic physical properties (wet liquid qualities). Healthy volunteers aged 18–34 participated in a within-subject randomized study comparing participants’ worst pain during brief thermal stimuli with (1) No Immersive Virtual Reality (VR), versus (2) during VR + no tactile feedback versus (3) VR + real water (with tactile feedback from co-located real objects). Tactile feedback significantly decreased pain intensity (VR analgesia, p < 0.01), compared to VR with no tactile feedback, and compared to No VR (baseline). Tactile feedback made the virtual water feel significantly more real, increased participant’s sense of presence, and both VR conditions were distracting (significantly reduced accuracy on an attention demanding task). As a non-pharmacologic analgesic, mixed reality reduced pain by 35% in the current study, comparable to the analgesia from a moderate dose of hydromorphone in previous published experimental studies. Tactile feedback also significantly increased avatar embodiment, the participants illusion of ownership of the virtual hands, which has potential to improve the effectiveness of avatar therapy for chronic pain in future studies. Mixed reality should be tested as treatment in pain patients.
Depression and anxiety during and after episodes of COVID-19 in the community
Authors: Alacevich Caterina , Thalmann Inna , Nicodemo Catia , de Lusignan Simon , Petrou Stavros
Published: May 2023

Understanding the connection between physical and mental health with evidence-based research is important to inform and support targeted screening and early treatment. The objective of this study was to document the co-occurrence of physical and mental health conditions during and after the experience of symptomatic SARS-CoV-2 illness episodes. Drawing from a national symptoms' surveillance survey conducted in the UK in 2020, this study shows that individuals with symptomatic forms of SARS-CoV-2 (identified by anosmia with either fever, breathlessness or cough) presented significantly higher odds of experiencing moderate and severe anxiety (2.41, CI 2.01–2.90) and depression (3.64, CI 3.06–4.32). Respondents who recovered from physical SARS-CoV-2 symptoms also experienced higher odds of anxiety and depression in comparison to respondents who never experienced symptoms. The findings are robust to alternative estimation models that compare individuals with the same socioeconomic and demographic characteristics and who experienced the same local and contextual factors such as mobility and social restrictions. The findings have important implications for the screening and detection of mental health disorders in primary care settings. They also suggest the need to design and test interventions to address mental health during and after physical illness episodes.
circDYRK1A tethers biological behaviors of gastric carcinoma using novel bioinformatics analysis and experimental validations
Authors: Zhu Zirui , Lu Huiwen , Zhao Xu , Sun Yimeng , Yao Junqiao , Xue Chi , Huang Baojun
Published: May 2023

Gastric cancer has been one of the wide public health burdens with its high morbidity and mortality over several decades. As the unconventional modules among RNA families, circular RNAs present their blazing biological effects during gastric carcinogenesis. Though diverse hypothetical mechanisms were reported, further tests were necessitated for authentication. Herein, this study pinpointed a representative circDYRK1A which screened from vast amounts of public data sets using surprisingly novel bioinformatics approaches together with validations from the in vitro findings and then concluded that circDYRK1A tethered the biological behavior and swayed the clinicopathological features with gastric cancer patients thus providing an in-depth awareness for gastric carcinoma.
U-shaped link of health checkup data and need for care using a time-dependent cox regression model with a restricted cubic spline
Authors: Nakatochi Masahiro , Sugishita Akitaka , Watanabe Chihiro , Fuchita Etsuko , Mizuno Masaaki
Published: May 2023

We explored risk indicators likely to result in older adults needing certified long-term care in Japan and ascertained whether this relationship forms a U-shaped link. We analyzed a community-based cohort of residents in Kitanagoya City, Aichi Prefecture, Japan. Participants were 3718 individuals aged 65 years and above who underwent health examinations between April 1, 2011 and March 31, 2012. For continuous clinical variables, we applied a time-dependent Cox regression model. Two types of models were applied—a linear and nonlinear model with restricted cubic splines—to assess the U-shaped association. Statistical significance (set at 0.05) for the nonlinearity was tested by comparing the spline and linear models. Among the participants, 701 were certified as needing Level 1 care or higher during a follow-up. Among the continuous clinical variables, the nonlinear model for body mass index, systolic blood pressure, high-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase revealed significant U-shaped associations as compared with the linear model in which the outcome was a certification of the need for nursing care. These results provide an important insight into the usefulness of nonlinear models for predicting the risk of such certification.
Pattern and predictors of death from aluminum and zinc phosphide poisoning using multi-kernel optimized relevance vector machine
Authors: Abdelghafar Sara , Farrag Tamer Ahmed , Zanaty Azza , Alshater Heba , Darwish Ashraf , Hassanien Aboul Ella
Published: May 2023

The use of metal phosphides, particularly aluminum phosphide, poses a significant threat to human safety and results in high mortality rates. This study aimed to determine mortality patterns and predictive factors for acute zinc and aluminum phosphide poisoning cases that were admitted to Menoufia University Poison and Dependence Control Center from 2017 to 2021. Statistical analysis revealed that poisoning was more common among females (59.7%), aged between 10 and 20 years, and from rural regions. Most cases were students, and most poisonings were the result of suicidal intentions (78.6%). A new hybrid model named Bayesian Optimization-Relevance Vector Machine (BO-RVM) was proposed to forecast fatal poisoning. The model achieved an overall accuracy of 97%, with high positive predictive value (PPV) and negative predictive value (NPV) values of 100% and 96%, respectively. The sensitivity was 89.3%, while the specificity was 100%. The F1 score was 94.3%, indicating a good balance between precision and recall. These results suggest that the model performs well in identifying both positive and negative cases. Additionally, the BO-RVM model has a fast and accurate processing time of 379.9595 s, making it a promising tool for various applications. The study underscores the need for public health policies to restrict the availability and use of phosphides in Egypt and adopt effective treatment methods for phosphide-poisoned patients. Clinical suspicion, positive silver nitrate test for phosphine, and analysis of cholinesterase levels are useful in diagnosing metal phosphide poisoning, which can cause various symptoms.
Model and simulator of inlet air flow in grinding installation with electromagnetic mill
Authors: Krauze Oliwia
Published: May 2023

Comminution of raw materials consumes great shares of energy and operating costs of production and processing plants. Savings may be achieved, e.g., by developing new grinding equipment, such as the electromagnetic mill with its dedicated grinding installation; and by applying efficient control algorithms to these elements. Good quality control relies on mathematical models, and testing of versatile control algorithms is much simplified if a plant simulation environment is available. Thus, in this research, measurements were collected at the grinding installation with electromagnetic mill. Then, a model was developed that characterised the flow of transport air in the inlet part of the installation. The model was also implemented in software to provide the pneumatic system simulator. Verification and validation tests were conducted. They confirmed the correct behaviour of the simulator and good compliance with the experimental data, for both steady-states and transients. The model is then suitable for design and parametrization of air flow control algorithms and for their testing in simulation.
Analysis of the effect of cerium on the formation of non-metallic inclusions in low-carbon steel
Authors: Szucki Michał , Kalisz Dorota , Gerasin Sergii , Mrówka Natalia Maria , Iwanciw Jerzy , Semiryagin Sergey
Published: May 2023

The research focused on the influence of cerium on the chemical composition and morphology of non-metallic inclusions in pre-oxidised steel to which Al, Ca, and Ce was added in different amount and order. Calculations were carried out using our own computer program. The simulation results obtained according to two calculation models helped identify precipitates from the Ce–O–S system. The possibility of CeN formation was also identified. The trace amounts of these inclusions were also found in the results. Consideration of the physicochemical phenomena at the boundary, as well as the interfacial partitioning and the sulfur partition coefficient, influences the favourable chemical composition of the inclusions, limiting it mainly to compounds from the Al2O3, Ce2O3, and CaS systems. It was found that the addition of Ce before Ca causes the elimination of MnS precipitates and Ca-containing inclusions in the steel.