bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractOncolytic 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

Abstractα-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

AbstractBacterial 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

AbstractCellular 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

AbstractThis 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

AbstractThis 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

AbstractThe 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

AbstractA 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

AbstractTo 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

AbstractInnate 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

AbstractSevere 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

AbstractUnderstanding 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

AbstractGastric 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

AbstractWe 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

AbstractThe 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

AbstractComminution 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.