bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of tepotinib in Asian patients with advanced NSCLC with MET exon 14 skipping enrolled in VISION
Authors: Kato Terufumi , Yang James Chih-Hsin , Ahn Myung-Ju , Sakai Hiroshi , Morise Masahiro , Chen Yuh-Min , Han Ji-Youn , Yang Jin-Ji , Zhao Jun , Hsia Te-Chun , Berghoff Karin , Bruns Rolf , Vioix Helene , Lang Simone , Johne Andreas , Le Xiuning , Paik Paul K. 
Published: April 2024

Abstract
Background
Tepotinib, a MET inhibitor approved for the treatment of MET exon 14 (METex14) skipping NSCLC, demonstrated durable clinical activity in VISION (Cohort A + C; N = 313): objective response rate (ORR) 51.4% (95% CI: 45.8, 57.1); median duration of response (mDOR) 18.0 months (95% CI: 12.4, 46.4). We report outcomes in Asian patients from VISION (Cohort A + C) (cut-off: November 20, 2022).

Methods
Patients with advanced METex14 skipping NSCLC, detected by liquid or tissue biopsy, received tepotinib 500 mg (450 mg active moiety) once daily. Primary endpoint: objective response (RECIST 1.1) by independent review. Secondary endpoints included: DOR, progression-free survival (PFS), overall survival (OS), safety, and health-related quality of life (HRQoL).

Results
Across treatment lines in 106 Asian patients (39.6% female, 43.4% smoking history, 79.2% adenocarcinoma, 47.2% treatment-naive), ORR was 56.6% (95% CI: 46.6, 66.2), mDOR 18.5 months (10.4, ne), mPFS 13.8 months (10.8, 22.0), and mOS 25.5 months (19.3, 36.4). Consistent efficacy observed, regardless of baseline characteristics. HRQoL remained stable during treatment. Treatment-related adverse events (TRAEs) occurred in 95.3% of patients (39.6% Grade ≥3). Most common TRAEs: peripheral edema (62.3%), creatinine increase (38.7%).

Conclusions
Tepotinib demonstrated robust and durable efficacy, with a manageable safety profile, in Asian patients with METex14 skipping NSCLC.

Clinical trial registration
NCT02864992
A highly crystalline face-on π-conjugated polymer based on alkoxythiophene-flanked benzobisthiazole for organic photovoltaics
Authors: Doi Shuhei , Mikie Tsubasa , Yamanaka Kodai , Sato Yuki , Ohkita Hideo , Saito Masahiko , Osaka Itaru 
Published: April 2024

AbstractThe use of noncovalent intramolecular interactions constitutes a powerful design strategy for preparing π-conjugated polymers featuring high backbone coplanarities and thereby high crystallinities. Herein, we report the design and synthesis of an alkoxythiophene-flanked benzobisthiazole (BBTz) as a new building unit for π-conjugated polymers, which was subsequently copolymerized to give a simple BBTz-bithiophene copolymer with alkyl and alkoxy groups (PDBTz2). Owing to the S···O noncovalent intramolecular interactions between the alkoxy oxygens and thiazole sulfurs in BBTz, PDBTz2 showed greater coplanarity and crystallinity than its alkyl counterpart, PDBTz1. Interestingly, the backbone orientation was completely altered from the edge-on orientation observed for PDBTz1 to a face-on orientation for PDBTz2, which is preferable for organic photovoltaics (OPVs). In addition, the electron-donating nature of the alkoxy group increased the HOMO energy level of PDBTz2 compared to that of PDBTz1, which enabled photoinduced hole transfer from a nonfullerene acceptor, Y6, to the polymer. As a result, the short-circuit current density of an organic photovoltaic cell based on PDBTz2 and Y6 was significantly greater than that of a cell based on PDBTz1 and Y6. This study confirmed that alkoxythiophene-flanked BBTz is a promising building unit for high-performance π-conjugated polymers.
Stability of child appetitive traits and association with diet quality at 5 years and 9–11 years old: Findings from the ROLO longitudinal birth cohort study
Authors: Delahunt Anna , Killeen Sarah Louise , O’Brien Eileen C. , Geraghty Aisling A. , O’Reilly Sharleen L. , McDonnell Ciara M. , Cushion Rosemary , Mehegan John , McAuliffe Fionnuala M. 
Published: April 2024

Abstract
Background
We explored change in child appetitive traits from 5 to 9–11 years old and examined associations between appetitive traits at both timepoints and child diet quality.

Methods
This is secondary analyses of the ROLO longitudinal birth cohort study, including mother-child dyads from the 5 and 9–11-year old follow-up. The Children’s Eating Behaviour Questionnaire measured child appetitive traits, with 167 children having matched data for both timepoints. The Healthy Eating Index (HEI) measured diet quality. Linear mixed models and multiple linear regression were completed.

Results
Mean (SD) score for ‘Emotional Overeating’ (1.63 (0.51) vs. 1.99 (0.57), p = <0.001) and ‘Enjoyment of Food’ (3.79 (0.72) vs. 3.98 (0.66), p = <0.001) increased from 5 to 9–11 years. Mean score for ‘Desire to Drink’ (2.63 (0.94) vs. 2.45 (0.85), p = 0.01), ‘Satiety Responsiveness (3.07 (0.66) vs. 2.71 (0.66), p = <0.001), ‘Slowness Eating’ (3.02 (0.77) vs. 2.64 (0.78), p = <0.001), and ‘Food Fussiness’ (3.00 (1.04) vs. 2.81 (0.96), p = 0.001) decreased. At 5-years-old, ‘Food Responsiveness’ and ‘Enjoyment of Food’ were positively associated with HEI and ‘Desire to Drink’, ‘Satiety Responsiveness’ and ‘Food Fussiness’ were negatively associated with HEI. At 9–11-years, ‘Enjoyment of Food’ was positively and ‘Desire to Drink’ and ‘Food ‘Fussiness’ were negatively associated with HEI.

Conclusions
Food approach appetitive traits increased over time, whereas food avoidant appetitive traits tended to decrease. At both time points ‘Food Fussiness’ and ‘Desire to Drink” were inversely associated with HEI. Further research on how appetitive traits track over childhood and how this relates to dietary quality and weight is warranted.
Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease
Authors: Zhao Yajie , Chukanova Maria , Kentistou Katherine A. , Fairhurst-Hunter Zammy , Siegert Anna Maria , Jia Raina Y. , Dowsett Georgina K. C. , Gardner Eugene J. , Lawler Katherine , Day Felix R. , Kaisinger Lena R. , Tung Yi-Chun Loraine , Lam Brian Yee Hong , Chen Hsiao-Jou Cortina , Wang Quanli , Berumen-Campos Jaime , Kuri-Morales Pablo , Tapia-Conyer Roberto , Alegre-Diaz Jesus , Barroso Inês , Emberson Jonathan , Torres Jason M. , Collins Rory , Saleheen Danish , Smith Katherine R. , Paul Dirk S. , Merkle Florian , Farooqi I. Sadaf , Wareham Nick J. , Petrovski Slavé , O’Rahilly Stephen , Ong Ken K. , Yeo Giles S. H. , Perry John R. B. 
Published: April 2024

AbstractObesity is a major risk factor for many common diseases and has a substantial heritable component. To identify new genetic determinants, we performed exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare loss-of-function variants in two genes (BSN and APBA1) with effects substantially larger than those of well-established obesity genes such as MC4R. In contrast to most other obesity-related genes, rare variants in BSN and APBA1 were not associated with normal variation in childhood adiposity. Furthermore, BSN protein-truncating variants (PTVs) magnified the influence of common genetic variants associated with BMI, with a common variant polygenic score exhibiting an effect twice as large in BSN PTV carriers than in noncarriers. Finally, we explored the plasma proteomic signatures of BSN PTV carriers as well as the functional consequences of BSN deletion in human induced pluripotent stem cell-derived hypothalamic neurons. Collectively, our findings implicate degenerative processes in synaptic function in the etiology of adult-onset obesity.
Seroprevalence and molecular detection of foot and mouth disease virus in cattle in selected districts of Wolaita Zone, Southern Ethiopia
Authors: Bandaw Tamenech , Gebremeskel Haben Fesseha , Muluneh Ayelech , Mengistu Tilaye Shibiru , Kebede Isayas Asefa 
Published: April 2024

AbstractFoot and mouth disease (FMD) is a highly contagious, endemic, and acute viral cattle ailment that causes major economic damage in Ethiopia. Although several serotypes of the FMD virus have been detected in Ethiopia, there is no documented information about the disease's current serostatus and serotypes circulating in the Wolaita zone. Thus, from March to December 2022, a cross-sectional study was conducted to evaluate FMDV seroprevalence, molecular detection, and serotype identification in three Wolaita Zone sites. A multistage sample procedure was used to choose three peasant associations from each study region, namely Wolaita Sodo, Offa district, and Boloso sore district. A systematic random sampling technique was employed to pick 384 cattle from the population for the seroprevalence research, and 10 epithelial tissue samples were purposefully taken from outbreak individuals for molecular detection of FMDV. The sera were examined using 3ABC FMD NSP Competition ELISA to find antibodies against FMDV non-structural proteins, whereas epithelial tissue samples were analyzed for molecular detection using real-time RT-PCR, and sandwich ELISA was used to determine the circulating serotypes. A multivariable logistic regression model was used to evaluate the associated risk variables. The total seroprevalence of FMD in cattle was 46.88% (95% CI 41.86–51.88), with Wolaita Sodo Town having the highest seroprevalence (63.28%). As a consequence, multivariable logistic regression analysis revealed that animal age, herd size, and interaction with wildlife were all substantially related to FMD seroprevalence (p < 0.05). During molecular detection, only SAT-2 serotypes were found in 10 tissue samples. Thus, investigating FMD outbreaks and identifying serotypes and risk factors for seropositivity are critical steps in developing effective control and prevention strategies based on the kind of circulating serotype. Moreover, further research for animal species other than cattle was encouraged.
Molecular dynamics simulations to explore the binding mode between the amyloid-β protein precursor (APP) and adaptor protein Mint2
Authors: Wang Min , Liu Kaifeng 
Published: April 2024

AbstractAlzheimer's disease (AD) presents a significant challenge in neurodegenerative disease management, with limited therapeutic options available for its prevention and treatment. At the heart of AD pathogenesis is the amyloid-β (Aβ) protein precursor (APP), with the interaction between APP and the adaptor protein Mint2 being crucial. Despite previous explorations into the APP-Mint2 interaction, the dynamic regulatory mechanisms by which Mint2 modulates APP binding remain poorly understood. This study undertakes molecular dynamics simulations across four distinct systems—free Mint2, Mint2 bound to APP, a mutant form of Mint2, and the mutant form bound to APP—over an extensive 400 ns timeframe. Our findings reveal that the mutant Mint2 experiences significant secondary structural transformations, notably the formation of an α-helix in residues S55-K65 upon APP binding, within the 400 ns simulation period. Additionally, we observed a reduction in the active pocket size of the mutant Mint2 compared to its wild-type counterpart, enhancing its APP binding affinity. These insights hold promise for guiding the development of novel inhibitors targeting the Mints family, potentially paving the way for new therapeutic strategies in AD prevention and treatment.
Chloride ions in health and disease
Authors: Raut Satish K. , Singh Kulwinder , Sanghvi Shridhar , Loyo-Celis Veronica , Varghese Liyah , Singh Ekam R. , Gururaja Rao Shubha , Singh Harpreet 
Published: April 2024

Abstract
Chloride is a key anion involved in cellular physiology by regulating its homeostasis and rheostatic processes. Changes in cellular Cl− concentration result in differential regulation of cellular functions such as transcription and translation, post-translation modifications, cell cycle and proliferation, cell volume, and pH levels. In intracellular compartments, Cl− modulates the function of lysosomes, mitochondria, endosomes, phagosomes, the nucleus, and the endoplasmic reticulum. In extracellular fluid (ECF), Cl− is present in blood/plasma and interstitial fluid compartments. A reduction in Cl− levels in ECF can result in cell volume contraction. Cl− is the key physiological anion and is a principal compensatory ion for the movement of the major cations such as Na+, K+, and Ca2+. Over the past 25 years, we have increased our understanding of cellular signaling mediated by Cl−, which has helped in understanding the molecular and metabolic changes observed in pathologies with altered Cl− levels. Here, we review the concentration of Cl− in various organs and cellular compartments, ion channels responsible for its transportation, and recent information on its physiological roles.
Speech-Language Outcomes in the COVID-19 Milieu for Multilingual Jamaican Preschoolers and Considerations for Telepractice Assessments
Authors: Kokotek Leslie E. , Washington Karla N. , Cunningham Barbara Jane , Acquavita Shauna P. 
Published: April 2024

Purpose:
The purpose of this study was to characterize the communicative participation and functional speech intelligibility (i.e., how children use communication and how well they are understood across everyday life) of typically developing (TD) bilingual Jamaican preschoolers and those with functionally defined speech sound disorders (fSSDs) in the COVID-19 milieu. Findings were also compared to an existing corpus of baseline data to document and explore differences in children's speech-language outcomes secondary to pandemic-related social restrictions.

Method:

Thirty bilingual Jamaican preschoolers, 21 TD and nine with fSSDs, were assessed during the pandemic via telepractice. Association and univariate mean testing were completed to characterize children's communicative participation and functional speech intelligibility. Data were then compared to an existing corpus of baseline data (collected in person between 2013 and 2019), which included direct child assessment and parent reports and consisted of TD (
n
= 226) Jamaican Creole-English–speaking preschoolers and those with fSSDs (
n
= 39) to compare performance profiles across data sets. All participants attended schools in Kingston, Jamaica.

Results:
Measures of communicative participation remained stable in the context of the COVID-19 milieu for children in the TD and fSSD groups, but functional speech intelligibility outcomes for children with fSSDs deviated between in-person findings collected from children pre-pandemic. Between-groups differences were also found on measures of speech production accuracy but were no longer significant when considering telepractice as a covariate.

Conclusions:
Findings from this investigation serve to characterize the communicative participation and functional speech intelligibility of TD bilingual Jamaican preschoolers and those with fSSDs in the COVID-19 milieu. By extension, the results comparing data from preschoolers collected during the pandemic to an existing corpus of baseline data from a different group of preschoolers provide critical insights about multilingual children's speech-language outcomes in the context of acutely changing environmental circumstances.

Supplemental Material:

https://doi.org/10.23641/asha.25461505
Comparing Two Smoothing Approaches in Estimating Kinematic Parameters
Authors: Kuberski Stephan R. , Gafos Adamantios I. 
Published: April 2024

Purpose:
We compare two signal smoothing and differentiation approaches: a frequently used approach in the speech community of digital filtering with approximation of derivatives by finite differences and a spline smoothing approach widely used in other fields of human movement science.

Method:
In particular, we compare the values of a classic set of kinematic parameters estimated by the two smoothing approaches and assess, via regressions, how well these reconstructed values conform to known laws about relations between the parameters.

Results:
Substantially smaller regression errors were observed for the spline smoothing than for the filtering approach.

Conclusion:
This result is in broad agreement with reports from other fields of movement science and underpins the superiority of splines also in the domain of speech.
Testing the Continuum/Spectrum Model in Russian-Speaking Children With and Without Developmental Language Disorder
Authors: Gomozova Militina , Lezzhova Valeriia , Dragoy Olga , Lopukhina Anastasiya 
Published: April 2024

Purpose:
Previously, Lancaster and Camarata (2019) showed that the continuum/spectrum model of the developmental language disorder (DLD) best explained the high heterogeneity of symptoms in children with DLD. We hypothesize that the continuum/spectrum approach can include not only children with DLD but also typically developing (TD) children with different timelines and patterns of language acquisition. This model can explain individual language profiles and deficits in children.

Method:

We assessed language abilities in a group of Russian-speaking children with DLD aged 4–7 years (
n
= 53) and their age- and gender-matched peers without speech and language diagnoses (
n
= 53, TD). We evaluated the children's performance at four language levels in production and comprehension domains, using 11 subtests of the standardized language assessment for Russian: Russian Child Language Assessment Battery (RuCLAB). Using the
k
-means cluster method and RuCLAB scores, we obtained two clusters of children and analyzed their language performance in individual subtests.

Results:
The analysis revealed that the two clusters of children both included DLD and TD participants: Group 1, with higher test scores (TD = 45, DLD = 24 children), and Group 2, with lower scores (TD = 8, DLD = 29). Children from Group 1 mostly had lower scores at one of the language levels, whereas those from Group 2 struggled at several language levels. Furthermore, children with DLD from both groups tended to be more sensitive to linguistic features such as word length, noun case, and sentence reversibility compared to TD children.

Conclusions:
The presence of two mixed groups shows that children with diagnosed DLD could perform on par with TD children, whereas some younger TD children could perform similarly to children with DLD. Our findings support the continuum/spectrum model: Linguistic skills in preschool children are a continuum, varying from high to poor skills at all language levels in comprehension and production. To describe a child's language profile, the tasks assessing all language levels should be used.

Supplemental Material:

https://doi.org/10.23641/asha.25521400
Track initialisation for multiple formations based on neutrosophic Hough transform
Authors: Penggang Yang , Kun Wang , Guangdong Feng 
Published: April 2024

AbstractTrack crossing is a major issue in the initialisation of multiple‐flight trajectories. To solve this problem, the authors propose a track initialisation algorithm. It uses characteristics of formation flight to find centroids of each formation with DBSCAN algorithm. Then, it initialises the track based on the centroid. The author use a Neutrosophic Hough Transform (NHT) method to improve accuracy and computational speed. That helps address errors caused by the approximation of straight lines between true points resulting from the clustering algorithm. The authors made three experiments using track initialisation data from two flight formations with five target aircraft each, over a span of three frames. NHT, Fuzzy HT, Improved Hough Transform (HT) and HT are compared. Results revealed that the average runtime of NHT was 10.2153 s. The F‐measure of NHT was 100.00%, while that of Fuzzy HT was 9.8347 s. The F‐measure of Fuzzy HT was 80.00%. The Improved HT was 12.0723 s. The F‐measure of Improved HT was 11.76% and HT was 13.783 s. And the F‐measure of HT was 6.87%. The authors lost some computation speed to achieve higher prediction accuracy. The accuracy of the NHT is higher than other methods.
A stream come true: Connecting tidal tails, shells, streams, and planes with galaxy kinematics and formation history
Authors: Valenzuela Lucas M. , Remus Rhea-Silvia 
Published: April 2024

Context. The rapidly improving quality and resolution of both low surface brightness observations and cosmological simulations of galaxies enable us to address the important question of how the formation history is imprinted in the outer unrelaxed regions of galaxies, and to inspect the correlations of these imprints with another tracer of galaxy formation, the internal kinematics.
Aims. Using the hydrodynamical cosmological simulation called Magneticum Pathfinder, we identified tidal tails, shells, streams, and satellite planes, and connected them to the amount of rotational support and the formation histories of the host galaxies. This presents the first combined statistical census considering all these four types of features in hydrodynamical cosmological simulations.
Methods. Tidal features were visually classified from a three-dimensional rendering of the simulated galaxies by several scientists independently. Only features that were identified by at least half of the participating individuals were considered to be existing features. The data on satellite planes and kinematic properties of the simulated galaxies were taken from previous work. The results were compared to observations, especially from the MATLAS survey.
Results. Generally, prominent features are much more common around elliptical than around disk galaxies. Shells are preferentially found around kinematically slowly rotating galaxies in both simulations and observations, while streams can be found around all types of galaxies, with a slightly higher probability to be present around less rotationally supported galaxies. Tails and satellite planes, however, appear independently of the internal kinematics of the central galaxy, indicating that they are formed through processes that have not (yet) affected the internal kinematics. Prolate rotators have the overall highest probability to exhibit tidal features, but the highest likelihood for a specific type of feature is found for galaxies with kinematically distinct cores (KDCs), nearly 20% of which exhibit streams.
Conclusions. As shells are formed through radial merger events while streams are remnants of circular merger infall, this suggests that the orbital angular momentum of the merger event plays a more crucial role in transforming the host galaxy than previously anticipated. The existence of a shell around a given slow rotator furthermore is a sign of a radial merger formation for this particular slow rotator because one-third of the galaxies with a shell were transformed into slow rotators by the merger event that also caused the shells. The appearance of a stream around a KDC is a direct indicator for the multiple merger formation pathway of that KDC as opposed to the major merger pathway.
Laboratory simulations of ice growth in space: An expected nonuniform ice mantle composition
Authors: Jiménez-Escobar A. , Ciaravella A. , Cecchi-Pestellini C. , Sie N.-E. , Lee C.-Y. , Huang C.-H. , Caro G. M. Muñoz , Chen Y.-J. 
Published: April 2024

Context. In dense, cold molecular regions, gas-phase chemical species freeze out onto grain surfaces. These icy condensates become an important reservoir of volatile elements and feedstock for molecular diversity.
Aims. While there is a fairly general agreement on the chemical composition of icy mantles, there are differences in how the various molecular components are perceived to be present. Should the materials composing the ice be mixed or are they segregated into distinct chemical zones?
Methods. To answer such a question, we performed a few exploratory experiments that allowed the adsorbing surface (mimic dust grains) to slowly relax to very low temperatures while gas-phase mixtures of H2O, NH3, and CO embed onto it.
Results. We find that mantles are far from being uniform, and they could evolve into completely mixed ices only if the ambient temperature undergoes a catastrophic collapse.
Conclusions. Under the typical conditions of an interstellar dense cloud, ices present a high degree of molecular segregation, with possible consequences on the ice chemistry and the desorption mechanisms.