bluuebunny/crossref_metadata_2025 huggingface dataset:
Scaled asymptotic solution nets for unlabeled seepage equation solutions with variable well flow
Authors: Wang Qian , Li Daolun , Zha Wenshu , Shen Luhang , Li Xiang , Guo Bumin , Xu Yantao
Published: January 2025

The seepage equation is essential for understanding fluid flow in porous media, crucial for analyzing fluid behavior in various pore structures and supporting reservoir engineering. However, solving this equation under complex conditions, such as variable well flow rates, poses significant challenges. Although physics-informed neural networks have been effective in addressing partial differential equations, they often struggle with the complexities of such physical phenomena. This paper presents an improved method using physical asymptotic solution nets combined with scaling before activation (SBA) and gradient constraints to solve the seepage equation in porous media under varying well flow rates without labeled data. The model consists of two neural networks: one that approximates the asymptotic solution of the seepage equation and another that corrects approximation errors to ensure both mathematical and physical accuracy. When the well flow rate changes, the network may fail to fully satisfy the asymptotic solution due to pressure distribution variations, resulting in sub-optimal outcomes. To address this, we incorporate gradient information into the loss function to reinforce physical constraints and utilize the SBA method to enhance the approximation. This gradient information is derived from the pressure distribution at the previous flow rate, and the SBA method regulates weight adjustments through an adjustment coefficient constrained by the loss function, preventing sub-optimal local minima during optimization. Experimental results show that our method achieves an accuracy range of 10−4 to 10−2.
Cosmic extremes of luminosity
Authors: Warren Donald C.
Published: January 2025

What is the brightest object in the sky? The obvious answer is the Sun. But the difference between intrinsic brightness and perceived brightness complicates matters.
The gradual, then sudden, demise of an East Antarctic ice shelf
Authors: Miller Johanna L.
Published: January 2025

Decades of satellite imagery held previously unrecognized clues to the ice shelf’s impending collapse—and could help researchers foresee the next one.
Individual differences elucidate the perceptual benefits associated with robust temporal fine-structure processing
Authors: Borjigin Agudemu , Bharadwaj Hari M.
Published: January 2025

The auditory system is unique among sensory systems in its ability to phase lock to and precisely follow very fast cycle-by-cycle fluctuations in the phase of sound-driven cochlear vibrations. Yet, the perceptual role of this temporal fine structure (TFS) code is debated. This fundamental gap is attributable to our inability to experimentally manipulate TFS cues without altering other perceptually relevant cues. Here, we circumnavigated this limitation by leveraging individual differences across 200 participants to systematically compare variations in TFS sensitivity to performance in a range of speech perception tasks. TFS sensitivity was assessed through detection of interaural time/phase differences, while speech perception was evaluated by word identification under noise interference. Results suggest that greater TFS sensitivity is not associated with greater masking release from fundamental-frequency or spatial cues but appears to contribute to resilience against the effects of reverberation. We also found that greater TFS sensitivity is associated with faster response times, indicating reduced listening effort. These findings highlight the perceptual significance of TFS coding for everyday hearing.
Deriving a genetic regulatory network from an optimization principle
Authors: Sokolowski Thomas R. , Gregor Thomas , Bialek William , Tkačik Gašper
Published: January 2025

Many biological systems operate near the physical limits to their performance, suggesting that aspects of their behavior and underlying mechanisms could be derived from optimization principles. However, such principles have often been applied only in simplified models. Here, we explore a detailed mechanistic model of the gap gene network in the
Drosophila
embryo, optimizing its 50+ parameters to maximize the information that gene expression levels provide about nuclear positions. This optimization is conducted under realistic constraints, such as limits on the number of available molecules. Remarkably, the optimal networks we derive closely match the architecture and spatial gene expression profiles observed in the real organism. Our framework quantifies the tradeoffs involved in maximizing functional performance and allows for the exploration of alternative network configurations, addressing the question of which features are necessary and which are contingent. Our results suggest that multiple solutions to the optimization problem might exist across closely related organisms, offering insights into the evolution of gene regulatory networks.
TRAMP assembly alters the conformation and RNA binding of Mtr4 and Trf4-Air2
Authors: Denson Joshua M. , Zhang Naifu , Ball Darby , Thompson Kayla , Johnson Sean J. , D’Arcy Sheena
Published: January 2025

The TRAMP complex contains two enzymatic activities essential for RNA processing upstream of the nuclear exosome. Within TRAMP, RNA is 3′ polyadenylated by a subcomplex of Trf4/5 and Air1/2 and unwound 3′ to 5′ by Mtr4, a DExH helicase. The molecular mechanisms of TRAMP assembly and RNA shuffling between the two TRAMP catalytic sites are poorly understood. Here, we report solution hydrogen–deuterium exchange data with thermodynamic and functional assays to uncover these mechanisms for yeast TRAMP with Trf4 and Air2 homologs. We show that TRAMP assembly constrains RNA-recognition motifs that are peripheral to catalytic sites. These include the Mtr4 Arch and Air2 zinc knuckles 1, 2, and 3. While the Air2 Arch-interacting motif likely constrains the Mtr4 Arch via transient interactions, these do not fully account for the importance of the Mtr4 Arch in TRAMP assembly. We further show that tRNA binding by single active-site subunits, Mtr4 and Trf4-Air2, differs from the double active-site TRAMP. TRAMP has reduced tRNA binding on the Mtr4 Fist and RecA2 domains, offset by increased tRNA binding on Air2 zinc knuckles 2 and 3. Competition between these RNA-binding sites may drive tRNA transfer between TRAMP subunits. We identify dynamic changes upon TRAMP assembly and RNA-recognition motifs that transfer RNA between TRAMP catalytic sites.
Mitochondrial DNA lineages determine tumor progression through T cell reactive oxygen signaling
Authors: Yardeni Tal , Olali Arnold Z. , Chen Hsiao-Wen , Wang Liqing , Halton Jeffrey A. , Zenab Angi , Morrow Ryan , Butic Arrienne , Murdock Deborah G. , Waymire Katrina G. , MacGregor Grant R. , Boursi Ben , Beier Ulf H. , Hancock Wayne W. , Wallace Douglas C.
Published: January 2025

Mitochondrial DNA (mtDNA) is highly polymorphic, and host mtDNA variation has been associated with altered cancer severity. To determine the basis of this mtDNA–cancer association, we analyzed conplastic mice with the C57BL/6J (B6) nucleus but two naturally occurring mtDNA lineages,

mtDNA
B6

and

mtDNA
NZB

, where

mtDNA
NZB

mitochondria generate more oxidative phosphorylation (OXPHOS)-derived reactive oxygen species (mROS). In a cardiac transplant model,

mtDNA
B6

Foxp3+ T regulatory (Treg) cells supported long-term allograft survival, whereas

mtDNA
NZB

Treg cells failed to suppress host T effector (Teff) cells, leading to acute rejection. When challenged with melanoma or colon cancer cells, the

mtDNA
NZB

mice exhibited strikingly impaired tumor growth while

mtDNA
B6

mice showed Treg-dependent inhibition of Teff cells and allowed rapid tumor growth. Transcriptional analysis showed that activation of

mtDNA
NZB

Teff cells increased mitochondrial gene expression while activation of

mtDNA
NZB

Treg cells impaired mitochondrial gene expression and resulted in

mtDNA
NZB

Treg cell exhaustion. Induction of the mitochondrially targeted catalytic antioxidant, mCAT, in hematopoietic cells normalized

mtDNA
NZB

Treg function in both transplant and tumor models, indicating a key role for mROS in promoting Treg dysfunction. Anti-PD-L1 therapy did not modulate these effects, indicating that modulation of host mitochondrial function provides an independent approach for enhancing tumor cell destruction.
Regulation of Cajal bodies: Unexpected connection to 60S ribosomes
Authors: Courvan Edward M.C. , Parker Roy R.
Published: January 2025

Cajal bodies are essential sites for the biogenesis of small nuclear and nucleolar ribonucleoproteins. In this issue, Courvan and Parker discuss new work from Neugebauer and colleagues (https://doi.org/10.1083/jcb.202305081) that carefully profiles Cajal Body components and finds an unexpected role for 60S ribosomal proteins.
Comparing experimental and numerical approaches in the analysis of n-TiO2/p-Si photodiodes
Authors: Karaca Abdullah , Yıldız D E , Yıldırım Murat
Published: January 2025

Heterojunction photodiodes consisting of n-TiO2/p-Si were produced using the ALD method on a single-sided polished p-type Si wafer. The characteristics of the Al/TiO2/Si/Al heterojunction device were assessed through current-voltage (I-V) measurements. The ideality factor (n) and the light-detecting characteristics of the photodiode, investigations on photosensitivityresponsivity specific detectivity (*D)and noise equivalent power (NEP) were conducted based on the correlation between photocurrent and light intensity. The photo-response efficiency was evaluated through transient photocurrent (I-t) assessments across varying light power levels. The I-V curve examination under various illumination sources revealed that the photodiode's responsiveness increased as the TiO2 thickness decreased. The impact on the characteristic capabilities of the n-TiO2/p-Si heterostructure as the TiO2 film thickness increased was scrutinized in relation to layer resistance and structural defect states. Consistent results were obtained through experimental investigations, with comparative analyses conducted between theoretical and experimental data to validate the findings.
Fourier Ptychographic Microscopy image aberration correction method based on multi-feature fusion residual network
Authors: Wang XiaoLi , Luo YanLi , Wang Hao , Li Jie , Wang Yan , Wang Xinbo , Lin Zechuan
Published: January 2025

AbstractObjective: The study aims to address optical aberrations caused by sample non-uniformity or imaging system deviations in Fourier Ptychographic Microscopy (FPM), a technique enabling high-resolution microscopic imaging with a large field of view. The proposed approach involves utilizing a multi-feature fusion residual network method for aberration correction, leveraging residual networks and multi-scale convolutional kernels to extract deep residual features and enhance the ability to capture relevant image characteristics.Approach: This method optimizes network performance using grouped convolutions and attention mechanisms without significantly increasing the parameter count. By combining Zernike modes, accurate estimation and correction of aberrations are achieved, leading to a significant improvement in imaging quality.Main results: The research demonstrates the effective correction of aberrations using this method, enabling high-resolution image reconstruction while preserving rich texture details. Validation results based on simulated and real images showcase the method's efficacy.Significance: By introducing the multi-feature fusion residual network method, this study addresses a significant challenge posed by aberrations in FPM, enhancing imaging quality and offering a new effective approach for high-resolution microscopic imaging. This has important implications for fields such as biomedicine that demand strict image quality standards. Keywords: Fourier Ptychographic Microscopy; Aberration Correction; Multi-Feature Fusion; Residual Network; Zernike Modes
Green fabrication of TiO2-ZnO nanocomposite: synthesis, characterization and their photocatalytic, antibacterial, wound healing and cytotoxic activities
Authors: Priya P Vengatesh , Jeyasundari J
Published: January 2025

In the current investigation, the green synthesis of TiO2, ZnO nanoparticles (NPs) and TiO2-ZnO nanocomposite (NC) from the aqueous extract of Terminalia catappa (T.C) leaves and the assessment of their photocatalytic, cytotoxicity, antibacterial, and wound healing properties. The synthesized NPs and NC was characterized in order to know the optical, structural, morphological and composition etc. According to the XRD analysis, crystallites size 24 nm was measured for TiO2-ZnO NC. The optical properties of composite revealed that the band energy (Eg) was found to be 2.9 eV. FT-IR and XPS were used to confirm the functional groups of T.C extract, metal oxide stretches, surface interfaces and chemical state. HR-TEM micrographs confirmed the particle size (21–27 nm) and spherical morphology. SEM for NC revealed small particles with high tendencies to form larger spherical agglomerations. EDX spectra for the composites revealed the elemental composition of metal oxides with plant extract. Furthermore, the photocatalytic activity of NC in aqueous solution of Methylene Blue (MB) dye was investigated under visible light irradiation. The high photodegradation efficiency value of NC observed at 45 min was 98%. In the MTT assay, TiO2-ZnO NC exhibited dose-dependent cytotoxicity effects on fibroblast cells (L929 cell line). In addition, diameter inhibition zones demonstrated that NC showed dose-dependent bacterial activities against various disease-causing strains of Gram-negative and Gram-positive bacteria. The results of wound scratch assay showed that NC enhanced the cell migration and proliferation with noticeable cell shrinkage observed in the wound model. The present study indicates that the green synthesis of TiO2-ZnO NC from T.C aqueous leaf extract has the potential to be used as a photocatalyst for the degradation of organic pollutants and as an antibacterial agent against various disease-causing pathogens and hence could be useful for developing wound healing drugs.
Enhancement of 316 L stainless steel mechanical properties through TiC particle introduction via metal powder injection molding
Authors: Da Gu , Dun Wu , Zexu Chen , Zheng Cao , Junfeng Cheng , Dong Wang , Xiangyu Lu , Chunlin Liu
Published: January 2025

Metal powder injection molding (MIM) has been a popular technique in production of alloy materials. Through this technique, near-net-shape alloy products can be molded with one-step production. Stainless steel 316 L (SS 316 L) is an important material in aerospace and marine industry for its excellent material strength and resistance to corrosion. As the industry grows with upgraded techniques, the standard for next generation material strength has improved tremendously. Here we present a practical method strengthening SS 316 L via MIM technique, which might provide a pathway for exploration of high strength materials. TiC was introduced into SS 316 matrix with polyoxymethylene (POM) binder. The metallography indicates that the introduction of TiC facilitates the refinement of the 316 L grain. As the TiC content increases from 0 wt% to 3 wt%, the material properties improve significantly, including a rise in hardness from 151 HV to 301 HV, tensile strength from 689 MPa to 792 MPa, and yield strength from 221 MPa to 339 MPa. Additionally, there is a noticeable reduction in the coefficient of friction and the wear cross-section.
Tailoring magnetic exchange coupling in Zr2Co11/FeCo nanocomposites via dual-source inert gas condensation: a one-step synthesis approach
Authors: Yao Yin , Sun Yan , Sun Jianzhe , Bai Jianhui
Published: January 2025

This study investigated the synthesis and magnetic properties of Zr2Co11/FeCo nanocomposites via a one-step dual-source inert gas condensation method. The composite particles were prepared with varying FeCo mass percentages (5%, 10%, and 15%), and their structural and magnetic characteristics were examined. X-ray diffraction confirmed the successful integration of FeCo into the Zr2Co11 matrix. Magnetic measurements revealed enhanced saturation magnetization and effective exchange coupling in Zr2Co11/FeCo-1 and Zr2Co11/FeCo-2. However, excessive FeCo in Zr2Co11/FeCo-3 resulted in less efficient coupling, as indicated by kinks in the hysteresis loop and negative regions in the Henkel plot. These findings underscore the importance of optimizing FeCo content to achieve superior magnetic properties, offering potential for advanced magnetic materials.
Flow cytometry evaluation of acute myeloid leukemia minimal residual disease based on an understanding of the normal maturation patterns in the blast compartments
Authors: Roshal Mikhail , Gao Qi
Published: January 2025

Objective

Detection of minimal/measurable disease (MRD) in acute myeloid leukemia (AML) is critical for both clinical decision-making and prognostication, yet remains a challenge. Flow cytometry is a well-established method for MRD detection. Flow cytometric (FC) evaluation of MRD must consider a complex maturational pattern of normal hematopoietic development to separate normal from abnormal progenitors. Here, we offer an example of an interpretive approach based on a thorough understanding of stage- and lineage-specific hematopoietic maturation.

Methods

We provide a comprehensive overview of blast maturation from early precursors (hematopoietic stem cells) to committed late-stage unilineage progenitors and commonly observed stage-specific abnormalities based on cases we have encountered in practice. We emphasize the importance of stage-specific comparisons for accurate MRD detection by flow cytometry.

Results

The AML blasts almost invariably show abnormal phenotypes, and the phenotypes may evolve upon therapy. The detected phenotypes are necessarily confined to the target antigens included in the panel. It is therefore critical to evaluate a range of antigens to establish a specific stage/state of lineage commitment and detect potential common abnormalities. Moreover, enough cells must be acquired to allow for the detection of MRD at desired levels. Significant technical and analytical validation is critical.

Conclusions

Flow cytometry offers a powerful single-cell-based platform for MRD detection in AML, and the results have been proven critical for disease management. Leukemia-associated phenotype-informed difference from the normal approach presented in this review presents an analytical framework for sensitive and accurate MRD detection.
kMetaShot: a fast and reliable taxonomy classifier for metagenome-assembled genomes
Authors: Defazio Giuseppe , Tangaro Marco Antonio , Pesole Graziano , Fosso Bruno
Published: January 2025

The advent of high-throughput sequencing (HTS) technologies unlocked the complexity of the microbial world through the development of metagenomics, which now provides an unprecedented and comprehensive overview of its taxonomic and functional contribution in a huge variety of macro- and micro-ecosystems. In particular, shotgun metagenomics allows the reconstruction of microbial genomes, through the assembly of reads into MAGs (metagenome-assembled genomes). In fact, MAGs represent an information-rich proxy for inferring the taxonomic composition and the functional contribution of microbiomes, even if the relevant analytical approaches are not trivial and still improvable. In this regard, tools like CAMITAX and GTDBtk have implemented complex approaches, relying on marker gene identification and sequence alignments, requiring a large processing time. With the aim of deploying an effective tool for fast and reliable MAG taxonomic classification, we present here kMetaShot, a taxonomy classifier based on k-mer/minimizer counting. We benchmarked kMetaShot against CAMITAX and GTDBtk by using both in silico and real mock communities and demonstrated how, while implementing a fast and concise algorithm, it outperforms the other tools in terms of classification accuracy. Additionally, kMetaShot is an easy-to-install and easy-to-use bioinformatic tool that is also suitable for researchers with few command-line skills. It is available and documented at https://github.com/gdefazio/kMetaShot.
Virus Evolution in Prolonged Infections of Immunocompromised Individuals
Authors: Raglow Zoe , Lauring Adam S
Published: January 2025

Background

Many viruses can cause persistent infection and/or viral shedding in immunocompromised hosts. This is a well-described occurrence not only with SARS-CoV-2 but for many other viruses as well. Understanding how viruses evolve and mutate in these patients and the global impact of this phenomenon is critical as the immunocompromised population expands.

Content

In this review, we provide an overview of populations at risk for prolonged viral shedding, clinical manifestations of persistent viral infection, and methods of assessing viral evolution. We then review the literature on viral evolution in immunocompromised patients across an array of RNA viruses, including SARS-CoV-2, norovirus, influenza, and poliovirus, and discuss the global implications of persistent viral infections in these hosts.

There is significant evidence for accelerated viral evolution and accumulation of mutations in antigenic sites in immunocompromised hosts across many viral pathogens. However, the implications of this phenomenon are not clear; while there are rare reports of transmission of these variants, they have not clearly been shown to predict disease outbreaks or have significant global relevance. Emerging methods including wastewater monitoring may provide a more sophisticated understanding of the impact of variants that evolve in immunocompromised hosts on the wider host population.
Integrating Pharmacogenomics into the Broader Construct of Genomic Medicine: Efforts by the ClinGen Pharmacogenomics Working Group (PGxWG)
Authors: Gong Li , Klein Clarissa J , Caudle Kelly E , Moyer Ann M , Scott Stuart A , Whirl-Carrillo Michelle , Klein Teri E ,   ClinGen Pharmacogenomics Working Group (PGxWG), Aminkeng Folefac , Amr Sami , Ashcraft Kristine , Bernhardt Brooke , Blaxwell Burns C , Bly Zo , Cipriani Amber , Cody Neal A , Dandara Collet , Del Tredici Andria L , Empey Philip E , Fieg Elizabeth , Gaedigk Andrea , Gregornik David , Harrison Steven , Hart Jennifer , Hoffman James M , Hunter Jessica Ezzell , Iwuchukwu Otito , Landrum Melissa , Langlais Kristofor , Lee Min Ta , Li Rongling , Malheiro Adriana , McLeod Howard L , Monte Andrew , Morales Joannella , Naik Hetanshi , Obeng Aniwaa Owusu , Oni-Orisan Akinyemi , Ramos Erin M , Ren Zhaoxia , Ritchie Marylyn D , Rogers Sara , Scherer Steven E , Shaaban Sherin , Swen Jesse J , Wagner Alex , Woodahl Erica , McIntyre Joanne , Merritt Keren , Wright Matt W
Published: January 2025

Pharmacogenomics (PGx) is focused on the relationship between an individual's genetic makeup and their response to medications, with the overarching aim of guiding prescribing decisions to improve drug efficacy and reduce adverse events. The PGx and genomic medicine communities have worked independently for over 2 decades, developing separate standards and terminology, making implementation of PGx across all areas of genomic medicine difficult. To address this issue, the Clinical Genome Resource (ClinGen) Pharmacogenomics Working Group (PGxWG) was established by the National Institutes of Health (NIH)-funded ClinGen to initially create frameworks for evaluating gene–drug response clinical validity and actionability aligned with the ClinGen frameworks for evaluating monogenic gene–disease relationships, and a framework for classifying germline PGx variants similar to the American College of Medical Genetics (ACMG) and Association of Molecular Pathology (AMP) system for interpretation of disease-causing variants. These frameworks will leverage decades of work from well-established PGx resources facilitating buy-in among PGx stakeholders. In this report, we describe the background and major activities of the ClinGen PGxWG, and how this initiative will facilitate the critical inclusion of PGx into the larger context of genomic medicine.
Genetic and Phenotypic Intra-Clade Variation in Candida auris Isolated from Critically Ill Patients in a New York City Tertiary Care Center
Authors: Smithgall Marie C , Kilic Abdullah , Weidmann Maxwell , Ofori Kenneth , Gu Yue , Koganti Lahari , Mi Shijun , Xia Hongai , Shi Jun , Pang Jiuhong , Mansukhani Mahesh , Hsiao Susan , Wu Fann
Published: January 2025

Background

Candida auris is an emerging multidrug-resistant pathogen. Interpretation of susceptibility testing can be difficult since minimum inhibitory concentration (MIC) breakpoints have not been fully established.

Methods

All C. auris isolates from unique patients identified at a large urban hospital between 2020 and 2024 (n = 66) underwent whole-genome sequencing (WGS). Genomic DNA was extracted from pure culture isolates and underwent PCR-free library preparation. WGS was performed on an Illumina platform (NextSeq2000) with an average coverage of 50×. Genomic analysis was conducted via an adapted GATK-based pipeline using the B11205 strain as the reference genome based on the CDC (MycoSNP) protocol. All isolates underwent FKS1 gene Sanger sequencing for confirmation of WGS results. Genotypic results were correlated with antifungal susceptibility testing.

Results

All clinical isolates were part of Clade I and carried azole resistance mutations in ERG11, TAC1b, and CDR1, consistent with 100% phenotypic fluconazole resistance. Across all isolates, 5 distinct missense variants in FKS1 were identified: one case with p.Ser639Tyr, one case with both a p.Arg1354Ser and a p.Asp642His, 7 cases with p.Met690Ile, and 9 cases with p.Val1818Ile. Isolates with known echinocandin resistance conferring mutations p.Ser639Tyr and p.Arg1354Ser were resistant to micafungin and anidulafungin. Two isolates with Met690Ile were resistant to caspofungin alone.

Conclusions

With potential resistance to all 3 major antifungal classes of drugs, C. auris is an emerging public health threat. Early detection of echinocandin resistance by molecular methods could impact treatment course to include novel antifungal agents. Further study of the FKS1 Met690Ile variant is warranted.
Polygenic Risk Scores in Human Disease
Authors: Maamari Dimitri J , Abou-Karam Roukoz , Fahed Akl C
Published: January 2025

Background

Polygenic risk scores (PRS) are measures of genetic susceptibility to human health traits. With the advent of large data repositories combining genetic data and phenotypic information, PRS are providing valuable insights into the genetic architecture of complex diseases and are transforming the landscape of precision medicine.

Content

PRS have emerged as tools with clinical utility in human disease. Herein, details on how to develop PRS are provided, followed by 5 areas in which they can be used to improve human health: (a) augmenting risk prediction, (b) refining diagnosis, (c) guiding treatment choices, (d) making clinical trials more efficient, and (e) improving public health. Finally, some of the ongoing challenges to the clinical implementation of PRS are noted.

PRS can offer valuable information for providers and patients, including identifying risk of disease earlier in life and before the onset of clinical risk factors, guiding treatment decisions, improving public health outcomes, and making clinical trials more efficient. The future of genomic-informed risk assessments of disease is through integrated risk models that combine genetic factors including PRS, monogenic, and somatic DNA information with nongenetic risk factors such as clinical risk estimators and multiomic data. However, adopting PRS in a clinical setting at scale faces some challenges, including cross-ancestry performance, standardization and calibration of risk models, downstream clinical decision-making from risk information, and seamless integration into existing health systems.
SARS-CoV-2 Diversity and Transmission on a University Campus across Two Academic Years during the Pandemic
Authors: Casto Amanda M , Paredes Miguel I , Bennett Julia C , Luiten Kyle G , Han Peter D , Gamboa Luis S , McDermot Evan , Gottlieb Geoffrey S , Acker Zachary , Lo Natalie K , McDonald Devon , McCaffrey Kathryn M , Figgins Marlin D , Lockwood Christina M , Shendure Jay , Uyeki Timothy M , Starita Lea M , Bedford Trevor , Chu Helen Y , Weil Ana A
Published: January 2025

Background

Institutions of higher education (IHE) have been a focus of SARS-CoV-2 transmission studies but there is limited information on how viral diversity and transmission at IHE changed as the pandemic progressed.

Methods

Here we analyze 3606 viral genomes from unique COVID-19 episodes collected at a public university in Seattle, Washington from September 2020 to September 2022.

Results

Across the study period, we found evidence of frequent viral transmission among university affiliates with 60% (n = 2153) of viral genomes from campus specimens genetically identical to at least one other campus specimen. Moreover, viruses from students were observed in transmission clusters at a higher frequency than in the overall dataset while viruses from symptomatic infections were observed in transmission clusters at a lower frequency. Although only a small percentage of community viruses were identified as possible descendants of viruses isolated in university study specimens, phylodynamic modeling suggested a high rate of transmission events from campus into the local community, particularly during the 2021–2022 academic year.

Conclusions

We conclude that viral transmission was common within the university population throughout the study period but that not all university affiliates were equally likely to be involved. In addition, the transmission rate from campus into the surrounding community may have increased during the second year of the study, possibly due to return to in-person instruction.
Hypertrophic cardiomyopathy management: a systematic review of the clinical practice guidelines and recommendations
Authors: Sanghvi Mihir M , Dhall Eamon , Anwar A. Chahal C , O'Mahony Constantinos , Mohiddin Saidi A , Savvatis Konstantinos , Ricci Fabrizio , Munroe Patricia B , Petersen Steffen E , Aung Nay , Khanji Mohammed Y
Published: January 2025

Aims

In light of recent advances in imaging techniques, molecular understanding and therapeutic options in hypertrophic cardiomyopathy (HCM), we performed a systematic review of current guidelines for the diagnosis and management of HCM in order to identify consensus and discrepant areas in the clinical practice guidelines.

Methods and results

We systematically reviewed the English language guidelines and recommendations for the management of HCM in adults. MEDLINE and EMBASE databases were searched for guidelines published in the last 10 years. Following a systematic search, three guidelines on the diagnosis and management of HCM were identified, all of which were robustly developed (AGREE rigour of development score ≥50%). These guidelines were authored by the major European (European Society of Cardiology; 2023), American (American Heart Association /American College of Cardiology/American Medical Society for Sports Medicine /Heart Rhythm Society/Pediatric and Congenital Electrophysiology Society/Society for Cardiovascular Magnetic Resonance; 2024), and Japanese [Japanese Circulation Society (JCS)/Japanese Heart Failure Society (JHFS); 2018] cardiovascular societies. There was broad consensus on echocardiographic recommendations, the medical and invasive management of HCM, the application of genetic testing and family screening, and exercise and reproductive recommendations in HCM. There were areas of variability in the definition and diagnostic criteria for HCM, cardiovascular magnetic resonance imaging recommendations, and assessment of sudden cardiac death (SCD) risk and prevention strategies. Due to the JCS/JHFS guidelines being older, there are no recommendations on the use of cardiac myosin ATPase inhibitors.

Conclusion

Contemporary guidelines for HCM achieve consensus across a broad range of criteria and recommendations concerning diagnosis and management. However, variations in the approach towards risk assessment for SCD exist between the guidelines. There are also more subtle differences concerning diagnostic criteria and the utility of late gadolinium enhancement for risk stratification, which will likely evolve as the evidence-base broadens.
Atrial fibrillation ablation timing: where is the sweet spot?
Authors: Kalman Jonathan M , Kistler Peter M , Hindricks Gerhard , Sanders Prashanthan
Published: January 2025

Convincing evidence for the efficacy of ablation as first-line therapy in paroxysmal AF (PAF) and its clear superiority to medical therapy for rhythm control in both PAF and persistent AF (PsAF) has generated considerable interest in the optimal timing of ablation. Based on this data, there is a widespread view that the principle of ‘the earlier the better’ should be generally applied. However, the natural history of AF is highly variable and non-linear, and for this reason, it is difficult to be emphatic that all patients are best served by ablation early after their initial AF episodes. Sufficient evidence exists to indicate a conservative approach is reasonable in patients with infrequent and non-progressive episodes (i.e. absence of progressive increase in burden culminating in PsAF) in whom symptoms remain mild and well-controlled. A conservative management phase should be marked by assiduous attention to risk factor modification, changes in frequency and duration of AF episodes, and patient preferences. If and when AF does begin to progress, accumulating evidence indicates that early ablation accompanied by ongoing attention to risk factors provides the best outcomes.
The Cumulative Burden of Social Risk Factors and 10-Year Change in Quality of Life
Authors: Reid Ro-Jay , Safford Monika , Lambert W Marcus , Bryan Joanna , Pinheiro Laura C , Sterling Madeline R , Bowling C Barrett , Levitan Emily B , Banerjee Samprit , Durant Raegan , Kim Michael , Lau Jennifer D , Goyal Parag
Published: January 2025

Background

Social risk factors are linked to adverse health outcomes, but their total impact on long-term quality of life is obscure. We hypothesized that a higher burden of social risk factors is associated with greater decline in quality of life over 10 years.

Methods

We examined associations between social risk factors count and decline >5 points in (i) physical component summary, and (ii) mental component summary scores from the Short Form-12 among Black and White participants in the Reasons for Geographic and Racial Differences in Stroke study (n = 14 401).

Results

For physical component summary, White participants with 1 social risk factor had relative risk (RR) for decline of 1.14 [95% confidence intervals (CI): 1.07–1.12]. Those with ≥2 social risk factors had RR of 1.26 [95% CI: 1.17–1.35], after adjusting for baseline demographics, health behaviors, medical conditions, medications, and physiological variables. Black participants with 1 social risk factor had RR of 1.03 [95% CI: 0.93–1.15]. Those with ≥2 social risk factors had RR of 1.24 [95% CI: 1.13–1.36]. For mental component summary, White participants with 1 social risk factor had RR for decline of 1.19 [95% CI: 1.04–1.37]. Those with ≥2 social risk factors had RR of 1.47 [95% CI: 1.28–1.68]. Black participants with 1 social risk factor had RR of 1.18 [95% CI: 0.96–1.45]. Those with ≥2 social risk factors had RR of 1.38 [95% CI: 1.14–1.66].

Conclusions

More social risk factors increased the risk of decline of quality of life for Black and White individuals, especially impacting mental health.
The Antimilitarist Feminist Network: Addressing Mexico’s Security Failures
Authors: García Daniela Philipson
Published: January 2025

Despite adopting progressive policies and making significant progress in gender parity, Mexico faces important security challenges that undermine gender equality. Mexico's security policies, especially its military-based solutions, risk undoing the country's ambitious gender equality agenda. In response to increasing security failures and militarization, Mexican antimilitarist feminist activists have pushed back against the government with some success despite setbacks. But what are the underlying preconditions for the rise of antimilitarist feminists? And how are they organizing in response to increasing militarization? This paper begins by describing the context and recent history of militarization and antimilitarism in Mexico. Then it explores the underlying preconditions that enable the emergence of antimilitarist feminist mobilizations: feminist peace and security theorizing and political democratization and human rights frameworks. Drawing on semistructured interviews with feminist activists, it finds that the Antimilitarist Feminist Network has been pivotal in exposing Mexico's contradictions and failures regarding its policies on security and gender equality. The Antimilitarist Feminist Network (re)defines security and (re)imagines alternatives to militarization by promoting and demanding women's meaningful participation and feminist perspectives in security policymaking.
Can States Be Interviewed?
Authors: Markiewicz Tadek
Published: January 2025

Abstracts

While states are not human beings, they are institutionalized social groups. It is humans who constitute and run them. Consequently, it is argued that countries can be interviewed. This claim is based on in-depth interviews with seventy Israeli and British officials, which “captured” states’ anxiety. In ontological security studies, countries’ anxieties are typically inferred from historical and narrative analysis. The article lays another path to establish that states are anxious. Despite the increasing acknowledgement of the “emotional turn” in international relations, there is a notable lack of methodological focus on how emotions impact statecraft. This study bridges the gap by showing how interviewing can investigate the internal lives of states. The research also addresses critiques of ontological security studies, namely the challenge of applying an individual-level concept to state behavior and empirically validating its relevance in statecraft. It traced how officials’ anxiety about their country’s policies “scales up” to the state level. The rich evidence—coming from country officials themselves—affirmed ontological security’s capacity to explain state behavior and underscored the importance of integrating political psychology into international relations research. Moreover, it is the first study to use elite interviews to investigate whether countries experience ontological insecurity.
Supporting wild bee development with a bacterial symbiont
Authors: Nguyen Phuong N , Rehan Sandra M
Published: January 2025

Aims

Wild bees foster diverse microbiota that may determine survival success of developing larvae. Here, we compare survivorship and microbial communities of Ceratina calcarata small carpenter bees reared from eggs across three treatments: maternally collected control provisions with diverse microbiota, sterile provisions, and probiotic provisions supplemented with a beneficial symbiont, Apilactobacillus kunkeei.

Methods and results

Survival probability and adult masses differed across treatments, with the probiotic treatment resulting in highest survivorship and masses. By comparing the bacterial (16S rRNA), fungal (ITS), and plant (rbcL) communities of adults reared across treatments, we characterized distinct microbial communities across each that suggest the microbiome may be sensitive to microbial succession and competition.

Conclusions

We describe positive implications for the usage of probiotics on wild bees. Furthermore, the sensitivity of bee microbiota’s relationships to their host, floral resources, and the environment suggests that holistic approaches best encapsulate the complex network of interactions between bees and their microbes.
Accelerating biosimilar market access: the case for allowing earlier standing
Authors: Tu S Sean , Goode Rachel , Turner Matthew , Van de Wiele Victor
Published: January 2025

Biosimilars, which are affordable alternatives to biologic medicines, face delays in market entry due to the current patent litigation framework under the Biologic Price Competition and Innovation Act. Currently, biosimilar manufacturers can only initiate patent litigation to attempt to clear weak and invalid patents after submitting their Biologic License Application to the Food and Drug Administration (FDA), which happens after completing extensive, and costly clinical trials. By contrast, generic drug manufacturers can start litigation earlier due to shorter development times and less stringent clinical requirements, allowing them to launch immediately after the primary patent expires. We propose allowing biosimilars to begin patent litigation at the start of phase 3 clinical trials, the final stage of biosimilar development, where the product and manufacturing process and product profile are largely finalized. This change would enable biosimilar firms to resolve patent issues well before the brand biologic’s primary patent expiration date, potentially reducing market entry delays by about 1.8 years. This article examines the issues surrounding initiation of biosimilar litigation and suggests litigation reforms to expedite biosimilar market availability.
Investigation of the safety of Radium-223 chloride in combination with external beam radiotherapy for bone metastases of prostate cancer
Authors: Makino Soichi , Miyazawa Kazunari , Katsuoka Yoji , Ooe Takeru , Aikawa Ken , Segawa Akira , Kobayashi Hiroshi
Published: January 2025

This study aimed to investigate the safety of combining radium-223 chloride (Ra-223) therapy with external beam radiation therapy (EBRT) for patients with multiple bone metastases from castration-resistant prostate cancer (CRPC), including lesions requiring urgent treatment such as those causing neurological symptoms due to spinal cord compression. We retrospectively analyzed data from patients with CRPC and bone metastases treated with Ra-223 therapy at our hospital between September 1, 2018, and December 31, 2023. Adverse events were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Of the 23 patients referred, data from 17 were included; 8 received concurrent Ra-223 therapy and EBRT, whereas others received only Ra-223 therapy. The median follow-up period was 20 months. Grade (G) 2 or higher adverse events occurred in seven patients (41.2%), and G 3 or higher in 2 (11.7%). None of the patients who received EBRT with fields involving the gastrointestinal tract experienced diarrhea, constipation, bleeding, perforation, or obstruction. Ra-223 therapy with EBRT did not increase adverse events compared with studies of Ra-223 therapy without EBRT. One case of G 5 Pneumocystis carinii pneumonia, likely because of steroid use for neurological symptoms and the patient’s underlying diabetes mellitus, was noted. The effects of EBRT cannot be entirely excluded, so minimizing field size and dose is recommended when combining Ra-223 therapy and EBRT. Our findings indicate that concurrent Ra-223 therapy and EBRT could be safe for managing patients with symptomatic bone metastases and castration-resistant prostate cancer who require specialized treatment, provided sufficient attention is given to the field and the prescribed dose.
Combustion-related isoprene contributes substantially to the formation of wintertime secondary organic aerosols
Authors: Zhang Yanli , Men Yatai , Guo Hao , Shen Guofeng , Gao Yang , Xiong Rui , Tao Shu , Wang Xinming
Published: January 2025

Isoprene is a key reactive organic gas involved in organic aerosol formation. While biogenic isoprene from terrestrial plants has been extensively studied and is recognized as a major contributor to secondary organic aerosol (SOA), high levels of observed SOA, especially in winter, cannot be fully explained by biogenic isoprene alone. In this study, we developed a comprehensive bottom-up emission inventory for isoprene, incorporating both biogenic and combustion sources and modeling their contributions to SOA in China from 2000 to 2016. Combustion-related isoprene emissions from open biomass burning and residential fuel combustion were estimated at 52.0 (39.1–65.7) Gg in 2000, declining to 14.8 (10.6–19.0) Gg by 2016. Open biomass burning contributes ∼40% of combustion-related isoprene emissions. Though, annually, combustion-related isoprene emissions were much smaller than the biogenic emissions, they did account for 32%–80% of total isoprene emissions in many north and west provinces in the colder months in 2016, and were even higher during the early 2000s owing to more biofuel-burning emissions. Model simulation results indicated that combustion-related isoprene could contribute 25%–40% of winter SOA in northern regions. Wintertime isoprene-derived SOA levels declined since 2000, corresponding with decreased combustion-related isoprene emissions; however, the extent of this decline varied regionally due to the influence of other precursors like nitrogen oxides (NOx). In the northeast region with high NOx levels, while combustion-related isoprene emissions decreased by >80% from 2000 to 2016, isoprene-derived SOA declined by only ∼20%. These findings highlight the previously underappreciated contributions of combustion-related isoprene to observed high wintertime isoprene-derived SOA levels.
Effects of Dietary Interventions in Patients With Migraine: A Systematic Review
Authors: Roldán-Ruiz Alberto , Bertotti Gabriele , López-Moreno Miguel
Published: January 2025

Context

Migraine is a disabling neurological disorder. Diet may be a factor to consider because measures of diet quality have been linked to both frequency and severity of attacks.

Objectives

To investigate the effects of dietary interventions on the clinical symptoms of migraine, quality of life, and body composition of patients with migraine.

Data Sources

The MEDLINE, Embase, and Web of Sciences databases were searched since database inception to February 13, 2024. We included articles on randomized clinical trials that assessed the effect dietary interventions on clinical symptoms of migraines and the quality of life and body composition of individuals with migraine.

Data Extraction

Data from the included articles were independently extracted by 2 researchers; another independent reviewer further verified the extractions. The Cochrane risk-of-bias tool was used to evaluate the risk of bias of selected studies, and the Physiotherapy Evidence Database scale was used to assess the methodological quality.

Results

Eight articles were included in this review. Of these, 3 reported on studies that assessed the ketogenic diet (KD), 2 reported on the Dietary Approaches to Stop Hypertension (DASH), and 3 reported on studies of other dietary strategies. Strong evidence exists regarding the effectiveness of the KD and DASH in reducing the frequency of migraine attacks, whereas their efficacy in improving patients’ quality of life was supported only by limited evidence. There also is strong evidence regarding the effectiveness of DASH in reducing migraine’s severity and patients’ body weight. Insufficient evidence was found regarding the effectiveness of the other dietary interventions on all variables.

Conclusions

The DASH and KD may help reduce migraine frequency and severity. However, more high-quality studies are needed to confirm their effectiveness.

Systematic Review Registration

PROSPERO No. CRD42024516161.