bluuebunny/crossref_metadata_2025 huggingface dataset:
The win ratio in cardiology trials: lessons learnt, new developments, and wise future use
Authors: Pocock Stuart J , Gregson John , Collier Timothy J , Ferreira Joao Pedro , Stone Gregg W
Published: October 2024

The win ratio method for analysing a composite clinical hierarchy of outcomes is growing in popularity especially in cardiovascular trials. This article gives a perspective on its use so far and the issues derived from that experience. Specifically, it focuses on the limitations of a conventional composite outcome; how does the win ratio work, what does it mean, and how to display its findings; guidance on choosing an appropriate clinical hierarchy of outcomes including clinical events, quantitative outcomes, and other options; the additional value of the win difference as a measure of absolute benefit: extension to stratified win ratio, subgroup analysis, matched win ratio, and covariate adjustment; determining trial size for a win ratio outcome; specific insights such as adaptive designs, use of repeat events, and use of margins and time averages for quantitative outcomes; a critique of potential misuses; availability of statistical software; and a statistical appendix on the methodological details. Throughout, each principle is illustrated by examples from specific cardiology trials. The article concludes with a set of recommendations for future use of the win ratio.
Contact with young children is a major risk factor for pneumococcal colonization in older adults
Authors: Wyllie Anne L , Yolda-Carr Devyn , Hislop Maikel S , Mbodj Sidiya , Wurst Loren , Waghela Pari , Alexander-Parrish Ronika , Grant Lindsay R , Arguedas Adriano , Gessner Bradford D , Weinberger Daniel M
Published: October 2024

Important questions remain about the sources of transmission of pneumococcus to older adults in the community. This is critical for understanding the potential effects of using pneumococcal conjugate vaccines (PCVs) in children and older adults. For non-institutionalized individuals, we hypothesized that the most likely source of adult-to-adult transmission is within the household. We designed a longitudinal study to sample adults ≥60 years of age living in the same household (New Haven, CT, USA), without younger residents in the household. Saliva samples and social and health questionnaires were obtained every 2 weeks for a period of 10 weeks. DNA extracted from culture-enriched saliva was tested using qPCR for pneumococcus genes piaB, lytA, and serotype. Across two study seasons (November 2020–August 2021, November 2021–September 2022), 121 individuals from 61 households completed all six visits; 62 individuals were enrolled in both seasons. Overall, 52/1088 (4.8%) samples tested positive for pneumococcus, with 27/121 (22.3%) individuals colonized at least once. Several individuals were colonized at multiple time points; two individuals were colonized at 5/6 time points and two at all six. In 5 instances, both household members were carriers in the same season, though not necessarily at the same time. Pneumococcal carriage was substantially higher among individuals who had contact with children (10.0% vs. 1.6%). Contact with young children was the most important factor that influenced pneumococcal acquisition rates. While there were several instances where both adult household members were colonized at the same time or at sequential visits, these individuals typically had contact with children. As such, PCV immunization can directly protect older adults who have contact with children.
Quest for Orthologs in the Era of Biodiversity Genomics
Authors: Langschied Felix , Bordin Nicola , Cosentino Salvatore , Fuentes-Palacios Diego , Glover Natasha , Hiller Michael , Hu Yanhui , Huerta-Cepas Jaime , Coelho Luis Pedro , Iwasaki Wataru , Majidian Sina , Manzano-Morales Saioa , Persson Emma , Richards Thomas A , Gabaldón Toni , Sonnhammer Erik , Thomas Paul D , Dessimoz Christophe , Ebersberger Ingo
Published: October 2024

The era of biodiversity genomics is characterized by large-scale genome sequencing efforts that aim to represent each living taxon with an assembled genome. Generating knowledge from this wealth of data has not kept up with this pace. We here discuss major challenges to integrating these novel genomes into a comprehensive functional and evolutionary network spanning the tree of life. In summary, the expanding datasets create a need for scalable gene annotation methods. To trace gene function across species, new methods must seek to increase the resolution of ortholog analyses, e.g. by extending analyses to the protein domain level and by accounting for alternative splicing. Additionally, the scope of orthology prediction should be pushed beyond well-investigated proteomes. This demands the development of specialized methods for the identification of orthologs to short proteins and noncoding RNAs and for the functional characterization of novel gene families. Furthermore, protein structures predicted by machine learning are now readily available, but this new information is yet to be integrated with orthology-based analyses. Finally, an increasing focus should be placed on making orthology assignments adhere to the findable, accessible, interoperable, and reusable (FAIR) principles. This fosters green bioinformatics by avoiding redundant computations and helps integrating diverse scientific communities sharing the need for comparative genetics and genomics information. It should also help with communicating orthology-related concepts in a format that is accessible to the public, to counteract existing misinformation about evolution.
How to (or how not to) implement crowdsourcing for the development of health interventions: lessons learned from four African countries
Authors: Kpokiri Eneyi E , Phiri Mwelwa M , Martinez-Alvarez Melisa , Tembo Mandikudza , Chikwari Chido Dziva , Nzvere Farirai , Doyle Aoife M , Tucker Joseph D , Hensen Bernadette
Published: October 2024

Crowdsourcing strategies are useful in the development of public health interventions. Crowdsourcing engages end users in a co-creation process through challenge contests, designathons or online collaborations. Drawing on our experience of crowdsourcing in four African countries, we provide guidance on designing crowdsourcing strategies across seven steps: deciding on the type of crowdsourcing strategy, convening a steering committee, developing the content of the call for ideas, promotion, evaluation, recognizing finalists and sharing back ideas or implementing the solutions.
Ambient temperature exposure and rapid infant weight gain
Authors: Alterman Neora , Nevo Daniel , Calderon-Margalit Ronit , Youssim Iaroslav , Weinstein Bar , Kloog Itai , Hauzer Michael , Raz Raanan
Published: October 2024

Background

Childhood obesity is a major public health concern, and the global rate is rising. Rapid infant weight gain is a risk factor for later overweight. Studies have linked prenatal ambient temperature exposure to fetal growth, and preliminary evidence suggests postnatal exposure may be associated with infant weight gain.

Methods

Using a population-based historical cohort study including 1 100 576 infants born 2011–2019, we assessed the relationship between prenatal and one-month postnatal ambient temperature exposure and rapid infant weight gain. We used a hybrid spatiotemporal model to assess temperatures at the family’s recorded residence at birth. Repeated weight measurements between birth and 15 months were used to model the outcome using the SuperImposition by Translation and Rotation (SITAR) method. We employed generalized linear models and distributed lag models to estimate the association between prenatal and postnatal exposure and rapid infant weight gain, defined as the upper tertile of the SITAR growth velocity.

Results

Overall, higher ambient temperatures were associated with rapid infant weight gain. The cumulative adjusted relative risk for the highest exposure quintile during pregnancy compared with the lowest quintile was 1.33 [95% confidence interval (CI): 1.25, 1.40], and the corresponding association for the first postnatal month was 1.19 (95% CI: 1.15, 1.23). Exposure to high ambient temperature during early and mid-pregnancy, as well as the first postnatal month, was associated with rapid weight gain, while during late pregnancy, exposure to low temperatures was associated with this outcome.

Conclusions

Prenatal and postnatal ambient temperatures are associated with rapid infant weight gain.
Effect of diffusivity of amyloid beta monomers on the formation of senile plaques
Authors: Kuznetsov Andrey V
Published: October 2024

Alzheimer’s disease (AD) presents a perplexing question: why does its development span decades, even though individual amyloid beta (Aβ) deposits (senile plaques) can form rapidly in as little as 24 hours, as recent publications suggest? This study investigated whether the formation of senile plaques can be limited by factors other than polymerization kinetics alone. Instead, their formation may be limited by the diffusion-driven supply of Aβ monomers, along with the rate at which the monomers are produced from amyloid precursor protein and the rate at which Aβ monomers undergo degradation. A mathematical model incorporating the nucleation and autocatalytic process (via the Finke–Watzky model), as well as Aβ monomer diffusion, was proposed. The obtained system of partial differential equations was solved numerically, and a simplified version was investigated analytically. The computational results predicted that it takes approximately 7 years for Aβ aggregates to reach a neurotoxic concentration of 50 μM. Additionally, a sensitivity analysis was performed to examine how the diffusivity of Aβ monomers and their production rate impact the concentration of Aβ aggregates.
Windings of Prime Geodesics
Authors: Burrin Claire , von Essen Flemming
Published: October 2024

The winding of a closed oriented geodesic around the cusp of the modular orbifold is computed by the Rademacher symbol, a classical function from the theory of modular forms. In this article, we introduce a new construction of winding numbers to record the winding of closed oriented geodesics about a prescribed cusp of a general cusped hyperbolic orbifold. For various arithmetic families of surfaces, this winding number can again be expressed by a Rademacher symbol, and access to the spectral theory of automorphic forms yields statistical results on the distribution of closed (primitive) oriented geodesics with respect to their winding.
PP2A negatively regulates NK cell T-bet expression and anti-tumor effector function
Authors: Shinzawa Yui , Hara Daisuke , Shinguryo Yuki , Yokoyama Satoru , Kawada Manabu , Hayakawa Yoshihiro
Published: October 2024

The transcription factor T-bet is essential for the anti-tumor effector function of natural killer (NK) cells, but the mechanism regulating its expression in NK cells remains unclear. In this study, we aimed to identify an NK cell-intrinsic regulator that controls T-bet expression. Using T-bet-luciferase reporter assay screening, we identified a protein phosphatase inhibitor as a potential activator of T-bet expression. A series of protein phosphatase 2A (PP2A)-specific inhibitors (PP2Ai) or PP2A siRNA induced the expression of T-bet. In PP2Ai-treated mice, the expression of T-bet and its downstream effector molecules, granzyme B and IFN-γ, was also upregulated in NK cells. Mechanistically, PP2Ai increased the phosphorylation of mTOR and ribosomal protein S6 in NK cells, and mTOR inhibitor canceled the effects of PP2Ai in NK cells. Importantly, NK cells isolated from PP2Ai-treated mice showed higher cytotoxicity and IFN-γ production; therefore, they increased the anti-tumor effector function of NK cells. Accordingly, PP2Ai treatment inhibited lung metastasis of B16 melanoma by NK cell- and mTOR-dependent mechanisms. These results suggest that PP2A negatively regulates NK cell T-bet expression and effector function by an mTOR-dependent mechanism.
Metagenomic and -transcriptomic analyses of microbial nitrogen transformation potential, and gene expression in Swiss lake sediments
Authors: Baumann Kathrin B L , Mazzoli Alessandra , Salazar Guillem , Ruscheweyh Hans-Joachim , Müller Beat , Niederdorfer Robert , Sunagawa Shinichi , Lever Mark A , Lehmann Moritz F , Bürgmann Helmut
Published: October 2024

The global nitrogen (N) cycle has been strongly altered by anthropogenic activities, including increased input of bioavailable N into aquatic ecosystems. Freshwater sediments are hotspots with regards to the turnover and elimination of fixed N, yet the environmental controls on the microbial pathways involved in benthic N removal are not fully understood. Here, we analyze the abundance and expression of microbial genes involved in N transformations using metagenomics and -transcriptomics across sediments of 12 Swiss lakes that differ in sedimentation rates and trophic regimes. Our results indicate that microbial N loss in these sediments is primarily driven by nitrification coupled to denitrification. N-transformation gene compositions indicated three groups of lakes: agriculture-influenced lakes characterized by rapid depletion of oxidants in the sediment porewater, pristine-alpine lakes with relatively deep sedimentary penetration of oxygen and nitrate, and large, deep lakes with intermediate porewater hydrochemical properties. Sedimentary organic matter (OM) characteristics showed the strongest correlations with the community structure of microbial N-cycling communities. Most transformation pathways were expressed, but expression deviated from gene abundance and did not correlate with benthic geochemistry. Cryptic N-cycling may maintain transcriptional activity even when substrate levels are below detection. Sediments of large, deep lakes generally showed lower in-situ N gene expression than agriculture-influenced lakes, and half of the pristine-alpine lakes. This implies that prolonged OM mineralization in the water column can lead to the suppression of benthic N gene expression.
Deep learning transient electromagnetic inversion for seawater intrusion
Authors: Wang Liang , Dai Yunfeng , Liu Wei , Zhou Sheng , Long Xia , Xi Zhenzhu , Xue Junping , Wang Wei
Published: October 2024

To enhance the capability of the transient electromagnetic method (TEM) in detecting seawater intrusion and delineating the boundaries in coastal areas, we developed a deep learning inversion method for TEM data based on the Swin Transformer model in this study. First many standardized resistivity models were designed and generated to describe the subsurface resistivity structures associated with seawater intrusion in coastal areas. Then, TEM forward modeling was performed to compute the corresponding TEM responses, thereby constructing a seawater intrusion-oriented training dataset. Next, the robust Swin Transformer model was employed as the backbone network to build a deep learning inversion model, named SITEMNet, to derive a direct nonlinear transformation that maps TEM responses to subsurface resistivity models. The proposed SITEMNet inversion technique was validated using simulated data scenarios and actual field TEM measurements, showing great promise in accurately identifying seawater intrusion interface and geological formations.
Optimization of ore pillar recovery based on weighting combined with uncertainty measurement theory
Authors: Qian Jun , Xu Wenqiang , Lan Chunlu , Wang Chunlai , Li Changfeng , Yu Qingjun , Li Yuze , Tang Yutao , Zhang Jianwei , Wang Guannan , Zhao Dongsheng , Qu Zhanpeng , Zhao Jiangbo
Published: October 2024

Given the multi-objective nature and inherent uncertainty in evaluating ore pillar mining schemes, the analytic hierarchy process and entropy method were applied to determine factor weights. A new combined weighting method was proposed to obtain more objective and accurate results. Seven quantitative and four qualitative indicators were selected based on various mining performance factors and grading standards. A combined weighting–uncertainty measurement theory evaluation model was then constructed, integrating weight values and confidence levels from the recognition criteria. This model was applied to evaluate three proposed schemes, determining their relative merits and ranking. The evaluation demonstrated that the combined weighting–uncertainty measurement model outperformed both the fuzzy theory and the TOPSIS method in delivering comprehensive, objective, and reliable results for assessing ore pillar mining schemes.
Comparison of torsional and SH-waves in isotropic and anisotropic media based on laboratory measurements
Authors: Ding Pinbo , Li Xiang-yang , Zhang Feng , Chen Haitao
Published: October 2024

Utilization of the torsional wave signal has been reported in medical testing and engineering detection. A torsional wave is a shear-wave train whose vibrating direction (polarization) forms a torsional motion. However, there is a lack of understanding of its characteristics and potential for subsurface investigations. Here, compressional (P), shear (S), and torsional (T) transducers are constructed using different piezoelectric-transformer (PZT) chips in the laboratory, and the characteristics of the torsional (T) wave propagating in isotropic and fracture-induced anisotropic media are analyzed in line with conventional P- and S-waves, covering waveform, amplitude, arrival time, and velocity at different propagating angles. The results indicate that the velocity and anisotropy values measured using the T transducer are almost the same as the SH-wave. For propagation in isotropic and anisotropic media, the wavefield generated by the T transducer is very simple with no mode conversions and source-generated interferences, which is similar to the SH-wavefield, while the SV-wavefield comprises a series of complex events from mode conversions and interferences. For propagating in fluid-saturated fractured rocks, the torsional wavefield also comprises a fast and slow wave train, which is referred to as torsional wave splitting, and is similar to the shear-wave splitting from S transducers. Furthermore, the anisotropy parameters measured using P, S, and T transducers show a good correlation with the fracture density, and the P-wave anisotropy is higher in air-saturated rocks than water-saturated rocks, while the shear-wave anisotropy measured by the S and T transducers is sensitive to fracture density. Like the P transducer, the T transducer is polarization-independent, or directional invariant. Therefore, utilizing the T transducer may simplify the field logistics during 3D shear-wave surveys. However, field torsional wave generation is a major issue that needs further study.
Frequencies of house fly proto-Y chromosomes across populations are predicted by temperature heterogeneity within populations
Authors: Foy Patrick D , Loetzerich Sara R , Boxler David , Burgess Edwin R , Trout Fryxell R T , Gerry Alec C , Hinkle Nancy C , Machtinger Erika T , Olds Cassandra , Tarone Aaron M , Watson Wes , Scott Jeffrey G , Meisel Richard P
Published: October 2024

Sex chromosomes often differ between closely related species and can even be polymorphic within populations. Species with multifactorial sex determination segregate for multiple different sex-determining loci within populations, making them uniquely informative of the selection pressures that drive the evolution of sex chromosomes. The house fly (Musca domestica) is a model species for studying multifactorial sex determination because male-determining genes have been identified on all six of the chromosomes, which means that any chromosome can be a “proto-Y.” Natural populations of house flies also segregate for a recently derived female-determining locus, meaning house flies also have a proto-W chromosome. The different proto-Y chromosomes are distributed along latitudinal clines on multiple continents, their distributions can be explained by seasonality in temperature, and they have temperature-dependent effects on physiological and behavioral traits. It is not clear, however, how the clinal distributions interact with the effect of seasonality on the frequencies of house fly proto-Y and proto-W chromosomes across populations. To address this question, we measured the frequencies of house fly proto-Y and proto-W chromosomes across nine populations in the United States of America. We confirmed the clinal distribution along the eastern coast of North America, but it is limited to the eastern coast. In contrast, the annual mean daily temperature range predicts proto-Y chromosome frequencies across the entire continent. Our results therefore suggest that temperature heterogeneity can explain the distributions of house fly proto-Y chromosomes in a way that does not depend on the cline.
Targeting HPV for the prevention, diagnosis, and treatment of Cervical Cancer
Authors: Ni Huiling , Huang Canhua , Ran Zhi , Li Shan , Kuang Chunmei , Zhang Yu , Yuan Kai
Published: October 2024

Despite advances in screening and prevention, cervical cancer (CC) remains an unresolved public health issue and poses a significant global challenge, particularly for women in low-income regions. Human papillomavirus (HPV) infection, especially with the high-risk strains, is a primary driver of cervical carcinogenesis. Emerging evidence indicates that integrating HPV testing with existing approaches, such as cervical cytology and visual inspection, offers enhanced sensitivity and specificity in CC screening. HPV infection-associated biomarkers, including HPV E6/E7 oncogenes, p16^INK4a, DNA methylation signatures, and non-coding RNAs, offer valuable insights into disease progression and the development of personalized interventions. Preventive and therapeutic vaccination against HPV, along with tertiary prevention strategies such as the use of antiviral and immune-modulating drugs for HPV-related lesions, show great clinical potential. At the mechanistic level, single-cell RNA sequencing analysis and the development of organoid models for HPV infection provide new cellular and molecular insights into HPV-related CC pathogenesis. This review focuses on the crucial roles of HPV in the prevention, diagnosis, and treatment of CC, with particular emphasis on the latest advancements in screening and disease intervention.
Massive chest wall bleeding 3 days after lung wedge resection caused by a protruding staple
Authors: Fang Jincheng , Liu Quan , Wu Chuangyan , Li Jinsong
Published: October 2024

We report a case of massive chest wall bleeding after lung wedge resection caused by a protruding staple. On the third postoperative day, the patient experienced sudden left posterior back pain without any apparent trigger, accompanied by signs of shock. Computed tomography imaging revealed a significant accumulation of blood in the pleural cavity on the side of the surgery. A reoperation was performed, during which we identified active arterial bleeding from a small vessel at the second intercostal space on the posterior chest wall. Hemostasis was achieved using electrocautery. Further examination revealed a protruding staple at the left upper lobe resection margin, which we speculated was likely causing abrasion against the chest wall and leading to the bleeding. This case reveals the potential risk posed by protruding staples. Appropriate precautions should be taken to prevent this rare but dangerous occurrence.
Enhancing Semantic Segmentation in High-Resolution TEM Images: A Comparative Study of Batch Normalization and Instance Normalization
Authors: Kazimi Bashir , Sandfeld Stefan
Published: October 2024

Integrating deep learning into image analysis for transmission electron microscopy (TEM) holds significant promise for advancing materials science and nanotechnology. Deep learning is able to enhance image quality, to automate feature detection, and to accelerate data analysis, addressing the complex nature of TEM datasets. This capability is crucial for precise and efficient characterization of details on the nano—and microscale, e.g., facilitating more accurate and high-throughput analysis of nanoparticle structures. This study investigates the influence of batch normalization (BN) and instance normalization (IN) on the performance of deep learning models for semantic segmentation of high-resolution TEM images. Using U-Net and ResNet architectures, we trained models on two different datasets. Our results demonstrate that IN consistently outperforms BN, yielding higher Dice scores and Intersection over Union metrics. These findings underscore the necessity of selecting appropriate normalization methods to maximize the performance of deep learning models applied to TEM images.
Control of Grain Boundary Formation in Atomically Resolved Nanocrystalline Carbon Monolayers: Dependence on Electron Energy
Authors: Leist Christopher , Makurat Max , Jiao Andy , Liu Xue , Schneider Grégory F , Kaiser Ute
Published: October 2024

In this study, we explore the dynamics of grain boundaries in nanocrystalline carbon monolayers, focusing on their variation with electron beam energy and electron dose rate in a spherical and chromatic aberration-corrected transmission electron microscope. We demonstrate that a clean surface, a high-dose rate, and a 60 keV electron beam are essential for precise local control over the dynamics of grain boundaries. The structure of these linear defects has been evaluated using neural network-generated polygon mapping.
Using two- and three-dimensional landmark data to examine the shape variation of Elliptio complanata from two heavily impounded rivers in northern New York (USA)
Authors: Nagel-Myers Judith , Walrath Krista A , Bowdish Maeve C
Published: October 2024

Despite vast improvements in the quantification of shape variation with geometric morphometric methods, evaluating morphological variation in unionids has remained difficult due to the lack of measurable landmarks on shells and their overall morphological plasticity. In this study, we supplement traditional two-dimensional landmark data with three-dimensional landmark data. Using photogrammetry, we generate three-dimensional models that are landmarked. This approach adds a new, third dimension to capture shape changes, providing a more detailed understanding of the shell topography. With this method, we explore the differences in shell shape along river stretches of two heavily impounded rivers in northern New York (USA). We ask whether isolation by distance, presence of dams and/or difference in land use around sampling localities impact the shell morphologies of Elliptio complanata populations. Our data suggest that, although separated for almost a century, these unionid populations do not show a pattern of increased morphological difference with distance. But we find that broad, rounded morphs that are posteriorly extended occur more frequently in reservoir environments while unaltered river habitats have a higher number of slim and more elongated variants.
Dual decoding of cell types and gene expression in spatial transcriptomics with PANDA
Authors: Wang Meng-Guo , Chen Luonan , Zhang Xiao-Fei
Published: October 2024

Sequencing-based spatial transcriptomics technologies have revolutionized our understanding of complex biological systems by enabling transcriptome profiling while preserving spatial context. However, spot-level expression measurements often amalgamate signals from diverse cells, obscuring potential heterogeneity. Existing methods aim to deconvolute spatial transcriptomics data into cell type proportions for each spot using single-cell RNA sequencing references but overlook cell-type-specific gene expression, essential for uncovering intra-type heterogeneity. We present PANDA (ProbAbilistic-based decoNvolution with spot-aDaptive cell type signAtures), a novel method that concurrently deciphers spot-level gene expression into both cell type proportions and cell-type-specific gene expression. PANDA integrates archetypal analysis to capture within-cell-type heterogeneity and dynamically learns cell type signatures for each spot during deconvolution. Simulations demonstrate PANDA’s superior performance. Applied to real spatial transcriptomics data from diverse tissues, including tumor, brain, and developing heart, PANDA reconstructs spatial structures and reveals subtle transcriptional variations within specific cell types, offering a comprehensive understanding of tissue dynamics.
bcRflow: a Nextflow pipeline for characterizing B cell receptor repertoires from non-targeted transcriptomic data
Authors: Schlegel Brent T , Morikone Michael , Mu Fangping , Tang Wan-Yee , Kohanbash Gary , Rajasundaram Dhivyaa
Published: October 2024

B cells play a critical role in the adaptive recognition of foreign antigens through diverse receptor generation. While targeted immune sequencing methods are commonly used to profile B cell receptors (BCRs), they have limitations in cost and tissue availability. Analyzing B cell receptor profiling from non-targeted transcriptomics data is a promising alternative, but a systematic pipeline integrating tools for accurate immune repertoire extraction is lacking. Here, we present bcRflow, a Nextflow pipeline designed to characterize BCR repertoires from non-targeted transcriptomics data, with functional modules for alignment, processing, and visualization. bcRflow is a comprehensive, reproducible, and scalable pipeline that can run on high-performance computing clusters, cloud-based computing resources like Amazon Web Services (AWS), the Open OnDemand framework, or even local desktops. bcRflow utilizes institutional configurations provided by nf-core to ensure maximum portability and accessibility. To demonstrate the functionality of the bcRflow pipeline, we analyzed a public dataset of bulk transcriptomic samples from COVID-19 patients and healthy controls. We have shown that bcRflow streamlines the analysis of BCR repertoires from non-targeted transcriptomics data, providing valuable insights into the B cell immune response for biological and clinical research. bcRflow is available at https://github.com/Bioinformatics-Core-at-Childrens/bcRflow.
Perfusion MRI-based differentiation between early tumor progression and pseudoprogression in glioblastoma and its use in clinical practice
Authors: van Dorth Daniëlle , Croese Robert J I , Jiang Feng Yan , Schmitz-Abecassis Bárbara , Taphoorn Martin J B , Smits Marion , Dirven Linda , van Osch Matthias J P , de Bresser Jeroen , Koekkoek Johan A F
Published: October 2024

Background

Early treatment effects in patients with glioblastoma are frequently discussed during multidisciplinary team meetings (MDTM), after which a decision regarding (dis)continuation of tumor-targeted treatment is made. This study examined whether a separate and systematic evaluation of perfusion MRI (pMRI) could impact such treatment decisions in the early stage.

Methods

This retrospective observational study evaluated the diagnostic accuracy for detecting early tumor progression of 4 different approaches including conventional MRI, pMRI with Arterial Spin Labeling (ASL), and/or Dynamic Susceptibility Contrast (DSC) MRI, and compared those to the MDTM evaluation in clinical practice.

Results

Sixty-five glioblastoma patients with clinical and radiological data until 9 months after irradiation were included. For all approaches, the sensitivity for detecting early true disease progression was poor to moderate (32%–62%). Area under the curve values were comparable (range 0.63–0.74), but highest for the MDTM evaluation (0.74). In the cases of inconclusive MDTM (26%), systematic pMRI evaluation showed a higher sensitivity compared to conventional MRI (respectively, 36% vs 0%), while the specificity was 100% for all MRI approaches. Multivariable regression analysis showed that a lower KPS score (OR = 0.84 [95% CI: 0.77–0.91]) and pMRI indicative of tumor progression (OR = 0.09 [95% CI: 0.02–0.52]) were independently associated with concluding tumor progression at the MDTM.

Conclusion

MDTM assessment in daily clinical practice has a higher diagnostic accuracy in distinguishing early tumor progression from pseudoprogression compared to a separate, systematic evaluation of pMRI. Systematic evaluation of pMRI might be helpful if the clinical MDTM assessment is uncertain.
Variation in Relative Risk Perceptions and Tobacco Use by Race and Socioeconomic Status Among Older Adults Who Smoke: Evidence From the Population Assessment of Tobacco and Health Study
Authors: Snell L Morgan , Barnes Andrew J , Eissenberg Thomas
Published: October 2024

Introduction

Older adults who smoke face significant risk of tobacco-related diseases and hold misperceptions about health risks posed by nicotine product use. This study examined whether socioeconomic status (SES) and race are associated with variation in cigarette/e-cigarette relative risk perceptions, whether relative risk perceptions are associated with tobacco use behaviors, and whether SES and race moderate associations between perceptions and use behaviors.

Methods

Five waves of Population Assessment of Tobacco and Health (PATH) Study yielded data from 1879 adults aged 55 years and older who smoked within the past 30 days during Wave 1. Adjusted longitudinal logistic models estimated associations between higher versus lower SES (“low SES”: less than high school diploma/GED and annual household income <$25 000) and race (White vs. Black/African American [AA]) and e-cigarette/cigarette relative risk perceptions, behavioral intentions, and e-cigarette use.

Results

Lower-SES adults were more likely to report that e-cigarettes were very/extremely harmful to health (adjusted OR [AOR]: 1.74, p < .01) and less likely to report that e-cigarettes were less harmful than cigarettes (AOR: 0.65, p < .01). Black/AA adults were less likely to report that e-cigarettes were less harmful than cigarettes. Participants rating e-cigarettes as equally/more harmful than cigarettes exhibited lower odds of intending to quit smoking or switch to e-cigarettes. Finally, Black/AA adults who also perceived e-cigarettes equally/more harmful than cigarettes exhibited greater odds of trying to reduce rather than quit smoking (AOR: 1.58, p = .02).

Conclusions

Many older adults who smoke perceive e-cigarettes as equally or more harmful than cigarettes, particularly low-SES and Black/AA older adults. Differences in relative risk perceptions among high-priority populations could negatively influence cessation attempts and switching behaviors.

Implications

This study found that Black/AA and low-SES older adults who smoke cigarettes were more likely to perceive e-cigarettes as harmful or more harmful than cigarettes. The absence of accurate, evidence-based information regarding the relative health risks associated with the long-term use of various tobacco products may impede policy efforts to reduce disparities in smoking-related disease through increased cessation and/or harm reduction.
Chemotherapy-induced cognitive impairment and its long-term development in patients with breast cancer: results from the observational CICARO study
Authors: Kerkmann Anna , Schinke Christian , Dordevic Adam , Kern Johannes , Bangemann Nikola , Finck Josefine , Blohmer Jens-Uwe , Ruprecht Klemens , Göpfert Jens C , Otto Carolin , Materne Bianca , Endres Matthias , Boehmerle Wolfgang , Huehnchen Petra
Published: October 2024

Background

Chemotherapy-induced cognitive impairment (CICI) is a well-recognized side effect of breast cancer treatment. However, prospective long-term evaluations of CICI using standardized neuropsychological tests are scarce.

Patients and Methods

This prospective longitudinal cohort study investigated cognitive dysfunction and its impact on quality of life and everyday functioning in patients with breast cancer receiving first-line chemotherapy compared to patients with breast cancer without chemotherapy. Assessment occurred prior to chemotherapy, postchemotherapy (median 6 months), and 2-3 years later. We used standardized neuropsychological tests, questionnaires, and scales to assess patients’ quality of life and functioning. Additionally, serum analysis for neurodegenerative markers and autoantibodies was conducted.

Results

We included n = 53 patients. Overall cognitive function declined statistically significantly (P = .046) postchemotherapy compared to control patients, mostly driven by a reduced figural memory (P = .011). Patients who received chemotherapy showed a greater reduction in quality of life (increased fatigue symptoms, P = .023; reduced Karnofsky index, P < .001); however, without a statistically significant effect on cognitive decline. The neurodegenerative markers Neurofilament light chain (NfL) and phosphorylated Neurofilament heavy chain (pNfH) increased statistically significantly (P < .001) postchemotherapy and pNfH correlated with overall cognitive function. After 2-3 years, both cognitive performance and quality of life were comparable between chemotherapy-treated and control patients.

Conclusion

Our findings suggest that chemotherapy statistically significantly contributes to overall cognitive dysfunction in patients with breast cancer, which disappears after 2-3 years, indicating a recovery in both objectively measurable cognitive function and subjective quality of life. Future research should examine larger sample sizes and explore screening indicators, particularly pNfH.
An mRNA methylase and demethylase regulate sorghum salt tolerance by mediating N6-methyladenosine modification
Authors: Zheng Hongxiang , Dang Yingying , Gao Yinping , Li Simin , Wu FengHui , Zhang Fangning , Wang Xuemei , Du Xihua , Wang Lei , Song Jie , Sui Na
Published: October 2024

N 6-methyladenosine (m6A) modification is a crucial and widespread molecular mechanism governing plant development and stress tolerance. The specific impact of m6A regulation on plants with inherently high salt tolerance remains unclear. Existing research primarily focuses on the overexpression or knockout of individual writer or eraser components to alter m6A levels. However, a comprehensive study simultaneously altering overall m6A modification levels within the same experiment is lacking. Such an investigation is essential to determine whether opposing changes in m6A modification levels exert entirely different effects on plant salt tolerance. In this study, we identified the major writer member mRNA adenosine methylase A (SbMTA) in sorghum (Sorghum bicolor) as critical for sorghum survival. The sbmta mutant exhibits a phenotype characterized by reduced overall m6A, developmental arrest, and, ultimately, lethality. Overexpression of SbMTA increased m6A levels and salt tolerance, while overexpression of the m6A eraser alkylated DNA repair protein AlkB homolog 10B (SbALKBH10B) in sorghum showed the opposite phenotype. Comparative analyses between sorghum with different m6A levels reveal that SbMTA- and SbALKBH10B-mediated m6A alterations significantly impact the stability and expression levels of genes related to the abscisic acid signaling pathway and growth under salt stress. In summary, this study unveils the intricate relationship between m6A modifications and salt tolerance in sorghum, providing valuable insights into how m6A modification levels on specific transcripts influence responses to salt stress.
Efficient genetic transformation and gene editing of Chinese cabbage using Agrobacterium rhizogenes
Authors: Wang Yaolong , Yang Xuedong , Wang Wenlong , Wang Yan , Chen Xiaoshan , Wu Han , Gao Zhanyuan , Xu Huanhuan , Liu Tongkun , Li Ying , Xiao Dong , Liu Wusheng , Hou Xilin , Zhang Changwei
Published: October 2024

A method using Agrobacterium rhizogenes-mediated callus production and plant regeneration enables efficient genetic transformation and gene editing in Chinese cabbage.
OsPUB75–OsHDA716 mediates deactivation and degradation of OsbZIP46 to negatively regulate drought tolerance in rice
Authors: Sun Ying , Gu Xinyue , Qu Chengfeng , Jin Ning , Qin Tian , Jin Liang , Huang Junli
Published: October 2024

Histone deacetylases (HDACs) play crucial roles in plant stress responses via modification of histone as well as nonhistone proteins; however, how HDAC-mediated deacetylation of nonhistone substrates affects protein functions remains elusive. Here, we report that the reduced potassium dependency3/histone deacetylase1–type histone deacetylase OsHDA716 and plant U-box E3 ubiquitin ligase OsPUB75 form a complex to regulate rice drought response via deactivation and degradation of basic leucine zipper (bZIP) transcription factor OsbZIP46 in rice (Oryza sativa). OsHDA716 decreases abscisic acid (ABA)-induced drought tolerance, and mechanistic investigations showed that OsHDA716 interacts with and deacetylates OsbZIP46, a key regulator in ABA signaling and drought response, thus inhibiting its transcriptional activity. Furthermore, OsHDA716 recruits OsPUB75 to facilitate ubiquitination and degradation of deacetylated OsbZIP46. Therefore, the OsPUB75–OsHDA716 complex exerts double restrictions on the transcriptional activity and protein stability of OsbZIP46, leading to repression of downstream drought-responsive gene expression and consequently resulting in reduced drought tolerance. Conversely, OsbZIP46 acts as an upstream repressor to repress OsHDA716 expression, and therefore OsHDA716 and OsbZIP46 form an antagonistic pair to reciprocally inhibit each other. Genetic evidence showed that OsHDA716 works with OsbZIP46 in a common pathway to antagonistically regulate rice drought response, revealing that plants can fine-tune stress responses by the complex interplay between chromatin regulators and transcription factors. Our findings unveil an acetylation-dependent regulatory mechanism governing protein functions and shed light on the precise coordination of activity and stability of key transcription factors through a combination of different posttranslational modifications.
Explanations of and interventions against affective polarization cannot afford to ignore the power of ingroup norm perception
Authors: You Zi Ting , Lee Spike W S
Published: October 2024

Affective polarization, or animosity toward opposing political groups, is a fundamentally intergroup phenomenon. Yet, prevailing explanations of it and interventions against it have overlooked the power of ingroup norm perception. To illustrate this power, we begin with evidence from 3 studies which reveal that partisans' perception of their ingroup's norm of negative attitudes toward the outgroup is exaggerated and uniquely predicts their own polarization-related attitudes. Specifically, our original data show that in predicting affective polarization (i.e. how one feels about one's partisan outgroup), the variance explained by ingroup norm perception is 8.4 times the variance explained by outgroup meta-perception. Our reanalysis of existing data shows that in predicting support for partisan violence (i.e. how strongly one endorses and is willing to engage in partisan violence), ingroup norm perception explains 52% of the variance, whereas outgroup meta-perception explains 0%. Our pilot experiment shows that correcting ingroup norm perception can reduce affective polarization. We elucidate the theoretical underpinnings of the unique psychological power of ingroup norm perception and related ingroup processes. Building on these empirical and theoretical analyses, we propose approaches to designing and evaluating interventions that leverage ingroup norm perception to curb affective polarization. We specify critical boundary conditions that deserve prioritized attention in future intervention research. In sum, scientists and practitioners cannot afford to ignore the power of ingroup norm perception in explaining and curbing affective polarization.
Moral wiggle room and group favoritism among political partisans
Authors: Robbett Andrea , Walsh Henry , Matthews Peter Hans
Published: October 2024

How does the availability of excuses for self-interested behavior impact group favoritism? We report the results of a preregistered experiment, conducted on the eve of the 2022 midterm elections, in which American political partisans made payoff distribution choices for themselves and a partner who was known to be a co-partisan or opposing partisan. Under full information, participants exhibit significant group favoritism. However, when the payoff consequences for one's partner are initially hidden, participants exploit this excuse to act selfishly regardless of who their partner is and ignorance rates are identical for in-group and out-group members. As a result, moral wiggle room has a significantly larger impact on selfish behavior for those interacting with co-partisans than opposing partisans, leading to a reduction in group favoritism.
Affective polarization is uniformly distributed across American States
Authors: Holliday Derek E , Lelkes Yphtach , Westwood Sean J
Published: October 2024

US partisans view each other with increasing negativity. While many attribute the growth of such affective polarization to nationally cross-cutting forces, such as ideological partisan sorting or access to partisan media, others emphasize the effects of contextual and institutional forces. For the first time, we introduce and explore data sufficiently granular to fully map the extent of partisan animosity across the US states. With a massive, nationally representative survey we find that, counter to expectations, variation in affective polarization across states is relatively small, and is instead largely a function of individual-level attitudinal (but not demographic) characteristics. While elections pit regions of the country against others, our results suggest affective polarization is a national, not regional, problem, requiring national interventions.
Understanding reaction to corporate activism: The moderating role of polarization
Authors: Braga Luiza , Grinstein Amir , Tardin Matheus , Perin Marcelo
Published: October 2024

In our polarized societies, more companies are taking a stand on divisive sociopolitical issues. However, given the mixed findings from previous studies, it remains unclear whether Corporate Activism (CA) is more likely to hurt or help a company's performance and reputation, or shape the public's attitudes toward the sociopolitical issue involved. To better understand the impact of CA in polarized societies, it is valuable to study moderating factors, especially those linked to polarization. A meta-analysis of 72 scholarly works is conducted to examine the impact of CA on various outcomes (e.g. ads and social media engagement, cognitive and attitudinal reactions, public's intentions and actions, emotional reactions, social and ethical engagement, workplace, and employee perceptions) and the role of moderators (a sociopolitical issue's political leaning and controversy level, political orientation of the target audience, key demographics). The analysis reveals a positive, albeit small, effect size (0.085 [95% CI (0.0542, 0.1158)]) with the most impact on two outcomes: cognitive and attitudinal reactions, and emotional reactions. It further reveals that companies adopting liberal-leaning CAs elicit more favorable responses than those adopting conservative CAs and that liberals respond positively to CA, while conservatives are more neutral. However, when there is alignment between the CA's political leaning and the audience's political orientation, conservatives have a stronger positive response than liberals. Also, younger audiences view CA more positively. Finally, per national culture, while power distance and individualism positively moderate the reaction to CA, uncertainty avoidance has a negative effect.