bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Precursory Signals of Localized Torrential Rainfall From Geostationary Satellite and Radar Observations: A Case Study of the 2022 Seoul Flood
Authors: Kim Gyuyeon , Choi Yong-Sang , Ho Junho
Published: July 2024

The Korean Peninsula frequently experiences localized torrential rainfall (LTR) in the summer. However, on August 8, 2022, a peculiar LTR occurred by the continuous generation of convective clouds within a few hours, numerical weather prediction model was hard to forecast such a high intensity of LTR. This study explores the possibility of uncovering potential precursory signals using remote sensing techniques in both Geostationary Korea Multi-Purpose Satellite 2A (GK2A) and the operational RKSG (Camp Humphreys) Weather Surveillance Radar 88 Doppler (WSR-88D). Using cloud properties from GK2A, cloud top temperature showed a decrease and maintained low values below 220 K 1–1.5 h before the LTR events. However, discerning the exact onset of LTR in already mature stage clouds using only GK2A variables proved challenging. Instead, liquid water content from RKSG sharply increased before the LTR started. Our calculation of the LTR potential from a combination of GK2A and RKSG cloud properties shows a more accurate precursory signal of LTR than from GK2A cloud properties solely or RKSG either. This study highlights the synergistic benefits of combining geostationary satellite and radar observations to understand and predict early precursors of LTR events.
Teachers’ use and perceptions of Let’s Talk about Children
Authors: Raitila Pilvi , Heiskanen Noora , Karhu Anne
Published: July 2024

Schools play significant roles in promoting pupils’ well-being. This study explores teachers’ experiences using the research-based, psychoeducational method Let’s Talk about Children (LTC) to support pupils’ well-being and identify possible risk factors in cooperation with home and school. The study’s data comprise 83 LTC training participants’ writing about their experiences with the method as first-time users. The results indicate that the teachers noticed several benefits and potential uses of LTC, but they reported that the method requires adaptation. The experienced LTC benefits were early intervention, increased knowledge about pupils, encouragement and improved relationships with families. Challenges included a poor fit with teachers’ work, rigid materials and challenging interactions. Teachers noticed benefits from LTC use, but adjusting the method to their work was challenging. These results will enable the method’s further development.
A Bayesian Model Based on Local Phenotypic Resistance Data to Inform Empiric Antibiotic Escalation Decisions
Authors: Bamber Ranjeet , Sullivan Brian , Gorman Léo , Lee Winnie W. Y. , Avison Matthew B. , Dowsey Andrew W. , Williams Philip B.
Published: July 2024

Introduction

Clinicians commonly escalate empiric antibiotic therapy due to poor clinical progress without microbiology guidance. When escalating, they should take account of how resistance to an initial antibiotic affects the probability of resistance to subsequent options. The term "escalation antibiogram" (EA) has been coined to describe this concept. One difficulty when applying the EA concept to clinical practice is understanding the uncertainty in results and how this changes for specific patient subgroups.

Methods

A Bayesian model was developed to estimate antibiotic resistance rates in Gram-negative bloodstream infections based on phenotypic resistance data. The model generates a series of “credible” curves to fit the resistance data, each with the same probability of representing the true rate given the inherent uncertainty. To avoid overfitting, an integrated penalisation term adaptively smooths the curves given the level of evidence.

Results

Rates of resistance to empiric first-choice and potential escalation antibiotics were calculated for the whole hospitalised population based on 10,486 individual bloodstream infections, and for a range of specific patient groups, including ICU (intensive care unit), haematolo-oncology, and paediatric patients. The model generated an expected value (posterior mean) with 95% credible interval to illustrate uncertainty, based on the size of the patient subgroup. For example, the posterior means of piperacillin/tazobactam resistance rates in Gram-negative bloodstream infection are different between patients on ICU and the general hospital population: 27.3% (95% CI 18.1–37.2 vs. 13.4% 95% CI 11.0–16.1) respectively. The model can also estimate the probability of inferiority between two antibiotics for a specific patient population. Differences in optimal escalation antibiotic options between specific patient groups were noted.

Conclusions

EA analysis informed by our Bayesian model is a useful tool to support empiric antibiotic switches, providing an estimate of local resistance rates, and a comparison of antibiotic options with a measure of the uncertainty in the data. We demonstrate that EAs calculated for the whole hospital population cannot be assumed to apply to specific patient group.
Assessment of Strength and Power Capacities in Elite Male Soccer: A Systematic Review of Test Protocols Used in Practice and Research
Authors: Asimakidis Nikolaos D. , Mukandi Irvin N. , Beato Marco , Bishop Chris , Turner Anthony N.
Published: July 2024

Background

Strength and power represent two crucial physical qualities for the attainment of a high level of performance considering the frequency and the importance of explosive actions occurring during elite soccer match-play. Evaluation of strength and power is a multifaceted concept involving a vast array of tests and outcome variables. Nevertheless, a comprehensive and systematic search of strength and power assessment procedures in elite soccer has yet to be undertaken.

Objectives

The aims of this systematic review were to: (1) identify the tests and outcome variables used to assess strength and power of elite male soccer players; (2) provide normative values for the most common tests of strength and power across different playing levels; and (3) report the reliability values of these strength and power tests.

Methods

A systematic review of the academic databases MEDLINE, CINAHL, SPORTDiscus, Web of Science and OVID for studies published until August 2023 was conducted, following the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were eligible for inclusion if they: (1) were original research studies, published in a peer-reviewed journal, and written in English language; (2) had the primary aim to assess strength and/or power; (3) players were male and older than 17 years of age (i.e., mean age of the group); and (4) their playing level was defined as “professional”, “international” or “elite”.

Results

Regarding strength testing, 115 studies and 29 different tests were identified. The three most frequent strength tests were the knee extensor isokinetic strength test (58 studies), the knee flexor isokinetic strength test (55 studies) and the Nordic hamstring strength test (13 studies). In terms of power testing, 127 studies with 31 different tests were included. The three most frequent power tests were the countermovement jump with hands fixed on hips (99 studies), the squat jump (48 studies) and the vertical jump with arm swing (29 studies).

Conclusions

The wide range of different tests and outcome variables identified in this systematic review highlights the large diversity in the employed testing procedures. The establishment of a hybrid testing approach, combining standardised and widely accepted tests for establishing normative standards and enabling comparisons across different contexts, with flexible context-specific testing batteries, has the potential to maximise the impact of testing information for practitioners. In addition, the limited reporting of reliability data across studies highlights the need for practitioners to establish their own reliability measure within their specific contexts, informing the selection of certain tests and outcome variables.
Health literacy and falls among community-dwelling older people in China: is there a sex difference?
Authors: Li Shaojie , Wang Jingjing , Ren Longbing , Ye Pengpeng , Niu Wenyi , Yu Mingzhi , Hu Yang , Jiang Yuling , Wu Yifei , Tian Maoyi , Zhao Yali , Yao Yao
Published: July 2024

Background

Health literacy is one of the important determinants of healthy aging, yet few studies have focused on the association between health literacy and falls.

Aims

This study aims to explore the relationship between health literacy and falls, with a focus on sex differences among older people in China.

Methods

This cross-sectional study enrolled 2,144 older people aged ≥ 60 years from Shandong Province, China in 2021. We used general health literacy screening scale to assess health literacy, and collected the incidence of falls in the past year. Logistic regression models were employed to analyze the relationship between health literacy and falls. We investigated the sex differences by subgroup analyses.

Results

The prevalence of adequate health literacy and falls was 21.7% (95% CI: 20.0–23.5%) and 25.4% (95% CI: 23.6–27.3%), respectively. In a fully-adjusted model, adequate health literacy was associated with a lower prevalence of falls in older adults (OR = 0.71, 95%CI: 0.52–0.96). Subgroup analysis revealed sex differences in this relationship (Pfor interaction <0.05). Specifically, the female group showed no significant relationship between health literacy and falls (OR = 0.92, 95% CI: 0.59–1.44); however, the male group demonstrated a robust and significant relationship (OR = 0.58, 95% CI: 0.37–0.90).

Conclusions

Older people with adequate health literacy have lower prevalence of falls, which appears to differ by sex. This relationship was significant among men but not among women. These findings emphasize the need for policymakers and healthcare providers to consider sex differences when designing and implementing programs aimed at improving health literacy and preventing falls in the older population. Improving health literacy among older women could be a strategic component in bridging sex inequality in falls.
Key performance indicators for monitoring of anemia management and iron status in children attending a pediatric dialysis unit: the experience of Ain Shams University
Authors: Khalil Mariam A. , Kasem Mohammed F. , El-Hakim Ihab Z. , Abd Elhafez Amany M. , El Farsy Mohamed S. , Said Ragia M.
Published: July 2024

Background

Anemia in children on maintenance hemodialysis (HD) leads to poor quality of life. Our study aimed to assess and monitor anemia and iron status management in children on maintenance HD over 18 months using key performance indicators.

Methods

Key performance indicators, formulated as the percentage of patients achieving the KDIGO (2012) guideline-recommended targets for hemoglobin (Hb) (11–12 g/dl), transferrin saturation (TSAT) (20–40%) and serum ferritin (200–500 ng/ml), were reported quarterly over the 18-month-period of this study.

Results

This study was carried out over an 18 month-period, from April 1st, 2020, till October 31st, 2021. A total of 78 patients (45 males and 33 females) were included; mean age 12.16 ± 3.3 years and HD duration range 3.0—140.88 months, median 16.51 months. The three most common primary causes of CKD were Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) (29.5%), unknown cause (24.4%), and chronic glomerular diseases (20.5%). The quarterly reported percentages of patients achieving the recommended targets for Hb, TSAT, and serum ferritin ranges were 18.2–35.7%, 38.8–57.1%, and 11.9–26.6%, respectively.

Conclusion

Although the mean Hb trend was nearing the KDIGO (2012) target, the key performance indicators showed that only a small percentage of our HD patients were achieving the targets for Hb, TSAT, & serum ferritin, thus alerting us to the need to revise our protocol for the management of anemia and iron status.

Graphical abstract
Mannan‑, VLP-, and flagellin-based adjuvants for allergen-specific immunotherapy: a review of the current literature
Authors: Pignard Clara , Schiller Hannah , Seyffer Alisa , Schülke Stefan
Published: July 2024

Currently, allergen-specific immunotherapy (AIT) with active ingredients derived from the causative allergen source is the only disease-modifying treatment for allergic patients. However, compared to, e.g., live-attenuated vaccines for the prevention of infectious diseases, purified allergens for AIT in many cases display only a low immunogenicity. This reduces treatment efficacy and prolongs treatment duration. Here, adjuvants may be a promising tool, allowing for dose reduction of the respective allergen while increasing immunogenicity of co-applied allergens and/or modulating allergen-specific immune responses toward T helper 1 (Th1) or regulatory phenotypes or the production of blocking antibody isotypes. Currently available adjuvants can be distinguished into first-generation adjuvants (promoting immune responses via aggregation and controlled release of co-applied allergens from a depot) and second-generation adjuvants (triggering immune responses via the activation of pattern recognition receptors expressed by immune cells). This review summarizes the mechanisms and effects of adjuvants currently or previously used for AIT (aluminum hydroxide, calcium phosphate, microcrystalline tyrosine, and monophosphoryl lipid A [MPLA]) and focuses on novel developments using mannan-, virus-like particle (VLP)-, and flagellin-based adjuvants and therapeutics for the treatment of allergic diseases.
„Sie dürfen sich nicht auf ihrer Muttersprache unterhalten und das finde ich tatsächlich auch gut“ – Sprachbezogene Diskriminierung in der Grundschule
Authors: Lange Sarah Désirée , Alhallak Zahia , Plohmer Anna
Published: July 2024

Mit der Studie wird bezweckt, ausgehend von Beschreibungen und Begründungen von Lehrkräften zu ihrem Umgang mit Mehrsprachigkeit potenziell linguizistische Überzeugungen aufzudecken, um Strukturen sichtbar zu machen, die sich möglicherweise benachteiligend auf mehrsprachige Kinder auswirken. Dazu wurden qualitative, vignettenbasierte Interviews der DFG-geförderten BLUME II-Vignettenstudie mit 43 berufstätigen Grundschullehrkräften ausgewertet. Die inhaltsanalytische Auswertung ergab acht zentrale Themen, die zu vier Legitimationen verdichtet wurden, mit denen das Exkludieren von Familiensprachen begründet wird: Die Lehrkräfte legitimieren den Ausschluss von Familiensprachen im Unterricht mit den eigenen begrenzten oder nicht vorhandenen sprachlichen Kompetenzen. Weiterhin legitimieren die Lehrkräfte mehrsprachige Kinder aus der Unterrichtsplanung auszuschließen mit der Vielfältigkeit der Familiensprachen innerhalb der Klasse und indem sie das Beherrschen des Deutschen als Voraussetzung für erfolgreiche, soziale Integration sehen. Als weitere Legitimation werden Sprachverbote benannt, denen sich die Lehrkräfte größtenteils verpflichtet fühlen. Auffällig sind bei der Beschreibung der Ergebnisse die vielen sprachbezogenen Defizitzuschreibungen und dass es sich bei allen Legitimierungen um Externalisierungen handelt. Die Ergebnisse verweisen auf die Schlüsselrolle von Grundschullehrkräften in der Reproduktion sprachbezogener Diskriminierung und regen dazu an, subjektive Begründungen und Argumentationsmuster für potenziell linguizistische Praktiken im Grundschulalltag kritisch zu hinterfragen, um besser zu verstehen, wie sprachbezogene Diskriminierung verhindert werden kann.
Inducers and Inhibitors of Pyroptotic Death of Granulosa Cells in Models of Premature Ovarian Insufficiency and Polycystic Ovary Syndrome
Authors: Berkel Caglar
Published: July 2024

Granulosa cells (GCs), the largest cell population and primary source of steroid hormones in the ovary, are the important somatic ovarian components. They have critical roles in folliculogenesis by supporting oocyte, facilitating its growth, and providing a microenvironment suitable for follicular development and oocyte maturation, thus having essential functions in maintaining female fertility and in reproductive health in general. Pyroptotic death of GCs and associated inflammation have been implicated in the pathogenesis of several reproductive disorders in females including Premature Ovarian Insufficiency (POI) and Polycystic Ovary Syndrome (PCOS). Here, I reviewed factors, either intrinsic or extrinsic, that induce or inhibit pyroptosis in GCs in various models of these disorders, both in vitro and in vivo, and also covered associated molecular mechanisms. Most of these studied factors influence NLRP3 inflammasome- and GSDMD (Gasdermin D)-mediated pyroptosis in GCs, compared to other inflammasomes and gasdermins (GSDMs). I conclude that a more complete mechanistic understanding of these factors in terms of GC pyroptosis is required to be able to develop novel strategies targeting inflammatory cell death in the ovary.
Global Distribution and Projected Variations of Compound Drought‐Extreme Precipitation Events
Authors: Deng Siqi , Zhao Dongsheng , Chen Ziwei , Liu Lei , Zhu Yu , Wang Ke , Gao Xuan , Wu Hanqian , Zheng Du
Published: July 2024

The compound drought‐extreme precipitation event (CDEP) is one of the most impactful successive compound events that shift from drought to extreme precipitation in the same location within a short period. Due to its dual characteristics of drought and flood, CDEP tends to be more destructive than the impact of individual drought or flood. Yet few studies have analyzed the likelihood of CDEP at different time intervals and their potential variations under global warming. In this study, we assessed the coincidence rate between droughts and extreme precipitation events at 1‐month (CDEP‐1), 2‐month (CDEP‐2), and 3‐month (CDEP‐3) intervals, as well as their potential changes in a 1.5 and 2°C warming world (under both SSP2‐4.5 and SSP5‐8.5 scenarios). Our results suggest that global droughts and extreme precipitation events have coincided more frequently at 1‐month interval than at 2‐ and 3‐month intervals during the period 1985–2014. The global average coincidence rates of CDEP‐1, CDEP‐2, and CDEP‐3 are 24%, 10%, and 7%, respectively. Notably, the coincidence rate of CDEP‐1 exceeded 40% in Eastern Asia, north‐eastern North America, and India, indicating that more than 40% of droughts have been followed by extreme precipitation events in the next month after drought termination. Under both SSP2‐4.5 and SSP5‐8.5 scenarios, climate warming will increase the coincidence rate of CDEP‐1, CDEP‐2, and CDEP‐3, especially will lead to higher values in the coincidence rate of CDEP‐1. This study contributes to a better understanding of the patterns of CDEP and helps to develop more targeted risk management strategies.
The Anthropocene Is More Than a Time Interval
Authors: Edgeworth Matthew , Bauer Andrew M. , Ellis Erle C. , Finney Stanley C. , Gill Jacquelyn L. , Gibbard Philip L. , Maslin Mark , Merritts Dorothy J. , Walker Michael J. C.
Published: July 2024

Following the recent rejection of a formal Anthropocene series/epoch by the Subcommission on Quaternary Stratigraphy (SQS) of the International Commission on Stratigraphy (ICS), and its subsequent confirmation by the International Union of Geological Sciences (IUGS), the opportunity arises to reset the definition of the Anthropocene. The case for informally recognizing the Anthropocene to be a major planetary event of Earth system transformation offers a promising way forward, but this has been criticized by proponents of an Anthropocene series/epoch. In order to move on from the assumption that it must be a time interval, and to foster a more transdisciplinary and inclusive approach, the main points of the critique must be directly addressed.
A Contiguous Taltson‐Thelon Margin Revisited
Authors: Cutts J. A. , Dyck B. V. , Perrot M. G. , Davies J. H. F. L. , Osinchuk A. M. , Šilerová D. , Stern R. A. , Chiaradia M. , Canam R.
Published: July 2024

The amalgamation of Laurentia was initiated along the western margin of the Rae craton. However, the tectonic setting that generated magmatic rocks along this margin has long been debated, with the Thelon tectonic zone in the north having formed in an arc setting, and the Taltson magmatic zone in the south variably attributed to either continental arc or intracratonic magmatism. The magmatic rocks of the Great Slave Lake shear zone (GSLsz) lie between these two tectonic belts and, thus, may be critical to the interpretation of the evolution of the western Rae margin. To understand the origin of the rocks in the GSLsz, we have applied U‐Pb geochronology, trace‐element geochemistry, and O and Hf isotope analyses to zircons from a suite of samples that transect the La Loche River fault (LRf)—a major structure that bisects the GSLsz. Samples collected to the north of the LRf are Neoarchean in age, have mantle‐like δ18O (4.7–5.8‰) and chondritic to juvenile εHf values (0–4.5), whereas those to the south are exclusively Paleoproterozoic in age and have more elevated δ18O (6.3–7‰) and much more evolved εHf values (−12 to −6); these results indicate that the LRf marks a crustal‐scale suture between the Slave craton and the Taltson magmatic zone. Our isotopic data, together with other regional constraints from the area, are most consistent with the Taltson magmatic zone having formed in a continental arc setting emplaced into ca. 2.3 Ga juvenile basement crust.
Association study of GBA1 variants with MSA based on comprehensive sequence analysis -Pitfalls in short-read sequence analysis depending on the human reference genome-
Authors: Orimo Kenta , Mitsui Jun , Matsukawa Takashi , Tanaka Masaki , Nomoto Junko , Ishiura Hiroyuki , Omae Yosuke , Kawai Yosuke , Tokunaga Katsushi ,   NCBN Controls WGS Consortium, Ishibashi-Ueda Hatsue , Tomita Tsutomu , Noguchi Michio , Takahashi Ayako , Goto Yu-ichi , Yoshida Sumiko , Hattori Kotaro , Matsumura Ryo , Iida Aritoshi , Maruoka Yutaka , Gatanaga Hiroyuki , Shimomura Akihiko , Sugiyama Masaya , Suzuki Satoshi , Miyo Kengo , Matsubara Yoichi , Umezawa Akihiro , Hata Kenichiro , Kaname Tadashi , Ozaki Kouichi , Tokuda Haruhiko , Watanabe Hiroshi , Niida Shumpei , Noiri Eisei , Kitajima Koji , Omae Yosuke , Miyahara Reiko , Shimanuki Hideyuki , Kawai Yosuke , Tokunaga Katsushi , Toda Tatsushi , Tsuji Shoji
Published: July 2024

Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by various combinations of autonomic failure, parkinsonism, and cerebellar ataxia. To elucidate variants associated with MSA, we have been conducting short-read-based whole-genome sequence analysis. In the process of the association studies, we initially focused on GBA1, a previously proposed susceptibility gene for MSA, to evaluate whether GBA1 variants can be efficiently identified despite its extraordinarily high homology with its pseudogene, GBA1LP. To accomplish this, we conducted a short-read whole-genome sequence analysis with alignment to GRCh38 as well as Sanger sequence analysis and compared the results. We identified five variants with inconsistencies between the two pipelines, of which three variants (p.L483P, p.A495P–p.V499V, p.L483_M489delinsW) were the results of misalignment due to minor alleles in GBA1P1 registered in GRCh38. The miscalling events in these variants were resolved by alignment to GRCh37 as the reference genome, where the major alleles are registered. In addition, a structural variant was not properly identified either by short-read or by Sanger sequence analyses. Having accomplished correct variant calling, we identified three variants pathogenic for Gaucher disease (p.S310G, p.L483P, and p.L483_M489delinsW). Of these variants, the allele frequency of p.L483P (0.003) in the MSA cases was higher than that (0.0011) in controls. The meta-analysis incorporating a previous report demonstrated a significant association of p.L483P with MSA with an odds ratio of 2.85 (95% CI; 1.05 – 7.76, p = 0.0400).
Unraveling iron oxides as abiotic catalysts of organic phosphorus recycling in soil and sediment matrices
Authors: Basinski Jade J. , Bone Sharon E. , Klein Annaleise R. , Thongsomboon Wiriya , Mitchell Valerie , Shukle John T. , Druschel Gregory K. , Thompson Aaron , Aristilde Ludmilla
Published: July 2024

In biogeochemical phosphorus cycling, iron oxide minerals are acknowledged as strong adsorbents of inorganic and organic phosphorus. Dephosphorylation of organic phosphorus is attributed only to biological processes, but iron oxides could also catalyze this reaction. Evidence of this abiotic catalysis has relied on monitoring products in solution, thereby ignoring iron oxides as both catalysts and adsorbents. Here we apply high-resolution mass spectrometry and X-ray absorption spectroscopy to characterize dissolved and particulate phosphorus species, respectively. In soil and sediment samples reacted with ribonucleotides, we uncover the abiotic production of particulate inorganic phosphate associated specifically with iron oxides. Reactions of various organic phosphorus compounds with the different minerals identified in the environmental samples reveal up to twenty-fold greater catalytic reactivities with iron oxides than with silicate and aluminosilicate minerals. Importantly, accounting for inorganic phosphate both in solution and mineral-bound, the dephosphorylation rates of iron oxides were within reported enzymatic rates in soils. Our findings thus imply a missing abiotic axiom for organic phosphorus mineralization in phosphorus cycling.
Bdelloid rotifers deploy horizontally acquired biosynthetic genes against a fungal pathogen
Authors: Nowell Reuben W. , Rodriguez Fernando , Hecox-Lea Bette J. , Mark Welch David B. , Arkhipova Irina R. , Barraclough Timothy G. , Wilson Christopher G.
Published: July 2024

Coevolutionary antagonism generates relentless selection that can favour genetic exchange, including transfer of antibiotic synthesis and resistance genes among bacteria, and sexual recombination of disease resistance alleles in eukaryotes. We report an unusual link between biological conflict and DNA transfer in bdelloid rotifers, microscopic animals whose genomes show elevated levels of horizontal gene transfer from non-metazoan taxa. When rotifers were challenged with a fungal pathogen, horizontally acquired genes were over twice as likely to be upregulated as other genes — a stronger enrichment than observed for abiotic stressors. Among hundreds of upregulated genes, the most markedly overrepresented were clusters resembling bacterial polyketide and nonribosomal peptide synthetases that produce antibiotics. Upregulation of these clusters in a pathogen-resistant rotifer species was nearly ten times stronger than in a susceptible species. By acquiring, domesticating, and expressing non-metazoan biosynthetic pathways, bdelloids may have evolved to resist natural enemies using antimicrobial mechanisms absent from other animals.
Symmetric and asymmetric DNA N6-adenine methylation regulates different biological responses in Mucorales
Authors: Lax Carlos , Mondo Stephen J. , Osorio-Concepción Macario , Muszewska Anna , Corrochano-Luque María , Gutiérrez Gabriel , Riley Robert , Lipzen Anna , Guo Jie , Hundley Hope , Amirebrahimi Mojgan , Ng Vivian , Lorenzo-Gutiérrez Damaris , Binder Ulrike , Yang Junhuan , Song Yuanda , Cánovas David , Navarro Eusebio , Freitag Michael , Gabaldón Toni , Grigoriev Igor V. , Corrochano Luis M. , Nicolás Francisco E. , Garre Victoriano
Published: July 2024

DNA N6-adenine methylation (6mA) has recently gained importance as an epigenetic modification in eukaryotes. Its function in lineages with high levels, such as early-diverging fungi (EDF), is of particular interest. Here, we investigated the biological significance and evolutionary implications of 6mA in EDF, which exhibit divergent evolutionary patterns in 6mA usage. The analysis of two Mucorales species displaying extreme 6mA usage reveals that species with high 6mA levels show symmetric methylation enriched in highly expressed genes. In contrast, species with low 6mA levels show mostly asymmetric 6mA. Interestingly, transcriptomic regulation throughout development and in response to environmental cues is associated with changes in the 6mA landscape. Furthermore, we identify an EDF-specific methyltransferase, likely originated from endosymbiotic bacteria, as responsible for asymmetric methylation, while an MTA-70 methylation complex performs symmetric methylation. The distinct phenotypes observed in the corresponding mutants reinforced the critical role of both types of 6mA in EDF.
Integrating muti-omics data to identify tissue-specific DNA methylation biomarkers for cancer risk
Authors: Yang Yaohua , Chen Yaxin , Xu Shuai , Guo Xingyi , Jia Guochong , Ping Jie , Shu Xiang , Zhao Tianying , Yuan Fangcheng , Wang Gang , Xie Yufang , Ci Hang , Liu Hongmo , Qi Yawen , Liu Yongjun , Liu Dan , Li Weimin , Ye Fei , Shu Xiao-Ou , Zheng Wei , Li Li , Cai Qiuyin , Long Jirong
Published: July 2024

The relationship between tissue-specific DNA methylation and cancer risk remains inadequately elucidated. Leveraging resources from the Genotype-Tissue Expression consortium, here we develop genetic models to predict DNA methylation at CpG sites across the genome for seven tissues and apply these models to genome-wide association study data of corresponding cancers, namely breast, colorectal, renal cell, lung, ovarian, prostate, and testicular germ cell cancers. At Bonferroni-corrected P < 0.05, we identify 4248 CpGs that are significantly associated with cancer risk, of which 95.4% (4052) are specific to a particular cancer type. Notably, 92 CpGs within 55 putative novel loci retain significant associations with cancer risk after conditioning on proximal signals identified by genome-wide association studies. Integrative multi-omics analyses reveal 854 CpG-gene-cancer trios, suggesting that DNA methylation at 309 distinct CpGs might influence cancer risk through regulating the expression of 205 unique cis-genes. These findings substantially advance our understanding of the interplay between genetics, epigenetics, and gene expression in cancer etiology.
Cartesian atomic cluster expansion for machine learning interatomic potentials
Authors: Cheng Bingqing
Published: July 2024

Machine learning interatomic potentials are revolutionizing large-scale, accurate atomistic modeling in material science and chemistry. Many potentials use atomic cluster expansion or equivariant message-passing frameworks. Such frameworks typically use spherical harmonics as angular basis functions, followed by Clebsch-Gordan contraction to maintain rotational symmetry. We propose a mathematically equivalent and simple alternative that performs all operations in the Cartesian coordinates. This approach provides a complete set of polynormially independent features of atomic environments while maintaining interaction body orders. Additionally, we integrate low-dimensional embeddings of various chemical elements, trainable radial channel coupling, and inter-atomic message passing. The resulting potential, named Cartesian Atomic Cluster Expansion (CACE), exhibits good accuracy, stability, and generalizability. We validate its performance in diverse systems, including bulk water, small molecules, and 25-element high-entropy alloys.
Single-cell EpiChem jointly measures drug–chromatin binding and multimodal epigenome
Authors: Dong Chao , Meng Xiaoxuan , Zhang Tong , Guo Zhifang , Liu Yaxi , Wu Peihuang , Chen Shiwei , Zhou Fanqi , Ma Yanni , Xiong Haiqing , Shu Shaokun , He Aibin
Published: July 2024

Studies of molecular and cellular functions of small-molecule inhibitors in cancer treatment, eliciting effects by targeting genome and epigenome associated proteins, requires measurement of drug-target engagement in single-cell resolution. Here we present EpiChem for in situ single-cell joint mapping of small molecules and multimodal epigenomic landscape. We demonstrate single-cell co-assays of three small molecules together with histone modifications, chromatin accessibility or target proteins in human colorectal cancer (CRC) organoids. Integrated multimodal analysis reveals diverse drug interactions in the context of chromatin states within heterogeneous CRC organoids. We further reveal drug genomic binding dynamics and adaptive epigenome across cell types after small-molecule drug treatment in CRC organoids. This method provides a unique tool to exploit the mechanisms of cell type-specific drug actions.
A chromosome-level genome assembly and evolutionary analysis of Coregonus ussuriensis Berg
Authors: Huang Tianqing , Liu Enhui , Cao Baorui , Li Wenwen , Wang Gaochao , Gu Wei , Ma Haibing , Dong Fulin , Wang Bingqian , Xu Gefeng
Published: July 2024

Coregonus ussuriensis Berg, distributed widely in cold waters above 45° N latitude, is a savored freshwater whitefish that has been included in the list of endangered animals as a consequence of overfishing. Lack of genomic information seriously hampers evolutionary and genetic research on C. ussuriensis warranting the need to assemble a high-quality reference genome to promote its genetic breeding. We assembled and constructed a reference chromosome-level C. ussuriensis genome (sequence length, 2.51 Gb; contig N50 length, 4.27 Mb) using PacBio sequencing and Hi-C assembly technology, 3,109 contigs were assembled into scaffolds, resulting in a genome assembly with 40 chromosomes and a scaffold N50 length of 62.20 Mb. In addition, 43,320 protein-coding genes were annotated. The peak Ks position in the species comparison reflects the whole-genome replication event of C. ussuriensis. This chromosome-level genome provides reference data for further studies on the molecular breeding of C. ussuriensis.
Real samples sensitive dopamine sensor based on poly 1,3-benzothiazol-2-yl((4-carboxlicphenyl)hydrazono)acetonitrile on a glassy carbon electrode
Authors: Alsoghier Hesham M. , Abd-Elsabour Mohamed , Alhamzani Abdulrahman G. , Abou-Krisha Mortaga M. , Assaf Hytham F.
Published: July 2024

Herein, a novel electrochemical sensor that was used for the first time for sensitive and selective detection of dopamine (DA) was fabricated. The new sensor is based on the decoration of the glassy carbon electrode surface (GC) with a polymer film of 1,3-Benzothiazol-2-yl((4-carboxlicphenyl)hydrazono)) acetonitrile (poly(BTCA). The prepared (poly(BTCA) was examined by using different techniques such as 1H NMR, 13C NMR, FTIR, and UV-visible spectroscopy. The electrochemical investigations of DA were assessed using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The results obtained showed that the modifier increased the electrocatalytic efficiency with a noticeable increase in the oxidation peak current of DA in 0.1 M phosphate buffer solution (PBS) at an optimum pH of 7.0 and scan rate of 200 mV/s when compared to unmodified GC. The new sensor displays a good performance for detecting DA with a limit of detection (LOD 3σ), and limit of quantification (LOQ 10σ) are 0.28 nM and 94 nM respectively. The peak current of DA is linearly proportional to the concentration in the range from 0.1 to 10.0 µM. Additionally, the fabricated electrode showed sufficient reproducibility, stability, and selectivity for DA detection in the presence of different interferents. The proposed poly(BTCA)/GCE sensor was effectively applied to detect DA in the biological samples.
Explainable drug repurposing via path based knowledge graph completion
Authors: Jiménez Ana , Merino María José , Parras Juan , Zazo Santiago
Published: July 2024

Drug repurposing aims to find new therapeutic applications for existing drugs in the pharmaceutical market, leading to significant savings in time and cost. The use of artificial intelligence and knowledge graphs to propose repurposing candidates facilitates the process, as large amounts of data can be processed. However, it is important to pay attention to the explainability needed to validate the predictions. We propose a general architecture to understand several explainable methods for graph completion based on knowledge graphs and design our own architecture for drug repurposing. We present XG4Repo (eXplainable Graphs for Repurposing), a framework that takes advantage of the connectivity of any biomedical knowledge graph to link compounds to the diseases they can treat. Our method allows methapaths of different types and lengths, which are automatically generated and optimised based on data. XG4Repo focuses on providing meaningful explanations to the predictions, which are based on paths from compounds to diseases. These paths include nodes such as genes, pathways, side effects, or anatomies, so they provide information about the targets and other characteristics of the biomedical mechanism that link compounds and diseases. Paths make predictions interpretable for experts who can validate them and use them in further research on drug repurposing. We also describe three use cases where we analyse new uses for Epirubicin, Paclitaxel, and Predinisone and present the paths that support the predictions.
Amplification of temperature extremes in Arabian Peninsula under warmer worlds
Authors: Vinodhkumar Buri , Ullah Safi , Kumar T. V. Lakshmi , Al-Ghamdi Sami G.
Published: July 2024

The Paris Agreement and the Special Report on Global Warming of 1.5 °C from the Intergovernmental Panel on Climate Change (IPCC) highlighted the potential risks of climate change across different global warming levels (GWLs). The increasing occurrence of extreme high-temperature events is linked to a warmer climate that is particularly prevalent in the Arabian Peninsula (AP). This study investigates future changes in temperatures and related extremes over AP, under four GWLs, such as 1.5 °C, 2.0 °C, 3.0 °C, and 4.0 °C, with three different Shared Socioeconomic Pathways (SSPs: SSP1-2.6, SSP2-4.5, and SSP5-8.5). The study uses high-resolution datasets of 27 models from the NASA Earth Exchange Global Daily Downscaled Projections of the Coupled Model Intercomparison Project Phase 6 (NEX-GDDP-CMIP6). The results showed that the NEX-GDDP-CMIP6 individual models and their multi-model means reasonably captured the extreme temperature events. The summer maximum and winter minimum temperatures are projected to increase by 0.11–0.67 °C and 0.09–0.70 °C per decade under the selected SSPs. Likewise, the projected temperature extremes exhibit significant warming with varying degrees across the GWLs under the selected SSPs. The warm temperature extremes are projected to increase, while the cold extremes are projected to decrease under all GWLs and the selected SSPs. Overall, the findings provide a comprehensive assessment of temperature changes over AP in response to global warming, which can be helpful in the development of climate adaptation and mitigation strategies.
Metastatic renal cell carcinoma with occult primary: a multicenter prospective cohort
Authors: Jacquin Nicolas , Flippot Ronan , Masliah-Planchon Julien , Grisay Guillaume , Brillet Riwan , Dupain Célia , Kamal Maud , Guillou Isabelle , Gruel Nadège , Servant Nicolas , Gestraud Pierre , Wong Jennifer , Cockenpot Vincent , Goncalves Andreia , Selves Janick , Blons Hélène , Rouleau Etienne , Delattre Olivier , Gervais Claire , Le Tourneau Christophe , Bièche Ivan , Allory Yves , Albigès Laurence , Watson Sarah
Published: July 2024

Metastatic carcinoma of presumed renal origin (rCUP) has recently emerged as a new entity within the heterogeneous entity of Cancers of Unknown Primary (CUP) but their biological features and optimal therapeutic management remain unknown. We report the molecular characteristics and clinical outcome of a series of 25 rCUP prospectively identified within the French National Multidisciplinary Tumor Board for CUP. This cohort strongly suggests that rCUP share similarities with common RCC subtypes and benefit from renal-tailored systemic treatment. This study highlights the importance of integrating clinical and molecular data for optimal diagnosis and management of CUP.
Overcoming big bottlenecks in vascular regeneration
Authors: Fantini Dalia A. , Yang Guang , Khanna Astha , Subramanian Divya , Phillippi Julie A. , Huang Ngan F.
Published: July 2024

Bioengineering and regenerative medicine strategies are promising for the treatment of vascular diseases. However, current limitations inhibit the ability of these approaches to be translated to clinical practice. Here we summarize some of the big bottlenecks that inhibit vascular regeneration in the disease applications of aortic aneurysms, stroke, and peripheral artery disease. We also describe the bottlenecks preventing three-dimensional bioprinting of vascular networks for tissue engineering applications. Finally, we describe emerging technologies and opportunities to overcome these challenges to advance vascular regeneration.
Somatic CpG hypermutation is associated with mismatch repair deficiency in cancer
Authors: Flynn Aidan , Waszak Sebastian M , Weischenfeldt Joachim
Published: July 2024

Somatic hypermutation in cancer has gained momentum with the increased use of tumour mutation burden as a biomarker for immune checkpoint inhibitors. Spontaneous deamination of 5-methylcytosine to thymine at CpG dinucleotides is one of the most ubiquitous endogenous mutational processes in normal and cancer cells. Here, we performed a systematic investigation of somatic CpG hypermutation at a pan-cancer level. We studied 30,191 cancer patients and 103 cancer types and developed an algorithm to identify somatic CpG hypermutation. Across cancer types, we observed the highest prevalence in paediatric leukaemia (3.5%), paediatric high-grade glioma (1.7%), and colorectal cancer (1%). We discovered germline variants and somatic mutations in the mismatch repair complex MutSα (MSH2-MSH6) as genetic drivers of somatic CpG hypermutation in cancer, which frequently converged on CpG sites and TP53 driver mutations. We further observe an association between somatic CpG hypermutation and response to immune checkpoint inhibitors. Overall, our study identified novel cancer types that display somatic CpG hypermutation, strong association with MutSα-deficiency, and potential utility in cancer immunotherapy.
Ion carrier modulated MRI contrast
Authors: Duncan Anna M. , Ellis Connor M. , Levingston Hannah , Kerckhoffs Aidan , Mózes Ferenc E. , Langton Matthew J. , Davis Jason J.
Published: July 2024

The activated specific transmembrane symport of cations/anions and associated water provides a mechanism by which a significant switch in MRI contrast/relaxivity can be generated with paramagnetically loaded liposomes.
The corrosion behavior of borosilicate glass in the presence of cementitious waste forms
Authors: Katsenovich Yelena , Drozd Vadym , Kandel Shambhu , Lagos Leonel , Asmussen R. Matthew
Published: July 2024

Ca significantly suppresses glass corrosion, shown by slower dissolution rates—one magnitude lower for boron and two for rhenium—in both Ca-amended and grout-contacted solutions compared to the pH 12 buffer solution.
Ultrathin 2D/2D ZnIn2S4/La2Ti2O7 nanosheets with a Z-scheme heterojunction for enhanced photocatalytic hydrogen evolution
Authors: Wang Hanbing , Ning Yunqi , Tang Qi , Li Xueyang , Hao Mengdi , Wei Qun , Zhao Tingting , Lv Daqi , Tian Hongwei
Published: July 2024

The synergy of a Z-scheme heterojunction and a 2D/2D structure enhanced photocatalytic hydrogen evolution performance.
Tuning the dimensionality in chiral and racemic organic/tin hybrids with halides
Authors: Caussin Louis , Jouaiti Abdelaziz , Chartrand Daniel , Skene W. G. , Ferlay Sylvie
Published: July 2024

Synthesis and optical characterization of two series of chiral 1D/0D tin-based halides, together with their racemic analogues.
A bimetallic NiFe MOF with ultra-thin two-dimensional nanosheet structure effectively accelerates oxygen evolution reaction
Authors: He Jiaqi , Deng Xin , Sun Wenting , Shang Wenjing , Lou Yongbing , Chen Jinxi
Published: July 2024

Bimetallic NiFe MOFs are synthesized by hydrothermal and electro-deposition. Benefiting from the synergistic effect of Fe and Ni, the catalyst exhibits favorable OER catalytic activity and excellent stability.
Diet enriched with high-phenolic cocoa potentiates hippocampal brain-derived neurotrophic factor expression and neurogenesis in healthy adult micewith subtle effects on memory
Authors: Melgar-Locatelli Sonia , Mañas-Padilla M. Carmen , Castro-Zavala Adriana , Rivera Patricia , del Carmen Razola-Díaz María , Monje Francisco J. , Rodríguez-Pérez Celia , Castilla-Ortega Estela
Published: July 2024

Boosting brain health: Cocoa diet enhances hippocampal neurogenesis and BDNF expression, improving cognitive function.
A reconfigurable, healable and recyclable 3D printed orthosis for adolescent idiopathic scoliosis
Authors: He Xiu-Chong , Lai Jian-Cheng , Zheng Peng-Fei , Li Cheng-Hui
Published: July 2024

A 3D printed orthosis with dynamicity for adolescent idiopathic scoliosis.
Biomimetic engineering of a neuroinflammation-targeted MOF nanozyme scaffolded with photo-trigger released CO for the treatment of Alzheimer's disease
Authors: Liu Chun , Zhang Wenting , Zhang Haochen , Zhao Chuanqi , Du Xiubo , Ren Jinsong , Qu Xiaogang
Published: July 2024

Alzheimer's disease (AD) is one of the most fatal and irreversible neurodegenerative diseases, which causes a huge emotional and financial burden on families and society.
Macrocyclic bis-diphosphenes demonstrating bimetallic exo- and endo-cyclic binding modes
Authors: Kreimer Lisa N. , Hadlington Terrance J.
Published: July 2024

Macrocyclic bis-diphosphenes, formally heavier derivatives of macrocyclic azobenzenes, are accessed for the first time.
2D capsid formation within an oscillatory energy landscape: orderly self-assembly depends on the interplay between a dynamic potential and intrinsic relaxation times
Authors: Niblo Jessica K. , Swartley Jacob R. , Zhang Zhongmin , DuBay Kateri H.
Published: July 2024

Temporal oscillations of the interparticle potential can modify the window of self-assembly in a way that depends on the intrinsic relaxation timescales of the system.
Exploring the role of viologen and iodocuprate in the enhanced resistive switching performance of Anderson polyoxometalate-based three-component hybrids
Authors: Chen Huai-Bin , He Mei-Yun , Li Tao , Deng Chu-Chu , Xiao Hui-Ping , Qi Ming-Qiang , Kong Xiang-Jian , Li Hao-Hong , Li Xin-Xiong , Zheng Shou-Tian
Published: July 2024

The introduction of MV2+ into Anderson-type (MnMo6O18L2)3− can trigger the resistive switching (RS) performance, and the further grafting of electron-rich Cu2I3 gives rise to enhanced RS behavior with high thermal tolerance and long-term stability.
Understanding P-Rex regulation: structural breakthroughs and emerging perspectives
Authors: Jones Gareth D. , Ellisdon Andrew M.
Published: July 2024

Rho GTPases are a family of highly conserved G proteins that regulate numerous cellular processes, including cytoskeleton organisation, migration, and proliferation. The 20 canonical Rho GTPases are regulated by ∼85 guanine nucleotide exchange factors (GEFs), with the largest family being the 71 Diffuse B-cell Lymphoma (Dbl) GEFs. Dbl GEFs promote GTPase activity through the highly conserved Dbl homology domain. The specificity of GEF activity, and consequently GTPase activity, lies in the regulation and structures of the GEFs themselves. Dbl GEFs contain various accessory domains that regulate GEF activity by controlling subcellular localisation, protein interactions, and often autoinhibition. This review focuses on the two phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3)-dependent Rac exchangers (P-Rex), particularly the structural basis of P-Rex1 autoinhibition and synergistic activation. First, we discuss structures that highlight the conservation of P-Rex catalytic and phosphoinositide binding activities. We then explore recent breakthroughs in uncovering the structural basis for P-Rex1 autoinhibition and detail the proposed minimal two-step model of how PI(3,4,5)P3 and Gβγ synergistically activate P-Rex1 at the membrane. Additionally, we discuss the further layers of P-Rex regulation provided by phosphorylation and P-Rex2-PTEN coinhibitory complex formation, although these mechanisms remain incompletely understood. Finally, we leverage the available data to infer how cancer-associated mutations in P-Rex2 destabilise autoinhibition and evade PTEN coinhibitory complex formation, leading to increased P-Rex2 GEF activity and driving cancer progression and metastasis.