bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Proteogenomic Profiling Reveals the Molecular Characteristics of Colorectal Cancer at Distinct Stages of Progression
Authors: Li Lingling , Jiang Dongxian , Liu Hui , Guo Chunmei , Zhang Qiao , Li Xuedong , Chen Xiaojian , Chen Zheqi , Feng Jinwen , Tan Subei , Huang Wen , Huang Jie , Xu Chen , Liu Chen-Ying , Yu Wei , Hou Yingyong , Ding Chen 
Published: June 2024

Abstract
Colorectal cancer is the second most common malignant tumor worldwide. Analysis of the changes that occur during colorectal cancer progression could provide insights into the molecular mechanisms driving colorectal cancer development and identify improved treatment strategies. In this study, we performed an integrated multiomic analysis of 435 trace tumor samples from 148 patients with colorectal cancer, covering nontumor, intraepithelial neoplasia (IEN), infiltration, and advanced stage colorectal cancer phases. Proteogenomic analyses demonstrated that KRAS and BRAF mutations were mutually exclusive and elevated oxidative phosphorylation in the IEN phase. Chr17q loss and chr20q gain were also mutually exclusive, which occurred predominantly in the IEN and infiltration phases, respectively, and impacted the cell cycle. Mutations in TP53 were frequent in the advanced stage colorectal cancer phase and associated with the tumor microenvironment, including increased extracellular matrix rigidity and stromal infiltration. Analysis of the profiles of colorectal cancer based on consensus molecular subtype and colorectal cancer intrinsic subtype classifications revealed the progression paths of each subtype and indicated that microsatellite instability was associated with specific subtype classifications. Additional comparison of molecular characteristics of colorectal cancer based on location showed that ANKRD22 amplification by chr10q23.31 gain enhanced glycolysis in the right-sided colorectal cancer. The AOM/DSS-induced colorectal cancer carcinogenesis mouse model indicated that DDX5 deletion due to chr17q loss promoted colorectal cancer development, consistent with the findings from the patient samples. Collectively, this study provides an informative resource for understanding the driving events of different stages of colorectal cancer and identifying the potential therapeutic targets.
Significance: Characterization of the proteogenomic landscape of colorectal cancer during progression provides a multiomic map detailing the alterations in each stage of carcinogenesis and suggesting potential diagnostic and therapeutic approaches for patients.
Optimizing ATR Inhibition and Cisplatin Synergy in Ewing Sarcoma
Authors: Ohmura Shunya , Grünewald Thomas G. P. 
Published: June 2024

SummaryEWSR1::FLI1-mediated dysregulation of cellular machinery opens up potential new avenues for Ewing sarcoma treatment. A recent study demonstrates that pharmacologic ATR kinase inhibition dramatically synergizes with low-dose cisplatin through EWSR1::FLI1-dependent rewiring of transcription, DNA repair, and translation machinery, which could maximize the therapeutic window of the combinatory therapy.See related article by Jess et al., p. 3533
At Home “Tips” for Headache Management: The Use of Self-Trendelenburg to Help Determine the Cause of Worsening Headaches: A Case Series
Authors: Rozen Todd D. 
Published: June 2024

In office use of the Trendelenburg position has been shown to be a beneficial clinical tool to help decipher if a CSF pressure/volume component is part of the underlying etiologic process for a patient’s persistent headache. Utilizing the Trendelenburg position at home could potentially be an additional diagnostic tool for the treating headache physician. Our headache practice has been using at home self-Trendelenburg for the past two years and will present the clinical scenarios in which it seems to be the most helpful utilizing a case series of patients.
These include:
1.	In those who just had a lumbar puncture and call for worsening headaches and do not have an obvious orthostatic component.
2.	In those who had a spinal epidural blood patch for a presumed CSF leak and state there was no improvement.
3.	In those who are on daily preventive CSF volume lowering medications and call in with worsening headaches.
4.	In those with known CSF pressure dependent headaches high or low but who are not on daily preventive CSF volume modulatory medications.
5.	In those with a history of migraine or other primary headache disorder to see if a new type of headache is possibly from a CSF leak or an abnormal reset of CSF pressure to an elevated state.
6.	In those with triggered only headaches like cough or exertional headache.
Utilizing at home self-Trendelenburg can provide valuable information for the treating headache physician on possible underlying headache etiology and can guide specific treatment strategies. Its simplicity and quick declaration of results is very patient pleasing.
Development and Validation of a Mortality Risk Score for Repaired Tetralogy of Fallot
Authors: Mayourian Joshua , Sleeper Lynn A. , Lee Ji Hae , Lu Minmin , Geva Alon , Mulder Barbara , Babu‐Narayan Sonya V. , Wald Rachel M. , Sompolinsky Tehila , Valente Anne Marie , Geva Tal 
Published: June 2024

Background
Robust risk assessment is crucial for the growing repaired tetralogy of Fallot population at risk of major adverse clinical outcomes; however, current tools are hindered by lack of validation. This study aims to develop and validate a risk prediction model for death in the repaired tetralogy of Fallot population.

Methods and Results

Patients with repaired tetralogy of Fallot enrolled in the INDICATOR (International Multicenter Tetralogy of Fallot Registry) cohort with clinical, arrhythmia, cardiac magnetic resonance, and outcome data were included. Patients from London, Amsterdam, and Boston sites were placed in the development cohort; patients from the Toronto site were used for external validation. Multivariable Cox regression was used to evaluate factors associated with time from cardiac magnetic resonance until the primary outcome: all‐cause death. Of 1552 eligible patients (n=1221 in development, n=331 in validation; median age at cardiac magnetic resonance 23.4 [interquartile range, 15.6–35.6] years; median follow up 9.5 years), 102 (6.6%) experienced the primary outcome. The multivariable Cox model performed similarly during development (concordance index, 0.83 [95% CI, 0.78–0.88]) and external validation (concordance index, 0.80 [95% CI, 0.71–0.90]) and identified older age at cardiac magnetic resonance, obesity, type of tetralogy of Fallot repair, higher right ventricular end‐systolic volume index, and lower biventricular global function index as independent predictors of death. A risk‐scoring algorithm dividing patients into low‐risk (score ≤4) versus high‐risk (score >4) groups was validated to effectively discriminate risk of death (15‐year survival of 95% versus 74%, respectively;
P
<0.001).

Conclusions
This externally validated mortality risk prediction algorithm can help identify vulnerable patients with repaired tetralogy of Fallot who may benefit from targeted interventions.
Acute Intermittent Hypoxia With High-Intensity Gait Training in Chronic Stroke: A Phase II Randomized Crossover Trial
Authors: Hornby T. George , Plawecki Abbey , Lotter Jennifer K. , Shoger Lindsay H. , Voigtmann Christina J. , Inks Erin , Henderson Christopher E. 
Published: June 2024

BACKGROUND:
Studies in individuals with chronic stroke indicate high-intensity training (HIT) focused on walking improves locomotor function, which may be due to repeated activation of locomotor circuits and serotonin-dependent modulation of motor output. Separate studies in animals and individuals with spinal cord injury suggest acute intermittent hypoxia (AIH) can augment the effects of locomotor interventions through similar serotonin-dependent mechanisms, although no studies have coupled AIH with HIT in individuals poststroke. The goal of this study was to evaluate the safety and efficacy of AIH+HIT versus HIT alone in individuals with chronic stroke.

METHODS:

This phase II double-blind randomized, crossover trial recruited individuals between 18 and 85 years old, >6 months poststroke, and self-selected speeds <1.0 m/s. Participants received up to 15 sessions of AIH for 30 minutes using 15 cycles of hypoxia (60–90 seconds; 8%–9% O
2
) and normoxia (30–60 seconds; 21% O
2
), followed by 1 hour of HIT targeting >75% heart rate reserve. The control condition received normoxia for 30 minutes before HIT. Following the first training phase, participants performed the second phase >1 month later. The primary outcomes were self-selected speed and fastest speed, a 6-minute walk test, and peak treadmill speed. A 3-way mixed-model ANOVA assessed the effects of time, training, and order of interventions.

RESULTS:

Of 55 individuals screened, 35 were randomized to AIH+HIT or normoxia+HIT first, and 28 individuals completed both interventions, revealing greater gains in self-selected speeds (0.14 [0.08–0.18] versus 0.05 [0.01–0.10] m/s), fastest speed (0.16 [0.10–0.21] versus 0.06 [0.02–0.10] m/s), and peak treadmill speed (0.21 [0.14–0.29] versus 0.11 [0.06–0.16] m/s) following AIH+HIT versus normoxia+HIT (
P
<0.01) with no order effects. Greater gains in spatiotemporal symmetry were observed with AIH+HIT, with worse outcomes for those prescribed serotonin-mediated antidepressant medications.

CONCLUSIONS:
AIH+HIT resulted in greater gains in locomotor function than normoxia+HIT. Subsequent phase III trials should further evaluate the efficacy of this intervention.

REGISTRATION:

URL:
https://clinicaltrials.gov/
; Unique identifier: NCT04472442.
Interpreting God’s Protection through a Dynamic Faith Partnership
Authors: Hartswood Eve , Nyang’ama Thomas Bright C. , Mazinyane Lindirabe , Wild-Wood Emma , Grant Elizabeth , Thipa Joseph Andrew 
Published: June 2024

Abstract
This article examines how Christians in a faith partnership between Malawi and Scotland sought and defined God’s protection as they responded to the challenges of the COVID-19 pandemic. Malawi and Scotland have different cultures, societies and economic prosperity but a shared Presbyterian history, and long-standing faith partnerships through the two national churches. Qualitative interviews articulate striking comparisons of expectations of God’s protection when confronting global disease. This research shows how the dynamics of this partnership allowed both member churches to contribute to each other’s needs and hold a critical solidarity in each other’s interpretation of God’s protection.
Interaction effects of substrate fermentation and larval density on black soldier fly life-history traits
Authors: Opare L.O. , Holm S. , Esperk T. 
Published: June 2024

Abstract
Agricultural by-products can serve as an excellent food source for edible insects, but their high-fibre properties can present challenges. One solution to this is fermentation, which can enhance their nutritional value by breaking down the fibre. However, little research has been conducted on how this method interacts with other environmental factors in insect rearing. To address this gap, our study aimed to investigate the impact of substrate fermentation and larval density on black soldier fly (BSF) larvae. We compared fermented substrates (fermented spent grain and additionally fermented ensiled grass) with standard fibrous substrates (spent grain and ensiled grass) and applied two larval density treatments (high and low). Our findings revealed that prepupal mass was significantly greater in fermented substrates than in standard fibrous substrates, with variations dependent on the substrate and larval density treatments. Larval density significantly influenced prepupal mass only in the fermented spent grain treatment. Substrate type influenced development time, with fermented spent grain resulting in a shorter development time than ensiled grass. However, substrate fermentation and larval density did not affect development time. Substrate fermentation only increased larval survival when individuals were reared on spent grain at high larval density. There were no significant differences in survival between fermented and standard substrates in other substrate and larval density combinations. Our study demonstrates that fermentation could serve as a way to amend fibrous substrates, making them suitable for rearing BSF larvae; however, its effects depend on environmental factors such as larval density.
Leveraging Deterministic Weather Forecasts for In Situ Probabilistic Temperature Predictions via Deep Learning
Authors: Landry David , Charantonis Anastase , Monteleoni Claire 
Published: June 2024

Abstract
We propose a neural network approach to produce probabilistic weather forecasts from a deterministic numerical weather prediction. Our approach is applied to operational surface temperature outputs from the Global Deterministic Prediction System up to 10-day lead times, targeting METAR observations in Canada and the United States. We show how postprocessing performance is improved by training a single model for multiple lead times. Multiple strategies to condition the network for the lead time are studied, including a supplementary predictor and an embedding. The proposed model is evaluated for accuracy, spread, distribution calibration, and its behavior under extremes. The neural network approach decreases the continuous ranked probability score (CRPS) by 15% and has improved distribution calibration compared to a naive probabilistic model based on past forecast errors. Our approach increases the value of a deterministic forecast by adding information about the uncertainty, without incurring the cost of simulating multiple trajectories. It applies to any gridded forecast including the recent machine learning–based weather prediction models. It requires no information regarding forecast spread and can be trained to generate probabilistic predictions from any deterministic forecast.

Significance Statement
Weather is difficult to predict a long time in advance because we cannot measure the state of the atmosphere precisely enough. Consequently, it is common practice to run forecasts several times and look at the differences to evaluate how uncertain the prediction is. This process of running ensemble forecasts is expensive and consequently not always feasible. We propose a middle ground where we add uncertainty information to forecasts that were run only once, using artificial intelligence. Our method increases the value of these forecasts by adding information about the uncertainty without incurring the cost of multiple full simulations.
Expert and Public Preferences and Perceptions of Different Color Schemes and Map Overlays on a Tropical Cyclone Wind Exceedance Forecast Graphic
Authors: Rosen Zoey , Long Marilee , Schumacher Andrea , DeMaria Mark , Brammer Alan 
Published: June 2024

Abstract
Map graphics are often used for hazard risk communication, layered with numerical, verbal, and visual information to describe an uncertain threat. In the hurricane context, graphics are used to communicate the probability of different threats over a forecasting period. While hurricane graphics have been studied in the past, they have not been designed with colorblind-friendly accessibility and localization in mind. This study presents the results of a mixed-method study, testing the perceptions of different color schemes and map overlays on a wind exceedance map graphic with samples of experts (emergency managers and meteorologists) and the public. Nineteen experts from Florida and Louisiana were interviewed about their preferences for and risk perceptions of the design elements of the new wind exceedance graphic. The graphic prototypes were also tested using a public sample (n = 624) from Florida and Louisiana to study participants’ design preferences and risk perceptions. Both expert and public samples preferred a yellow-to-red scheme, though experts thought the yellow-to-red scheme presented the hazard as riskier and the public thought the reds-only scheme was riskier. Experts and the public preferred a map graphic with overlays; they scored a map graphic with overlays as riskier than a version without overlays. Understanding the connection between color scheme preference and risk perception for both experts and the public has important implications on risk communication as new graphics are designed. The conclusion of this study provides avenues for future research for experts who want to apply universal design aspects into hurricane graphics.

Significance Statement
This study investigates user preferences and risk perceptions for a new wind exceedance hurricane graphic designed with universal design principles. Experts (emergency managers and meteorologists) and the public from Florida and Louisiana participated in a mixed-method study, capturing qualitatively and quantitatively how a yellow-to-red and reds-only color scheme, as well as interstate or city overlays, impacted their engagement with the graphic. Studying the design features of forecast graphics from a social science perspective before they are operational is important, as the findings from this study reveal how different groups could perceive the graphic.
Factors correlated with hearing aids adherence in older adults: a prospective controlled study
Authors: Ghiselli Sara , Soncini Arianna , Fabrizi Enrico , Salsi Daria , Cuda Domenico 
Published: June 2024

Objective To investigate which factors influence the adherence to hearing aid (HA) use in elderly patients with moderate-to-severe hearing loss. Methods This observational, prospective, single-centre study enrolled patients with moderate-to-severe hearing loss. They were evaluated before and 1 year after having either one or two HAs fitted. Results A total of 86 patients were enrolled in the study and of these 69.8% (60 of 86; USER group) continued to use their HA at 1 year after fitting; six patients had not continued their use (NON-USERS). The USER group was younger than the NON-USER group, but the difference was not significant. The USER group had a significantly better unaided auditory threshold at baseline than the NON-USER group. HA use resulted in improvements in speech audiometry and auditory threshold. There was also a maintenance of cognitive function in the USER group. Conclusion Use of HA for 1 year resulted in improved auditory performance and an absence of a deterioration of cognitive function. Trial registration: This research was retrospectively registered under no. NCT04333043 at ClinicalTrials.gov ( http://www.clinicaltrials.gov/ ) on the 26 March 2020. This research has been registered with the Ethics Committee of the Area Vasta Emilia Nord under number 104, date of approval 17/07/2017.
Hypersensitivity to CGRP as a predictive biomarker of migraine prevention with erenumab
Authors: Al-Khazali Haidar M , Ashina Håkan , Christensen Rune Häckert , Wiggers Astrid , Rose Kathrine , Iljazi Afrim , Amin Faisal Mohammad , Ashina Messoud , Snellman Josefin , Maio-Twofoot Tina , Schytz Henrik W 
Published: June 2024

Background The present study aimed to investigate the predictive value of calcitonin gene-related peptide (CGRP)-induced migraine attacks for effectiveness to erenumab treatment in people with migraine. Methods In total, 139 participants with migraine underwent a single experimental day involving a 20-min infusion with CGRP. Following this, the participants entered a 24-week treatment period with erenumab. The primary endpoints were the predictive value of CGRP-induced migraine attacks on the effectiveness of erenumab, defined as ≥50% reduction in monthly migraine days, or ≥ 50% reduction in either monthly migraine or monthly headache days of moderate to severe intensity. Results Among participants with CGRP-induced migraine attacks, 60 of 99 (61%) achieved ≥50% reduction in monthly migraine days during weeks 13–24 with erenumab. Conversely, 13 of 25 (52%) where CGRP infusion did not induce a migraine achieved the same endpoint ( p = 0.498). There were no significant differences between the ≥50% reduction in either monthly migraine or monthly headache days of moderate to severe intensity between CGRP-sensitive and non-sensitive participants ( p = 0.625). Conclusions Our findings suggest that the CGRP-provocation model cannot be used to predict erenumab's effectiveness. It remains uncertain whether this finding extends to other monoclonal antibodies targeting the CGRP ligand or to gepants. Trial Registration: The study was registered at ClinicalTrials.gov (NCT04592952).
Plasma metabolomics and lipidomics reveal potential novel biomarkers in early gastric cancer: An explorative study
Authors: Wang Feng , Pang Ruifang , Zhao Xudong , Zhou Bin , Tian Yuan , Ma Yongchen , Rong Long 
Published: June 2024

Background Early identification and therapy can significantly improve the outcome for gastric cancer. However, there is still no perfect biomarker available for the detection of early gastric cancer. This study aimed to investigate the alterations in the plasma metabolites of early gastric cancer using metabolomics and lipidomics based on high-performance liquid chromatography-mass spectrometry (HPLC-MS), which detected potential biomarkers that could be used for clinical diagnosis. Methods To investigate the changes in metabolomics and lipidomics, a total of 30 plasma samples were collected, consisting of 15 patients with early gastric cancer and 15 healthy controls. Extensive HPLC-MS-based untargeted metabolomic and lipidomic investigations were conducted. Differential metabolites and metabolic pathways were uncovered through the utilization of statistical analysis and bioinformatics analysis. Candidate biomarker screening was performed using support vector machine-based multivariate receiver operating characteristic analysis. Results A disturbance was observed in a combined total of 19 metabolites and 67 lipids of the early gastric cancer patients. The analysis of KEGG pathways showed that the early gastric cancer patients experienced disruptions in the arginine biosynthesis pathway, the pathway for alanine, aspartate, and glutamate metabolism, as well as the pathway for glyoxylate and dicarboxylate metabolism. Plasma metabolomics and lipidomics have identified multiple biomarker panels that can effectively differentiate early gastric cancer patients from healthy controls, exhibiting an area under the curve exceeding 0.9. Conclusion These metabolites and lipids could potentially serve as biomarkers for the screening of early gastric cancer, thereby optimizing the strategy for the detection of early gastric cancer. The disrupted pathways implicated in early gastric cancer provide new clues for additional understanding of gastric cancer's pathogenesis. Nonetheless, large-scale clinical data are required to prove our findings.
Painful Nonunion in Patients With Clinically Plantigrade Diabetes-Associated Charcot Foot Arthropathy
Authors: Pinzur Michael S. , Cho Elizabeth , Schiff Adam P. , Hamid Kamran 
Published: June 2024

Background: It has been assumed that diabetic patients with peripheral neuropathy should not have pain associated with Charcot foot arthropathy. Methods: During a 19-year period, 14 diabetic patients (15 feet) presented for treatment with pain following resolution of the acute phases of midfoot Charcot foot arthropathy. All were clinically plantigrade with plain radiographic evidence of bony union without deformity. Pain did not resolve with the use of appropriate therapeutic footwear. When used, CT scans uniformly demonstrated nonunion. Results: All 14 patients had resolution of their presenting pain following successful arthrodesis. Nonunion was confirmed at surgery in all of the patients. One patient developed a fatal pulmonary embolus following removal of the external fixator. Two required late exostectomy for bony overgrowth at the surgical site of fusion for nonunion. Conclusion: This small series of patients would suggest that nonunion of the Charcot neuroarthropathy process was responsible for complaints of pain not able to be managed with therapeutic footwear. Successful arthrodesis resolved the pain. CT imaging may help identify a treatable source of pain in this population.