bluuebunny/crossref_metadata_2025 huggingface dataset:
Practical Optimization of Perforation Design with a General Correlation for Proppant and Slurry Transport from the Wellbore
Authors: Dontsov Egor , Ponners Christopher , Torbert Kevin , McClure Mark
Published: January 2024

During plug and perf completion, perforation pressure drop is used to encourage a uniform distribution of flow between clusters by overcoming stress shadowing, stress variability, and nonuniform breakdown pressure. However, proppant inertia, gravitational settling, and perforation erosion contribute to nonuniformity, even with an aggressive limited-entry design. In prior work, Dontsov (2023) developed a correlation for predicting proppant outflow from the wellbore as a function of slurry velocity, perforation phasing, and other parameters. In the present study, the Dontsov (2023) correlation is integrated into a wellbore dynamics simulator capturing key physical processes that control slurry and proppant outflow from the wellbore, such as erosion, stress shadowing, and near-wellbore tortuosity. The simulator is fast running and incorporated into a tool for Monte Carlo uncertainty quantification and design optimization. First, we run a series of sensitivity analysis simulations to evaluate the effect of key model inputs. The simulations demonstrate processes that can cause heel bias, toe bias, or heel/toe bias in the erosion distribution. Next, we apply the tool to analyze field datasets from the Eagle Ford and the Montney. Downhole imaging of erosion data enables model calibration. Calibration is necessary because differences in casing, cement, and formation properties cause differences in erosion behavior and flow distribution. Parameters controlling the magnitude of erosion and stress shadow are modified to match the trends observed from the downhole imaging. After calibration is performed, the model is applied to maximize the uniformity of proppant placement by optimizing perforation phasing, diameter, count, and cluster spacing.
Cementing: The Good, the Bad, and the Isolated - Techniques to Measure Cement Quality and its Impact on Well Performance
Authors: Haustveit Kyle , Haffener Jackson , Young Steven , Dwyer John , Glaze Garrett , Green Brett , Ketter Chris , Williams Tyler , Brinkley Kourtney , Elliott Brendan
Published: January 2024

Cement isolation is considered by some a critical component of effective well completions in horizontal, multi-stage, hydraulically stimulated oil and gas wells. Virtually every new unconventional well includes multiple cement jobs which cost tens to hundreds of thousands of dollars each. As cluster spacing gets tighter, the importance of high-quality cementing becomes even more pronounced, or does it? This paper explores the various diagnostic techniques used to measure cement isolation, including ultrasonic imaging, optical fiber, radioactive tracer, and downhole pressure gauges on sleeve completion assemblies. The paper ties these diagnostic techniques back to well performance for both new completions and refracs.

The study examines multiple US basins and reveals that the necessity of high-quality cement isolation is potentially related to the size of the annulus being cemented. Smaller annuli are more difficult to cement due to higher Equivalent Circulating Densities (ECDs) caused by friction, but well performance may be less impacted by poor cement in these scenarios because the large pressure drop in the annulus during stimulation contains much of the stimulation in and around the intended interval. However, this does not mean that poor cementing in smaller annuli can be overlooked, as it can still have an impact on well performance.

The paper presents case studies that evaluate the importance of cement isolation in both new completions and refracs with various annulus sizes and well spacings. The findings are applicable to cemented laterals completed with multi-stage stimulations in oil and gas reservoirs as well as in enhanced geothermal applications, where effective fracture uniformity is one key to performance.

Overall, this paper provides valuable insights into the importance of cement isolation in horizontal, multi-stage, hydraulically stimulated oil and gas wells. It emphasizes the need for accurate diagnostic techniques to measure cement isolation and the importance of high-quality cementing to ensure optimal well performance.
Time-Dependent Integration of Fiber Optic Results with Post-Treatment Rate Transient Analysis
Authors: Bourdon N. M. , Miskimins J. L. , Rich J. P.
Published: January 2024

A long-term monitoring project included collection of fiber-optic data in one well of a multi-well development for the first few years of production. We demonstrate a benefit to including the fiber data in rate transient analysis (RTA). The fiber data also reveals communication between stages along the monitored well and communication with the offset wells. We use a calibrated hydraulic fracture model to simulate fracture stimulation of wells in the development. Fiber data gathered at the time of stimulation included both distributed acoustic sensing (DAS) and distributed temperature sensing (DTS). Additionally, DTS was acquired over two years of production and used to help calibrate the model and associated RTA. For comparison purposes, RTA was performed on the wells with and without consideration of the DTS data to quantify the benefit of including the fiber data. We conclude that the fiber data was highly beneficial in both the fracture propagation modeling and the resulting RTA process. The time-lapse data allowed for visual interpretation of how the flow behavior of different stimulation stages along the lateral are not constant. Early time heel or toe dominance can, and likely will, disappear over time. The data also indicates that the child wells were in communication with each other at varying levels during treatment and post-production. We provide a workflow for incorporating these varied data to provide a long-term overview of multi-well production and interference behavior. Additionally, we provide insight on the use of years of DTS datasets for unconventional wells, which are still relatively rare in the literature.
Optimizing Stage Lengths by Leveraging Fracture Interference
Authors: Rodgers Evan , Williams Tony , Rittenburg Dylan , Lawrence Matthew
Published: January 2024

Objectives/Scope

This paper covers a case study in the Denver-Julesburg (DJ) Basin that reveals stage lengths can be dynamically varied when wells are tightly spaced to optimize pad drainage and completion cost in homogeneous rock strata. Alternating stage designs in offset wells can support increased stage lengths up to 6x standard (exceeding 1,000 ft) and still treat and produce as uniformly as smaller stages, due to the cooperative effect of the overlapping fracture network created by neighboring infill wells. These findings were corroborated by fiber optic data acquired during frac (cross-well strain) and post-flowback production monitoring and interference testing. We also observed Formations within damage zones altered from faults can affect drainage results.

Methods, Procedures, Process

Differing stage lengths (X, 2X, 3X and 6X) were trialed in three wells in a six well section. Fiber optic diagnostics were acquired during frac for cross-well strain evaluation and 60 days post-flowback for production monitoring and interference testing. Locations and extent of fracture interactions were observed during the fracturing process, and later compared to the production and interference testing results after flowback.

Results, Observations, Conclusions

The post-completion diagnostics corroborated the during frac cross-well strain data. Interference testing reveals communication as well as unique geological features in the areas identified by the cross-well strain data. There is little if any difference in cross-well strain or production behavior of standard-length X stages offset by X stage lengths and X offset by 2X or 3X stage lengths. Performance of the 3X and 6X stages is nearly identical to the X stage lengths, in both production and interference from a uniformity and production volume.

Novel/Additive Information

When wells are known to interfere or communicate, completion designs can be modified dynamically to work with overlapping stage designs, optimizing completion costs without sacrificing treatment uniformity nor production. Stage lengths of offset wells, depending on the play and geologic structure, may be dramatically larger than previously thought when offset against smaller stages, while still allowing for sufficient reservoir access and drainage, leading to reduced pad development time.
Validation of Conductive Fracture Imaging with Cross Well Strain and Permanent Fiber Optic Flow Profiling
Authors: Reshetnikov A. , Taylor S. , Nazarova A. , Haffener J.
Published: January 2024

The study applies Conductive Fracture Imaging (CFI) on Hydraulic Fracturing Test Site-2 in the Delaware Basin, USA, acquired in 2019. The CFI results are independently delivered and compared with strain data recorded by permanent distributed fiber optic sensor arrays in a vertical data well (the Boxwood 5PH) and two horizontal wells (Boxwood 3H and Boxwood 4H). Boxwood 4H's permanent fiber provides Distributed Acoustic Sensing (DAS) cluster flow and proppant allocation analytics, as well as distributed strain sensing (DSS) for cluster level shut-in pressure build-up tests.

The objective of this study is to directly compare CFI results with in-well DAS and DSS fiber optic measurements. CFI utilizes microseismic events as active sources for reflection imaging of the conductive portion of hydraulic fractures, offering high-resolution images of the seismically active zone for precise description of cluster level fluid allocation and conductivity.

CFI has been benchmarked successfully against established fiber optic diagnostics, providing insights into conductive fracture geometries, cluster efficiencies, and in-well production flow profiling. Key advantages of CFI include imaging fluid and proppant allocation at the cluster level, offering a four-dimensional view of dynamic transport, estimating fracture height, and providing valuable data on hydraulic and conductive fracture geometries.

The study reveals strong correlations between CFI and cross-well strain intensity measured by fiber monitors, as well as good agreement with in-well DAS stimulation fluid allocation. Furthermore, CFI shows clear correlations with cluster level DSS strain changes during the production phase, accurately resolving cluster positions along the wellbore. Cluster level reflectivity values from CFI demonstrate a robust agreement with DSS strain change peak values observed on the same clusters.
Hydraulic Fracturing Design Considerations for Carbon Capture, Utilization, and Storage (CCUS)
Authors: Sierra Leopoldo , Lovingfoss Connor
Published: January 2024

Hydraulic fracturing, a well-established technique in the oil and gas industry, has gained significant attention as a potential method to improve the short- and long-term efficiency of the Carbon Capture, Utilization, and Storage (CCUS) process. Most of the scoping studies on CCUS have centered on the reservoir aspects, such as storage and CO2 movement. Very little has been done evaluating what the fracture designs might look like in this process.

This paper presents a review of the application of hydraulic fracturing in CCUS projects, examining its technical feasibility, fluids, sustaining agents, wellbore orientation, and fracture orientation considerations required to assure its technical and economic success. It will consider rock properties, depleted oil or gas reservoirs conditions, or deep saline aquifers horizons and compressed CO2 supply at the storage site; simulations have been performed using primarily super critical CO2 (scCO2) and conventional fluids to perform the hydraulic fracturing. In addition to the sCO2 usage and proppants required to tail the generated fractures; the wellbore orientation effect in reference to the stress plane is also considered in the paper.

Finally the short- and long-term benefit of the hydraulic fracturing will be evaluated by simulating the CO2 injection behavior.

The review encompasses an analysis of the various key stages involved in CCUS hydraulic fracturing process, starting from the review of rock properties, wellbore orientation, perforation strategy, selection of suitable fluid and propping agents for efficient and safe stimulation of a well candidate. The potential benefits of the proper hydraulic fracturing process implementation will be translated in an enhanced storage capacity and improved injectivity.

The extensive simulations considering the sCO2 as the primary fluid system for fracturing purposes, combined with the wellbore orientation and other parameters will show the direct benefit of the combinations of the hydraulic fracturing and the CCUS processes, including: The use of sCO2 and proppants for hydraulic fracturing purposes in CCUSThe influence of the wellbore and hydraulic fracture orientation in the success of the CCUS process

The paper aims to explore the potential of CCUS in conjunction with hydraulic fracturing to increase the efficiency of CO2 disposal and analyze methods to maximize its effectiveness. It will be beneficial for those contemplating CCUS, complementing other CCUS evaluations to provide a more complete picture of the feasibility as well as technical hurdles that must be overcome to implement this concept.
Evaluation of a Rapid Diagnostic Tool to Estimate Geometry Evolution of Multiple Simultaneously Propagating Fractures from Cross-Well Fiber Optic Strain Measurements
Authors: Leggett Smith , Chen Ming
Published: January 2024

Cross-well low-frequency distributed acoustic sensing (LF-DAS) strain rate measurements generate data useful for hydraulic fracture diagnostics. These data contain information about hydraulic fracture geometry; however, interpreting the data has relied on time-consuming and computationally expensive numerical interpretation methods. This study aims to evaluate the applicability of a rapid diagnostic tool, known as the "zero strain rate location method" (ZSRLM), for characterizing the geometry of multiple fractures propagating simultaneously.

Simulations of multiple fracture propagation are conducted using a planar 3D multi-fracture simulator that incorporates 3D rock deformation, fluid flow in the wellbore, fluid leak-off, and multi-scale fracture propagation regimes. A super-time-stepping algorithm is employed to solve the nonlinear parabolic equations governing fluid-driven fractures. The far-field strain profile induced by multiple propagating fractures along a cross-well fiber optic cable is computed using the displacement discontinuity method. Various scenarios are simulated by adjusting key completion parameters, including the number of clusters, cluster spacing, in-situ stress states, and geomechanical properties. The ZSRLM is then applied to the computed strain field to estimate fracture extents and propagation rates. The accuracy of the ZSRLM is assessed by comparing the estimated fracture geometry parameters with the known simulated values.

Our observations indicate that the ZSRLM is not effective when two or more fractures approach the observation well at similar times, as it becomes challenging to discern unique strain-rate converging patterns on waterfall plots for each fracture. However, when fracture arrivals at the monitor well are offset, distinct strain rate patterns emerge, enabling the application of the ZSRLM. Errors between simulated and estimated fracture extent propagation rates are quantified. Finally, the ZSRLM is applied to a field case involving multi-cluster fracture propagation, and the interpretation of the results is discussed in light of these findings.

This research demonstrates the applicability of the ZSRLM for diagnosing the velocities and final extents of multiple fractures propagating simultaneously. The method offers a rapid means of characterizing stimulations using cross-well LF-DAS measurements, which can inform decisions regarding completion design, well spacing, and landing zone. The study contributes to the advancement of efficient fracture diagnostics in the industry, reducing the reliance numerical interpretation methods.
Hybrid Long Short-Term Memory and Convolutional Neural Network Architecture for Electric Submersible Pump Condition Prediction and Diagnosis
Authors: Liu DongJiang , Feng Guoqiang , Feng Guoyong , Xie Lijie
Published: January 2024

Electric submersible pump (ESP) is one of the common artificial lift technologies in offshore production systems. ESP failures are the main cause of the decline in the production efficiency of oil wells. Early warning and diagnosis of ESP failures are crucial to improve well production efficiency. In this study, a hybrid model of long short-term memory neural network and convolutional neural network (LSTM-CNN) for accurate early warning and diagnosis of ESP faults is proposed, based on electrical data as the basis of analysis. Using hyper-parameters to optimize the LSTM neural network structure and highly fit the field electrical data so that it can be applied to anomaly prediction before ESP faults, the results show that the optimized LSTM model with R2 (test set) = 0.79, root mean square error (RMSE) (test set) = 0.89, which can predict the future electrical data more accurately, and the predicted data are plotted in the polar coordinate system to simulate the ammeter card as the validation set. The ammeter card data set is simulated by collecting electrical data from different working conditions, which is expanded using data expansion, and different CNN models are trained to fine-tune the parameters using transfer learning. The results show that the GoogLeNet model has a significant diagnostic accuracy of 97%, which is 2% and 18% better than VGG16 and ResNet34, respectively. The model evaluation shows that the GoogLeNet model has good recall, F1-Score, and confusion matrix. The trained GoogLeNet model was applied to the validation set, and the hybrid LSTM-GoogLeNet model was found to be well-suited for ESP warning and diagnosis.
The integration of migration into municipal sustainable development planning in the city of UMhlathuze
Authors: Sibiya Lindokuhle D. , Moyo Inocent
Published: January 2024

Migration, as a global phenomenon, affects municipalities not only in South Africa but across the globe, therefore, it must be factored into municipal policy, planning, and budget processes. Sustainable Development Goal target 10.7.2 aims at facilitating orderly, safe, regular, and responsible migration and mobility of people through the implementation of planned and well-managed migration policies at global, national, regional, and local levels. Applying the concept of institutional liberalism to understand inclusive and democratic institutional planning, this paper explores and reports the integration of migration into municipal development planning in the City of uMhlathuze, KwaZulu-Natal, South Africa. Following a case study qualitative approach, 20 municipal officials were interviewed, municipal documents were extensively reviewed to collect data and data were analysed using thematic analysis. The findings reveal that despite an increasing number of foreign migrants in the municipality, migration is not integrated into municipal development planning. Given that migration is directly linked to at least 11 of the 17 SDGs, this paper argues that the SDGs cannot be domesticated and achieved at the local government level if migrants are excluded in development planning processes.
Improved detection of magnetic interactions in proteins
based on long-lived coherences
Authors: Sadet Aude , Ianc Octavian , Teleanu Florin , Ciumeică Andrei , Lupulescu Adonis , Vasos Paul
Published: January 2024

Living systems rely on molecular building blocks with low structural symmetry. Therefore, the constituent amino-acids and nucleotides yield short-lived nuclear magnetic responses to electromagnetic radiation. Magnetic signals are at the basis of molecular imaging, structure determination and interaction studies in the liquid state. Interactions between magnetic nuclei can only be detected provided the lifetimes of spin order are sufficient. In J-coupled pairs of nuclei, long-lived coherences (LLC’s) can be excited between states with different spin-permutation symmetry. In solution state, as the molecular weight of analytes increases, coherences with long lifetimes are needed to yield advantageous through-space magnetisation transfers. In protein Lysozyme, weighing 14.3 kDa, we sustained coherences with lifetimes twice as long as those of classical magnetisation for the aliphatic protons of glycine residues. We found that, in this protein of significant molecular weight, LLC’s yield substantial through-space magnetisation transfers: in agreement with theory, spin-order transfer stemming from LLC’s overcame transfers from classical coherences by factors 2-3. Furthermore, the permutation symmetry of LLC-based transfers allowed mapping the positions of interacting atoms in the protein structure with respect to the molecular plane of glycine residues in a stereospecific manner. These findings can extend the scope of liquid-state high-resolution spectroscopy in the analysis of biomolecular complexes of high molecular weight.
DNA methylation is associated with oxidative stress and genomic deregulation in diabetes mellitus
Authors: Sen Subhrojit
Published: January 2024

Retrotransposons may undergo aberrant methylation leading to genomic deregulation in diabetes mellitus. The present study evaluated the methylation of retrotransposons namely Alu, B1, and LINE-1 elements in glucose-induced endothelial cells (ECs) and T1DM. The correlation between methylation of these retrotransposons and oxidative stress was investigated. Additionally, methylation of FN1, VEGFa, and EDN1 genes was analyzed. Hot start PCR of the bisulfite converted DNA isolated from the ECs and kidneys for the methylation of retrotransposons was analyzed. Quantification of methylated DNA in ECs was performed by ELISA. The methylation of the FN1, VEGFa, and EDN1 genes was examined. Oxidative stress was evaluated by measuring the superoxide anion, mitochondrial reactive oxygen species (ROS), 8-Hydroxyguanosine (8-OHdG), and NF-kappaB p(65). Hypermethylation of Alu and LINE-1 elements occurred in the high glucose- induced ECs. B1 hypermethylation was observed in the kidneys of T1DM mice. Hyperglycemia resulted in LINE-1 hypermethylation in the kidneys of T1DM mice. Hypermethylation of the FN1, VEGFa and EDN1 genes occurred in the high glucose-induced ECs and diabetic kidneys. Hypermethylation of the retrotransposons, oxidative stress and NF-kappaB p(65) were inhibited by 5-Aza-Dc and ginseng treatment. This study illustrated that retrotransposon hypermethylation and oxidative stress were evident in the glucose-induced ECs and T1DM along with hypermethylation of the FN1, VEGFa and EDN1 genes. The study also demonstrated the association between hypermethylation of these retrotransposons and oxidative stress in diabetes.
Comprehensiveness and Instructional Quality of YouTube Videos on Clinical Record-Keeping Training in Medical Education
Authors: Emekli Emre , Kıyak Yavuz Selim
Published: January 2024

Objective
Clinical record-keeping is recognized as a core competency in medical education. This study aimed to evaluate comprehensiveness and instructional quality of videos available on the YouTube platform for teaching clinical record-keeping.
Material and Method:
YouTube was searched by using relevant keywords. Based on eligibility criteria, 59 videos were included in the study. Videos were assessed for country of origin, video length, number of likes, dislikes, comments, daily views, like ratio, and video power index. Tools to measure the quality of clinical notes, which are QNOTE and RED Checklist …, have been used to assess comprehensiveness of the videos. Instructional quality was assessed using the instructional video quality checklist (IVQC).
Results
The comprehensiveness score was 60.4 ± 17.89 (out of 100), while instructional quality score was 11.19 ± 3.61 (out of 27). IVQC scores were significantly higher in the university/professional organizations and academics compared to the others (p < 0,001). However, there was no significant difference between the groups in comprehensiveness scores (p = 0,131).
Conclusion
YouTube videos missing important rate of components of clinical record-keeping. Moreover, the instructional quality of the videos falls below half of the expected levels. These problems still persist in the videos uploaded by universities/professional organizations and academics. Therefore, YouTube videos should be used cautiously for clinical record-keeping training by medical students and medical educators.
WITHDRAWN: The association between adult penile length and IQ: evidences from 139 countries
Authors: Wang Cuntong , Wangding Yihe
Published: January 2024

Objective This study investigates the global correlation between adult penile length and Intelligence Quotient (IQ).Methodology: The study utilizes data from 115,387 males aged 18–65 across 139 countries, examining penile size and IQ measurements. After adjusting for variables including GDP per capita, educational spending, daily maximum temperature, and BMI, we performed partial correlation and regression analyses on penile length and IQ, along with an interethnic comparison.Results A statistically significant negative correlation was found between flaccid penile length and IQ (P < 0.001), indicating higher IQs in individuals with shorter penile lengths, and notable ethnic differences were observed (P < 0.001).Conclusions The inverse relationship between flaccid penile length and IQ could be linked to genetic, evolutionary, or environmental factors, offering insights into the penile size-IQ connection.
Effects of antibiotics on secondary metabolism and oxidative stress in oilseed rape seeds
Authors: Li Ke , zhao Mengting , zhou Shanshan , niu Lili , zhao Lu , Xu Dongmei
Published: January 2024

Cruciferae brassica oilseed rape is the third largest oilseed crop in the world and the first in China, as well as a fertilizer-dependent crop. With the increased application of organic fertilizers from livestock manure in agricultural production in recent years, the resulting antibiotic pollution and its ecological health effects have attracted widespread attention. In this study, typical tetracycline and sulfonamide antibiotics tetracycline (TC) and sulfamethoxazole (SMZ) were used to investigate the effects of antibiotics on rapeseed quality and oxidative stress at the level of secondary metabolism on the basis of examining the effects of the two drugs on the growth of soil-cultivated rapeseed seedlings. The results showed that both plant height and biomass of rapeseed seedlings were significantly suppressed and ROS were significantly induced in rapeseed by exposure to high concentrations (2.5 mg/kg) of TC and SMZ. Carotenoids, tocopherols and SOD enzymes were involved in the oxidative stress response to scavenge free radicals in rapeseed, but phenolic acids and flavonoids contents were decreased, which reduced the quality of the seeds to some extent.
Application of novel algorithm on a retrospective series to implement the molecular classification for endometrial cancer.
Authors: Arcieri Martina , Occhiali Tommaso , Giorgiutti Cristina , Tius Veronica , Pregnolato Sara , Mariuzzi Laura , Orsaria Maria , Andreetta Claudia , Titone Francesca , Damante Giuseppe , D'Elia Angela Valentina , Biasioli Anna , Martina Monica Della , Fanfani Francesco , Ercoli Alfredo , Driul Lorenza , Scambia Giovanni , Vizzielli Giuseppe , Restaino Stefano
Published: January 2024

Background The study aimed to validate the Betella algorithm, focusing on molecular analyses exclusively for endometrial cancer patients, where molecular classification alters risk assessment based on ESGO/ESTRO/ESP 2020 guidelines.
Methods Conducted between March 2021 and March 2023, the retrospective research involved endometrial cancer patients undergoing surgery and comprehensive molecular analyses. These included p53 and mismatch repair proteins immunohistochemistry, as well as DNA sequencing for POLE exonuclease domain. We applied the Betella alghoritm to our population and evaluated the proportion of patients in which the molecular analysis changed the risk class attribution.
Results Among 102 patients, 97% obtained complete molecular analyses. The cohort exhibited varying molecular classifications: 10.1% as POLE ultra-mutated, 30.3% as mismatch repair deficient, 11.1% as p53 abnormal, and 48.5% as non-specified molecular classification. Multiple classifiers were present in 3% of cases. Integrating molecular classification into risk group calculation led to risk group migration in 11.1% of patients: 7 moved to lower risk classes due to POLE mutations, while 4 shifted to higher risk due to p53 alterations. Applying Betella algorithm, we can spare the POLE sequencing in 65 cases (65.7%) and p53 immunochemistry in 17 cases (17.2%).
Conclusion The application of this new proposed algorithm appears safe for the patients while rationalizing resources that could be otherwise allocated, making it not only useful for low resources settings, but for all settings in general.
Epigenome-Wide Association Studies in Cases and Controls With High and Low Genetic Risk for Schizophrenia
Authors: Höffler Kira , Stavrum Anne-Kristin , O`Connell Kevin , Weibell Melissa , Djurovic Srdjan , Andreassen Ole , Melle Ingrid , Hellard Stephanie Le , Spíndola Letícia
Published: January 2024

Schizophrenia (SCZ) is a severe psychiatric disorder caused by a complex interplay of genetic and environmental factors. Genome-wide association studies (GWASs) have identified numerous genetic variants associated with SCZ, yet genetic risk does not fully predict the disorder. Some individuals with a high genetic risk do not develop SCZ, whereas others with lower genetic risk do. This discrepancy suggests that non-genetic factors, potentially mediated by epigenetic modifications, play a role in SCZ etiology. Our study aimed to identify DNA methylation differences between SCZ patients and healthy controls within high and low genetic risk groups for SCZ, thereby reducing genetic risk heterogeneity and focusing on non-genetic influences. In our cohort of 491 SCZ patients and 765 controls, we selected those in the highest and lowest 30% of the SCZ polygenic risk score (SCZ-PRS) distribution. We then conducted targeted epigenome-wide association studies (EWASs) in these specific high and low genetic risk groups. This analysis identified two differentially methylated regions (DMRs) in the high genetic risk group, annotated to PF4 and ZNF727, and two DMRs in the low genetic risk group, mapped to EMILIN1 and HLA-DPB2 (comb-p seed p = 0.001, Šidák-corrected p < 0.05). Additionally, our findings suggest that a general case-control EWAS, adjusted for SCZ-PRS, might miss epigenetic markers unique to either the high or low genetic risk groups. In conclusion, performing EWASs on PRS-stratified groups can identify novel DNA methylation signatures associated with disease status.
SWELE Programme for improving mental wellbeing in children and adolescents with special educational needs: protocol of a quasi-experimental study
Authors: Lee Regina Lai Tong , Chien Wai-Tong , Chong Connie Yuen-Yu , Chau Wai-Ho , Choi Kai-Chow , Chan Sally Wai-Chi , Brown Michael
Published: January 2024

Background: Unstructured play has also been found effective on promoting positive emotions and emotional competence among early adolescents. Unstructured Outdoor Play coupled with Mindfulness-based Interventions via SWELE programme can foster the mental health and wellbeing of children and adolescents with SEN during COVID-19 pandemic. Currently there is a lack of the unstructured play-based programme in the special schools in Hong Kong. Thus, the aim of the SWELE Programme is to raise the public’s awareness how unstructured play with mindfulness interventions on ‘Supporting Wellness in E-Child Learning Environments’ (SWELE) programme combining unstructured outdoor play with mindfulness-based activities to promote mental health in SEN children and adolescents (students), in the context of the COVID-19 pandemic.
Method/design: This 16-week programme focuses on Supporting Wellness in E-Child Learning Environments (SWELE) programme by combining unstructured outdoor play with mindfulness-based interventions to promote mental health in special education needs (SEN) students (ages 6-19), in the context of the post COVID-19 pandemic. A mixed method design with a quantitative measure using a pre- and post-tests quasi-experiment behavioural observational method without a control group to evaluate the effectiveness of a SWELE Programme on SEN students’ mental wellbeing; and with a qualitative design to conduct 6-8 focus group interviews (schoolteachers, parents, SEN students, school nurses) in six special groups (two groups from each special school) to explore the SEN students’ experiences in participating the SWELE programme.
Discussion: With the outlined predefined analysis, we will assess the impact of a 16-week unstructured outdoor play programme on the emotional, anxiety, playful behaviour and mental health of children and adolescents with SEN in the special schools in Hong Kong.
Trial Registration: ClinicalTrial.gov, NCT06112483. Registered on 31 October 2023.
Co-ingestion of cereals and legumes during infant complementary feeding: starch and protein in vitro digestion
Authors: Rodriguez Marianela D. , León Alberto E. , Bustos Mariela C.
Published: January 2024

This study explores the impact of co-ingesting cereals and legumes on starch and protein during simulated infant in vitro digestion. Various legumes (chickpeas, lentils, peas) were added to cereals (durum wheat, brown rice, white maize), and their effects on starch and protein hydrolysis were analyzed. Substituting 50% of cereal with legumes increased proteins, minerals, and dietary fiber. Infant food with legumes exhibited smoother pasting properties. Legumes in cereal purées led to varying starch hydrolysis trends, with the lowest values in durum wheat with chickpea and all cereal blends with peas. Resistant starch levels exceeding 50% were found in infant food samples. Digested protein hydrolysis increased with legumes in durum wheat, except for peas. Brown rice mixtures decreased significantly compared to the control with chickpeas (61%) and peas (42%), while lentil blends increased by 46%. Legumes generally did not significantly affect starch bioavailability, even with α-amylase inhibitors. Lentil-cereal purées could enhance infant food nutritional value.
Preclinical characterisation of gallium-68 labeled ferrichrome siderophore stereoisomers for PET imaging applications.
Authors: Krasulova Kristyna , Neuzilova Barbora , Bendova Katerina Dvorakova , Novy Zbynek , Popper Miroslav , Hajduch Marian , Petrik Milos
Published: January 2024

Background: Siderophores are small iron-binding molecules produced by microorganisms to facilitate iron acquisition from the environment. Radiolabelled siderophores offer a promising solution for infection imaging, as they can specifically target the pathophysiological mechanisms of pathogens. Gallium-68 can replace the iron in siderophores, enabling molecular imaging with positron emission tomography (PET). Stereospecific interactions play a crucial role in the recognition of receptors, transporters, and iron utilisation. Furthermore, these interactions have an impact on the host environment, affecting pharmacokinetics and biodistribution. This study examines the influence of siderophore stereoisomerism on imaging properties, with a focus on ferrirubin (FR) and ferrirhodin (FRH), two cis-trans isomeric siderophores of the ferrichrome type.
Results: Tested siderophores were labelled with gallium-68 with high radiochemical purity. The resulting complexes differed in their in vitro characteristics. [68Ga]Ga-FRH showed less hydrophilic properties and higher protein binding values than [68Ga]Ga-FR. The stability studies confirmed the high radiochemical stability of both [68Ga]Ga-siderophores in all examined media. Both siderophores were found to be taken up by S. aureus, K. pneumoniae and P. aeruginosa with similar efficacy. The biodistribution tested in normal mice showed rapid renal clearance with low blood pool retention and fast clearance from examined organs for [68Ga]Ga-FR, whereas [68Ga]Ga-FRH showed moderate retention in blood, resulting in slower pharmacokinetics. PET/CT imaging of mice injected with [68Ga]Ga-FR and [68Ga]Ga-FRH confirmed findings from ex vivo biodistribution studies. In a mouse model of S. aureus myositis, both radiolabeled siderophores showed radiotracer accumulation at the site of infection.
Conclusions: The 68Ga-complexes of stereoisomers ferrirubin and ferrirhodin revealed different pharmacokinetic profiles. In vitro uptake was not affected by isomerism. Both compounds had uptake with the same bacterial culture with similar efficacy. PET/CT imaging showed that the [68Ga]Ga-complexes accumulate at the site of S. aureus infection, highlighting the potential of [68Ga]Ga-FR as a promising tool for infection imaging. In contrast, retention of the radioactivity in the blood was observed for [68Ga]Ga-FRH. In conclusion, the stereoisomerism of potential radiotracers should be considered, as even minor structural differences can influence their pharmacokinetics and, consequently, the results of PET imaging.
Cachexia Index is a Prognostic Indicator in Patients with Metastatic Urothelial Carcinoma Treated with Gemcitabine plus Cisplatin Chemotherapy
Authors: Mimura Yoshihisa , Naiki Taku , Sugiyama Yosuke , Tasaki Yoshihiko , Odagiri Kunihiro , Etani Toshiki , Nagai Takashi , Iida Moeko , Kimura Yuka , Ito Nanami , Hotta Yuji , Yasui Takahiro , Furukawa-Hibi Yoko
Published: January 2024

Background
The objective of our study was to assess the cachexia index (CXI) as a prognostic indicator for patients with metastatic urothelial carcinoma (mUC) treated with gemcitabine plus cisplatin (GC) chemotherapy.
Methods
This study included 55 patients with mUC who underwent GC chemotherapy between 2008 and 2022 as first-line chemotherapy. The CXI at the start of chemotherapy was determined as follows: CXI = (serum albumin × skeletal muscle mass index)/(neutrophil count/lymphocyte count). Patients were categorized into two groups based on a median CXI value (CXI high and CXI low). We used Kaplan–Meier curves and multivariate Cox proportional hazards regression models to assess the association between the CXI and overall survival (OS).
Results
At the start of GC chemotherapy, significant differences were not found in patients' characteristics. The median OS was significantly shorter in the CXI low group (9.8 months [95% confidence interval (CI), 5.1–12.6]) than in the CXI high group (22.0 months [95% CI, 15.4–NA], P < 0.05). Multivariate analysis revealed that low CXI was a predictor of a poor prognosis (P < 0.05, hazard ratio 2.446, 95% CI 1.087–5.501).
Conclusion
CXI might be useful as a prognostic indicator for patients with mUC undergoing first-line GC chemotherapy.
Examining the user experience of artificial intelligence tools in academic writing: The perceptions lecturers practices
Authors: Shofiah Nurul , Putera Zulmy Faqihuddin
Published: January 2024

In academic writing, AI technology has emerged as an innovative solution capable of enhancing the efficiency and quality of students' writing. This study seeks to explore the perspectives of lecturers, who are increasingly interested in and reliant on AI technology to augment the quality of their academic compositions. Furthermore, this study aims to comprehend lecturer' perceptions regarding using artificial intelligence tools in academic writing and how AI technology impacts learning. Grounded in the Technology Acceptance Model (TAM), this research encompasses perceived usefulness, perceived ease of use, attitude towards usage, intention to use behaviour, and actual usage. The study's respondents consist of 10 instructors from three universities in Malang City, Indonesia. First, the research findings indicate that using artificial intelligence tools yields various advantages for lecturer, including grammar checks, plagiarism detection, sentence improvement suggestions, and analyses of content relevance and structural coherence. Second, Instructors positively welcome using AI technology as a supplementary tool to support the learning and research processes; however, concerns about its potential over-dependence might diminish College student abilities to think creatively and critically. The outcomes of this research are expected to inform the development of future interventions aimed at maximizing the benefits of AI technology in education.
Bio-inspired multimodal learning with organic neuromorphic electronics for behavioral conditioning in robotics
Authors: de Burgt Yoeri van , Krauhausen Imke , Griggs Sophie , McCulloch Iain , Toonder Jaap , Gkoupidenis Paschalis
Published: January 2024

Biological systems interact directly with the environment and learn by receiving multimodal feedback via sensory stimuli that shape the formation of internal neuronal representations. Drawing inspiration from biological concepts such as exploration and sensory processing that eventually lead to behavioral conditioning, we present a robotic system handling objects through multimodal learning. A small-scale organic neuromorphic circuit locally integrates and adaptively processes multimodal sensory stimuli, enabling the robot to interact intelligently with its surroundings. The real-time handling of sensory stimuli via low-voltage organic neuromorphic devices with synaptic functionality forms multimodal associative connections that lead to behavioral conditioning, and thus the robot learns to avoid potentially dangerous objects. This work demonstrates that adaptive neuro-inspired circuitry with multifunctional organic materials, can accommodate locally efficient bio-inspired learning for advancing intelligent robotics.
Knowledge, attitude, and practice toward food preservatives among pregnant women
Authors: Yuan Shuai , Liu Weimei , Shen Zhixin , Ren Meitian , Hao Shuangying
Published: January 2024

Food preservatives extend shelf life but can be toxic. Sodium benzoate, a common preservative, can harm fetuses. Knowledge of preservatives’ health impact, especially among pregnant women, is limited. This study aimed to explore the knowledge, attitude, and practice (KAP) of pregnant women regarding food preservatives. This cross-sectional study enrolled pregnant women in Henan Province (China) between March and April 2023. The study collected 515 valid questionnaires [303 (58.83%) < 30 years]. The knowledge, attitude, and practice scores were 10.21 ± 2.90 (possible range: 0–17), 29.59 ± 2.73 (possible range: 8–40), and 22.86 ± 3.56 (possible range: 6–30; 76.20%), respectively. Multivariable logistic regression analysis showed that the knowledge (OR = 1.144, 95%CI: 1.061–1.234, P < 0.001), attitude (OR = 1.112, 95%CI: 1.028–1.203, P = 0.008) were significantly associated with the practice. The structural equation model (SEM) showed that the knowledge of food preservatives directly affected attitude (β = 0.168, P = 0.005) and practice (β = 0.250, P = 0.021) and indirectly affected practice (β = 0.047, P = 0.004). The food preservatives attitude directly affected practice (β = 0.280, P = 0.021). In conclusion, pregnant women in Henan have poor knowledge but favorable attitudes and active practices toward food preservatives. This study identified knowledge items that should be targeted by education interventions.
The association between empathy and burnout in medical students: a systematic review and meta-analysis
Authors: Cairns Patrick , Isham Aleksandra Eriksen , Zachariae Robert
Published: January 2024

Background
Burnout levels in medical students are higher than in other student groups. Empathy is an increasingly desired outcome of medical school. Empathy is negatively associated with burnout in physicians. Our objective was to quantitatively review the available literature on associations between empathy and burnout in medical students, and to explore associations between specific empathy aspects (cognitive and affective) and burnout sub-dimensions (emotional exhaustion, depersonalization and personal accomplishment).
Methods
A comprehensive search of the literature published up until January 2024 was undertaken in the PubMed, EMBASE, CINAHL, The Cochrane Library, and PsycINFO databases. Two independent reviewers screened 498 records and quality-rated and extracted data from eligible studies. The effect size correlations (ESr) were pooled using a random-effects model and between-study variation explored with meta-regression. The review was preregistered with PROSPERO (#CRD42023467670) and reported following the PRISMA guidelines.
Results
Twenty-one studies including a total of 27,129 medical students published between 2010 and 2023 were included. Overall, empathy and burnout were negatively and statistically significantly associated (ESr: -0.15, 95%CI [-0.21; -0.10], p < .001). When analyzing sub-dimensions, cognitive empathy was negatively associated with emotional exhaustion (ESr: -0.10, 95%CI [-0.17; -0.03], p = .006) and depersonalization (ESr: -0.15, 95%CI [-0.24; 0.05], p = .003), and positively associated with personal accomplishment (ESr: 0.21, 95%CI [0.12; 0.30], p < .001). Affective empathy was not statistically significantly associated with emotional exhaustion, depersonalization or personal accomplishment. Supplementary Bayesian analysis indicated the strongest evidence for the positive association between cognitive empathy and personal accomplishment. Response rate and gender moderated the relationship so that higher response rates and more male respondents strengthen the negative association between empathy and burnout.
Conclusion
Greater empathy, in particular cognitive empathy, is associated with lower burnout levels in medical students. This appears to be primarily driven through cognitive empathy's positive association with personal accomplishment.
Protocol Registration: #CRD42023467670
RETRACTED: Hierarchical Pore Engineering by Graphene Nanoscroll for All-Solid-State Fiber Supercapacitors
Authors: Oh Seongjae , Lee Seon , Kim Hyunsoo , Song Young-Chul , Kim Hyun , Lee Youngbok , Lim Seong Chu , Suh Dongseok , Kim Shi Hyeong , Kim Keon Jung
Published: January 2024

The authors have requested that this preprint be removed from Research Square.
Trophic niche overlap & increasing populations of a nonnative invader in the coastal Everglades
Authors: Kahmann Grace , Rehage Jennifer , Massie Jordan , Nelson James , Corujo Rolando Santos , Viadero Natasha , James Ryan , Boucek Ross , Crane Derek , Rezek Ryan
Published: January 2024

The Florida Everglades is a critically important, but highly threatened ecosystem that is becoming increasingly susceptible to the invasion of non-native species. This study investigated the ecological role of the invasive peacock eel (Macrognathus siamensis) within this ecosystem using 19 years of electrofishing data. We investigated the population trends of peacock eels at the marsh-mangrove ecotone of the Shark River Estuary, emphasizing the environmental factors contributing to their abundance and the potential interactions they may have with native fish assemblages and coastal food webs. We used stable isotope analysis to provide insights into the basal resource contribution to peacock eels and hypervolume analysis methods to determine peacock eel niche size and overlap with native species. Results of this study found that peacock ell abundance has rapidly increased, and their populations are strongly affected by hydroclimatic regimes—with warmer water temperatures and greater marsh inundation periods explaining greater abundance. We found that the trophic niche of peacock eels, though significantly smaller in volume, overlaps 98.8% with native sunfishes (Lepomis spp.) suggesting a potential for inter-specific competition. In recent years, the catch of peacock eels has outnumbered the catch of all native sunfishes combined. Peacock eel populations are predicted to continue to increase, highlighting the importance of continued monitoring of their impact on native fish assemblages and food webs.