bluuebunny/crossref_metadata_2025_split huggingface dataset:
HRK downregulation and augmented BCL-xL binding to BAK confer apoptotic protection to therapy-induced senescent melanoma cells
Authors: Alcon Clara , Kovatcheva Marta , Morales-Sánchez Paula , López-Polo Vanessa , Torres Teresa , Puig Susana , Lu Albert , Samitier Josep , Enrich Carlos , Serrano Manuel , Montero Joan 
Published: December 2024

AbstractSenescent cells are commonly detected in tumors after chemo and radiotherapy, leading to a characteristic cellular phenotype that resists apoptotic cell death. In this study, we used multiple melanoma cell lines, molecular markers, and therapies to investigate the key role of the BCL-2 family proteins in the survival of senescent cells. We first used BH3 profiling to assess changes in apoptotic priming upon senescence induction. Unexpectedly, not all cell types analyzed showed a decrease in apoptotic priming, BIM was downregulated, there was variability in BAX expression and BAK remained constant or increased. Therefore, there was not a clear pattern for pro-survival adaptation. Many studies have been devoted to find ways to eliminate senescent cells, leading to one of the most studied senolytic agents: navitoclax, a promiscuous BH3 mimetic that inhibits BCL-2, BCL-xL and BCL-W. While it is known that the BCL-2 family of proteins is commonly upregulated in senescent cells, the complexity of the apoptotic network has not been fully explored. Interestingly, we found distinct protein expression changes always leading to a BCL-xL mediated pro-survival adaptation, as assessed by BH3 profiling. When analyzing potential therapeutic strategies, we observed a stronger senolytic activity in these melanoma cell lines when specifically targeting BCL-xL using A-1331852, navitoclax or the PROTAC BCL-xL degrader DT2216. We found that the sensitizer protein HRK was systematically downregulated when senescence was induced, leading to an increased availability of BCL-xL. Furthermore, we identified that the main apoptotic inhibition was shaped by BCL-xL and BAK binding increase that prevented mitochondrial permeabilization and apoptosis. To our knowledge, this is the first time that the molecular basis for BCL-xL anti-apoptotic adaptation in senescence is described, paving the way for the development of new molecules that either prevent HRK downregulation or displace BCL-xL binding to BAK to be used as senolytics.
TIP60 enhances cisplatin resistance via regulating ΔNp63α acetylation in SCC
Authors: Hira Akshay , Zhang Jin , Kadakia Madhavi P. 
Published: December 2024

AbstractNon-melanoma skin cancer, including basal and squamous cell carcinoma, is the most common form of cancer worldwide, with approximately 5.4 million new cases diagnosed each year in the United States. While the chemotherapeutic drug cisplatin is often used to treat squamous cell carcinoma (SCC) patients, low response rates and disease recurrence are common. In this study, we show that TIP60 and ΔNp63α levels correlate with cisplatin resistance in SCC cell lines, suggesting that TIP60 contributes to the failure of platinum-based drugs in SCC by regulating the stability and transcriptional activity of ΔNp63α. Depletion of endogenous TIP60 or pharmacological inhibition of TIP60 led to a decrease in ΔNp63α protein and acetylation levels in multiple SCC cell lines. We showed that TIP60 upregulates ΔNp63α protein levels in cisplatin-resistant SCC cell lines by protecting it from cisplatin-mediated degradation and increasing its protein stability. Stable expression of TIP60 or ΔNp63α individually promoted resistance to cisplatin and reduced cell death, while loss of either TIP60 or ΔNp63α induced G2/M arrest, increased cell death, and sensitized cells to cisplatin. Moreover, pharmacological inhibition of TIP60 reduced acetylation of ΔNp63α and sensitized resistant cells to cisplatin. Taken together, our study indicates that TIP60-mediated stabilization of ΔNp63α increases cisplatin resistance and provides critical insights into the mechanisms by which ΔNp63α confers cisplatin resistance by promoting cell proliferation and inhibiting apoptosis. Furthermore, our data suggests that inhibition of TIP60 may be therapeutically advantageous in overcoming cisplatin resistance in SCC and other epithelial cancers.
Detecting global and local hierarchical structures in cell-cell communication using CrossChat
Authors: Wang Xinyi , Almet Axel A. , Nie Qing 
Published: December 2024

AbstractCell-cell communication (CCC) occurs across different biological scales, ranging from interactions between large groups of cells to interactions between individual cells, forming a hierarchical structure. Globally, CCC may exist between clusters or only subgroups of a cluster with varying size, while locally, a group of cells as sender or receiver may exhibit distinct signaling properties. Current existing methods infer CCC from single-cell RNA-seq or Spatial Transcriptomics only between predefined cell groups, neglecting the existing hierarchical structure within CCC that are determined by signaling molecules, in particular, ligands and receptors. Here, we develop CrossChat, a novel computational framework designed to infer and analyze the hierarchical cell-cell communication structures using two complementary approaches: a global hierarchical structure using a multi-resolution clustering method, and multiple local hierarchical structures using a tree detection method. This framework provides a comprehensive approach to understand the hierarchical relationships within CCC that govern complex tissue functions. By applying our method to two nonspatial scRNA-seq datasets sampled from COVID-19 patients and mouse embryonic skin, and two spatial transcriptomics datasets generated from Stereo-seq of mouse embryo and 10x Visium of mouse wounded skin, we showcase CrossChat’s functionalities for analyzing both global and local hierarchical structures within cell-cell communication.
3D variability analysis reveals a hidden conformational change controlling ammonia transport in human asparagine synthetase
Authors: Coricello Adriana , Nardone Alanya J. , Lupia Antonio , Gratteri Carmen , Vos Matthijn , Chaptal Vincent , Alcaro Stefano , Zhu Wen , Takagi Yuichiro , Richards Nigel G. J. 
Published: December 2024

AbstractAdvances in X-ray crystallography and cryogenic electron microscopy (cryo-EM) offer the promise of elucidating functionally relevant conformational changes that are not easily studied by other biophysical methods. Here we show that 3D variability analysis (3DVA) of the cryo-EM map for wild-type (WT) human asparagine synthetase (ASNS) identifies a functional role for the Arg-142 side chain and test this hypothesis experimentally by characterizing the R142I variant in which Arg-142 is replaced by isoleucine. Support for Arg-142 playing a role in the intramolecular translocation of ammonia between the active site of the enzyme is provided by the glutamine-dependent synthetase activity of the R142 variant relative to WT ASNS, and MD simulations provide a possible molecular mechanism for these findings. Combining 3DVA with MD simulations is a generally applicable approach to generate testable hypotheses of how conformational changes in buried side chains might regulate function in enzymes.
Tunnelling escape of waves
Authors: Miller David A. B. , Kuang Zeyu , Miller Owen D. 
Published: December 2024

AbstractApplications of waves in communications, information processing and sensing need a clear understanding of how many strongly coupled channels or degrees of freedom exist in and out of volumes of space and how the coupling falls off for larger numbers. Numerical results are possible, and some heuristics exist, but there has been no simple physical picture and explanation for arbitrary volumes. By considering waves from a bounding spherical volume, we show a clear onset of a tunnelling escape of waves that both defines a limiting number of well-coupled channels for any volume and explains the subsequent rapid fall-off of coupling strengths. The approach works over all size scales, from nanophotonics and small radiofrequency antennas up to imaging optics. It gives a unified view from the multipole expansions common for antennas and small objects to the limiting plane and evanescent waves of large optics, showing that all such waves can escape to propagation to some degree, by tunnelling if necessary, and gives a precise diffraction limit.
Zebrafish model for functional screening of flow-responsive genes controlling endothelial cell proliferation
Authors: Bowley George , Irving Sophie , Hoefer Imo , Wilkinson Robert , Pasterkamp Gerard , Darwish Hazem M. S. , White Stephen , Francis Sheila E. , Chico Tim , Noel Emily , Serbanovic-Canic Jovana , Evans Paul C. 
Published: December 2024

AbstractLocal haemodynamics control arterial homeostasis and dysfunction by generating wall shear stress (WSS) which regulates endothelial cell (EC) physiology. Here we use a zebrafish model to identify genes that regulate EC proliferation in response to flow. Suppression of blood flow in zebrafish embryos (by targeting cardiac troponin) reduced EC proliferation in the intersegmental vessels (ISVs) compared to controls exposed to flow. The expression of candidate regulators of proliferation was analysed in EC isolated from zebrafish embryos by qRT-PCR. Genes shown to be expressed in EC were analysed for the ability to regulate proliferation in zebrafish vasculature exposed to flow or no-flow conditions using a knockdown approach. wnk1 negatively regulated proliferation in no-flow conditions, whereas fzd5, gsk3β, trpm7 and bmp2a promoted proliferation in EC exposed to flow. Immunofluorescent staining of mammalian arteries revealed that WNK1 is expressed at sites of low WSS in the murine aorta, and in EC overlying human atherosclerotic plaques. We conclude that WNK1 is expressed in EC at sites of low WSS and in diseased arteries and may influence vascular homeostasis by reducing EC proliferation.
Memory reactivation generates new, adaptive behaviours that reach beyond direct experience
Authors: Rawson Annalise B. , Nalluru Sumedha , O’Reilly Jill X. , Barron Helen C. 
Published: December 2024

Abstract
Periods of rest and sleep help us find hidden solutions to new problems and infer unobserved relationships between discrete events. However, the mechanisms that formulate these new, adaptive behavioural strategies remain unclear. One possibility is that memory reactivation during periods of rest and sleep has the capacity to generate new knowledge that extends beyond direct experience. Here, we test this hypothesis using a pre-registered study design that includes a rich behavioural paradigm in humans. We use contextual Targeted Memory Reactivation (TMR) to causally manipulate memory reactivation during awake rest. We demonstrate that TMR during rest enhances performance on associative memory tests, with improved discovery of new, non-directly trained associations, and no change observed for directly trained associations. Our findings suggest that memory reactivation during awake rest plays a critical role in extracting new, unobserved associations to support adaptive behavioural strategies such as inference.
Dynamic changes in human brain connectivity following ultrasound neuromodulation
Authors: Atkinson-Clement Cyril , Alkhawashki Mohammad , Gatica Marilyn , Ross James , Kaiser Marcus 
Published: December 2024

AbstractNon-invasive neuromodulation represents a major opportunity for brain interventions, and transcranial focused ultrasound (FUS) is one of the most promising approaches. However, some challenges prevent the community from fully understanding its outcomes. We aimed to address one of them and unravel the temporal dynamics of FUS effects in humans. Twenty-two healthy volunteers participated in the study. Eleven received FUS in the right inferior frontal cortex while the other 11 were stimulated in the right thalamus. Using a temporal dynamic approach, we compared resting-state fMRI seed-based functional connectivity obtained before and after FUS. We also assessed behavioural changes as measured with a task of reactive motor inhibition. Our findings reveal that the effects of FUS are predominantly time-constrained and spatially distributed in brain regions functionally connected with the directly stimulated area. In addition, mediation analysis highlighted that FUS applied in the right inferior cortex was associated with behavioural alterations which was directly explained by the applied acoustic pressure and the brain functional connectivity change we observed. Our study underscored that the biological effects of FUS are indicative of behavioural changes observed more than an hour following stimulation and are directly related to the applied acoustic pressure.
Probing electronic-structure pH-dependency of Au nanoparticles through X-ray Absorption Spectroscopy
Authors: Imbir Gabriela , Wach Anna , Czapla-Masztafiak Joanna , Wójcik Anna , Sá Jacinto , Szlachetko Jakub 
Published: December 2024

AbstractResearch on gold nanoparticles (Au NPs) remains a field of intense activity due to their broad range of applications in diverse fields like catalysis, renewable energy, environmental science, and medicine. Herein, the morphological and electronic structures investigation of Au NPs prepared at different pH values is reported. The dependence of the localized surface plasmon resonance wavelength and electronic structure with size was determined by combining transmission electron microscopy, and various spectroscopic methods led by X-ray absorption spectroscopy. The X-ray absorption experiments evidenced that the citrate-stabilized Au NPs bulk electronic structure remains intact over a broad range of pHs, and changes were detected resulting from differences in NPs surface terminations.
Artificial intelligence enabled smart mask for speech recognition for future hearing devices
Authors: Hameed Hira , Lubna  , Usman Muhammad , Kazim Jalil Ur Rehman , Assaleh Khaled , Arshad Kamran , Hussain Amir , Imran Muhammad , Abbasi Qammer H. 
Published: December 2024

AbstractIn recent years, Lip-reading has emerged as a significant research challenge. The aim is to recognise speech by analysing Lip movements. The majority of Lip-reading technologies are based on cameras and wearable devices. However, these technologies have well-known occlusion and ambient lighting limitations, privacy concerns as well as wearable device discomfort for subjects and disturb their daily routines. Furthermore, in the era of coronavirus (COVID-19), where face masks are the norm, vision-based and wearable-based technologies for hearing aids are ineffective. To address the fundamental limitations of camera-based and wearable-based systems, this paper proposes a Radio Frequency Identification (RFID)-based smart mask for a Lip-reading framework capable of reading Lips under face masks, enabling effective speech recognition and fostering conversational accessibility for individuals with hearing impairment. The system uses RFID technology to make Radio Frequency (RF) sensing-based Lip-reading possible. A smart RFID face mask is used to collect a dataset containing three different classes of vowels (A, E, I, O, U), Consonants (F, G, M, S), and words (Fish, Goat, Meal, Moon, Snake). The collected data are fed into well-known machine-learning models for classification. A high classification accuracy is achieved by individual classes and combined datasets. On the RFID combined dataset, the Random Forest model achieves a high classification accuracy of 80%.
Diversity of extracellular vesicles derived from calli, cell culture and apoplastic fluid of tobacco
Authors: Kocholatá Michaela , Malý Jan , Kříženecká Sylvie , Janoušková Olga 
Published: December 2024

AbstractIn recent years, there has been a growing interest in plant extracellular vesicles (pEVs) due to their immense potential for medical applications, particularly as carriers for drug delivery. To use the benefits of pEVs in the future, it is necessary to identify methods that facilitate their production in sufficient quantities while maintaining high quality. In this study, a comparative analysis of yields of tobacco pEV derived from apoplastic fluid, sterile calli, and suspension cultures, was performed to identify the most suitable plant material for vesicle isolation. Subsequent experiments focused on assessing the efficiency of small interfering RNA (siRNA) loading into callus-derived vesicles, employing various methods such as sonication, incubation, incubation supplemented with saponin, lipofection, and electroporation. Differences in loading efficiency among vesicles derived from apoplastic fluid, calli, and suspension cultures were observed. Moreover, our investigation extended to the presence of tobacco secondary metabolites, specifically anabasine and nicotine, within vesicles originating from three distinct tobacco sources. The outcomes of our study highlight variations not only in vesicle yields based on their source but also in their loadability and the presence of nicotine and anabasine. These findings contribute valuable insights into optimizing the production and application of pEVs for future medicinal purposes.
Are Speech Sound Difficulties Risk Factors for Difficulties in Language and Reading Skills? A Systematic Review and Meta-Analysis
Authors: Walquist-Sørli Line , Caglar-Ryeng Ømur , Furnes Bjarte , Nergård-Nilssen Trude , Donolato Enrica , Melby-Lervåg Monica 
Published: December 2024

Background:
Children with speech sound difficulties often require educational psychology services, yet systematic reviews examining the association between these difficulties and language or reading problems are lacking. This meta-analysis examines whether these children are at higher risk of language and reading difficulties compared to their peers.

Method:
The study analyzed 290 effect sizes from cross-sectional and longitudinal studies that compared language and reading skills between children with speech sound difficulties and controls. Additionally, we evaluated 37 effect sizes from correlational studies in general populations to examine the relationship between speech sound skills and language or reading skills.

Results:

Children with speech sound difficulties showed significant concurrent language (Hedges'
g
= −0.60) and reading (Hedges'
g
= −0.58) problems. Correlational studies also demonstrated a relationship between speech sound skills and language (
r
= .23) and reading (
r
= .23) skills. Phonological awareness and study quality were significant moderators. Longitudinal studies showed persistent or increasing group differences over time in language (Hedges'
g
= −0.85) and reading (Hedges'
g
= −0.50). These findings were consistent regardless of the severity or types of speech sound difficulties, nonverbal IQ, country, age, and publication year. However, a precision-effect test and the precision-effect estimate with standard errors analysis suggested a potential decrease in effect size due to publication bias from small sample sizes in primary studies.

Conclusion:
Children with speech sound difficulties are at an increased risk of language and reading difficulties, emphasizing the need for broader language assessments and early interventions to mitigate future academic difficulties.

Supplemental Material:

https://doi.org/10.23641/asha.27849828
Linguistic Processing of Unattended Speech Under a Cocktail Party Listening Scenario
Authors: Lu Lingxi , Wu Danni , Zhang Xiaoyu , Chen Liangjie 
Published: December 2024

Purpose:
In the context of a cocktail party listening environment, the processing of different linguistic hierarchy levels in unattended speech and their influence on target speech recognition remain controversial. This study aims to investigate how different levels of linguistic structures (such as syllable, word, and sentence) in competing speech influence the recognition of target speech in a speech-to-speech masking situation.

Method:
Thirty-six participants were instructed to recognize target speech when it was masked by competing speech varied in masking types across syllables, words, and sentence. The perceived spatial location was altered to examine the interaction between linguistic unmasking effects and spatial unmasking effects. Recognition performance (i.e., intelligibility threshold) was determined by fitting psychometric functions to the recognition accuracies across four signal-to-noise ratios (−14, −10, −6, and − 2 dB) to evaluate each subject's ability to cope with challenging listening conditions.

Results:
We revealed a significant decline in target speech recognition when the masking speech was linguistically structured and intelligible. Specifically, masking speech with higher linguistic complexity, such as coherent sentences, resulted in more significant interference compared to those with lower complexity, like sequences of syllables. The linguistic release from masking, resulting from a decrease in linguistic complexity of maskers shifting from sentences to syllables, was found to be correlated with, and also linearly additive to, the spatial release from masking due to the spatial separation of the masker and target.

Conclusions:
These findings illustrate the influence of linguistic complexity in masking speech on the recognition of target speech, suggesting the involvement of higher-level linguistic processing of irrelevant speech in noisy environment.
A Scoping Review of Intervention Outcomes for School Students With Communication Difficulties
Authors: McCormack Jane , Ttofari Kerry , Denman Deborah , Dixon Gaenor , Crosbie Sharon , Cronin Anna 
Published: December 2024

Purpose:
For speech-language pathologists (SLPs) working in schools, outcome measurement is an important element of practice, enabling us to evaluate the efficacy of our service provision and guiding future decision making, funding, and resource allocation. When selecting outcomes to measure, it is helpful to consider both the level at which change may be occurring and the extent or impact of that change. The primary aim of this review was to identify the outcomes measured in intervention studies for school-aged children with speech, language, and communication difficulties (SLCD) using the International Classification of Functioning, Disability and Health to classify the outcomes. A second aim was to identify tools used in research studies to measure the outcomes.

Method:
A systematic search of five databases was undertaken to identify papers reporting outcomes for school students who had received intervention targeting SLCD. Articles written in English and published between January 2000 and August 2021 were included. The Taxonomy for Categorizing Outcome Measures for SLCD was created to enable a review of outcomes and measurement tools.

Results:

There were 125 papers included in the final review. Most papers (
n
= 109, 87.2%) reported on studies that included outcome measures that captured changes at Body Function level, while approximately half captured Activity-level change. Only 24 (19.2%) explored changes at Participation level.

Conclusions:
Change at the Body Function or Activity levels does not always reflect change at the Participation level. Measuring outcomes at the Participation level enables SLPs to determine the real-world impact of the adjustments they have recommended or the intervention they have provided. However, in order to measure outcomes at the Participation level, we need the tools for capturing those changes for school-aged students with SLCD.