bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative single-cell analysis of the adult heart and coronary vasculature
Authors: Balachandran Saranya , Pozojevic Jelena , Sreenivasan Varun K. A. , Spielmann Malte
Published: November 2022

The structure and function of the circulatory system, including the heart, have undergone substantial changes with the vertebrate evolution. Although the basic function of the heart is to pump blood through the body, its size, shape, speed, regeneration capacity, etc. vary considerably across species. Here, we address the differences among vertebrate hearts using a single-cell transcriptomics approach. Published datasets of macaque (Macaca fascicularis), mouse, and zebrafish hearts were integrated and compared to the human heart as a reference. While the three mammalian hearts integrated well, the zebrafish heart showed very little overlap with the other species. Our analysis revealed a mouse-specific cell subpopulation of ventricular cardiomyocytes (CM), represented by strikingly different expression patterns of specific genes related to high-energy metabolism. Interestingly, the observed differences between mouse and human CM coincided with actual biological differences between the two species. Smooth muscle and endothelial cells (EC) exhibited species-specific differences in clustering and gene expression, respectively, which we attribute to the tissues selected for sequencing, given different focuses of the original studies. Finally, we compared human and zebrafish heart-specific fibroblasts (FB) and identified a distinctively high expression of genes associated with heart regeneration following injury in zebrafish. Together, our results show that integration of numerous datasets of different species and different sequencing technologies is feasible and that this approach can identify species-specific differences and similarities in the heart.
Impacts of ocean warming on the settlement success and post-settlement survival of Pacific crown-of-thorns starfish (Acanthaster cf. solaris)
Authors: Lang Bethan J. , Caballes Ciemon F. , Uthicke Sven , Doll Peter C. , Donelson Jennifer M. , Pratchett Morgan S.
Published: November 2022

Ocean warming and population irruptions of crown-of-thorns starfish (CoTS; Acanthaster cf. solaris) are two of the greatest threats to coral reefs. As such, there is significant interest in understanding how CoTS may be directly impacted by rising ocean temperatures. Settlement of planktonic larvae and subsequent metamorphosis is purported to be a major population bottleneck in marine invertebrates, yet it is unknown how ocean warming will impact these processes in CoTS. Herein, the effect of temperature (28 °C ambient, 30 °C, 32 °C, 34 °C) on the settlement success, metamorphic success, and post-settlement survival of this corallivore was explored. While larval settlement was robust to elevated temperature, with at least 94% of larvae settling after 48 h across all temperatures, it was observed that settlement success was lower on substrate that had been pre-treated ≥ 32 °C. Metamorphic success was also significantly constrained at temperatures ≥ 32 °C. At 32 °C and 34 °C metamorphic success was 16% and 63% lower than at ambient temperature, respectively. Significant adverse effects of warming on post-settlement survival were observed at even cooler temperatures, with 10% lower survival at 30 °C compared to at ambient temperature, and at 34 °C, survival was 34% lower. Substantial reductions in metamorphic success and early post-settlement survival at elevated temperatures, as well as negative impacts of warming on the settlement substrate and its capacity to induce settlement, may present a bottleneck for recruitment in a warmer ocean.
Trends and patterns of initial percutaneous nephrolithotomy and subsequent procedures among commercially-insured US adults with urinary system stone disease: a 10-year population-based study
Authors: Johnston Stephen S. , Johnson Barbara H. , Rai Pragya , Grange Philippe , Amos Tony , Ghosh Sudip , Buchholz Noor
Published: November 2022

Purpose

To describe trends and patterns of initial percutaneous nephrolithotomy (PCNL) and subsequent procedures from 2010 to 2019 among commercially-insured US adults with urinary system stone disease (USSD).

Methods

Retrospective study of administrative data from the IBM® MarketScan® Database. Eligible patients were aged 18–64 years and underwent PCNL between 1/1/2010 and 12/31/2019. Measures of interest for analysis of trends and patterns included the setting of initial PCNL (inpatient vs. outpatient), percutaneous access (1 vs. 2-step), and the incidence, time course, and type of subsequent procedures (extracorporeal shockwave lithotripsy [SWL], ureteroscopy [URS], and/or PCNL) performed up-to 3 years after initial PCNL.

Results

A total of 8,348 patients met the study eligibility criteria. During the study period, there was a substantial shift in the setting of initial PCNL, from 59.9% being inpatient in 2010 to 85.3% being outpatient by 2019 (P < 0.001). The proportion of 1 vs. 2-step initial PCNL fluctuated over time, with a low of 15.1% in 2016 and a high of 22.0% in 2019 but showed no consistent yearly trend (P = 0.137). The Kaplan–Meier estimated probability of subsequent procedures following initial PCNL was 20% at 30 days, 28% at 90 days, and 50% at 3 years, with slight fluctuations by initial PCNL year. From 2010 to 2019, the proportion of subsequent procedures accounted for by URS increased substantially (from 30.8 to 51.8%), whereas SWL decreased substantially (from 39.5 to 14.7%) (P < 0.001).

Conclusions

From 2010 to 2019, PCNL procedures largely shifted to the outpatient setting. Subsequent procedures after initial PCNL were common, with most occurring within 90 days. URS has become the most commonly-used subsequent procedure type.
Direct detection and quantification of Toxoplasma gondii in meat samples from feral raccoons (Procyon lotor) in Germany by magnetic-capture real-time PCR
Authors: Engel Lydia , Hamedy Ahmad , Koethe Martin
Published: November 2022

Because the number of wild raccoons in Germany is increasing constantly, it appears to be economic reasonable to use their meat as food. For this purpose, it is essential to generate data regarding the pathogen load of the meat to be consumed and handled. It is known that raccoons, particularly in Germany, show a high seroprevalence ofToxoplasma gondii. Because serological data only indicates contact of a host to a parasite additional direct detection is needed to prove presence of parasitic stages in particular tissues. Therefore, a total of 150 samples from raccoons with known serostatus were tested and quantified using magnetic-capture real-time PCR forToxoplasma gondii.As it represents potentially consumption-relevant parts of raccoons, meat from forelimb and hindlimb was examined. Samples were stratified into three groups based on the animals’ serostatus (each 50 negative, low positive, and high positive). All samples from seronegative animals were found negative by MC-PCR as well. In a total of 56 meat samples from 100 seropositive animals,T. gondiiDNA was detected. Statistically significant more samples were positive by MC-PCR in the high positive than in the low positive serostatus group (38/50 vs. 18/50,p < 0.0001). Furthermore, samples from the former group were also found to have statistically significant higher DNA equivalent values compared to samples from the low positive serostatus group (p < 0.0001). These results suggest that meat from seropositive raccoons may contain considerable numbers ofT. gondiipresenting a potential public health risk for humans whilst handling and consumption.
A re-appraisal of mesenchymal-epithelial transition (MET) in endometrial epithelial remodeling
Authors: Spooner-Harris Madelyn , Kerns Karl , Zigo Michal , Sutovsky Peter , Balboula Ahmed , Patterson Amanda L.
Published: November 2022

Mesenchymal-epithelial transition (MET) is a mechanism of endometrial epithelial regeneration. It is also implicated in adenocarcinoma and endometriosis. Little is known about this process in normal uterine physiology. Previously, using pregnancy and menses-like mouse models, MET occurred only as an epithelial damage/repair mechanism. Here, we hypothesized that MET also occurs in other physiological endometrial remodeling events, outside of damage/repair, such as during the estrous cycle and adenogenesis (gland development). To investigate this, Amhr2-Cre-YFP/GFP mesenchyme-specific reporter mice were used to track the fate of mesenchymal-derived (MD) cells. Using EpCAM (epithelial marker), EpCAM+YFP+ MD-epithelial cells were identified in all stages of the estrous cycle except diestrus, in both postpartum and virgin mice. EpCAM+YFP+ MD-epithelial cells comprised up to 80% of the epithelia during estrogen-dominant proestrus and significantly declined to indistinguishable from control uteri in diestrus, suggesting MET is hormonally regulated. MD-epithelial cells were also identified during postnatal epithelial remodeling. MET occurred immediately after birth at postnatal day (P) 0.5 with EpCAM+GFP+ cells ranging from negligible (0.21%) to 82% of the epithelia. EpCAM+GFP+ MD-epithelial cells declined during initiation of adenogenesis (P8, avg. 1.75%) and then increased during gland morphogenesis (P14, avg. 10%). MD-epithelial cells expressed markers in common with non-MD-epithelial cells (e.g., EpCAM, FOXA2, ESR1, PGR). However, MD-epithelial cells were differentially regulated postnatally and in adults, suggesting a functional distinction in the two populations. We conclude that MET occurs not only as an epithelial damage/repair mechanism but also during other epithelial remodeling events, which to our knowledge has not been demonstrated in other tissues.
Hawk owl irruptions: spatial and temporal variation in rodent abundance drive push and pull dynamics
Authors: Dale Svein , Sonerud Geir A.
Published: November 2022

Bird irruptions are thought to be triggered by low food availability in breeding areas, thereby causing emigration (push factor). However, few studies have tested whether emigrating individuals are drawn towards areas of high food availability (pull factor). The Northern hawk owl (Surnia ulula), a rodent specialist, occurs irruptively to southern parts of Fennoscandia. We analysed whether irruption size during 1980–2020 in southeastern Norway was related to rodent abundance at four sites 450–990 km to the north-northeast (potential source areas) and at two sites in southeastern Norway to test push and pull dynamics of irruptions. Irruptions occurred when rodent abundance in potential source areas were low, supporting the push hypothesis. High rodent abundance in potential source areas 1–2 years before irruptions suggested that irruptions were preceded by high reproduction. Upon arrival to southeastern Norway, hawk owls did not encounter high rodent abundance in their main habitat (boreal forest). However, hawk owls stayed in boreal forest in hills in years with higher microtine rodent abundance, but occurred in farmland areas in the lowlands when microtine rodents were less abundant. Use of lowlands coincided with higher than median numbers of wood mouse (Apodemus sylvaticus) for 87% of the hawk owls settling in the lowlands, thus suggesting support for the pull hypothesis. In conclusion, hawk owl irruptions to southern Fennoscandia were triggered by low food availability in northern areas (push factor), and appeared to be drawn by high food availability in southeastern Norway to some degree (pull factor).
Effects of add-on Celecoxib treatment on patients with schizophrenia spectrum disorders and inflammatory cytokine profile trial (TargetFlame): study design and methodology of a multicentre randomized, placebo-controlled trial
Authors: Strube Wolfgang , Aksar Aslihan , Bauer Ingrid , Barbosa Susana , Benros Michael , Blankenstein Christiane , Campana Mattia , Davidovic Laetitia , Glaichenhaus Nicolas , Falkai Peter , Görlitz Thomas , Hansbauer Maximilian , Heilig Daniel , Khalfallah Olfa , Leboyer Marion , Martinuzzi Emanuela , Mayer Susanne , Moussiopoulou Joanna , Papazova Irina , Perić Natasa , Wagner Elias , Schneider-Axmann Thomas , Simon Judit , Hasan Alkomiet
Published: November 2022

Neuroinflammation has been proposed to impact symptomatology in patients with schizophrenia spectrum disorders. While previous studies have shown equivocal effects of treatments with add-on anti-inflammatory drugs such as Aspirin,N-acetylcysteine and Celecoxib, none have used a subset of prospectively recruited patients exhibiting an inflammatory profile. The aim of the study is to evaluate the efficacy and safety as well as the cost-effectiveness of a treatment with 400 mg Celecoxib added to an ongoing antipsychotic treatment in patients with schizophrenia spectrum disorders exhibiting an inflammatory profile. The “Add-on Celecoxib treatment in patients with schizophrenia spectrum disorders and inflammatory cytokine profile trial (TargetFlame)” is a multicentre randomized, placebo-controlled phase III investigator-initiated clinical trial with the following two arms: patients exhibiting an inflammatory profile receiving either add-on Celecoxib 400 mg/day or add-on placebo. A total of 199 patients will be assessed for eligibility by measuring blood levels of three pro-inflammatory cytokines, and 109 patients with an inflammatory profile, i.e. inflamed, will be randomized, treated for 8 weeks and followed-up for additional four months. The primary endpoint will be changes in symptom severity as assessed by total Positive and Negative Syndrome Scale (PANSS) score changes from baseline to week 8. Secondary endpoints include various other measures of psychopathology and safety. Additional health economic analyses will be performed. TargetFlame is the first study aimed at evaluating the efficacy, safety and cost-effectiveness of the antiphlogistic agent Celecoxib in a subset of patients with schizophrenia spectrum disorders exhibiting an inflammatory profile. With TargetFlame, we intended to investigate a novel precision medicine approach towards anti-inflammatory antipsychotic treatment augmentation using drug repurposing.

Clinical trial registration:http://www.drks.de/DRKS00029044andhttps://trialsearch.who.int/Trial2.aspx?TrialID=DRKS00029044
Forecasting seasonal to sub-seasonal rainfall in Great Britain using convolutional-neural networks
Authors: Barnes Andrew Paul , McCullen Nick , Kjeldsen Thomas Rodding
Published: November 2022

Traditional weather forecasting approaches use various numerical simulations and empirical models to produce a gridded estimate of rainfall, often spanning multiple regions but struggling to capture extreme events. The approach presented here combines modern meteorological forecasts from the ECMWF SEAS5 seasonal forecasts with convolutional neural networks (CNNs) to improve the forecasting of total monthly regional rainfall across Great Britain. The CNN is trained using mean sea-level pressure and 2-m air temperature forecasts from the ECMWF C3S service using three lead-times: 1 month, 3 months and 6 months. The training is supervised using the equivalent benchmark rainfall data provided by the CEH-GEAR (Centre for Ecology and Hydrology, gridded estimates of areal rainfall). Comparing the CNN to the ECMWF predictions shows the CNN out-performs the ECMWF across all three lead times. This is done using an unseen validation dataset and based on the root mean square error (RMSE) between the predicted rainfall values for each region and benchmark values from the CEH-GEAR dataset. The largest improvement is at a 1-month lead time where the CNN model scores a RMSE 6.89 mm lower than the ECMWF. However, these differences are exacerbated at the extremes with the CNN producing, at a 1-month lead time, RMSEs which are 28.19 mm lower than the corresponding predictions from the ECMWF. Following this, a sensitivity analysis shows the CNN model predicts increased rainfall values in the presence of a low sea-level pressure anomaly around Iceland, followed by a high sea-level pressure anomaly south of Greenland.
Screening performances of an 8-item UPSIT Italian version in the diagnosis of Parkinson’s disease
Authors: Landolfi Annamaria , Picillo Marina , Pellecchia Maria Teresa , Troisi Jacopo , Amboni Marianna , Barone Paolo , Erro Roberto
Published: November 2022

Hyposmia is a common finding in Parkinson’s disease (PD) and is usually tested through the University of Pennsylvania Smell Identification Test (UPSIT). The aim of our study is to provide a briefer version of the Italian-adapted UPSIT test, able to discriminate between PD patients and healthy subjects (HS). By means of several univariate and multivariate (machine-learning-based) statistical approaches, we selected 8 items by which we trained a partial-least-square discriminant analysis (PLS-DA) and a decision tree (DT) model: class predictions of both models performed better with the 8-item version when compared to the 40-item version. An area under the receiver operating characteristic (AUC-ROC) curve built with the selected 8 odors showed the best performance (sensitivity 86.8%, specificity 82%) in predicting the PD condition at a cut-off point of ≤ 6. These performances were higher than those previously calculated for the 40-item UPSIT test (sensitivity 82% and specificity 88.2 % with a cut-off point of ≤ 21). Qualitatively, our selection contains one odor (i.e., apple) which is Italian-specific, supporting the need for cultural adaptation of smell testing; on the other hand, some of the selected best discriminating odors are in common with existing brief smell test versions validated on PD patients of other cultures, supporting the view that disease-specific odor patterns may exist and deserve a further evaluation.
Clinical score for early diagnosis of myotonic dystrophy type 2
Authors: Ivanovic Vukan , Peric Stojan , Pesovic Jovan , Tubic Radoje , Bozovic Ivo , Petrovic Djordjevic Ivana , Savic-Pavicevic Dusanka , Meola Giovanni , Rakocevic-Stojanovic Vidosava
Published: November 2022

Introduction

Myotonic dystrophy type 2 (DM2) is a rare, multisystemic, autosomal dominant disease with highly variable clinical presentation. DM2 is considered to be highly underdiagnosed.

Objective

The aim of this study was to determine which symptoms, signs, and diagnostic findings in patients referred to neurological outpatient units are the most indicative to arouse suspicion of DM2. We tried to make a useful and easy-to-administer clinical scoring system for early diagnosis of DM2-DM2 early diagnosis score (DM2-EDS).

Patients and methods

Two hundred ninety-one patients with a clinical suspicion of DM2 were included: 69 were genetically confirmed to have DM2, and 222 patients were DM2 negative. Relevant history, neurological, and paraclinical data were obtained from the electronic medical records.

Results

The following parameters appeared as significant predictors of DM2 diagnosis: cataracts (beta = 0.410, p < 0.001), myotonia on needle EMG (beta = 0.298, p < 0.001), hand tremor (beta = 0.211, p = 0.001), positive family history (beta = 0.171, p = 0.012), and calf hypertrophy (beta = 0.120, p = 0.043). In the final DM2-EDS, based on the beta values, symptoms were associated with the following values: cataracts (present 3.4, absent 0), myotonia (present 2.5, absent 0), tremor (present 1.7, absent 0), family history (positive 1.4, negative 0), and calf hypertrophy (present 1.0, absent 0). A cut-off value on DM2-EDS of 3.25 of maximum 10 points had a sensitivity of 84% and specificity of 81% to diagnose DM2.

Conclusion

Significant predictors of DM2 diagnosis in the neurology outpatient unit were identified. We made an easy-to-administer DM2-EDS score for early diagnosis of DM2.
Flipped Learning 4.0. An extended flipped classroom model with Education 4.0 and organisational learning processes
Authors: Sein-Echaluce María Luisa , Fidalgo-Blanco Ángel , Balbín Ana María , García-Peñalvo Francisco José
Published: November 2022

This article integrates two visions on the creation of knowledge by students: an academic vision where the person who creates knowledge uses high-level cognitive abilities and, therefore, acquires deeper learning, and an organisational learning vision, where the creation of knowledge adds value to the organisation and the individuals who work in this matter. It starts from a validated flipped classroom model and then adds procedures and cycles of knowledge that make it an active methodology, in such a way that it simultaneously supports organisational learning, using cooperative competencies characteristic of Education 4.0. This proposed hybrid model has been applied online during confinement due to the COVID-19 pandemic and, subsequently, in dual mode (students partly in person and the rest online at the same time) and face-to-face mode. The evidence of this research shows that the creation of knowledge by the students, cooperatively and with an organisational learning perspective, has repercussions for improvements in their academic performance by producing deeper learning. In addition, the development of cooperative skills is observed to create and manage a large amount of helpful knowledge for them and other students in their learning process.
Learning across media in a second language
Authors: Tarchi Christian , Mason Lucia
Published: November 2022

The present study investigated the impact of the medium on learning in L2. Specifically, learning performances from L2 material were compared across three media: text, video, and subtitled video. The participants were 126 undergraduate students who were randomly assigned across three conditions: a text condition, a video condition, and a subtitles condition. First, students were asked to complete three questionnaires on control variables. Second, students were asked to read/watch a learning material and answer comprehension, recall, transfer, and calibration questions twice: immediately and a week after. Results reveal that the participants in the video condition outperformed those in the text condition in delayed comprehension and recall. Overall, learning performances were substantially equivalent across media when assessed immediately after processing the material, but subtitled videos had the potential to boost deeper learning performances only in highly skilled learners.
The prognostic effects of circulating myeloid-derived suppressor cells in non-small cell lung cancer: systematic review and meta-analysis
Authors: Bronte Giuseppe , Calabrò Luana , Olivieri Fabiola , Procopio Antonio Domenico , Crinò Lucio
Published: November 2022

Immunotherapy is the main standard treatment for non-small cell lung cancer (NSCLC) patients. Immune suppressive cells in tumor microenvironment can counteract its efficacy. Myeloid-derived suppressor cells (MDSCs) include two major subsets: polymorphonuclear (PMN-MDSCs) and monocytic (M-MDSCs). Many studies explored the prognostic impact of these cell populations in NSCLC patients. The aim of this systematic review is to select studies for a meta-analysis, which compares prognosis between patients with high vs low circulating MDSC levels. We collected hazard ratios (HRs) and relative 95% confidence intervals (CIs) in terms of progression-free survival (PFS) or recurrence-free survival (RFS), and overall survival (OS). Among 139 studies retrieved from literature search, 14 eligible studies (905 NSCLC patients) met inclusion criteria. Low circulating MDSC levels favor a better PFS/RFS (HR = 1.84; 95% CI = 1.28–2.65) and OS (HR = 1.78; 95% CI = 1.29–2.46). The subgroup analysis based on MDSC subtypes (total-, PMN-, and M-MDSCs) obtained a statistical significance only for M-MDSCs, both in terms of PFS/RFS (HR = 2.67; 95% CI = 2.04–3.50) and OS (HR = 2.10; 95% CI = 1.61–2.75). NSCLC patients bearing high M-MDSC levels in peripheral blood experience a worse prognosis than those with low levels, both in terms of PFS/RFS and OS. This finding suggests that detecting and targeting this MDSC subset could help to improve NSCLC treatment efficacy.
Immigrant workers and firm resilience on the export market
Authors: Marchal Léa , Sabbadini Giulia
Published: November 2022

This paper studies whether firms employing immigrant workers are more resilient to an increase in competition in their export markets. Exploiting the surge of Chinese imports following its accession to the World Trade Organization and using a sample of French manufacturing exporters from 2002 to 2015, we find that an increase in the growth rate of Chinese competition in a foreign market has a negative effect on both the two-year survival and growth rate of sales of French exporters on that foreign market. This negative effect on firm performance is mitigated by the employment of immigrant workers.
Virulence genes contributing to Aeromonas veronii pathogenicity in Nile tilapia (Oreochromis niloticus): approaching the development of live and inactivated vaccines
Authors: Youssef Hadeer A. , Ayoub Hala F. , Soror Eman I. , Matter Aya F.
Published: November 2022

This study aimed to develop and evaluate live and inactivated vaccines to Aeromonas veronii pathogenicity in Nile tilapia. Therefore, five well-identified Aeromonas veronii isolates, including A (HY1), A (HY2), A (HY3), A (HY4), and A (HY6) isolated from diseased Nile tilapia (Oreochromis niloticus), were used for vaccine preparation. Virulence genes detected by a polymerase chain reaction (PCR) and lethal dose determination were conducted. Nile tilapia, each with a body weight of 25 ± 0.5 g were divided into six experimental groups (each of 20): T1 group (control), fish were injected with saline as a negative control, T2 group (formalin-killed vaccine) for the A (HY2) strain, T3 group ( formalized killed vaccine) for the A (HY4), T4 group (autoclaved vaccine) for the A (HY2), T5 group (autoclaved vaccine) for A (HY4), and T6 (live vaccine) for A (HY1), triplicate. At the end of the immunization period, all groups were challenged by A. veronii, A (HY2). Blood samples were drawn 21 days post-immunization and 3 days after the challenge test for antibody titer assay. The results showed that the pathogenicity of strains A (HY2) and A (HY4) was the strongest, as the lethality rates (LR) were 100% and 90%, respectively, whereas the pathogenicity was moderate for strains A (HY3) and A (HY6) (LR 60% for each). A (AY1) was the weakest strain as no dead fish was found for this strain. The presence of alt, act, aerolysin, lipase, and fla genes as the main cause of the pathogenesis. The best protective efficacy was obtained from the live vaccine, A (HY1) with a protective rate of about 94.12% (relative percentage of survival, RPS), compared to autoclaved killed vaccines and formalin-killed vaccines. Based on immunoglobulin estimation (IgM) and RPS%, our data concluded that A (HY1) live vaccine had the best vaccine prophylactic effect against the highly pathogenic strain A(HY2).
EEG Microstate Dynamics Associated with Dream-Like Experiences During the Transition to Sleep
Authors: Diezig Sarah , Denzer Simone , Achermann Peter , Mast Fred W. , Koenig Thomas
Published: November 2022

Consciousness always requires some representational content; that is, one can only be conscious about something. However, the presence of conscious experience (awareness) alone does not determine whether its content is in line with the external and physical world. Dreams, apart from certain forms of hallucinations, typically consist of non-veridical percepts, which are not recognized as false, but rather considered real. This type of experiences have been described as a state of dissociation between phenomenal and reflective awareness. Interestingly, during the transition to sleep, reflective awareness seems to break down before phenomenal awareness as conscious experience does not immediately fade with reduced wakefulness but is rather characterized by the occurrence of uncontrolled thinking and perceptual images, together with a reduced ability to recognize the internal origin of the experience. Relative deactivation of the frontoparietal and preserved activity in parieto-occipital networks has been suggested to account for dream-like experiences during the transition to sleep. We tested this hypothesis by investigating subjective reports of conscious experience and large-scale brain networks using EEG microstates in 45 healthy young subjects during the transition to sleep. We observed an inverse relationship between cognitive effects and physiological activation; dream-like experiences were associated with an increased presence of a microstate with sources in the superior and middle frontal gyrus and precuneus. Additionally, the presence of a microstate associated with higher-order visual areas was decreased. The observed inverse relationship might therefore indicate a disengagement of cognitive control systems that is mediated by specific, inhibitory EEG microstates.
The oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with hormone receptor-positive HER2-negative (HR + /HER2 −) advanced/metastatic breast cancer
Authors: Bardia Aditya , Mayer Ingrid , Winer Eric , Linden Hannah M. , Ma Cynthia X. , Parker Barbara A. , Bellet Meritxell , Arteaga Carlos L. , Cheeti Sravanthi , Gates Mary , Chang Ching-Wei , Fredrickson Jill , Spoerke Jill M. , Moore Heather M. , Giltnane Jennifer , Friedman Lori S. , Chow Maneval Edna , Chan Iris , Jhaveri Komal
Published: November 2022

Purpose

GDC-0810 (ARN-810) is a novel, non-steroidal, orally bioavailable, selective estrogen receptor degrader (SERD) that potentially inhibits ligand-dependent and ligand-independent estrogen receptor (ER)-mediated signaling.

Methods

A phase Ia/Ib/IIa dose escalation, combination treatment with palbociclib or a luteinizing hormone-releasing hormone, and expansion study determined the safety, pharmacokinetics, and recommended phase 2 dose (RP2D) of GDC-0810 in postmenopausal women with ER + (HER2 −) locally advanced or metastatic breast cancer (MBC). Baseline plasma ctDNA samples were analyzed to determine the ESR1 mutation status.

Results

Patients (N = 152) received GDC-0810 100–800 mg once daily (QD) or 300–400 mg twice daily, in dose escalation, expansion, as single agent or combination treatment. Common adverse events regardless of attribution to study drug were diarrhea, nausea, fatigue, vomiting, and constipation. There was one dose-limiting toxicity during dose escalation. The maximum tolerated dose was not reached. GDC-0810 600 mg QD taken with food was the RP2D. Pharmacokinetics were predictable. FES reduction (> 90%) highlighting pharmacodynamic engagement of ER was observed. Outcomes for the overall population and for patients with tumors harboring ESR1 mutations included partial responses (4% overall; 4% ESR1), stable disease (39% overall; 42% ESR1), non-complete response/non-progressive disease (13% overall; 12% ESR1), progressive disease (40% overall; 38% ESR1), and missing/unevaluable (5% overall; 5% ESR1). Clinical benefit (responses or SD, lasting ≥ 24 weeks) was observed in patients in dose escalation (n = 16, 39%) and expansion (n = 24, 22%).

Conclusion

GDC-0810 was safe and tolerable with preliminary anti-tumor activity in heavily pretreated patients with ER + advanced/MBC, with/without ESR1 mutations, highlighting the potential for oral SERDs.

Clinical Trial and registration date April 4, 2013. NCT01823835 .
The Importance of Embodiment and Agency in Parents’ Positive Attitudes Towards Shared Reading with Their Children
Authors: Kucirkova Natalia , Grøver Vibeke
Published: November 2022

Parents’ attitudes are an important indicator of whether and how parents engage in shared book reading (SBR) at home. This study analysed Norwegian parents’ attitudes towards reading books with their children aged between 1–4.5 years. Thematic analysis of data from 24 interviews revealed two main themes in parents’ accounts: agency (the child’s independence, the adult’s control as well as their shared control during SBR) and embodiment (physical presence and intimate experience of a SBR session). Both themes correspond to parents’ preference for reading print rather than digital books with their children. Findings are discussed from the socio-material theoretical perspective, with attention to their practical and policy implications.
Non-propositionalism and the Suppositional Rule
Authors: Beevers Tom
Published: November 2022

It can often seem like the attitude we hold towards a conditional should be our attitude in the consequent on the supposition of the antecedent. Following by Williamson (Suppose and Tell: The Semantics and Heuristics of Conditionals. Oxford University Press, 2020), we call this The suppositional rule (SR). The Adams-style non-propositional theories of indicatives upholds some key implications of SR, allowing, for instance, our credence in a conditional to be the probability of the consequent given the antecedent. Williamson (Suppose and Tell: The Semantics and Heuristics of Conditionals. Oxford University Press, 2020) has recently provided a series of inconsistency arguments against SR. He thereby intends to undermine non-propositional views as well as other rivals to his favoured material conditional account. I outline a strategy which theorists of all stripes can employ to avoid Williamson’s arguments. I then show how non-propositionalists can implement this strategy. I show how they can uphold SR when it is intuitively compelling, whilst allowing it to fail when it is not.
Laboratory variation in the grading of dysplasia of duodenal adenomas in familial adenomatous polyposis patients
Authors: Soons E. , Siersema P. D. , van Lierop L. M. A. , Bisseling T. M. , van Kouwen M. C. A. , Nagtegaal I. D. , van der Post R. S. , Atsma F.
Published: November 2022

To prevent duodenal and ampullary cancer in familial adenomatous polyposis (FAP) patients, a diagnosis of high grade dysplasia (HGD) plays an important role in the clinical management. Previous research showed that FAP patients are both over- and undertreated after a misdiagnosis of HGD, indicating unwarranted variation. We aimed to investigate the laboratory variation in dysplasia grading of duodenal adenomas and explore possible explanations for this variation. We included data from all Dutch pathology laboratories between 1991 and 2020 by retrieving histology reports from upper endoscopy specimens of FAP patients from the Dutch nationwide pathology databank (PALGA). Laboratory variation was investigated by comparing standardized proportions of HGD. To describe the degree of variation between the laboratories a factor score was calculated. A funnel plot was used to identify outliers. A total of 3050 specimens from 25 laboratories were included in the final analyses. The mean observed HGD proportion was 9.4%. The top three HGD-diagnosing laboratories diagnosed HGD 3.9 times more often than the lowest three laboratories, even after correcting for case-mix. No outliers were identified. Moderate laboratory variation was found in HGD diagnoses of duodenal tissue of FAP patients after adjusting for case-mix. Despite the fact that no outliers were observed, there may well be room for quality improvement. Concentration of these patients in expertise centers may decrease variation. To further reduce unwarranted variation, we recommend (inter)national guidelines to become more uniform in their recommendations regarding duodenal tissue sampling and consequences of HGD diagnoses.
A systematic review of student agency in international higher education
Authors: Inouye Kelsey , Lee Soyoung , Oldac Yusuf Ikbal
Published: November 2022

The agency of international students has long been neglected and undertheorised, though recent literature indicates that this has started to change. This paper systematically reviews 51 studies that address student agency in international higher education. Focusing on research published in the last two decades (2000–2020), the review draws on studies that foreground student voices, or international students’ perspectives, rather than the perspectives of teachers, administrators or policymakers. A detailed discussion of how international student agency is positioned in the literature found that agency appears as either: a research object, as part of a theoretical or conceptual framework, or an emergent finding. Furthermore, our analysis suggests that the term “agency” is often used as a buzzword rather than as a fleshed-out concept. Thus, drawing on this initial analysis, the review synthesises varying but overlapping conceptualisations of international student agency in the literature into an integrative framework. Implications for future research are drawn, based on our findings about the understudied populations and methodological limitations in the literature.
Responses of Bunias orientalis to Short-term Fungal Infection and Insect Herbivory are Independent of Nutrient Supply
Authors: Binama Blaise , Behrendt Miriam , Müller Caroline
Published: November 2022

Plants have to allocate their resources in both growth and defense under different environmental challenges. Several plant species have become invasive particularly in disturbed fertile habitats, which may influence their resource allocation. We studied the effects of nitrate fertilization (low versus high) on various plant responses towards a pathogenic fungus, Alternaria brassicae, and a herbivorous insect species, Mamestra brassicae, in a population of Bunias orientalis, which is invasive in parts of central Europe. Aboveground biomass and leaf trichome density were enhanced in plants under high fertilization. In contrast, the short-term fungal infection and herbivory had no effect on aboveground biomass. Leaf water, nitrogen content and glucosinolate concentrations were neither affected by fertilization nor in response to antagonist attack. The total soluble sugar content, especially fructose, as well as leaf peroxidase activity increased significantly in leaves upon fungal infection, but independent of fertilization. Larval biomass gain and herbivore survival were likewise unaffected by fertilization. Our findings highlight that under conditions of high fertilization, B. orientalis plants allocate more resources into growth and morphological defenses than chemical defenses. In contrast, induced responses to short-term antagonist attack seem independent of nitrate availability in this population.
Green heterogeneous catalysts for cleaner solvent-free production of acetates
Authors: Izquierdo Silvia , Silvero Guadalupe , Durán-Valle Carlos J. , López-Coca Ignacio M.
Published: November 2022

The development of new chemical synthetic methodologies that transform industrial chemical processes into more sustainable ones, constitutes one of the challenges and objectives of chemical research both in academia and in industry. The use of activated carbons as heterogeneous catalysts represents one of the most beneficial options for process efficiency in terms of reaction rate, yield, and ease of work-up. We have produced six new activated carbons by treatment of three affordable commercial carbons with either nitric acid, or with sulfuric acid. The complete characterization of these nine activated carbons has been carried out through the measurement of nitrogen adsorption capacity, porosimetry, elemental organic analysis, X-ray photoelectron spectroscopy, scanning electron microscopy and determination of the point of zero charge; transmission electron microscopy was also performed on two of them. The catalytic activity of these nine catalysts has been tested in the acetylation reaction of hydroxyl groups, undoubtedly one of the most versatile and widely used chemical transformations both at the laboratory and industrial scale. The results show that by means of a simple and affordable modification of commercial xerogel with sulfuric acid, a more efficient catalyst is formed. Acetylation with the best catalyst is completed in 90 min at room temperature and the product is easily isolated in quantitative yield. The system can be reutilized for five runs with only a small loss of catalytic activity.
The Role and Value of Chaplains in an Australian Ambulance Service: A Comparative Study of Chaplain and Paramedic Perspectives
Authors: Tunks Leach Katie , Simpson Paul , Lewis Joanne , Levett-Jones Tracy
Published: November 2022

Chaplains are embedded in several ambulance services across Australia, however as Australia’s religiosity is currently in decline and questions are being asked about retaining chaplains, little is actually known about their role and value within Ambulance services. The aim of this paper is to present the key findings from interviews with chaplains about their role and value of being ambulance chaplains. These findings are then compared with those of paramedics derived from an earlier phase of this study. Thirteen chaplains participated in semi-structured interviews, and data were analysed using framework analysis. The results indicated that ambulance chaplains provided paramedic-centred emotional and spiritual care through proactively and reactively supporting paramedics in their work. Chaplains saw value in their relational approach which facilitated trust and access, did not seek to ‘fix’ or diagnose but instead offered physical and emotional presence, and promoted supportive conversations. Chaplains and paramedics valued operationally trained and equipped ambulance chaplains who provided a relational, around the clock, ‘frontline’ staff support presence in paramedic workplaces, regardless of the paramedic’s personal religious/spiritual beliefs.
Late-Night Digital Media Use in Relation to Chronotype, Sleep and Tiredness on School Days in Adolescence
Authors: Kortesoja Laura , Vainikainen Mari-Pauliina , Hotulainen Risto , Merikanto Ilona
Published: November 2022

Previous studies on late-night digital media use and adolescent sleep have not considered how chronotype, a natural tendency to be awake or asleep at certain time, is associated with this relationship. Therefore, the nature of the relationship between late-night digital media use and sleep in different chronotypes remains still unknown. The sample consisted of 15–20-year-old Finnish adolescents (n = 1084, mean age = 16.9 years, SD = 0.93, 45.7% female). This study examined whether chronotype, measured as diurnal type and midpoint of sleep, was associated with the time of evening/night when digital media was used. Associations between the use of different forms of digital media and sleep quality, sleep duration and tiredness on school days were also investigated. Finally, the mediation effect of late-night digital media use to the relationship between chronotype and sleep was examined. Generalized linear models showed that evening chronotype, weekend midpoint of sleep, and the time of evening or night at which digital media was used were associated with more insufficient sleep and tiredness, lower sleep quality and shorter sleep duration on school days. The total use of all media forms, i.e., late-night digital media for music, movies/series, social media, and studying, were associated with shorter sleep duration and more insufficient sleep and daytime tiredness. Late-night social media use also mediated the association between diurnal type and sleep quality. Watching movies or listening to music late at night was the strongest mediator of the association between diurnal type and sleep and tiredness. The most prominent finding shows that of the all different media forms, watching movies or listening to music late at night were associated with increased daytime tiredness, whereas late social media use was associated with poor sleep quality. These interactions were pronounced especially for evening-types. The findings of the current study suggest that the negative effects of late-night media use are reflected especially in sleep quality and daytime tiredness among evening-types during adolescence.
A systematic review investigating the role and impact of pharmacist interventions in cardiac rehabilitation
Authors: Ahmed Aamna , Guo Ping , Jalal Zahraa
Published: November 2022

Background

Cardiovascular disease (CVD) is a predominant cause of mortality. Pharmacists play an important role in secondary prevention of CVD, however, their role in cardiac rehabilitation is under-reported and services are under-utilised.

Aim

To explore the role of pharmacists in cardiac rehabilitation, the impact of their interventions on patient outcomes, and prospects of future role development.

Method

Databases searched were PubMed, Embase, Medline, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PsycINFO from January 2006 to October 2021. Randomised and non-randomised controlled trials were selected if they assessed the role of pharmacists in cardiac rehabilitation. Cochrane risk of bias tool, Joanna Briggs Institute (JBI) Critical Appraisal Tool for Quasi-Experimental Studies and the National Heart, Lung and Blood Institute (NIH) quality assessment tool, were used to assess quality and a narrative synthesis was conducted.

Results

The search yielded 786 studies, only five met the inclusion criteria. The pharmacist-led interventions included patient education, medication review and reconciliation, and medication adherence encouragement. Four out of the five studies showed that pharmacist-led interventions in cardiac rehabilitation significantly improved patient clinical and non-clinical outcomes. One study showed a statistically significant reduction in low density lipoprotein-cholesterol (LDL-C) levels to optimal target of < 70 mg/dL (80% vs 60%,p = 0.0084). Two studies reported better medication adherence, and two studies showed greater improvement in all domains of health-related quality of life observed in the intervention group.

Conclusion

Pharmacist-led interventions in cardiac rehabilitation could lower CVD risk factors and hence recurrence. Although these findings support pharmacists’ involvement in cardiac rehabilitation, larger intervention studies are needed to evaluate the feasibility of pharmacist-led interventions and their impact on hospital admissions and mortality risk.
Institutional Environment Pressures Perceived by Bilateral Development Cooperation Agency's Constituents
Authors: Fushimi Katsutoshi
Published: November 2022

Public organisations have rarely been the subjects of neo-institutional research. Intra-organisational behaviour has also been under-researched. This study examined how four distinct groups of Bilateral Development Cooperation Agency's staff perceive institutional environment pressures from home and host countries. One-hundred thirty-one valid responses obtained through an online survey were analysed. Staff in both the headquarters and overseas offices felt a powerful home country accountability pressure. This tendency is prominent for management staff. The test results, as seen through the lens of a neo-institutional perspective, suggest that overseas office staff prioritise accountability to home country stakeholders over that to host country stakeholders.
Short pedagogical training in supporting university teachers’ professional vision: A comparison of prospective and current faculty teachers
Authors: Heinonen Neea , Katajavuori Nina , Murtonen Mari , Södervik Ilona
Published: November 2022

This study investigates the effects of a short pedagogical training on university teachers’ professional vision and (mis)conceptions concerning teaching and learning, utilizing a mixed-methods approach. Participants’ written interpretations of a video-based teaching–learning situation were analyzed and comparisons were made between prospective and current faculty teachers. Before the course, participants missed almost half of the pedagogically relevant incidents in a classroom. Generally, the short pedagogical training was successful in supporting all participants’ professional vision development. The training successfully provided all teachers’ with more in-depth reasoning skills as a result of the course. Thus, improvements in participants’ reasoning skills were identified, but interestingly not in their noticing capability. In addition, prospective teachers had more misconceptions concerning teaching and learning both before and after the training. Finally, the study discusses the implications for research on how teachers’ beliefs and conceptions are related to professional vision.