bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is there a preferred platinum and fluoropyrimidine regimen for advanced HER2-negative esophagogastric adenocarcinoma? Insights from 1293 patients in AGAMENON–SEOM registry
Authors: Arias-Martinez Aranzazu , Martínez de Castro Eva , Gallego Javier , Arrazubi Virginia , Custodio Ana , Fernández Montes Ana , Diez Marc , Hernandez Raquel , Limón María Luisa , Cano Juana María , Vidal-Tocino Rosario , Macias Ismael , Visa Laura , Martin Richard Marta , Sauri Tamara , Hierro Cinta , Gil Mireia , Cerda Paula , Martínez Moreno Elia , Martínez Lago Nieves , Mérida-García Antonio José , Gómez González Lucía , García Navalón Francisco Javier , Ruiz Martín Maribel , Marín Gema , López-López Flora , Ruperez Blanco Ana Belen , Fernández Alejandro Francisco , Jimenez-Fonseca Paula , Carmona-Bayonas Alberto , Alvarez-Manceñido Felipe 
Published: February 2024

Abstract
Background
The optimal chemotherapy backbone for HER2-negative advanced esophagogastric cancer, either in combination with targeted therapies or as a comparator in clinical trials, is uncertain. The subtle yet crucial differences in platinum-based regimens' safety and synergy with combination treatments need consideration.

Methods
We analyzed cases from the AGAMENON–SEOM Spanish registry of HER2-negative advanced esophagogastric adenocarcinoma treated with platinum and fluoropyrimidine from 2008 to 2021. This study focused exclusively on patients receiving one of the four regimens: FOLFOX (5-FU and oxaliplatin), CAPOX (capecitabine and oxaliplatin), CP (capecitabine and cisplatin) and FP (5-FU and cisplatin). The aim was to determine the most effective and tolerable platinum and fluoropyrimidine-based chemotherapy regimen and to identify any prognostic factors.

Results
Among 1293 patients, 36% received either FOLFOX (n = 468) or CAPOX (n = 466), 20% CP (n = 252), and 8% FP (n = 107). FOLFOX significantly increased PFS (progression free survival) compared to CP, with a hazard ratio of 0.73 (95% CI 0.58–0.92, p = 0.009). The duration of treatment was similar across all groups. Survival outcomes among regimens were similar, but analysis revealed worse ECOG–PS (Eastern Cooperative Oncology Group–Performance Status), > 2 metastatic sites, bone metastases, hypoalbuminemia, higher NLR (neutrophil-to-lymphocyte ratio), and CP regimen as predictors of poor PFS. Fatigue was common in all treatments, with the highest incidence in FOLFOX (77%), followed by FP (72%), CAPOX (68%), and CP (60%). Other notable toxicities included neuropathy (FOLFOX 69%, CAPOX 62%), neutropenia (FOLFOX 52%, FP 55%), hand–foot syndrome in CP (46%), and thromboembolic events (FP 12%, CP 11%).

Conclusions
FOLFOX shown better PFS than CP. Adverse effects varied: neuropathy was more common with oxaliplatin, while thromboembolism was more frequent with cisplatin.
Induzierbares CRISPR-Kill-System zur zelltypspezifischen Gewebeeliminierung
Authors: Gehrke Fabienne , Puchta Holger 
Published: February 2024

AbstractRecently, the repertoire of CRISPR/Cas-based techniques has been expanded with CRISPR-Kill, enabling tissue engineering through targeted genome elimination. Through SaCas9-mediated induction of multiple double-strand breaks in evolutionary conserved repetitive genomic regions, targeted cell death can be achieved. To exert temporal control over cell ablation, a chemically inducible system has been implemented in Arabidopsis thaliana, providing a valuable tool for the investigation of the developmental plasticity of specific cell types.
Männlicher Haarausfall – was uns unsere Gene verraten
Authors: Henne Sabrina K. , Nöthen Markus M. , Heilmann-Heimbach Stefanie 
Published: February 2024

AbstractUp to 80 % of European men experience some degree of male-pattern hair loss (MPHL) during their lifetime. The condition is highly heritable and current treatment options are limited, emphasizing the need for a better understanding of its biological causes. In recent years, molecular genetic studies have provided significant insights into the genetic and biological causes of MPHL. This article summarizes important findings and discusses their potential for improving hair loss prediction and treatment.
Wie RNA-Thermometer die Sekretion von Virulenzfaktoren kontrollieren
Authors: Javadi Soheila , Pienkoss Stephan , Narberhaus Franz 
Published: February 2024

AbstractPathogenic bacteria use outer membrane vesicles (OMVs) and highly adapted machineries like the type 3 secretion system (T3SS) to deliver virulence factors into host cells. The secretion of such effector proteins is tightly regulated. In the foodborne human pathogen Yersinia pseudotuberculosis, several thermo-responsive RNA elements, termed RNA thermometers, are strategically positioned at critical checkpoints of virulence regulation. They use a temperature-dependent, zipper-like mechanism to control translation initiation of genes for several T3SS components and an exotoxin.
Expression of FOXI1 and POU2F3 varies among different salivary gland neoplasms and is higher in Warthin tumor
Authors: Hoki Masahito , Yamada Yosuke , Hiratomo Emi , Hirata Masahiro , Takeuchi Yasuhide , Yoshimatsu Masayoshi , Kikuchi Masahiro , Kishimoto Yo , Marx Alexander , Haga Hironori 
Published: February 2024

Abstract
Purpose
Salivary gland tumors are histologically diverse. Ionocytes and tuft cells, rare epithelial cells found in normal salivary glands, might be associated with salivary tumors. Here, we explored the expression of FOXI1 and POU2F3, master regulators of ionocytes and tuft cells, respectively, for common salivary neoplasms using immunohistochemistry.

Methods
We analyzed normal salivary tissues and nine salivary gland tumors; Warthin tumors (WT), pleomorphic adenomas (PA), basal cell adenomas, and oncocytomas were benign, whereas mucoepidermoid, adenoid cystic, acinic cell, salivary duct carcinomas, and polymorphous adenocarcinomas were malignant.

Results
Normal salivary glands contained a few FOXI1- and POU2F3-positive cells in the ducts instead of the acini, consistent with ionocytes and tuft cells, respectively. Among the benign tumors, only WTs and PAs consistently expressed FOXI1 (10/10 and 9/10, respectively). The median H-score of WTs was significantly higher than that of PAs (17.5 vs. 4, P = 0.01). While WTs and PAs harbored POU2F3-positive cells (10/10 and 9/10, respectively), the median H-score was higher in WTs than in PAs (10.5 vs 4, respectively). Furthermore, WTs exhibited a unique staining pattern of FOXI1- and POU2F3-positive cells, which were present in luminal and abluminal locations, respectively. Whereas none of the malignant tumors expressed FOXI1, only adenoid cystic carcinoma consistently expressed POU2F3 (5/5), with a median H-score of 4.

Conclusion
The expression patterns of the characteristic transcription factors found in ionocytes and tuft cells vary among salivary gland tumor types and are higher in WT, which might be relevant for understanding and diagnosing salivary gland neoplasms.
Hybrid river stage forecasting based on machine learning with empirical mode decomposition
Authors: Heddam Salim , Vishwakarma Dinesh Kumar , Abed Salwan Ali , Sharma Pankaj , Al-Ansari Nadhir , Alataway Abed , Dewidar Ahmed Z. , Mattar Mohamed A. 
Published: February 2024

AbstractThe river stage is certainly an important indicator of how the water level fluctuates overtime. Continuous control of the water stage can help build an early warning indicator of floods along rivers and streams. Hence, forecasting river stages up to several days in advance is very important and constitutes a challenging task. Over the past few decades, the use of machine learning paradigm to investigate complex hydrological systems has gained significant importance, and forecasting river stage is one of the promising areas of investigations. Traditional in situ measurements, which are sometime restricted by the existing of several handicaps especially in terms of regular access to any points alongside the streams and rivers, can be overpassed by the use of modeling approaches. For more accurate forecasting of river stages, we suggest a new modeling framework based on machine learning. A hybrid forecasting approach was developed by combining machine learning techniques, namely random forest regression (RFR), bootstrap aggregating (Bagging), adaptive boosting (AdaBoost), and artificial neural network (ANN), with empirical mode decomposition (EMD) to provide a robust forecasting model. The singles models were first applied using only the river stage data without preprocessing, and in the following step, the data were decomposed into several intrinsic mode functions (IMF), which were then used as new input variables. According to the obtained results, the proposed models showed improved results compared to the standard RFR without EMD for which, the error performances metrics were drastically reduced, and the correlation index was increased remarkably and great changes in models’ performances have taken place. The RFR_EMD, Bagging_EMD, and AdaBoost_EMD were less accurate than the ANN_EMD model, which had higher R≈0.974, NSE≈0.949, RMSE≈0.330 and MAE≈0.175 values. While the RFR_EMD and the Bagging_EMD were relatively equal and exhibited the same accuracies higher than the AdaBoost_EMD, the superiority of the ANN_EMD was obvious. The proposed model shows the potential for combining signal decomposition with machine learning, which can serve as a basis for new insights into river stage forecasting.
Cardiovascular risk factors and carotid intima-media thickness with neurocognitive dysfunction in people living with HIV on stable combination anti-retroviral therapy
Authors: Nayak Unnathi , Dsouza Nikhil Victor , Rai P. V. Santosh , Achappa Basavaprabhu , Holla Ramesh , Murlimanju B. V. 
Published: February 2024

AbstractThe goal of this clinical research was to determine the relationship between carotid intima-media thickness (cIMT), cardiovascular risk factors, and neuro-cognitive function in people living with HIV (PLHIV) and were on stable combination anti-retroviral therapy (cART). This is a cross-sectional study performed at a single center, including 149 patients who visited the anti-retroviral therapy center of our tertiary care hospital. Among the PLHIV of our research, 62.4% had at least one associated cardiovascular risk factor, and 61.1% of them had abnormally high cIMT (≥ 0.9 mm on any one side, p = 0.035). These factors and being the male gender (p = 0.028) were associated with a greater Framingham 10-year risk percentage. Hypercholesterolemia was observed in 30.9% of the PLHIV and a higher body mass index (≥ 25 kg/m2) was found in 26.8% of them. The cognitive impairment was milder in 71.8% of cases and moderate in 9.4% of PLHIV. The Chi-square test revealed that a higher proportion of participants who had lower HDL-C levels (p = 0.045), smokers (p = 0.029), systolic blood pressure ≥ 140 mmHg (p = 0.012), and lower educational status (p = 0.017) had a poorer cognitive performance. In our sample population, a higher prevalence of elevated cIMT, cardiovascular risk factors, and mild and moderate cognitive deficiency was observed in PLHIV, who were on stable cART. However, routine assessment of the neuropsychological functions and management of modifiable risk factors are not performed in our patients. Further exploration of the relationship between cardiovascular risks, cIMT, and cognitive impairment in PLHIV is essential to formulate the guidelines and delay the onset of neurocognitive disorders in these patients.
Resveratrol-loaded invasome gel: A promising nanoformulation for treatment of skin cancer
Authors: Samir Bassant , El-Kamel Amal , Zahran Noha , Heikal Lamia 
Published: February 2024

AbstractSkin cancer is a widespread type of cancer representing 30% of all cancer types worldwide. Resveratrol (RSV) is an anticancer drug used for skin cancer treatment. Several limitations of RSV such as poor aqueous solubility, first-pass metabolism, and instability limit their topical use. The study aimed to develop and optimize RSV-loaded invasomes for topical administration as well as assess their efficacy in vivo. The optimized RSV-loaded invasomes showed small particle size (208.7 ± 74 nm), PDI (0.3 ± 0.03), high % entrapment efficiency (77.7 ± 6%), and negative zeta potential (−70.4 ± 10.9 mV). They showed an initial burst effect followed by controlled drug release for 24 h. RSV-loaded invasomal gel revealed the highest skin deposition percentage (65%) in ex vivo rat skin, the highest potency (low IC50 of 6.34 μg/mL), and the highest cellular uptake when tested on squamous cancerous cells (SCCs) when compared to other formulations. The antitumor effect of topical RSV-loaded invasomes was also evaluated in vivo in Ehrlich-induced mice models. The results revealed that RSV-loaded invasomal gel exhibited the smallest tumor volume with no signs of organ toxicity indicating its safety in skin cancer treatment. Upregulation of BAX and Caspase-3 gene levels and downregulation of NF-kB and BCL2 protein levels were demonstrated using RT-PCR and ELISA tests, respectively. Interestingly, the present study is the first to develop RSV-loaded invasomal gel for topical skin cancer treatment. According to our results, invasomes are considered promising lipid-based nanosystems for topical RSV delivery having high skin penetration ability and anticancer effect in the treatment of skin carcinoma.
Graphical Abstract
Long-term prognostic value of thyroid hormones in left ventricular noncompaction
Authors: Liu L. , Cai S. , Chen A. , Dong Y. , Zhou L. , Li L. , Zhang Z. , Hu Z. , Zhang Z. , Xiong Y. , Hu Z. , Li Y. , Lu M. , Wu L. , Zheng L. , Ding L. , Fan X. , Yao Y. 
Published: February 2024

Abstract
Purpose
Thyroid function is closely related to the prognosis of cardiovascular diseases. This study aimed to explore the predictive value of thyroid hormones for adverse cardiovascular outcomes in left ventricular noncompaction (LVNC).

Methods
This longitudinal cohort study enrolled 388 consecutive LVNC patients with complete thyroid function profiles and comprehensive cardiovascular assessment. Potential predictors for adverse outcomes were thoroughly evaluated.

Results
Over a median follow-up of 5.22 years, primary outcome (the combination of cardiovascular mortality and heart transplantation) occurred in 98 (25.3%) patients. For secondary outcomes, 75 (19.3%) patients died and 130 (33.5%) patients experienced major adverse cardiovascular events (MACE). Multivariable Cox analysis identified that free triiodothyronine (FT3) was independently associated with both primary (HR 0.455, 95%CI 0.313–0.664) and secondary (HR 0.547, 95%CI 0.349–0.858; HR 0.663, 95%CI 0.475–0.925) outcomes. Restricted cubic spline analysis illustrated that the risk for adverse outcomes increased significantly with the decline of serum FT3. The LVNC cohort was further stratified according to tertiles of FT3 levels. Individuals with lower FT3 levels in the tertile 1 group suffered from severe cardiac dysfunction and remodeling, resulting in higher incidence of mortality and MACE (Log-rank P < 0.001). Subgroup analysis revealed that lower concentration of FT3 was linked to worse prognosis, particularly for patients with left atrial diameter ≥ 40 mm or left ventricular ejection fraction ≤ 35%. Adding FT3 to the pre-existing risk score for MACE in LVNC improved its predictive performance.

Conclusion
Through the long-term investigation on a large LVNC cohort, we demonstrated that low FT3 level was an independent predictor for adverse cardiovascular outcomes.

Graphical Abstract
Explaining the﻿ non-adoption of blockchain technology in global value chains: a micro-foundational perspective
Authors: Hubenova Tsvetelina , Lindeque Johan P. , Peter Marc K. 
Published: February 2024

AbstractThe business potential of blockchain technology in global value chains (GVCs) includes the creation of permanent records of information, to facilitate specifications regulation, to mitigate risk using smart contracts and through full, transparent transaction traceability at reduced costs. Blockchain as a general-purpose technology (GPT) thus has the potential to increase the effectiveness and efficiency of value creation for firm specific advantages owned and/or controlled by multinational enterprises (MNE), yet adoption of blockchain is uneven. This study adopts a micro-foundational lens to explain the non-adoption of blockchain technology in multinational enterprises’ (MNE) global value chains (GVC), emphasizing the influence of the technology, organization and environment (TOE) influences on the technology acceptance (TAM) for blockchain, due to the impact on managers’ perception of blockchain's usefulness and ease of use. The empirical results are based on a multiple-case study research design, that collected interview data from supply chain managers in small, medium, and large-sized manufacturing MNEs that participate in global value chains that differ in their governance patterns. The results identified fifteen different drivers of the non-adoption of blockchain technology across the technological, organizational and external environments of the MNE. The results of the study allow a parsimonious model of blockchain technology non-adoption that is aligned with the digital technology adoption literature using a TOE–TAM approach.
Integrating Multiscale Geospatial Analysis for Monitoring Crop Growth, Nutrient Distribution, and Hydrological Dynamics in Large-Scale Agricultural Systems
Authors: Akanbi Olatunde D. , Bhuvanagiri Deepa C. , Barcelos Erika I. , Nihar Arafath , Gonzalez Hernandez Brian , Yarus Jeffrey M. , French Roger H. 
Published: February 2024

AbstractMonitoring crop growth, soil conditions, and hydrological dynamics are imperative for sustainable agriculture and reduced environmental impacts. This interdisciplinary study integrates remote sensing, digital soil mapping, and hydrological data to elucidate intricate connections between these factors in the state of Ohio, USA. Advanced spatiotemporal analysis techniques were applied to key datasets, including the MODIS sensor satellite imagery, USDA crop data, soil datasets, Aster GDEM, and USGS stream gauge measurements. Vegetation indices derived from MODIS characterized crop-specific phenology and productivity patterns. Exploratory spatial data analysis show relationships of vegetation dynamics and soil properties, uncovering links between plant vigor, edaphic fertility, and nutrient distributions. Correlation analysis quantified these relationships and their seasonal evolution. Examination of stream gauge data revealed insights into spatiotemporal relationships of nutrient pollution and stream discharge. By synthesizing diverse geospatial data through cutting-edge data analytics, this work illuminated complex interactions between crop health, soil nutrients, and water quality in Ohio. The methodology and findings provide actionable perspectives to inform sustainable agricultural management and environmental policy. This study demonstrates the significant potential of open geospatial resources when integrated using a robust spatiotemporal framework. Integrating additional measurements and high-resolution data sources through advanced analytics and interactive visualizations could strengthen these insights.
Dispersive Wave Focusing on a Shear Current: Part 1—Linear Approximations
Authors: Ellingsen Simen Å. , Zheng Zibo , Abid Malek , Kharif Christian , Li Yan 
Published: February 2024

AbstractWe consider the evolution and kinematics during dispersive focussing, for a group of waves propagating atop currents varying with depth. Our analysis assumes long-crested linear waves propagating at arbitrary angles relative to the current. Although low steepness is assumed, the linear model is often a reasonable approximation for understanding rogue waves. A number of analytical approximate relations are derived assuming different sub-surface current profiles, including linearly varying current, exponentially varying current, and currents of arbitrary depth profile which are weakly sheared following the approximation of Stewart and Joy (Deep Sea Res. Abs. 21, 1974). The orbital velocities are likewise studied. While shear currents have modest influence on the motion of the envelope of the wave group, they significantly change wave kinematics. Horizontal orbital velocities are either amplified or suppressed depending on whether the shear is opposing or following, respectively. To illustrate these phenomena we consider a real-world example using velocity profiles and wave spectra measured in the Columbia River estuary. Near the surface at the point where focusing occurs, horizontal orbital velocities are, respectively, increased and decreased by factors of 1.4 and 0.7 for focusing groups propagating on following and opposing shear (respectively, upstream and downstream in the earth-fixed reference system). The implications for the forces a focusing wave group can exert on vessels and installations are profound, emphasising the importance of considering current profiles in maritime operations.
Exploring the Experiences of NEET-Situated Young People Within the Context of the COVID-19 Pandemic Using Resonance Theory
Authors: Norvell Gustavsson Isa , Jonsson Frida 
Published: February 2024

AbstractThis study explores the experiences of young people who are not in education, employment, or training (NEET) within the context of the COVID-19 pandemic in Sweden, using resonance theory as an analytical lens. It contributes knowledge about the importance of school and work (or lack thereof) for these youths during a time of uncertainty and gives insight into their quality of life and well-being from a social and relational perspective. The findings shed light on how the COVID-19 pandemic aggravated an already strained situation for this group while highlighting the importance of relationships, not only with friends and family, but with society as a whole. Adopting a non-materialistic approach to NEET situated young people’s quality of life and well-being allowed resonant experiences to become evident in various aspects of their lives, which may be overlooked if the norms of an educationally underpinned work-centrism are in focus. The study calls for a broadened view on what constitutes or characterizes a good life for young people at the margins of the labor market and education system, while emphasizing the need to move beyond narrow concerns about integration into education or employment, towards focusing on their well-being.