bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positive Health dialogue tool and value-based healthcare: a qualitative exploratory study during residents’ outpatient consultations
Authors: Bock Lotte A , Noben Cindy Y G , Yaron Gili , George Erwin L J , Masclee Adrian A M , Essers Brigitte A B , Van Mook Walther N K A 
Published: November 2021

ObjectiveTo explore how residents experienced the application of the Positive Health dialogue tool (PH-tool) during outpatient consultations and its influence on the delivery of value-based healthcare (VBHC).DesignQualitative study using non-participant observations of outpatient consultations during which residents used the PH-tool, followed by longitudinal individual, semistructured interviews. To analyse the data from observations and interviews, observational form notes’ summarisation and categorisation, and an iterative-inductive thematic approach was used.ParticipantsEight residents—five from the ear, nose, and throat-department and three from the gastroenterology-hepatology-department—were selected through convenience sampling, accounting for 79 observations and 79 interviews.ResultsResidents had bivalent experiences with using the PH-tool. Residents discussed three main benefits: a gained insight into the individual patient’s context and functioning, a changed dynamics in resident–patient communication, and an increased awareness regarding value in terms of patient-related outcomes and healthcare costs. Three barriers became apparent: doubts regarding the PH-tool’s relevance and scope, boundaries of superspecialised medical professionals, and a lack of demarcation in clinical practice.ConclusionThe PH-tool use can be beneficial for residents during outpatient consultations with new patients and follow-up in cases of multidimensional problems, particularly in cases of chronic conditions and generalist care. In these situations, the tool yielded valuable patient information beyond physical health, helped foster patient engagement, and enabled tailoring the treatment plan to individual patients’ needs. On the other hand, the PH-tool was not a good fit for simple problems, clearly demarcated help requests, periodic follow-up consultations, or verbose patients. In addition, it was not suitable for superspecialised care, because it yielded an abundance of general information. For particular patients and problems, using the PH-tool seems a promising strategy to increase VBHC delivery. Nevertheless, further research and detailing is needed to better align the PH-tool’s broad intent and clinical practice.
Applications of the Columbus steerable guidewire
Authors: von Hessling Alexander , Reyes del Castillo Tomás , Lehmann Lutz , Roos Justus Erasmus , Karwacki Grzegorz 
Published: November 2021

The Columbus steerable guidewire (Rapid Medical, Israel) is a 0.014 inch guidewire with a remotely controlled deflectable tip intended for neuronavigational purposes. 1 The tip can be shaped by pulling or pushing the handle. Pulling the handle decreases the radius (from 4 mm to 2 mm) and curves the tip, while pushing the handle increases the curvature radius and straightens the tip until it bends in the opposite direction. The amount of deflection is at the discretion of the operator. Video 1 The response of the Columbus guidewire to rotational movements is inferior to that of standard wires, and the tip is very soft and malleable but brings great support when bent. We present two cases where the Columbus guidewire was used. In the first case, the Columbus enabled us to probe a posterior cerebral artery arising from a giant basilar tip aneurysm without wall contact. In the second case, the Columbus was used as a secondary wire to help cannulate the pericallosal artery in a patient with a recurrent anterior complex aneurysm; this subsequently permitted successful stent-assisted coiling of the aneurysm.Video 1­
Detecting and Analyzing Collusive Entities on YouTube
Authors: Dutta Hridoy Sankar , Jobanputra Mayank , Negi Himani , Chakraborty Tanmoy 
Published: November 2021

YouTube sells advertisements on the posted videos, which in turn enables the content creators to monetize their videos. As an unintended consequence, this has proliferated various illegal activities such as artificial boosting of views, likes, comments, and subscriptions. We refer to such
videos
(gaining likes and comments artificially) and
channels
(gaining subscriptions artificially) as “collusive entities.” Detecting such collusive entities is an important yet challenging task. Existing solutions mostly deal with the problem of spotting fake views, spam comments, fake content, and so on, and oftentimes ignore how such fake activities emerge via collusion. Here, we collect a large dataset consisting of two types of collusive entities on YouTube—
videos
submitted to gain collusive likes and comment requests and
channels
submitted to gain collusive subscriptions.

We begin by providing an in-depth analysis of collusive entities on YouTube fostered by various
blackmarket services
. Following this, we propose models to detect three types of collusive YouTube entities: videos seeking collusive likes, channels seeking collusive subscriptions, and videos seeking collusive comments. The third type of entity is associated with temporal information. To detect videos and channels for collusive likes and subscriptions, respectively, we utilize one-class classifiers trained on our curated collusive entities and a set of novel features. The SVM-based model shows significant performance with a true positive rate of 0.911 and 0.910 for detecting collusive videos and collusive channels, respectively. To detect videos seeking collusive comments, we propose
CollATe
, a novel end-to-end neural architecture that leverages time-series information of posted comments along with static metadata of videos.
CollATe
is composed of three components: metadata feature extractor (which derives metadata-based features from videos), anomaly feature extractor (which utilizes the time-series data to detect sudden changes in the commenting activity), and comment feature extractor (which utilizes the text of the comments posted during collusion and computes a similarity score between the comments). Extensive experiments show the effectiveness of
CollATe
(with a true positive rate of 0.905) over the baselines.
Comorbidities and Environmental Factors Associated with Atopic Dermatitis in Children and Adults in Dermatology-Venereology in Cotonou, Benin
Authors: Dégboé Bérénice , Atadokpèdé Félix , Nguessie Christabelle , Kouassi Alida , Elégbédé Nadège , Maffo Nina , Akpadjan Fabrice , Adégbidi Hugues 
Published: November 2021

Introduction. The objective of this work was to document the comorbidities and environmental factors associated with atopic dermatitis (AD) in dermatology Venereology in Cotonou. Methods. A cross-sectional, prospective, and analytical study included, from January 2016 to December 2018, in the Dermatology-Venereology Department of the National Teaching Hospital Hubert Koutoukou Maga (CNHU-HKM) of Cotonou, children and adults after free and informed consent, in whom the diagnosis of AD was retained according to the criteria of the United Kingdom Working Party. Severity was assessed using SCORAD (severity scoring of atopic dermatitis). Results. The overall prevalence of AD was 7.7%. AD was more frequent in children (56.8% and 40.6%) and adults (59.8% and 37.4%) from urban and periurban areas (0.003 <

p
<
0.034

). It was more frequent in children who regularly dewormed and those with complete vaccination (0.001 <

p
<
0.01

). In 54.8% of children and 58.9% of adults, flare-ups occurred during the warm season. The main associated comorbidities were rhinitis and conjunctivitis in both children (49.7% and 36.1%, respectively) and adults (32.7% and 26.2%, respectively). The main triggering factors in children were heat (43.2%), pneumallergens (28.4%), and skin irritants (22.6%). In adults, we noted skin irritants (58.9%), heat (47.7%), and psychological factors (34.6%). In adults, the use of detergent soaps was associated with lichenified and severe AD (0.003 <

p
<
0.006

) and that of lightening soaps with acute AD (

p
=
0.042

). Conclusion. AD in the Dermatology-Venereology Department of the CNHU-HKM of Cotonou was associated with comorbidities. It was influenced by environmental factors related to the tropical climate and by skin irritants or allergens.
Comparison of Phase Estimation Methods for Quantitative Susceptibility Mapping Using a Rotating-Tube Phantom
Authors: Keenan Kathryn E. , Berman Ben P. , Rýger Slávka , Russek Stephen E. , Wang Wen-Tung , Butman John A. , Pham Dzung L. , Dagher Joseph 
Published: November 2021

Quantitative Susceptibility Mapping (QSM) is an MRI tool with the potential to reveal pathological changes from magnetic susceptibility measurements. Before phase data can be used to recover susceptibility (

Δ
χ

), the QSM process begins with two steps: data acquisition and phase estimation. We assess the performance of these steps, when applied without user intervention, on several variations of a phantom imaging task. We used a rotating-tube phantom with five tubes ranging from

Δ
χ
=
0.05

ppm to

Δ
χ
=
0.336

ppm. MRI data was acquired at nine angles of rotation for four different pulse sequences. The images were processed by 10 phase estimation algorithms including Laplacian, region-growing, branch-cut, temporal unwrapping, and maximum-likelihood methods, resulting in approximately 90 different combinations of data acquisition and phase estimation methods. We analyzed errors between measured and expected phases using the probability mass function and Cumulative Distribution Function. Repeatable acquisition and estimation methods were identified based on the probability of relative phase errors. For single-echo GRE and segmented EPI sequences, a region-growing method was most reliable with Pr (relative error <0.1) = 0.95 and 0.90, respectively. For multiecho sequences, a maximum-likelihood method was most reliable with Pr (relative error <0.1) = 0.97. The most repeatable multiecho methods outperformed the most repeatable single-echo methods. We found a wide range of repeatability and reproducibility for off-the-shelf MRI acquisition and phase estimation approaches, and this variability may prevent the techniques from being widely integrated in clinical workflows. The error was dominated in many cases by spatially discontinuous phase unwrapping errors. Any postprocessing applied on erroneous phase estimates, such as QSM’s background field removal and dipole inversion, would suffer from error propagation. Our paradigm identifies methods that yield consistent and accurate phase estimates that would ultimately yield consistent and accurate

Δ
χ

estimates.
Dipeptidyl Peptidase (DPP)-4 Inhibitor Impairs the Outcomes of Patients with Type 2 Diabetes Mellitus After Curative Resection for Colorectal Cancer
Authors: Saito Akira , Kitayama Joji , Horie Hisanaga , Koinuma Koji , Kawashima Rie , Ohzawa Hideyuki , Yamaguchi Hironori , Kawahira Hiroshi , Mimura Toshiki , Lefor Alan Kawarai , Sata Naohiro 
Published: November 2021

Dipeptidyl peptidase IV inhibitor (DPP-4i) has been shown to act either as a promoter or as a suppressor for cancer. Although epidemiologic studies suggest that DPP-4i does not correlate with the development of malignancies, its effects on cancer metastases are controversial. We evaluated the impact of DPP-4i on postoperative outcomes of the diabetic patients with colorectal cancer and microscopic features of the resected tumors. In 260 consecutive patients with type 2 diabetes mellitus (T2DM) who underwent curative resection of colorectal cancer, the correlation between DPP-4i use and prognosis was retrospectively examined. Expression of Zeb1 on tumor cells and density of infiltrating immune cells were quantitatively evaluated with multicolor IHC in 40 tumors from DPP-4i users, 40 tumors from propensity score–matched users, and 40 tumors from nonusers. Postoperative disease-free survival (DFS) was significantly lower in 135 patients treated with DPP-4i compared with 125 nontreated patients [5-year DFS, 73.7% vs. 87.4%; HR, 1.98; 95% confidence interval (CI), 1.05–3.71; P = 0.035]. IHC revealed that the number of Zeb1+ tumor cells increased in tumors from DPP-4i–treated patients than tumors from nonusers (P &lt; 0.01). The densities of CD3+ and CD8+ T cells were significantly lower in tumors from DPP-4i users (P &lt; 0.01) with decreased density of tertiary lymphoid structures (P &lt; 0.001). However, the density of M2-type tumor-associated macrophages with CD68+ CD163+ phenotypes was significantly higher (P &lt; 0.01) in tumors from DPP-4i users. Exposure of colorectal cancer to DPP-4i may accelerate epithelial-to-mesenchymal transition (EMT) creating a tumor-permissive immune microenvironment, which might impair the outcomes of the patients with colorectal cancer and T2DM.

Significance:
DPP-4i has been shown to enhance the antitumor effects of immunotherapy. However, we found that DPP-4i significantly impairs the outcomes of patients with colorectal cancer who underwent curative resection, possibly through acceleration of EMT and creation of a tumor-permissive immune microenvironment. This suggests that DPP-4i must be used with caution until its safety is fully confirmed by further studies of the mechanistic effects on existing cancers in humans.
AKAP18δ Anchors and Regulates CaMKII Activity at Phospholamban-SERCA2 and RYR
Authors: Carlson Cathrine R. , Aronsen Jan Magnus , Bergan-Dahl Anna , Moutty Marie Christine , Lunde Marianne , Lunde Per Kristian , Jarstadmarken Hilde , Wanichawan Pimthanya , Pereira Laetitia , Kolstad Terje R.S. , Dalhus Bjørn , Subramanian Hariharan , Hille Susanne , Christensen Geir , Müller Oliver J. , Nikolaev Viacheslav , Bers Donald M. , Sjaastad Ivar , Shen Xin , Louch William E. , Klussmann Enno , Sejersted Ole M. 
Published: November 2021

Background:

The sarcoplasmic reticulum (SR) Ca
2+
-ATPase 2 (SERCA2) mediates Ca
2+
reuptake into SR and thereby promotes cardiomyocyte relaxation, whereas the ryanodine receptor (RYR) mediates Ca
2+
release from SR and triggers contraction. Ca
2+
/CaMKII (CaM [calmodulin]-dependent protein kinase II) regulates activities of SERCA2 through phosphorylation of PLN (phospholamban) and RYR through direct phosphorylation. However, the mechanisms for CaMKIIδ anchoring to SERCA2-PLN and RYR and its regulation by local Ca
2+
signals remain elusive. The objective of this study was to investigate CaMKIIδ anchoring and regulation at SERCA2-PLN and RYR.

Methods:
A role for AKAP18δ (A-kinase anchoring protein 18δ) in CaMKIIδ anchoring and regulation was analyzed by bioinformatics, peptide arrays, cell-permeant peptide technology, immunoprecipitations, pull downs, transfections, immunoblotting, proximity ligation, FRET-based CaMKII activity and ELISA-based assays, whole cell and SR vesicle fluorescence imaging, high-resolution microscopy, adenovirus transduction, adenoassociated virus injection, structural modeling, surface plasmon resonance, and alpha screen technology.

Results:

Our results show that AKAP18δ anchors and directly regulates CaMKIIδ activity at SERCA2-PLN and RYR, via 2 distinct AKAP18δ regions. An N-terminal region (AKAP18δ-N) inhibited CaMKIIδ through binding of a region homologous to the natural CaMKII inhibitor peptide and the Thr17-PLN region. AKAP18δ-N also bound CaM, introducing a second level of control. Conversely, AKAP18δ-C, which shares homology to neuronal CaMKIIα activator peptide (N2B-s), activated CaMKIIδ by lowering the apparent Ca
2+
threshold for kinase activation and inducing CaM trapping. While AKAP18δ-C facilitated faster Ca
2+
reuptake by SERCA2 and Ca
2+
release through RYR, AKAP18δ-N had opposite effects. We propose a model where the 2 unique AKAP18δ regions fine-tune Ca
2+
-frequency-dependent activation of CaMKIIδ at SERCA2-PLN and RYR.

Conclusions:
AKAP18δ anchors and functionally regulates CaMKII activity at PLN-SERCA2 and RYR, indicating a crucial role of AKAP18δ in regulation of the heartbeat. To our knowledge, this is the first protein shown to enhance CaMKII activity in heart and also the first AKAP (A-kinase anchoring protein) reported to anchor a CaMKII isoform, defining AKAP18δ also as a CaM-KAP.
Alternative Splicing Mediated by RNA-Binding Protein RBM24 Facilitates Cardiac Myofibrillogenesis in a Differentiation Stage-Specific Manner
Authors: Lu Serena Huei-An , Lee Kang-Zheng , Hsu Paul Wei-Che , Su Liang-Yu , Yeh Yu-Chen , Pan Chien-Yuan , Tsai Su-Yi 
Published: November 2021

Background:
Mutations in genes encoding sarcomeric proteins lead to failures in sarcomere assembly, the building blocks of contracting muscles, resulting in cardiomyopathies that are a leading cause of morbidity and mortality worldwide. Splicing variants of sarcomeric proteins are crucial at different stages of myofibrillogenesis, accounting for sarcomeric structural integrity. RBM24 (RNA-binding motif protein 24) is known as a tissue-specific splicing regulator that plays an essential role in cardiogenesis. However, it had been unclear if the developmental stage-specific alternative splicing facilitated by RBM24 contributes to sarcomere assembly and cardiogenesis. Our aim is to study the molecular mechanism by which RBM24 regulates cardiogenesis and sarcomere assembly in a temporal-dependent manner.

Methods:

We ablated
RBM24
from human embryonic stem cells (hESCs) using CRISPR/Cas9 techniques.

Results:

Although
RBM24
−/−
hESCs still differentiated into sarcomere-hosting cardiomyocytes, they exhibited disrupted sarcomeric structures with punctate Z-lines due to impaired myosin replacement during early myofibrillogenesis. Transcriptomics revealed >4000 genes regulated by
RBM24
. Among them, core myofibrillogenesis proteins (eg, ACTN2 [α-actinin 2], TTN [titin], and MYH10 [non-muscle myosin IIB]) were misspliced. Consequently, MYH6 (muscle myosin II) cannot replace nonmuscle myosin MYH10, leading to myofibrillogenesis arrest at the early premyofibril stage and causing disrupted sarcomeres. Intriguingly, we found that the ABD (actin-binding domain; encoded by exon 6) of the Z-line anchor protein ACTN2 is predominantly excluded from early cardiac differentiation, whereas it is consistently included in human adult heart. CRISPR/Cas9-mediated deletion of exon 6 from
ACTN2
in hESCs, as well as forced expression of full-length ACTN2 in
RBM24
−/−
hESCs, further corroborated that inclusion of exon 6 is critical for sarcomere assembly. Overall, we have demonstrated that RBM24-facilitated inclusion of exon 6 in
ACTN2
at distinct stages of cardiac differentiation is evolutionarily conserved and crucial to sarcomere assembly and integrity.

Conclusions:
RBM24 acts as a master regulator to modulate the temporal dynamics of core myofibrillogenesis genes and thereby orchestrates sarcomere organization.
Evolving Multimodal Robot Behavior via Many Stepping Stones with the Combinatorial Multiobjective Evolutionary Algorithm
Authors: Huizinga Joost , Clune Jeff 
Published: November 2021

Abstract
An important challenge in reinforcement learning is to solve multimodal problems, where agents have to act in qualitatively different ways depending on the circumstances. Because multimodal problems are often too difficult to solve directly, it is often helpful to define a curriculum, which is an ordered set of subtasks that can serve as the stepping stones for solving the overall problem. Unfortunately, choosing an effective ordering for these subtasks is difficult, and a poor ordering can reduce the performance of the learning process. Here, we provide a thorough introduction and investigation of the Combinatorial Multiobjective Evolutionary Algorithm (CMOEA), which allows all combinations of subtasks to be explored simultaneously. We compare CMOEA against three algorithms that can similarly optimize on multiple subtasks simultaneously: NSGA-II, NSGA-III, and ε-Lexicase Selection. The algorithms are tested on a function-optimization problem with two subtasks, a simulated multimodal robot locomotion problem with six subtasks, and a simulated robot maze-navigation problem where a hundred random mazes are treated as subtasks. On these problems, CMOEA either outperforms or is competitive with the controls. As a separate contribution, we show that adding a linear combination over all objectives can improve the ability of the control algorithms to solve these multimodal problems. Lastly, we show that CMOEA can leverage auxiliary objectives more effectively than the controls on the multimodal locomotion task. In general, our experiments suggest that CMOEA is a promising algorithm for solving multimodal problems.
Dopamine, Cognitive Flexibility, and IQ: Epistatic Catechol-O-MethylTransferase:DRD2 Gene–Gene Interactions Modulate Mental Rigidity
Authors: Zmigrod Leor , Robbins Trevor W. 
Published: November 2021

Abstract
Cognitive flexibility has been hypothesized to be neurochemically rooted in dopamine neurotransmission. Nonetheless, underpowered sample sizes and contradictory meta-analytic findings have obscured the role of dopamine genes in cognitive flexibility and neglected potential gene–gene interactions. In this largest neurocognitive-genetic study to date (n = 1400), single nucleotide polymorphisms associated with elevated prefrontal dopamine levels (catechol-O-methyltransferase; rs4680) and diminished striatal dopamine (C957T; rs6277) were both implicated in Wisconsin Card Sorting Test performance. Crucially, however, these genetic effects were only evident in low-IQ participants, suggesting high intelligence compensates for, and eliminates, the effect of dispositional dopamine functioning on flexibility. This interaction between cognitive systems may explain and resolve previous empirical inconsistencies in highly educated participant samples. Moreover, compensatory gene–gene interactions were discovered between catechol-O-methyltransferase and DRD2, such that genotypes conferring either elevated prefrontal dopamine or diminished striatal dopamine—via heightened striatally concentrated D2 dopamine receptor availability—are sufficient for cognitive flexibility, but neither is necessary. The study has therefore revealed a form of epistatic redundancy or substitutability among dopamine systems in shaping adaptable thought and action, thus defining boundary conditions for dopaminergic effects on flexible behavior. These results inform theories of clinical disorders and psychopharmacological interventions and uncover complex fronto-striatal synergies in human flexible cognition.
Slithering Stories We Live By: Animal Educators’ Construction and Enactment of Positive Snake Narratives
Authors: Rosenfeld Cynthia 
Published: November 2021

Abstract
Representations of snakes abound in literature, oral traditions, and visual arts. Often constructed as sneaky or sinister, the cultural evaluation of snakes can perhaps best be stated by the adage, “The only good snake is a dead snake.” Such messages become the “stories we live by.” This evaluation is widespread but not universal. Educators are agents of alternative stories that exist in struggle with dominant ones. This study used ethnographic methods to explore how the setting, audience, storytelling educators, and story told all shape the conceptualization of “snake.” The setting may resist or perpetuate a negative cultural evaluation of snakes. Presuppositions, convictions, and available examples of modeling influence whether audience members choose to adopt a new story or retain the old one. Through their discourse, enactments, and material displays, educators offer an embodied, sensorial story with the central message, “The only good snake is a live snake.”