bluuebunny/crossref_metadata_2025_split huggingface dataset:
Response Rate and Molecular Correlates to Encorafenib and Binimetinib in BRAF-V600E Mutant High-Grade Glioma
Authors: Schreck Karisa C. , Strowd Roy E. , Nabors Louis B. , Ellingson Benjamin M. , Chang Michael , Tan Sze K. , Abdullaev Zied , Turakulov Rust , Aldape Kenneth , Danda Neeraja , Desideri Serena , Fisher Joy , Iacoboni Michaella , Surakus Trisha , Rudek Michelle A. , Bettegowda Chetan , Grossman Stuart A. , Ye Xiaobu 
Published: March 2024

Abstract

Purpose:
Although fewer than 5% of high-grade gliomas (HGG) are BRAF-V600E mutated, these tumors are notable as BRAF-targeted therapy shows efficacy for some populations. The purpose of this study was to evaluate response to the combination of encorafenib with binimetinib in adults with recurrent BRAF-V600–mutated HGG.

Patients and Methods:
In this phase 2, open-label, Adult Brain Tumor Consortium (ABTC) trial (NCT03973918), encorafenib and binimetinib were administered at their FDA-approved doses continuously in 28-day cycles. Eligible patients were required to have HGG or glioblastoma with a BRAF-V600E alteration that was recurrent following at least one line of therapy, including radiotherapy.

Results:
Five patients enrolled between January 2020 and administrative termination in November 2021 (due to closure of the ABTC). Enrolled patients received treatment for 2 to 40 months; currently one patient remains on treatment. Centrally determined radiographic response rate was 60%, with one complete response and two partial responses. Methylation profiling revealed that all tumors cluster most closely with anaplastic pleomorphic xanthoastrocytoma (PXA). Transcriptional profile for MAPK-response signature was similar across all tumors at baseline and did not correlate with response in this small population. Circulating tumor DNA measured in plasma samples before treatment, during response, and upon progression showed feasibility of detection for the BRAF-V600E alteration. No new safety signal was detected.

Conclusions:
Encorafenib and binimetinib exhibit positive tumor responses in patients with recurrent BRAF-V600E mutant HGG in this small series, warranting therapeutic consideration. Although toxicity remains a concern for BRAF-targeted therapies, no new safety signal was observed in these patients.
Associations of Proteomics With Hypertension and Systolic Blood Pressure: KORA S4/F4/FF4 and KORA Age1/Age2 Cohort Studies
Authors: Lin Jie-sheng , Petrera Agnese , Hauck Stefanie M. , Müller Christian L. , Peters Annette , Thorand Barbara 
Published: March 2024

BACKGROUND:
Hypertension, a complex condition, is primarily defined based on blood pressure readings without involving its pathophysiological mechanisms. We aimed to identify biomarkers through a proteomic approach, thereby enhancing the future definition of hypertension with insights into its molecular mechanisms.

METHODS:
The discovery analysis included 1560 participants, aged 55 to 74 years at baseline, from the KORA (Cooperative Health Research in the Region of Augsburg) S4/F4/FF4 cohort study, with 3332 observations over a median of 13.4 years of follow-up. Generalized estimating equations were used to estimate the associations of 233 plasma proteins with hypertension and systolic blood pressure (SBP). For validation, proteins significantly associated with hypertension or SBP in the discovery analysis were validated in the KORA Age1/Age2 cohort study (1024 participants, 1810 observations). A 2-sample Mendelian randomization analysis was conducted to infer causalities of validated proteins with SBP.

RESULTS:
Discovery analysis identified 49 proteins associated with hypertension and 99 associated with SBP. Validation in the KORA Age1/Age2 study replicated 7 proteins associated with hypertension and 23 associated with SBP. Three proteins, NT-proBNP (N-terminal pro-B-type natriuretic peptide), KIM1 (kidney injury molecule 1), and OPG (osteoprotegerin), consistently showed positive associations with both outcomes. Five proteins demonstrated potential causal associations with SBP in Mendelian randomization analysis, including NT-proBNP and OPG.

CONCLUSIONS:
We identified and validated 7 hypertension-associated and 23 SBP-associated proteins across 2 cohort studies. KIM1, NT-proBNP, and OPG demonstrated robust associations, and OPG was identified for the first time as associated with blood pressure. For NT-proBNP (protective) and OPG, causal associations with SBP were suggested.
Temporal Ordering of Biomarkers in Dutch-Type Hereditary Cerebral Amyloid Angiopathy
Authors: Koemans Emma A. , Rasing Ingeborg , Voigt Sabine , van Harten Thijs W. , van der Zwet Reinier G.J. , Kaushik Kanishk , Schipper Manon R. , van der Weerd Nelleke , van Zwet Erik W. , van Etten Ellis S. , van Osch Matthias J.P. , Kuiperij Bea , Verbeek Marcel M. , Terwindt Gisela M. , Greenberg Steven M. , van Walderveen Marianne A.A. , Wermer Marieke J.H. 
Published: March 2024

BACKGROUND:
The temporal ordering of biomarkers for cerebral amyloid angiopathy (CAA) is important for their use in trials and for the understanding of the pathological cascade of CAA. We investigated the presence and abnormality of the most common biomarkers in the largest (pre)symptomatic Dutch-type hereditary CAA (D-CAA) cohort to date.

METHODS:

We included cross-sectional data from participants with (pre)symptomatic D-CAA and controls without CAA. We investigated CAA-related cerebral small vessel disease markers on 3T-MRI, cerebrovascular reactivity with functional 7T-MRI (fMRI) and amyloid-β
40
and amyloid-β
42
levels in cerebrospinal fluid. We calculated frequencies and plotted biomarker abnormality according to age to form scatterplots.

RESULTS:

We included 68 participants with D-CAA (59% presymptomatic, mean age, 50 [range, 26–75] years; 53% women), 53 controls (mean age, 51 years; 42% women) for cerebrospinal fluid analysis and 36 controls (mean age, 53 years; 100% women) for fMRI analysis. Decreased cerebrospinal fluid amyloid-β
40
and amyloid-β
42
levels were the earliest biomarkers present: all D-CAA participants had lower levels of amyloid-β
40
and amyloid-β
42
compared with controls (youngest participant 30 years). Markers of nonhemorrhagic injury (>20 enlarged perivascular spaces in the centrum semiovale and white matter hyperintensities Fazekas score, ≥2, present in 83% [n=54]) and markers of impaired cerebrovascular reactivity (abnormal BOLD amplitude, time to peak and time to baseline, present in 56% [n=38]) were present from the age of 30 years. Finally, markers of hemorrhagic injury were present in 64% (n=41) and only appeared after the age of 41 years (first microbleeds and macrobleeds followed by cortical superficial siderosis).

CONCLUSIONS:
Our results suggest that amyloid biomarkers in cerebrospinal fluid are the first to become abnormal in CAA, followed by MRI biomarkers for cerebrovascular reactivity and nonhemorrhagic injury and lastly hemorrhagic injury. This temporal ordering probably reflects the pathological stages of CAA and should be taken into account when future therapeutic trials targeting specific stages are designed.
Characterizing the vaginal microbiome in a sexually fluid primate (Pan paniscus)
Authors: Samartino Shelby D. , Bartlett Thad Q. , Wikberg Eva C. 
Published: March 2024

Abstract
While there have been recent breakthroughs in human vaginal microbiome research, very few non-human primate (NHP) vaginal microbiome studies exist due to difficulty in obtaining samples. In this study, we sought to: (1) characterize the bonobo vaginal microbiota for the first time, and (2) determine the relationship between vaginal pH and swelling size. During a 21-day study period, we collected observational data and 71 vaginal swabs from three cohoused adult females at the Ape Cognition and Conservation Initiative. After filtering and classification, a total of 3452 amplicon sequence variants were recruited from 12 vaginal samples. The most dominant phylum represented was Actinobacteria, and the most abundant genera were Gardnerella, Atopobium, and Prevotella. The mean pH score was 6.1 (range: 5.1-7.0), and pH levels varied with relative swelling size. This is the first study to examine the vaginal microbial composition in this species, and it conforms to previous NHP studies in that there was not the same bacterial dominance of Lactobacillus spp. often highlighted in human vaginal microbiota studies. Our findings suggest there may be other factors contributing to the protection of the bonobo vaginal environment, but future analysis of a larger sample is needed to fully understand how sociality and sexuality shape vaginal microbiota and host health.
Bursaphelenchus zealandicus sp. n. (Tylenchina: Aphelenchoididae), a new species of the hofmanni-group from Pinus radiata in New Zealand
Authors: Zhao Zeng Qi , Gu Jianfeng , Greenwood Tanya , Rogan Brent , Ho Wellcome , Taylor Robert 
Published: March 2024

Summary
Bursaphelenchus zealandicus sp. n. was extracted from a dead pine tree (Pinus radiata) in Kinleith Forest, Taupo, New Zealand (NZ). This is the fourth Bursaphelenchus species from NZ. Bursaphelenchus zealandicus sp. n. is characterised by a body length of 562 (466-730) μm and 580 (470-706) μm of males and females, respectively, slim body (a = 34.7 and 33.1, respectively), stylet 11.4 (9.7-13.0) μm long for males and 10.7 (9.4-12.1) μm for females, lateral field with three lines, the mean value of the vulva position 71.8%, lacking a vulval flap in lateral view, length of the post-uterine branch ca 41.6% of the vulva-anus distance, the female tail long and conical (c = 19.3), tapering to a finely rounded terminus, ventrally curved like a hook, the male with spicules 12.3 μm long in chord, having an obvious developed rostrum and condylus, the rostrum sharply pointed, the male tail terminus with a distinct bursa seen in dorso-ventral position, a single pre-anal papilla, two pairs of ventro-sublateral papillae (one pair pre-anal (P2), one pair post-anal (P3) just in front of the bursa) and one pair of ventral mid-line glandular papillae (P4) present. The combination of three lateral lines and the position of caudal papillae reveal a relationship of the new species to other three-lined groups (hofmanni-group, eggersi-group, eremus-group, leoni-group); however, the shape of the spicules is different and unique among the known species of Bursaphelenchus. Its taxonomic status has been confirmed by analyses of the near full length small subunit (SSU), the internal transcribed spacer region (ITS1 and 2), D2-D3 expansion segments of the large subunit (LSU) of the ribosomal rDNA and the mitochondrial cytochrome c oxidase subunit I (COI) gene.
Designing Bespoke Visual Mediation Tools Using ‘Viscourse’ for Intergenerational Research
Authors: Ruscoe Amelia , Baker Penny 
Published: March 2024

Abstract
Visual methods are an innovative design space for study methodologies with young children. The accessibility of visual media, and flexibility of their design and use, has spurred methodological innovations that stretch the boundaries of intergenerational research. This article explores the visual dialogic nexus in research methods tailored to investigate discourse. The research sought to uncover the perspectives of young children and their teachers about their discursive affordances in the first year of school. Employing an iterative design process, bespoke visual mediation tools were collaboratively created with a visual artist to capture the intergenerational viewpoints of the participants. This article reconceptualises discourses as ‘viscourses’ through a Foucauldian post-structuralist lens. This reframing emphasizes the impact of the discursive gaze and manipulation of art elements and principles as themes for scrutiny during the design phase. The resulting visual mediation tools underwent pilot testing with two focus groups of 5-year-old children and their class teachers. Findings from the pilot study underscore the potential of visual mediation tools for generating authentic contexts that enable participants to ‘inhabit’ a time and place within a semiotic space. The method facilitates capture of multi-faceted data, including evidence of children’s higher order thinking concerning abstract phenomenon.
Student Experiences of Implementation of Accommodations
Authors: DeKorver Brittland , Brown Gordon , Witcher Shontaye 
Published: March 2024

Abstract
Teachers want their students to learn, and they want that learning to be equitable, with opportunities for all students. But not all students have the same needs for success. Therefore, classroom accommodations are provided through Disability Offices within universities. These accommodations are intended to be implemented in each course the student takes. Yet the actual enactment of accommodations relies on facilitation and implementation by each instructor in collaboration with the student, which may lead to variance in the level of accommodations. This project examined student interviews and student and faculty survey data to construct a narrative analysis of students’ experiences when they discuss their accommodations with their instructors. This manuscript reports a characterization of these interactions and how these interactions shape students’ success in the classroom, with recommendations for both students and instructors.
Data Assimilation Impact of GNSS RO Measurements from Cube Satellites on Arctic Weather Forecasts
Authors: Choi Yonghan , Kim Joowan , Kim Joo-Hong , Cha Dong-Hyun 
Published: March 2024

Abstract
In this study, the effects of assimilating Global Navigation Satellite System (GNSS) radio occultation (RO) observations from existing and recently added commercial cube satellites on analyses and forecasts over the Arctic region were investigated by conducting observing system experiments (OSEs). Profiles of refractivity were assimilated with a local observation operator using the three-dimensional variational method. The analyses and forecasts from the OSEs were verified against ERA5 reanalysis, radiosonde observations, and buoy observations. In addition to the averaged impact on forecast skill, the impact of GNSS RO observations was further examined for an individual Arctic cyclone case, focusing on the added value of the cube satellite data. The effects of GNSS RO observations from existing satellites on analyses and forecasts over the Arctic region are positive, and the assimilation of GNSS RO observations from cube satellites leads to additional improvements, particularly for temperature in the upper troposphere and lower stratosphere (UTLS). Temperature biases in the UTLS are significantly reduced in the analyses, and the improved analyses result in better forecasts of upper-level potential vorticity and cyclone development when GNSS RO observations from cube satellites are assimilated. This result demonstrates the potential of GNSS RO data from cube satellites to enhance forecasts over the Arctic region.
The First Operational Version of Taiwan Central Weather Bureau’s One-Tier Global Atmosphere–Ocean Coupled Forecast System for Seasonal Prediction
Authors: Juang Hann-Ming Henry , Wu Tzu-Yu , Liu Pang-Yen Brian , Lin Hsin-Yi , Lee Ching-Teng , Kueh Mien-Tze , Fan Jia-Fong , Chen Jen-Her River , Lu Mong-Ming , Lin Pay-Liam 
Published: March 2024

Abstract
The first version of the Taiwan Central Weather Bureau one-tier (TCWB1T) fully coupled global atmospheric and oceanic modeling forecast system had been developed and implemented as a routine operation for seasonal prediction at Central Weather Bureau (CWB) in 2017, with a minor revision in 2020. Based on NCEP CFSv1, the global atmospheric model in NCEP CFSv1 was replaced by CWB’s atmospheric global spectral model (GSM) and coupled with the GFDL MOM3. Several parameters have been tested and tuned in the CWB atmospheric GSM, achieving an optimal configuration with better sea surface temperature (SST) predictions for integration more than one year. Using NCEP CFSR as the initial condition, TCWB1T conducted hindcasts from 1982 to 2011 and forecasts from 2012 to 2019 to analyze its performance. The results of these hindcasts and forecasts show that the TCWB1T can make useful predictions as verified against the observations of OISST, ERSST, CFSR, and GPCP based on the methods of EOF, RMSE, anomaly correlation, ranked probability skill score (RPSS), reliability diagram (RD), and relative operating characteristics (ROCs). TCWB1T also has the same level of skill scores as NCEP CFSv2 and/or the ECMWF fifth-generation seasonal forecast system (SEAS5), based on EOF, anomaly pattern correlation, climatological bias, RMSE, temporal correlation, and anomaly correlation percentage of forecast skill. TCWB1T shows forecast skill that is better in winter than in summer. Overall, it indicates that TCWB1T can be used for seasonal ENSO predictions.
Steering Flow Sensitivity in Forecast Models for Hurricane Ian (2022)
Authors: Colby Frank P. , Barlow Mathew , Penny Andrew B. 
Published: March 2024

Abstract
Hurricane Ian made landfall along Florida’s west coast at 1905 UTC 28 September 2022 near the Fort Myers area as a high-impact storm. Here, we examine the potential link between track forecast errors near the time of landfall and errors in both the synoptic-scale upper-level flow and a shortwave moving within that flow. Five days before the actual landfall (0000 UTC 23 September), most model guidance indicated landfall would occur close to where Ian eventually came ashore. But by 0000 UTC 25 September, model forecasts were all forecasting landfall in the Florida Panhandle. One day later, the models again agreed with each other but for a landfall 100–200 km north of Tampa, Florida. By 0000 UTC 27 September, forecast models indicated landfall would occur near Tampa. Model forecasts continued shifting to the right and finally converged on Punta Gorda, Florida, as the landfall location, less than 24 h before landfall. In this short article, we hypothesize that the track of Ian depended on subtle interactions with an extratropical wave in the middle and upper atmosphere. Deterministic and ensemble model forecasts reveal that the interactions were very sensitive to the characteristics of this wave and the synoptic-scale flow in which the wave was embedded. A 1–2-dam difference in the geopotential heights played a major role in whether Ian moved north into the Panhandle or toward the east, making landfall in central Florida.

Significance Statement
The purpose of this work is to look at possible causes of error in forecasts of Hurricane Ian’s landfall with the intent of saving lives and reducing damage, which can run to the billions of dollars. The path that hurricanes take is strongly influenced by the larger-scale weather patterns around them. We find that small errors in the upper-level flow patterns north of the hurricane appear to have played an important role in the forecast. These errors were present in both the general flow and a wave moving through that flow, resulting in small but significant changes to the forecast path. Understanding the cause of forecast errors is a key step both in improving forecasts and in identifying types of events that are more difficult to forecast.
Advanced Sea Ice Modeling for Short-Term Forecasting for Alaska’s Coasts
Authors: Fujisaki-Manome Ayumi , Hu Haoguo , Wang Jia , Westerink Joannes J. , Wirasaet Damrongsak , Ling Guoming , Choi Mindo , Moghimi Saeed , Myers Edward , Abdolali Ali , Dawson Clint , Janzen Carol 
Published: March 2024

Abstract
In Alaska’s coastal environment, accurate information of sea ice conditions is desired by operational forecasters, emergency managers, and responders. Complicated interactions among atmosphere, waves, ocean circulation, and sea ice collectively impact the ice conditions, intensity of storm surges, and flooding, making accurate predictions challenging. A collaborative work to build the Alaska Coastal Ocean Forecast System established an integrated storm surge, wave, and sea ice model system for the coasts of Alaska, where the verified model components are linked using the Earth System Modeling Framework and the National Unified Operational Prediction Capability. We present the verification of the sea ice model component based on the Los Alamos Sea Ice Model, version 6. The regional, high-resolution (3 km) configuration of the model was forced by operational atmospheric and ocean model outputs. Extensive numerical experiments were conducted from December 2018 to August 2020 to verify the model’s capability to represent detailed nearshore and offshore sea ice behavior, including landfast ice, ice thickness, and evolution of air–ice drag coefficient. Comparisons of the hindcast simulations with the observations of ice extent presented the model’s comparable performance with the Global Ocean Forecast System 3.1 (GOFS3.1). The model’s skill in reproducing landfast ice area significantly outperformed GOFS3.1. Comparison of the modeled sea ice freeboard with the Ice, Cloud, and Land Elevation Satellite-2 product showed a mean bias of −4.6 cm. Daily 5-day forecast simulations for October 2020–August 2021 presented the model’s promising performance for future implementation in the coupled model system.

Significance Statement
Accurate sea ice information along Alaska’s coasts is desired by the communities for preparedness of hazardous events, such as storm surges and flooding. However, such information, in particular predicted conditions, remains to be a gap. This study presents the verification of the state-of-art sea ice model for Alaska’s coasts for future use in the more comprehensive coupled model system where ocean circulation, wave, and sea ice models are integrated. The model demonstrates comparable performance with the existing operational ocean–ice coupled model product in reproducing overall sea ice extent and significantly outperformed it in reproducing landfast ice cover. Comparison with the novel satellite product presented the model’s ability to capture sea ice freeboard in the stable ice season.