bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning Analytics in Open, Distance, and Digital Education (ODDE)
Authors: Prinsloo Paul 
Published: September 2022

AbstractData, and specifically student data, has always been an integral part of good teaching as well as providing evidence for strategic and operational planning, resource allocation, pedagogy, and student support. As Open, Distance, and Digital Education (ODDE) become increasingly datafied, institutions have access to greater volumes, variety, and granularity of student data, from more diverse sources than ever before. This provides huge opportunity for institutions, and specifically educators and course support teams, to better understand learning, and provide more appropriate and effective student support.With the emergence of learning analytics (LA) in 2011, the measurement, collection, analysis, and reporting of data about learners and their contexts, for purposes of understanding and optimizing learning and the environments in which it occurs, gained momentum, both as research focus and practice. Since then, LA have become institutionalized in many higher education institutions, mostly in residential institutions located in the Global North, and established a prolific presence in research on student learning in digitized environments. While LA has become institutionalized in the Open University (UK), it remains an emerging research focus and practice in many ODDE institutions across the world.This chapter considers the implications of LA for ODDE research and practice by first providing a brief overview of the evolution of LA, and specifically the theoretical influences in this evolution. A selection of major research findings and discourses in LA are then discussed, before the chapter is concluded with some open questions for a research agenda for LA in ODDE.
Emergent metric space-time from matrix theory
Authors: Brahma Suddhasattwa , Brandenberger Robert , Laliberte Samuel 
Published: September 2022

Abstract
The IKKT matrix model yields an emergent space-time. We further develop these ideas and give a proposal for an emergent metric. Based on previous numerical studies of this model, we provide evidence that the emergent space-time is continuous and infinite in extent, both in space and in time, and that the metric is spatially flat. The time evolution describes the transition from a string-theoretic emergent phase to a phase in which the SO(9) symmetry of the model is spontaneously broken to SO(6) × SO(3), with three dimensions of space expanding, becoming classical and at later times evolving like in a radiation-dominated universe, and the remaining six dimensions of space stabilized at the string scale. We speculate on how this analysis can be extended to yield an early universe cosmology which, in addition to the above-mentioned properties, also leads to a roughly scale-invariant spectrum of cosmological fluctuations and gravitational waves.
Potent anticancer activity of a novel iridium metallodrug via oncosis
Authors: Ortega-Forte Enrique , Hernández-García Samanta , Vigueras Gloria , Henarejos-Escudero Paula , Cutillas Natalia , Ruiz José , Gandía-Herrero Fernando 
Published: September 2022

AbstractOncosis (from Greek ónkos, meaning “swelling”) is a non-apoptotic cell death process related to energy depletion. In contrast to apoptosis, which is the main form of cell death induced by anticancer drugs, oncosis has been relatively less explored but holds potential to overcome drug resistance phenomena. In this study, we report a novel rationally designed mitochondria-targeted iridium(III) complex (OncoIr3) with advantageous properties as a bioimaging agent. OncoIr3 exhibited potent anticancer activity in vitro against cancer cells and displayed low toxicity to normal dividing cells. Flow cytometry and fluorescence-based assays confirmed an apoptosis-independent mechanism involving energy depletion, mitochondrial dysfunction and cellular swelling that matched with the oncotic process. Furthermore, a Caenorhabditis elegans tumoral model was developed to test this compound in vivo, which allowed us to prove a strong oncosis-derived antitumor activity in animals (with a 41% reduction of tumor area). Indeed, OncoIr3 was non-toxic to the nematodes and extended their mean lifespan by 18%. Altogether, these findings might shed new light on the development of anticancer metallodrugs with non-conventional modes of action such as oncosis, which could be of particular interest for the treatment of apoptosis-resistant cancers.
Graphical abstract
Spline-based shape optimization of large-scale composite leaf spring models using Bayesian strategies with multiple constraints
Authors: Winter Jens , Fiebig Sierk , Franke Thilo , Bartz Ronald , Vietor Thomas 
Published: September 2022

AbstractThe presented paper describes a shape optimization workflow using Bayesian strategies. It is applied to a novel automotive axle system consisting of leaf springs made from glass fiber reinforced plastics (GFRP). Besides the primary objectives of cost and mass reduction, the assembly has to meet multiple technical constraints with respect to various loading conditions. The related large-scale finite element model is fully parameterized by splines, hence the general shape of the guide curve as well as the spring’s height, width and material properties can be altered by the corresponding workflow. For this purpose, a novel method is developed to automatically generate high-quality meshes depending on the geometry of the respective springs. The size and complexity of the model demands the implementation of efficient optimization techniques with a preferably small number of required response function evaluations. Therefore, an existing optimization framework is extended by state-of-the-art Bayesian methods, including different kernel combinations and multiple acquisition function approaches, which are then tested, evaluated and compared. To properly address the use of GFRP as spring material in the objective function, an appropriate cost model is derived. Emerging challenges, such as conflicting targets regarding direct material costs and potential lightweight measures, are considered and investigated. The intermediate steps of the developed optimization procedure are tested on various sample functions and simplified models. The entire workflow is finally applied to the complete model and evaluated. Concluding, ideas and possibilities in improving the optimization process, such as the use of models with varying complexity, are discussed.
Towards automatic classification of cardiovascular magnetic resonance Task Force Criteria for diagnosis of arrhythmogenic right ventricular cardiomyopathy
Authors: Bourfiss Mimount , Sander Jörg , de Vos Bob D. , te Riele Anneline S. J. M. , Asselbergs Folkert W. , Išgum Ivana , Velthuis Birgitta K. 
Published: September 2022

Abstract
Background
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is diagnosed according to the Task Force Criteria (TFC) in which cardiovascular magnetic resonance (CMR) imaging plays an important role. Our study aims to apply an automatic deep learning-based segmentation for right and left ventricular CMR assessment and evaluate this approach for classification of the CMR TFC.

Methods
We included 227 subjects suspected of ARVC who underwent CMR. Subjects were classified into (1) ARVC patients fulfilling TFC; (2) at-risk family members; and (3) controls. To perform automatic segmentation, a Bayesian Dilated Residual Neural Network was trained and tested. Performance of automatic versus manual segmentation was assessed using Dice-coefficient and Hausdorff distance. Since automatic segmentation is most challenging in basal slices, manual correction of the automatic segmentation in the most basal slice was simulated (automatic−basal). CMR TFC calculated using manual and automatic−basal segmentation were compared using Cohen’s Kappa (κ).

Results
Automatic segmentation was trained on CMRs of 70 subjects (39.6 ± 18.1 years, 47% female) and tested on 157 subjects (36.9 ± 17.6 years, 59% female). Dice-coefficient and Hausdorff distance showed good agreement between manual and automatic segmentations (≥ 0.89 and ≤ 10.6 mm, respectively) which further improved after simulated correction of the most basal slice (≥ 0.92 and ≤ 9.2 mm, p < 0.001). Pearson correlation of volumetric and functional CMR measurements was good to excellent (automatic (r = 0.78–0.99, p < 0.001) and automatic−basal (r = 0.88–0.99, p < 0.001) measurements). CMR TFC classification using automatic−basal segmentations was comparable to manual segmentations (κ 0.98 ± 0.02) with comparable diagnostic performance.

Conclusions
Combining automatic segmentation of CMRs with correction of the most basal slice results in accurate CMR TFC classification of subjects suspected of ARVC.

Graphical abstract
Efficacy and safety of long-term botulinum toxin treatment for acquired cervical dystonia: a 25-year follow-up
Authors: Petracca Martina , Lo Monaco Maria Rita , Ialongo Tamara , Di Stasio Enrico , Cerbarano Maria Luana , Maggi Loredana , De Biase Alessandro , Di Lazzaro Giulia , Calabresi Paolo , Bentivoglio Anna Rita 
Published: September 2022

AbstractBotulinum toxin A (BoNT/A) is the first-line treatment for idiopathic cervical dystonia (ICD) and is widely used in the clinical setting. To date, scanty data are available on the effectiveness of BoNT in treating acquired cervical dystonia (ACD). Here we present a long-term follow-up of ACD patients treated with BoNT/A that focused on safety and efficacy. The study included subjects who had received at least six treatments of three commercially available BoNT/A drugs [abobotulinumtoxinA (A/Abo), incobotulinumtoxinA (A/Inco) and onabotulinumtoxinA (A/Ona)]. Safety and efficacy were assessed based on patients' self-reports regarding adverse effects (AE), duration of improvement of dystonia and/or pain relief. Global clinical improvement was measured on a six-point scale. 23 patients with ACD were administered 739 treatments (A/Abo in 235, A/Inco in 72, A/Ona in 432) with a mean number of treatments of 31 ± 20 (range 6–76) and duration of 10 ± 6 weeks (range 2–25). The mean dose was 737 ± 292 U for A/Abo, 138 ± 108 U for A/Inco and 158 ± 80 U for A/Ona. The average benefit duration was 89 ± 26 (A/Abo), 88 ± 30 days (A/Inco), and 99 ± 55 days (A/Ona) (p = 0.011); global clinical improvement for all sessions was 4 ± 1. ANOVA one-way analysis indicated that A/Ona had the best profile in terms of duration (p < 0.05), whereas A/Abo had the best pain relief effect (p = 0.002). Side effects were reported in 9% of treatments (67/739), with ten treatments (1%) complicated by two side effects. Most side effects were rated mild to moderate; severe side effects occurred following three treatments with the three different BoNT; two required medical intervention. No allergic reactions were reported. Even after 25 years of repeated treatments, all serotypes of BoNT demonstrate positive effects in treating ACD with long-lasting efficacy and safety.
Heterozygous variants in the DVL2 interaction region of DACT1 cause CAKUT and features of Townes–Brocks syndrome 2
Authors: Christians Anne , Kesdiren Esra , Hennies Imke , Hofmann Alejandro , Trowe Mark-Oliver , Brand Frank , Martens Helge , Gjerstad Ann Christin , Gucev Zoran , Zirngibl Matthias , Geffers Robert , Seeman Tomáš , Billing Heiko , Bjerre Anna , Tasic Velibor , Kispert Andreas , Ure Benno , Haffner Dieter , Dingemann Jens , Weber Ruthild G. 
Published: September 2022

AbstractMost patients with congenital anomalies of the kidney and urinary tract (CAKUT) remain genetically unexplained. In search of novel genes associated with CAKUT in humans, we applied whole-exome sequencing in a patient with kidney, anorectal, spinal, and brain anomalies, and identified a rare heterozygous missense variant in the DACT1 (dishevelled binding antagonist of beta catenin 1) gene encoding a cytoplasmic WNT signaling mediator. Our patient’s features overlapped Townes–Brocks syndrome 2 (TBS2) previously described in a family carrying a DACT1 nonsense variant as well as those of Dact1-deficient mice. Therefore, we assessed the role of DACT1 in CAKUT pathogenesis. Taken together, very rare (minor allele frequency ≤ 0.0005) non-silent DACT1 variants were detected in eight of 209 (3.8%) CAKUT families, significantly more frequently than in controls (1.7%). All seven different DACT1 missense variants, predominantly likely pathogenic and exclusively maternally inherited, were located in the interaction region with DVL2 (dishevelled segment polarity protein 2), and biochemical characterization revealed reduced binding of mutant DACT1 to DVL2. Patients carrying DACT1 variants presented with kidney agenesis, duplex or (multi)cystic (hypo)dysplastic kidneys with hydronephrosis and TBS2 features. During murine development, Dact1 was expressed in organs affected by anomalies in patients with DACT1 variants, including the kidney, anal canal, vertebrae, and brain. In a branching morphogenesis assay, tubule formation was impaired in CRISPR/Cas9-induced Dact1−/− murine inner medullary collecting duct cells. In summary, we provide evidence that heterozygous hypomorphic DACT1 variants cause CAKUT and other features of TBS2, including anomalies of the skeleton, brain, distal digestive and genital tract.
Experimental evaluation of laparoscopic laser speckle contrast imaging to visualize perfusion deficits during intestinal surgery
Authors: Heeman Wido , Wildeboer Aurelia C. L. , Al-Taher Mahdi , Calon Joost E. M. , Stassen Laurents P. S. , Diana Michele , Derikx Joep P. M. , van Dam Gooitzen M. , Boerma E. Christiaan , Bouvy Nicole D. 
Published: September 2022

Abstract
Background
Ischemia at the site of an intestinal anastomosis is one of the most important risk factors for anastomotic leakage (AL). Consequently, adequate intestinal microperfusion is essential for optimal tissue oxygenation and anastomotic healing. As visual inspection of tissue viability does not guarantee an adequate objective evaluation of intestinal microperfusion, surgeons are in dire need of supportive tools to decrease anastomotic leakage after colorectal surgery.

Methods
In this feasibility study, laparoscopic laser speckle contrast imaging (LSCI) was used to evaluate intestinal microperfusion in an experimental ischemic bowel loop model. Both large and small ischemic loops were created from the small intestine of a pig; each loop was divided into 5 regions of interest (ROI) with varying levels of ischemia. Speckle contrast and local capillary lactate (LCL) was measured in all ROIs.

Results
Both real-time visualization of intestinal microperfusion and induced perfusion deficits was achieved in all bowel loops. As a result, the emergence of regions of intestinal ischemia could be predicted directly after iatrogenic perfusion limitation, whereas without LSCI signs of decreased intestinal viability could only be seen after 30 minutes. Additionally, a significant relation was found between LCL and LSCI.

Conclusion
In conclusion, LSCI can achieve real-time intraoperative visualization of intestinal microperfusion deficits, allowing for accurate prediction of long-term postoperative ischemic complications. With this revealing capacity, LSCI could potentially facilitate surgical decision-making when constructing intestinal anastomoses in order to mitigate ischemia-related complications such as AL.
Exercise training as part of multidisciplinary rehabilitation in cancer survivors: an observational study on changes in physical performance and patient-reported outcomes
Authors: Weemaes Anouk T. R. , Weijenberg Matty P. , Lenssen Antoine F. , Beelen Milou 
Published: September 2022

Abstract

Purpose

To describe changes in physical performance and patient-reported outcomes in cancer survivors who participated in an exercise program as part of usual-care multidisciplinary rehabilitation and the influence of training adaptations during the coronavirus-19 (COVID-19) pandemic.

Methods
In an observational cohort study, cancer survivors underwent usual-care multidisciplinary rehabilitation including a 10-week exercise program. During the COVID-19 pandemic, the exercise program was adapted with reduced training time and frequency. Mean changes and 95% confidence intervals in physical performance (peak oxygen uptake (VO2peak), peak work rate during a steep ramp test (SRT-WRpeak), 6-min walking distance, muscle strength) and patient-reported outcomes (health-related quality of life, fatigue, anxiety, and depression) were assessed between the start and the end of the exercise program. Linear regression analysis, adjusting for baseline levels of outcomes, was used to investigate differences in changes in outcomes between participants who underwent the original and the adapted program.

Results
All outcomes statistically significantly improved over time, regardless of adaptations in the exercise program. VO2peak increased with 9.6% and 7.7% in the original and adapted program, respectively. Significant smaller improvements were observed in SRT-WRpeak (− 3.9%) and upper body muscle strength (− 10.8%) after participation in the adapted compared to the original program. No significant between-group differences were observed for other outcomes.

Conclusion
Physical performance and patient-reported outcomes statistically and clinically significantly improved in cancer survivors who participated in an exercise program as part of usual-care multidisciplinary rehabilitation. Improvements of performance outcomes were smaller since the training adaptations, though only significant for SRT-WRpeak and upper body strength.
Pertuzumab, trastuzumab, and chemotherapy in HER2-positive gastric/gastroesophageal junction cancer: end-of-study analysis of the JACOB phase III randomized clinical trial
Authors: Tabernero Josep , Hoff Paulo M. , Shen Lin , Ohtsu Atsushi , Shah Manish A. , Siddiqui Asna , Heeson Sarah , Kiermaier Astrid , Macharia Harrison , Restuccia Eleonora , Kang Yoon-Koo 
Published: September 2022

Abstract
Background
Dual-targeted anti-HER2 therapy significantly improves outcomes in HER2-positive breast cancer and could be beneficial in other HER2-positive cancers. JACOB’s end-of study analyses aimed to evaluate the long-term efficacy and safety of pertuzumab plus trastuzumab and chemotherapy for previously untreated HER2-positive metastatic gastric or gastroesophageal junction cancer.

Methods
Eligible patients were randomized 1:1 to pertuzumab/placebo plus trastuzumab and chemotherapy every 3 weeks. Primary endpoint: overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), and safety.

Results
The intention-to-treat population comprised 388 patients in the pertuzumab arm and 392 in the placebo arm. The safety population comprised 385 and 388 patients, respectively. Median follow-up was ≥ 44.4 months. Median OS was increased by 3.9 months (hazard ratio 0.85 [95% confidence intervals, 0.72–0.99]) and median PFS by 1.3 months (hazard ratio 0.73 [95% confidence intervals, 0.62–0.85]) in the pertuzumab vs. the placebo arm. ORR was numerically higher (57.0% vs. 48.6%) and median DoR 1.8 months longer with pertuzumab treatment. There was a trend for more favorable hazard ratios in certain subgroups related to HER2 amplification/overexpression. Safety was comparable between arms, except for serious and grade 3–5 adverse events, and any-grade diarrhea, which were more frequent with pertuzumab.

Conclusions
JACOB did not meet its primary endpoint. Nonetheless, the study continues to demonstrate some, albeit limited, evidence of treatment activity and an acceptable safety profile for pertuzumab plus trastuzumab and chemotherapy in previously untreated HER2-positive metastatic gastric or gastroesophageal junction cancer after long-term follow-up.
Trial registration NCT01774786; https://clinicaltrials.gov/ct2/show/NCT01774786.
Minimally invasive versus open transforaminal lumbar interbody fusion: a prospective, controlled observational study of short-term outcome
Authors: Hartmann Sebastian , Lang Anna , Lener Sara , Abramovic Anto , Grassner Lukas , Thomé Claudius 
Published: September 2022

AbstractInstrumented stabilization with intersomatic fusion can be achieved by open (O-TLIF) or minimally invasive (MIS-TLIF) transforaminal surgical access. While less invasive techniques have been associated with reduced postoperative pain and disability, increased manipulation and insufficient decompression may contradict MIS techniques. In order to detect differences between both techniques in the short-term, a prospective, controlled study was conducted. Thirty-eight patients with isthmic or degenerative spondylolisthesis or degenerative disk disease were included in this prospective, controlled study (15 MIS-TLIF group vs. 23 O-TLIF group) after failed conservative treatment. Patients were examined preoperatively, on the first, third, and sixth postoperative day as well as after 2, 4, and 12 weeks postoperatively. Outcome parameters included blood loss, duration of surgery, pre- and postoperative pain (numeric rating scale [NRS], visual analog scale [VAS]), functionality (Timed Up and Go test [TUG]), disability (Oswestry Disability index [ODI]), and quality of life (EQ-5D). Intraoperative blood loss (IBL) as well as postoperative blood loss (PBL) was significantly higher in the O-TLIF group ([IBL O-TLIF 528 ml vs. MIS-TLIF 213 ml, p = 0.001], [PBL O-TLIF 322 ml vs. MIS-TLIF 30 ml, p = 0.004]). The O-TLIF cohort showed significantly less leg pain postoperatively compared to the MIS-TLIF group ([NRS leg 3rd postoperative day, p = 0.027], [VAS leg 12 weeks post-op, p = 0.02]). The MIS group showed a significantly better improvement in the overall ODI (40.8 ± 13 vs. 56.0 ± 16; p = 0.05). After 3 months in the short-term follow-up, the MIS procedure tends to have better results in terms of patient-reported quality of life. MIS-TLIF offers perioperative advantages but may carry the risk of increased nerve root manipulation with consecutive higher radicular pain, which may be related to the learning curve of the procedure.
Behavioral Addictions Questionnaire (BAQ): Validation of a New Tool for the Screening of Multiple Addictive Behaviors in the Italian Population
Authors: Mastropietro Stefania , Favieri Francesca , Forte Giuseppe , Locuratolo Nicoletta , Mannarelli Daniela , Pauletti Caterina , Fattapposta Francesco , Casagrande Maria 
Published: September 2022

AbstractThis study deals with the uncertainty in defining behavioral addictions (BAs). BAs are characterized by specific compulsive behaviors, regardless of potential negative consequences. However, to differentiate a behavior from a leisure activity to an addictive one is still an object of debate in the literature. Accordingly, this study aimed to assess the psychometric properties of the Behavioral Addictions Questionnaire (BAQ) as a possible screening tool for multiple BAs (i.e., shopping, food addiction, gambling, sex, work, exercise, Internet, videogames, and smartphone). BAQ aims to give a dimensional and quantitative assessment of addictive behaviors in a continuum, including both the adaptive and maladaptive features of the behaviors. Five hundred and seventy-six healthy adults (age range: 18–88) participated in the study, completing a survey including the BAQ questionnaire. Considering both exploratory and confirmatory factor analyses, statistical examination suggested good psychometric properties, with adequate validity in all its subscales (i.e., the goodness of fit). Moreover, also higher reliability was confirmed for each dimension detected (i.e., all alpha over 0.65). The BAQ represents a comprehensive screening instrument that benefits from appropriate validity and reliability for assessing BAs. Therefore, it can be used in clinical fields and research. Moreover, the feature of BAs on a continuum, and the severity index adopted by the study, can help from a preventive perspective. However, further validation of the BAQ is needed in other countries and contexts.