bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-treatment peripheral blood immunophenotyping and response to neoadjuvant chemotherapy in operable breast cancer
Authors: Leon-Ferre Roberto A. , Whitaker Kaitlyn R. , Suman Vera J. , Hoskin Tanya , Giridhar Karthik V. , Moore Raymond M. , Al-Jarrad Ahmad , McLaughlin Sarah A. , Northfelt Donald W. , Hunt Katie N. , Conners Amy Lynn , Moyer Ann , Carter Jodi M. , Kalari Krishna , Weinshilboum Richard , Wang Liewei , Ingle James N. , Knutson Keith L. , Ansell Stephen M. , Boughey Judy C. , Goetz Matthew P. , Villasboas Jose C. 
Published: June 2024

Abstract
Background
Tumor immune infiltration and peripheral blood immune signatures have prognostic and predictive value in breast cancer. Whether distinct peripheral blood immune phenotypes are associated with response to neoadjuvant chemotherapy (NAC) remains understudied.

Methods
Peripheral blood mononuclear cells from 126 breast cancer patients enrolled in a prospective clinical trial (NCT02022202) were analyzed using Cytometry by time-of-flight with a panel of 29 immune cell surface protein markers. Kruskal–Wallis tests or Wilcoxon rank-sum tests were used to evaluate differences in immune cell subpopulations according to breast cancer subtype and response to NAC.

Results
There were 122 evaluable samples: 47 (38.5%) from patients with hormone receptor-positive, 39 (32%) triple-negative (TNBC), and 36 (29.5%) HER2-positive breast cancer. The relative abundances of pre-treatment peripheral blood T, B, myeloid, NK, and unclassified cells did not differ according to breast cancer subtype. In TNBC, higher pre-treatment myeloid cells were associated with lower pathologic complete response (pCR) rates. In hormone receptor-positive breast cancer, lower pre-treatment CD8 + naïve and CD4 + effector memory cells re-expressing CD45RA (TEMRA) T cells were associated with more extensive residual disease after NAC. In HER2 + breast cancer, the peripheral blood immune phenotype did not differ according to NAC response.

Conclusions
Pre-treatment peripheral blood immune cell populations (myeloid in TNBC; CD8 + naïve T cells and CD4 + TEMRA cells in luminal breast cancer) were associated with response to NAC in early-stage TNBC and hormone receptor-positive breast cancers, but not in HER2 + breast cancer.

Trial registration
NCT02022202. Registered 20 December 2013.
CelFiE-ISH: a probabilistic model for multi-cell type deconvolution from single-molecule DNA methylation haplotypes
Authors: Unterman Irene , Avrahami Dana , Katsman Efrat , Triche Timothy J. , Glaser Benjamin , Berman Benjamin P. 
Published: June 2024

AbstractDeconvolution methods infer quantitative cell type estimates from bulk measurement of mixed samples including blood and tissue. DNA methylation sequencing measures multiple CpGs per read, but few existing deconvolution methods leverage this within-read information. We develop CelFiE-ISH, which extends an existing method (CelFiE) to use within-read haplotype information. CelFiE-ISH outperforms CelFiE and other existing methods, achieving 30% better accuracy and more sensitive detection of rare cell types. We also demonstrate the importance of marker selection and of tailoring markers for haplotype-aware methods. While here we use gold-standard short-read sequencing data, haplotype-aware methods will be well-suited for long-read sequencing.
Prediction models for amputation after diabetic foot: systematic review and critical appraisal
Authors: Huang Jingying , Yang Jin , Qi Haiou , Xu Miaomiao , Xu Xin , Zhu Yiting 
Published: June 2024

Abstract
Background
Numerous studies have developed or validated prediction models aimed at estimating the likelihood of amputation in diabetic foot (DF) patients. However, the quality and applicability of these models in clinical practice and future research remain uncertain. This study conducts a systematic review and assessment of the risk of bias and applicability of amputation prediction models among individuals with DF.

Methods
A comprehensive search was conducted across multiple databases, including PubMed, Web of Science, EBSCO CINAHL Plus, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Biomedical Literature Database (CBM), and Weipu (VIP) from their inception to December 24, 2023. Two investigators independently screened the literature and extracted data using the checklist for critical appraisal and data extraction for systematic reviews of prediction modeling studies. The Prediction Model Risk of Bias Assessment Tool (PROBAST) checklist was employed to evaluate both the risk of bias and applicability.

Results
A total of 20 studies were included in this analysis, comprising 17 development studies and three validation studies, encompassing 20 prediction models and 11 classification systems. The incidence of amputation in patients with DF ranged from 5.9 to 58.5%. Machine learning-based methods were employed in more than half of the studies. The reported area under the curve (AUC) varied from 0.560 to 0.939. Independent predictors consistently identified by multivariate models included age, gender, HbA1c, hemoglobin, white blood cell count, low-density lipoprotein cholesterol, diabetes duration, and Wagner’s Classification. All studies were found to exhibit a high risk of bias, primarily attributed to inadequate handling of outcome events and missing data, lack of model performance assessment, and overfitting.

Conclusions
The assessment using PROBAST revealed a notable risk of bias in the existing prediction models for amputation in patients with DF. It is imperative for future studies to concentrate on enhancing the robustness of current prediction models or constructing new models with stringent methodologies.
Understanding stakeholder attitudes towards low-head pumped hydro storage technology
Authors: Ansorena Ruiz Ruben , Schürenkamp David , Bricker Jeremy D. , Olvermann Madita , Goseberg Nils 
Published: June 2024

Abstract
Background
The share of renewable energy feeding the European grid has been growing over the years, even though the intermittency of some renewable energy sources can induce electric grid instability. Energy storage has proven to be an effective way of reducing grid instability. Various solutions for large-scale energy storage are being researched nowadays. This study focusses on the innovative low-head pumped hydro storage (LH PHS) technology, a large-scale energy storage scheme suitable for shallow seas (5 – 30 m depth). Implementation of renewable energy technologies, such as wind farms in Europe, Asia and North America, has faced public opposition which has delayed or even cancelled the implementation of renewable energy projects. Literature about public perception of projects highlights the importance of involving stakeholders from the early stages of project planning. Considering this, the present study aims to collect stakeholder opinions (via an online survey) to determine what is necessary for a smooth implementation of LH PHS in the North Sea, both from technical and policy points of view.

Results
Stakeholders from commercial parties, government authorities and local groups recognized the potential of LH PHS as a means to increase the share of renewable energies within the European power grid. Economics, bureaucratic burden, and structural safety have emerged as primary aspects of concern respecting the implementation of LH PHS. The impression of the respondents is that a low-head pumped hydro station would not have negative effects on their organizations. Furthermore, most of the engineering firms participating in the study communicated that their knowledge and resources could be involved in the construction of such an energy storage facility.

Conclusion
As identified stakeholder concerns such as economics and structural safety are currently being researched, effective communication of the findings of this research is paramount to keep stakeholders informed of the ongoing progress. Two-way communication between researchers and stakeholders is recommended to enhance public acceptance of future technologies. Furthermore, is it advisable to undertake an examination of the available energy policies relevant to LH PHS.
A comprehensive exploration of astrocytes in migraine: a bibliometric and visual analysis
Authors: Wei Shijie , Du Tianqi , Zhang Lili , Li Xuhao , Wang Zhe , Ning Yike , Tang Yu , Wu Xinyu , Han Jing 
Published: June 2024

Abstract
Background
Migraine, as a prevalent neurologic disorder, involves intricate and yet incompletely elucidated pathophysiological mechanisms. A plethora of research findings underscores the pivotal role played by astrocytes in the progression of migraines. In order to elucidate the current advances and directions in research pertaining to astrocytes in migraines, we conducted bibliometric analysis of relevant literature and visualized the results. Subsequently, we expound upon these findings to contribute to the evolving understanding of the role of astrocytes in migraine pathophysiology.

Methods
On November 21, 2023, we conducted a search on Web of Science (WOS), restricting the document type to articles or reviews and language to English. Following a meticulous selection process involving three researchers, we identified the literature to be included in our analysis. Subsequently, we employed Microsoft Office Excel programs, R, VOSviewer, Scimago Graphica, and CiteSpace software to conduct visualization analysis of basic information and trends regarding journals, countries/regions, and influential authors, institutions, keywords, and papers.

Results
As of November 21, 2023, relevant literature has been published in 71 journals across 27 countries/regions. This corpus comprises contributions from 576 authors affiliated with 220 institutions, encompassing 865 keywords and referencing 6065 scholarly articles. CEPHALALGIA stands out as the most influential journal in this field, while authors PIETROBON D and DALKARA T have significant impact. The United States is highly influential, with CNR and UNIV PADUA emerging as highly influential institutions. The predominant category is Neurosciences.

Conclusions
Future investigators may continue to focus on migraines with aura, familial hemiplegic migraine (FHM), and the crucial calcitonin gene-related peptide (CGRP) system. Employing advanced observational techniques, such as imaging, researchers should pay attention to cellular and tissue structures, such as microglia and the trigeminal ganglion, as well as mechanisms involving inflammation and central sensitization. Moreover, animal models are paramount in obtaining high-quality evidence.
How to treat mixed behavior segments in supervised machine learning of behavioural modes from inertial measurement data
Authors: Resheff Yehezkel S. , Bensch Hanna M. , Zöttl Markus , Harel Roi , Matsumoto-Oda Akiko , Crofoot Margaret C. , Gomez Sara , Börger Luca , Rotics Shay 
Published: June 2024

AbstractThe application of supervised machine learning methods to identify behavioural modes from inertial measurements of bio-loggers has become a standard tool in behavioural ecology. Several design choices can affect the accuracy of identifying the behavioural modes. One such choice is the inclusion or exclusion of segments consisting of more than a single behaviour (mixed segments) in the machine learning model training data. Currently, the common practice is to ignore such segments during model training. In this paper we tested the hypothesis that including mixed segments in model training will improve accuracy, as the model would perform better in identifying them in the test data. We test this hypothesis using a series of data simulations on four datasets of accelerometer data coupled with behaviour observations, obtained from four study species (Damaraland mole-rats, meerkats, olive baboons, polar bears). Results show that when a substantial proportion of the test data are mixed behaviour segments (above ~ 10%), including mixed segments in machine learning model training improves the accuracy of classification. These results were consistent across the four study species, and robust to changes in segment length, sample size, and degree of mixture within the mixed segments. However, we also find that in some cases (particularly in baboons) models trained with mixed segments show reduced accuracy in classifying test data containing only single behaviour (pure) segments, compared to models trained without mixed segments. Based on these results, we recommend that when the classification model is expected to deal with a substantial proportion of mixed behaviour segments (> 10%), it is beneficial to include them in model training, otherwise, it is unnecessary but also not harmful. The exception is when there is a basis to assume that the training data contains a higher rate of mixed segments than the actual (unobserved) data to be classified—such a situation may occur particularly when training data are collected in captivity and used to classify data from the wild. In this case, excess inclusion of mixed segments in training data should probably be avoided.
Stand diversity increases pine resistance and resilience to compound disturbance
Authors: Germain Sara J. , Lutz James A. 
Published: June 2024

Abstract
Background
Drought, fire, and insects are increasing mortality of pine species throughout the northern temperate zone as climate change progresses. Tree survival may be enhanced by forest diversity, with growth rates often higher in mixed stands, but whether tree defenses are likewise aided remains in question. We tested how forest diversity-productivity patterns relate to growth and defense over three centuries of climate change, competition, wildfire, and bark beetle attack. We used detailed census data from a fully mapped 25.6-ha forest dynamics plot in California, USA to conduct a spatially explicit, dendroecological assessment of large-diameter Pinus lambertiana survival following fire reintroduction. Our structural equation models investigated direct and indirect pathways by which growth, defense, and forest composition together mediated pine resistance and resilience.

Results
In the historical era of frequent, mixed-severity fire (pre-1900), trees that were ultimately resistant or susceptible to the post-fire bark beetle epidemic all showed similar growth and defenses, as measured by axial resin duct traits. During the era of fire exclusion (1901–2012), however, susceptible trees had slower growth. Following fire re-entry in 2013, both growth and defense declined precipitously for susceptible trees, resulting in fatal bark beetle attack. Spatial analysis showed that monodominant crowding by shade-tolerant competitors contributed to the long-term stress that prevented susceptible trees from recuperating defenses quickly following fire re-entry. For beetle-resistant trees, however, we found positive feedbacks between diversity, growth, and survival: trees in species-rich communities had higher growth rates pre-fire, which promoted a rapid recuperation of defenses following fire that helped trees resist bark beetle attack. Overall, this associational resistance outweighed associational susceptibility (+8.6% vs. −6.4% change in individual tree survival odds), suggesting a relaxation effect that ultimately allowed 58% of large pines to survive.

Conclusions
Though climate change threatens forest biodiversity, biodiversity is key to forest climate adaptation in return. Our findings demonstrate centennial-scale feedbacks by which forest diversity increases pine resistance and resilience to climate-amplified disturbances. The spatially explicit, dendroecological framework provides new insights into diversity-productivity theory, while also informing climate-adaptive forest management by identifying thresholds of tree density and richness that maximize large pine survival.
Silencing circ-RNA-049637 influences hydatid outer cyst wall formation by liver fibrosis
Authors: Kalifu Baheti , Meng Yuan , Ma Zhi-Gang , Ma Chao , Tian Guang-Lei , Wang Jin-Guo , Chen Xiong 
Published: June 2024

Abstract
Introduction and objectives
In diseases characterized by fibrosis, hepatic stellate cells (HSCs) are mesenchymal cells that play an important role in liver fibrosis. circRNAs are involved in regulating hydatid exocyst formation through miRNA sponge adsorption. The mechanisms of hepatic cystic hydatid outer cyst formation, HSC, and liver fibrosis are unclear.

Materials and methods
Based on our sequencing data, we validated the mechanism by which circRNA-049637 regulated hepatic cystic hydatid growth and promoted outer fibrocystic wall formation.

Results
Our results revealed that circRNA_049637 silencing promoted the proliferation of LX-2 human HSCs, affected the cell cycle, and increased the mRNA and protein expression levels of liver fibrosis-related indicators such as α-SMA, COL1A1, COL3A1, and TGFβRII.

Conclusions
CircRNA_049637 may induce the formation of hepatic hydatid cysts by promoting hepatic fibrosis via HSC activation.
The new neural pressure support (NPS) mode and the helmet: did we find the dynamic duo?
Authors: Costa Alessandro , Merlo Federico , Pagni Aline , Navalesi Paolo , Grasselli Giacomo , Cammarota Gianmaria , Colombo Davide 
Published: June 2024

AbstractBackgroundNoninvasive ventilation (NIV) is commonly used in clinical practice to reduce intubation times and enhance patient comfort. However, patient-ventilator interaction (PVI) during NIV, particularly with helmet interfaces, can be challenging due to factors such as dead space and compliance. Neurally adjusted ventilatory assist (NAVA) has shown promise in improving PVI during helmet NIV, but limitations remain. A new mode, neural pressure support (NPS), aims to address these limitations by providing synchronized and steep pressurization. This study aims to assess whether NPS per se improves PVI during helmet NIV compared to standard pressure support ventilation (PSV).MethodsThe study included adult patients requiring NIV with a helmet. Patients were randomized into two arms: one starting with NPS and the other with PSV; the initial ventilatory parameters were always set as established by the clinician on duty. Physiological parameters and arterial blood gas analysis were collected during ventilation trials. Expert adjustments to initial ventilator settings were recorded to investigate the impact of the expertise of the clinician as confounding variable. Primary aim was the synchrony time (Timesync), i.e., the time during which both the ventilator and the patient (based on the neural signal) are on the inspiratory phase. As secondary aim neural-ventilatory time index (NVTI) was also calculated as Timesyncdivided to the total neural inspiratory time, i.e., the ratio of the neural inspiratory time occupied by Timesync.ResultsTwenty-four patients were enrolled, with no study interruptions due to safety concerns. NPS demonstrated significantly longer Timesync(0.64 ± 0.03 s vs. 0.37 ± 0.03 s,p < 0.001) and shorter inspiratory delay (0.15 ± 0.01 s vs. 0.35 ± 0.01 s,p < 0.001) compared to PSV. NPS also showed better NVTI(78 ± 2% vs. 45 ± 2%,p < 0.001). Ventilator parameters were not significantly different between NPS and PSV, except for minor adjustments by the expert clinician.ConclusionsNPS improves PVI during helmet NIV, as evidenced by longer Timesyncand better coupling compared to PSV. Expert adjustments to ventilator settings had minimal impact on PVI. These findings support the use of NPS in enhancing patient-ventilator synchronization and warrant further investigation into its clinical outcomes and applicability across different patient populations and interfaces.Trial registrationThis study was registered onwww.clinicaltrials.govNCT06004206 Registry URL:https://clinicaltrials.gov/study/NCT06004206on September 08, 2023.
Phase III randomized trial of intensity-modulated proton therapy (IMPT) versus intensity-modulated photon therapy (IMRT) for the treatment of head and neck oropharyngeal carcinoma (OPC).
Authors: Frank Steven J. , Busse Paul , Rosenthal David Ira , Hernandez Mike , Swanson David Michael , Garden Adam S. , Sturgis Erich M. , Ferrarotto Renata , Gunn Gary Brandon , Patel Samir H , LEE NANCY Y. , Lin Alexander , Snider James W , McDonald Mark William , Henson Christina , Bajaj Gopal Krishna , Kalman Noah , Parvathaneni Upendra , Katz Sanford R. , Foote Robert Leonard ,   MD Anderson Clinical Trial Consortium
Published: June 2024

6006 Background: IMPT has unique biologic and physical properties compared with IMRT, limits radiation dose beyond the targeted tumor volumes, and is a novel de-intensification strategy for the management of head and neck tumors. This study was designed to compare the outcomes for patients with OPC after chemoradiation therapy (CRT) with IMRT vs IMPT. Methods: This is a multi-center, randomized, phase III non-inferiority OPC trial Stage III/IV (AJCC 7th) squamous cell carcinoma stratified patients by human papillomavirus status, smoking status, and receipt of induction chemotherapy (IC). The primary endpoint was the rate of progression-free survival (PFS) rate at 3 years, where progression was defined as disease recurrence or death. Under the null hypothesis, H0: r ≥ 1.535 established the margin for non-inferiority of IMPT. Secondary endpoints include overall survival (OS), treatment-related malnutrition, and gastrostomy-tube dependence. Analyses were conducted on intent-to-treat (ITT; n=440), per-protocol (PP; n=296), and as-treated (AT; n=397) populations. Results: Patients (n=440) were randomized to undergo IMRT(n=219) or IMPT (n=221) at 21 institutions. The median age was 61 years and HPV/p16 was positive in 95%. IC was the initial treatment in 13% of patients. All patients were treated with CRT to 70 Gy in 33 fx with bilateral neck treatment, and post-CRT surgical lymph node dissection occurred in 8%. The median follow-up was 3.14 years. In the ITT analysis, the hazard ratio (HR) for disease progression or death at 3 y was 0.87 (95%CI 0.56,1.35); p=0.006 and the corresponding HR for death (OS) was 0.63 (95%CI 0.36-1.10) suggesting a protective affect with IMPT. In PP analysis, the PFS HR was 0.85 (95%CI 0.52,1.38); p=0.009 and HR for death (OS) was 0.60 (95%CI 0.32-1.12). In the AT analysis, PFS HR was 0.88 (95%CI 0.56,1.37); p=0.007 and the corresponding HR for death (OS) was 0.70 (95%CI 0.40-1.22). For each analysis above, the null hypothesis was rejected and IMPT was non-inferior to IMRT. PP gastrostomy-tube dependence decreased with IMPT vs. IMRT from 42% to 28% (p=0.019), and more IMPT patients sustained their nutrition with end of treatment weight loss < 5% from baseline: 24% vs 14% (p=0.037). Conclusions: IMPT is non-inferior to IMRT and has emerged as a standard of care CRT approach for OPC that reduces malnutrition and gastrostomy-tube dependence. Clinical trial information: NCT01893307 .