bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of Rituximab biosimilar (Riximyo®) following a single switch from the reference product in patients with Non-Hodgkin’s lymphoma: a retrospective study
Authors: Song Nina K , Musa Hala , Soriano Michael , Hibbs David E , Ramzan Iqbal , Ong Jennifer A 
Published: September 2024

AbstractUnlike small molecule drugs and generic products, the active component of biologics and biosimilars are not identical chemical entities. Despite bioequivalence, there is limited evidence in clinical practice (i.e. Phase IV post-marketing surveillance) regarding the safety of biosimilar rituximab and even less so for “switching therapy” with respect to safety. Drug substitution by switching aims to realise cost savings by changing therapy involving a reference (biologic) product to a biosimilar. A retrospective analysis of safety outcomes including treatment-emergent adverse effects (TEAEs), rates of death and discontinuation of therapy, for all patients that received switching therapy (from reference to biosimilar rituximab, n = 33) was compared to patients who did not did not switch therapy (received biosimilar rituximab only, n = 18) at an Australian metropolitan cancer centre, over a six-month period. There was no statistical significant differences for any safety outcomes examined. Switching therapy for patients receiving rituximab does not lead to poorer safety outcomes.
Flexible representative democracy
Authors: Abramowitz Ben , Mattei Nicholas 
Published: September 2024

Abstract
We introduce Flexible Representative Democracy (FRD), a novel hybrid of Representative Democracy and Direct Democracy in which voters can alter the issue-dependent weights of a set of elected representatives. In line with the literature on Interactive Democracy, our model allows the voters to actively determine the degree to which the system is direct versus representative. However, unlike Liquid Democracy, Flexible Representative Democracy uses strictly non-transitive delegations, making delegation cycles impossible, and maintains a fixed set of accountable, elected representatives. We present Flexible Representative Democracy and analyze it using a computational approach with issues that are binary and symmetric. We compare the outcomes of various voting systems using Direct Democracy with majority voting as an ideal baseline. First, we demonstrate the shortcomings of Representative Democracy in our model. We provide NP-Hardness results for electing an ideal set of representatives, discuss pathologies, and demonstrate empirically that common multi-winner election rules for selecting representatives do not perform well in expectation. To analyze the effects of adding delegation to representative voting systems, we begin by providing theoretical results on how issue-specific delegations determine outcomes. Finally, we provide empirical results comparing the outcomes of various voting systems: Representative Democracy, Proxy Voting, and FRD with issue-specific delegations. Our results show that variants of Proxy Voting yield no discernible benefit over unweighted representatives and reveal the potential for Flexible Representative Democracy to improve outcomes as voter participation increases.
ACL reconstruction demonstrates better stability compared to ACL repair for patients with Schenck III and IV knee dislocations
Authors: Fahlbusch Hendrik , Behrendt Peter , Frings Jannik , Berninger Markus T. , Korthaus Alexander , Akoto Ralph , Frosch Karl-Heinz , Krause Matthias 
Published: September 2024

Abstract
Purpose
This study compared mid-term outcomes of two anterior cruciate ligament (ACL) restoration techniques within an early total surgical care of acute knee dislocation: repair with additional internal bracing (ACLIB) and reconstruction with autograft (ACLR). Initial results at 12 months demonstrated that ACLR offered superior stability compared to ACLIB.

Methods
Retrospective clinical study of patients with acute type III or IV KD. ACLIB or ACLR procedures were performed accompanied by simultaneous suture and internal bracing of the posterior cruciate ligament (PCL) and repair with lateral augmentation of the medial and lateral complex injuries utilizing Arciero’s reconstruction technique. Patient-reported outcome measurements (PROMs), instrumental stability assessment via the Rolimeter-Test, and stress radiographs were analyzed.

Results
The study involved 20 patients (5 IIIM, 5 IIIL, and 10 IV injuries) with an average follow-up of 35.2 ± 7.4 months. Notable differences in anterior tibial translation on stress radiography favouring ACLR persisted at 24-month follow-up in side-to-side difference (SSD) (ACLIB 2.8 ± 2.5 mm vs. ACLR 0.3 ± 2.6 mm; p = 0.0487), but Rolimeter test variance diminished (SSD ACLIB 2.5 ± 0.9 mm vs. ACLR 1.8 ± 1.7 mm). Both groups showed excellent PROMs (Lysholm Score: ACLIB 84.4 ± 15.8 vs. ACLR 89.9 ± 9.0; IKDC Score: ACLIB 77.1 ± 16.2 vs. ACLR 77.7 ± 8.6).

Conclusion
Our results indicate improved anterior stability at 12 months, which persisted at 24 months after ACL reconstruction compared with ACL repair by stress radiography. Both groups showed favourable patient-reported outcomes throughout the follow-up period. Notable rates of postoperative knee stiffness were observed in both groups. These were successfully managed with early, one-time arthroscopic arthrolysis within the first seven months of treatment, resulting in no major range of motion limitations at the 24-month follow-up.

Level of evidence
Retrospective cohort study, III.
Comprehensive microRNA analyses using vitreous humor of ocular sarcoidosis
Authors: Asakage Masaki , Usui Yoshihiko , Komatsu Hiroyuki , Maruyama Kazuichi , Nezu Naoya , Shimizu Hiroyuki , Tsubota Kinya , Yamakawa Naoyuki , Umezu Tomohiro , Takanashi Masakatsu , Kuroda Masahiko , Goto Hiroshi 
Published: September 2024

Abstract
Purpose
MicroRNAs (miRNAs) are non-coding RNAs which have attracted attention as biomarkers in a variety of diseases. However, extensive unbiased analysis of miRNA in vitreous humor of sarcoidosis patients has not been reported. In the present study, we comprehensively analyzed the dysregulated miRNAs in ocular sarcoidosis to search for potential biomarkers.

Materials and Methods
This study included seven patients diagnosed with ocular sarcoidosis (five definite and two presumed). Five patients with unclassified uveitis and 24 with non-inflammatory diseases served as controls. MicroRNA expression levels in vitreous humor samples were measured by microarray, and differentially expressed miRNAs between sarcoidosis and other diseases were explored. Next, pathway enrichment analysis was performed to evaluate the functions of the dysregulated miRNAs, and machine learning was used to search for candidate biomarkers.

Results
A total of 614 upregulated miRNAs and 8 downregulated miRNAs were detected in vitreous humor of patients with ocular sarcoidosis compared with patients with unclassified uveitis and non-inflammatory diseases. Some dysregulated miRNAs were involved in the TGF-β signaling pathway. Furthermore, we identified miR-764 as the best predictor for ocular sarcoidosis using Boruta selection.

Conclusions
In this study, comprehensive miRNA analysis of vitreous humor samples identified dysregulated miRNAs in ocular sarcoidosis. This study suggests new insights into molecular pathogenetic mechanisms of sarcoidosis and may provide useful information toward developing novel diagnostic biomarkers and therapeutic targets for sarcoidosis.
Can a Hebbian-like learning rule be avoiding the curse of dimensionality in sparse distributed data?
Authors: Osório Maria , Sa-Couto Luis , Wichert Andreas 
Published: September 2024

AbstractIt is generally assumed that the brain uses something akin to sparse distributed representations. These representations, however, are high-dimensional and consequently they affect classification performance of traditional Machine Learning models due to the “curse of dimensionality”. In tasks for which there is a vast amount of labeled data, Deep Networks seem to solve this issue with many layers and a non-Hebbian backpropagation algorithm. The brain, however, seems to be able to solve the problem with few layers. In this work, we hypothesize that this happens by using Hebbian learning. Actually, the Hebbian-like learning rule of Restricted Boltzmann Machines learns the input patterns asymmetrically. It exclusively learns the correlation between non-zero values and ignores the zeros, which represent the vast majority of the input dimensionality. By ignoring the zeros the “curse of dimensionality” problem can be avoided. To test our hypothesis, we generated several sparse datasets and compared the performance of a Restricted Boltzmann Machine classifier with some Backprop-trained networks. The experiments using these codes confirm our initial intuition as the Restricted Boltzmann Machine shows a good generalization performance, while the Neural Networks trained with the backpropagation algorithm overfit the training data.
Variational analysis of sensory feedback mechanisms in powerstroke–recovery systems
Authors: Yu Zhuojun , Thomas Peter J. 
Published: September 2024

AbstractAlthough the raison d’etre of the brain is the survival of the body, there are relatively few theoretical studies of closed-loop rhythmic motor control systems. In this paper we provide a unified framework, based on variational analysis, for investigating the dual goals of performance and robustness in powerstroke–recovery systems. To demonstrate our variational method, we augment two previously published closed-loop motor control models by equipping each model with a performance measure based on the rate of progress of the system relative to a spatially extended external substrate—such as a long strip of seaweed for a feeding task, or progress relative to the ground for a locomotor task. The sensitivity measure quantifies the ability of the system to maintain performance in response to external perturbations, such as an applied load. Motivated by a search for optimal design principles for feedback control achieving the complementary requirements of efficiency and robustness, we discuss the performance–sensitivity patterns of the systems featuring different sensory feedback architectures. In a paradigmatic half-center oscillator-motor system, we observe that the excitation–inhibition property of feedback mechanisms determines the sensitivity pattern while the activation–inactivation property determines the performance pattern. Moreover, we show that the nonlinearity of the sigmoid activation of feedback signals allows the existence of optimal combinations of performance and sensitivity. In a detailed hindlimb locomotor system, we find that a force-dependent feedback can simultaneously optimize both performance and robustness, while length-dependent feedback variations result in significant performance-versus-sensitivity tradeoffs. Thus, this work provides an analytical framework for studying feedback control of oscillations in nonlinear dynamical systems, leading to several insights that have the potential to inform the design of control or rehabilitation systems.
Perspective or Spectacle? Teaching thoracic aortic anatomy in a mixed reality assisted educational approach– a two-armed randomized pilot study
Authors: Zimmer Lea , Hatzl Johannes , Uhl Christian , Kilian Samuel , Bischoff Moritz S. , Böckler Dittmar , Meisenbacher Katrin 
Published: September 2024

Abstract
Purpose
Anatomical understanding is an important basis for medical teaching, especially in a surgical context. The interpretation of complex vascular structures via two-dimensional visualization can yet be difficult, particularly for students. The objective of this study was to investigate the feasibility of an MxR-assisted educational approach in vascular surgery undergraduate education, comparing an MxR-based teaching-intervention with CT-based material for learning and understanding the vascular morphology of the thoracic aorta.

Methods
In a prospective randomized controlled trial learning success and diagnostic skills following an MxR- vs. a CT-based intervention was investigated in 120 thoracic aortic visualizations. Secondary outcomes were motivation, system-usability as well as workload/satisfaction. Motivational factors and training-experience were also assessed. Twelve students (7 females; mean age: 23 years) were randomized into two groups undergoing educational intervention with MxR or CT.

Results
Evaluation of learning success showed a mean improvement of 1.17 points (max.score: 10; 95%CI: 0.36–1.97). The MxR-group has improved by a mean of 1.33 [95% CI: 0.16–2.51], against 1.0 points [95% CI: -0.71- 2.71] in the CT-group. Regarding diagnostic skills, both groups performed equally (CT-group: 58.25 ± 7.86 vs. MxR-group:58.5 ± 6.60; max. score 92.0). 11/12 participants were convinced that MxR facilitated learning of vascular morphologies. The usability of the MxR-system was rated positively, and the perceived workload was low.

Conclusion
MxR-systems can be a valuable addition to vascular surgery education. Further evaluation of the technology in larger teaching situations are required. Especially regarding the acquisition of practical skills, the use of MxR-systems offers interesting application possibilities in surgical education.
State of the art treatment with Impella® in cardiac surgery in Austria
Authors: Wiedemann Dominik , Dumfarth Julia , Zierer Andreas F. , Zimpfer Daniel 
Published: September 2024

SummarySince 2022, the mechanical left ventricular support system Impella 5.5® has been used in Austria for patients with cardiogenic shock, advanced heart failure, post-cardiotomy and low output syndrome. The surgical insertion of the Impella 5.5 via the subclavian artery or alternatively via the ascending aorta has become an established procedure for medium-term treatment in patients with cardiogenic shock and bridging scenarios, such as bridge to recovery, bridge to left ventricular assist device (LVAD), bridge to decision, and bridge to heart transplant (HTx) in Austria. All Impella left ventricular heart pumps share the common feature of unloading the left ventricle, with the Impella 5.5 achieving a full cardiac output of 5.5 l/min. The stable positioning via transaxillary or transaortic insertion enables rapid extubation and mobilization of patients in the intensive care unit (ICU), leading to a significantly shorter ICU stay. The combined support of Impella 5.5 with venoarterial extracorporeal membrane oxygenation (VA-ECMO) has also proven effective in certain scenarios. Several nonrandomized studies demonstrated the effectiveness and safety of the Impella 5.5 in practice, which have been included in multiple international guidelines. The advantages of the Impella 5.5 in practice include the easy handling with high positional stability, and low complications rates. This article describes the significance of surgical Impella treatment in Austria from the perspective of Austrian clinical experts.
Specialized protist communities on mycorrhizal fungal hyphae
Authors: Zhang Changfeng , Geisen Stefan , Berendsen Roeland L. , van der Heijden Marcel G. A. 
Published: September 2024

AbstractArbuscular mycorrhizal (AM) fungi not only play a crucial role in acquiring nutrients for plants but also serve as a habitat for soil microbes. Recent studies observed that AM fungal hyphae are colonized by specific bacterial communities. However, so far it has not been explored whether fungal hyphae and mycorrhizal networks also harbor specific communities of protists, a key group of microbes in the soil microbiome. Here, we characterized protist communities in soil in a compartment with plant roots and on hyphae collected from hyphal compartments without plant roots. We detected specific protist communities on fungal hyphae. Fourteen protistan amplicon sequences variants (ASVs) were significantly associated with fungal hyphae, half of which belonged to the Cercozoa group. This research, for the first-time detected specific protist ASVs directly associated with abundant AM fungus hyphae, highlighting the complexity of the hyphal food web.
Should Scotland provide genome-wide sequencing for the diagnosis of rare developmental disorders? A cost-effectiveness analysis
Authors: Abbott Michael , Ryan Mandy , Hernández Rodolfo , McKenzie Lynda , Heidenreich Sebastian , Hocking Lynne , Clark Caroline , Ansari Morad , Moore David , Lampe Anne , McGowan Ruth , Berg Jonathan , Miedzybrodzka Zosia 
Published: September 2024

Abstract
Aims
This study aims to evaluate the cost effectiveness of genetic and genomic testing strategies for the diagnosis of rare developmental disorders in NHS Scotland.

Methods
Six genetic and genomic testing strategies were evaluated using a decision tree model. First-line, second-line and last-resort trio genome sequencing (GS), and second-line and last-resort trio exome sequencing (ES) were compared with standard genetic testing. The cost effectiveness of each strategy was expressed in terms of incremental cost per additional diagnosis. The impact of uncertainty on cost-effectiveness results was explored using deterministic and probabilistic sensitivity analysis.

Results
2nd-line ES was a cost-saving option, increasing diagnostic yield by 13.9% and decreasing cost by £1027 per trio compared to standard genetic testing. Compared to ES, strategies involving GS increased costs significantly, with only a moderate or zero improvement in diagnostic yield. Sensitivity analysis indicated that significant reductions in cost or improvements in diagnostic yield are required before 1st-line GS becomes cost effective.

Conclusion
2nd-line ES (after chromosomal microarray; replacing gene panel testing) for the diagnosis of developmental disorders is a cost-saving option for the Scottish NHS. Ongoing economic evaluation is required to monitor the evolving cost and diagnostic yield of GS and ES over time.
Toxicity profiles of immune checkpoint inhibitors in nervous system cancer: a comprehensive disproportionality analysis using FDA adverse event reporting system
Authors: Liu Rongrong , Zhao Hui , Lu Zenghong , Zeng Lingshuai , Shi Huaqiu , Wu Longqiu , Wang Jing , Zhong Fangjun , Liu Chuanjian , Zhang Yu , Qiu Zhengang 
Published: September 2024

AbstractBackground: Immune-related adverse events (irAEs) always occur during treatment with immune checkpoint inhibitors (ICIs). Patients with nervous system cancer (NSC) may gain clinical benefit from ICIs, but irAEs in NSC patients are rarely examined. Therefore, our study systematically summarized reports of irAEs in NSC. Methods: We obtained information from the FDA adverse event reporting system from the first quarter (Q1) of 2013 to the fourth quarter (Q4) of 2022. We examined use of a combination of ICIs and chemotherapy (ICI_Chemo) or chemotherapy only (ICI_Chemo) for patients with NSC. Multiple disproportionality analyses were applied to assess irAEs. Multiomics data from the gene expression omnibus (GEO) database were analyzed to explore potential molecular mechanisms associated with irAEs in NSC patients. Results: Fourteen irAEs were identified in 8,357 NSC patients after removing duplicates; the top five events were seizure, confused state, encephalopathy, muscular weakness and gait disturbance. Older patients were more likely to develop irAEs than were younger patients. From the start of ICIs_Chemo to irAE occurrence, there was a significant difference in the time to onset of irAEs between age groups. irAEs may occur via mechanisms involving the inflammatory response, secretion of inflammatory mediators, and aberrant activation of pathologic pathways. Conclusions: This study helps to characterize irAEs in NSC patients treated with ICIs. We combined GEO database analysis to explore the potential molecular mechanisms of irAEs. The results of this study provide a basis for improving the toxic effects of ICIs in NSC patients.
Broad geographic variation in age- and sex-dependent origin of harvested eurasian wigeon (Mareca penelope) revealed by stable-hydrogen (δ2H) isotope analyses of feathers
Authors: Holopainen Sari , Piironen Antti , Kusack Jackson W. , Hobson Keith A. , Ellis Matthew B. , Sørensen Iben Hove , Warrender Heather , Laaksonen Toni 
Published: September 2024

AbstractMigratory waterfowl are a harvested resource shared among multiple European countries, exposing them to potential overexploitation. Management of take is challenging since the life cycle of migratory waterfowl consists of several stages distributed among several locations, with possible spatio-temporal overlap among populations with differing population trends. Successful harvest management in such situations requires knowledge about the connections between breeding and non-breeding locations, and where birds are harvested. Breeding populations of Eurasian wigeon (Mareca penelope) are declining in Finland, underlining the need for more effective harvest management. Relative proportions and temporal distribution of local breeding birds and migrants from a larger Russian breeding population within the Finnish hunting bag has been unknown to date. We studied spatio-temporal origins of Finnish harvested wigeon by measuring stable-hydrogen (δ2H) isotope values from legally harvested birds. We modelled the changes in δ2H values of the feather samples within the hunting season using Gaussian processes and found that the origin of harvested wigeon in Finland changed during the hunting season and differed by age and sex. In juveniles and adult females but not in adult males, origin of harvested birds shifted from local and possibly western Russian birds to more long-distance migratory birds during the harvest season. These patterns likely reflected sex- and age-specific differences in migratory behaviour of Eurasian wigeon in the East Atlantic flyway, which can be used to guide future management and conservation of this species through the implementation of spatio-temporal harvest regulation.
Soft skills and their relationship with life satisfaction and cognitive reserve in adulthood and older age
Authors: Feraco Tommaso , Casali Nicole , Carbone Elena , Meneghetti Chiara , Borella Erika , Carretti Barbara , Muffato Veronica 
Published: September 2024

AbstractSoft skills are key factors for success in multiple contexts of daily life, as well as for life satisfaction, but little is known about their role in late adulthood and older age. In this study, we aimed to investigate the relationships of soft skills, as defined by the World Economic Forum, with two indicators of successful/healthy aging: life satisfaction and cognitive reserve. A sample of 435 adults aged 50 and over completed self-reported measures of soft skills, life satisfaction, and cognitive reserve. As control, fluid (reasoning) and crystalized (vocabulary) intelligence were assessed too, along with socio-demographic characteristics. A series of regression analyses showed that soft skills were positively related to both life satisfaction and, to a lower extent, cognitive reserve, above and beyond gender, age, and both fluid and crystallized intelligence. Interestingly, these associations were independent from participants’ age. Overall, these results highlight the importance of considering soft skills also over the middle-late adult life course, due to the potential role of these individual qualities in supporting an individual’s well-being and an active and engaged lifestyle, with implications for the promotion of a healthy aging.