bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of risperidone/paliperidone versus placebo on cognitive functioning over the first 6 months of treatment for psychotic disorder: secondary analysis of a triple-blind randomised clinical trial
Authors: Allott Kelly , Yuen Hok Pan , Baldwin Lara , O’Donoghue Brian , Fornito Alex , Chopra Sidhant , Nelson Barnaby , Graham Jessica , Kerr Melissa J. , Proffitt Tina-Marie , Ratheesh Aswin , Alvarez-Jimenez Mario , Harrigan Susy , Brown Ellie , Thompson Andrew D. , Pantelis Christos , Berk Michael , McGorry Patrick D. , Francey Shona M. , Wood Stephen J. 
Published: June 2023

AbstractThe drivers of cognitive change following first-episode psychosis remain poorly understood. Evidence regarding the role of antipsychotic medication is primarily based on naturalistic studies or clinical trials without a placebo arm, making it difficult to disentangle illness from medication effects. A secondary analysis of a randomised, triple-blind, placebo-controlled trial, where antipsychotic-naive patients with first-episode psychotic disorder were allocated to receive risperidone/paliperidone or matched placebo plus intensive psychosocial therapy for 6 months was conducted. A healthy control group was also recruited. A cognitive battery was administered at baseline and 6 months. Intention-to-treat analysis involved 76 patients (antipsychotic medication group: 37; 18.6Mage [2.9] years; 21 women; placebo group: 39; 18.3Mage [2.7]; 22 women); and 42 healthy controls (19.2Mage [3.0] years; 28 women). Cognitive performance predominantly remained stable (working memory, verbal fluency) or improved (attention, processing speed, cognitive control), with no group-by-time interaction evident. However, a significant group-by-time interaction was observed for immediate recall (p = 0.023), verbal learning (p = 0.024) and delayed recall (p = 0.005). The medication group declined whereas the placebo group improved on each measure (immediate recall: p = 0.024; ηp2 = 0.062; verbal learning: p = 0.015; ηp2 = 0.072 both medium effects; delayed recall: p = 0.001; ηp2 = 0.123 large effect). The rate of change for the placebo and healthy control groups was similar. Per protocol analysis (placebo n = 16, medication n = 11) produced similar findings. Risperidone/paliperidone may worsen verbal learning and memory in the early months of psychosis treatment. Replication of this finding and examination of various antipsychotic agents are needed in confirmatory trials. Antipsychotic effects should be considered in longitudinal studies of cognition in psychosis.Trial registration: Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au/; ACTRN12607000608460).
Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
Authors: Oddsson Asmundur , Sulem Patrick , Sveinbjornsson Gardar , Arnadottir Gudny A. , Steinthorsdottir Valgerdur , Halldorsson Gisli H. , Atlason Bjarni A. , Oskarsson Gudjon R. , Helgason Hannes , Nielsen Henriette Svarre , Westergaard David , Karjalainen Juha M. , Katrinardottir Hildigunnur , Fridriksdottir Run , Jensson Brynjar O. , Tragante Vinicius , Ferkingstad Egil , Jonsson Hakon , Gudjonsson Sigurjon A. , Beyter Doruk , Moore Kristjan H. S. , Thordardottir Helga B. , Kristmundsdottir Snaedis , Stefansson Olafur A. , Rantapää-Dahlqvist Solbritt , Sonderby Ida Elken , Didriksen Maria , Stridh Pernilla , Haavik Jan , Tryggvadottir Laufey , Frei Oleksandr , Walters G. Bragi , Kockum Ingrid , Hjalgrim Henrik , Olafsdottir Thorunn A. , Selbaek Geir , Nyegaard Mette , Erikstrup Christian , Brodersen Thorsten , Saevarsdottir Saedis , Olsson Tomas , Nielsen Kaspar Rene , Haraldsson Asgeir , Bruun Mie Topholm , Hansen Thomas Folkmann ,   DBDS Genomic Consortium, Brunak Søren , Nielsen Kasper Rene , Brun Mie Topholm , Stefánsson Hreinn , Þorsteinsdóttir Unnur , Steingrimsdottir Thora , Jacobsen Rikke Louise , Lie Rolv T. , Djurovic Srdjan , Alfredsson Lars , Lopez de Lapuente Portilla Aitzkoa , Brunak Soren , Melsted Pall , Halldorsson Bjarni V. , Saemundsdottir Jona , Magnusson Olafur Th. , Padyukov Leonid , Banasik Karina , Rafnar Thorunn , Askling Johan , Klareskog Lars , Pedersen Ole Birger , Masson Gisli , Havdahl Alexandra , Nilsson Bjorn , Andreassen Ole A. , Daly Mark , Ostrowski Sisse Rye , Jonsdottir Ingileif , Stefansson Hreinn , Holm Hilma , Helgason Agnar , Thorsteinsdottir Unnur , Stefansson Kari , Gudbjartsson Daniel F. 
Published: June 2023

AbstractGenotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
Allosteric activation of cell wall synthesis during bacterial growth
Authors: Shlosman Irina , Fivenson Elayne M. , Gilman Morgan S. A. , Sisley Tyler A. , Walker Suzanne , Bernhardt Thomas G. , Kruse Andrew C. , Loparo Joseph J. 
Published: June 2023

AbstractThe peptidoglycan (PG) cell wall protects bacteria against osmotic lysis and determines cell shape, making this structure a key antibiotic target. Peptidoglycan is a polymer of glycan chains connected by peptide crosslinks, and its synthesis requires precise spatiotemporal coordination between glycan polymerization and crosslinking. However, the molecular mechanism by which these reactions are initiated and coupled is unclear. Here we use single-molecule FRET and cryo-EM to show that an essential PG synthase (RodA-PBP2) responsible for bacterial elongation undergoes dynamic exchange between closed and open states. Structural opening couples the activation of polymerization and crosslinking and is essential in vivo. Given the high conservation of this family of synthases, the opening motion that we uncovered likely represents a conserved regulatory mechanism that controls the activation of PG synthesis during other cellular processes, including cell division.
Trichalcogenasupersumanenes and its concave-convex supramolecular assembly with fullerenes
Authors: Sun Yixun , Wang Xin , Yang Bo , Chen Muhua , Guo Ziyi , Wang Yiting , Li Ji , Xu Mingyu , Zhang Yunjie , Sun Huaming , Dang Jingshuang , Fan Juan , Li Jing , Wei Junfa 
Published: June 2023

AbstractSynthesis of buckybowls have stayed highly challenging due to the large structural strain caused by curvedπsurface. In this paper, we report the synthesis and properties of two trichalcogenasupersumanenes which three chalcogen (sulfur or selenium) atoms and three methylene groups bridge at the bay regions of hexa-peri-hexabenzocoronene. These trichalcogenasupersumanenes are synthesized quickly in three steps using an Aldol cyclotrimerization, a Scholl oxidative cyclization, and a Stille type reaction. X-ray crystallography analysis reveals that they encompass bowl diameters of 11.06 Å and 11.35 Å and bowl depths of 2.29 Å and 2.16 Å for the trithiasupersumanene and triselenosupersumanene, respectively. Furthermore, trithiasupersumanene derivative with methyl chains can form host-guest complexes with C60or C70, which are driven by concave-convexπ ⋯ πinteractions and multiple C–H ⋯ πinteractions between bowl and fullerenes.
Vaccine-induced protection against SARS-CoV-2 requires IFN-γ-driven cellular immune response
Authors: Wang Xiaolei , Yuen Terrence Tsz-Tai , Dou Ying , Hu Jingchu , Li Renhao , Zeng Zheng , Lin Xuansheng , Gong Huarui , Chan Celia Hoi-Ching , Yoon Chaemin , Shuai Huiping , Ho Deborah Tip-Yin , Hung Ivan Fan-Ngai , Zhang Bao-Zhong , Chu Hin , Huang Jian-Dong 
Published: June 2023

AbstractThe overall success of worldwide mass vaccination in limiting the negative effect of the COVID-19 pandemics is inevitable, however, recent SARS-CoV-2 variants of concern, especially Omicron and its sub-lineages, efficiently evade humoral immunity mounted upon vaccination or previous infection. Thus, it is an important question whether these variants, or vaccines against them, induce anti-viral cellular immunity. Here we show that the mRNA vaccine BNT162b2 induces robust protective immunity in K18-hACE2 transgenic B-cell deficient (μMT) mice. We further demonstrate that the protection is attributed to cellular immunity depending on robust IFN-γ production. Viral challenge with SARS-CoV-2 Omicron BA.1 and BA.5.2 sub-variants induce boosted cellular responses in vaccinated μMT mice, which highlights the significance of cellular immunity against the ever-emerging SARS-CoV-2 variants evading antibody-mediated immunity. Our work, by providing evidence that BNT162b2 can induce significant protective immunity in mice that are unable to produce antibodies, thus highlights the importance of cellular immunity in the protection against SARS-CoV-2.
Discovery of senolytics using machine learning
Authors: Smer-Barreto Vanessa , Quintanilla Andrea , Elliott Richard J. R. , Dawson John C. , Sun Jiugeng , Campa Víctor M. , Lorente-Macías Álvaro , Unciti-Broceta Asier , Carragher Neil O. , Acosta Juan Carlos , Oyarzún Diego A. 
Published: June 2023

AbstractCellular senescence is a stress response involved in ageing and diverse disease processes including cancer, type-2 diabetes, osteoarthritis and viral infection. Despite growing interest in targeted elimination of senescent cells, only few senolytics are known due to the lack of well-characterised molecular targets. Here, we report the discovery of three senolytics using cost-effective machine learning algorithms trained solely on published data. We computationally screened various chemical libraries and validated the senolytic action of ginkgetin, periplocin and oleandrin in human cell lines under various modalities of senescence. The compounds have potency comparable to known senolytics, and we show that oleandrin has improved potency over its target as compared to best-in-class alternatives. Our approach led to several hundred-fold reduction in drug screening costs and demonstrates that artificial intelligence can take maximum advantage of small and heterogeneous drug screening data, paving the way for new open science approaches to early-stage drug discovery.
Analysis and modeling of cancer drug responses using cell cycle phase-specific rate effects
Authors: Gross Sean M. , Mohammadi Farnaz , Sanchez-Aguila Crystal , Zhan Paulina J. , Liby Tiera A. , Dane Mark A. , Meyer Aaron S. , Heiser Laura M. 
Published: June 2023

AbstractIdentifying effective therapeutic treatment strategies is a major challenge to improving outcomes for patients with breast cancer. To gain a comprehensive understanding of how clinically relevant anti-cancer agents modulate cell cycle progression, here we use genetically engineered breast cancer cell lines to track drug-induced changes in cell number and cell cycle phase to reveal drug-specific cell cycle effects that vary across time. We use a linear chain trick (LCT) computational model, which faithfully captures drug-induced dynamic responses, correctly infers drug effects, and reproduces influences on specific cell cycle phases. We use the LCT model to predict the effects of unseen drug combinations and confirm these in independent validation experiments. Our integrated experimental and modeling approach opens avenues to assess drug responses, predict effective drug combinations, and identify optimal drug sequencing strategies.
Scarless wound healing programmed by core-shell microneedles
Authors: Zhang Ying , Wang Shenqiang , Yang Yinxian , Zhao Sheng , You Jiahuan , Wang Junxia , Cai Jingwei , Wang Hao , Wang Jie , Zhang Wei , Yu Jicheng , Han Chunmao , Zhang Yuqi , Gu Zhen 
Published: June 2023

AbstractEffective reprogramming of chronic wound healing remains challenging due to the limited drug delivery efficacy hindered by physiological barriers, as well as the inappropriate dosing timing in distinct healing stages. Herein, a core-shell structured microneedle array patch with programmed functions (PF-MNs) is designed to dynamically modulate the wound immune microenvironment according to the varied healing phases. Specifically, PF-MNs combat multidrug-resistant bacterial biofilm at the early stage via generating reactive oxygen species (ROS) under laser irradiation. Subsequently, the ROS-sensitive MN shell gradually degrades to expose the MN core component, which neutralizes various inflammatory factors and promotes the phase transition from inflammation to proliferation. In addition, the released verteporfin inhibits scar formation by blocking Engrailed-1 (En1) activation in fibroblasts. Our experiments demonstrate that PF-MNs promote scarless wound repair in mouse models of both acute and chronic wounds, and inhibit the formation of hypertrophic scar in rabbit ear models.
Revealing proteome-level functional redundancy in the human gut microbiome using ultra-deep metaproteomics
Authors: Li Leyuan , Wang Tong , Ning Zhibin , Zhang Xu , Butcher James , Serrana Joeselle M. , Simopoulos Caitlin M. A. , Mayne Janice , Stintzi Alain , Mack David R. , Liu Yang-Yu , Figeys Daniel 
Published: June 2023

AbstractFunctional redundancy is a key ecosystem property representing the fact that different taxa contribute to an ecosystem in similar ways through the expression of redundant functions. The redundancy of potential functions (or genome-level functional redundancy $${{{{{{\rm{FR}}}}}}}_{g}$$

FR

g

) of human microbiomes has been recently quantified using metagenomics data. Yet, the redundancy of expressed functions in the human microbiome has never been quantitatively explored. Here, we present an approach to quantify the proteome-level functional redundancy $${{{{{{\rm{FR}}}}}}}_{p}$$

FR

p

in the human gut microbiome using metaproteomics. Ultra-deep metaproteomics reveals high proteome-level functional redundancy and high nestedness in the human gut proteomic content networks (i.e., the bipartite graphs connecting taxa to functions). We find that the nested topology of proteomic content networks and relatively small functional distances between proteomes of certain pairs of taxa together contribute to high $${{{{{{\rm{FR}}}}}}}_{p}$$

FR

p

in the human gut microbiome. As a metric comprehensively incorporating the factors of presence/absence of each function, protein abundances of each function and biomass of each taxon, $${{{{{{\rm{FR}}}}}}}_{p}$$

FR

p

outcompetes diversity indices in detecting significant microbiome responses to environmental factors, including individuality, biogeography, xenobiotics, and disease. We show that gut inflammation and exposure to specific xenobiotics can significantly diminish the $${{{{{{\rm{FR}}}}}}}_{p}$$

FR

p

with no significant change in taxonomic diversity.
Impaired histone inheritance promotes tumor progression
Authors: Tian Congcong , Zhou Jiaqi , Li Xinran , Gao Yuan , Wen Qing , Kang Xing , Wang Nan , Yao Yuan , Jiang Jiuhang , Song Guibing , Zhang Tianjun , Hu Suili , Liao JingYi , Yu Chuanhe , Wang Zhiquan , Liu Xiangyu , Pei Xinhai , Chan Kuiming , Liu Zichuan , Gan Haiyun 
Published: June 2023

AbstractFaithful inheritance of parental histones is essential to maintain epigenetic information and cellular identity during cell division. Parental histones are evenly deposited onto the replicating DNA of sister chromatids in a process dependent on the MCM2 subunit of DNA helicase. However, the impact of aberrant parental histone partition on human disease such as cancer is largely unknown. In this study, we construct a model of impaired histone inheritance by introducing MCM2-2A mutation (defective in parental histone binding) in MCF-7 breast cancer cells. The resulting impaired histone inheritance reprograms the histone modification landscapes of progeny cells, especially the repressive histone mark H3K27me3. Lower H3K27me3 levels derepress the expression of genes associated with development, cell proliferation, and epithelial to mesenchymal transition. These epigenetic changes confer fitness advantages to some newly emerged subclones and consequently promote tumor growth and metastasis after orthotopic implantation. In summary, our results indicate that impaired inheritance of parental histones can drive tumor progression.
Vection underwater illustrates the limitations of neutral buoyancy as a microgravity analog
Authors: Bury Nils-Alexander , Jenkin Michael , Allison Robert S. , Herpers Rainer , Harris Laurence R. 
Published: June 2023

AbstractNeutral buoyancy has been used as an analog for microgravity from the earliest days of human spaceflight. Compared to other options on Earth, neutral buoyancy is relatively inexpensive and presents little danger to astronauts while simulating some aspects of microgravity. Neutral buoyancy removes somatosensory cues to the direction of gravity but leaves vestibular cues intact. Removal of both somatosensory and direction of gravity cues while floating in microgravity or using virtual reality to establish conflicts between them has been shown to affect the perception of distance traveled in response to visual motion (vection) and the perception of distance. Does removal of somatosensory cues alone by neutral buoyancy similarly impact these perceptions? During neutral buoyancy we found no significant difference in either perceived distance traveled nor perceived size relative to Earth-normal conditions. This contrasts with differences in linear vection reported between short- and long-duration microgravity and Earth-normal conditions. These results indicate that neutral buoyancy is not an effective analog for microgravity for these perceptual effects.
The one-step fabrication of porous hASC-laden GelMa constructs using a handheld printing system
Authors: Jo SeoYul , Lee JiUn , Lee Hyeongjin , Ryu Dongryeol , Kim GeunHyung 
Published: June 2023

AbstractThe fabrication of highly porous cell-loaded structures in tissue engineering applications has been a challenging issue because non-porous cell-laden struts can cause severe cell necrosis in the middle region owing to poor transport of nutrients and oxygen. In this study, we propose a versatile handheld 3D printer for the effective fabrication of porous cell-laden methacrylated gelatin (GelMa) with high porosity (≈97%) by air injection and a bubble-making system using mesh filters through which a mixture of air/GelMa bioink is passed. In particular, the pore size and foamability of the cell constructs could be manipulated using various processing parameters (rheological properties of GelMa, filter size and number, and air-bioink volume ratio). To demonstrate the feasibility of the cell construct as a tissue engineering substitute for muscle regeneration, in vitro cellular activities and in vivo regeneration ability of human adipose stem cells were assessed. The in vitro results demonstrated that the human adipose stem cells (hASCs) fabricated using the handheld 3D printer were alive and well-proliferated. Furthermore, the in vivo results showed that the hASCs-constructs directly printed from the handheld 3D printer showed significant restoration of functionality and efficient muscle regeneration in the volumetric muscle loss model of mice. Based on these results, the fabrication method of the porous cell-laden construct could be a promising tool for regenerating muscle tissues.
Transcriptom and miRNA data of PUFA-enriched stimulated murine macrophage and human endothelial cell lines
Authors: Roessler Claudia , Schumann Julia 
Published: June 2023

AbstractInflammation is associated with the adaptation of macrophages and endothelial cells, and the dysregulation of these differentiation processes has been directly linked to both acute and chronic disease states. As cells in constant contact with blood, macrophages and endothelial cells are also under the direct influence of immunomodulatory dietary components such as polyunsaturated fatty acids (PUFA). RNA sequencing analyses allow us to understand the global changes in gene expression occurring during cell differentiation, including both transcriptional (transcriptome) and post-transcriptional (miRNAs) levels. We generated a comprehensive RNA sequencing dataset of parallel transcriptome and miRNA profiles of PUFA-enriched and pro-inflammatory stimulated macrophages and endothelial cells aiming to uncover the underlying molecular mechanisms. PUFA concentrations and duration of supplementation were based on dietary ranges, allowing for metabolism and plasma membrane uptake of fatty acids. The dataset may serve as a resource to study transcriptional and post-transcriptional changes associated with macrophage polarisation and endothelial dysfunction in inflammatory settings and their modulation by omega-3 and omega-6 fatty acids.
Racial and ethnic difference in the risk of fractures in the United States: a systematic review and meta-analysis
Authors: Bao Yueyang , Xu Yingke , Li Zhuowei , Wu Qing 
Published: June 2023

AbstractThis systematic review and meta-analysis examined the association between race and ethnicity and fracture risk in the United States. We identified relevant studies by searching PubMed and EMBASE for studies published from the databases’ inception date to December 23, 2022. Only observational studies conducted in the US population that reported the effect size of racial-ethnic minority groups versus white people were included. Two investigators independently conducted literature searches, study selection, risk of bias assessment, and data abstraction; discrepancies were resolved by consensus or consultation of a third investigator. Twenty-five studies met the inclusion criteria, and the random-effects model was used to calculate the pooled effect size due to heterogeneity between the studies. Using white people as the reference group, we found that people of other races and ethnic groups had a significantly lower fracture risk. In Black people, the pooled relative risk (RR) was 0.46 (95% confidence interval (CI), 0.43–0.48, p < 0.0001). In Hispanics, the pooled RR was 0.66 (95% CI, 0.55–0.79, p < 0.0001). In Asian Americans, the pooled RR was 0.55 (95% CI, 0.45–0.66, p < 0.0001). In American Indians, the pooled RR was 0.80 (95% CI, 0.41–1.58, p = 0.3436). Subgroup analysis by sex in Black people revealed the strength of association was greater in men (RR = 0.57, 95% CI = 0.51–0.63, p < 0.0001) than in women (RR = 0.43, 95% CI = 0.39–0.47, p < 0.0001). Our findings suggest that people of other races and ethnic groups have a lower fracture risk than white people.