bluuebunny/crossref_metadata_2025_split huggingface dataset:
THOR is a targetable epigenetic biomarker with clinical implications in breast cancer
Authors: Apolónio Joana Dias , Dias João S. , Fernandes Mónica Teotónio , Komosa Martin , Lipman Tatiana , Zhang Cindy H. , Leão Ricardo , Lee Donghyun , Nunes Nuno Miguel , Maia Ana-Teresa , Morera José L. , Vicioso Luis , Tabori Uri , Castelo-Branco Pedro 
Published: December 2022

Abstract
Background
Breast cancer (BC) is the most frequently diagnosed cancer and a leading cause of death among women worldwide. Early BC is potentially curable, but the mortality rates still observed among BC patients demonstrate the urgent need of novel and more effective diagnostic and therapeutic options. Limitless self-renewal is a hallmark of cancer, governed by telomere maintenance. In around 95% of BC cases, this process is achieved by telomerase reactivation through upregulation of the human telomerase reverse transcriptase (hTERT). The hypermethylation of a specific region within the hTERT promoter, termed TERT hypermethylated oncological region (THOR) has been associated with increased hTERT expression in cancer. However, its biological role and clinical potential in BC have never been studied to the best of our knowledge. Therefore, we aimed to investigate the role of THOR as a biomarker and explore the functional impact of THOR methylation status in hTERT upregulation in BC.

Results
THOR methylation status in BC was assessed by pyrosequencing on discovery and validation cohorts. We found that THOR is significantly hypermethylated in malignant breast tissue when compared to benign tissue (40.23% vs. 12.81%, P < 0.0001), differentiating malignant tumor from normal tissue from the earliest stage of disease. Using a reporter assay, the addition of unmethylated THOR significantly reduced luciferase activity by an average 1.8-fold when compared to the hTERT core promoter alone (P < 0.01). To further investigate its biological impact on hTERT transcription, targeted THOR demethylation was performed using novel technology based on CRISPR-dCas9 system and significant THOR demethylation was achieved. Cells previously demethylated on THOR region did not develop a histologic cancer phenotype in in vivo assays. Additional studies are required to validate these observations and to unravel the causality between THOR hypermethylation and hTERT upregulation in BC.

Conclusions
THOR hypermethylation is an important epigenetic mark in breast tumorigenesis, representing a promising biomarker and therapeutic target in BC. We revealed that THOR acts as a repressive regulatory element of hTERT and that its hypermethylation is a relevant mechanism for hTERT upregulation in BC.
Bariatric surgery-induced weight loss and associated genome-wide DNA-methylation alterations in obese individuals
Authors: Talukdar Fazlur Rahman , Escobar Marcillo David Israel , Laskar Ruhina Shirin , Novoloaca Alexei , Cuenin Cyrille , Sbraccia Paolo , Nisticò Lorenza , Guglielmi Valeria , Gheit Tarik , Tommasino Massimo , Dogliotti Eugenia , Fortini Paola , Herceg Zdenko 
Published: December 2022

AbstractBackgroundObesity is a multifactorial and chronic condition of growing universal concern. It has recently been reported that bariatric surgery is a more successful treatment for severe obesity than other noninvasive interventions, resulting in rapid significant weight loss and associated chronic disease remission. The identification of distinct epigenetic patterns in patients who are obese or have metabolic imbalances has suggested a potential role for epigenetic alterations in causal or mediating pathways in the development of obesity-related pathologies. Specific changes in the epigenome (DNA methylome), associated with metabolic disorders, can be detected in the blood. We investigated whether such epigenetic changes are reversible after weight loss using genome-wide DNA methylome analysis of blood samples from individuals with severe obesity (mean BMI ~ 45) undergoing bariatric surgery.ResultsOur analysis revealed 41 significant (Bonferronip < 0.05) and 1169 (false discovery ratep < 0.05) suggestive differentially methylated positions (DMPs) associated with weight loss due to bariatric surgery. Among the 41 significant DMPs, 5 CpGs were replicated in an independent cohort of BMI-discordant monozygotic twins (the heavier twin underwent diet-induced weight loss). The effect sizes of these 5 CpGs were consistent across discovery and replication sets (p < 0.05). We also identified 192 differentially methylated regions (DMRs) among whichSMAD6andPFKFB3genes were the top hypermethylated and hypomethylated regions, respectively. Pathway enrichment analysis of the DMR-associated genes showed that functional pathways related to immune function and type 1 diabetes were significant. Weight loss due to bariatric surgery also significantly decelerated epigenetic age 12 months after the intervention (mean =  − 4.29;p = 0.02).ConclusionsWe identified weight loss-associated DNA-methylation alterations targeting immune and inflammatory gene pathways in blood samples from bariatric-surgery patients. The top hits were replicated in samples from an independent cohort of BMI-discordant monozygotic twins following a hypocaloric diet. Energy restriction and bariatric surgery thus share CpGs that may represent early indicators of response to the metabolic effects of weight loss. The analysis of bariatric surgery-associated DMRs suggests that epigenetic regulation of genes involved in endothelial and adipose tissue function is key in the pathophysiology of obesity.
Radiomics assessment of carotid intraplaque hemorrhage: detecting the vulnerable patients
Authors: Zhang Shuai , Gao Lin , Kang Bing , Yu Xinxin , Zhang Ran , Wang Ximing 
Published: December 2022

Abstract
Background
Intraplaque hemorrhage (IPH), one of the key features of vulnerable plaques, has been shown to be associated with increased risk of stroke. The aim is to develop and validate a CT-based radiomics nomogram incorporating clinical factors and radiomics signature for the detection of IPH in carotid arteries.

Methods
This retrospective study analyzed the patients with carotid plaques on CTA from January 2013 to January 2021 at two different institutions. Radiomics features were extracted from CTA images. Demographics and CT characteristics were evaluated to build a clinical factor model. A radiomics signature was constructed by the least absolute shrinkage and selection operator method. A radiomics nomogram combining the radiomics signature and independent clinical factors was constructed. The area under curves of three models were calculated by receiver operating characteristic analysis.

Results
A total of 46 patients (mean age, 60.7 years ± 10.4 [standard deviation]; 36 men) with 106 carotid plaques were in the training set, and 18 patients (mean age, 61.4 years ± 10.1; 13 men) with 38 carotid plaques were in the external test sets. Stenosis was the independent clinical factor. Eight features were used to build the radiomics signature. The area under the curve (AUC) of the radiomics nomogram was significantly higher than that of the clinical factor model in both the training (p = 0.032) and external test (p = 0.039) sets.

Conclusions
A CT-based radiomics nomogram showed satisfactory performance in distinguishing carotid plaques with and without intraplaque hemorrhage.
Isoflurane vs. propofol for sedation in invasively ventilated patients with acute hypoxemic respiratory failure: an a priori hypothesis substudy of a randomized controlled trial
Authors: Becher Tobias , Meiser Andreas , Guenther Ulf , Bellgardt Martin , Wallenborn Jan , Kogelmann Klaus , Bracht Hendrik , Falthauser Andreas , Nilsson Jonas , Sackey Peter , Kellner Patrick 
Published: December 2022

Abstract
Background
Acute hypoxemic respiratory failure (AHRF) is a leading concern in critically ill patients. Experimental and clinical data suggest that early sedation with volatile anesthestics may improve arterial oxygenation and reduce the plasma and alveolar levels of markers of alveolar epithelial injury and of proinflammatory cytokines.

Methods
An a priori hypothesis substudy of a multicenter randomized controlled trial (The Sedaconda trial, EUDRA CT Number 2016-004551-67). In the Sedaconda trial, 301 patients on invasive mechanical ventilation were randomized to 48 h of sedation with isoflurane or propofol in a 1:1 ratio. For the present substudy, patients with a ratio of arterial pressure of oxygen (PaO2) to inspired fraction of oxygen (FiO2), PaO2/FiO2, of ≤ 300 mmHg at baseline were included (n = 162). The primary endpoint was the change in PaO2/FiO2 between baseline and the end of study sedation. A subgroup analysis in patients with PaO2/FiO2 ≤ 200 mmHg was performed (n = 82).

Results
Between baseline and the end of study sedation (48 h), oxygenation improved to a similar extent in the isoflurane vs. the propofol group (isoflurane: 199 ± 58 to 219 ± 76 mmHg (n = 70), propofol: 202 ± 62 to 236 ± 77 mmHg (n = 89); p = 0.185). On day seven after randomization, PaO2/FiO2 was 210 ± 79 mmHg in the isoflurane group (n = 41) and 185 ± 87 mmHg in the propofol group (n = 44; p = 0.411). In the subgroup of patients with PaO2/FiO2 ≤ 200 mmHg, PaO2/FiO2 increase between baseline and end of study sedation was 152 ± 33 to 186 ± 54 mmHg for isoflurane (n = 37), and 150 ± 38 to 214 ± 85 mmHg for propofol (n = 45; p = 0.029). On day seven, PaO2/FiO2 was 198 ± 69 mmHg in patients randomized to isoflurane (n = 20) and 174 ± 106 mmHg in patients randomized to propofol (n = 20; p = 0.933). Both for the whole study population and for the subgroup with PaO2/FiO2 ≤ 200 mmHg, no significant between-group differences were observed for PaCO2, pH and tidal volume as well as 30-day mortality and ventilator-free days alive.

Conclusions
In patients with AHRF, inhaled sedation with isoflurane for a duration of up to 48 h did not lead to improved oxygenation in comparison to intravenous sedation with propofol.
Trial registration The main study was registered in the European Medicines Agency’s EU Clinical Trial register (EudraCT), 2016-004551-67, before including the first patient. The present substudy was registered at German Clinical Trials Register (DRKS, ID: DRKS00018959) on January 7th, 2020, before opening the main study data base and obtaining access to study results.
Weather and crime: a systematic review of the empirical literature
Authors: Corcoran Jonathan , Zahnow Renee 
Published: December 2022

AbstractThe weather-crime association has intrigued scholars for more than 150 years. While there is a long-standing history of scholarly interest in the weather-crime association, the last decade has evidenced a marked increase in the volume and diversity of empirical studies concerned with weather and its social implications including crime. In this paper we conduct a review of the empirical literature on weather and crime. This is the first review on the topic for more than 30 years. We highlight the theoretic and empirical challenges that persist and act to impede our understanding and chart four interrelated thematic areas that require concerted attention. These are to: (1) strengthen and integrate theoretical explanations of the weather-crime association; (2) model multi-dimensional processes of the weather-crime association; (3) broaden the situational, climatic, and cultural contexts of study; and (4) to translate research into policy and practice. We conclude by advocating for scholarship to advance the four thematic areas such that we progress towards a more complete and robust understanding of the weather-crime association.
The impairment of intramural periarterial drainage in brain after subarachnoid hemorrhage
Authors: Sun Yanrong , Liu E. , Pei Yanhong , Yao Qinhan , Ma Haowen , Mu Yakun , Wang Yingjie , Zhang Yan , Yang Xiaomei , Wang Xing , Xue Jiajia , Zhai Jiliang , Carare Roxana O. , Qin Lihua , Yan Junhao 
Published: December 2022

AbstractInterstitial fluid (ISF) from brain drains along the basement membranes of capillaries and arteries as Intramural Periarterial Drainage (IPAD); failure of IPAD results in cerebral amyloid angiopathy (CAA). In this study, we test the hypothesis that IPAD fails after subarachnoid haemorrhage (SAH). The rat SAH model was established using endovascular perforation method. Fluorescence dyes with various molecular weights were injected into cisterna magna of rats, and the pattern of IPAD after SAH was detected using immunofluorescence staining, two-photon fluorescent microscope, transmission electron microscope and magnetic resonance imaging tracking techniques. Our results showed that fluorescence dyes entered the brain along a periarterial compartment and were cleared from brain along the basement membranes of the capillaries, with different patterns based on individual molecular weights. After SAH, there was significant impairment in the IPAD system: marked expansion of perivascular spaces, and ISF clearance rate was significantly decreased, associated with the apoptosis of endothelial cells, activation of astrocytes, over-expression of matrix metalloproteinase 9 and loss of collagen type IV. In conclusion, experimental SAH leads to a failure of IPAD, clinically significant for long term complications such as CAA, following SAH.
Actualizing community–academic partnerships in research: a case study on rural perinatal peer support
Authors: Hards April , Cameron Audrey , Sullivan Eva , Kornelsen Jude 
Published: December 2022

Abstract
Background
Within the field of patient and public involvement in health service research, there is a growing movement towards not only involving patients in research but engaging them as co-producers of knowledge. We explore such a co-productive research relationship in a case study on rural perinatal mental health, with the aim of collaboratively developing knowledge based on both the relevant lived experience of a community partner, and the systemic knowledge of academic researchers.

Methods
Data was gathered through a community forum and subsequent interviews with social service program administrators from rural British Columbia, Canada. Interviews were analyzed separately by the community partner and academic researchers using principles of thematic analysis. Both the community partner and academic researchers were involved from project genesis to data collection, analysis, interpretation, and manuscript writing.

Results
Common themes identified by the academic and community researchers included needs for peer support, barriers to peer support, and gaps in mental health care. Divergently, the academic researcher focused on systems-level challenges while the community partner emphasized the impact of power dynamics within health systems. Researchers generated five methodological values propositions from the process of co-production, including (a) mutual respect for all viewpoints, (b) a rejection of assumed hierarchy, (c) commitments to truth speaking, (d) attention to process, and (e) equivalence of contribution.

Conclusions
Co-production highlights the value of lived experience in health research, sets it in conversation with scientific inquiry, and moves away from hierarchies of assumed knowledge often embedded in traditional health care research. Incorporating both academic researcher and community partner writing into our paper reflects a commitment to maintaining the integrity and authenticity of lived experience, an affirmation of its equal validity as a source of knowledge, and a rejection of qualifying patient voices. The exploration of this co-production research relationship lays groundwork for future research teams considering collaborative methodology. We suggest co-productive research as a means of addressing the epistemic injustice that arises in health care research from the privileging of certain forms of knowledge, and the exclusion of others, namely that derived from patient experience.
Child development with the D-score: turning milestones into measurement
Authors: van Buuren Stef , Eekhout Iris 
Published: December 2022

The chapter equips the reader with a basic understanding of robust psychometric methods that are needed to turn developmental milestones into measurements, introducing the fundamental issues in defining a unit for child development and demonstrates the relevant quantitative methodology. It reviews quantitative approaches to measuring child development;introduces the Rasch model in a non-technical way;shows how to estimate model parameters from real data;puts forth a set of principles for model evaluation and assessment of scale quality;analyses the relation between early D-scores and later intelligence;and compares the D-scores from three studies that all use the same instrument.
A Review of Agricultural Academic Safety, Health, and Biosecurity Curriculum Standards
Authors: Morris Glen C. , Morris Glen C. , Ehlers Shawn G. , Field William E. , Tormoehlen Roger , Ehlers Shawn G. , Field William E. , Tormoehlen Roger 
Published: December 2022

Highlights

Agricultural academic standards have different distribution among even some heavily agriculturally involved states.

Education standards that pertain to agricultural safety and health are more generic and focus on farm machinery and livestock handling.

Education standards that pertain to agricultural biosecurity are more general and tend not to focus on specific biosecurity areas of identification and prevention.

Abstract. This article examines the published agricultural education standards from California, Indiana, Texas, Virginia, Wisconsin, and The National Council for Agricultural Education. The overall aim was to access the attention given to, or inconsistencies in, agricultural safety, health, and biosecurity standards that are increasingly becoming central to agricultural production. This effort was part of a curricula design project to expand and enhance the Gearing Up for Safety – Production Agricultural Safety Curriculum for Young and Beginning Workers to ensure adequate coverage of biosecurity topics in secondary education programs. Agricultural education programs which involved topics of safety, health, and biosecurity, included curricula with outcomes and objectives that are created from competencies or standards. It was found that current standards give little attention, generally, to agricultural safety, health, and biosecurity. The academic standards reviewed had little consistency in the associated topics of safety and health, or biosecurity. The National Council for Agricultural Education and Wisconsin agricultural safety, health, and biosecurity standards constituted around 20% of the overall agricultural standard count. However, in most other states, the overall agricultural safety standards constituted as little as 3% of the overall standards. The lack of consistency in the standards, especially with respect to identification of desired learning outcomes makes curricula development efforts more difficult and less likely to meet actual needs in the field. The need to develop uniform educational standards that reflect the increasing importance being given to food safety, biosecurity and workplace safety and health was identified. Keywords: Agricultural academic standards, Agricultural health, Agricultural safety, Biosecurity standards, Education standards.
Investigation on CEED-RES Problem Using Modified Lagrange Method
Authors: Manikandan K. , Sasikumar S. , Arulraj R. 
Published: December 2022

The notion of a micro grid system is used to prevent transmission losses and to ensure a dependable power supply to a limited geographical area. It has been a mandatory protocol to apply accessible Renewable Energy Sources (RES) in order to reduce hazardous pollutants released into the atmosphere as a result of fossil fuel burning. Economic load dispatch (ELD) is concerned with the most cost-effective sizing of distributed energy resources (DERs). By limiting the hazardous content of pollutants emitted into the atmosphere, emission dispatch determines the ideal size of DERs.
A multi-objective Combined Economic-Emission Dispatch (CEED) is created, which determines the appropriate DER sizing while minimizing both fuel costs and pollution emissions. Using Python programming in IDLE, this work conducts all ELD, Emission Dispatch, and CEED on a renewable-integrated micro grid and grid connected mode independently. The results are then compared with conventional method effectiveness of the proposed technique. In this paper, the algorithm proposed in python language to check the accuracy, multidisciplinary integration and ease of understanding. This article is developed based on conventional CEED solution and validated with the help of Python programming for a typical IEEE test system.
Modelling IoT Behaviour in Supply Chain Business Processes with BPMN: A Systematic Literature Review
Authors: Abouzid Ihsane , Bekali Younes Karfa , Saidi Rajaa 
Published: December 2022

The Internet of Things (IoT) enables to connect physical world to digital processes, allowing real-world data to be fed into business processes. This revolution helps in the making of more informed business decisions as well as the automation and/or improvement of business processes tasks. The successful integration of IoT into business operations is required to realize these benefits. Supporting the modelling of IoT-enhanced business proccesess is the first step toward this goal. Despite the fact that numerous papers studied this topic, it is unclear what the current state of the art is in terms of modelling solutions and gaps. We conduct a systematic literature review in this work to determine how current solutions model IoT into business operations, and whether the standard Business Process Model and Notation (BPMN) has emerged as the de facto standard for business process modelling [20, 26]). The Object Management Group (OMG) developed BPMN, which is now an ISO standard BPMN is already enough for a full modelling of IoT integration, or the extensions are needed. We found and analysed the several existing alternative solutions after reviewing all the literature on this issue. Furthermore, we discuss some key aspects of the planned additions that should be addressed in the near future, such as the absence of standardization.
Design of the quadrangular prism beam splitting receiving system in the MEMS-based scanning LIDAR
Authors: Lee Xiaobao , Zhou Weilong , Huang Zhuomian 
Published: December 2022

The detector bandwidth and photosensitive surface aperture are the key
parameters in the high-precision and high-definition scanning 3D
imaging LIDAR system, which usually require a high detector bandwidth
and large photosensitive surface aperture. In order to solve the
problem of a high bandwidth and small photosensitive surface of
existing InGaAs detectors, this paper proposes a beam splitting method
using a pair of quadrangular prisms to realize beam splitting the
reception of return laser beams, which increases both the receiving
field of view (FOV) and the effective photosensitive surface of the
detector. The principle and structure of the prism beam splitter are
discussed; a beam splitting receiving optical system with a pair of
quadrangular prisms is presented, and the beam splitting effect
verified by its simulation experiment is analyzed. With this novel, to
the best of our knowledge, light splitting receiving method, the
receiving FOV can be effectively increased to

±

5
∘

, and the effective photosensitive
surface aperture of the detector can be increased from 0.5 to
1.0 mm.