bluuebunny/crossref_metadata_2025 huggingface dataset:
The pathogenic germline ETV4 P433L mutation identified in multiple primary lung cancer affect tumor stem-like property by Wnt/β-catenin pathway
Authors: Liu Yu , Fang Lingling , Wang Yalong , Fan Tao , Wang Liyu , Xiao Chu , Deng Ziqin , Cai Wenpeng , Zheng Bo , Qiu Junfeng , Li Chunxiang , He Jie
Published: October 2024

The occurrence of multiple primary lung cancer (MPLC) has witnessed a significant surge in recent years within the Chinese population. MPLC is distinguished by its potential genetic susceptibility and notable genetic heterogeneity. Investigating the etiology of MPLC holds substantial clinical importance.The whole genome sequencing (WGS) and genome-wide linkage analysis were performed in a family affected by a dominant form of lung abnormalities. Specifically, five family members were diagnosed with MPLC, while nine members had pulmonary nodules and one normal member. To confirm the potential pathogenic germline mutations sites, Sanger sequencing was performed in an additional 162 MPLC family patients. Furthermore, molecular biology experiments were conducted to investigate the function and the mechanism of the identified pathogenic mutation site in lung cancer A549 and H322, both in vitro and in vivo. Linkage analysis revealed the presence of shared genomic regions among affected family members. Subsequent exome sequencing identified a deleterious variant within these linkage intervals, specifically a heterozygous mutation in ETS-oncogene transcription factors 4 (ETV4). This particular variant was found in affected family members at a rate of 13 out of 15 individuals. Furthermore, ETV4 P433L mutation could be detected in an additional MPLC family patients and mutation frequency was 3.7% (6 out of 162). The ETV4 P433L mutations site was introduced into lung cancer cell lines, resulting in altered migration and stem-like properties of the cancer cells. Further investigation revealed that the activation of the Wnt/β-catenin signaling pathway, which is associated with stemness, could be attributed to the presence of the ETV4 P433L mutation, suggesting its involvement in tumor promotion. A novel pathogenic germline mutation, ETV4 P433L, was identified in a dominant MPLC family, with a mutation rate of 3.7% among MPLC family patients. The ETV4 P433L mutation was found to impact the stem-like properties and migration of tumors through Wnt/β-catenin signaling pathway.
Effective protective mechanisms of HO-1 in diabetic complications: a narrative review
Authors: Zhang Jing-jing , Ni Ping , Song Yi , Gao Man-jun , Guo Xi-ying , Zhao Bao-qing
Published: October 2024

Diabetes mellitus is a metabolic disorder with persistent hyperglycemia caused by a variety of underlying factors. Chronic hyperglycemia can lead to diverse serious consequences and diversified complications, which pose a serious threat to patients. Among the major complications are cardiovascular disease, kidney disease, diabetic foot ulcers, diabetic retinopathy, and neurological disorders. Heme oxygenase 1 (HO-1) is a protective enzyme with antioxidant, anti-inflammatory and anti-apoptotic effects, which has been intensively studied and plays an important role in diabetic complications. By inducing the expression and activity of HO-1, it can enhance the antioxidant, anti-inflammatory, and anti-apoptotic capacity of tissues, and thus reduce the degree of damage in diabetic complications. The present study aims to review the relationship between HO-1 and the pathogenesis of diabetes and its complications. HO-1 is involved in the regulation of macrophage polarization and promotes the M1 state (pro-inflammatory) towards to the M2 state (anti-inflammatory). Induction of HO-1 expression in dendritic cells inhibits them maturation and secretion of pro-inflammatory cytokines and promotes regulatory T cell (Treg cell) responses. The induction of HO-1 can reduce the production of reactive oxygen species, thereby reducing oxidative stress and inflammation. Besides, HO-1 also has an important effect in novel programmed cell death such as pyroptosis and ferroptosis, thereby playing a protective role against diabetes. In conclusion, HO-1 plays a significant role in the occurrence and development of diabetic complications and is closely associated with a variety of complications. HO-1 is anticipated to serve as a novel target for addressing diabetic complications, and it holds promise as a potential therapeutic agent for diabetes and its associated complications. We hope to provide inspiration and ideas for future studies in the mechanism and targets of HO-1 through this review.
Peptide-mediated gene and protein delivery systems to plant mitochondria for modifying mitochondrial functions
Authors: Abe Naoya , Numata Keiji
Published: October 2024

Plant mitochondria are essential for energy production and male sterility. The genetic transformation of plant mitochondria has attracted attention due to its potential to improve the mitochondrial function and agricultural productivity of energy crops. However, mitochondrial genome editing has been challenging because the delivery of the macromolecules needed for genome engineering to mitochondria has not been established until now. In addition, the genome editing efficiency in mitochondria needs to be improved as much as possible due to the lack of a selection marker for mitochondria. To achieve mitochondrial modification, the proteins and/or DNA/RNA needed for genome editing should be delivered to mitochondria precisely and efficiently. Peptides have been utilized to improve delivery efficiency to plant mitochondria. Thus, we herein review advances in delivery technologies related to plant mitochondrial genome engineering using various functional peptides.
A population of Vasa2 and Piwi1 expressing cells generates germ cells and neurons in a sea anemone
Authors: Miramón-Puértolas Paula , Pascual-Carreras Eudald , Steinmetz Patrick R. H.
Published: October 2024

Germline segregation, essential for protecting germ cells against mutations, occurs during early embryogenesis in vertebrates, insects and nematodes. Highly regenerative animals (e.g., cnidarians), however, retain stem cells with both germinal and somatic potentials throughout adulthood, but their biology and evolution remain poorly understood. Among cnidarians (e.g., sea anemones, jellyfish), stem cells are only known in few hydrozoans (e.g., Hydra). Here, we identify and characterize a rare, multipotent population of stem and/or progenitor cells expressing the conserved germline and multipotency proteins Vasa2 and Piwi1 in the sea anemone Nematostella vectensis. Using piwi1 and vasa2 transgenic reporter lines, we reveal that the Vasa2+/Piwi1+ cell population generates not only gametes, but also a diversity of proliferative somatic cells, including neural progenitors, in juveniles and adults. Our work has uncovered a multipotent population of Vasa2+/Piwi1+ stem/progenitor cells that forms the cellular basis to understand body plasticity and regenerative capacities in sea anemones and corals.
Impact-based forecasting of tropical cyclone-related human displacement to support anticipatory action
Authors: Kam Pui Man , Ciccone Fabio , Kropf Chahan M. , Riedel Lukas , Fairless Christopher , Bresch David N.
Published: October 2024

Tropical cyclones (TCs) displace millions every year. While TCs pose hardships and threaten lives, their negative impacts can be reduced by anticipatory actions like evacuation and humanitarian aid coordination. In addition to weather forecasts, impact forecast enables more effective response by providing richer information on the numbers and locations of people at risk of displacement. We introduce a fully open-source implementation of a globally consistent and regionally calibrated TC-related displacement forecast at low computational costs, combining meteorological forecast with population exposure and respective vulnerability. We present a case study of TC Yasa which hit Fiji in December 2020. We emphasise the importance of considering the uncertainties associated with hazard, exposure, and vulnerability in a global uncertainty analysis, which reveals a considerable spread of possible outcomes. Additionally, we perform a sensitivity analysis on all recorded TC displacement events from 2017 to 2020 to understand how the forecast outcomes depend on these uncertain inputs. Our findings suggest that for longer forecast lead times, decision-making should focus more on meteorological uncertainty, while greater emphasis should be placed on the vulnerability of the local community shortly before TC landfall. Our open-source codes and implementations are readily transferable to other users, hazards, and impact types.
Modelling scenarios for water supply and sanitation technologies in Jordan
Authors: Garfias Royo Margarita , Parikh Himanshu , Campos Luiza , Talozi Samer , Parikh Priti
Published: October 2024

The influx of refugees, population growth and current agricultural practices have led to an increase in water demand in Jordan, placing pressure on existing water provision. Climate change further exacerbates declining water availability. Against this backdrop, the techno-economic feasibility of four water supply and sanitation alternatives for small and medium scale cities in Jordan were explored, using local unit costs and Al-Mafraq as a case study. City level piped network combined with household rooftop rainwater harvesting and surface runoff collection into local ponds and piped networks with treatment using the nature-based solution of root-zone for sanitation were demonstrated to provide the highest benefits in terms of cost, convenience and water conservation. Our work highlights the need to invest in long-term urban infrastructure networks to promote sustainable future growth of cities. This is vital to address severe water scarcity challenges that ultimately impact those at the urban fringes most.
Human DNA polymerase ε is a source of C>T mutations at CpG dinucleotides
Authors: Tomkova Marketa , McClellan Michael John , Crevel Gilles , Shahid Akbar Muhammed , Mozumdar Nandini , Tomek Jakub , Shepherd Emelie , Cotterill Sue , Schuster-Böckler Benjamin , Kriaucionis Skirmantas
Published: October 2024

C-to-T transitions in CpG dinucleotides are the most prevalent mutations in human cancers and genetic diseases. These mutations have been attributed to deamination of 5-methylcytosine (5mC), an epigenetic modification found on CpGs. We recently linked CpG>TpG mutations to replication and hypothesized that errors introduced by polymerase ε (Pol ε) may represent an alternative source of mutations. Here we present a new method called polymerase error rate sequencing (PER-seq) to measure the error spectrum of DNA polymerases in isolation. We find that the most common human cancer-associated Pol ε mutant (P286R) produces an excess of CpG>TpG errors, phenocopying the mutation spectrum of tumors carrying this mutation and deficiencies in mismatch repair. Notably, we also discover that wild-type Pol ε has a sevenfold higher error rate when replicating 5mCpG compared to C in other contexts. Together, our results from PER-seq and human cancers demonstrate that replication errors are a major contributor to CpG>TpG mutagenesis in replicating cells, fundamentally changing our understanding of this important disease-causing mutational mechanism.
Zinc, copper, and selenium levels in vitiligo: a systematic review and meta-analysis
Authors: Anam Khan , Ananyan Sampath , Rishabh Mittal , Dinesh Asati , Ashwin Kotnis
Published: October 2024

Vitiligo is a dermatological disease characterized by loss of melanocytes, causing non-scaly white macules on the skin. Zinc, copper, and selenium are important micronutrients that play a role in the normal functioning of the body and have been found to potentially aid in vitiligo treatment, although the relationship between their serum levels and vitiligo is not yet fully understood. This is a systematic review aimed at assessing the levels of serum zinc, copper, and selenium and their association with vitiligo. This review was performed following the Preferred Reporting Items of the systematic Review and Meta-Analysis (PRISMA) checklist and Cochrane guidelines. A comprehensive literature search was conducted on PubMed, Google Scholar and 41 studies published between 1970 and 2022 including 3353 vitiligo cases and 10,638 controls were included in the meta-analysis conducted from August 2022 till September 2023. The quality of the studies was assessed using the National Heart Lung and Blood Institute Study Quality Assessment tool, and the risk of bias was represented using the RobVis tool. The statistical analysis was performed using Review Manager (RevMan) Version 5.4. This meta-analysis indicate a significant decline in serum zinc levels (Z = 4.97; P < 0.0001; SMD = − 0.86; 95% CI − 1.19 to − 0.52) in vitiligo group with high statistical heterogeneity (Tau2 = 0.74; Chi2 = 513.95, d.f. = 26 [P < 0.00001]; I2 = 95%). Similarly for serum copper levels there was decline (Z = 2.43; P < 0.0001; SMD = − 0.50; 95% confidence interval [CI] − 0.91 to − 0.10) in vitiligo group and high statistical heterogeneity (Tau2 = 0.92; Chi2 = 475.10, d.f. = 22 [P < 0.00001]; I2 = 95%). On the other hand, there was a increase of serum selenium levels in the vitiligo group (Z = 0.56; P < 0.0001; SMD = 0.23; 95% confidence interval [CI], 0.58 to 1.04) and the results reveals high statistical heterogeneity among studies (Tau2 = 1.93; Chi2 = 406.44, d.f. = 11 [P < 0.00001]; I2 = 97%) in vitiligo patients compared to healthy controls. Publication bias was not found for the studies analysed. This study analyses the association of serum micronutrient levels and vitiligo among patients and controls from published research along with sub-group analysis specific to Asian populations using a meta-analysis. Low serum levels of Zinc and copper and high selenium levels are associated with Vitiligo.
New connections of medication use and polypharmacy with the gut microbiota composition and functional potential in a large population
Authors: Larsson Anna , Ericson Ulrika , Jönsson Daniel , Miari Mariam , Athanasiadis Paschalis , Baldanzi Gabriel , Brunkwall Louise , Hellstrand Sophie , Klinge Björn , Melander Olle , Nilsson Peter M. , Fall Tove , Maziarz Marlena , Orho-Melander Marju
Published: October 2024

Medication can affect the gut microbiota composition and function. The aim of this study was to investigate connections between use of common non-antibiotic medicines and the gut microbiota composition and function in a large Swedish cohort (N = 2223). Use of 67 medications and polypharmacy (≥ 5 medications), based on self-reported and prescription registry data, were associated with the relative abundance of 881 gut metagenomic species (> 5% prevalence) and 103 gut metabolic modules (GMMs). Altogether, 97 associations of 26 medications with 40 species and of four medications with five GMMs were observed (false discovery rate < 5%). Several earlier findings were replicated like the positive associations of proton pump inhibitors (PPIs) with numerous oral species, and those of metformin with Escherichia species and with lactate consumption I and arginine degradation II. Several new associations were observed between, among others, use of antidepressants, beta-blockers, nonsteroidal anti-inflammatory drugs and calcium channel blockers, and specific species. Polypharmacy was positively associated with Enterococcus faecalis, Bacteroides uniformis, Rothia mucilaginosa, Escherichia coli and Limosilactobacillus vaginalis, and with 13 GMMs. We confirmed several previous findings and identified numerous new associations between use of medications/polypharmacy and the gut microbiota composition and functional potential. Further studies are needed to confirm the new findings.
Performance of yellow and pink oyster mushroom dyes in dye sensitized solar cell
Authors: Pirdaus Nur Alfarina , Ahmad Nurfadzilah , Dahlan Nofri Yenita , Redzuan Ainur Nisha , Zalizan Aisyatul Husna , Muhammad-Sukki Firdaus , Bani Nurul Aini , Abdul Patah Muhamad Fazly , Wan-Mohtar Wan Abd Al Qadr Imad
Published: October 2024

A solar photovoltaic (PV) cell, is an electrical device that uses the PV effect to convert light energy into electricity. The application of oyster mushroom dyes in dye sensitized solar cell (DSSC) is a novel strategy to substitute the costly chemical production process with easily extractable, environmentally acceptable dyes. Both dyes of yellow and pink oyster mushrooms were extracted using the same process but dried into powder form using two techniques, warm drying and freeze drying. The characterization was carried out utilizing current-voltage (I-V) characterization for electrical properties, Ultraviolet-Visible (UV-Vis) spectrophotometer for optical properties, Field Emission Scanning Electron Microscopy (FESEM), and Atomic Force Microscopy (AFM) for the structural properties. It was found that freeze-dried pink and yellow oyster mushroom had shown the good properties for DSSC application as it produced energy bandgap which lies within the range of efficient dye sensitizer; 1.7 eV and 2.2 eV, the most uniform distribution of pores and a nearly spherical form in FESEM analysis, and AFM result obtained with the highest root mean square (RMS) roughness value (26.922 and 34.033) with stereoscopic morphologies. The data proved that mushroom dyes can be incorporated in DSSC with the optimization of drying method in the extraction process, dilution of dye and the layer of deposition on the glass substrate. The current density-voltage (J–V) characteristics of fabricated DSSC was characterized using Newport Oriel Sol3A solar simulator under AM 1.5 Sun condition (100 mW/cm2, 25 oC). From the result obtained by solar simulator, the fabricated FTO/TiO2/Pleurotus djamor dye/Pt indicated the Voc of 0.499 V and Jsc of 0.397 mA/cm2.
Factors shaping pelagic-benthic coupling in the process of settlement in an Arctic fjord
Authors: Ronowicz Marta , Balazy Piotr , Chełchowski Maciej , Kuklinski Piotr , Patuła Weronika , Sowa Anna , Søreide Janne E. , Weydmann-Zwolicka Agata
Published: October 2024

Benthic organisms typically possess a planktonic propagule stage in the form of larvae or spores, which enables them to spread over large distances before settlement, and promotes tight pelago-benthic coupling. However, factors driving dispersal and epibenthos recruitment in shallow hard-bottom Arctic communities are poorly known. We therefore conducted a year-round in situ colonization experiment in Isfjorden (Svalbard), and found out that variation in early-stage epibenthic assemblages was explained by the combination of: abiotic (45.9%) and biotic variables (23.9%), and their interactions (30.2%). The upward-facing experimental plates were dominated by coralline algae, and this is the first study showing that at high latitudes coralline algae Lithothamnion sp. settle in high numbers on available substrates during the polar night in winter. The downward-facing plates, which had much less exposure to light, contained more diverse organisms, with a predominance of polychaetas and bryozoans. However, in summer, the barnacle Semibalanus balanoides outcompeted all the other recruits, as a result of massive occurrence of meroplanktonic Cirripedia larvae, triggered by the phytoplankton bloom. In conclusion, the rate and success of epibenthic settlements were dependent mostly on light availability and temperature, suggesting that larval settlement will be impacted by global warming with some taxa benefitting, while others losing.
The role of rice husk in Oreochromis niloticus safety enhancement by bio-adsorbing copper oxide nanoparticles following its green synthesis: an endeavor to advance environmental sustainability
Authors: Hamed Aliaa , Badran Shereen R.
Published: October 2024

Lowering nanoparticles (NPs) toxicity before discharge into aquatic environments and employing agricultural waste materials for environmental sustainability are necessary nowadays. Since this has never been done, this work examines how green CuO NPs treated with rice husk (RH) as a bio-adsorbent may be safer for Nile tilapia (Oreochromis niloticus) than chemically manufactured ones. So, five groups of fish were randomly placed in glass aquaria. One group was a control, and four groups received 50 mg/L green and chemically produced CuO NPs (GS and CS) with and without RH for 24, 48, and 96 h. RH was collected from all groups, and the results showed GS-CuO NPs had a greater adsorptive capacity than CS-CuO NPs after all time intervals. After analyzing fish indicators in all groups compared to the control, higher Cu bioaccumulation was exhibited in the liver and gills. The liver and gills showed elevated levels of glutathione peroxidase (GPx), catalase (CAT), and thiobarbituric acid reactive substances (TBARS), while the levels of glutathione reduced (GSH) were significantly lower. In addition, Cu exposure impaired liver and gill histology. Finally, our results indicated that using RH as an adsorbent for CuO NPs after their green synthesis instead of chemical synthesis before they enter the aquatic environment can enhance the overall health of fish and environmental sustainability.
Integrating holotomography and deep learning for rapid detection of NPM1 mutations in AML
Authors: Kim Hyunji , Kim Geon , Park HeyJung , Lee Mahn Jae , Park YongKeun , Jang Seongsoo
Published: October 2024

Rapid and accurate diagnosis of acute myeloid leukemia (AML) remains a significant challenge, particularly in the context of myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm with NPM1 mutations. This study introduces an innovative approach using holotomography (HT), a 3D label-free quantitative phase imaging technique, to detect NPM1 mutations. We analyzed a dataset of 2073 HT myeloblast images from 48 individuals, including both NPM1 wild-type and mutated samples, to distinguish subcellular morphological changes associated with NPM1 mutations. Employing a convolutional neural network, we analyzed 3D cell morphology, focusing on refractive index distributions. The machine learning model showed high accuracy, with an area under the receiver operating characteristic curve of 0.9375 and a validation accuracy of 76.0%. Our findings reveal distinct morphological differences between the NPM1 wild-type and mutation at the subcellular level. This study demonstrates the potential of HT combined with deep learning for early, efficient, and cost-effective diagnosis of AML, offering a promising alternative to traditional stepwise genetic testing methods and providing additional assistance in morphological myeloblast discrimination. This approach may revolutionize the diagnostic process in leukemia, facilitating early detection and potentially reducing the reliance on extensive genetic testing.
Identification and analysis of differentially expressed lncRNAs and their ceRNA networks in DMD/mdx primary myoblasts
Authors: Gorji Abdolvahab Ebrahimpour , Ahmadian Kasra , Roudbari Zahra , Sadkowski Tomasz
Published: October 2024

This study explored the significance of long non-coding RNAs (lncRNAs), particularly their role in maintaining dystrophin protein stability and regulating myocyte proliferation and differentiation. The investigation focused on DMD/mdx mouse skeletal muscle primary myoblasts, aiming to identify lncRNAs potential as biomarkers and therapeutic targets for Duchenne muscular dystrophy (DMD). Utilizing CLC Genomics Workbench software, 554 differentially expressed lncRNAs were identified in DMD/mdx mice compared to wild-type (WT) control. Among them, 373 were upregulated, and 181 were downregulated. The study highlighted specific lncRNAs (e.g., 5930430L01Rik, Gm10143, LncRNA1490, LncRNA580) and their potential regulatory roles in DMD key genes like IGF1, FN1, TNNI1, and MYOD1. By predicting miRNA and their connections with lncRNA and mRNA (ceRNA network) using tools such as miRNet, miRSYSTEM and miRCARTA, the study revealed potential indirect regulation of Dystrophin, IGF1R and UTRN genes by identified lncRNAs (e.g. 2310001H17Rik-203, C130073E24Rik-202, LncRNA2767, 5930430L01Rik and LncRNA580). These findings suggest that the identified lncRNAs may play crucial roles in the development and progression of DMD through their regulatory influence on key gene expression, providing valuable insights for potential therapeutic interventions.
A proteomics perspective on 2 years of high-intensity training in horses: a pilot study
Authors: Johansson L. , Ringmark S. , Bergquist J. , Skiöldebrand E. , Widgren A. , Jansson A.
Published: October 2024

The human plasma proteome is rather well studied, but not that of other species, including horses. The aims of this study were to (1), explore differences in plasma proteomic profile of young elite harness trotters kept under standardised conditions and subjected to two different training programmes for 2 years and (2) explore changes in proteomic profile over time during the training period. From September at age 1.5 year to March at age 2 years, 16 Standardbred horses were exposed to the same training programme. In March, high-intensity training was introduced and the horses were divided into two training groups (High and Low). Blood samples were collected at rest in December as 1.5-year-olds, July as 2-year-olds, December as 2.5-year-olds and December as 3.5-year-olds. Untargeted proteomics was performed and a hypothesis-generating approach was used in statistical analysis (t-tests). At the age of 2.5 years, the level of serotransferrin was higher in the High group (P = 0.01) and at least at one sampling occasion, proteins associated with fat metabolism, oxidant/antioxidant processes, cardiovascular responses, bone formation and inflammation were lower in High group compared to Low (P < 0.05). Analyses of changes over time revealed that levels of proteins involved in energy metabolism, red cell metabolism, circulation, oxidant/antioxidant activity, bone formation, inflammation, immune modulation and cellular and vascular damage changed (P < 0.05). The results indicate that proteomics analysis of blood plasma could be a viable tool for evaluation of exercise adaptations, performance and for health monitoring, with several potential biomarkers identified in this study.
A besyian regularisation neural network approach for hepatitis B virus spread prediction and immune system therapy model
Authors: Galal Ahmed M. , Haider Qusain , Hassan Ali , Arshad Mubashar , Alam Mohammad Mahtab , Al-Essa Laila A. , Habenom Haile
Published: October 2024

The primary aim of the article is to analyze the response of the human immune system when it encounters the hepatitis B virus. This is done using a mathematical system of differential equations. The differential equation system has six components, likely representing various aspects of the immune response or virus dynamics. A Bayesian regularization neural network has been presented in the process of training. These networks are employed to find solutions for different categories or scenarios related to hepatitis B infection. The Adams method is used to generate reference data sets. The back-propagated artificial neural network, based on Bayesian regularization, is trained and validated using the generated data. The data is divided into three sets: 90% for training and 5% each for testing and validation. The correctness and effectiveness of the proposed neural network model have been assessed using various evaluation metrics. The metrics have been used in this study are Mean Square Error (MSE), histogram errors, and regression plots. These measures provide support to the neural network to approximate the immune response to the hepatitis B virus.
Systematic review and meta-analysis of standalone digital interventions for cognitive symptoms in people without dementia
Authors: Cabreira Veronica , Wilkinson Tim , Frostholm Lisbeth , Stone Jon , Carson Alan
Published: October 2024

Cognitive symptoms are prevalent across neuropsychiatric disorders, increase distress and impair quality of life. Self-guided digital interventions offer accessibility, scalability, and may overcome the research-to-practice treatment gap. Seventy-six trials with 5214 participants were identified. A random-effects meta-analysis investigated the effects of all digital self-guided interventions, compared to controls, at post-treatment. We found a small-to-moderate positive pooled effect on cognition (k = 71; g = −0.51, 95%CI −0.64 to −0.37; p < 0.00001) and mental health (k = 30; g = −0.41, 95%CI −0.60 to −0.22; p < 0.0001). Positive treatment effects on fatigue (k = 8; g = −0.27, 95%CI −0.53 to −0.02; p = 0.03) and quality of life (k = 22; g = −0.17, 95%CI −0.34 to −0.00; p = 0.04) were only marginally significant. No significant benefit was found for performance on activities of daily living. Results were independent of control groups, treatment duration, risk of bias and delivery format. Self-guided digital transdiagnostic interventions may benefit at least a subset of patients in the short run, yet their impact on non-cognitive outcomes remains uncertain.
SMARCD1 is an essential expression-restricted metastasis modifier
Authors: Ross Christina , Gong Li-Yun , Jenkins Lisa M. , Ha Ngoc-han , Majocha Megan , Hunter Kent W.
Published: October 2024

Breast cancer is the most frequently diagnosed cancer worldwide, constituting 15% of cases in 2023. The predominant cause of breast cancer-related mortality is metastasis, and a lack of metastasis-targeted therapies perpetuates dismal outcomes for late-stage patients. By using meiotic genetics to study inherited transcriptional network regulation, we have identified, to the best of our knowledge, a new class of “essential expression-restricted” genes as potential candidates for metastasis-targeted therapeutics. Building upon previous work implicating the CCR4-NOT RNA deadenylase complex in metastasis, we demonstrate that RNA-binding proteins NANOS1, PUM2, and CPSF4 also regulate metastatic potential. Using various models and clinical data, we pinpoint Smarcd1 mRNA as a target of all three RNA-BPs. Strikingly, both high and low expression of Smarcd1 correlate with positive clinical outcomes, while intermediate expression significantly reduces the probability of survival. Applying the theory of “essential genes” from evolution, we identify 50 additional genes that require precise expression levels for metastasis to occur. Specifically, small perturbations in Smarcd1 expression significantly reduce metastasis in mouse models and alter splicing programs relevant to the ER+/HER2-enriched breast cancer. Identification subtype-specific essential expression-restricted metastasis modifiers introduces a novel class of genes that, when therapeutically “nudged” in either direction, may significantly improve late-stage breast cancer patients.
Discovery of a potent, Kv7.3-selective potassium channel opener from a Polynesian traditional botanical anticonvulsant
Authors: Abbott Geoffrey W. , Manville Rían W.
Published: October 2024

Plants remain an important source of biologically active small molecules with high therapeutic potential. The voltage-gated potassium (Kv) channel formed by Kv7.2/3 (KCNQ2/3) heteromers is a major target for anticonvulsant drug development. Here, we screened 1444 extracts primarily from plants collected in California and the US Virgin Islands, for their ability to activate Kv7.2/3 but not inhibit Kv1.3, to select against tannic acid being the active component. We validated the 7 strongest hits, identified Thespesia populnea (miro, milo, portia tree) as the most promising, then discovered its primary active metabolite to be gentisic acid (GA). GA highly potently activated Kv7.2/3 (EC50, 2.8 nM). GA is, uniquely to our knowledge, 100% selective for Kv7.3 versus other Kv7 homomers; it requires S5 residue Kv7.3-W265 for Kv7.2/3 activation, and it ameliorates pentylenetetrazole-induced seizures in mice. Structure-activity studies revealed that the FDA-approved vasoprotective drug calcium dobesilate, a GA analog, is a previously unrecognized Kv7.2/3 channel opener. Also an active aspirin metabolite, GA provides a molecular rationale for the use of T. populnea as an anticonvulsant in Polynesian indigenous medicine and presents novel pharmacological prospects for potent, isoform-selective, therapeutic Kv7 channel activation.
Polar domain walls induced by sequential symmetry breaking in frustrated mechanical metamaterials
Authors: Zhou Yuan , Zhang Yafei , Wen Zhixuan , Chen Chang Qing
Published: October 2024

Frustration hinders ideal local interactions in systems ranging from artificial spin ices with ice rules to mechanical metamaterials featuring regular floppy modes. While geometric frustrations have been known to promote complex ordered patterns in tessellated lattice structures, there is growing interest in global frustrations due to the topologically nontrivial geometry of metamaterials. However, multiferroic orders in globally frustrated metamaterials have remained elusive. Here, we present polar domain walls constrained in flexible mechanical metamaterials with global frustration and sequential symmetry breaking. We showcase that under simple compressive loading, competing interactions in globally frustrated metamaterials give rise to mixed deformations with high-order buckling modes described by an emergent order parameter. Utilizing an elastic mechanism model, we unveil the process of sequential symmetry breaking and capture the formation of polar domain walls exhibiting a chiral distribution within a multi-well potential landscape. We further demonstrate how to eliminate frustration through torsional loading, leading to symmetry restoration. These results provide insights into the intricate interactions between order and frustration, inspiring the modulation of domain walls in macroscopic systems.
Influence of dislocation cells on hydrogen embrittlement in wrought and additively manufactured Inconel 718
Authors: Santos Maldonado Claudia-Tatiana , Zafra Alfredo , Martínez Pañeda Emilio , Sandmann Paul , Morana Roberto , Pham Minh-Son
Published: October 2024

Hydrogen embrittlement (HE) is a major issue for the mechanical integrity of high-strength alloys exposed to hydrogen-rich environments, with diffusion and trapping of hydrogen being critical phenomena. Here, the role of microstructure on hydrogen diffusion, trapping and embrittlement in additively manufactured (AM) and wrought Inconel 718 is compared, revealing the key role played by dislocation cells. Trapping behaviour in hydrogen-saturated alloys is analysed by thermal desorption spectroscopy and numerical simulations. A high density of hydrogen traps in cell walls, attributed to dense dislocations and Laves phases, are responsible for the local accumulation of hydrogen, causing significant loss in strength, and triggering cracking along dislocation cell walls. The influential role of dislocation cells alters fracture behaviour from intergranular in the wrought alloy to intragranular for the AM alloy, due to the large proportion of dislocation cells in AM alloys. In addition, the cellular network of dislocations accelerates hydrogen diffusion, enabling faster and deeper penetration of hydrogen in the AM alloy. These results indicate that the higher HE susceptibility of nickel superalloys is intrinsically associated with the interaction of hydrogen with dislocation walls.
Methodological choices and clinical usefulness for machine learning predictions of outcome in Internet-based cognitive behavioural therapy
Authors: Hentati Isacsson Nils , Ben Abdesslem Fehmi , Forsell Erik , Boman Magnus , Kaldo Viktor
Published: October 2024

Background

While psychological treatments are effective, a substantial portion of patients do not benefit enough. Early identification of those may allow for adaptive treatment strategies and improved outcomes. We aimed to evaluate the clinical usefulness of machine-learning (ML) models predicting outcomes in Internet-based Cognitive Behavioural Therapy, to compare ML-related methodological choices, and guide future use of these.

Methods

Eighty main models were compared. Baseline variables, weekly symptoms, and treatment activity were used to predict treatment outcomes in a dataset of 6695 patients from regular care.

Results

We show that the best models use handpicked predictors and impute missing data. No ML algorithm shows clear superiority. They have a mean balanced accuracy of 78.1% at treatment week four, closely matched by regression (77.8%).

Conclusions

ML surpasses the benchmark for clinical usefulness (67%). Advanced and simple models perform equally, indicating a need for more data or smarter methodological designs to confirm advantages of ML.
Compound and cascading droughts and heatwaves decrease maize yields by nearly half in Sinaloa, Mexico
Authors: Sutanto Samuel J. , Zarzoza Mora Susana B. , Supit Iwan , Wang Mengru
Published: October 2024

The impact of droughts and heatwaves on agriculture losses has been exacerbated by the occurrence of compound and cascading events. Here we present a study that evaluates the impact of these events both as singly and as compound and cascading on maize yield in Sinaloa Mexico from 1990 to 2022, using the WOFOST crop model. Drought and heatwave events were identified using the Standardized Precipitation Index and threshold method, respectively. Results show that yield reduction (25%) is found during extreme drought events, emphasizing the vulnerability of maize farming to unfavorable drought conditions. While heatwaves alone did not show a significant impact on maize yields, the compound and cascading droughts and heatwaves amplified the loss of maize yields by up to 44% compared to normal conditions. This study highlights the need for adaptive strategies in agriculture to sustain food security during extreme events, especially in the context of multi hazard framework.
Increasing dam failure risk in the USA due to compound rainfall clusters as climate changes
Authors: Hwang Jeongwoo , Lall Upmanu
Published: October 2024

A changing climate, with intensifying precipitation may contribute to increasing failures of dams by overtopping. We present the first analysis of rainfall sequences and events associated with recent hydrologic failures of 552 dams in the United States. We find that the maximum 1-day rainfall associated with failure was often not extreme compared to dam spillway design criteria, even when accounting for rainfall statistics changing with time at each site. However, the combination of the total rainfall 5 to 30 days prior and the maximum 1-day rainfall associated with dam failure is rare. Persistent atmospheric circulation patterns that lead to recurrent rainfall events, rather than just more moisture in the atmosphere is a possible reason. The probability of these compound precipitation risks has increased across much of the country. With over 90,000 aging dams still in service, the increasing likelihood of intense rainfall sequences raises concerns about future dam failures.
Stress granules are not present in Kras mutant cancers and do not control tumor growth
Authors: Libert Maxime , Quiquempoix Sophie , Fain Jean S , Pyr dit Ruys Sébastien , Haidar Malak , Wulleman Margaux , Herinckx Gaëtan , Vertommen Didier , Bouchart Christelle , Arsenijevic Tatjana , Van Laethem Jean-Luc , Jacquemin Patrick
Published: October 2024

Stress granules (SG) are membraneless ribonucleoprotein-based cytoplasmic organelles that assemble in response to stress. Their formation is often associated with an almost global suppression of translation, and the aberrant assembly or disassembly of these granules has pathological implications in neurodegeneration and cancer. In cancer, and particularly in the presence of oncogenic KRAS mutations, in vivo studies concluded that SG increase the resistance of cancer cells to stress. Hence, SG have recently been considered a promising target for therapy. Here, starting from our observations that genes coding for SG proteins are stimulated during development of pancreatic ductal adenocarcinoma, we analyze the formation of SG during tumorigenesis. We resort to in vitro, in vivo and in silico approaches, using mouse models, human samples and human data. Our analyses do not support that SG are formed during tumorigenesis of KRAS-driven cancers, at least that their presence is not universal, leading us to propose that caution is required before considering SG as therapeutic targets.
Light-driven nitrogen fixation routes for green ammonia production
Authors: Collado Laura , Pizarro Alejandro H. , Barawi Mariam , García-Tecedor Miguel , Liras Marta , de la Peña O'Shea Víctor A.
Published: October 2024

The global goal for decarbonization of the energy sector and the chemical industry could become a reality by a massive increase in renewable-based technologies.
Construction of cationic covalent organic framework for efficient gold extraction
Authors: Jiang Yequan , Liu Jie , Huang Zhengcheng , Li Jianqiang , Luo Feng
Published: October 2024

We report a rare ionic covalent organic framework (named as ECUT-iCOF-5) synthesized by the Knoevenagel reaction using an ionic liquid monomer for gold extraction with high extraction ability.
Two-dimensional carbazole-based COFs for high-performance lithium–sulfur batteries
Authors: Xiao Yuchen , Wei Shanyue , Wang Xuan , Liu Jia , Wu Xiaowei , Xie Yiming , Lu Can-Zhong
Published: October 2024

Carbazole-based COFs were synthesized and show excellent capacity retentions and stability in lithium–sulfur batteries.
Fe3O4 nanostructure films as solar-thermal conversion materials for ammonia synthesis
Authors: Fu Rong , Lei Di , Li Zhenlu , Zhang Hangjian , Zhao Xiaofei , Tao Shuo
Published: October 2024

Fe3O4 film is composed of dispersed nanoparticles and irregular nanopores, where photons can be trapped by multi-reflection. The solar-thermal temperature can raise to above 350 °C and meet the temperature requirement for ammonia synthesis.
Csp2–H/F bond activation and borylation with iron
Authors: Zars Ethan , Pick Lisa , Kankanamge Achala , Gau Michael R. , Meyer Karsten , Mindiola Daniel J.
Published: October 2024

[{K(18-C-6)}2(tBupyrr2pyr)Fe(N2)] splits the Csp2–H and Csp2–F bond of benzene and fluorobenzene to form [{K(18-C-6)}(tBupyrr2pyr)Fe(C6H5)] and reaction with ClBcat yields [K(18-C-6)(thf)2][(tBupyrr2pyr)FeCl]. Usage of B2pin2 traps the hydride of the arene as [K(18-C-6)HB2Pin2].
Incorporation of enzyme-mimic species in porous materials for the construction of porous biomimetic catalysts
Authors: Liu Zikun , Ling Jia-Long , Liu Yang-Yang , Zheng Bu-Hang , Wu Chuan-De
Published: October 2024

This feature article summarizes the recent advances in constructing porous biomimetic catalyst platforms by using porous materials as the supporting matrices.
Modelling and analysis of polarisation characteristics in lithium insertion electrodes considering charge transfer and contact resistances
Authors: Ariyoshi Kingo , Nagashima Yuma
Published: October 2024

Polarization equation to explain the change in the polarization curve of lithium insertion electrodes from linear to exponential.
Correction: Malachite green: a long-buried water-soluble AIEgen with near-infrared fluorescence for living cell nucleus staining
Authors: Luo Yuan , Zhou Lihua , Du Lili , Xie Yangzi , Lou Xiang-Yang , Cai Lintao , Tang Ben Zhong , Gong Ping , Zhang Pengfei
Published: October 2024

Correction for ‘Malachite green: a long-buried water-soluble AIEgen with near-infrared fluorescence for living cell nucleus staining’ by Yuan Luo et al., Chem. Commun., 2024, 60, 1452–1455, https://doi.org/10.1039/D3CC05535C.
Hydrothermal synthesis and structure of organically templated layered neptunyl(vi) phosphate (NpO2)3(PO4)2(Terpy)
Authors: Zhang Lei , Wang Yu , Xu Mengyu , Kokot Alex M. , Qiu Jie , Burns Peter C.
Published: October 2024

First reported (NpVIO2)2(PO4)22− sheets based upon the uranophane anion topology, that are bonded via π–π interactions between the NpVIO2(Terpy)2+ ligands that are perpendicular to the sheets.
Effect of the interchain interaction on the crystallization kinetics and crystal structure of polylactic acid under nitrogen
Authors: Peng Qianyun , Li Shaojie , Liu Feng , Li Guangxian , Liao Xia
Published: October 2024

In order to prepare polylactic acid (PLA) foam material with excellent performance by utilizing nitrogen (N2), the crystallization behavior of PLA under N2 has been studied.
Machine learning assisted calibration of PVT simulations for SiC crystal growth
Authors: Taucher Lorenz , Ramadan Zaher , Hammer René , Obermüller Thomas , Auer Peter , Romaner Lorenz
Published: October 2024

In this study, machine learning models were successfully applied as substitutes for the computationally expensive numerical PVT simulation, enabling calibration as well as in-depth investigations, including sensitivity and uncertainty analysis.
Investigation of perovskite materials for solar cells using scanning tunneling microscopy
Authors: Wang Yule , Cui Bin-bin , Zhao Yiming , Lin Tao , Li Juan
Published: October 2024

This article presents recent research progress of scanning tunneling microscopy/spectroscopy applied to perovskite materials for solar cells, providing valuable insights into their fundamental properties at the atomic scale.
Influence of pseudo-Jahn–Teller activity on the singlet–triplet gap of azaphenalenes
Authors: Majumdar Atreyee , Jindal Komal , Das Surajit , Ramakrishnan Raghunathan
Published: October 2024

Geometry optimization at post-MP2 quantum chemistry levels capture symmetry lowering of cyclazine and its polyaza analogues with nitrogen at electron-deficient sites.
From loose to tight: unveiling bond stretch isomerism in π-complexes of Li, Na and K
Authors: Ramya Pilankatta K. , Shivhare Ayush , Deshmukh Milind M. , Suresh Cherumuttathu H.
Published: October 2024

Bond-stretch isomers, resulting from organic molecules interaction with alkali metals, show varying carbon–metal bond lengths.
The effect of separation distance on hydrogen spillover in Os promoted Co@HCS catalysts
Authors: Molefe Tshepo , Forbes Roy Peter , Coville Neil John
Published: October 2024

Decreasing the carbon shell thickness increased the reducibility of Co3O4. The reducibility of Co3O4 was further achieved by adding an Os promoter outside of the sphere showing that H spillover was favoured over H2 diffusion/Co reduction by carbon.
Balancing exploration and exploitation in de novo drug design
Authors: Langevin Maxime , Bianciotto Marc , Vuilleumier Rodolphe
Published: October 2024

Using a mean-variance framework, we present a simple model to bridge the optimization objective of goal-directed generation with the need for diversity. We motivate theoretically that it minimizes risk measures when selecting multiple molecules.
MolBar: a molecular identifier for inorganic and organic molecules with full support of stereoisomerism
Authors: van Staalduinen Nils , Bannwarth Christoph
Published: October 2024

MolBar: an identifier for organic and inorganic molecules capturing various forms of stereochemistry. Using Cartesian coordinates as input, this identifier aids chemical space exploration and enables duplicate detection in molecular databases.
An insightful study on the reduction and extraction of neptunium assisted by molybdenum
Authors: Hao Huaixin , Liu Yaoyang , Cao Hong , Wang Zhipeng , Xu Chao , Chen Jing
Published: October 2024

Mo dramatically boosts the extraction of Np(v) by TRPO through the catalytic reduction effect in both the aqueous phase and organic phase.
Toxicological evaluation of SVOCs in exhaust emissions from light-duty vehicles using different fuel alternatives under sub-freezing conditions
Authors: Yang Mo , Aakko-Saksa Päivi , Hakkarainen Henri , Rönkkö Topi , Koponen Päivi , Zeng Xiao-Wen , Dong Guang-Hui , Jalava Pasi I.
Published: October 2024

SVOC toxicity in vehicle exhaust varies by fuel. Stricter diesel regulations haven't reduced toxicity. Gasoline exhaust poses the highest risk, with compressed natural gas and ethanol/gasoline also showing notable toxicity.
Unveiling the role of structural vacancies in Mn-based Prussian blue analogues for energy storage applications
Authors: Gao Chongwei , Chen Ming , Li Jiantao , Wang Xunan , Zhang Guobin , Tan Xi , Zhang Shuhua , Feng Guang , Zhai Dengyun , Kang Feiyu
Published: October 2024

In this study, we explore two potential pathways for vacancy formation in Mn-based Prussian blue analogues, providing new insights for structural regulation.