bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroendocrine tumours found at endoscopy: diagnosis and staging
Authors: Khan Mohid S , Srirajaskanthan Raj , Frydman Aviva , Pritchard D Mark 
Published: September 2024

Due to their increasing incidence, neuroendocrine neoplasms (NENs) are being detected more frequently by endoscopists while they are performing diagnostic upper or lower gastrointestinal (GI) endoscopies. These procedures are usually performed for unrelated indications or for screening, with the tumours often being detected incidentally. The most common scenario is of an endoscopist being surprised by receiving a histology report of a well-differentiated neuroendocrine tumour (NET) after biopsying a small polyp that was initially thought to be benign. This article aims to provide some guidance about what to do next in that situation. All patients with NET should, however, be referred to a fully constituted NEN multidisciplinary team for definitive investigations and management.In general, the site, size and number of any possible NENs should be fully assessed during the initial endoscopy and representative endoscopic images should be captured. If the initial endoscopic assessment was inadequate, the procedure may need to be repeated. Possible NENs should be sampled using biopsy forceps. Endoscopic resection should only be attempted following histological confirmation of the diagnosis and tumour grade and after additional investigations have been performed to fully stage the tumour and determine its hormone production status. This is essential so that patients do not undergo either unnecessary or inadequate endoscopic resections.This article discusses the endoscopic features and subsequent assessment of NENs that arise in the stomach, duodenum, terminal ileum and rectum, as these are the common tumour sites within the GI tract.
Neuropsychiatric symptoms in cognitive decline and Alzheimer’s disease: biomarker discovery using plasma proteomics
Authors: Rabl Miriam , Clark Christopher , Dayon Loïc , Popp Julius 
Published: September 2024

Background and objectivesNeuropsychiatric symptoms (NPS) are common in older people with cognitive impairment and Alzheimer’s disease (AD). No biomarkers to detect the related pathology or predict the clinical evolution of NPS are available yet. This study aimed to identify plasma proteins that may serve as biomarkers for NPS and NPS-related clinical disease progression.MethodsA panel of 190 plasma proteins was quantified using Luminex xMAP in the Alzheimer’s Disease Neuroimaging Initiative cohort. NPS and cognitive performance were assessed at baseline and after 1 and 2 years. Logistic regression, receiver operating characteristic analysis and cross-validation were used to address the relations of interest.ResultsA total of 507 participants with mild cognitive impairment (n=396) or mild AD dementia (n=111) were considered. Selected plasma proteins improved the prediction of NPS (area under the curve (AUC) from 0.61 to 0.76, p<0.001) and future NPS (AUC from 0.63 to 0.80, p<0.001) when added to a reference model. Distinct protein panels were identified for single symptoms. Among the selected proteins, ANGT, CCL1 and IL3 were associated with NPS at all three time points while CCL1, serum glutamic oxaloacetic transaminase and complement factor H were also associated with cognitive decline. The associations were independent of the presence of cerebral AD pathology as assessed using cerebrospinal fluid biomarkers.ConclusionsPlasma proteins are associated with NPS and improve prediction of future NPS.
Germination responses of carob (Ceratonia siliqua L.) seeds to salinity and water stresses: implications for the restoration of Mediterranean marginal lands
Authors: Dadach Mohammed , Bhatt Arvind , Gairola Sanjay , Elnaggar Attiat , El-Keblawy Ali 
Published: September 2024

The iconic Mediterranean tree, Ceratonia siliqua L., holds substantial potential for restoring arid and semi-arid marginal lands. However, there is limited knowledge about the interaction of various abiotic factors and environmental stressors on seed germination of C. siliqua. Therefore, we examined the influence of salinity levels (0, 75, 150, 225 mmol/L) and water stress using (polyethylene glycol (PEG)6000) (−0.4, −0.8, −1.2 MPa) on C. siliqua seed germination under varying thermoperiods (15/25 and 25/35 °C) and photoperiods (12 h of light and complete darkness). Our findings indicate that higher temperatures (25/35 °C) significantly reduced germination of seeds compared to lower temperatures (15/25 °C). However, the photoperiods showed no significant impact, especially under minimal salinity stress and low osmotic potentials (75 mmol/L NaCl and −0.4 MPa PEG). In general, C. siliqua seeds exhibited enhanced performance in darkness at higher osmotic potentials, while increased stress prolonged the germination period. The dry weight of seedlings decreased with higher osmotic potential, although 75 mmol/L NaCl promoted seedling biomass production. Our results confirm C. siliqua resilience to high salinity and moderate drought, offering practical applications for its successful reintroduction and cultivation in challenging Mediterranean environmental conditions.
CircRREB1 Mediates Metabolic Reprogramming and Stemness Maintenance to Facilitate Pancreatic Ductal Adenocarcinoma Progression
Authors: Rong Zeyin , Xu Jin , Yang Jianhui , Wang Wei , Tang Rong , Zhang Zifeng , Tan Zhen , Meng Qingcai , Hua Jie , Liu Jiang , Zhang Bo , Liang Chen , Yu Xianjun , Shi Si 
Published: September 2024

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal tumor with limited treatment options and poor patient survival. Circular RNAs (circRNA) play crucial regulatory roles in the occurrence and development of various cancers, including PDAC. In this study, using circRNA sequencing of diverse PDAC samples, we identified circRREB1 as an oncogenic circRNA that is significantly upregulated in PDAC and is correlated with an unfavorable patient prognosis. Functionally, loss of circRREB1 markedly inhibited glycolysis and stemness, whereas elevated circRREB1 elicited the opposite effects. Mechanistically, circRREB1 interacted with PGK1, disrupting the association between PTEN and PGK1 and increasing PGK1 phosphorylation to activate glycolytic flux. Moreover, circRREB1 promoted WNT7B transcription by directly interacting with YBX1 and facilitating its nuclear translocation, consequently activating the Wnt/β-catenin signaling pathway to maintain PDAC stemness. Overall, these results highlight circRREB1 as a key regulator of metabolic and stemness properties of PDAC.
Significance: CircRREB1 stimulates PGK1 to induce glycolysis and activates the Wnt/β-catenin signaling pathway to maintain stemness in pancreatic cancer, indicating the potential of circRREB1 as a biomarker and therapeutic target.
Combined Autophagy Inhibition and Dendritic Cell Recruitment Induces Antitumor Immunity and Enhances Immune Checkpoint Blockade Sensitivity in Pancreatic Cancer
Authors: Oyama Koki , Nakata Kohei , Tsutsumi Chikanori , Hayashi Masataka , Zhang Bo , Mochida Yuki , Shinkawa Tomohiko , Hirotaka Kento , Zhong Pingshan , Date Satomi , Luo Haizhen , Kubo Akihiro , Higashijima Nobuhiro , Yamada Yutaka , Abe Toshiya , Ideno Noboru , Koikawa Kazuhiro , Iwamoto Chika , Ikenaga Naoki , Ohuchida Kenoki , Onishi Hideya , Morisaki Takashi , Kuba Keiji , Oda Yoshinao , Nakamura Masafumi 
Published: September 2024

Abstract
The effect of immune checkpoint inhibitors is extremely limited in patients with pancreatic ductal adenocarcinoma (PDAC) due to the suppressive tumor immune microenvironment. Autophagy, which has been shown to play a role in antitumor immunity, has been proposed as a therapeutic target for PDAC. In this study, single-cell RNA sequencing of autophagy-deficient murine PDAC tumors revealed that autophagy inhibition in cancer cells induced dendritic cell (DC) activation. Analysis of human PDAC tumors substantiated a negative correlation between autophagy and DC activation signatures. Mechanistically, autophagy inhibition increased the intracellular accumulation of tumor antigens, which could activate DCs. Administration of chloroquine, an autophagy inhibitor, in combination with Flt3 ligand–induced DC infiltration inhibited tumor growth and increased tumor-infiltrating T lymphocytes. However, autophagy inhibition in cancer cells also induced CD8+ T-cell exhaustion with high expression of immune checkpoint LAG3. A triple-therapy comprising chloroquine, Flt3 ligand, and an anti-LAG3 antibody markedly reduced tumor growth in orthotopic syngeneic PDAC mouse models. Thus, targeting autophagy in cancer cells and activating DCs sensitize PDAC tumors to immune checkpoint inhibitor therapy, warranting further development of this treatment approach to overcome immunosuppression in pancreatic cancer.
Significance: Inhibiting autophagy in pancreatic cancer cells enhances intracellular accumulation of tumor antigens to induce dendritic cell activation and synergizes with immunotherapy to markedly inhibit the growth of pancreatic ductal adenocarcinoma.
Update on Whole-Body MRI Surveillance for Pediatric Cancer Predisposition Syndromes
Authors: Greer Mary-Louise C. , States Lisa J. , Malkin David , Voss Stephan D. , Doria Andrea S. 
Published: September 2024

Abstract
Whole-body MRI (WBMRI) is an integral part of screening infants, children, and adolescents for presymptomatic neoplasms in certain cancer predisposition syndromes, which include Li–Fraumeni and constitutional mismatch repair deficiency syndromes, among others. The list of syndromes in which WBMRI adds value, as part of a comprehensive surveillance protocol, continues to evolve in response to new evidence, growing experience, and more widespread adoption. In July 2023, the AACR reconvened an international, multidisciplinary panel to revise and update recommendations stemming from the 2016 AACR Special Workshop on Childhood Cancer Predisposition. That initial meeting resulted in a series of publications in Clinical Cancer Research in 2017, including “Pediatric Cancer Predisposition Imaging: Focus on Whole-Body MRI.” This 2024 review of WBMRI in cancer predisposition syndrome updates the 2017 WBMRI publication, the revised recommendations derived from the 2023 AACR Childhood Cancer Predisposition Workshop based on available data, societal guidelines, and expert opinion. Different aspects of acquiring and interpreting WBMRI, including diagnostic accuracy, are discussed. The application of WBMRI in resource-poor environments, as well as integration of whole-body imaging techniques with emerging technologies, such as cell-free DNA (“liquid biopsies”) and artificial intelligence/machine learning, is also considered.
Abstract A076: LINE-1 ORF1p mimics viral innate immune evasion mechanisms in pancreatic cancer
Authors: You Eunae , Patel Bidish , Rojas Alexandra , Sun Siyu , Ho Natalie , Phillips Ildiko , Raabe Michael , Song Yuhui , Xu Katherine , Kocher Joshua , Richieri Peter , Taylor Martin , Nieman Linda , Greenbaum Benjamin , Ting David 
Published: September 2024

Abstract
Aberrant expression of repeat elements displaying viral mimicry is a common feature found in both mouse models and human pancreatic ductal adenocarcinoma (PDAC). However, cancer cells must employ mechanisms to manage this "viral" repeat element load to avoid triggering innate immune responses. Here, we demonstrate that the long interspersed nuclear element 1 (LINE-1) ORF1 protein (ORF1p) in PDAC cells plays a role in shielding repeat RNAs from activating pathogen recognition receptor (PRR)-mediated antiviral responses, independent of retrotransposition. Suppression of ORF1p using lentiviral shRNA induces innate immune responses through the PRRs, RIG-I and MAVS (double-stranded RNA sensors). Interestingly, PDAC cell lines with low ORF1p lack these two receptors, suggesting convergent mechanisms to suppress PRR signaling. Furthermore, RNA immunoprecipitation sequencing (RIP-seq) demonstrates ORF1p association with repeat RNA, including LINE and SINE elements that typically trigger antiviral responses. Subcellular localization of ORF1p in processing bodies (p-bodies) reveals specific interaction with MOV10, a dsRNA helicase crucial for antiviral responses. Loss of ORF1p results in significant growth reduction in vitro and in vivo, which supports ORF1p as a potential immune oncology therapeutic target. Altogether, our results demonstrate a novel function of ORF1p in shielding cytoplasmic repeat RNA from PRR sensing, shedding light on how PDAC cells evade host immune responses triggered by viral-like repeat RNA.
Citation Format: Eunae You, Bidish Patel, Alexandra Rojas, Siyu Sun, Natalie Ho, Ildiko Phillips, Michael Raabe, Yuhui Song, Katherine Xu, Joshua Kocher, Peter Richieri, Martin Taylor, Linda Nieman, Benjamin Greenbaum, David Ting. LINE-1 ORF1p mimics viral innate immune evasion mechanisms in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A076.
Impact of Nonalcoholic Hepatic Steatosis on the Warranty Period of a Coronary Artery Calcium Score of 0: Results From the Multi-Ethnic Study of Atherosclerosis
Authors: Ichikawa Keishi , Lim Jaewon , McClelland Robyn L. , Susarla Shriraj , Krishnan Srikanth , Benzing Travis , Kianoush Sina , Aldana-Bitar Jairo , Manubolu Venkat S. , Budoff Matthew J. 
Published: September 2024

BACKGROUND:
For individuals with a coronary artery calcium (CAC) score of 0, CAC rescans at appropriate timings are recommended, depending on individual risk profiles. Although nonalcoholic fatty liver disease, recently redefined as metabolic-associated fatty liver disease, is a risk factor for atherosclerotic cardiovascular disease events, its relationship with the warranty period of a CAC score of 0 has not been elucidated.

METHODS:
A total of 1944 subjects from the MESA (Multi-Ethnic Study of Atherosclerosis) with a baseline CAC score of 0, presence or absence of nonalcoholic hepatic steatosis, and at least 1 follow-up computed tomography scan were included. Nonalcoholic hepatic steatosis was defined using nonenhanced computed tomography and liver/spleen attenuation ratio <1. The association between nonalcoholic hepatic steatosis and new CAC incidence (CAC score >0) was evaluated using a Weibull survival model.

RESULTS:

Nonalcoholic hepatic steatosis was identified in 268 (14%) participants. Participants with nonalcoholic hepatic steatosis had higher CAC incidence than those without nonalcoholic hepatic steatosis. Nonalcoholic hepatic steatosis was independently associated with new CAC incidence after adjustment for atherosclerotic cardiovascular disease risk factors (hazard ratio, 1.28 [95% CI, 1.05–1.57];
P
=0.015). Using a 25% testing yield (25% of participants with zero CAC at baseline would be expected to have developed a CAC score >0), the warranty period of a CAC score of 0 in participants with nonalcoholic hepatic steatosis was shorter than in those without nonalcoholic hepatic steatosis (4.7 and 6.3 years). This association was consistent regardless of sex, race/ethnicity, age, and 10-year atherosclerotic cardiovascular disease risk.

CONCLUSIONS:
Nonalcoholic hepatic steatosis had an impact on the warranty period of a CAC score of 0. The study suggests that the time period until a CAC rescan should be shorter in those with nonalcoholic hepatic steatosis and a CAC score of 0.
Worldwide CTEPH Registry: Long-Term Outcomes With Pulmonary Endarterectomy, Balloon Pulmonary Angioplasty, and Medical Therapy
Authors: Delcroix Marion , Pepke-Zaba Joanna , D’Armini Andrea M. , Fadel Elie , Guth Stefan , Hoole Stephen P. , Jenkins David P. , Kiely David G. , Kim Nick H. , Madani Michael M. , Matsubara Hiromi , Nakayama Kazuhiko , Ogawa Aiko , Ota-Arakaki Jaquelina S. , Quarck Rozenn , Sadushi-Kolici Roela , Simonneau Gérald , Wiedenroth Christoph B. , Yildizeli Bedrettin , Mayer Eckhard , Lang Irene M. 
Published: September 2024

BACKGROUND:
The European Chronic Thromboembolic Pulmonary Hypertension (CTEPH) registry, conducted between 2007 and 2012, reported the major impact of pulmonary endarterectomy (PEA) on the long-term survival of patients with CTEPH. Since then, 2 additional treatments for inoperable CTEPH have become available: balloon pulmonary angioplasty (BPA), and an approved oral drug therapy with the guanylate cyclase stimulator riociguat. The current registry aimed to evaluate the effect of these new therapeutic approaches in a worldwide context.

METHODS:
Participation in this international global registry included 34 centers in 20 countries. Between February 2015 and September 2016, 1009 newly diagnosed, consecutive patients were included and followed until September 2019.

RESULTS:

Overall, 605 patients (60%) underwent PEA and 185 (18%) underwent BPA; 76% of the 219 remaining patients not receiving mechanical intervention (ie, neither PEA nor BPA) were treated with pulmonary hypertension drugs. Of patients undergoing PEA and BPA, 38% and 78% also received drugs for pulmonary hypertension, respectively. Median age at diagnosis was higher in the BPA and No PEA/BPA groups than in the PEA group: 66 and 69, respectively, versus 60 years. Pulmonary vascular resistance (PVR) was similar in all groups, with an average of 643 dynes.s.cm
−5
. During the observation period (>3 years; ≤5.6 years), death was reported in 7%, 11%, and 27% of patients treated by PEA and BPA, and those receiving no mechanical intervention (
P
<0.001). In Kaplan-Meier analysis, 3-year survival was 94%, 92%, and 71% in the 3 groups, respectively. PEA 3-year survival improved by 5% from that observed between 2007 and 2012. There was no survival difference in patients receiving vitamin K antagonists and non–vitamin K oral anticoagulants (
P
=0.756). In Cox regression, reduced mortality was associated with: PEA and BPA in the global cohort; history of venous thromboembolism and lower PVR in the PEA group; lower right atrial pressure in the BPA group; and use of pulmonary hypertension drugs, oxygen therapy, and lower right atrial pressure, as well as functional class in the group receiving no mechanical intervention.

CONCLUSIONS:
This second international CTEPH registry reveals important improvement in patient survival since the introduction of BPA and an approved drug for pulmonary hypertension. The type of anticoagulation regimen did not influence survival.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02656238.
Relating Rainfall Retrieval Parameters to Network and Environmental Features to Improve Rainfall Estimates from Commercial Microwave Links in the Tropics
Authors: Walraven Bas , Overeem Aart , Coenders-Gerrits Miriam , Hut Rolf , van der Valk Luuk , Uijlenhoet Remko 
Published: September 2024

Abstract
Potentially, the greatest benefit of commercial microwave links (CMLs) as opportunistic rainfall sensors lies in regions that lack dedicated rainfall sensors, most notably low- and middle-income countries. However, current CML rainfall retrieval algorithms are predominantly tuned and applied to (European) CML networks in temperate or Mediterranean climates. This study investigates whether local quantitative precipitation estimates from CMLs in a tropical region, specifically Sri Lanka, can be improved by optimizing two dominant parameters in the rainfall retrieval algorithm RAINLINK, namely, the wet antenna attenuation correction factor Aa and the relative contribution of minimum and maximum received signal levels α. Using a grid search, based on 10 months of CML data from 22 link–gauge clusters consisting of 105 sublinks that lie within 1 km of a daily rain gauge, the optimal values of Aa and α are first derived for the entire country and compared to the default RAINLINK values. Subsequently, the CMLs are grouped by link length, frequency, climate zone, and daily rainfall depth classes, and Aa and α are derived for each of these classes. Calibrating parameters on all clusters across the country only leads to minor improvements. The actual optimal Aa and α values depend on the performance metric favored. Calibrating on network properties, particularly short link length and high-frequency classes, does significantly improve rainfall estimates. By relating the optimal Aa and α values to known network metadata, the results from this study are potentially applicable to other tropical CML networks that lack nearby reference rainfall data.

Significance Statement
The purpose of this study is to improve rainfall estimates from commercial microwave links in Sri Lanka by optimizing two important rainfall retrieval algorithm parameters. Our results show that relating the optimal parameter values to operating frequency and pathlength improves rainfall estimates more than applying a single optimal parameter set to the entire network. By relating the optimal parameter values to readily known network properties, we aim to make these results applicable to other tropical countries, particularly low- and middle-income countries, that lack adequate reference rainfall data to calibrate rainfall estimates from commercial microwave links on.
The effect of an educational intervention on healthy lifestyle knowledge and behaviour among middle-aged women
Authors: Mohammadi Maryam , Mohammadnabizadeh Sahar , Mowlaei Leila , Ramezankhani Ali , Rakhshan Fatemeh , Soleimanzadeh Mahsa 
Published: September 2024

Objectives: This study aimed to assess the impact of an educational intervention on middle-aged women’s knowledge and behaviour regarding various aspects of a healthy lifestyle. Design: Quasi-experimental study involving 150 middle-aged women (divided into experimental and control groups). Setting: Participants were selected from health centres of Tehran, Iran. Method: Data collection included demographic information, knowledge of a healthy lifestyle and healthy lifestyle behaviour. Participants in both the intervention and control groups completed the questionnaires before and 2 months after the educational intervention. The intervention involved 10 minutes of face-to-face training followed by distribution of training booklets provided by the Ministry of Health in Iran. Statistical analyses were conducted using SPSS. Results: Within the intervention group, significant differences were observed in total healthy lifestyle knowledge and subscales for physical activity knowledge, anthropometry knowledge, healthy diet knowledge, and smoking knowledge, between the pre- and post-intervention periods. Other than for smoking behaviour, there was no significant difference in healthy behaviours pre- and post-intervention for the experimental and also the control group. Conclusion: While there was an increase in knowledge about healthy lifestyles following the intervention, this knowledge increase was not associated with a change in healthy lifestyle behaviours. Attention should therefore be given to other influences including socio-economic factors, mental health status, environmental factors, cultural influences, duration of the intervention and psychological factors if changes in healthy behaviour are to be achieved.