bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emerging genetic complexity and rare genetic variants in neurodegenerative brain diseases
Authors: Perrone Federica , Cacace Rita , van der Zee Julie , Van Broeckhoven Christine 
Published: April 2021

AbstractKnowledge of the molecular etiology of neurodegenerative brain diseases (NBD) has substantially increased over the past three decades. Early genetic studies of NBD families identified rare and highly penetrant deleterious mutations in causal genes that segregate with disease. Large genome-wide association studies uncovered common genetic variants that influenced disease risk. Major developments in next-generation sequencing (NGS) technologies accelerated gene discoveries at an unprecedented rate and revealed novel pathways underlying NBD pathogenesis. NGS technology exposed large numbers of rare genetic variants of uncertain significance (VUS) in coding regions, highlighting the genetic complexity of NBD. Since experimental studies of these coding rare VUS are largely lacking, the potential contributions of VUS to NBD etiology remain unknown. In this review, we summarize novel findings in NBD genetic etiology driven by NGS and the impact of rare VUS on NBD etiology. We consider different mechanisms by which rare VUS can act and influence NBD pathophysiology and discuss why a better understanding of rare VUS is instrumental for deriving novel insights into the molecular complexity and heterogeneity of NBD. New knowledge might open avenues for effective personalized therapies.
Embedding, aligning and reconstructing clinical notes to explore sepsis
Authors: Zhu Xudong , Plasek Joseph M. , Tang Chunlei , Al-Assad Wasim , Zhang Zhikun , Xiong Yun , Wang Liqin , Yerneni Sharmitha , Ortega Carlos , Kang Min-Jeoung , Zhou Li , Bates David W. , Dykes Patricia C. 
Published: April 2021

Abstract
Objective
Our goal was to research and develop exploratory analysis tools for clinical notes, which now are underrepresented to limit the diversity of data insights on medically relevant applications.

Results
We characterize how exploratory analysis can affect representation learning on clinical narratives and present several self-developed tools to explore sepsis. Our experiments focus on patients with sepsis in the MIMIC-III Clinical Database or in our institution’s research patient data repository. We found that global embeddings assist in learning local representations of clinical notes. Second, aligning at any specific time facilitates the use of learning models by pooling more available clinical notes to form a training set. Furthermore, reconstruction of the timeline enhances downstream-processing techniques by emphasizing temporal expressions and temporal relationships in clinical documentation. We demonstrate that clustering helps plot various types of clinical notes against a scale, which conveys a sense of the range or spread of the data and is useful for understanding data correlations. Appropriate exploratory analysis tools provide keen insights into preprocessing clinical notes, thereby further enhancing downstream analysis capabilities, making data driven medicine possible. Our examples can help generate better data representation of clinical documentation for models with improved performance and interpretability.
Monitoring skin blood flow to rapidly identify alterations in tissue perfusion during fluid removal using continuous veno-venous hemofiltration in patients with circulatory shock
Authors: Mongkolpun Wasineenart , Bakos Péter , Vincent Jean-Louis , Creteur Jacques 
Published: April 2021

Abstract
Background
Continuous veno-venous hemofiltration (CVVH) can be used to reduce fluid overload and tissue edema, but excessive fluid removal may impair tissue perfusion. Skin blood flow (SBF) alters rapidly in shock, so its measurement may be useful to help monitor tissue perfusion.

Methods
In a prospective, observational study in a 35-bed department of intensive care, all patients with shock who required fluid removal with CVVH were considered for inclusion. SBF was measured on the index finger using skin laser Doppler (Periflux 5000, Perimed, Järfälla, Sweden) for 3 min at baseline (before starting fluid removal, T0), and 1, 3 and 6 h after starting fluid removal. The same fluid removal rate was maintained throughout the study period. Patients were grouped according to absence (Group A) or presence (Group B) of altered tissue perfusion, defined as a 10% increase in blood lactate from T0 to T6 with the T6 lactate ≥ 1.5 mmol/l. Receiver operating characteristic curves were constructed and areas under the curve (AUROC) calculated to identify variables predictive of altered tissue perfusion. Data are reported as medians [25th–75th percentiles].

Results
We studied 42 patients (31 septic shock, 11 cardiogenic shock); median SOFA score at inclusion was 9 [8–12]. At T0, there were no significant differences in hemodynamic variables, norepinephrine dose, lactate concentration, ScvO2 or ultrafiltration rate between groups A and B. Cardiac index and MAP did not change over time, but SBF decreased in both groups (p < 0.05) throughout the study period. The baseline SBF was lower (58[35–118] vs 119[57–178] perfusion units [PU], p = 0.03) and the decrease in SBF from T0 to T1 (ΔSBF%) higher (53[39–63] vs 21[12–24]%, p = 0.01) in group B than in group A. Baseline SBF and ΔSBF% predicted altered tissue perfusion with AUROCs of 0.83 and 0.96, respectively, with cut-offs for SBF of ≤ 57 PU (sensitivity 78%, specificity 87%) and ∆SBF% of ≥ 45% (sensitivity 92%, specificity 99%).

Conclusion
Baseline SBF and its early reduction after initiation of fluid removal using CVVH can predict worsened tissue perfusion, reflected by an increase in blood lactate levels.
End-to-end network slice architecture and distribution across 5G micro-operator leveraging multi-domain and multi-tenancy
Authors: Badmus Idris , Laghrissi Abdelquoddouss , Matinmikko-Blue Marja , Pouttu Ari 
Published: April 2021

AbstractLocal 5G networks are emerging as a new form for 5G deployment, targeting service delivery for vertical-specific purposes and other local users. These networks are also known as micro-operator networks for which prior work has established different deployment scenarios, namely Closed, Open and Mixed Networks. To achieve network flexibility, customization and privacy required by various vertical sectors, such as industry, health and energy, it is essential to have a well-defined network slicing architecture and adequate implementation procedure. In this paper, a sophisticated end-to-end network slicing architecture is proposed for different deployment scenarios of the local 5G micro-operator concept. The proposed architecture incorporates a broad four-layer concept, leveraging a multi-tenancy layer for different tenants and their end users, a descriptive service layer, a multi-domain slicing management and orchestration layer, and a resource layer. We further propose a network slice instance (NSI) communication service distribution technique for local 5G micro-operators. This is achieved by expanding/leveraging the communication service management function in the multi-tenant layer into a multi-tenant manager and an orchestrator of communication services. In addition, we describe how the communication service orchestrator will address all the possible multitenant-slice situations during the distribution of a network slice instance to multiple tenants. The novel methods described in the paper present a solution for not only network slice communication service distribution across different micro-operator’s tenants but also for future use cases, especially, when the allocated slice is responsible for multiple tenants or when a tenant requests multiple NSIs.
Mapping evidence on the effects of gender-affirming hormone therapy on the hard and soft tissues of the craniofacial complex in transgender people: a protocol for a scoping review
Authors: Van den Bosch M. F. , Wiepjes C. M. , Den Heijer M. , Schoonmade L. J. , Jonkman R. E. G. , Meursinge Reynders R. A. 
Published: April 2021

Abstract
Background
Gender-affirming hormone (GAH) therapy aims to support the transition of transgender people to their gender identity. GAHs can induce changes in their secondary sex characteristics such as the development of breasts in transgender females and increased muscle mass in transgender males. The face and its surrounding tissues also have an important role in gender confirmation. The aim of this scoping review is to systematically map the available evidence in order to provide an overview of the effects of GAH therapy on the hard and soft tissues of the craniofacial complex in transgender people.

Methods/design
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA) extension for Scoping Reviews was consulted for reporting this protocol. The methods were based on the Arksey and O’Malley’s framework and the Reviewer’s Manual of the Joanna Briggs Institute for conducting scoping reviews. Ten transgender people were involved in the development of the primary research question through short interviews. The eligibility criteria were defined for transgender people undergoing GAH therapy and for quantitative and qualitative outcomes on the hard and soft tissues of the craniofacial complex. Eligible sources of evidence include observational, experimental, qualitative, and mixed method studies. No exclusion criteria will be applied for the language of publication and the setting. To identify eligible sources of evidence, we will conduct searches from inception onwards in PubMed, Embase.com, the Cochrane Library, Web of Science Core Collection, Scopus, CINAHL, LIVIVO, and various grey literature sources such as Google Scholar. Two reviewers will independently select eligible studies in these information sources and will subsequently conduct data extraction. The same operators will chart, categorize, and summarize the extracted data. A narrative summary of findings will be conducted. Frequency counts of quantitative and qualitative data on items such as concepts, populations, interventions, and other characteristics of the eligible sources will be given. Where possible, these items will be mapped descriptively.

Discussion
We chose the scoping review over the systematic review approach, because the research questions are broad-spectrum and the literature is expected to be widely scattered. No systematic review has previously assessed this topic. Identifying knowledge gaps in this area and summarizing and disseminating research findings are important for a wide spectrum of stakeholders, in particular, for transgender people who want to undergo additional interventions such as plastic or orthognathic surgery or orthodontics.

Systematic review registration
This protocol was registered in the Open Science Framework: https://osf.io/e3qj6
BSS: a brokering model for service selection using integrated weighting approach in cloud environment
Authors: Chauhan Sameer Singh , Pilli Emmanuel S. , Joshi R. C. 
Published: April 2021

AbstractCloud providers shares their resources and services through collaboration in order to increase resource utilization, profit and quality of services. The offered services with different access patterns, similar characteristics, varied performance levels and cost models create a heterogeneous service environment. It becomes a challenging task for users to decide a suitable service as per their application requirements. Cloud broker, an inter-mediator is required in service management to help both cloud providers and users. Cloud broker has to store all the information related to services and feedback of users on those services in order to provide the best services to end-users. Brokering model for service selection (BSS) has been proposed which employs integrated weighting approach in cloud service selection. Subjective and objective weights of QoS attributes are combined to compute integrated total weight. Subjective weight is obtained from users’ feedback on QoS attributes of a cloud service while objective weight is computed from benchmark tested data of cloud services. Users’ feedback and preferences given to QoS parameters are employed in subjective weight computation. Objective weight is computed using Shannon’s Entropy method. Total weight is obtained by combining subjective and objective weights. BSS method is employed to rank cloud services. Simulation with a case study on real dataset has been done to validate the effectiveness of BSS. The obtained results demonstrate the consistency of model for handling rank reversal problem and provides better execution time than other state-of-the art solutions.
TNFα secreted by glioma associated macrophages promotes endothelial activation and resistance against anti-angiogenic therapy
Authors: Wei Qingxia , Singh Olivia , Ekinci Can , Gill Jaspreet , Li Mira , Mamatjan Yasin , Karimi Shirin , Bunda Severa , Mansouri Sheila , Aldape Kenneth , Zadeh Gelareh 
Published: April 2021

AbstractOne of the most prominent features of glioblastoma (GBM) is hyper-vascularization. Bone marrow-derived macrophages are actively recruited to the tumor and referred to as glioma-associated macrophages (GAMs) which are thought to provide a critical role in tumor neo-vascularization. However, the mechanisms by which GAMs regulate endothelial cells (ECs) in the process of tumor vascularization and response to anti-angiogenic therapy (AATx) is not well-understood. Here we show that GBM cells secrete IL-8 and CCL2 which stimulate GAMs to produce TNFα. Subsequently, TNFα induces a distinct gene expression signature of activated ECs including VCAM-1, ICAM-1, CXCL5, and CXCL10. Inhibition of TNFα blocks GAM-induced EC activation both in vitro and in vivo and improve survival in mouse glioma models. Importantly we show that high TNFα expression predicts worse response to Bevacizumab in GBM patients. We further demonstrated in mouse model that treatment with B20.4.1.1, the mouse analog of Bevacizumab, increased macrophage recruitment to the tumor area and correlated with upregulated TNFα expression in GAMs and increased EC activation, which may be responsible for the failure of AATx in GBMs. These results suggest TNFα is a novel therapeutic that may reverse resistance to AATx. Future clinical studies should be aimed at inhibiting TNFα as a concurrent therapy in GBMs.
Why participation in an international clinical trial platform matters during a pandemic? Launching REMAP-CAP in Japan
Authors: Kamata Kazuhiro , Jindai Kazuaki , Ichihara Nao , Saito Hiroki , Kato Hideaki , Kunishima Hiroyuki , Shintani Ayumi , Nishida Osamu , Fujitani Shigeki 
Published: April 2021

AbstractREMAP-CAP, a randomized, embedded, multifactorial adaptive platform trial for community-acquired pneumonia, is an international clinical trial that is rapidly expanding its scope and scale in response to the COVID-19 pandemic. Japan is now joining REMAP-CAP with endorsement from Japanese academic societies. Commitment to REMAP-CAP can significantly contribute to population health through timely identification of optimal COVID-19 therapeutics. Additionally, it will promote the establishment of a national and global network of clinical trials to tackle future pandemics of emerging and re-emerging infectious diseases, in collaboration with multiple stakeholders, including front-line healthcare workers, governmental agencies, regulatory authorities, and academic societies.
Groundwater aquifer detection using the electrical resistivity method at Ito Campus, Kyushu University (Fukuoka, Japan)
Authors: Wahab Shafiqullah , Saibi Hakim , Mizunaga Hideki 
Published: April 2021

AbstractAn electrical resistivity survey was carried out using the pole–pole configuration around the Sayanokami spring area in the northern part of Ito Campus (Kyushu University, Fukuoka, Japan) to study the groundwater aquifer and its electrical characteristics. A Code Division Multiple Transmission (CDMT) system was used. The CDMT system transmits 24 currents simultaneously and measures 24 potential responses with monitoring of actual current waveforms. The system can inject current from multiple electrodes into the underground environment simultaneously using different individual current waveforms. The two-dimensional (2-D) inversion results of the electrical resistivity data indicate three layers from top to bottom, as follows: (a) a thin layer with a thickness of 3 m and a low resistivity (< 50 Ω m) representing topsoil; (b) a groundwater aquifer layer with an average resistivity between 50 and 170 Ω m and with a thickness ranging from 7 to 10 m, and (c) a highly resistive bedrock layer with resistivities higher than 200 Ω m and occupying depths from 15 m to the base of the model.
Machine learning methods in sport injury prediction and prevention: a systematic review
Authors: Van Eetvelde Hans , Mendonça Luciana D. , Ley Christophe , Seil Romain , Tischer Thomas 
Published: April 2021

Abstract
Purpose
Injuries are common in sports and can have significant physical, psychological and financial consequences. Machine learning (ML) methods could be used to improve injury prediction and allow proper approaches to injury prevention. The aim of our study was therefore to perform a systematic review of ML methods in sport injury prediction and prevention.

Methods
A search of the PubMed database was performed on March 24th 2020. Eligible articles included original studies investigating the role of ML for sport injury prediction and prevention. Two independent reviewers screened articles, assessed eligibility, risk of bias and extracted data. Methodological quality and risk of bias were determined by the Newcastle–Ottawa Scale. Study quality was evaluated using the GRADE working group methodology.

Results
Eleven out of 249 studies met inclusion/exclusion criteria. Different ML methods were used (tree-based ensemble methods (n = 9), Support Vector Machines (n = 4), Artificial Neural Networks (n = 2)). The classification methods were facilitated by preprocessing steps (n = 5) and optimized using over- and undersampling methods (n = 6), hyperparameter tuning (n = 4), feature selection (n = 3) and dimensionality reduction (n = 1). Injury predictive performance ranged from poor (Accuracy = 52%, AUC = 0.52) to strong (AUC = 0.87, f1-score = 85%).

Conclusions
Current ML methods can be used to identify athletes at high injury risk and be helpful to detect the most important injury risk factors. Methodological quality of the analyses was sufficient in general, but could be further improved. More effort should be put in the interpretation of the ML models.
Sharing meals: promising nutritional interventions for primary health care including nursing students and elderly people
Authors: Alne Ellen Kristine Frøyland , Øie Tove , Søiland Malene , Gjesdal Kine 
Published: April 2021

Abstract
Background
The risk of malnutrition among elderly people is high and living alone increases the risk. As the number of older persons living alone is expected to increase due to the demographic development of an increasing older population, more knowledge about low-cost, sustainable nutritional interventions is needed. The purpose of this study was to investigate how nursing students can be a resource in the nutritional care of older persons living alone by sharing weekly meals.

Methods
Twenty-three nursing students and 23 elderly people who lived alone and received home nursing care participated in the project period of 9 weeks and shared 1–2 weekly meals. Shortly after the study period, 13 students and 4 elderly persons were interviewed in individual, face-to-face, semi-structured interviews. The questions included their experiences, the perceived impact of sharing meals, and facilitators and barriers of such meal interventions. The interview material was transcribed and analyzed using qualitative content analysis as described by Graneheim and Lundman.

Results
Our study found that both nursing students and older persons expressed positive experiences from sharing meals. Nursing students with some nutritional knowledge can provide a useful, sustainable supplement to the home-care nursing staff’s limited resources and time. Improvements were found, including preparation of ready meals and the meal environment, different facilitators and barriers of the meal experience, and the possible positive impact on the elderly persons’ nutritional status, which affects meal enjoyment, appetite, food intake and weight.

Conclusion
During their practical placement in the community, nursing students can provide a useful contribution to the nutritional care of elderly persons who are at nutritional risk living alone at home by the intervention of sharing a meal together. This is a low-cost supplement to other primary health-care measures that can affect both nutritional status and adjust the appropriate care for patients. This study demonstrates a small contribution to the complex nutritional care literature based on the growing elderly population in home care and the nursing student as a valuable resource for the multidisciplinary team approach necessary to meet this challenge.
Efficacy of extracellular vesicles from dental pulp stem cells for bone regeneration in rat calvarial bone defects
Authors: Imanishi Yuka , Hata Masaki , Matsukawa Ryohei , Aoyagi Atsushi , Omi Maiko , Mizutani Makoto , Naruse Keiko , Ozawa Shogo , Honda Masaki , Matsubara Tatsuaki , Takebe Jun 
Published: April 2021

Abstract
Background
Extracellular vesicles (EVs) are known to be secreted by various cells. In particular, mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have tissue repair capacity and anti-inflammatory properties. Dental pulp stem cells (DPSCs), which are MSCs isolated from pulp tissue, are less invasive to the body than other MSCs and can be collected from young individuals. In this study, we investigated the efficacy of EVs secreted by DPSCs (DPSC-EVs) for bone formation.

Methods
DPSC-EVs were isolated from the cell culture medium of DPSCs. DPSC-EVs were unilaterally injected along with collagen (COL), beta-tricalcium phosphate (β-TCP) or hydroxyapatite (HA) into rat calvarial bone defects. The effects of DPSC-EVs were analyzed by micro-computed tomography (micro-CT) and histological observation.

Results
Micro-CT showed that administration of DPSC-EVs with the abovementioned scaffolds resulted in bone formation in the periphery of the defects. DPSC-EVs/COL specifically resulted in bone formation in the center of the defects. Histological observation revealed that DPSC-EVs/COL promoted new bone formation. Administration of DPSC-EVs/COL had almost the same effect on the bone defect site as transplantation of DPSCs/COL.

Conclusions
These results suggest that DPSC-EVs may be effective tools for bone tissue regeneration.