bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial variability of cold waves over Southern Africa and their potential physical mechanisms
Authors: Meque Arlindo O , Pinto Izidine S , Chuwah Clifford
Published: December 2024

Despite significant evidence of global warming, cold waves still happen occasionally and are of great concern in regions such as Southern Africa as they are associated with negative impacts such as loss of lives, destruction of infrastructure, loss of crops and livestock and high peak demand of electricity consumption. In this study, we examine the cold wave characteristics over the southern African region for the extended austral winter (May to September) over the 1979–2021 period, using minimum temperature from the European Centre for Medium-Range Weather Forecasts and Berkeley Earth Surface Temperature reanalysis products. Cold waves are calculated using the excess cold factor. Principal component analysis was performed on the cold waves to extract their dominant modes. Linear regression, Spearman rank correlation as well as lagged correlations were employed to find the links between the cold wave characteristics and different climate drives. Results from the study reveal that the lowest nighttime temperatures are found in interior South Africa and Lesotho. There is a decreasing trend in terms of the number of cold wave events over southern Africa, especially north of latitude 15˚S. Local and remote seasonal sea surface temperatures (SST) have the potential to change the likelihood of cold wave characteristics over Southern Africa. Also, seasonal mean circulation results contain seasonal mean ridge/trough structures, which suggests the role of these synoptic features and cold fronts in modulating cold waves over Southern Africa. A future study is needed to analyze the impact of these climate drivers at daily and intraseasonal timescales. There is moderate to high lead correlation between El Ninõ Southern Oscillation (ENSO) and some of the cold wave characteristics, hence ENSO, SST surrounding Southern Africa are good indicators for predicting cold waves over the region. Findings from this study can be useful in improving weather and climate forecasting over the region. Also, these results can support local authorities and communities at risk in developing early actions for tackling cold waves.
Development of climate indices relevant for agriculture in Africa under different climate change scenarios based on GCM and RCM ensembles
Authors: Ziegler Katrin , Abel Daniel , Weber Torsten , Paeth Heiko
Published: December 2024

Africa is facing significant changes in different aspects of life caused by climate change. Our study analyses the temporal and spatial changes of several thermal, hygric, and agricultural indices in Africa and eleven subregions. The agricultural indices strongly depend on the rainy season’s onset and crop specific parameters for which maize acts as an example crop. We use ensembles of General Circulation Models (GCM_ens) from Coupled Model Intercomparison Project and Regional Climate Models (RCM_ens) driven by the respective GCMs within Coordinated Regional Downscaling Experiment-Coordinated Output for Regional Evaluation under the representative concentration pathways 2.6 (rcp26) and 8.5 (rcp85) until the end of the century. The results show complex changes in precipitation-related indices depending on the subregion, model family, scenario, and period. Focusing on the far-future (2071–2100), RCM_ens rcp85 simulates the largest changes compared to rcp26 and both GCM ensembles for most precipitation indices. A later onset of the first rainy season is depicted for most subregions. Regarding heat and drought, all indices project a strong change toward hotter and drier conditions for all subregions and models with large discrepancies between the emission scenarios. Combining both precipitation and temperature changes and further being sensitive to the temporal occurrence within a year, the used agricultural indices show mixed signals. However, most subregions are going to face an increasing crop water need but no clear trend of irrigation requirement or water availability as exemplified for maize. Overall, the RCMs project larger future climate changes than the GCMs under rcp85.
Counted Looping and Waveform Plots
Authors: Essick John
Published: December 2024

The properties of a digitized waveform are studied as readers write a sine-wave plotting program. Plotting of the digitized sine-wave data is facilitated by Python’s Matplotlib library, while the digitized data are generated by three counted-looping methods—for loop, list comprehension, and vectorization. The latter method is realized through the array-based mathematics of the NumPy library. Python’s iterable data structures called list and string are discussed, along with the various ways prewritten software can be imported into a Python program. Finally, the procedure for placing a Matplotlib plot on a GUI is implemented. In a Do It Yourself project, readers create a for-loop-based simulation that explores the statistics of tossed coins and a Use It! example implements a for loop to sum a sequence of numeric values.
Conditional Looping and Real-Time Plots
Authors: Essick John
Published: December 2024

Readers learn to use Python’s conditional looping structure—the while loop—to create a real-time plot of a sine wave. The advantage of using Matplotlib’s animation module, along with its blitting feature, for real-time plots is explored and the method for placing an animation on a GUI is executed. The tuple data structure is defined, while the procedure for indexing and slicing iterable data structures (such as strings, lists, NumPy arrays, and tuples) is explained. A Do It Yourself project directs readers in writing a while-loop-based program that executes until it finds the solution that satisfies a given mathematical criterion, and a Use It! example demonstrates how to implement the break command to terminate program looping.
Web Browser Engineering
Authors: Panchekha Pavel , Harrelson Chris
Published: December 2024

The web is at the center of modern computing. Every year the web expands its reach to more and more of what we do with computers. It now goes far beyond its original use for document-based information sharing: many people now spend their entire day in a browser, not using a single other application! So given this centrality, it's worth knowing how the web works. And in particular, it's worth focusing on the browser, which is the user agent and the mediator of the web's interactions, which ultimately is what makes the web's principles real. But web browsers are still opaque, not just to students but to faculty and industry programmers. This book dissipates this mystery by systematically explaining all the major components of a web browser.
External quality assessment in African clinical laboratories: A systematic review and meta-analysis
Authors: Cherie Negesse , Chane Elias , Angelo Abiy Ayele , Teketelew Bisrat Birke , Tamir Mebratu , Berta Dereje Mengesha
Published: December 2024

Objectives

External quality assessment (EQA) helps evaluate and improve the quality of laboratory testing by providing unbiased reviews. The study aimed to synthesize pooled EQA performance of clinical laboratories across the African region.

Methods

The review was registered in PROSPERO (CRD42024562987) and reported based on the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. An extensive search was employed using the PubMed, Scopus, Cochrane, and Embase databases as well as gray literature. After duplicates were removed, the remaining articles were evaluated based on title, abstract, and full text. Methodologic quality was assessed using the JBI critical appraisal checklist. Random effects meta-analysis was used to estimate the pooled performance of EQA at 95% CIs. In addition, the I2 statistic was used to assess heterogeneity, and a funnel plot along with Egger regression were employed to evaluate publication bias. Trim and fill analysis was also performed to adjust the publication bias.

Results

From an electronic database search, a total of 622 articles were retrieved. Of these, 17 articles met the inclusion criteria, encompassing a total sample size of 4509 participating laboratories. In this study, the overall pooled performance of EQA in the African region was 71.25% (95% CI, 63.12-79.39). The result indicated statistically significant heterogeneity (I2 = 96.36). The funnel plot displayed an asymmetrical distribution of the studies, and Egger regression revealed significant publication bias (P = .002).

Conclusions

The findings revealed that the pooled EQA performance of laboratories in Africa did not meet the typical standard of 80%, indicating a need for continuous improvement. We suggest conducting further studies to gain better insights.
MapTurns: mapping the structure, H-bonding, and contexts of beta turns in proteins
Authors: Newell Nicholas E
Published: December 2024

Motivation

Beta turns are the most common type of secondary structure in proteins after alpha helices and beta sheets and play many key structural and functional roles. Turn backbone (BB) geometry has been classified at multiple levels of precision, but the current picture of side chain (SC) structure and interaction in turns is incomplete, because the distribution of SC conformations associated with each sequence motif has commonly been represented only by a static image of a single, typical structure for each turn BB geometry, and only motifs which specify a single amino acid (e.g. aspartic acid at turn position 1) have been systematically investigated. Furthermore, no general evaluation has been made of the SC interactions between turns and their BB neighborhoods. Finally, the visualization and comparison of the wide range of turn conformations has been hampered by the almost exclusive characterization of turn structure in BB dihedral-angle (Ramachandran) space.

Results

This work introduces MapTurns, a web server for motif maps, which employ a turn-local Euclidean-space coordinate system and a global turn alignment to comprehensively map the distributions of BB and SC structure and H-bonding associated with sequence motifs in beta turns and their local BB contexts. Maps characterize many new SC motifs, provide detailed rationalizations of sequence preferences, and support mutational analysis and the general study of SC interactions, and they should prove useful in applications such as protein design.

Availability and implementation

MapTurns is available at www.betaturn.com. Sample code is available at: https://github.com/nenewell/MapTurns/tree/main.
End-to-end simulation of nanopore sequencing signals with feed-forward transformers
Authors: Beslic Denis , Kucklick Martin , Engelmann Susanne , Fuchs Stephan , Renard Bernhard Y , Körber Nils
Published: December 2024

Motivation

Nanopore sequencing represents a significant advancement in genomics, enabling direct long-read DNA sequencing at the single-molecule level. Accurate simulation of nanopore sequencing signals from nucleotide sequences is crucial for method development and for complementing experimental data. Most existing approaches rely on predefined statistical models, which may not adequately capture the properties of experimental signal data. Furthermore, these simulators were developed for earlier versions of nanopore chemistry, which limits their applicability and adaptability to the latest flow cell data.

Results

To enhance the quality of artificial signals, we introduce seq2squiggle, a novel transformer-based, non-autoregressive model designed to generate nanopore sequencing signals from nucleotide sequences. Unlike existing simulators that rely on static k-mer models, our approach learns sequential contextual information from segmented signal data. We benchmark seq2squiggle against state-of-the-art simulators on real experimental R9.4.1 and R10.4.1 data, evaluating signal similarity, basecalling accuracy, and variant detection rates. Seq2squiggle consistently outperforms existing tools across multiple datasets, demonstrating superior similarity to real data and offering a robust solution for simulating nanopore sequencing signals with the latest flow cell generation.

Availability and implementation

seq2squiggle is freely available on GitHub at: github.com/ZKI-PH-ImageAnalysis/seq2squiggle.
Unlocking the power of multi-institutional data: Integrating and harmonizing genomic data across institutions
Authors: Chen Yuan , Shen Ronglai , Feng Xiwen , Panageas Katherine
Published: December 2024

Cancer is a complex disease driven by genomic alterations, and tumor sequencing is becoming a mainstay of clinical care for cancer patients. The emergence of multi-institution sequencing data presents a powerful resource for learning real-world evidence to enhance precision oncology. GENIE BPC, led by American Association for Cancer Research, establishes a unique database linking genomic data with clinical information for patients treated at multiple cancer centers. However, leveraging sequencing data from multiple institutions presents significant challenges. Variability in gene panels can lead to loss of information when analyses focus on genes common across panels. Additionally, differences in sequencing techniques and patient heterogeneity across institutions add complexity. High data dimensionality, sparse gene mutation patterns, and weak signals at the individual gene level further complicate matters. Motivated by these real-world challenges, we introduce the Bridge model. It uses a quantile-matched latent variable approach to derive integrated features to preserve information beyond common genes and maximize the utilization of all available data, while leveraging information sharing to enhance both learning efficiency and the model’s capacity to generalize. By extracting harmonized and noise-reduced lower-dimensional latent variables, the true mutation pattern unique to each individual is captured. We assess model’s performance and parameter estimation through extensive simulation studies. The extracted latent features from the Bridge model consistently excel in predicting patient survival across six cancer types in GENIE BPC data.
Debiased high-dimensional regression calibration for errors-in-variables log-contrast models
Authors: Zhao Huali , Wang Tianying
Published: December 2024

Motivated by the challenges in analyzing gut microbiome and metagenomic data, this work aims to tackle the issue of measurement errors in high-dimensional regression models that involve compositional covariates. This paper marks a pioneering effort in conducting statistical inference on high-dimensional compositional data affected by mismeasured or contaminated data. We introduce a calibration approach tailored for the linear log-contrast model. Under relatively lenient conditions regarding the sparsity level of the parameter, we have established the asymptotic normality of the estimator for inference. Numerical experiments and an application in microbiome study have demonstrated the efficacy of our high-dimensional calibration strategy in minimizing bias and achieving the expected coverage rates for confidence intervals. Moreover, the potential application of our proposed methodology extends well beyond compositional data, suggesting its adaptability for a wide range of research contexts.
Epidermal stem cell-derived exosomes improve wound healing by promoting the proliferation and migration of human skin fibroblasts
Authors: Kang Deni , Wang Xiaoxiang , Chen Wentao , Mao Lujia , Zhang Weiqiang , Shi Yan , Xie Julin , Yang Ronghua
Published: December 2024

Background

Epidermal stem cells (ESCs) are primarily located in the basal layer of the epidermis and play a crucial role in wound healing. ESCs-derived exosomes (ESCs-Exo) are emerging as promising candidates for skin regeneration and wound healing. However, the underlying mechanisms remain unclear. This study aims to investigate the role and mechanisms of ESCs-Exo in promoting the proliferation, migration, and collagen synthesis of human skin fibroblasts (HSFBs).

Methods

This study generated, isolated, and characterized ESC-Exos. The effects of ESCs-Exo on the proliferation of human skin fibroblasts (HSFBs) were detected via Cell Counting Kit-8 (CCK8), 5-Ethynyl-2'-deoxyuridine (EdU), and Proliferating Cell Nuclear Antigen (PCNA) and Marker of Proliferation Ki-67 (MKI67) gene expression methods. The effect of ESCs-Exo on the migration of HSFBs was detected via a transwell assay and a scratch test. The concentrations of collagen secreted by the HSFBs and the mRNAs of the two kinds of collagen expressed by the HSFBs were analyzed. We also analyzed the phosphorylation of Protein Kinase N1 (PKN1) and the expression of cyclins via western blotting. Finally, the effect of ESCs-Exo on wound healing was verified by animal experiments, and the key genes and signaling pathways of ESCs-Exo were excavated by transcriptomic analysis.

Results

Western blotting revealed that the exosomes of ESCs highly expressed established markers such as Alix, CD63, and CD9. ESC-Exos significantly promoted HSFB proliferation and migration in a dose-dependent manner, as well as HSFB collagen synthesis, and effectively increased the ratio of collagen III/I. In addition, bioinformatics analysis showed that the expression of key gene C-X-C motif chemokine ligand 9 was lower in the ESCs-Exo group, which may promote wound healing by regulating PKN1-cyclin and tumor necrosis factor signaling pathways. Animal experiments demonstrated that ESCs-Exo could reduce inflammation and accelerate wound healing.

Conclusions

In this study, we found that ESCs-Exo may improve wound healing by promoting the proliferation and migration of HSFBs.
Effect of bromodomain and extraterminal inhibitors with different bromodomain selectivity on mesenchymal stem cells
Authors: Tanimoto Riho , Wong Yung-Sing , Ebara Mitsuhiro , Uto Koichiro
Published: December 2024

This study examines the influence of bromodomain and extraterminal inhibitors with different selectivity for bromodomains on human mesenchymal stem cells. Our findings demonstrate that bromodomain and extraterminal inhibitors with higher selectivity for the second bromodomain exhibit lower cytotoxicity in human mesenchymal stem cells, suggesting that the inhibition of osteogenic differentiation in human mesenchymal stem cells is primarily due to the inhibition of the first bromodomain of bromodomain-containing protein 4, rather than the inhibition of its second bromodomain.
Identification of ZNF850 as a novel CTG repeat expansion-related gene in myotonic dystrophy type 1 patient-derived iPSCs
Authors: Kamon Masayoshi , Wakatsuki Shuji , Nakamori Masayuki , Takahashi Masanori P , Mori-Yoshimura Madoka , Komaki Hirofumi , Araki Toshiyuki
Published: December 2024

Myotonic dystrophy type 1 (DM1) is a dominantly inherited multi-system disease caused by expanded CTG repeats in the 3′ untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. Similar to other repeat disorders, the expanded trinucleotide repeat is unstable and demonstrates a tendency to increase repeat size with age in affected tissues. DNA mismatch repair system is implicated in somatic instability. It has been demonstrated that DM1 patient-derived induced pluripotent stem cells (DM1-iPSCs) show repeat instability, in which involvement of mismatch repair proteins has been suggested. Here we identified ZNF850 as a novel CTG repeat expansion-related molecule in DM1-iPSCs. ZNF850 was downregulated in a DM1-iPSC clone whose CTG repeat is exceptionally stable. We found that RNAi-mediated ZNF850 downregulation in DM1-iPSCs significantly reduced the repeat expansion and resulting instability. In adult skeletal muscle tissue of DM1 patients, ZNF850 expression levels were positively correlated with the repeat size. Furthermore, we found that ZNF850 protein can bind to the expanded CTG repeat sequence, and is located in proximity to MutSβ components. These results suggest that ZNF850 might play a role in repeat instability in DM1 by recruiting MutSβ to the repeat sequence.
Horizontal acquisitions of growth potential
Authors: Xia Fan , Walker Gordon
Published: December 2024

We analyze the operating performance of horizontal acquisitions between firms that differ in their growth potential: (I) low-potential firms that buy targets with high potential; and (II) high-potential firms that buy low-potential targets. These two types of acquisition have been the topic of research at three levels of analysis: the industry, the firm, and the transaction. At the industry level, incumbents in the core and innovative startups in the periphery are presumed to have complementary assets managed more effectively through co-ownership. In this vein, studies have focused chiefly on incumbents buying startups. We redress this imbalance. At the firm level, research on real options for growth has examined how multi-business firms exploit their relatedness in entry and exit decisions. Here, we study growth potential in terms of real options in horizontal deals and analyze their effect on post-acquisition performance. At the transaction level, a number of studies have focused on post-acquisition organizational structure and the transfer of knowledge between incumbents and startups. We expand this research by estimating the presumed flow of growth potential capabilities in both High–Low and Low–High deals. Our method uses a difference-in-differences fixed effect model design with Coarsened Exact Matching and Kernel-weighted Propensity Score Matching among comparable firm pairs to measure synergy and to control for endogeneity and portfolio effects using data on U.S. firms over 30 years. We also use a novel accounting adjustment formula to calculate comparable post-M&A operating performance.
Skewed X chromosome inactivation as a response to sexually antagonistic selection
Authors: Greenberg Naomi L , Patten Manus M
Published: December 2024

In eutherians, one of the X chromosomes in each cell of the early female embryo is rendered transcriptionally silent through X chromosome inactivation. The choice of which X chromosome to inactivate takes place independently in each cell and is stably inherited through development, leading to a roughly 50:50 ratio of cells in the adult body expressing one or the other X chromosome. However, X chromosome inactivation can be skewed, with certain X chromosomes showing a heritable tendency to avoid inactivation. Using population-genetic models, we test whether genetic variation for this trait can be maintained by linked sexually antagonistic selection. In favour of this hypothesis, we find that a neutral modifier that affects the chances of its chromosome’s inactivation—e.g., a variant of the X controlling element (Xce)—can spread when linked to a sexually antagonistic gene. We explore the logic of this modifier’s spread, which we find to be similar in many respects to that of a modifier of dominance. We also test for the presence of a “drift barrier”—i.e., a population size below which the indirect selective force favouring the modifier becomes too weak to overcome drift. On balance, we find that sexual antagonism may encourage the spread of skewed X chromosome inactivation, but only under favourable conditions.
Moving beyond population variable importance: concept, theory and applications of individual variable importance
Authors: Dai Guorong , Shao Lingxuan , Chen Jinbo
Published: December 2024

In a non-parametric regression setting, we introduce a novel concept of ‘individual variable importance’, which assesses the relevance of certain covariates to an outcome variable among individuals with specific characteristics. This concept holds practical importance for both risk assessment and association identification. For example, it can represent (i) the usefulness of expensive biomarkers in risk prediction for individuals at a specified baseline risk, or (ii) age-specific associations between physiological indicators. We quantify individual variable importance using a ratio parameter between two conditional mean squared errors. To estimate and infer this parameter, we develop fully non-parametric estimators and establish their asymptotic properties. Our method performs well in simulation studies. Applying our approach to analyse a real dataset reveals a scientifically interesting result: the association between body shape and systolic blood pressure diminishes with increasing age. Our finding aligns with the medical literature based on standard parametric regression techniques, but our approach is more reliable due to its robustness to model misspecification. More importantly, the fully non-parametric nature of our method allows it to be applied in settings with complex relationships between variables, which cannot be correctly characterized by traditional parametric interaction analyses.
ZNF143 binds DNA and stimulates transcription initiation to activate and repress direct target genes
Authors: Dong Jinhong , Sathyan Kizhakke Mattada , Scott Thomas G , Mukherjee Rudradeep , Guertin Michael J
Published: December 2024

Transcription factors bind to sequence motifs and act as activators or repressors. Transcription factors interface with a constellation of accessory cofactors to regulate distinct mechanistic steps to regulate transcription. We rapidly degraded the essential and pervasively expressed transcription factor ZNF143 to determine its function in the transcription cycle. ZNF143 facilitates RNA polymerase initiation and activates gene expression. ZNF143 binds the promoter of nearly all its activated target genes. ZNF143 also binds near the site of genic transcription initiation to directly repress a subset of genes. Although ZNF143 stimulates initiation at ZNF143-repressed genes (i.e. those that increase transcription upon ZNF143 depletion), the molecular context of binding leads to cis repression. ZNF143 competes with other more efficient activators for promoter access, physically occludes transcription initiation sites and promoter-proximal sequence elements, and acts as a molecular roadblock to RNA polymerases during early elongation. The term context specific is often invoked to describe transcription factors that have both activation and repression functions. We define the context and molecular mechanisms of ZNF143-mediated cis activation and repression.
Conformational switching of Arp5 subunit regulates INO80 chromatin remodeling
Authors: Shukla Shagun , Paul Somnath , Garcia Jeison , Zhong Yuan , Juste Sara Sanz , Beauchemin Karissa , Bartholomew Blaine
Published: December 2024

The INO80 chromatin remodeler is a versatile enzyme capable of several functions, including spacing nucleosomes equal distances apart, precise positioning of nucleosomes based on DNA shape/sequence and exchanging histone dimers. Within INO80, the Arp5 subunit plays a central role in INO80 remodeling, evidenced by its interactions with the histone octamer, nucleosomal and extranucleosomal DNA, and its necessity in linking INO80’s ATPase activity to nucleosome movement. We find two distinct regions of Arp5 binding near the acidic pocket of nucleosomes. One region has an arginine anchor that binds nucleosomes and is vital for INO80 mobilizing nucleosomes. The other region has a hydrophobic/acid patch of Leu and Asp that binds free histone H2A–H2B dimers. These two regions have different roles in remodeling nucleosomes as seen both in vitro and in vivo and the hydrophobic/acidic patch of Arp5 is likely needed for displacing DNA from the H2A–H2B surface and dimer exchange by INO80.
DNA target binding-induced pre-crRNA processing in type II and V CRISPR-Cas systems
Authors: Chen Jiyun , Lin Xiaofeng , Xiang Wenwen , Chen Ying , Zhao Yueming , Huang Linglong , Liu Liang
Published: December 2024

Precursor (pre)-CRISPR RNA (crRNA) processing can occur in both the repeat and spacer regions, leading to the removal of specific segments from the repeat and spacer sequences, thereby facilitating crRNA maturation. The processing of pre-crRNA repeat by Cas effector and ribonuclease has been observed in CRISPR-Cas9 and CRISPR-Cas12a systems. However, no evidence of pre-crRNA spacer cleavage by any enzyme has been reported in these systems. In this study, we demonstrate that DNA target binding triggers efficient cleavage of pre-crRNA spacers by type II and V Cas effectors such as Cas12a, Cas12b, Cas12i, Cas12j and Cas9. We show that the pre-crRNA spacer cleavage catalyzed by Cas12a and Cas9 has distinct characteristics. Activation of the cleavage activity in Cas12a is induced by both single-stranded DNA (ssDNA) and double-stranded DNA target binding, whereas only ssDNA target binding triggers cleavage in Cas9 toward the pre-crRNA spacer. We present a series of structures elucidating the underlying mechanisms governing conformational activation in both Cas12a and Cas9. Furthermore, leveraging the trans-cutting activity of the pre-crRNA spacer, we develop a one-step DNA detection method characterized by its simplicity, high sensitivity, and excellent specificity.
Multi-center real-world data-driven web calculator for predicting outcomes in IDH-mutant gliomas: Integrating molecular subtypes and treatment modalities
Authors: Xu Houshi , Liu Beining , Wang Yue , Zhu Ruize , Jiang Shan , Soliman Lina Akmal Fouad Abdelhamid , Chai Huihui , Sun Maoyuan , Chen Jiawen , Li Kay Ka-Wai , Ng Ho-Keung , Zhang Zhenyu , Wei Junji , Shi Zhifeng , Mao Ying
Published: December 2024

Background

Isocitrate dehydrogenase (IDH)-mutant gliomas generally have a better prognosis than IDH-wild-type glioblastomas, and the extent of resection significantly impacts prognosis. However, there is a lack of integrated tools for predicting outcomes based on molecular subtypes and treatment modalities. This study aimed to identify factors influencing gross total resection (GTR) rates and to develop a clinical prognostic tool for IDH-mutant gliomas.

Methods

We analyzed 650 patients with IDH-mutant gliomas from 3 Chinese medical centers (Shanghai, Hong Kong, and Zhengzhou). Data included age, sex, extent of resection, radiotherapy status, tumor grade, histology, and molecular markers (1p19q, TERT promoter, BRAF, EGFR, 10q). Patients were categorized based on GTR status, and a nomogram predicting 3-, 5-, and 10-year overall survival (OS) was developed using Cox proportional hazards regression and validated with time-dependent ROC and calibration plot analyses.

Results

Non-GTR was associated with diffuse astrocytoma (73.0% vs. 53.5%), 1p19q non-codeletion (67.9% vs. 48.7%), and wildtype TERT promoter (63.6% vs. 52.4%). The nomogram, incorporating age, TERT promoter status, extent of resection, grade, and radiotherapy status, demonstrated strong discriminatory ability (AUC > 0.75) and good calibration. Decision curve analysis indicated that it outperformed WHO grade-based classification in identifying high-risk patients. An online calculator was developed for clinical use (http://www.szflab.site/nomogram/).

Conclusion

We developed and validated a nomogram and online tool that integrates molecular and clinical factors for predicting outcomes in IDH-mutant gliomas, enhancing clinical decision-making.
Feasibility of a Low-Intensity Intervention to Influence Antibiotic Prescribing Rates Use in Outpatient Settings: A Cluster Randomized Controlled Clinical Trial
Authors: Bej Taissa A , Wilson Brigid M , Akpoji Ukwen C , Mongilardi Nicole , Chengsupanimit Tayoot (Todd) , Song Sunah , Kowal Corinne , Stryczek Krysttel C , Hearns Rene , Honsberger Mark , Wilkerson Tai-Lyn , Firestone Christine , Subramaniam Soumya , Stevenson Lauren , Ball Sherry L , Jump Robin L P , Perez Federico
Published: December 2024

Background

Primary care providers (PCPs) may modify their antibiotic prescription practices if aware of their potentially damaging impact.

Methods

We conducted a cluster randomized controlled trial at 12 Veterans Affairs community-based outpatient clinics. PCPs at clinics randomized to the intervention group received quarterly antibiotic use reports with feedback about antibiotics prescribed for acute respiratory infections and adverse event letters alerting about Clostridioides difficile infection or antibiotic-resistant gram-negative bacteria among their patients. The main outcome, antibiotic prescriptions in primary care visits, was compared in the preintervention (April–September 2020), intervention (October 2020 to September 2021), and postintervention periods (September 2021 to September 2022).

Results

Among 52 PCPs at 6 clinics in the intervention group, 66% (33 of 52) and 54% (28 of 52) received ≥1 antibiotic use report and adverse event letter. In the intervention clinics, the proportion of primary care visits with antibiotic prescription during the preintervention, intervention, and postintervention periods was 1.4% (1088 of 77 697), 1.4% (2051 of 147 858), and 1.3% (1692 of 131 530). In the control clinics, this increased from 1.8% (1560 of 87 897) to 2.1% (3707 of 176 825) and 2.1% (3418 of 162 979), respectively, during the intervention and postintervention periods. The rate of visits with antibiotic prescription did not differ in the preintervention period (odds ratio [95% confidence interval], 1.10 [.87–1.39); P = .43) but did during the intervention (1.30 [1.04–1.62]; P = .022) and postintervention periods (1.38 [1.09–1.74]; P = .007). There were no differences in emergency department visits and hospitalizations.

Conclusions

PCPs from clinics assigned to a low-intensity intervention combining comparative feedback with adverse event notifications had lower antibiotic prescription rates.
“Never let a good crisis go to waste”: the effects of unanticipated police reform during the COVID-19 pandemic on perceived community willingness to obey the law and cooperate with the police
Authors: Kutnjak Ivković Sanja , Wu Yuning , Vincent Liu Yang , Kotlaja Marijana , Chang Kuang-Ming , Sun Ivan Y , Neyroud Peter , Maskály Jon
Published: December 2024

This study explores the effects of the COVID-19-driven reform in reactive activities (i.e. in-person handling of calls, arrests for minor crimes) and proactive activities (i.e. in-person community policing and problem-solving activities) on the perceived community willingness to obey the law and cooperate with the police. We use a 2021 in-person survey of 600 police officers from China and 613 police officers from Taiwan and employ confirmatory factor analysis to estimate the endogenous measures of procedural justice and public compliance and cooperation. We find that, for reactive activities, although reductions in the in-person handling of calls and arrests for minor crimes do not shape perceived levels of procedural justice, they have direct correlations with increased perceived community compliance/cooperation. The indirect effects show that a decrease in the in-person handling of calls has a total, positive effect on cooperation, and this effect is all through improved procedural justice. Meanwhile, a reduction in the number of arrests for minor crimes does not exert a total or indirect effect on cooperation. For proactive activities, a reduction in community policing and problem-solving activities does not influence perceived public compliance/cooperation directly. However, it exerts a positive, both total and indirect, effect on compliance/cooperation.
Higher risk of poor functional outcome and unfavourable clinical events for late-onset rheumatoid arthritis: results from the IORRA cohort
Authors: Sugitani Naohiro , Tanaka Eiichi , Inoue Eisuke , Abe Mai , Sugano Eri , Saka Kumiko , Ochiai Moeko , Yamaguchi Rei , Ikari Katsunori , Yamanaka Hisashi , Harigai Masayoshi
Published: December 2024

Objectives

To compare treatment outcomes in patients with late-onset RA (LORA) and younger-onset RA (YORA).

Methods

We analyzed patients diagnosed with early RA (disease duration < 2 years) between 2000 and 2016 in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort. Patients were categorized into LORA (onset at ≥65 years) and YORA (onset at <65 years). The primary outcomes were changes in Clinical Disease Activity Index (CDAI) and Japanese version of the Health Assessment Questionnaire (J-HAQ) at Year 5. The secondary outcomes included the incidence of prespecified adverse events.

Results

Methotrexate, biological disease-modifying anti-rheumatic drugs, and glucocorticoids were used in 70.6, 8.4 and 38.0% of the LORA group (n = 813, median age: 71 years), and 81.6, 19.4 and 32.0% of the YORA group (n = 2457, median age: 51 years). Both groups exhibited significant initial improvements in CDAI and J-HAQ scores. At Year 5, mean CDAI scores were 4.39 and 4.03 for the LORA and YORA groups, respectively. J-HAQ score for YORA remained stable below 0.5 after Year 2, whereas that for LORA worsened progressively. At Year 5, mean J-HAQ scores were 0.56 for LORA and 0.33 for YORA. Patients with LORA had a higher incidence of adverse events, with adjusted hazard ratios of 4.70 for death and 2.58 for malignancy.

Conclusions

Patients with LORA and YORA exhibited similar improvements in disease activity over 5 years; however, those with LORA demonstrated a more pronounced decline in physical function.
Digital economy, international openness, and innovation capability: empirical evidence from Urban China
Authors: Dong Guowei , Zhang Yanlei , Shi Yongjiang , Sun Tara Qian
Published: December 2024

Using urban panel data from 2011 to 2019 in China, this study employs various econometric models to analyze the impact and mechanism of digital economy (DE) development on urban innovation capabilities. The empirical results show that DE development significantly bolsters urban innovation in China, a finding that remains consistent even after conducting rigorous robustness tests, such as using historical data as instrumental variables. Importantly, an analysis using the spatial Durbin model reveals a positive spatial spillover effect—DE development in one city enhancing innovation capabilities in neighboring cities. This effect not only diminishes the regional innovation gap but also stimulates regional coordinated innovation. The study also illustrates that a city’s degree of international openness enhances the positive impact of DE development on urban innovation capabilities. This highlights that promoting regional openness is an important mechanism to facilitate the beneficial effect of DE development on urban innovation capabilities. Providing both theoretical foundation and empirical evidence for the impact of DE development, this paper contributes valuable insights into promoting innovation-driven development via digital ecosystem empowerment, formulating differentiated DE strategies, and maximizing the spatial spillover effects of the DE.
The Sociology of Property Value in a Climate-Changed United States
Authors: Elliott Rebecca
Published: December 2024

In the United States, individual and collective economic well-being is closely tied to homeownership. But there is an emerging set of complex issues where climate impacts intersect with housing markets. As climate disasters hit with greater intensity and frequency, the economic effects will be felt not only as the underlying assets are damaged or destroyed, but also as those experiences, and expectations of similar ones to come, are “priced in” to the judgments of what homes are worth. Drawing on scholarship on economic valuation, racism and housing markets, and homeownership in American political economy and culture, I outline a sociology of property value that can help us approach this matter analytically as it unfolds empirically. This approach allows us to see how social actors shape the climate-changed world by determining whether, how, and with what effects property values change. I illustrate these potential contributions through application to a court case in which the question of what was happening to property value—and whether, by extension, proximity to the water is an amenity or a risk—was the primary point of contention. The implications open onto fundamental questions about the future of safe and secure housing in a climate-changed United States.
Combination of 3 probiotics restores attenuated adult neurogenesis in germ-free mice
Authors: Namihira Masakazu , Inoue Nana , Watanabe Yohei , Hayashi Takuto , Murotomi Kazutoshi , Hirayama Kazuhiro , Sato Naoki
Published: December 2024

Gut microbiota plays an important role in regulating brain function and adult neurogenesis. Although probiotics have recently been reported as effective against certain psychiatric disorders, the underlying mechanisms remain unclear. In particular, the combination of 3 probiotic strains, Bacillus subtilis TO-A, Enterococcus faecium T-110, and Clostridium butyricum TO-A, hereafter referred to as ProB3, has been reported to potentially alleviate psychiatric symptoms in patients with schizophrenia. Herein, we show that ProB3 promotes adult neurogenesis in mice and restores its dysregulation in germ-free (GF) mice. ProB3 colonization in GF mice enhanced the proliferation of adult neural stem cells compared to specific-pathogen-free and GF mice. Furthermore, ProB3 colonization was sufficient to ameliorate the arrest of newborn neuron maturation and the diminution of quiescent neural stem cells in GF mice. ProB3 colonization in mice increased the levels of several metabolites in the blood, including theanine and 3-hydroxybutyrate, and imidazole peptides, including anserine, which promoted proliferation, neurogenesis, and maturation of newborn neurons in cultured human fetus neural stem cells, as well as mouse adult hippocampal neural stem cells. Collectively, these results indicate that the essential role of the gut microbiota in adult hippocampal neurogenesis can be effectively complemented by the intake of a specific 3-strain probiotic, ProB3, providing novel insights into the brain–gut axis.
False-positive dengue non-structural protein 1 in pregnancy
Authors: Sia Tonnii , Wong Tze-cheng , Ong Yee-chiing
Published: December 2024

Dengue is a vector-borne infection, which contributes to significant morbidity and mortality in endemic areas. It manifests rapidly within 2 wk from febrile, critical to recovery phase. The point-of-care test (POCT) comprises the non-structural protein 1 (NS1) antigen, IgM and IgG, which aids rapid diagnosis, leading to timely treatment. Despite the high specificity of various POCTs, a few false-positive NS1 cases have been reported. We report the first case of false-positive NS1 antigen in pregnancy. A 24-y-old female in her second trimester of pregnancy presented with fever and chills for 9 d and a non-productive cough for 3 d. The dengue POCT showed NS1 antigen positive, IgM and IgG negative. Her symptoms were resolved with treatment of urinary tract infection with cefuroxime. Urine culture subsequently yielded Escherichia coli. Her recovery and delivery were uneventful. Her NS1 antigen was persistently positive for 18 d. The confirmatory real time-PCR for dengue and pan-Flaviviruses was negative.
Climatic niche evolution and desert colonization in a South American lizard radiation
Authors: Araya-Donoso Raúl , Tamburrino Ítalo , San Juan Esteban , Lamborot Madeleine
Published: December 2024

Organisms in adaptive radiations are able to diversify and colonize multiple environments. Frequently, the evolution of key adaptations enables organisms to confront novel environmental challenges, promoting diversification. Here, we studied desert colonization in the Liolaemus radiation. We assessed the patterns of climatic niche evolution in the L. nigromaculatus section, one Liolaemus clade inhabiting the Atacama Desert. We found that evolution toward arid conditions occurred in two clades independently: one clade colonized the desert through warm coastal environments, and the other through cold highland environments on the Andes Mountains. The precipitation climatic niche evolved fast and early during this clade’s evolutionary history, following an early burst (EB) model of evolution, whereas the thermal climatic niche evolved under Brownian motion (BM) and at a lower rate. Additionally, we explored some features that could have facilitated desert colonization: a higher chromosome number was associated with warmer temperatures, lower selected body temperatures were associated with higher environmental temperatures and drier climates, larger and more elongated bodies with colder environments, and longer limbs and tails were associated with higher thermal variation. Our results highlight that organisms can confront challenging environments in multiple ways such that some niche axes may evolve faster during the colonization of novel environments, and that radiated groups may have the evolutionary potential to rapidly evolve these adaptations.
Immunoinformatics approach: Developing a multi‐epitope vaccine with novel carriers targeting monkeypox virus
Authors: Nejabat Sajjad , Khomartash Mehdi Shakouri , Mohammadimehr Mojgan , Adloo Zahra , Zanchi Fernando Berton , Ghorbani Mahdi , Nezafat Navid
Published: December 2024

Since May 2022, the global spread of monkeypox virus (MPXV) has presented a significant threat to public health. Despite this, there are limited preventive measures available. In this study, different computational tools were employed to design a multi‐epitope vaccine targeting MPXV. Three key MPXV proteins, M1R, B6R, and F3L, were chosen for epitope selection, guided by bioinformatic analyses to identify immunodominant epitopes for T‐ and B‐cell activation. To enhance immune stimulation and facilitate targeted delivery of the vaccine to specific cells, the selected epitopes were linked to novel carriers, including the extracellular domain of cytotoxic T lymphocyte–associated antigen 4 (CTLA‐4), a 12‐mer Clec9a binding peptide (CBP‐12), and a Toll‐like receptor 2 (TLR2) peptide ligand. The designed vaccine construct exhibited strong antigenicity along with nonallergenic and nontoxic properties, with favorable physicochemical characteristics. The validated vaccine's tertiary structure underwent evaluation for interactions with CD80/86, Clec9a, and TLR2 through molecular docking and molecular dynamics simulation. The results ensured the vaccine's stability and high affinity for the aforementioned receptors. In silico immune simulations studies revealed robust innate and adaptive immune responses, including enhanced mucosal immunity essential for protection against MPXV. Ultimately, the DNA sequence of the vaccine construct was synthesized and successfully cloned into the pET‐22b(+) vector. Our study, through integration of computational predictions, suggests the proposed vaccine's potential efficacy in safeguarding against MPXV; however, further in vitro and in vivo validations are imperative to assess real‐world effectiveness and safety.
GS‐4997 halts the progression of tubulointerstitial injury in lupus nephritis
Authors: Xiao Zheng , Li Guoli , Fu Shuangshuang , Chen Yinyin
Published: December 2024

Tubulointerstitial injury has been increasingly recognized as an important component in lupus nephritis (LN) pathology over the last decades. However, current clinical treatment options for this process remain limited. In this study, we aimed to investigate the potential benefits of GS‐4997, a selective inhibitor of ASK1, in tubulointerstitial injury of LN. Female MRL/lpr mice were used as a classical lupus‐prone murine model. Development of nephritis was assessed by monitoring of proteinuria, renal function, and histologic analysis. GS‐4997 (50 mg/kg) or vehicle were treated orally. In vitro study, human kidney‐2 (HK‐2) cells were stimulated with 1 μg/mL lipopolysaccharide (LPS) to mimic the response of renal tubular epithelial cells undergoing inflammatory responses during LN. GS‐4997 could inhibit the activation of the ASK1 in renal tubulointerstitium in MRL/lpr mice and LPS‐induced HK‐2 cells. GS‐4997 treatment improved renal function, proteinuria, and attenuated tubular injury, renal interstitial fibrosis, and inflammation both in vivo and in vitro. Additionally, we found that in MRL/lpr mice, GS‐4997 reduced deposition of IgG and C3 in the kidneys, antibody levels in the serum, splenic enlargement, and inflammatory cell infiltration in the spleen. Mechanistically, GS‐4997 inhibited the activation of downstream signaling molecules, p38 and JNK, in the ASK1 signaling pathway. Pharmacological inhibition of ASK1 may prevent the progression of tubulointerstitial injury via inhibiting the ASK1/MAPK pathway in LN. Therefore, our findings demonstrate the potential use of GS‐4997 for LN treatment.