bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phospholipase C‐ε defines a PACAP‐stimulated pathway for secretion in the chromaffin cell
Authors: Chen Xiaohuan , Coffman Breanna L. , Brindley Rebecca L. , Galpin Jason D. , Ahern Christopher A. , Currie Kevin P. M. , Smrcka Alan V. , Axelrod Daniel , Anantharam Arun 
Published: March 2023

AbstractAdrenomedullary chromaffin cells respond to splanchnic (sympathetic) nerve stimulation by releasing stress hormones into the circulation. The signal for hormone secretion is encoded in the neurotransmitters – especially acetylcholine (ACh) and pituitary adenylate cyclase activating polypeptide (PACAP) – that are released into the splanchnic‐chromaffin cell synapse. However, functional differences in the effects of ACh and PACAP on the chromaffin cell secretory response are not well defined. Here, selective agonists of PACAP receptors or nicotinic and muscarinic acetylcholine receptors were applied to chromaffin cells. The major differences in the effects of these agents were not on exocytosis, per se, but rather on the steps upstream of exocytosis. In almost every respect, the properties of individual fusion events triggered by PACAP and cholinergic agonists were similar. On the other hand, the properties of the Ca2+ transients evoked by PACAP differed in several ways from those evoked by muscarinic and nicotinic receptor stimulation. A defining feature of the PACAP‐stimulated secretory pathway was its dependence on signaling through exchange protein directly activated by cAMP (Epac) and PLCε. However, the absence of PLCε did not disrupt Ca2+ transients evoked by cholinergic agonists. Accordingly, inhibition of Epac activity did not disrupt secretion triggered by acetylcholine or specific agonists of muscarinic and nicotinic receptors. Thus, PACAP and acetylcholine stimulate chromaffin cell secretion via separate and independent pathways. This feature of stimulus‐secretion coupling may be important for sustaining hormone release from the adrenal medulla under conditions associated with the sympathetic stress response.
Impact of KRAS and BRAF mutations on treatment efficacy and survival in high‐grade gastroenteropancreatic neuroendocrine neoplasms
Authors: Elvebakken Hege , Hjortland Geir Olav , Garresori Herish , Andresen Per Arne , Janssen Emiel A. M. , Vintermyr Olav Karsten , Lothe Inger M. B. , Sorbye Halfdan 
Published: March 2023

AbstractHigh‐grade gastroenteropancreatic neuroendocrine neoplasms (HG GEP‐NEN) typically disseminate early. Treatment of metastatic disease has limited benefit and prognosis is generally discouraging. Data on the clinical impact of mutations in HG GEP‐NEN are scarce. There is an unmet need for reliable biomarkers to predict treatment outcome and prognosis in metastatic HG GEP‐NEN. Patients with metastatic HG GEP‐NEN diagnosed at three centres were selected for KRAS‐, BRAF mutation and microsatellite instability (MSI) analyses. Results were linked to treatment outcome and overall survival. After pathological re‐evaluation, 83 patients met inclusion criteria: 77 (93%) GEP neuroendocrine carcinomas (NEC) and six (7%) GEP neuroendocrine tumours (NET) G3. NEC harboured higher frequency of mutations than NET G3. Colon NEC harboured a particular high frequency of BRAF mutations (63%). Immediate disease progression on first‐line chemotherapy was significantly higher for NEC with BRAF mutation (73%) versus wild‐type (27%) (p = .016) and for colonic primary (65%) versus other NEC (28%) (p = .011). Colon NEC had a significant shorter PFS compared to other primary sites, a finding independent of BRAF status. Immediate disease progression was particularly frequent for BRAF mutated colon NEC (OR 10.2, p = .007). Surprisingly, BRAF mutation did not influence overall survival. KRAS mutation was associated with inferior overall survival for the whole NEC population (HR 2.02, p = .015), but not for those given first‐line chemotherapy. All long‐term survivors (>24 m) were double wild‐type. Three NEC cases (4.8%) were MSI. Colon NEC with BRAF mutation predicted immediate disease progression on first‐line chemotherapy, but did not affect PFS or OS. Benefit of first‐line platinum/etoposide treatment seems limited for colon NEC, especially for BRAF mutated cases. KRAS mutations did not influence treatment efficacy nor survival for patients receiving first‐line chemotherapy. Both frequency and clinical impact of KRAS/BRAF mutations in digestive NEC differ from prior results on digestive adenocarcinoma.
Nurse‐led clinical activity in kidney transplantation care in Spain: A cross‐sectional observational study
Authors: Pedreira‐Robles Guillermo , Garcimartín Paloma , Sevilla‐Guerra Sonia , Bach‐Pascual Anna , García‐Martínez Marta , Morín‐Fraile Victoria 
Published: March 2023

AbstractObjectivesTo explore the presence of specialist outpatient nursing activity in care for kidney transplant recipients in Spain and to determine the level of competence development of this activity according to the Advanced Practice Nurse model.DesignDescriptive, cross‐sectional study.Participants and MeasurementsAll outpatient nurses specialising in renal transplantation in the 39 transplant hospitals in Spain were included. To fulfil the study objectives, an ad hoc questionnaire and the ‘Advanced Practice Nurse Role Definition Instrument (IDREPA)’ were administered to assess the nurses' level of competence development.ResultsOf the facilities included in the study, 25 (64.1%) had posttransplant nursing activity, 13 (33.3%) had pretransplant nursing activity and 11 (28.2%) had nursing activity involving kidney donor candidates. Twenty‐seven specialist nurse's offices were identified. The results of the IDREPA reflect the presence of advanced practice in the domains of ‘expert care planning’ and ‘comprehensive care’. Three (11.1%) nurses met all criteria for advanced nursing practice.ConclusionThe results on specialised outpatient nursing activity at the 39 transplantation facilities in Spain indicate a low presence of this type of activity, with an even lower presence of advanced practice nurses.Implications for Clinical PracticeManagement teams should consider investing in the quality of care provided by advanced nurse practice to ensure that suitable treatment is provided and better clinical outcomes are obtained.
The spatial scope of agglomeration economies in Brazil
Authors: de Almeida Edilberto Tiago , Neto Raul da Mota Silveira , Rocha Roberta de Moraes 
Published: March 2023

AbstractThis paper provides evidence about location and colocation patterns of manufacturing entrepreneurship and spatial scope of agglomeration economies in the context of a developing country. Using microgeographic data for all Brazilian manufacturing activities and distance‐based measures, we find clear patterns of colocalization between entrants and existing establishments, and that these patterns occur mainly at short distances. For activities presenting colocalization between entrants and existing establishments, our results also indicate that a greater number of incumbent establishments in a given location positively affects the number of entrant establishments that decide to locate there, an effect that attenuates rapidly with distance (generally disappearing after 5 km). This pattern of attenuation is robust to both the inclusion of a comprehensive set of controls for observable and unobservable local characteristics and the use of instrumental variables to address remaining endogeneity concerns.
Individual variation in the avian gut microbiota: The influence of host state and environmental heterogeneity
Authors: Somers Shane E. , Davidson Gabrielle L. , Johnson Crystal N. , Reichert Michael S. , Crane Jodie M. S. , Ross R. Paul , Stanton Catherine , Quinn John L. 
Published: March 2023

AbstractThe gut microbiota have important consequences for host biological processes and there is some evidence that they also affect fitness. However, the complex, interactive nature of ecological factors that influence the gut microbiota has scarcely been investigated in natural populations. We sampled the gut microbiota of wild great tits (Parus major) at different life stages allowing us to evaluate how microbiota varied with respect to a diverse range of key ecological factors of two broad types: (1) host state, namely age and sex, and the life history variables, timing of breeding, fecundity and reproductive success; and (2) the environment, including habitat type, the distance of the nest to the woodland edge, and the general nest and woodland site environments. The gut microbiota varied with life history and the environment in many ways that were largely dependent on age. Nestlings were far more sensitive to environmental variation than adults, pointing to a high degree of flexibility at an important time in development. As nestlings developed their microbiota from one to two weeks of life, they retained consistent (i.e., repeatable) among‐individual differences. However these apparent individual differences were driven entirely by the effect of sharing the same nest. Our findings point to important early windows during development in which the gut microbiota are most sensitive to a variety of environmental drivers at multiple scales, and suggest reproductive timing, and hence potentially parental quality or food availability, are linked with the microbiota. Identifying and explicating the various ecological sources that shape an individual's gut bacteria is of vital importance for understanding the gut microbiota's role in animal fitness.
The value of 18F‐FDG PET/CT quantitative indexes in the diagnosis of nondestructive posttransplant lymphoproliferative disorders after pediatric liver transplantation
Authors: Si Zhuyuan , Lu Dongyan , Zhai Lili , Zheng Weiping , Dong Chong , Sun Chao , Wang Kai , Zhang Wei , Wei Xinzhe , Zhang Zhixin , Zhao Shengqiao , Gao Wei , Shen Zhongyang 
Published: March 2023

AbstractBackgroundPosttransplant lymphoproliferative disease (PTLD) is a serious complication after pediatric liver transplantation (pLT), which may lead to death. 18F‐FDG PET/CT is rarely considered in PTLD after pLT and lacks clear diagnostic guidelines, especially in the differential diagnosis of nondestructive PTLD. The aim of this study was to find a quantifiable 18F‐FDG PET/CT index to identify nondestructive PTLD after pLT.MethodsThis retrospective study collected the data of patients who underwent pLT, postoperative lymph node biopsy, and 18F‐FDG PET/CT at Tianjin First Central Hospital from January 2014 to December 2021. Quantitative indexes were established using lymph node morphology and the maximum standardized uptake value (SUVmax).ResultsA total of 83 patients met the inclusion criteria and were included in this retrospective study. To distinguish between PTLD‐negative cases and nondestructive PTLD cases, according to the receiver operating characteristic curve, (the shortest diameter of the lymph node at the biopsy site [SDL]/the longest diameter of the lymph node at the biopsy site [LDL])*(SUVmax at the biopsy site [SUVmaxBio]/SUVmax of the tonsils [SUVmaxTon]) had the maximum area under the curve (0.923; 95% confidence interval: 0.834–1.000), and the cutoff value was 0.264 according to the maximum value of Youden's index. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 93.6%, 94.7%, 97.8%, 85.7%, and 93.9%, respectively.Conclusions(SDL/LDL)*(SUVmaxBio/SUVmaxTon) has good sensitivity, specificity, positive predictive and negative predictive values, and accuracy, and can be used as a good quantitative index for the diagnosis of nondestructive PTLD.
Oscillatory and non‐oscillatory brain activity reflects fear expression in an immediate and delayed fear extinction task
Authors: Bierwirth Philipp , Antov Martin I. , Stockhorst Ursula 
Published: March 2023

AbstractFear extinction is pivotal for inhibiting fear responding to former threat‐predictive stimuli. In rodents, short intervals between fear acquisition and extinction impair extinction recall compared to long intervals. This is called Immediate Extinction Deficit (IED). Importantly, human studies of the IED are sparse and its neurophysiological correlates have not been examined in humans. We, therefore, investigated the IED by recording electroencephalography (EEG), skin conductance responses (SCRs), an electrocardiogram (ECG), and subjective ratings of valence and arousal. Forty male participants were randomly assigned to extinction learning either 10 min after fear acquisition (immediate extinction) or 24 h afterward (delayed extinction). Fear and extinction recall were assessed 24 h after extinction learning. We observed evidence for an IED in SCR responses, but not in the ECG, subjective ratings, or in any assessed neurophysiological marker of fear expression. Irrespective of extinction timing (immediate vs. delayed), fear conditioning caused a tilt of the non‐oscillatory background spectrum with decreased low‐frequency power (<30 Hz) for threat‐predictive stimuli. When controlling for this tilt, we observed a suppression of theta and alpha oscillations to threat‐predictive stimuli, especially pronounced during fear acquisition. In sum, our data show that delayed extinction might be partially advantageous over immediate extinction in reducing sympathetic arousal (as assessed via SCR) to former threat‐predictive stimuli. However, this effect was limited to SCR responses since all other fear measures were not affected by extinction timing. Additionally, we demonstrate that oscillatory and non‐oscillatory activity is sensitive to fear conditioning, which has important implications for fear conditioning studies examining neural oscillations.
Higher amplitudes in steady‐state visual evoked potentials driven by square‐wave versus sine‐wave contrast modulation – A dual‐laboratory study
Authors: Panitz Christian , Gundlach Christopher , Boylan Maeve R. , Keil Andreas , Müller Matthias M. 
Published: March 2023

AbstractSteady‐state visual evoked potentials (ssVEPs) are an established tool for assessing visuocortical responses in visual perception and attention. They have the same temporal frequency characteristics as a periodically modulated stimulus (e.g., in contrast or luminance) that drives them. It has been hypothesized that the amplitude of a given ssVEP may depend on the shape of the stimulus modulation function, but the size and robustness of these effects is not well established. The current study systematically compared the effect of the two most common functions in the ssVEP literature, square‐wave and sine‐wave functions. Across two laboratories, we presented mid‐complex color patterns to 30 participants with square‐wave or sine‐wave contrast modulation and at different driving frequencies (6 Hz, 8.57 Hz, 15 Hz). When ssVEPs were analyzed independently for the samples, with each laboratory's standard processing pipeline, ssVEP amplitudes in both samples decreased at higher driving frequencies and square‐wave modulation evoked higher amplitudes at lower frequencies (i.e., 6 Hz, 8.57 Hz) compared to sine‐wave modulation. These effects were replicated when samples were aggregated and analyzed with the same processing pipeline. In addition, when using signal‐to‐noise ratios as outcome measures, this joint analysis indicated a somewhat weaker effect of increased ssVEP amplitudes to square‐wave modulation at 15 Hz. The present study suggests that square‐wave modulation should be used in ssVEP research when the goal is to maximize signal amplitude or signal‐to‐noise ratio. Given effects of modulation function across laboratories, and data processing pipelines, the findings appear robust to differences in data collection and analysis.
Quantitative risk analysis of treatment plans for patients with tumor by mining historical similar patients from electronic health records using federated learning
Authors: Liu Yang , Bi Donghai 
Published: March 2023

AbstractThe determination of a treatment plan for a target patient with tumor is a difficult problem due to the existence of heterogeneity in patients’ responses, incomplete information about tumor states, and asymmetric knowledge between doctors and patients, and so on. In this paper, a method for quantitative risk analysis of treatment plans for patients with tumor is proposed. To reduce the impacts of the heterogeneity in patients’ responses on analysis results, the method conducts risk analysis by mining historical similar patients from Electronic Health Records (EHRs) in multiple hospitals using federated learning (FL). For this, the Recursive Feature Elimination based on the Support Vector Machine (SVM) and Deep Learning Important FeaTures (DeepLIFT) are extended into the FL framework to select key features and determine key feature weights for identifying historical similar patients. Then, in the database of each collaborative hospital, the similarities between the target patient and all historical patients are calculated, and the historical similar patients are determined. According to the statistics of tumor states and treatment outcomes of historical similar patients in all collaborative hospitals, the related data (including the probabilities of different tumor states and possible outcomes of different treatment plans) for risk analysis of the alternative treatment plans can be obtained, which can eliminate the asymmetric knowledge between doctors and patients. The related data are valuable for the doctor and patient to make their decisions. Experimental studies have been conducted to verify the feasibility and effectiveness of the proposed method.
The formation and function of plant metabolons
Authors: Dahmani Ismail , Qin Kezhen , Zhang Youjun , Fernie Alisdair R. 
Published: March 2023

SUMMARYMetabolons are temporary structural‐functional complexes of sequential enzymes of a metabolic pathway that are distinct from stable multi‐enzyme complexes. Here we provide a brief history of the study of enzyme–enzyme assemblies with a particular focus on those that mediate substrate channeling in plants. Large numbers of protein complexes have been proposed for both primary and secondary metabolic pathways in plants. However, to date only four substrate channels have been demonstrated. We provide an overview of current knowledge concerning these four metabolons and explain the methodologies that are currently being applied to unravel their functions. Although the assembly of metabolons has been documented to arise through diverse mechanisms, the physical interaction within the characterized plant metabolons all appear to be driven by interaction with structural elements of the cell. We therefore pose the question as to what methodologies could be brought to bear to enhance our knowledge of plant metabolons that assemble via different mechanisms? In addressing this question, we review recent findings in non‐plant systems concerning liquid droplet phase separation and enzyme chemotaxis and propose strategies via which such metabolons could be identified in plants. We additionally discuss the possibilities that could be opened up by novel approaches based on: (i) subcellular‐level mass spectral imaging, (ii) proteomics, and (iii) emergent methods in structural and computational biology.
Properties of the Cremona group endowed with the Euclidean topology
Authors: Bergner Hannah , Zimmermann Susanna 
Published: March 2023

AbstractConsider a Cremona group endowed with the Euclidean topology introduced by Blanc and Furter. It makes it a Hausdorff topological group that is not locally compact nor metrisable. We show that any sequence of elements of the Cremona group of bounded order that converges to the identity is constant. We use this result to show that Cremona groups do not contain any non‐stationary sequence of subgroups converging to the identity. We also show that, in general, paths in a Cremona group do not lift and do not satisfy a property similar to the definition of morphisms to a Cremona group.
Better to Give than to Receive: A Study of BRICS Countries Stock Markets
Authors: Panda Pradiptarathi , Ahmad Wasim , Thiripalraju M. 
Published: March 2023

This study uses the MGARCH-BEKK model and Diebold–Yilmaz (DY) volatility spillover index to examine volatility spillovers among BRICS countries’ stock markets. The study finds that the own volatility spillover is more than the cross-markets and has increased during the financial crisis. In contrast, the cross-markets volatility spillovers have decreased after the financial crisis. The total net return spillover increased during the crisis period (27.30%) and the pre-crisis period (25.50%) in comparison with the post-crisis period (6.30%) and the whole sample period (10.70%). Brazil is the highest net volatility transmitter among the BRICS countries’ stock markets, and China is the highest net volatility receiver. We learned from the volatility network connectedness that China is highly connected with India regarding volatility. Foreign institutional investors may use this study’s result to find diversification opportunities across the BRICS stock markets. JEL Codes: F3, G11, G12, G15
The impact of oral health literacy on dental anxiety and utilization of oral health services among dental patients: a cross sectional study
Authors: Badran Amira , Keraa Khaled , Farghaly Mahassen Mohamed 
Published: March 2023

Abstract
Background
Low oral health literacy levels and deficient oral health knowledge jeopardize the communication between dentists and patients in different communities. This study aimed to examine the impact and association of oral health literacy with patients’ levels of dental anxiety and their utilization of dental health services.

Methods
This cross-sectional study was conducted at the Misr International University (MIU) dental clinics. The study utilized a structured, interview led questionnaire that was administered by second year dental students, over the period of two successive academic years 2018–2019 and 2019–2020. A total of 440 student interviewed a convenience sample of 440 dental patients: including 269 females (61.1%) and 171 males (38.9%). The questionnaire consisted of four sections; a demographic section, a modified Arabic Rapid Estimate of Adult Literacy (ARELAD-30) Tool that measures the ability of the participants to read 30 commonly used dental terms. This questionnaire was modified by the authors to measure the participants’ knowledge by asking them to choose the most accurate meaning for each word based on their previous knowledge. Scoring was dependent on the participant’s immediate correct pronunciation, as well as comprehension of each word. The Arabic Modified Dental Anxiety Scale (AMDAS) was used to measure the level of dental anxiety, and the dental health service utilization was measured using the Utilization of oral health services questionnaire.

Results
One quarter (24.1%) of the participants read the 30 items of the A-REALD correctly. The average percentage of correct responses to the meaning of the dental terms was 71.2%. There was no statistically significant association between A-REALD and knowledge scores (Spearman’s Correlation coefficient ρ = -0.008, p-value = 0.872). There was a statistically significant inverse correlation between age and MDAS (Correlation coefficient ρ = -0.146, p-value = 0.002). A-REALD scores were inversely correlated with time since last visit (Regression coefficient = -0.027, p-value = 0.036, with 95% CI: -0.052 – -0.002).

Conclusion
Within the limitations of this study, it can be concluded that oral health literacy is significantly associated to dental health services utilization, while, dental anxiety is related to other variables, such as age and gender.