bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term outcome after surgical resection of non-high-risk gastrointestinal stromal tumours without adjuvant therapy
Authors: Berndsen Marta , Renberg Sara , Hølmebakk Toto , Hancke Emma , Puls Florian , Karlsson Fredrik , Stoldt Stephan , Bjerkehagen Bodil , Haglund de Flon Felix , Muth Andreas , Papakonstantinou Andri , Boye Kjetil , Lindskog Stefan 
Published: September 2023

Abstract

Background
Gastrointestinal stromal tumour (GIST) is the most common intra-abdominal sarcoma. Risk classification systems, commonly the modified National Institutes of Health consensus criteria, identify tumour properties relating to patient outcomes. However, owing to limited long-term evidence, most guidelines recommend up to 10-year follow-up for all risk groups except very low-risk GIST.

Methods
This retrospective multicentre study included patients who had complete resection of primary, non-metastatic GIST from three Scandinavian sarcoma centres: Gothenburg (2004–2020), Stockholm (2000–2019), and Oslo (2000–2017). Medical records were reviewed for clinical details regarding diagnosis, treatment, and follow-up, and recurrence-free and disease-specific survival evaluated.

Results
The total cohort consisted of 1213 patients with GIST. High-risk patients and those treated with tyrosine kinase inhibitors were excluded. The remaining 649 patients were included in the present analysis: 118 with very low-, 381 with low-, and 150 with intermediate-risk GISTs. Five-year recurrence-free survival rates were 100, 98.5, and 100 per cent for the intermediate-, low-, and very low-risk groups respectively (P = 0.246). Disease-specific survival rates 10 years after surgery were 100, 98.4, and 100 per cent for the intermediate-, low-, and very low-risk groups respectively (P = 0.262).

Conclusion
Patients with completely resected non-high-risk GISTs have an excellent long-term outcome, irrespective of risk group. Follow-up programmes to detect disease recurrences in these patients are probably not indicated.
Neuromelanin accumulation drives endogenous synucleinopathy in non-human primates
Authors: Chocarro Julia , Rico Alberto J , Ariznabarreta Goiaz , Roda Elvira , Honrubia Adriana , Collantes María , Peñuelas Iván , Vázquez Alfonso , Rodríguez-Pérez Ana I , Labandeira-García José L , Vila Miquel , Lanciego José L 
Published: September 2023

Abstract
Although neuromelanin is a dark pigment characteristic of dopaminergic neurons in the human substantia nigra pars compacta, its potential role in the pathogenesis of Parkinson’s disease (PD) has often been neglected since most commonly used laboratory animals lack neuromelanin. Here we took advantage of adeno-associated viral vectors encoding the human tyrosinase gene for triggering a time-dependent neuromelanin accumulation within substantia nigra pars compacta dopaminergic neurons in macaques up to similar levels of pigmentation as observed in elderly humans. Furthermore, neuromelanin accumulation induced an endogenous synucleinopathy mimicking intracellular inclusions typically observed in PD together with a progressive degeneration of neuromelanin-expressing dopaminergic neurons.
Moreover, Lewy body-like intracellular inclusions were observed in cortical areas of the frontal lobe receiving dopaminergic innervation, supporting a circuit-specific anterograde spread of endogenous synucleinopathy by permissive trans-synaptic templating.
In summary, the conducted strategy resulted in the development and characterization of a new macaque model of PD matching the known neuropathology of this disorder with unprecedented accuracy. Most importantly, evidence is provided showing that intracellular aggregation of endogenous α-synuclein is triggered by neuromelanin accumulation, therefore any therapeutic approach intended to decrease neuromelanin levels may provide appealing choices for the successful implementation of novel PD therapeutics.
Extracellular vesicles set the stage for brain plasticity and recovery by multimodal signalling
Authors: Hermann Dirk M , Peruzzotti-Jametti Luca , Giebel Bernd , Pluchino Stefano 
Published: September 2023

Abstract
Extracellular vesicles (EVs) are extremely versatile naturally occurring membrane particles that convey complex signals between cells. EVs of different cellular sources are capable of inducing striking therapeutic responses in neurological disease models. Differently from pharmacological compounds that act by modulating defined signalling pathways, EV-based therapeutics possess multiple abilities via a variety of effectors, thus allowing the modulation of complex disease processes that may have very potent effects on brain tissue recovery. When applied in vivo in experimental models of neurological diseases, EV-based therapeutics have revealed remarkable effects on immune responses, cell metabolism and neuronal plasticity. This multimodal modulation of neuroimmune networks by EVs profoundly influences disease processes in a highly synergistic and context-dependent way. Ultimately, the EV-mediated restoration of cellular functions helps to set the stage for neurological recovery.
With this review we first outline the current understanding of the mechanisms of action of EVs, describing how EVs released from various cellular sources identify their cellular targets and convey signals to recipient cells. Then, mechanisms of action applicable to key neurological conditions such as stroke, multiple sclerosis and neurodegenerative diseases are presented. Pathways that deserve attention in specific disease contexts are discussed. We subsequently showcase considerations about EV biodistribution and delineate genetic engineering strategies aiming at enhancing brain uptake and signalling.
By sketching a broad view of EV-orchestrated brain plasticity and recovery, we finally define possible future clinical EV applications and propose necessary information to be provided ahead of clinical trials. Our goal is to provide a steppingstone that can be used to critically discuss EVs as next generation therapeutics for brain diseases.
GPRASP1 loss-of-function links to arteriovenous malformations by endothelial activating GPR4 signals
Authors: Li Ruofei , Xiao Xiao , Yan Yupeng , Yu Liang , Lv Cheng , Zhang Yu , Hong Tao , Zhang Hongqi , Wang Yibo 
Published: September 2023

Abstract
Arteriovenous malformations (AVMs) are fast-flow vascular malformations and refer to important causes of intracerebral haemorrhage in young adults. Getting deep insight into the genetic pathogenesis of AVMs is necessary.
Herein, we identified two vital missense variants of G protein-coupled receptor (GPCR) associated sorting protein 1 (GPRASP1) in AVM patients for the first time and congruously determined to be loss-of-function variants in endothelial cells. GPRASP1 loss-of-function caused endothelial dysfunction in vitro and in vivo. Endothelial Gprasp1 knockout mice suffered a high probability of cerebral haemorrhage, AVMs and exhibited vascular anomalies in multiple organs. GPR4 was identified to be an effective GPCR binding with GPRASP1 to develop endothelial disorders. GPRASP1 deletion activated GPR4/cAMP/MAPK signalling to disturb endothelial functions, thus contributing to vascular anomalies. Mechanistically, GPRASP1 promoted GPR4 degradation. GPRASP1 enabled GPR4 K63-linked ubiquitination, enhancing the binding of GPR4 and RABGEF1 to activate RAB5 for conversions from endocytic vesicles to endosomes, and subsequently increasing the interactions of GPR4 and ESCRT members to package GPR4 into multivesicular bodies or late endosomes for lysosome degradation. Notably, the GPR4 antagonist NE 52-QQ57 and JNK inhibitor SP600125 effectively rescued the vascular phenotype caused by endothelial Gprasp1 deletion. Our findings provided novel insights into the roles of GPRASP1 in AVMs and hinted at new therapeutic strategies.
Inventors, firms and localities: insights into the nexus that forms and alters the evolution of regional knowledge spaces
Authors: Shin Hyunha , Kim Keungoui , Lee Junmin , Kogler Dieter F 
Published: September 2023

Abstract
The present investigation aims to provide insights into the nexus between firms and localities that ultimately shapes the evolution of regional knowledge spaces. The ‘inventive footprint’ of firms, indicated by the spatial distribution of associated inventors across regional economic settings, provides the foundation to analyse whether firms’ external knowledge sourcing contributes to their own evolution, and by extension to their home region’s technological capabilities. Findings indicate that firms’ innovation efforts beyond their home base are subsequently absorbed at home and thus that knowledge-sourcing activities by multi-locational firms significantly contributes to the evolution of regional knowledge space trajectories.
Impact of different in vitro models on functional performance of the self-expanding transcatheter heart valve
Authors: Sadat Najla , Lojenburg John Habakuk , Scharfschwerdt Michael , Fujta Buntaro , Ensminger Stephan 
Published: September 2023

Abstract

OBJECTIVES
Transcatheter heart valves (THVs) are investigated according to International Organization for Standardization requirements using in vitro heart simulators to evaluate hydrodynamic performance. In contrast to surgical valves, a THV’s performance heavily depends on the configuration and shape of the aortic anulus. In International Organization for Standardization regulations, there is no detailed definition for the construction of a compartment in which a THV has to be tested. Therefore, the aim of this in vitro study was to compare different in vitro models for functional testing of THVs.

METHODS
Porcine aortic conduits (23-mm diameter) were implanted in Dacron prostheses and calcified with double-distilled water and calcification buffer at 37°C over 83 million cycles in a Hi-Cycler (durability testing) mimicking nearly 3 patient-years. Hydrodynamic testing of Evolut PRO 26 mm was performed within 3 models (plexiglass, native conduit and calcified conduit; all 23-mm diameter) at a frequency of 64 bpm and different stroke volumes (55–105 ml).

RESULTS
Calcified conduits showed significantly higher mean pressure gradients (MPG) and lower effective orifice areas (EOA) in comparison to native conduits (without THV; P &lt; 0.001). EOA and MPG of Evolut PRO differed depending on the model tested. Calcified conduits resulted in the lowest EOA and highest MPG of the THV compared to plexiglass and the native conduit. Full expansion of the THV was least impaired in the native conduit, while lowest geometric orifice area, lowest minimal internal diameter and highest pin-wheeling index of Evolut PRO were seen in the calcified conduit.

CONCLUSIONS
Full expansion and functional performance of the Evolut PRO THV depends on the configuration of the testing compartment in an in vitro setting.
Procedural outcome and follow-up of stylet-driven leads compared with lumenless leads for left bundle branch area pacing
Authors: Sritharan Aarthiga , Kozhuharov Nikola , Masson Nicolas , Bakelants Elise , Valiton Valérian , Burri Haran 
Published: September 2023

Abstract

Aims
Left bundle branch area pacing (LBBAP) is most often delivered using lumenless leads (LLLs), but may also be performed using stylet-driven leads (SDLs). There are limited reports on the comparison of these tools, mainly limited to reports describing initial operator experience or without detailed procedural data. Our aim was to perform an in-depth comparison of SDLs and LLLs for LBBAP at implantation and follow-up in a larger cohort of patients with experience that extends beyond that of the initial learning curve.

Methods and results
A total of 306 consecutive patients (age 77 ± 11 years, 183 males) undergoing LBBAP implantation at a single centre were prospectively included. The population was split into two groups of 153 patients based on the initial use of an SDL (from 4 manufacturers) or an LLL. After having discounted the initial learning curve of 50 patients, there was no difference in the success rate between the initial use of lead type (96.0% with SDL vs. 94.3% with LLL, P = 0.56). There were no significant differences in success between lead models. Electrocardiogram and electrical parameters were comparable between the groups. Post-operative macro-dislodgement occurred in 4.3% of patients (essentially within the first day following implantation) and presumed micro-dislodgement with loss of conduction system capture or rise in threshold (occurring mostly during the first month) was observed in 4.7% of patients, without differences between groups.

Conclusion
Left bundle branch area pacing may be safely and effectively performed using either LLLs or SDLs, which provides implanters with alternatives for delivering this therapy.
Changing microbiome community structure and functional potential during permafrost thawing on the Tibetan Plateau
Authors: Tang Xiaotong , Zhang Miao , Fang Zhengkun , Yang Qing , Zhang Wan , Zhou Jiaxing , Zhao Bixi , Fan Tongyu , Wang Congzhen , Zhang Chuanlun , Xia Yu , Zheng Yanhong 
Published: September 2023

AbstractLarge amounts of carbon sequestered in permafrost on the Tibetan Plateau (TP) are becoming vulnerable to microbial decomposition in a warming world. However, knowledge about how the responsible microbial community responds to warming-induced permafrost thaw on the TP is still limited. This study aimed to conduct a comprehensive comparison of the microbial communities and their functional potential in the active layer of thawing permafrost on the TP. We found that the microbial communities were diverse and varied across soil profiles. The microbial diversity declined and the relative abundance of Chloroflexi, Bacteroidetes, Euryarchaeota, and Bathyarchaeota significantly increased with permafrost thawing. Moreover, warming reduced the similarity and stability of active layer microbial communities. The high-throughput qPCR results showed that the abundance of functional genes involved in liable carbon degradation and methanogenesis increased with permafrost thawing. Notably, the significantly increased mcrA gene abundance and the higher methanogens to methanotrophs ratio implied enhanced methanogenic activities during permafrost thawing. Overall, the composition and functional potentials of the active layer microbial community in the Tibetan permafrost region are susceptible to warming. These changes in the responsible microbial community may accelerate carbon degradation, particularly in the methane releases from alpine permafrost ecosystems on the TP.
Impact of different environmental pollution processes on bacterial key-indicators in tropical rivers: scoping review
Authors: Bohórquez-Herrera Jimena , Abad Matías Isaac David , Gutiérrez Castañeda Clara Gilma 
Published: September 2023

Abstract
Freshwater ecosystems are an essential resource for human use and natural populations, but they are exposed to different sources of man-made pollution. This study analyses how different environmental pollution processes influence the structure of bacterial communities in tropical rivers. A scoping review was performed to characterize the bacterial communities in freshwater ecosystems in tropical regions that have been reported to be associated with pollution of different kinds. The statistical analyses allowed us to categorize the genera found into three large groups (pollution generalists, middle types, and pollution specialists) according to the types of pollutants with which they were associated. The results show that Escherichia has a greater association with fecal contamination, while Enterococcus is more associated with domestic wastewater and organic and synthetic chemicals. The present study proposes Streptomyces as a potential indicator of waters with microbial contamination, as well as some other genera as possible indicators of waters with heavy metal contamination.
Longitudinal Associations Between Higher Self-Reported Energy, Gait Speed, and Cognition in Older Adults With Fatigue
Authors: Ehrenkranz Rebecca , Zhu Xiaonan , Glynn Nancy W , Bertolet Marnie , Berman Sarah B , Hengenius James B , Rosano Caterina 
Published: September 2023

Abstract

Background
Older adults reporting higher energy levels have better physical function. It is not known if these associations persist among older adults reporting fatigue or if higher energy is associated with cognitive function. We examined longitudinal associations between self-reported energy, gait speed, and cognition, stratified by fatigue, in 2 613 participants (aged 74.6 ± 2.87 years) in the Health, Aging and Body Composition Study.

Methods
Self-reported energy (0–10, dichotomized at median) and fatigue (present/absent) were measured at baseline. Usual and rapid-paced gait speed (m/s), modified Mini-Mental State Examination (3MS), and Digit Symbol Substitution Test (DSST) were measured at baseline and annually over 8 years. Linear mixed effect models compared changes in gait speed, 3MS, and DSST between higher and lower energy groups within fatigue strata.

Results
At baseline, 724 participants (27%) were fatigued; 240 (33%) coreported higher energy (9% of total). The remaining 1 889 participants were fatigue-free (73%); 1 221 (65%) coreported higher energy (47% of total). Those with fatigue and higher energy had average rapid gait declines of 0.007 m/s per year (p = .04) after adjustment for demographics, comorbidities, depressive symptoms, and exercise. DSST declines were found among only fatigue-free participants (β = 0.17, p = .01). No statistically significant associations with energy were found for fatigue-free participants, or for usual gait or 3MS.

Conclusions
Asking about older adults’ energy levels as well as fatigue may identify a subgroup of older adults protected against physical and cognitive decline, even among those with fatigue.
Towards a Judicial Sustainability Test in Cases Concerning the Enforcement of Intellectual Property Rights
Authors: Vrendenbarg Charlotte J S 
Published: September 2023

Abstract
The environmentally harmful yet common practice of storing and destroying IP-infringing goods is untenable. This contribution discusses a number of more sustainable alternative remedies that can be considered with the aim of creating a balance between the interests of rights holders in ending infringements and the societal interest in environmental protection, which lies in preventing the wasting of scarce raw materials and pollution of the air and soil. A sustainable IP enforcement practice is very much dependent on the willingness of rights holders and their attorneys to consider more sustainable alternatives. Courts also have a part to play, by applying what is called a sustainability test when examining the proportionality of the remedies and measures claimed by rights holders.
Positivity of Higher Exterior Powers of the Tangent Bundle
Authors: Gachet Cécile 
Published: September 2023

AbstractWe prove that a smooth projective variety $X$ of dimension $n$ with strictly nef third, fourth, or $(n-1)$-th exterior power of the tangent bundle is a Fano variety. Moreover, in the first two cases, we provide a classification for $X$ under the assumption that $\rho (X)\ne 1$.
Impact of Human Immunodeficiency Virus and Peripartum Period on Mycobacterium tuberculosis Infection Detection
Authors: Escudero Jaclyn N , Mecha Jerphason , Richardson Barbra A , Maleche-Obimbo Elizabeth , Matemo Daniel , Kinuthia John , John-Stewart Grace , LaCourse Sylvia M 
Published: September 2023

Abstract

Background
Pregnancy and human immunodeficiency virus (HIV) may influence tuberculosis infection detection using interferon (IFN)-γ release assay (QFT-Plus; Qiagen) and tuberculin skin test (TST).

Methods
Participants in Western Kenya underwent QFT-Plus and TST in pregnancy, 6 weeks postpartum (6wkPP) and 12 months postpartum (12moPP).

Results
400 participants (200 with HIV [WHIV], 200 HIV-negative) enrolled during pregnancy (median 28 weeks’ gestation [interquartile range, 24–30]). QFT-Plus positivity prevalence was higher than TST in pregnancy (32.5% vs 11.6%) and through 12moPP (6wkPP, 30.9% for QFT-Plus vs 18.0% for TST; 12moPP, 29.5% vs 17.1%; all P &lt; .001), driven primarily by QFT-Plus–positive/TST-negative discordance among HIV-negative women. Tuberculosis infection test conversion incidence was 28.4/100 person-years (PY) and higher in WHIV than HIV-negative women (35.5 vs 20.9/100 PY; hazard ratio, 1.73 [95% confidence interval, 1.04–2.88]), mostly owing to early postpartum TST conversion among WHIV. Among QFT-Plus–positive participants in pregnancy, Mycobacterium tuberculosis (Mtb)–specific IFN-γ responses were dynamic through 12moPP and lower among WHIV than HIV-negative women with tuberculosis infection at all time points.

Conclusions
QFT-Plus had higher diagnostic yield than TST in peripartum women. Peripartum QFT-Plus positivity was stable and less influenced by HIV than TST. Mtb–specific IFN-γ responses were dynamic and lower among WHIV. Tuberculosis infection test conversion incidence was high between pregnancy and early postpartum, potentially owing to postpartum immune recovery.
Clustering rare diseases within an ontology-enriched knowledge graph
Authors: Sanjak Jaleal , Binder Jessica , Yadaw Arjun Singh , Zhu Qian , Mathé Ewy A 
Published: September 2023

Abstract

Objective
Identifying sets of rare diseases with shared aspects of etiology and pathophysiology may enable drug repurposing. Toward that aim, we utilized an integrative knowledge graph to construct clusters of rare diseases.

Materials and Methods
Data on 3242 rare diseases were extracted from the National Center for Advancing Translational Science Genetic and Rare Diseases Information center internal data resources. The rare disease data enriched with additional biomedical data, including gene and phenotype ontologies, biological pathway data, and small molecule-target activity data, to create a knowledge graph (KG). Node embeddings were trained and clustered. We validated the disease clusters through semantic similarity and feature enrichment analysis.

Results
Thirty-seven disease clusters were created with a mean size of 87 diseases. We validate the clusters quantitatively via semantic similarity based on the Orphanet Rare Disease Ontology. In addition, the clusters were analyzed for enrichment of associated genes, revealing that the enriched genes within clusters are highly related.

Discussion
We demonstrate that node embeddings are an effective method for clustering diseases within a heterogenous KG. Semantically similar diseases and relevant enriched genes have been uncovered within the clusters. Connections between disease clusters and drugs are enumerated for follow-up efforts.

Conclusion
We lay out a method for clustering rare diseases using graph node embeddings. We develop an easy-to-maintain pipeline that can be updated when new data on rare diseases emerges. The embeddings themselves can be paired with other representation learning methods for other data types, such as drugs, to address other predictive modeling problems.
Model-based detection and classification of premature contractions from photoplethysmography signals
Authors: Regis Marta , Eerikäinen Linda M , Haakma Reinder , van den Heuvel Edwin R , Serra Paulo 
Published: September 2023

Abstract
The detection of arrhythmias from wearable devices is still an open challenge, while the availability of screening tools for the large population would allow reduced complications and costs. We propose a model-based approach to the detection and classification of premature contractions into atrial and ventricular. The extracted signal morphology and the deviations from the expected stationarity are used to detect and classify premature contractions. Our approach is self-contained, patient-specific and robust to mis-segmentation. Both model fit, and detection and classification accuracy of the proposed methods are evaluated on two real cases and a simulated dataset, and show promising results.