bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal structure of the HMGA AT-hook 1 domain bound to the minor groove of AT-rich DNA and inhibition by antikinetoplastid drugs
Authors: Nué-Martinez J. Jonathan , Maturana Marta , Lagartera Laura , Rodríguez-Gutiérrez Juan-Antonio , Boer Roeland , Campos J. Lourdes , Saperas Núria , Dardonville Christophe 
Published: October 2024

AbstractHigh mobility group (HMG) proteins are intrinsically disordered nuclear non-histone chromosomal proteins that play an essential role in many biological processes by regulating the expression of numerous genes in eukaryote cells. HMGA proteins contain three DNA binding motifs, the “AT-hooks”, that bind preferentially to AT-rich sequences in the minor groove of B-form DNA. Understanding the interactions of AT-hook domains with DNA is very relevant from a medical point of view because HMGA proteins are involved in different conditions including cancer and parasitic diseases. We present here the first crystal structure (1.40 Å resolution) of the HMGA AT-hook 1 domain, bound to the minor groove of AT-rich DNA. In contrast to AT-hook 3 which bends DNA and shows a larger minor groove widening, AT-hook 1 binds neighbouring DNA molecules and displays moderate widening of DNA upon binding. The binding affinity and thermodynamics of binding were studied in solution with surface plasmon resonance (SPR)-biosensor and isothermal titration calorimetry (ITC) experiments. AT-hook 1 forms an entropy-driven 2:1 complex with (TTAA)2-containing DNA with relatively slow kinetics of association/dissociation. We show that N-phenylbenzamide-derived antikinetoplastid compounds (1–3) bind strongly and specifically to the minor groove of AT-DNA and compete with AT-hook 1 for binding. The central core of the molecule is the basis for the observed sequence selectivity of these compounds. These findings provide clues regarding a possible mode of action of DNA minor groove binding compounds that are relevant to major neglected tropical diseases such as leishmaniasis and trypanosomiasis.
Optimization of polishing fluid composition for single crystal silicon carbide by ultrasonic assisted chemical-mechanical polishing
Authors: Ye Linzheng , Wu Jialong , Zhu Xijing , Liu Yao , Li Wenlong , Chuai Shida , Wang Zexiao 
Published: October 2024

AbstractSilicon carbide (SiC) is renowned for its exceptional hardness, thermal conductivity, chemical stability, and wear resistance. However, the existing process is difficult to meet the high standards of uniform corrosion in its polishing process and surface roughness and flatness after polishing, new polishing fluids and technique optimization are crucial for development. The study optimized and validated the composition of the polishing fluid used in ultrasonic-assisted chemical-mechanical polishing (UACMP). Abrasives significantly influenced the material removal rate (MRR) and surface roughness (Ra), contributing 67.63% and 56.43%, respectively. Organic bases and pH buffers significantly affected Ra, accounting for 19.66% and 21.44%, respectively. The optimum composition was determined, consisting of triethylamine (3wt%), potassium hydrogen phthalate (1wt%), a composite of silica and alumina abrasive particles (5wt%), and hydrogen peroxide (6wt%), which reduced the Ra from 95 nm to 3 nm. The MRR achieved 25.96 nm/min. In comparison to the 7 nm minimum roughness from the orthogonal test, the optimal scheme’s Ra was reduced by 57.14%, leading to a significant enhancement in overall surface quality. In this paper, a new type of additive is added to prepare the polishing liquid, which provides a new idea for the UACMP of SiC and has a great impact.
Differential chromatin accessibility and transcriptional dynamics define breast cancer subtypes and their lineages
Authors: Iglesia Michael D. , Jayasinghe Reyka G. , Chen Siqi , Terekhanova Nadezhda V. , Herndon John M. , Storrs Erik , Karpova Alla , Zhou Daniel Cui , Naser Al Deen Nataly , Shinkle Andrew T. , Lu Rita Jui-Hsien , Caravan Wagma , Houston Andrew , Zhao Yanyan , Sato Kazuhito , Lal Preet , Street Cherease , Martins Rodrigues Fernanda , Southard-Smith Austin N. , Targino da Costa André Luiz N. , Zhu Houxiang , Mo Chia-Kuei , Crowson Lisa , Fulton Robert S. , Wyczalkowski Matthew A. , Fronick Catrina C. , Fulton Lucinda A. , Sun Hua , Davies Sherri R. , Appelbaum Elizabeth L. , Chasnoff Sara E. , Carmody Madelyn , Brooks Candace , Liu Ruiyang , Wendl Michael C. , Oh Clara , Bender Diane , Cruchaga Carlos , Harari Oscar , Bredemeyer Andrea , Lavine Kory , Bose Ron , Margenthaler Julie , Held Jason M. , Achilefu Samuel , Ademuyiwa Foluso , Aft Rebecca , Ma Cynthia , Colditz Graham A. , Ju Tao , Oh Stephen T. , Fitzpatrick James , Hwang E. Shelley , Shoghi Kooresh I. , Chheda Milan G. , Veis Deborah J. , Chen Feng , Fields Ryan C. , Gillanders William E. , Ding Li 
Published: October 2024

AbstractBreast cancer (BC) is defined by distinct molecular subtypes with different cells of origin. The transcriptional networks that characterize the subtype-specific tumor-normal lineages are not established. In this work, we applied bulk, single-cell and single-nucleus multi-omic techniques as well as spatial transcriptomics and multiplex imaging on 61 samples from 37 patients with BC to show characteristic links in gene expression and chromatin accessibility between BC subtypes and their putative cells of origin. Regulatory network analysis of transcription factors underscored the importance of BHLHE40 in luminal BC and luminal mature cells and KLF5 in basal-like tumors and luminal progenitor cells. Furthermore, we identify key genes defining the basal-like (SOX6 and KCNQ3) and luminal A/B (FAM155A and LRP1B) lineages. Exhausted CTLA4-expressing CD8+ T cells were enriched in basal-like BC, suggesting an altered means of immune dysfunction. These findings demonstrate analysis of paired transcription and chromatin accessibility at the single-cell level is a powerful tool for investigating cancer lineage and highlight transcriptional networks that define basal and luminal BC lineages.
Climate induced microbiome alterations increase cadmium bioavailability in agricultural soils with pH below 7
Authors: Drabesch Sören , Lechtenfeld Oliver J. , Bibaj Esmira , León Ninin José M. , Lezama Pachecco Juan , Fendorf Scott , Planer-Friedrich Britta , Kappler Andreas , Muehe E. Marie 
Published: October 2024

AbstractClimate change and metals independently stress soil microbiomes, but their combined effects remain unresolved. Here we show that future climate affects soil cadmium through altered soil microbiome and nutrient cycles, with soil pH as critical factor. In soils with pH<7 and during summer temperatures, future climate increased porewater cadmium, shifting total and potentially active taxonomic microbiome structures. Microbial ammonium oxidation released protons liberating cadmium through cation exchange from mineral surfaces. When porewater cadmium levels became toxic to non-cadmium-tolerant bacteria, microbial activity, and nutrient cycling decreased, reducing carbon and nitrogen emissions. In contrast, pH>7 soil show no climate impacts on cadmium mobilization, though imprints on microbiome structure were apparent. Subsequent nutrient cycling increased under future climate, stimulating soil respiration and nitrous oxide release. These findings underscore complex interactions between climate change and soil contaminants affecting the soil microbiome and its activity and highlights potential impacts on crop production, groundwater quality, and climate feedback.
Role of local governments in EU member states’ climate policy and legislation
Authors: Kastelein Robert 
Published: October 2024

AbstractThis article provides a better understanding of the opportunities and challenges that local governments have in achieving climate objectives, both within EU member states’ national climate policy and national climate law, and how this relates to the literature on multi-level governance. More specifically, the differences and similarities between the national climate plans and national climate legislation of four selected member states (Germany, Ireland, Netherlands and Spain) have been examined. The findings from this can be related to the literature on multi-level governance when it comes to opportunities and challenges regarding the role that local governments fulfill. On the one hand, local governments are often seen as potential key drivers that can successfully work together and whose involvement can lead to more effective climate governance. On the other hand, local governments are legally and financially dependent on higher levels of government in the implementation of their assigned climate-related tasks and responsibilities.
Specific symptom change associated with ecological momentary assessments of intrusive trauma memories
Authors: Pollmann Yara , Clancy Kevin J. , Devignes Quentin , Ren Boyu , Kaufman Milissa L. , Rosso Isabelle M. 
Published: October 2024

AbstractAs the global prevalence of exposure to traumatic events rises, there is a growing need for accessible and scalable treatments for trauma-related disorders like posttraumatic stress disorder (PTSD). Intrusive reexperiencing symptoms, such as trauma-related intrusive memories (TR-IMs), are central to PTSD and a target of gold-standard treatments that are effective but resource-intensive. This study examined whether completing a brief ecological momentary assessment (EMA) protocol assessing the occurrence and phenomenology of TR-IMs was associated with decreases in intrusion symptom severity. Trauma-exposed adults (N = 139) experiencing at least 2 TR-IMs per week related to a DSM-5 criterion A traumatic event completed a 2-week EMA protocol. During this period, they reported on 18 sensory-perceptual and affective qualities of their TR-IMs three times per day and on posttraumatic stress symptom severity at day’s end. Longitudinal symptom measurements were entered into linear mixed-effects models to test the effect of Time on symptom severity. Over the 2-week protocol, intrusion symptom severity decreased, while other symptom cluster scores did not change. Within the intrusion symptoms, this effect was specific to TR-IMs and emotional reactivity to trauma reminders, and was not moderated by survey completion rate, total PTSD symptom severity, ongoing treatment, or time since trauma. This study was quasi-experimental and lacked a control group, therefore no definitive conclusions about clinical utility can be made. Nonetheless, these findings provide preliminary proof-of-principle and warrant future clinical trials assessing the clinical efficacy of EMAs of intrusive trauma memories as a scalable treatment option targeting intrusive memory symptoms.
Aberrant fragmentomic features of circulating cell-free mitochondrial DNA as novel biomarkers for multi-cancer detection
Authors: Liu Yang , Peng Fan , Wang Siyuan , Jiao Huanmin , Dang Miao , Zhou Kaixiang , Guo Wenjie , Guo Shanshan , Zhang Huanqin , Song Wenjie , Xing Jinliang 
Published: October 2024

AbstractFragmentomic features of circulating cell free mitochondrial DNA (ccf-mtDNA) including fragmentation profile, 5’ end base preference and motif diversity are poorly understood. Here, we generated ccf-mtDNA sequencing data of 1607 plasma samples using capture-based next generation sequencing. We firstly found that fragmentomic features of ccf-mtDNA were remarkably different from those of circulating cell free nuclear DNA. Furthermore, region-specific fragmentomic features of ccf-mtDNA were observed, which was associated with protein binding, base composition and special structure of mitochondrial DNA. When comparing to non-cancer controls, six types of cancer patients exhibited aberrant fragmentomic features. Then, cancer detection models were built based on the fragmentomic features. Both internal and external validation cohorts demonstrated the excellent capacity of our model in distinguishing cancer patients from non-cancer control, with all area under curve higher than 0.9322. The overall accuracy of tissue-of-origin was 89.24% and 87.92% for six cancer types in two validation cohort, respectively. Altogether, our study comprehensively describes cancer-specific fragmentomic features of ccf-mtDNA and provides a proof-of-principle for the ccf-mtDNA fragmentomics-based multi-cancer detection and tissue-of-origin classification.
Phage diversity in One Health
Authors: Pye Hannah V. , Krishnamurthi Revathy , Cook Ryan , Adriaenssens Evelien M. 
Published: October 2024

Abstract
One Health aims to bring together human, animal, and environmental research to achieve optimal health for all. Bacteriophages (phages) are viruses that kill bacteria and their utilisation as biocontrol agents in the environment and as therapeutics for animal and human medicine will aid in the achievement of One Health objectives. Here, we assess the diversity of phages used in One Health in the last 5 years and place them in the context of global phage diversity. Our review shows that 98% of phages applied in One Health belong to the class Caudoviricetes, compared to 85% of sequenced phages belonging to this class. Only three RNA phages from the realm Riboviria have been used in environmental biocontrol and human therapy to date. This emphasises the lack in diversity of phages used commercially and for phage therapy, which may be due to biases in the methods used to both isolate phages and select them for applications. The future of phages as biocontrol agents and therapeutics will depend on the ability to isolate genetically novel dsDNA phages, as well as in improving efforts to isolate ssDNA and RNA phages, as their potential is currently undervalued. Phages have the potential to reduce the burden of antimicrobial resistance, however, we are underutilising the vast diversity of phages present in nature. More research into phage genomics and alternative culture methods is required to fully understand the complex relationships between phages, their hosts, and other organisms in the environment to achieve optimal health for all.
Considerations for prioritising clinical research using bacteriophage
Authors: Edwards Sarah J.L. , Tao Yiran , Elias Rodas , Schooley Robert 
Published: October 2024

Abstract
Antimicrobial resistance (AMR) poses a significant global health threat, as it contributes to prolonged illness, higher mortality rates and increased healthcare costs. As traditional antibiotics become less effective, treatments such as bacteriophage therapy offer potential solutions. The question remains, however, on how to set research priorities in the face of a growing number of antibiotic-resistant pathogens, some common and/or dangerous. One standard way of making decisions about which research to prioritise is by using the disability-adjusted life year metric to estimate the current global impact of a disease or condition, combined with considerations of social justice although decisions made at a national level by governments, especially in low income countries with forecasting potential over future needs may look very different. Another approach is based on the needs of researchers and regulators given what we know about the technology itself. The biological characteristics of bacteriophage therapies set challenges to a universal and standardised prioritisation method. A proof of principle is still arguably needed. With a preliminary discussion of the scope and complexity of AMR and AMR therapeutics, we propose some implications of regulatory frameworks aiming to integrate bacteriophage therapy into mainstream medical practice while gathering scientific data on safety and efficacy, enhancing the collective action needed to combat AMR.
Cultural Perceptions of Language Development in a Population Sample of 54-Month-Old Children From Aotearoa New Zealand
Authors: Newbury Jayne , White Bridget , Meissel Kane , Panther Noriko , Cook Helena , Cowie Rahera , Reese Elaine 
Published: October 2024

Purpose:
There is a dearth of information on cultural perceptions of children's language development for ethnic minorities in New Zealand to guide service provision. The current study explored differences across ethnicities in mothers' report of language concern and child language scores within a complex cultural, social, educational, and political context.

Method:
Data from the antenatal and 54-month waves of Growing Up in New Zealand were utilized. At the 54-month wave interviews, 5,053 mothers were asked if language concerns had been raised and to rate their child's main language proficiency along with other measures.

Results:
Logistic regression models (including influencing variables) indicated Chinese, Indian, and other Asian mothers were less likely to report language concern, whereas Māori, Pacific, other Asian, and Middle Eastern, Latin American, and African children were more likely to score low on the language measure. Higher maternal education was associated with higher child main language scores, but not with language concerns. Child multilingualism was not associated with low language scores, and these mothers were less likely to raise concern.

Conclusions:
This study demonstrated differences by ethnicity in mothers' language concern and child main language scores, which are likely to affect access to speech-language pathology services, as these typically rely on parent concern being expressed. Cultural bias in the language measure may also be present. Further research is needed to ask ethnic communities their views on culturally appropriate ways to identify children with communication needs and to develop culturally safe services.
Constrained Emotional Sentence Production in Parkinson's Disease
Authors: Hazamy Audrey A. , Park Hyejin , Altmann Lori J. P. 
Published: October 2024

Purpose:
Deficits in the processing and production of emotional cues are well documented in the Parkinson's disease (PD) literature; however, few have ventured to explore how impairments may impact emotional language use in this population, particularly beyond the word level. Emotional language is an important multidimensional manner of communicating one's wants and needs; thus, the current study sought to explore how various aspects of language production may be impacted by the emotionality of a stimulus.

Method:
Eighteen persons with PD and 22 healthy adults completed a constrained emotional sentence production task in which the affective target word was either a noun or a verb. Output was analyzed for fluency, grammaticality, completeness, and response initiation times. Cognitive (i.e., working memory [WM], inhibition, and switching) and mood (i.e., depression and apathy) measures were examined as factors influencing performance.

Results:
Individuals with PD produced fewer fluent responses than healthy controls. Furthermore, they had fewer grammatical responses in their production of negative sentences and exhibited reduced information completeness when producing sentences containing positive stimuli. Group differences could not be wholly attributed to individual differences in WM or apathy.

Conclusions:
Our results support those of others that document language production deficits in individuals with PD above and beyond those impairments that can be explained by the select cognitive abilities explored here. Moreover, the emotionality of the topic may impact various aspects of communicative competence in persons with PD. For instance, disease processes associated with degeneration of neural substrates important for processing negative stimuli may also impact the grammaticality of productions containing negatively valenced content. Thus, it is important to consider how individuals in this population communicate during emotional circumstances.

Supplemental Material:

https://doi.org/10.23641/asha.27289413
Executive Function Associations With Audibility-Adjusted Speech Perception in Noise
Authors: Eckert Mark A. , Matthews Lois J. , Vaden Kenneth I. , Dubno Judy R. 
Published: October 2024

Purpose:
Speech recognition in noise is challenging for listeners and appears to require support from executive functions to focus attention on rapidly unfolding target speech, track misunderstanding, and sustain attention. The current study was designed to test the hypothesis that lower executive function abilities explain poorer speech recognition in noise, including among older participants with hearing loss who often exhibit diminished speech recognition in noise and cognitive abilities.

Method:
A cross-sectional sample of 400 younger-to-older adult participants (19 to < 90 years of age) from the community-based Medical University of South CarolinaLongitudinal Cohort Study of Age-related Hearing Loss were administered tasks with executive control demands to assess individual variability in a card-sorting measure of set-shifting/performance monitoring, a dichotic listening measure of selective attention/working memory, sustained attention, and processing speed. Key word recognition in the high- and low-context speech perception-in-noise (SPIN) tests provided measures of speech recognition in noise. The SPIN scores were adjusted for audibility using the Articulation Index to characterize the impact of varied hearing sensitivity unrelated to reduced audibility on cognitive and speech recognition associations.

Results:

Set-shifting, dichotic listening, and processing speed each explained unique and significant variance in audibility-adjusted, low-context SPIN scores (
p
s < .001), including after controlling for age, pure-tone threshold average (PTA), sex, and education level. The dichotic listening and processing speed effect sizes were significantly diminished when controlling for PTA, indicating that participants with poorer hearing sensitivity were also likely to have lower executive function and lower audibility-adjusted speech recognition.

Conclusions:
Poor set-shifting/performance monitoring, slow processing speed, and poor selective attention/working memory appeared to partially explain difficulties with speech recognition in noise after accounting for audibility. These results are consistent with the premise that distinct executive functions support speech recognition in noise.
A Computational Model Reveals How Varying Muscle Activation in the Lateral Pharyngeal Wall and Soft Palate Differentiates Velopharyngeal Closure Patterns
Authors: DiSalvo Matthew D. , Blemker Silvia S. , Mason Kazlin N. 
Published: October 2024

Purpose:
Finite element (FE) models have emerged as a powerful method to study biomechanical complexities of velopharyngeal (VP) function. However, existing models have overlooked the active contributions of the lateral pharyngeal wall (LPW) in VP closure. This study aimed to develop and validate a more comprehensive FE model of VP closure to include the superior pharyngeal constrictor (SPC) muscle within the LPW as an active component of VP closure.

Method:
The geometry of the velum and the lateral and posterior pharyngeal walls with biomechanical activation governed by the levator veli palatini (LVP) and SPC muscles were incorporated into an FE model of VP closure. Differing muscle activations were employed to identify the impact of anatomic contributions from the SPC muscle, LVP muscle, and/or velum for achieving VP closure. The model was validated against normative magnetic resonance imaging data at rest and during speech production.

Results:
A highly accurate and validated biomechanical model of VP function was developed. Differing combinations and activation of muscles within the LPW and velum provided insight into the relationship between muscle activation and closure patterns, with objective quantification of anatomic change necessary to achieve VP closure.

Conclusions:
This model is the first to include the anatomic properties and active contributions of the LPW and SPC muscle for achieving VP closure. Now validated, this method can be utilized to build robust, comprehensive models to understand VP dysfunction. This represents an important advancement in patient-specific modeling of VP function and provides a foundation to support development of computational tools to meet clinical demand.