bluuebunny/crossref_metadata_2025 huggingface dataset:
Subsurface Hydrogen Generation: Low Cost and Low Footprint Method of Hydrogen Production
Authors: Berenblyum Roman , Surguchev Michael
Published: April 2022

Hydrogen is one of the key components in clean energy systems of the future (Hydrogen Council, 2017). Currently, clean hydrogen production requires either availability of large quantities of renewable energy (in competition with other high power demanding industries) in a capitally expansive electrolysis process or need for carbon capture and storage solutions for the steam methane reforming process. Hydrogen Source developed and is commercializing Hydrogen Generation from Hydrocarbons Subterrain technology allowing to reduce both costs and associated emissions. The process allows converting non- commercial gas reserves to clean hydrogen available for recovery and commercial use with costs considerably below today's state-of-the-art hydrogen production technologies such as electrolysis or steam methane reforming.

The paper presents the experimental studies, including adiabatic reactor, core, and combustion tube experiments, confirming process efficiency and simulation studies using state-of-the-art reservoir simulation tools, laying basis for technoeconomic evaluation of the process at the field level. Experimental investigations confirmed process efficiency. Numerical simulation, monte-carlo and P10-P50-P90 statistical analysis showed hydrogen production costs on the scale of 0.1-0.5 $/kg with low associated emissions.

Techno-economic estimates of application to several field case evaluations for offshore and onshore hydrogen production are presented. Potential for technology application worldwide is also presented.
Development and Deployment of a Novel Single-Trip Multistage Proppant Fracturing System in the Norwegian Continental Shelf
Authors: Young Dustin , Koløy Tom Rune , Keerthivasan Vijay , Satimov Serik
Published: April 2022

A major North Sea operator was looking to improve production from low permeable reservoirs in mature assets. Under-displaced, high proppant concentration fracs must be pumped in an efficient manner to unlock the value potential. A new single-trip, multistage stage proppant fracturing system was developed to tackle these operational constraints and reliably perform in challenging offshore environments. This paper presents the evolution of this system from a concept to field implementation on the Norwegian Continental Shelf.

The developed solution, a frac sleeve (FS) system operated by a service tool assembly (STA) which can be run on drillpipe or coiled tubing. The unique feature of this system is that it allows multistage stimulation in a single trip without utilizing slips or packers, which could pose the risk of a stuck STA. Suited for both open-hole and cemented applications, the system is particularly beneficial for wells with limited slack-off capabilities. Key considerations of the design included operability in proppant-packed environments, erosion resistance, and multiple contingencies built into the STA to allow operational flexibility.

An extensive qualification program was successfully executed to validate the system's functionality, particularly in hostile, proppant-packed environments, including an erosion test wherein 2,000 tons of proppant was pumped through the STA at 30 bbl/min. In preparation for field deployment, drillpipe and liner simulations were run, and operational planning and risk assessments were held. Following these assessments, the system was deployed for the North Sea operator in a trial well in summer 2021. During the stimulation program, an under-displaced, high rate, and high proppant concentration frac was pumped in each stage, followed by immediate closing of the sleeves prior to reversing out the remaining under displaced proppant. This paper captures the wins, challenges, and key learnings from the initial trial well, and how these learnings were used to optimize the second well.

Also detailed is the lifecycle of a novel, patented proppant-stimulation technology starting from initial concept to downhole deployment. Enabling optimized, proppant fracturing in an operationally efficient manner plays a crucial role in improving the productivity and economic viability of a well, and allows for improved oil recovery (IOR) from existing offshore infrastructure. The findings and lessons learned in this paper will contribute to the state of knowledge regarding proppant fracturing on the Norwegian Continental Shelf.
Overcoming the Seven Wastes of Reservoir Modelling Projects
Authors: Sætrom Jon , Sandø T. C.
Published: April 2022

Software tools that allow the user to automatically generate many models that capture and propagate uncertainty in the subsurface have existed for decades. Despite their existence, true adoption of these types of tools have been limited. Reasons for low acceptance/adoption can stem from: Challenges in maintainability/transparency of the automated modeling workflows.High investment cost in terms of time and resources required to set up and maintain the workflows.Company processes for reservoir modeling not designed for an uncertainty centric paradigmExpected deliverables from the modeling project not aligned with an uncertainty centric paradigm.

Hence, despite our best efforts to use state of the art tools, we often observe that modeling projects easily become victims of the Seven Wastes of Reservoir Modeling Projects: 1. Non-utilized human talent; 2. Defects, 3. Handoffs and delays; 4. Relearning and task switching; 5. Non-value adding features; 6. Overspecialization; and 7. Loss of information.

In this paper we evaluate learnings from the past 30 years of reservoir modeling projects in the oil and gas industry. Specifically looking at methods that aim at quantifying the uncertainty in the subsurface using multiple realizations – also known as ensemble-based methods. We will highlight what we perceive are the major challenges that companies currently face - the so called Seven Wastes of Reservoir Modeling Projects - and outline potential ways to overcome these challenges based on lessons learned from more than 100 modeling projects on fields world-wide over the last 10 years. Furthermore, we highlight the importance of not falling victim to the many cognitive bias effects that can limit us in improving our understanding and consequently the value of our reservoirs. We demonstrate how a combination of fit for purpose algorithms and process help put subsurface teams in a mindset of continuous learning that helps reduce the typical pitfalls seen in traditional reservoir modeling projects. The benefit of the proposed way of working is that subsurface teams greatly reduce the time it takes from incorporating new data or new hypotheses about the subsurface, until having a full ensemble of models that can be used to support the business decision at hand. As a result, we potentially reduce the cycle time from new data, or new ideas to conditioned models from months or years to hours or days.
Effect of Heterocyclic Atoms (O, N, S) on surfactant solutions investigated by molecular dynamics simulation
Authors: Liu Zhinan , Li Bailin , Wang Li , Guo Shuhai
Published: April 2022

The effects of heterocyclic atoms (O, N, S) in non-hydrocarbons on the properties at non-hydrocarbon/surfactant/water interface were investigated by molecular dynamics simulation. The model surfactant was sodium cetyl metaxylene sulfonate (2 ,4-Dimethyl-5-(1'-butyl) Sodium dodecyl benzene sulfonate). The interface properties were analyzed , which include density profile, interfacial formation energy and interfacial tension, radial distribution function and hydrophobic chain order parameters. The simulation results indicated that interface thickness is relevant to the electronegativity of heterocyclic atoms, and the arrangement of hydrophobic tails is relevance with the energy of heterocyclic atoms bond with carbon atoms. It is also bound up with the self-loop strain. Then, the radial distribution function and hydrophobic tail sequence parameters were calculated to further verify and explain this phenomenon in the equilibrated model systems. The stability of the interface formed with sulfonate surfactants is O> N> S according to the heterocyclic atom. When the number of rings in non-hydrocarbons changes, the interface stability also follows this rule. At the same time, it is found that the stability of the interface increases as the number of rings adding.
Epidemiology of Type 1 and Type 2 Diabetes Mellitus in Kazakhstan: Data from Unified National Electronic Health System 2014-2019
Authors: Gaipov Abduzhappar , Galiyeva Dinara , Gusmanov Arnur , Sakko Yesbolat , Issanov Alpamys , Atageldiyeva Kuralay , Kadyrzhanuly Kainar , Nurpeissova Aiymzhan , Rakhimzhanova Marzhan , Durmanova Aigul , Sarria-Santamera Antonio
Published: April 2022

Background: We aimed to explore descriptive epidemiology of T1 and T2 Diabetes Mellitus (DM) and to investigate demographic factors and comorbidities associated with all-cause mortality by aggregating and utilizing large-scale administrative healthcare data from the Unified National Electronic Health System (UNEHS) for 2014-2019 years period.Methods: We used Kaplan-Meier and log-rank test to calculate failure function and differences in survival by age, sex, ethnicity, and comorbidities with all-cause mortality for Type 1 and Type 2 DM. Cox proportional hazards regression analysis was used to obtain crude and adjusted hazard ratios.Results: Prevalence of Type 1 and Type 2 DM increased 1.7 times from 2014 to 2019. Mortality of Type 1 and Type 2 DM also increased 4 times and 6 times from 2014 to 2019, respectively. Male sex, older age and Kazakh ethnicity were associated with a higher risk of all-cause death compared to females, younger age and other nationalities than Kazakh in patients with Type 1 and Type 2 DM. Coronary artery disease, diabetic nephropathy, stroke, amputations and neoplasms were associated with a higher risk of all-cause death. Conclusion: The prevalence and mortality rate of Type 1 and Type 2 DM increased during the years 2014 - 2019 in Kazakhstan. Male sex, older age and Kazakh ethnicity were associated with a higher risk of all-cause death compared to females, younger age and other nationalities than Kazakh. Coronary artery disease, diabetic nephropathy, stroke, amputations and neoplasms were associated with a higher risk of all-cause death.
Predictors of mHealth use in promoting adherence to pre-exposure prophylaxis among female sex workers: An evaluation of the Jichunge intervention in Dar es Salaam, Tanzania
Authors: Mbotwa Christopher , Kazaura Method , Moen Kåre , Leshabari Melkizedeck , Metta Emmy , Leyna Germana , Mmbaga Elia J
Published: April 2022

Background: There is evidence that pre-exposure prophylaxis (PrEP) is effective in preventing HIV transmission, and PrEP is recommended by the World Health organization (WHO) for use by individuals at high risk of HIV infection. However, low adherence has been reported to hamper its effectiveness. Some evidence indicates that mHealth interventions may be a promising way of promoting PrEP adherence. Nevertheless, evaluations of mHealth interventions in Africa, the region most affected by HIV, are scarce. This study aimed at identifying the extent of and predictors for use of a smartphone based mHealth application among female sex workers in Dar es Salaam, Tanzania.Methods: As part of a quasi-experimental study in Tanzania, 470 female sex workers who were eligible for PrEP and who owned a smartphone were recruited using respondent driven sampling. All participants were provided with an mHealth application called Jichunge, a smartphone-based app designed to promote adherence to PrEP by offering users information, advise and support during start-up and use of PrEP. We collected data through structured interviews at baseline and extracted user data from the app for a period of 30 days. Modified Poisson regression model with robust standard errors was used to identify predictors for the optimal use of the Jichunge app. Results: Overall, the optimal use of the Jichunge app was 46.4%. Optimal use was significantly higher among women who were older (aPR=1.4, 95% CI: 1.11-1.67 for age 25-34 years, and aPR=1.6, 95% CI: 1.20-2.08 for age at least 35 years), who had secondary education or higher (aPR=1.7, 95% CI: 1.06-2.84), who had suboptimal social support (aPR=1.2, 95% CI: 1.03-1.48), who had high awareness of PrEP (aPR=1.3, 95% CI: 1.08-1.55), and who had experience using common mainstream social media applications (aPR=1.5, 95% CI: 1.18-1.98).Conclusion: Optimal use of the Jichunge app was substantially higher among women with higher age, higher education, higher PrEP awareness, less social support, and experience using common social media applications. Individual and interpersonal factors should be considered in planning mHealth interventions. Further studies to determine predictors of longer-term mHealth engagement are needed.Trial Registration: International Clinical Trials Registry Platform PACTR202003823226570; 04.03.2020; https://trialsearch.who.int/Trial2.aspx?TrialID=PACTR202003823226570
Genetic polymorphisms in SLCO2B1 and ABCC1 conjointly modulate atorvastatin intracellular accumulation in HEK293 recombinant cell lines
Authors: Elens Laure , Hoste Emilia , Paquot Adrien , Panin Nadtha , Horion Shaleena , Hamdaoui Halima El , Muccioli Giulio G , Haufroid Vincent
Published: April 2022

Atorvastatin (ATV), is commonly used to treat hypercholesterolemia. Although generally well tolerated, patients can suffer from muscle complaints and the occurrence of this discomfort is difficult to predict. Muscle side effects are assumed to be linked to the intramuscular ATV accumulation. The aim of our study was to investigate the relative implication of influx and efflux transporters expressed in the muscle tissue (OATP2B1, MRP1) in promoting or limiting the access of the drug into the cells. In addition, the impact of common single nucleotide polymorphisms (SNPs) in SLCO2B1 coding for OATP2B1 (rs12422149; c.935G > A) and in ABCC1 coding for MRP1 (rs45511401; c.2012G > T) was evaluated. Single or double transfectant HEK293 recombinant models overexpressing variant or wild-type OATP2B1 (influx) and/or MRP1 (efflux) proteins were developed. Our results confirm the implication of both OATP2B1 and MRP1 in ATV transport. Interestingly, ATV intracellular accumulation promoted by OATP2B1 influx was counteracted by MRP1 efflux. The c.935G > A SNP in SLCO2B1 was associated with a decreased OATP2B1 influx activity whereas the c.2012G > T SNP in ABCC1 appeared to increase MRP1 efflux activity towards ATV. In conclusion, intracellular ATV accumulation is regulated by transporter proteins and their functionality could play a role in ATV muscle side effect susceptibility.
PCP4 promotes the growth and castration-resistant development of prostate cancer
Authors: Wang Zhenting , Ren Jiannan , Yin Xianlai , Yang Peng , Liu Congchong
Published: April 2022

Purkinje cell protein 4 (PCP4), which shows homology to the calcium-binding β-chain, regulates the calmodulin (CaM)-dependent signaling pathway by modulating CaM-dependent protein kinase 2 (CaMKK2) activity in Purkinje cells. In this work, we demonstrate that PCP4, which plays a role in tumorigenesis, induces prostate cancer (PCa) cell proliferation and migration in vitro and in vivo. Moreover, androgen receptor (AR) regulates the expression and phosphorylation activity of CaMKK2 by inducing the transcription of PCP4 in castration-resistant PCa (CRPC). Thus, exogenous overexpression of PCP4 blocks the biological function that EPI, the inhibitor of AR, suppressed the expression and phosphorylation of CaMKK2 in hormone-sensitive LNCap cells. A clinicopathological study of PCP4 was subsequently conducted on a cohort of 51 human PCa patients, and protein and mRNA expression levels of PCP4 and CaMKK2 were positively correlated with the sensitivity of androgen-deprivation treatment (p < 0.05). Moreover, PCP4 and CaMKK2 were significantly correlated with PCa relapse. This study reveals the oncogenic activity of PCP4 in vitro and provides insights into relevant mechanisms that may lead to novel treatments for CRPC.
Physical Activity Induced Alterations of Gut Microbiota in Humans: A Systematic Review
Authors: Dziewiecka Hanna , Buttar Harpal , Kasperska Anna , Ostapiuk-Karolczuk Joanna , Domagalska Małgorzata , Cichoń Justyna , Skarpańska-Stejnborn Anna
Published: April 2022

Background: Gut microbiota are considered to have a great impact on human health and disease. While it is widely recognized that the gut microbiota of healthy individuals differs from those with obesity, inflammatory bowel disease, metabolic syndrome, and other chronic diseases, the alterations of gut microbiota with mild and vigorous physical activity is not fully understood. Accordingly, we performed this systematic review to address the question regarding the effects of mild and intense exercise on the gut microbiota in humans. Methods: The comparative analyses of gut microbiota were conducted following the PRISMA protocol to determine the differences in the active vs. nonactive individuals (phenotypes) (n=11), including the influence of physical activity intervention on the human gut microbiota (n=13); the differences in the gut microbiota of athletes vs. nonathletes (n=8); and the microbiota status at different stages of athletic performance or intervention (n=7). Literature searches were performed using four databases: PubMed, Web of Science, Scopus, and EBSCO, and 2090 articles were retrieved by using appropriate keywords. Results: After excluding 2052 articles, we ultimately selected 38 articles that met the eligibility criteria for this review. The data analyses revealed that physical activity markedly influenced the microbiota ratio of Firmicutes/Bacteroides, and the relative abundance of short-chain fatty acid (SCFA) producers and other types of bacteria in the GI tract. Conclusion: It is concluded that the level of physical activity modulates the gastrointestinal microbiota in humans. The vigorous exercise effect was most apparent among athletes compared to untrained individuals. The results showed that athletes harbor a more diverse type intestinal microflora than nonathletes, but with a relatively reduced abundance of SCFA- and lactic acid-producing bacteria, thereby suggesting an adverse effect of intense exercise on the population of gut microbiota.Trial registration: Prospero CRD42021264064
High-throughput transcriptome sequencing reveals the key stages of cardiovascular development in zebrafish embryos
Authors: Zhou Chune , Zhao Wei , Zhang Shuqiang , Ma Junguo , Sultan Yousef , Li Xiaoyu
Published: April 2022

Background: The cardiovascular developmental process is a tightly regulated network involving multiple genes. The current understanding of the molecular mechanism behind cardiovascular development is insufficient and requires further research. Results: Transcriptome sequencing of three developmental stages in zebrafish embryos was performed and revealed three key cardiovascular developmental stages. Then, the differentially expressed genes (DEGs) involved in cardiovascular development were screened out. The three developmental stages were 18hpf (T1), 24hpf (T2), and 48hpf (T3), and the three stages were confirmed by detecting differences in expression between cardiomyocyte and endothelial marker genes (cmlc, fli1) using in situ hybridization, which represents the characteristics of cardiovascular development. Thousands of DEGs were identified using transcriptome analysis. Of them, 2650 DEGs were in T1-vs-T2, including 2003 up-regulated and 602 down-regulated genes, 6446 DEGs were in T1-vs-T3, consisting of 4608 up-regulated and 1838 down-regulated genes, and 3275 DEGs were in T2-vs-T3, including 2420 up-regulated and 655 down-regulated genes. There were 644 common DEGs and 167 common five-fold higher differentially expressed genes (HDEGs) identified, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Significant differences was observed in the levels of gene expression among different developmental stages in multiple GO terms and KEGG pathways, such as cell migration to the midline involved in heart development, cardiovascular system development, circulatory system process for biological processes of GO terms; and cardiac muscle contraction, adrenergic signaling in cardiomyocytes for KEGG pathways. These results demonstrated that these three stages were important period for the development of the cardiovascular system. Lastly, we used quantitative real-time PCR (qPCR) to validate the reliability of RNA-sequencing by selecting 21 DEGs. Conclusion: These results demonstrated that these three stages represented an important period for cardiovascular system development and promoted a better understanding of the mechanism behind the development of the cardiovascular system and provided a solid foundation for additional functional studies of the DEGs.
Safety and Efficacy of Immune Checkpoint Inhibitors in Advanced Cancer patients with Autoimmune Disease: a Meta-Analysis
Authors: Chen Peng , Cai Qi , Huo Gengwei , Zhu Fuyi , Yue Ping , Yuan Dongqi
Published: April 2022

Background: Cancer patients with autoimmune disease (AID) usually have been excluded from the clinical trials of immune checkpoint inhibitors (ICIs). The safety and effectiveness of ICIs for these patients remain uncertainty.Methods: A systematic search was conducted in available electronic database. We collected the incidence of immune-related adverse events (irAEs), progression-free survival (PFS) and overall survival (OS) from included studies.Results: 11 studies including 5489 participants were incorporated in our meta-analysis. The pooled risk ratio (RR) for any grade and grade ≥3 irAEs were 1.79 (95% CI: 1.31-2.45) and 1.58 (95% CI: 1.06-2.36), respectively. When irAEs were from the same system as AID, we called the irAEs as AID-homogeneous irAEs, otherwise as AID-heterogeneous irAEs. Subgroup analysis found that the higher risk of AID-homogeneous irAEs contributed to the higher risk of overall irAEs of AID patients. The pooled hazard ratio (HR) for PFS and OS were 1.09 (95% CI: 0.96–1.25) and 1.10 (95% CI: 0.68–1.77), respectively. The results of subgroup analyses for PFS and OS matched the overall results well.Conclusion: AID patients were significantly associated with a higher risk of irAEs in any grade and ≥3 grade under ICIs therapy. Specifically, AID-homogeneous irAEs but AID-heterogeneous irAEs were higher in AID patients than without AID patients. No statistically significant difference in PFS and OS were observed in patients with and without AID.
Predictors for adoption of e-learning among health professional students during the COVID-19 lockdown in a Private University in Uganda
Authors: Komuhangi Alimah , Mpirirwe Hilda , Robert Lubanga , Githinji Florence Wamuyu , Nanyonga Rose Clarke
Published: April 2022

Background. Universities have come to terms with the fact that education, as we have traditionally delivered it, cannot be sustained under the current circumstances imposed on us by the Coronavirus diseases 2019 pandemic. Adoption of e-learning is one obvious way to foster continuity of learning. During the lockdown in Uganda, it was not known whether health professional students were willing to adopt e-learning as a way to foster continuity of learning. We therefore adopted a Technology Acceptance Model to determine the predictors for adoption of e-learning using learner and information technology variables. Methods. A cross-sectional study among 109 health professional student’s ≥18 years at Clarke International University was conducted. Adoption of e-learning was measured as self-report. Data were obtained using a smart survey and descriptively summarized. The differences in the study outcome were compared using the chi-square test. The factors that independently influenced adoption of e-learning were determined using binary logistic regression and reported as adjusted odds ratios (aORs) with a 95% confidence interval (CI). Results: Of the 109 respondents, 71 (65.1%) adopted e-learning. Our data showed low odds of adoption of e-learning among participants in first year (aOR, 0.34: 95%CI, 0.14-0.79), low e-learning expectations (aOR, 0.01: 95%CI, 0.01-0.34), no confidence in using IT devices (aOR, 0.16: 95%CI, 0.00-0.77), no prior experience in e-learning (aOR, 0.11: 95%CI, 0.02-0.68), not considering e-learning flexible (aOR, 0.25:95%CI, 0.08-0.86) and high cost of internet (aOR, 0.13: 95%CI, 0.02-0.84). Conclusion: We identified predictors of e-learning adoption which include: having completed at least one year of study, high e-learning expectations, and confidence in using IT devices, prior experience in e-learning, considering e-learning to be flexible and internet access. This information can be used by universities to enhance infrastructure and prepare potential e-learners. Keywords: E-learning adoption, health professional students, Coronavirus diseases 2019 lockdown
Planar thermal Hall effect of topological bosons in the Kitaev magnet α-RuCl3
Authors: Czajka Peter , Gao Tong , Hirschberger Max , Lampen-Kelley Paula , Banerjee Arnab , Quirk Nicholas , Mandrus David , Nagler Stephen , Ong N. Phuan
Published: April 2022

In the field of quantum spin liquids [1-3], the honeycomb magnet α-RuCl3 has attracted considerable interest because it is proximate to the Kitaev Hamiltonian HK [4-12]. In 2006, Kitaev [13] published the exact solution for the ground state of HK, and found that the excitations are Majoranas and vortices. The thermal Hall conductivity κxy of Majorana fermions is predicted to be half-quantized [13]. This effect has been reported in α-RuCl3 [17,18], but this observation has proven difficult to reproduce [19,20] and remains highly controversial. We report detailed measurements of the Onsager-like planar thermal Hall conductivity κxy in α-RuCl3, a spin-liquid candidate of topical interest. With the thermal current JQ and magnetic field B||a (zigzag axis), the observed κxy/T varies strongly with temperature T (1-10 K). Using a novel fitting procedure, we show that this temperature dependence matches the distinct form expected for topological bosonic modes in a Chern insulator-like model. Our analysis yields band energies that are in agreement with earlier experiments and that the excitations evolve into increasingly magnon-like modes at high B with a Chern number ≈ 1. The bosonic character is incompatible with half-quantization of κxy/T.
Mendelian Randomization of Circulating Proteome Identifies Actionable Targets in Heart Failure
Authors: Moncla Louis-Hippolyte Minvielle , Mathieu Samuel , Bossé Yohan , Thériault Sébastien , Arsenault Benoit , Mathieu Patrick
Published: April 2022

Background
Heart failure (HF) is a prevalent cause of mortality and morbidity. The molecular drivers of HF are still largely unknown.
Results
We aimed to identify circulating proteins causally associated with HF by leveraging genome-wide genetic association data for HF including 47,309 cases and 930,014 controls. We performed two-sample Mendelian randomization (MR) with multiple cis instruments as well as network and enrichment analysis using data from blood protein quantitative trait loci (pQTL) (2,965 blood proteins) measured in 3,301 individuals. 19 blood proteins were causally associated with HF and were enriched in ligand-receptor and glycosylation. Network pathway analysis of the blood proteins showed enrichment in NF-kappa B, TGF beta, lipid in atherosclerosis and fluid shear stress. Cross-phenotype analysis of HF identified genetic overlap with cardiovascular drugs, myocardial infarction, parental longevity and low-density cholesterol. Multi-trait MR identified causal associations between HF-associated blood proteins and cardiovascular outcomes. Multivariable MR showed that association of BAG3, MIF and APOA5 with HF were mediated by the blood pressure and coronary artery disease. According to the directional effect and biological action, 7 blood proteins are targets of existing drugs or are tractable for the development of novel therapeutics. Among the pathways, sialyl Lewis x and the activin type II receptor are potential druggable candidates.
Conclusions
Integrative MR analyses of the blood proteins identified causally-associated proteins with HF and revealed pleiotropy of the blood proteome with cardiovascular risk factors. Some of the proteins or pathway related mechanisms could be targeted as novel treatment approach in HF.
Factors Associated with Depression in Preclinical Medical Students: A Cross-Sectional Study in a Thai Medical School
Authors: Wisanuyothin Tattiya , Sawee Chinnawudh , Saisavoey Nattha , Thongchot Lakkana , Dangprapai Yodying
Published: April 2022

Background: Depression is one of the most common mental illnesses that decrease quality of life. Medical students worldwide are increasingly affected by depression. This article focuses on depression in the preclinical medical students whose learning environment is different from medical students in clinical years. The aim of this study is to determine: (1) the prevalence of depression in Thai preclinical medical students; and (2) the factors associated with depression. This study will contribute to more specific and proper interventions concerning depression in Thai preclinical medical students.Methods: A cross-sectional study was performed at the Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand. The Patient Health Questionnaire-9 (PHQ-9), Thai version was applied to explore prevalence of depression. The selected associated factors, including interpersonal relationships, mindfulness, and self-esteem were determined using peer-relationship questionnaire, family-relationship questionnaire, Thai version of the Philadelphia Mindfulness Scale (PHLMS) and Thai version of Rosenberg’s self-esteem scale respectively. Analysis was done using risk estimation by applying a contingency table and univariate logistic regression.Results: Among 275 preclinical medical students participating in this study, 71 (25.8%, 95%CI[ 0.207,0.310]) had a PHQ-9 score of 9 or more. Four associated factors were significantly correlated with lower PHQ-9 scores. These protective factors included (1) a personal counselor or peer support; (2) a good family relationship; (3) a higher score in the Thai version of the Philadelphia Mindfulness Scale (PHLMS); and (4) autonomy in the medical student’s decision to study medicine.Conclusion: The prevalence of depression among Thai preclinical medical students was found to be higher than that of the general population (18.4%). Several factors were associated with a lower PHQ-9 score, including having a personal counselor or peer support, the participant’s own decision to study at medical school, having a good family relationship, and having mindful thoughts.
Chlorogenic acid improves functional potential of follicles in mouse whole ovarian tissues in vitro
Authors: Abedpour Neda , Javanmard Masoumeh Zirak , Karimipour Mojtaba , Farjah Gholam Hossein
Published: April 2022

Background: Chlorogenic acid (CGA) is one of the well-known polyphenol compounds involved in several important biological and therapeutic functions. In optimizing a culture system to achieve complete development of follicles, we focus on the effects of CGA supplementation during in vitro culture (IVC) on follicular development, oxidative stress, antioxidant capacity, developmental gene expression, and functional potential in mouse cultured ovarian tissue.Methods and Results: The collected mouse whole ovaries were randomly divided into 4 groups: 1) non-cultured group (control 1): 7-day-old mice ovaries, 2) non-cultured group (control 2): 14-day-old mice ovaries, 3) cultured group (experimental 1): the culture plates contained only the basic culture medium, 4) cultured group (experimental 2): the culture plates contained basic culture medium + CGA (50, 100 and 200 µmol/L CGA). The following evaluations were done for all groups: histological evaluation, biochemical evaluation, the expression of genes related to follicular development and apoptosis by RT-qPCR, and analysis of 17-β-estradiol. The outcomes of the current study showed that supplementation of ovarian tissue culture media using CGA (100 µmol/L) significantly increased the survival, developmental and functional potential of follicles in mouse whole ovarian tissues after 7 days of culture. Furthermore, the result of this study revealed that CGA (100 µmol/L) could suppress oxidative damage and improve the culture system by enhancing the concentration of antioxidant and developmental gene expression. Conclusion: For the first time, results showed that the supplementation of ovarian tissue culture media using CGA could optimize the culture system.
Prenatal exposure to air pollution and the risk of eczema in childhood: A systematic review and meta-analysis
Authors: Yue Dengyuan , Shen Ting , Mao Jiaqing , Su Qing , Mao Yingying , Ye Xiaoqing , Ye Ding
Published: April 2022

An increasing number of studies investigated the association between air pollution during pregnancy and the risk of eczema in offspring. However, no meta-analysis has confirmed the existence and size of their association to date. We systematically searched PubMed, Web of Science, Cochrane Library, and Embase databases to select the observational controlled studies published from the inception date to October 16, 2021. Quality evaluation was guided by the Newcastle-Ottawa Scale (NOS). Sensitivity analysis was applied to assess the impact of each included study on the combined effects, and publication bias was examined by the Begg’s tests and Egger’s tests. A total of 12 articles involving 69,374 participants met our eligibility criteria. The significant association between the maternal exposure to NO2 (per 10 μg/m3 increased) and childhood eczema was observed, with a pooled risk estimate of 1.13 (95% CI: 1.06-1.19), but no association was observed between exposure to PM10, PM2.5, and SO2 and the risk of eczema in offspring. Besides, the effect of maternal NO2 exposure on childhood eczema was significant in the first and second trimesters, but not in the third trimester. There was notable variability in geographic location (p = 0.037) and air pollutant concentration (p = 0.031) based on meta-regression. Our findings indicated that prenatal exposure to NO2 was a risk factor for elevated risk of eczema in childhood, especially in the first and second trimesters. Further studies with larger sample sizes considering different constituents of air pollution and various exposure windows are needed to validate these associations.
Cadmium Dietary Exposure Assessment in Adult Population and Preschool Children in the Republic of Serbia
Authors: Janković Saša , Stošić Milena , Miljaković Evica Antonijević , Ćurčić Marijana , Ćosić Danijela Đukić , Đorđević Aleksandra Buha , Bulat Zorica , Antonijević Biljana
Published: April 2022

Cadmium (Cd) is a toxic metal, present in all matrices of the environment. Cadmium is a common food contaminant and human exposure to it may elicit many diverse health impairments.The aim of this study was to assess the dietary exposure to Cd for the adult population and preschool children in Serbia using the probabilistic methodology. We have measured Cd content in 11,227 food samples belonging to 50 food groups available on the Serbian market. Cadmium was detected in 90% of the tested food groups, and in 31% of the total samples. Food groups that contributed the most to total dietary Cd intake were potatoes in the adult population, and fruit and vegetable juices in children. Consumption data were taken from the GEMS/Food Consumption Cluster Diets database Calculated HI values showed that 54.4% of the adult population and 84.4% of the population of preschool children were under the unacceptable risk of Cd exposure. The results of this study are based on a worst-case scenario. Thus, they are rather preliminary and should be considered as an indication of the need for further, more refined input data, particularly in terms of consumption database, which would altogether contribute to the more realistic risk assessment as a high priority approach, especially in the case of the vulnerable subpopulations such as children.
Clinical Profile and Quality of Life in Climateric Women
Authors: Nogueira Cintia Mikaelle Cunha Santiago , Silva Bárbara Daniely dos Santos , Costa Hosana Mirelle Goes Silva , de Alcantara Jussara Rodrigues , Morais Fátima Raquel Rosado , Barros Renata Janice Morais Lima Ferreira , Rabelo Susy Maria Feitosa de Melo , Pereira Emanuelly Vieira , Cavalcanti José Rodolfo Lopes de Paiva , Fernandes Natália Teixeira , Filho Ana Virginia de Melo
Published: April 2022

BACKGROUND : Quality of life in climacteric women is intrinsically related to signs and symptoms influenced by estrogen decline, in addition to psychosocial factors linked to the natural aging process, in this context this study aims to outline a sociodemographic, clinical and quality of life profile. life of climacteric women servants of the University of the State of Rio Grande do Norte - UERN.METHODS: this is a research with a descriptive, exploratory and quantitative approach . The population consisted of female workers from UERN, aged between 40 and 65 years. The total sample consisted of 64 women who responded to the forms and only one refused to respond.RESULTS: the age range of the participants can be defined, so that 53.97% (n=34) are aged up to 50 years, 55.56% (n=35) are married or in a stable relationship. Regarding ethnicity, whites and browns had the same percentage of 44.44% (n=28). As for the city in which they reside, the largest number of women resides in Mossoró (RN), representing 82.53% (n=52) . The predominance of poor quality of life in the SF-36 was evidenced in the domains referring to pain, general health status and the domain referring to vitality. As for the SF-36 questionnaire, which represents the level of satisfaction with current health, 4.76% (n=3) stated that they fit the level considered excellent, 44.44% (n=28) very good, 46, 03% (n=29) were good and only 4.77% (n=3) represented a satisfaction with their current health considered bad. The intensity of symptoms related to estrogen deficiency, established by the Kupperman menopause index , was classified as: Mild 55.56% ( n° =35), moderate 41.27% ( n° =26) and severe 3.17% ( No. =2) .CONCLUSIONS: the occurrence of symptoms and perception of menopausal symptoms differ from woman to woman, to a greater or lesser extent. From this, it highlights the need for a qualified and individualized listening to the needs of these women in the health services and, in this way, it is possible to develop applicable solutions for solving problems based on the profile of each woman.
Isolation and Evaluation of Microorganisms from Locally Fermented Foods as Potential Chicken Probiotics
Authors: Jakera Shakera , Tajarudin Husnul Azan , Raz Naseha Sakina Md , Ng Charles Wai Chun , Salleh Rabeta Mohd
Published: April 2022

Probiotics are living microorganisms that are advantageous to health, particularly in the digestive tract. Probiotics for broilers could promote their growth and protect them from diseases by boosting their immune systems, strengthen their bones, and combat parasites. Antibiotics are commonly used in poultry feed as growth promoters to improve poultry performance. However, antibiotic residues will remain in chicken meat, bones, and organs, which may adversely impact human health. Therefore, this study examined potential chicken probiotics derived from locally fermented foods, such as shrimp paste and soy cake, as substitute to antibiotics. The microbes were cultivated on suitable media after isolating from the previous culture plates. bacteria and yeast were identified as potential probiotics for chickens. The microorganisms underwent in vitro analysis under the conditions mimicking chicken gastrointestinal tract (GIT) conditions at different pH values of 2.5, 3.5, 5, 6.5, 7, 7.5 and 8, temperature of 37°C and in anaerobic condition. Nine yeast and ten bacteria were selected as samples for this study. Their kinetic growth, survivability and biomass were also calculated. Comparisons were conducted on the remaining microorganisms, namely four yeast strains and three bacterial strains, and demonstrated probiotic potential with high specific growth rate, maximum cell concentration, shorter doubling time and higher survivability percentage at pH range from 2.5 to 8.0. The results of toxicity test revealed that some of the pre-selected probiotic prospective strains had produced several toxic compounds that could be harmful to chickens. Finally, based on the results of the investigation, one bacterium, Staphylococcus hominis, and one yeast, Cutaneotrichosporon arboriforme, were chosen to make probiotics for chickens, which were then evaluated in vivo to see how they impacted chicken growth. It was found that chickens supplied with these 2 probiotics boosted the growth of the chicken. In conclusion, based on their growth in the chicken digestive system environment and impacts on chicken growth rate, microbes isolated from locally fermented foods have promise as chicken probiotics.
Cooling enhancement using acacia gum based hydrogel in roof ponds: model room experimental analysis.
Authors: MG Amith , Joshi Vijesh V
Published: April 2022

The authors have requested that this preprint be removed from Research Square.
Novel STING-targeted PET radiotracer for alert and therapeutic evaluation of acute lung injury
Authors: Xu Duo , Jiang Zebo , Zhu Tianxing , Wang Fen , Xiao Yitai , Liang Zibin , Bi Lei , Huang Guolong , Shan Hong , Pang Pengfei , Li Dan
Published: April 2022

Acute lung injury (ALI), as a common clinical emergency, is pulmonary edema and diffuse lung infiltration caused by inflammation. The lack of non-invasive alert strategy, resulting in failure to carry out preventive treatment, means high mortality and poor prognosis. Stimulator of interferon genes (STING) is a key molecular biomarker of innate immunity in response to inflammation, but there is still a lack of STING-targeted strategy. In this study, the first STING-targeted PET tracer, [18F]FBTA, was labeled with high radiochemical yield and molar activity. We confirmed that [18F]FBTA has a strong STING binding affinity and can be used for PET imaging in ALI mice to alert early lung inflammation and to assess the efficacy of drug therapy. Our STING-targeted strategy also reveals that [18F]FBTA can trace ALI before reaching the computed tomography (CT) diagnostic criteria, and demonstrates its better specificity and distribution than [18F]fluorodeoxyglucose ([18F]FDG).
POLDIP3 facilitates the activation and maintenance of DNA damage checkpoint in response to replication stress
Authors: Zhang Sufang , Lee Ernest Y. C. , Lee Marietta Y. W. T. , Zhang Dong
Published: April 2022

The replication stress response is crucial for the maintenance of a stable genome. POLDIP3 was initially identified as one of the DNA polymerase δ (Pol δ) interacting proteins almost twenty years ago. Using a variety of in vitro biochemical assays, we previously established that POLDIP3 is a key regulator of the enzymatic activity of Pol δ. However, the in vivo function of POLDIP3 has been elusive for a long time. Here, we first generated POLDIP3 knockout (KO) cells using the CRISPR technology and investigated its biological functions in vivo. We showed that though the POLDIP3-KO cells manifest no pronounced defect in the global DNA synthesis under non-stress conditions, they are sensitive to a variety of replication fork blockers. Intriguingly, we found that POLDIP3 plays a crucial role in the activation and maintenance of the DNA damage checkpoint in response to exogenous as well as endogenous replication stress. Our results thus indicate that when the DNA replication fork is blocked, POLDIP3 can be recruited to the stalled replication fork and functions to bridge the early DNA damage checkpoint response and the later replication fork repair/restart.
Coping strategies used by Parents of children with chronic kidney conditions: A Qualitative Study
Authors: Parizad Naser , MaslakPak Masoumeh Hemmati , Feizi Aram , Khorsandi Fatemeh
Published: April 2022

Background: The chronic condition of children negatively affects them and their whole family, causing various psychosocial stresses. Meanwhile, parents use coping strategies to reduce these stresses and adapt to the child's health condition. Therefore, the present study aimed to explain the strategies employed by parents of children with chronic kidney conditions to cope with the child's condition.Methods: This qualitative study was conducted in Shahid Motahari Hospital, Urmia, Iran. In this study a total of 22 parents of children with chronic kidney conditions were recruited using purposive sampling. Data were collected using semi-structured face-to-face interviews, and the concepts were then extracted using content analysis.Results: The theme entitled "Striving for stability" was extracted from the results and consisted of two sub-themes of "Self-management" and "Situation management". The sub-theme of "Self-management" included concepts of "Seeking solace through inculcation" and "Taking refuge in spirituality" and the sub-theme of "Situation management" included concepts of "Striving to learn", "Determination to continue treatment", and "Striving to solve the problem".Conclusion: Awareness of parents' experiences of caring for a child with a chronic kidney condition is of critical importance in meeting the unmet needs of children and their parents and can serve as a guide for other parents. This knowledge can also be important in designing community-based interventions, where parents play a key role in implementing and evaluating the intervention.
Implementation of advance care planning decision aids for patients undergoing high-risk surgery: A field-testing study
Authors: YAMAMOTO KANAKO , Kaido Toshimi , Yokoi Tadao , Shimada Gen , Takeda Takashi , Nakayama Kazuhiro
Published: April 2022

Background: Patients undergoing high-risk surgery are at risk of sudden changes in worsening. Advance care planning (ACP) support for patients who want active treatment is insufficient in setting outcomes, as it only targets better end-of-life care. Therefore, it is necessary to clarify how ACP support is implemented in the field and its effects. This study aimed to assess whether the development of two patient decision aids (PtDAs) can support preoperative ACP in patients undergoing high-risk surgeries.Methods: This field-testing implemented two PtDAs that met the international criteria developed by the researchers to patients before surgery. The study participants included patients who were scheduled to be admitted to the intensive care unit after surgery at one acute care hospital in Japan and their families. The primary outcome was decision satisfaction evaluated by the SURE test, and the secondary outcomes were perception of the need to discuss ACP before surgery and mental health status. Data were collected before (preoperative outpatients, baseline) and after providing PtDAs (in the hospital) and after discharge. Results were analyzed using a mixed-methods approach.Results: Nine patients were enrolled, of whom seven and their families agreed to participate. The SURE test result after discharge was four points (indicating no decisional conflict) for patients who were able to discuss with the researcher, patient, and family before discharge. Assisting patients with ACP before undergoing a high-risk surgery allowed them to recognize in advance the need for ACP, have an opportunity to share their thoughts with family members, and begin planning their own lives. Patients and their families were prepared to promote shared decision-making with healthcare providers and implement ideas into action.Conclusions: Two PtDAs supporting ACP in patients undergoing a high-risk surgery were developed, evaluated, and accepted; however, they did not involve any discussion of patients’ ACP treatment wishes with their families. Medical personnel should be coached to connect with adequate support. PtDAs for ACP before surgery could promote shared decision-making among patients, families, and healthcare providers.