bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell brain organoid screening identifies developmental defects in autism
Authors: Li Chong , Fleck Jonas Simon , Martins-Costa Catarina , Burkard Thomas R. , Themann Jan , Stuempflen Marlene , Peer Angela Maria , Vertesy Ábel , Littleboy Jamie B. , Esk Christopher , Elling Ulrich , Kasprian Gregor , Corsini Nina S. , Treutlein Barbara , Knoblich Juergen A. 
Published: September 2023

AbstractThe development of the human brain involves unique processes (not observed in many other species) that can contribute to neurodevelopmental disorders1–4. Cerebral organoids enable the study of neurodevelopmental disorders in a human context. We have developed the CRISPR–human organoids–single-cell RNA sequencing (CHOOSE) system, which uses verified pairs of guide RNAs, inducible CRISPR–Cas9-based genetic disruption and single-cell transcriptomics for pooled loss-of-function screening in mosaic organoids. Here we show that perturbation of 36 high-risk autism spectrum disorder genes related to transcriptional regulation uncovers their effects on cell fate determination. We find that dorsal intermediate progenitors, ventral progenitors and upper-layer excitatory neurons are among the most vulnerable cell types. We construct a developmental gene regulatory network of cerebral organoids from single-cell transcriptomes and chromatin modalities and identify autism spectrum disorder-associated and perturbation-enriched regulatory modules. Perturbing members of the BRG1/BRM-associated factor (BAF) chromatin remodelling complex leads to enrichment of ventral telencephalon progenitors. Specifically, mutating the BAF subunit ARID1B affects the fate transition of progenitors to oligodendrocyte and interneuron precursor cells, a phenotype that we confirmed in patient-specific induced pluripotent stem cell-derived organoids. Our study paves the way for high-throughput phenotypic characterization of disease susceptibility genes in organoid models with cell state, molecular pathway and gene regulatory network readouts.
Structural mobility tunes signalling of the GluA1 AMPA glutamate receptor
Authors: Zhang Danyang , Ivica Josip , Krieger James M. , Ho Hinze , Yamashita Keitaro , Stockwell Imogen , Baradaran Rozbeh , Cais Ondrej , Greger Ingo H. 
Published: September 2023

AbstractAMPA glutamate receptors (AMPARs), the primary mediators of excitatory neurotransmission in the brain, are either GluA2 subunit-containing and thus Ca2+-impermeable, or GluA2-lacking and Ca2+-permeable1. Despite their prominent expression throughout interneurons and glia, their role in long-term potentiation and their involvement in a range of neuropathologies2, structural information for GluA2-lacking receptors is currently absent. Here we determine and characterize cryo-electron microscopy structures of the GluA1 homotetramer, fully occupied with TARPγ3 auxiliary subunits (GluA1/γ3). The gating core of both resting and open-state GluA1/γ3 closely resembles GluA2-containing receptors. However, the sequence-diverse N-terminal domains (NTDs) give rise to a highly mobile assembly, enabling domain swapping and subunit re-alignments in the ligand-binding domain tier that are pronounced in desensitized states. These transitions underlie the unique kinetic properties of GluA1. A GluA2 mutant (F231A) increasing NTD dynamics phenocopies this behaviour, and exhibits reduced synaptic responses, reflecting the anchoring function of the AMPAR NTD at the synapse. Together, this work underscores how the subunit-diverse NTDs determine subunit arrangement, gating properties and ultimately synaptic signalling efficiency among AMPAR subtypes.
An intensive longitudinal dataset of in-game player behaviour and well-being in PowerWash Simulator
Authors: Vuorre Matti , Magnusson Kristoffer , Johannes Niklas , Butlin James , Przybylski Andrew K. 
Published: September 2023

AbstractThe potential impacts that video games might have on players’ well-being are under increased scrutiny but poorly understood empirically. Although extensively studied, a level of understanding required to address concerns and advise policy is lacking, at least partly because much of this science has relied on artificial settings and limited self-report data. We describe a large and detailed dataset that addresses these issues by pairing video game play behaviors and events with in-game well-being and motivation reports. 11,080 players (from 39 countries) of the first person PC game PowerWash Simulator volunteered for a research version of the game that logged their play across 10 in-game behaviors and events (e.g. task completion) and 21 variables (e.g. current position), and responses to 6 psychological survey instruments via in-game pop-ups. The data consists of 15,772,514 gameplay events, 726,316 survey item responses, and 21,202,667 additional gameplay status records, and spans 222 days. The data and codebook are publicly available with a permissive CC0 license.
A simple approach for image-based modelling of the heart that enables robust simulation of highly heterogeneous electrical excitation
Authors: Colman Michael A. , Benson Alan P. 
Published: September 2023

AbstractRemodelling of cardiac tissue structure, including intercellular electrical coupling, is a major determinant of the complex and heterogeneous excitation patterns associated with cardiac arrhythmias. Evaluation of the precise mechanisms by which local tissue structure determines global arrhythmic excitation patterns is a major challenge that may be critically important for the development of effective treatment strategies. Computational modelling is a key tool in the study of cardiac arrhythmias, yet the established approaches for organ-scale modelling are unsuitable to capture the impact of local conduction heterogeneities; a novel approach is required to provide this multi-scale mechanistic insight. We present a fundamentally simple yet powerful approach to simulate electrical excitation in highly heterogeneous whole-heart models that exploits the underlying discreteness of the myocardium. Preliminary simulations demonstrate that this approach can capture lower conduction velocities and reproduce wave breakdown and the development of re-entry in a range of conditions.
Facile preparation of silver based radiosensitizers via biomineralization method for enhanced in vivo breast cancer radiotherapy
Authors: Ghaffarlou Mohammadreza , Mohammadi Ali , Mousazadeh Navid , Salehiabar Marziyeh , Kalantari Yahya , Charmi Jalil , Barsbay Murat , Ertas Yavuz Nuri , Danafar Hossein , Rezaeejam Hamed , Nosrati Hamed , Javani Siamak 
Published: September 2023

AbstractTo solve the traditional radiotherapy obstacles, and also to enhance the radiation therapy efficacy various radiosensitizers have been developed. Radiosensitizers are promising agents that under X-ray irradiation enhance injury to tumor tissue by accelerating DNA damage. In this report, silver-silver sulfide nanoparticles (Ag-Ag2S NPs) were synthesized via a facile, one-pot and environmentally friendly biomineralization method. Ag-Ag2S was coated with bovine serum albumin (BSA) in situ and applied as an X-ray sensitizer to enhance the efficiency of radiotherapy. Also, folic acid (FA) was conjugated to Ag-Ag2S@BSA to impart active targeting capability to the final formulation (Ag-Ag2S@BSA-FA). Prepared NPs were characterized by transmission electron microscopes (TEM), scanning electron microscope (SEM), dynamic light scattering (DLS), ultraviolet–visible spectroscopy (UV–Vis), X-ray diffraction analysis (XRD), and X-ray photoelectron spectroscopy (XPS) techniques. Results show that most of the NPs have well-defined uniform Janus structures. The biocompatibility of the NPs was then evaluated both in vitro and in vivo. A series of in vitro assays were performed on 4T1 cancer cells to evaluate the therapeutic efficacy of the designed NPs. In addition, the radio-enhancing ability of the NPs was tested on the 4T1 breast cancer murine model. MTT, live and dead cell staining, apoptosis, ROS generation, and clonogenic in vitro assays demonstrated the efficacy of NPs as radiosensitizers in radiotherapy. In vivo results as well as H&E staining tumor tissues confirmed tumor destruction in the group that received Ag-Ag2S@BSA-FA NPs and exposed to X-ray. The results showed that prepared tumor-targeted Ag-Ag2S@BSA-FA NPs could be potential candidates as radiosensitizers for enhanced radiotherapy.
Comprehensive analyses of the occurrence of a fungicide resistance marker and the genetic structure in Erysiphe necator populations
Authors: Pintye Alexandra , Németh Márk Z. , Molnár Orsolya , Horváth Áron N. , Matolcsi Fruzsina , Bókony Veronika , Spitzmüller Zsolt , Pálfi Xénia , Váczy Kálmán Z. , Kovács Gábor M. 
Published: September 2023

AbstractGenetically distinct groups of Erysiphe necator, the fungus causing grapevine powdery mildew infect grapevine in Europe, yet the processes sustaining stable genetic differences between those groups are less understood. Genotyping of over 2000 field samples from six wine regions in Hungary collected between 2017 and 2019 was conducted to reveal E. necator genotypes and their possible differentiation. The demethylase inhibitor (DMI) fungicide resistance marker A495T was detected in all wine regions, in 16% of the samples. Its occurrence differed significantly among wine regions and grape cultivars, and sampling years, but it did not differ between DMI-treated and untreated fields. Multilocus sequence analyses of field samples and 59 in vitro maintained isolates revealed significant genetic differences among populations from distinct wine regions. We identified 14 E. necator genotypes, of which eight were previously unknown. In contrast to the previous concept of A and B groups, European E. necator populations should be considered genetically more complex. Isolation by geographic distance, growing season, and host variety influence the genetic structuring of E. necator, which should be considered both during diagnoses and when effective treatments are planned.
Extreme events, trophic chain reactions, and shifts in phenotypic selection
Authors: Layton-Matthews Kate , Vriend Stefan J. G. , Grøtan Vidar , Loonen Maarten J. J. E. , Sæther Bernt-Erik , Fuglei Eva , Hansen Brage Bremset 
Published: September 2023

AbstractDemographic consequences of rapid environmental change and extreme climatic events (ECEs) can cascade across trophic levels with evolutionary implications that have rarely been explored. Here, we show how an ECE in high Arctic Svalbard triggered a trophic chain reaction, directly or indirectly affecting the demography of both overwintering and migratory vertebrates, ultimately inducing a shift in density-dependent phenotypic selection in migratory geese. A record-breaking rain-on-snow event and ice-locked pastures led to reindeer mass starvation and a population crash, followed by a period of low mortality and population recovery. This caused lagged, long-lasting reductions in reindeer carrion numbers and resultant low abundances of Arctic foxes, a scavenger on reindeer and predator of migratory birds. The associated decrease in Arctic fox predation of goose offspring allowed for a rapid increase in barnacle goose densities. As expected according to r- and K-selection theory, the goose body condition (affecting reproduction and post-fledging survival) maximising Malthusian fitness increased with this shift in population density. Thus, the winter ECE acting on reindeer and their scavenger, the Arctic fox, indirectly selected for higher body condition in migratory geese. This high Arctic study provides rare empirical evidence of links between ECEs, community dynamics and evolution, with implications for our understanding of indirect eco-evolutionary impacts of global change.
FAM3 family genes are associated with prognostic value of human cancer: a pan-cancer analysis
Authors: Dong Qing-Tai , Ma Dan-Dan , Gong Qi , Lin Zhen-Yu , Li Zhong-Hu , Ye Jia-Xin , Qin Chun-Hui , Jin Wei-Dong , Zhang Jian-Xin , Zhang Zhi-Yong 
Published: September 2023

AbstractFamily with sequence similarity three member (FAM3) plays a crucial role in the malignant development of various cancers of human. However, there remains doubtful what specific role of FAM3 family genes in pan-cancer. Our study aimed to investigate the role of FAM3 family genes in prognosis, immune subtype, tumor immune microenvironment, stemness score, and anticancer drug sensitivity of pan-cancer. We obtained data from UCSC Xena GDC and CellMiner databases, and used them to study the correlation of the expression, survival, immune subtype, tumor microenvironment, stemness score, and anticancer drug sensitivity between FAM3 family genes with pan-cancer. Furthermore, we investigated the tumor cellular functions and clinical prognostic value FAMC3 in pancreatic cancer (PAAD) using cellular experiments and tissue microarray. Cell Counting Kit-8 (CCK-8), transwell invasion, wound-healing and apoptosis assays were performed to study the effect of FAM3C on SW1990 cells’ proliferation, migration, invasion and apoptosis. Immunohistochemical staining was used to study the relationship between FAM3C expression and clinical characteristics of pancreatic cancer patients. The results revealed that FAM3 family genes are significantly differential expression in tumor and adjacent normal tissues in 7 cancers (CHOL, HNSC, KICH, LUAD, LUSC, READ, and STAD). The expression of FAM3 family genes were negatively related with the RNAss, and robust correlated with immune type, tumor immune microenvironment and drug sensitivity. The expression of FAM3 family genes in pan-cancers were significantly different in immune type C1 (wound healing), C2 (IFN-gamma dominant), C3 (inflammatory), C4 (lymphocyte depleted), C5 (immunologically quiet), and C6 (TGF-beta dominant). Meanwhile, overexpression FAM3C promoted SW1990 cells proliferation, migration, invasion and suppressed SW1990 cells apoptosis. While knockdown of FAM3C triggered opposite results. High FAM3C expression was associated with duodenal invasion, differentiation and liver metastasis. In summary, this study provided a new perspective on the potential therapeutic role of FAM3 family genes in pan-cancer. In particular, FAM3C may play an important role in the occurrence and progression of PAAD.
Gulls as a host for both gamma and deltacoronaviruses
Authors: Domańska-Blicharz Katarzyna , Miłek-Krupa Justyna , Pikuła Anna 
Published: September 2023

AbstractThe coronaviruses (CoV) are ubiquitous pathogens found in wide variety of hosts that constantly pose a threat to human and animal health as a result of their enormous capacity to generate genetic changes. Constant monitoring of virus reservoirs can constitute an early-warning tool and control the spread and evolution of the virus. Coronaviruses are common in wild birds, globally, and birds of the Charadriiformes in particular have been demonstrated to be carriers of delta- (dCoV) and gammacoronaviruses (gCoV). In this paper, we present the genetic characterisation of five CoV strains from black-headed (Chroicocephalus ridibundus) and common (Larus canus) gulls. Whole genome sequence analysis showed high similarity of detected dCoV in gulls to previously identified strains from falcon, houbara, pigeon and gulls from Asia (UAE, China). However, phylogenetic analysis revealed bifurcation within a common branch. Furthermore, the accumulation of numerous amino acid changes within the S-protein was demonstrated, indicating further evolution of dCoV within a single gull host. In turn, phylogenetic analysis for the most of the structural and non-structural genes of identified gCoV confirmed that the strain belongs to the duck coronavirus 2714 (DuCoV2714) species within Igacovirus subgenera, while for the spike protein it forms a separate branch not closely related to any gCoV species known to date. The current study provides new and significant insights into the evolution and diversification of circulating coronaviruses in members of Laridae family.
Extracorporeal membrane oxygenation and acute kidney injury: a single-center retrospective cohort
Authors: Gao Xiaolan , Ninan Jacob , Bohman John K. , Viehman Jason K. , Liu Chang , Bruns Danette , Song Xuan , Liu Xinyan , Yalamuri Suraj M. , Kashani Kianoush B. 
Published: September 2023

AbstractTo assess the relationship between acute kidney injury (AKI) with outcomes among patients requiring extracorporeal membrane oxygenation (ECMO). This is a single-center, retrospective cohort study of adult patients admitted to intensive care units (ICU) at a tertiary referral hospital requiring ECMO from July 1, 2015, to August 30, 2019. We assessed the temporal relationship of AKI and renal replacement therapy with ECMO type (VV vs. VA). The primary outcome was in-hospital mortality rates. We used Kruskal–Wallis or chi-square tests for pairwise comparisons, cause-specific Cox proportional hazards models were utilized for the association between AKI prevalence and in-hospital mortality, and a time-dependent Cox model was used to describe the association between AKI incidence and mortality. After the screening, 190 patients met eligibility criteria [133 (70%) AKI, 81 (43%) required RRT]. The median age was 61 years, and 61% were males. Among AKI patients, 48 (36%) and 85 (64%) patients developed AKI before and after ECMO, respectively. The SOFA Day 1, baseline creatinine, respiratory rate (RR), use of vasopressin, vancomycin, proton pump inhibitor, antibiotics, duration of mechanical ventilation and ECMO, and ICU length of stay were higher in AKI patients compared with those without AKI (P < 0.01). While ICU and in-hospital mortality rates were 46% and 50%, respectively, there were no differences based on the AKI status. The type and characteristics of ECMO support were not associated with AKI risk. Among AKI patients, 77 (58%) were oliguric, and 46 (60%) of them received diuretics. Urine output in the diuretic group was only higher on the first day than in those who did not receive diuretics (P = 0.03). Among ECMO patients, AKI was not associated with increased mortality but was associated with prolonged duration of mechanical ventilation and ICU length of stay.
Designing an efficient organic–inorganic hybrid nanocomposite for simultaneous oxidative/adsorptive desulfurization of model and real fuel oils
Authors: Sadrara Mina , Khorrami Mohammadreza Khanmohammadi 
Published: September 2023

AbstractIn this study, an efficient organic–inorganic hybrid nanocomposite was designed for deep oxidative/adsorptive removal of dibenzothiophene (DBT) from model and real fuel oils employing surface molecularly imprinted polymer (SMIP) and mesoporous silica nanoparticles (MSNs). On the surface of silanol-functionalized MCM-48-HPW prepared at different 12-tungstophosphoric acid (HPW wt%) as the oxidation catalyst, an imprinted polymethacrylic acid polymer (PMAA) as a selective adsorbent of DBT was formed using different amounts of DBT template. Then, various oxidant/sulfur molar ratios were applied during the desulfurization reactions according to the central composite design (CCD). The successful synthesis of the optimum SMIP-PMAA@MCM-48-HPW nanocomposite was confirmed by FTIR, XRD, N2-adsorption, SEM, TEM, TGA, and NMR techniques. The desulfurization percentage of the model oil reached 98.54% under the optimum conditions, and the catalyst percentage was found to be the most significant parameter for desulfurization efficiency. Comparison experiments showed that the combined role of oxidation and adsorption had an extensive impact on desulfurization efficiency. Under the optimized conditions, 96% DBT from gasoline was removed by the optimum nanocomposite. The optimum nanocomposite showed good stability and could be reused five times without a remarkable decrease in the desulfurization ability.
Sensorimotor adaptation in spatial orientation task: a fNIRS study
Authors: Yeo Sang Seok , Jang Tae Su , Yun Seong Ho 
Published: September 2023

AbstractIn sensorimotor conflicts, the brain forms and updates a new sensorimotor relationship through sensorimotor integration. As humans adapt to new sensorimotor mapping, goal-directed movements become increasingly precise. Using functional near-infrared spectroscopy, we investigated the changes in cortical activity during sensorimotor adaptation in a spatial orientation task with sensorimotor conflict. Individuals performed a reversed spatial orientation training in which the visual feedback guiding hand movements was reversed. We measured cortical activity and spatial orientation performance, including the response time, completion number, error, and accuracy. The results revealed the continuous activation in the left SMG during sensorimotor adaptation and decreased activation in the right SAC, AG and SMG after sensorimotor adaptation. These findings indicated the contribution of the left SMG to sensorimotor adaptation and the improved efficiency of cortical activity after sensorimotor adaptation, respectively. Our studies suggest the neural mechanisms related to sensorimotor adaptation to a reversed spatial orientation task.
Evaluating and prioritizing the healthcare waste disposal center locations using a hybrid multi-criteria decision-making method
Authors: Beheshtinia Mohammad Ali , Bahrami Fatemeh , Fathi Masood , Asadi Shahla 
Published: September 2023

AbstractHealthcare waste disposal center location (HCWDCL) impacts the environment and the health of living beings. Different and sometimes contradictory criteria in determining the appropriate site location for disposing of healthcare waste (HCW) complicate the decision-making process. This research presents a hybrid multi-criteria decision-making (MCDM) method, named PROMSIS, to determine the appropriate HCWDCL in a real case. The PROMSIS is the combination of two well-known MCDM methods, namely TOPSIS and PROMETHEE. Moreover, fuzzy theory is used to describe the uncertainties of the problem parameters. To provide a reliable decision on selecting the best HCWDCL, a comprehensive list of criteria is identified through a literature review and experts’ opinions obtained from the case study. In total, 40 criteria are identified and classified into five major criteria, namely economic, environmental, social, technical, and geological. The weight of the considered criteria is determined by the Analytical Hierarchy Process (AHP) method. Then, the score of the alternative HCWDCLs in each considered criterion is obtained. Finally, the candidate locations for disposing of HCWs are ranked by the proposed fuzzy PROMSIS method. The results show that the most important criteria in ranking the alternatives in the studied case are economic, environmental, and social, respectively. Moreover, the sub-criteria of operating cost, transportation cost, and pollution are identified as the most important sub-criteria, respectively.
Bacteriophages with depolymerase activity in the control of antibiotic resistant Klebsiella pneumoniae biofilms
Authors: Zurabov Fedor , Glazunov Egor , Kochetova Tatiana , Uskevich Viktoria , Popova Valentina 
Published: September 2023

AbstractKlebsiella pneumoniae is associated with a variety of infections, such as pneumonia, urogenital infection, liver abscess, and bloodstream infection. It is especially dangerous for patients in medical facilities, where it can cause ventilator-associated pneumonia or intensive care unit-acquired pneumonia. The emergence of multidrug-resistant and hypervirulent strains as well as the ability to form biofilms on various medical devices complicates the treatment of such infections and makes the use of antibiotics ineffective. The application of bacteriophages is a promising alternative for combating Klebsiella pneumoniae biofilms. In the present study a cocktail of 3 bacteriophages with depolymerase activity was used to control antibiotic resistant Klebsiella pneumoniae biofilms in vitro. Biofilms were examined using optical and scanning electron microscopy. The obtained results demonstrate that the studied bacteriophage cocktail can effectively disrupt Klebsiella pneumoniae biofilms.