bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting thalamocortical circuits for closed-loop stimulation in Lennox–Gastaut syndrome
Authors: Warren Aaron E L , Butson Christopher R , Hook Matthew P , Dalic Linda J , Archer John S , Macdonald-Laurs Emma , Schaper Frederic L W V J , Hart Lauren A , Singh Hargunbir , Johnson Lise , Bullinger Katie L , Gross Robert E , Morrell Martha J , Rolston John D 
Published: May 2024

Abstract
This paper outlines the therapeutic rationale and neurosurgical targeting technique for bilateral, closed-loop, thalamocortical stimulation in Lennox–Gastaut syndrome, a severe form of childhood-onset epilepsy. Thalamic stimulation can be an effective treatment for Lennox–Gastaut syndrome, but complete seizure control is rarely achieved. Outcomes may be improved by stimulating areas beyond the thalamus, including cortex, but the optimal targets are unknown. We aimed to identify a cortical target by synthesizing prior neuroimaging studies, and to use this knowledge to advance a dual thalamic (centromedian) and cortical (frontal) approach for closed-loop stimulation. Multi-modal brain network maps from three group-level studies of Lennox–Gastaut syndrome were averaged to define the area of peak overlap: simultaneous EEG-functional MRI of generalized paroxysmal fast activity, [18F]fluorodeoxyglucose PET of cortical hypometabolism and diffusion MRI structural connectivity associated with clinical efficacy in a previous trial of thalamic deep brain stimulation. The resulting ‘hotspot’ was used as a seed in a normative functional MRI connectivity analysis to identify connected networks. Intracranial electrophysiology was reviewed in the first two trial patients undergoing bilateral implantations guided by this hotspot. Simultaneous recordings from cortex and thalamus were analysed for presence and synchrony of epileptiform activity. The peak overlap was in bilateral premotor cortex/caudal middle frontal gyrus. Functional connectivity of this hotspot revealed a distributed network of frontoparietal cortex resembling the diffuse abnormalities seen on EEG-functional MRI and PET. Intracranial electrophysiology showed characteristic epileptiform activity of Lennox–Gastaut syndrome in both the cortical hotspot and thalamus; most detected events occurred first in the cortex before appearing in the thalamus. Premotor frontal cortex shows peak involvement in Lennox–Gastaut syndrome and functional connectivity of this region resembles the wider epileptic brain network. Thus, it may be an optimal target for a range of neuromodulation therapies, including thalamocortical stimulation and emerging non-invasive treatments like focused ultrasound or transcranial magnetic stimulation. Compared to thalamus-only approaches, the addition of this cortical target may allow more rapid detections of seizures, more diverse stimulation paradigms and broader modulation of the epileptic network. A prospective, multi-centre trial of closed-loop thalamocortical stimulation for Lennox–Gastaut syndrome is currently underway.
Combined low-dose dobutamine and exercise stress echocardiography: a new hybrid protocol to detect inducible ischaemia
Authors: Vakalis Konstantinos , Berrill Max , Jimeno Majimen , Chester Ruth , Rahman-Haley Shelley , Barron Anthony , Baltabaeva Aigul 
Published: May 2024

Abstract

Aims
Myocardial response to stress echocardiography may be elicited physiologically, through exercise, or pharmacologically, often with dobutamine. Both have advantages but also limitations due to reduced exercise capacity or side-effects to stressor agent/lack of closeness to true pathophysiology of ischaemic cascade. We have combined low-dose dobutamine and exercise, creating a ‘hybrid’ protocol to utilize the advantages of both techniques and limit the drawbacks. The aim of the study was to evaluate its safety and feasibility.

Methods and results
In the hybrid protocol, low-dose dobutamine infusion (up to 10 µg/kg/min) is enhanced by supine bicycle exercise at 3-min increments of workload of 25 W to achieve target heart rate (THR). We analysed safety and outcome data for all the patients who underwent this protocol from 2017 to 2022. Out of 835, 727 (87.1%) patients referred for evaluation of ischaemia underwent the hybrid protocol. The median age was 61 years old and 61% (442/727) were men. The median exercise time was 11 (9–13.5) min with a median maximum workload of 100 W (75–125). Out of 727, 670 (92.2%) achieved THR. Atropine was not used. Out of 727, 192 (26.4%) of studies were positive for ischaemia. Out of 122, 102 (83.6%) with positive stress who underwent invasive angiography had significant coronary disease. The incidence of complications was low: 1/727—severe arrhythmia, 5/727 (0.7%) developed a vasovagal episode, and 14/727 (1.9%) had a hypertensive response to exercise.

Conclusion
Our findings suggest that this protocol is safe, feasible, and has a high success rate in achieving THR.
Virulence characteristics of Gram-positive bacteria isolated from diabetic foot ulcers
Authors: Keogh Rebecca A , Huyvaert Savannah , Moore Garrett D , Horswill Alexander R , Doran Kelly S 
Published: May 2024

Abstract
Diabetic wound infections including diabetic foot ulcers (DFUs) are a major global health concern and a leading cause of non-traumatic amputations. Numerous bacterial species establish infection in DFUs, and treatment with antibiotics often fails due to widespread antibiotic resistance and biofilm formation. Determination of bacterial species that reside in DFU and their virulence potential is critical to inform treatment options. Here, we isolate bacteria from debridement tissues from patients with diabetes at the University of Colorado Anschutz Medical Center. The most frequent species were Gram-positive including Enterococcus faecalis, Staphylococcus aureus, and Streptococcus agalactiae, also known as Group B Streptococcus (GBS). Most tissues had more than one species isolated with E. faecalis and GBS frequently occurring in polymicrobial infection with S. aureus. S. aureus was the best biofilm producing species with E. faecalis and GBS isolates exhibiting little to no biofilm formation. Antibiotic susceptibility varied amongst strains with high levels of penicillin resistance amongst S. aureus, clindamycin resistance amongst GBS and intermediate vancomycin resistance amongst E. faecalis. Finally, we utilized a murine model of diabetic wound infection and found that the presence of S. aureus led to significantly higher recovery of GBS and E. faecalis compared to mice challenged in mono-infection.
The Evolution and Characterization of the RNA Interference Pathways in Lophotrochozoa
Authors: Formaggioni Alessandro , Cavalli Gianmarco , Hamada Mayuko , Sakamoto Tatsuya , Plazzi Federico , Passamonti Marco 
Published: May 2024

Abstract
In animals, three main RNA interference mechanisms have been described so far, which respectively maturate three types of small noncoding RNAs (sncRNAs): miRNAs, piRNAs, and endo-siRNAs. The diversification of these mechanisms is deeply linked with the evolution of the Argonaute gene superfamily since each type of sncRNA is typically loaded by a specific Argonaute homolog. Moreover, other protein families play pivotal roles in the maturation of sncRNAs, like the DICER ribonuclease family, whose DICER1 and DICER2 paralogs maturate respectively miRNAs and endo-siRNAs. Within Metazoa, the distribution of these families has been only studied in major groups, and there are very few data for clades like Lophotrochozoa. Thus, we here inferred the evolutionary history of the animal Argonaute and DICER families including 43 lophotrochozoan species. Phylogenetic analyses along with newly sequenced sncRNA libraries suggested that in all Trochozoa, the proteins related to the endo-siRNA pathway have been lost, a part of them in some phyla (i.e. Nemertea, Bryozoa, Entoprocta), while all of them in all the others. On the contrary, early diverging phyla, Platyhelminthes and Syndermata, showed a complete endo-siRNA pathway. On the other hand, miRNAs were revealed the most conserved and ubiquitous mechanism of the metazoan RNA interference machinery, confirming their pivotal role in animal cell regulation.
Hospital-Based Health Professionals’ Perceptions of Frailty in Older People
Authors: Manuel Kisani , Crotty Maria , Kurrle Susan E , Cameron Ian D , Lane Rachel , Lockwood Keri , Block Heather , Sherrington Catherine , Pond Dimity , Nguyen Tuan A , Laver Kate 
Published: May 2024

Abstract

Background and Objectives
There is a high prevalence of frailty amongst older patients in hospital settings. Frailty guidelines exist but implementation to date has been challenging. Understanding health professional attitudes, knowledge, and beliefs about frailty is critical in understanding barriers and enablers to guideline implementation, and the aim of this study was to understand these in rehabilitation multidisciplinary teams in hospital settings.

Research Design and Methods
Twenty-three semistructured interviews were conducted with health professionals working in multidisciplinary teams on geriatric and rehabilitation wards in Adelaide and Sydney, Australia. Interviews were audio recorded, transcribed, and coded by 2 researchers. A codebook was created and interviews were recoded and applied to the Framework Method of thematic analysis.

Results
Three domains were developed: diagnosing frailty, communicating about frailty, and managing frailty. Within these domains, 8 themes were identified: (1) diagnosing frailty has questionable benefits, (2) clinicians don’t use frailty screening tools, (3) frailty can be diagnosed on appearance and history, (4) frailty has a stigma, (5) clinicians don’t use the word “frail” with patients, (6) frailty isn’t always reversible, (7) there is a lack of continuity of care after acute admission, and (8) the community setting lacks resources.

Discussion and Implications
Implementation of frailty guidelines will remain challenging while staff avoid using the term “frail,” don’t perceive benefit of using screening tools, and focus on the individual aspects of frailty rather than the syndrome holistically. Clinical champions and education about frailty identification, reversibility, management, and communication techniques may improve the implementation of frailty guidelines in hospitals.
Improvement in quality of life after asfotase alfa treatment in adults with pediatric-onset hypophosphatasia: data from 5 patient-reported outcome measures
Authors: Dahir Kathryn M , Ing Steven W , Deal Chad , Messali Andrew , Bates Toby , Rush Eric T 
Published: May 2024

Abstract
Hypophosphatasia (HPP) is a rare, inherited metabolic disorder caused by deficient tissue-nonspecific alkaline phosphatase activity. This study assessed the impact of treatment with asfotase alfa on patient-reported outcomes (PROs) in adults with pediatric-onset HPP. A longitudinal, telephone-based survey was administered to eligible individuals enrolled in a patient support program. Interviews were conducted at study entry (prior to asfotase alfa initiation) and after 3, 6, and 12 mo. PROs—Patient Health Questionnaire-9 [PHQ-9], Work Productivity and Activity Impairment Questionnaire: Specific Health Problem [WPAI:SHP], Patient-Reported Outcomes Measurement Information System 29 [PROMIS-29], and Routine Assessment of Patient Index Data 3 [RAPID3]—were assessed at each time point. Appropriate statistical tests were performed to assess score changes. Among 50 enrolled patients (mean age: 46 yr [SD: 15.4]; 80% female; 94% White), 49 were evaluable at 3 mo, 44 at 6 mo, and 29 at 12 mo. By month 3, statistically significant improvements from baseline were detected in PHQ-9 scores (10.6 vs 5.8 [P &lt; .0001]), PROMIS-29 domain scores (overall physical function: 38.0 vs 43.0 [P = .001]; anxiety: 57.5 vs 51.5 [P = .0011]; fatigue: 63.3 vs 55.3 [P &lt; .0001]; sleep disturbances: 58.8 vs 54.3 [P = .0099]; ability to participate in social roles and activities: 42.6 vs 47.7 [P = .0012]; and pain interference: 63.8 vs 58.4 [P = .001]), and RAPID3 domain scores (functional status: 2.7 vs 1.1 [P &lt; .0001]; pain tolerance: 6.0 vs 3.2 [P &lt; .0001]; and global health estimate: 5.1 vs 2.7 [P &lt; .0001]). Improvements persisted at month 12. Patients also showed improvements in WPAI:SHP domain scores at month 6 (presenteeism: 39.6% vs 14.1% [P &lt; .0001] and work productivity loss: 41.9% vs 14.1% [P &lt; .0001]). Treatment with asfotase alfa was associated with improved quality of life across several domains.
Integration of eye-tracking and object detection in a deep learning system for quality inspection analysis
Authors: Cho Seung-Wan , Lim Yeong-Hyun , Seo Kyung-Min , Kim Jungin 
Published: May 2024

Abstract
During quality inspection in manufacturing, the gaze of a worker provides pivotal information for identifying surface defects of a product. However, it is challenging to digitize the gaze information of workers in a dynamic environment where the positions and postures of the products and workers are not fixed. A robust, deep learning-based system, ISGOD (Integrated System with worker’s Gaze and Object Detection), is proposed, which analyzes data to determine which part of the object is observed by integrating object detection and eye-tracking information in dynamic environments. The ISGOD employs a six-dimensional pose estimation algorithm for object detection, considering the location, orientation, and rotation of the object. Eye-tracking data were obtained from Tobii Glasses, which enable real-time video transmission and eye-movement tracking. A latency reduction method is proposed to overcome the time delays between object detection and eye-tracking information. Three evaluation indices, namely, gaze score, accuracy score, and concentration index are suggested for comprehensive analysis. Two experiments were conducted: a robustness test to confirm the suitability for real-time object detection and eye-tracking, and a trend test to analyze the difference in gaze movement between experts and novices. In the future, the proposed method and system can transfer the expertise of experts to enhance defect detection efficiency significantly.
Social interactions generate complex selection patterns in virtual worlds
Authors: Santostefano Francesca , Fraser Franco Maxime , Montiglio Pierre-Olivier 
Published: May 2024

Abstract
Understanding the influence of social interactions on individual fitness is key to improving our predictions of phenotypic evolution. However, we often overlook the different components of selection regimes arising from interactions among organisms, including social, correlational, and indirect selection. This is due to the challenging sampling efforts required in natural populations to measure phenotypes expressed during interactions and individual fitness. Furthermore, behaviours are crucial in mediating social interactions, yet few studies have explicitly quantified these selection components on behavioural traits. In this study, we capitalize on an online multiplayer video game as a source of extensive data recording direct social interactions among prey, where prey collaborate to escape a predator in realistic ecological settings. We estimate natural and social selection and their contribution to total selection on behavioural traits mediating competition, cooperation, and predator–prey interactions. Behaviours of other prey in a group impact an individual’s survival, and thus are under social selection. Depending on whether selection pressures on behaviours are synergistic or conflicting, social interactions enhance or mitigate the strength of natural selection, although natural selection remains the main driving force. Indirect selection through correlations among traits also contributed to the total selection. Thus, failing to account for the effects of social interactions and indirect selection would lead to a misestimation of the total selection acting on traits. Dissecting the contribution of each component to the total selection differential allowed us to investigate the causal mechanisms relating behaviour to fitness and quantify the importance of the behaviours of conspecifics as agents of selection. Our study emphasizes that social interactions generate complex selective regimes even in a relatively simple ecological environment.
Take me to the River: Sophie Anderson and Elaine of Astolat
Authors: McLoughlin John 
Published: May 2024

ABSTRACT
Sophie Gengembre Anderson (1823–1903) is not a painter of considerable critical acclaim; her work has been largely disregarded by art history and criticism, charged on the often-fatal count of sentimentality and lumped in with the kinds of ‘kitsch’ art rejected by modernism and its descendants. Despite this, her work continues to sell – at multi-million-dollar auctions and printed on cheap paraphernalia. Anderson’s appeal at these very different cultural echelons is testament to her technical effectiveness and to the enduring quality of her particular brand of Victorian mawkishness, and though her many paintings of children may never quite find purchase amidst the innovations and revelations of art in the recent century, these qualities do lend themselves to a deeply sympathetic mode of historical and literary painting. Anderson’s large, Tennyson-inspired literary depiction of Elaine of Astolat signalled her desire to enter the aggressively male-dominated space of historical and literary art and offers a valuable new perspective on a story and a character which has been so often – even obsessively – depicted by men. Elaine, which sits high above the entryway to Liverpool’s Walker Art Gallery, was one of the first such paintings by a woman to be purchased with public funds, and it represents a valuable entry-point for critique – both of the Victorian art establishment and of Tennyson’s Idylls of the King. Anderson’s artistic choices betray a profound sympathy for Elaine of Astolat and serve to highlight the pathos of a character who has seen her story and her character distorted from its inception.
Improving plastic degrading enzymes via directed evolution
Authors: Joho Yvonne , Vongsouthi Vanessa , Gomez Chloe , Larsen Joachim S , Ardevol Albert , Jackson Colin J 
Published: May 2024

Abstract
Plastic degrading enzymes have immense potential for use in industrial applications. Protein engineering efforts over the last decade have resulted in considerable enhancement of many properties of these enzymes. Directed evolution, a protein engineering approach that mimics the natural process of evolution in a laboratory, has been particularly useful in overcoming some of the challenges of structure-based protein engineering. For example, directed evolution has been used to improve the catalytic activity and thermostability of polyethylene terephthalate (PET)-degrading enzymes, although its use for the improvement of other desirable properties, such as solvent tolerance, has been less studied. In this review, we aim to identify some of the knowledge gaps and current challenges, and highlight recent studies related to the directed evolution of plastic-degrading enzymes.
Inclusion as a science, technology, and innovation policy objective in high-income countries: the decoupling dilemma
Authors: Kalliomäki Helka , Kalliokoski Johanna , Woodson Thomas , Kunttu Leena , Kuusisto Jari 
Published: May 2024

Abstract
This paper scrutinizes the objective of inclusion in contemporary science, technology, and innovation (STI) policies by analyzing its manifestations within the broad STI policy language promoting a closer interaction between science and society. We contribute to the STI policy literature by revisiting current conceptualizations that primarily center on marginalized groups. By analyzing the Broader Impacts Criterion and Responsible Research and Innovation frameworks in the USA and the European Union, we show that inclusion in the context of high-income countries is partially decoupling from marginalization and increasingly being instrumentalized to serve impact agendas. Our conceptual framework synthesizing the dimensions of goal setting and agency illustrates the broadening scope of inclusive policies and the emergent decoupling dilemma that has been neglected in the literature. Future research must account for the growing ambiguity of policy language that is facing new legitimacy questions and the blurring of objectives focused on supporting marginalized groups.
Lupine-induced crooked calf syndrome: mitigation through intermittent grazing management of cattle
Authors: Welch Kevin D , Lee Stephen T , Panter Kip E , Stegelmeier Bryan S , Stonecipher Clint A , Cook Daniel 
Published: May 2024

Abstract
Lupines are responsible for a condition in cattle referred to as “crooked calf syndrome” (CCS) that occurs when pregnant cattle graze teratogenic lupines. A proposed management strategy to limit these types of birth defects includes utilizing an intermittent grazing schedule to allow short durations of grazing lupine-infested areas interrupted by movement to a lupine-free pasture. The objective of this study was to determine if an intermittent schedule of ten continuous days of lupine treatment followed by 5 d off treatment would be sufficient to decrease, or prevent, the incidence of lupine-induced malformations. Continuous dosing of the teratogenic lupine (Lupinus leucophyllus) to pregnant cows for 30 d during the most susceptible stage of pregnancy (gestation days 40 to 70) resulted in severe skeletal birth defects in their calves. However, intermittent dosing of the teratogenic lupine demonstrated that interrupted intake of lupine reduced the severity, or eliminated, permanent skeletal malformations in calves born to cows dosed lupine. Toxicokinetic and ultrasound data demonstrated a clear inverse correlation between serum anagyrine (the primary teratogenic alkaloid in some lupines) concentrations in the dam and fetal movement. In the intermittent group, fetal movement quickly returned to normal after lupine feeding stopped and remained normal until lupine treatment resumed. Therefore, interrupting lupine intake for at least 5 d through an intermittent grazing program could reduce the severity of the CCS. Furthermore, this method would allow ranchers to move cattle back into lupine pastures after a brief interruption, which would allow for more efficient utilization of forage resources.