bluuebunny/crossref_metadata_2025 huggingface dataset:
Expanding the Reach of RNAi Therapeutics with Next Generation Lipophilic siRNA Conjugates
Authors: Brown Kirk , Nair Jayaprakash , Janas Maja , Anglero-Rodriguez Yesseinia , Peng Haiyan , Theile Christopher , Castellanos-Rizaldos Elena , Brown Christopher , Foster Donald , Kurz Jeffrey , Allen Jeffrey , Maganti Raj , Li Jing , Matsuda Shigeo , Chickering Tyler , Jung Michelle , Wassarman Kelly , Rollins Jeff , Woods Lauren Woods Lauren , Kelin Alex , Gunther Dale , Mobley Melissa , Petrulis John , McDougall Robin , Racie Tim , Bombardier Jessica , Cha Diana , Agarwal Saket , Johnson Lei , Jiang Yongfeng , Lentini Scott , Gilbert Jason , Nguyen Tuyen , Chigas Samantha , Blanc Sarah Le Blanc Sarah Le , Poreci Urjana , Kasper Anne , Rogers Arlin , Chong Saeho , Davis Wendell , Sutherland Jessica , Castoreno Adam , Milstein Stuart , Schlegel Mark , Zlatev Ivan , Charisse Klaus , Keating Mark , Manoharan Muthiah , Fitzgerald Kevin , Wu Jing-Tao , Maier Martin , Jadhav Vasant
Published: October 2021

RNA interference (RNAi) therapeutics are a new class of medicines that can address unmet medical needs by silencing disease-causing gene transcripts. While delivery of short interfering RNAs (siRNAs) to hepatocytes has yielded multiple drug approvals, novel delivery solutions are needed to expand the reach of RNAi therapeutics. Here we report that conjugation of 2'-O-hexadecyl (C16) to siRNAs enables efficient silencing in the central nervous system (CNS), eye, and lung of multiple nonclinical species with broad cell type specificity. Intrathecally delivered C16-siRNAs are active across CNS regions and cell types, with sustained silencing for at least three months, which is an especially important outcome considering the challenging dosing route. Similarly, intravitreal and intranasal administration of C16-siRNAs resulted in potent and sustained knockdown in the eye and lung, respectively. Efficient delivery facilitated through C16 conjugation to optimized siRNA designs has enabled candidate selection for investigational human clinical trials assessing therapeutic silencing beyond the liver with infrequent (e.g. bi-annual) dosing.
An Analytical Model for Dynamic Spectrum Sensing in Cognitive Radio Networks using Blockchain Management
Authors: Marriwala Nikhil , Taneja Simran
Published: October 2021

The recent advances in wireless communication have led to the problem of growing spectrum scarcity. The problem of spectrum allocation is due to advance research in wireless communication. As new wireless applications are emerging, day after another, and making use of the available wireless spectrum for communication, the demand for spectrum increase makes the available spectrum scarcer. Mostly part of the spectrum is not utilized significantly in the wireless network. Cognitive Radio (CR) is a new technology that enables an unlicensed secondary user to coexist with licensed primary users in licensed spectrum bands without inducing interference to licensed primary users communication. This technology can significantly ease the spectrum redundancy problem & enhance the efficiency of utilization of spectrum. Cognitive Radio Networks (CRN) or Dynamic Spectrum Access Networks are formed by several CR nodes and they are often called NeXt Generation (XG) communication networks. This XG communication network is expected to give high transfer speed to versatile clients through heterogeneous remote designs and dynamic range access procedures. CRNs have drawn in incredible exploration interest in the new years. Nonetheless, research on the security parts of CRNs has been exceptionally restricted. As CRN is like a remote organization, the idea of the remote media is outside, it is more helpless against assaults when contrasted with that of a wired organization. This channel might be stuck/abuse due to remote media information is to be listened to.
Effects of Nitrogen Fertilizer and Faba Bean Density in Rotation on Maize Production and Soil Parameters Under No-Till System
Authors: Ghorbi Samaneh , Ebadi Ali , Khomari Saeid , Hashemi Masoud
Published: October 2021

Achieving food security and environmental sustainability is a huge global challenge. Thus, the use of conservation Agriculture systems seems necessary. We investigated the effects of nitrogen fertilizer and various densities of faba bean ( vicia faba L.) on forage corn (Zea mays L.) production in the no-till system with faba bean residues preservation on the soil surface. The effect of faba bean densities on yield and its yield components, as well as soil chemical and physical properties, was studied Simultaneously. The results showed that various densities of faba bean and nitrogen fertilizer increased dry biomass production of forage corn by improving N content in plants, which was achieved by the density of 40 plants per m2 of faba bean + application of 200 kg N ha−1 of maize. Moreover, N content, crude protein, and fresh biomass production in forage corn were significantly increased by faba bean density and nitrogen fertilizer. Faba bean density also affected on yield and yield component of faba bean, and the highest nitrogen released value of faba bean root residues was obtained from the density of 40 plants per m2 and application of 200 kg N ha−1. Therefore, the density of 40 plants per m2 of faba bean in a rotation system with mays and application of 200 kg N ha−1 be recommended as a fertilizer control method where it reduces the application of N fertilizer and increases the sustainability of production in agricultural systems.
Physical and Mental Well-Being of Women in Neurodiverse Relationships : A Comparative Study
Authors: Arad Pnina , Shechtman Zipora , Attwood Tony
Published: October 2021

BackgroundThere are very few studies which look into the ways in which autism spectrum disorder (ASD) impacts romantic relationships. The existent sources of information indicate that women in neurodiverse relationships experience extreme emotional deprivation and suffer from severe harm to their physical and mental well-being. The aim of the present study was to conduct empirical research into the question of whether a relationship between a neurologically typical woman and a man with high-functioning autism is significantly different from a neurologically typical relationship and what effects relating with someone with autism may have on the physical and mental state as well as sense of well-being of neurologically typical women. MethodsThe research population included 648 women in three groups: 228 women whose partners were formally diagnosed on the autism spectrum; 203 women who suspected their partners to be on the autism spectrum; 217 women in the control group, with neurotypical partners, who were neither diagnosed nor was there any suspicion of autism. Data collection was performed through online self-report questionnaires. Data analysis was conducted with SPSS ver. 24.ResultsFindings showed significantly higher rates of psychological and physical abuse reported by women in neurodiverse relationships (study groups), in comparison to women in neurologically typical relationships (control group). Women in the study groups reported significantly lower perceived physical health, more somatic symptoms and higher somatic symptom severity, as well as significantly higher levels of depression, higher depressive symptom severity and significantly lower levels of subjective well-being than women in the control group. There was no significant difference between women whose partners have been formally diagnosed with autism and for women who suspect their partners to be on the autism spectrum. LimitationsThe main limitations of the study were reliance on self-report instruments, the use of convenience sampling and the impossibility of pointing towards causation.ConclusionsThe present study with its preliminary findings enriches the current literature, which is lacking. These findings help to better understand the condition of women in neurodiverse relationship and support the need to provide better therapy and health services for women and couples in neurodiverse relationships.
Positive and Negative Effects of Republicanism on US citizens’ Mobility During the First Period of the COVID Crisis
Authors: Barbalat Guillaume , Franck Nicolas
Published: October 2021

While Republican states have been criticized for their limited efforts to contain the spread of COVID-19, it is important to consider that political orientation can modify human behaviour via complex effects that are still poorly understood. During the first period of the pandemic, we found that the association of republicanism with US citizens' mobility varied depending on the nature of the exposure being considered. First, republicanism was associated with increased mobility when the stringency of anti-COVID measures increased. Second, republicanism was associated with decreased mobility when COVID-related deaths increased. Third, republicanism was associated with increased mobility over time, i.e. as time went by, citizens living in Republican states were more mobile than those in Democratic states. These findings raise caution on any over-interpretation of the impact of polarization in US politics on COVID-related behaviour. They prompt consideration of persuasive tools that emphasize risk perception to promote social distancing in Republican states, rather than relying heavily on stringent anti-COVID interventions.
Evaluation of Pediatric-Specific Wheelchair-Skills-Training Tools By Primary Users: A Descriptive Qualitative Study
Authors: Ouellet Béatrice , Rushton Paula W , Côté Andrée-Anne , Fortin-Haines Laurence , Lafleur Emma , Paré Isabelle , Barwick Melanie , Kirby R. Lee , Robert Maxime T , Routhier François , Burrola-Mendez Yohali , Best Krista L
Published: October 2021

Background

Children’s ability to engage in meaningful occupations is positively influenced by their ability to move independently. Preliminary evidence in children suggests that wheelchair skills training improves wheelchair skills, which are critical for wheelchair mobility. The Wheelchair Skills Training Program is a standardized program to teach wheelchair skills. However, it is underutilized in pediatric rehabilitation settings. To address perceived barriers to training, three pediatric-specific Wheelchair Skills Training Program tools for indoor skills were developed (i.e., a storybook, four instructional posters, and a workbook). This study aimed to document occupational therapists’ and pediatric manual wheelchair users’ satisfaction and perspectives on the usability, relevance, and feasibility of these tools.
Method

A descriptive qualitative research design was used. A focus group was conducted with occupational therapists and interviews were conducted pediatric manual wheelchair users to obtain their feedback on the tool prototypes to facilitate refinement and to ensure they meet users’ needs.
Results

Eight occupational therapists and five pediatric manual wheelchair users expressed general satisfaction with the tools, describing them as usable, relevant and feasible to integrate into wheelchair skills training with novice wheelchair users and younger children. All occupational therapists and three pediatric manual wheelchair users expressed the desire to use the tools for wheelchair skills training. Two children expressed that the tools were more relevant for beginner wheelchair users only. The participants suggested minor modifications to make the tools more accessible for children (e.g., more action in the story, increased precision of illustrations related to the characters’ position in the wheelchair).
Conclusion

Occupational therapists and pediatric manual wheelchair users perceived the tools to have high potential to facilitate the use of the Wheelchair Skills Training Program in pediatric rehabilitation settings. After making the recommended modifications, the tools will be ready for pilot testing in pediatric rehabilitation settings.
Generation of a Novel High-Affinity Antibody Binding to PCSK9 Catalytic Domain with Slow Dissociation Rate by CDR-Grafting, Alanine Scanning and Saturated Site-Directed Mutagenesis
Authors: Bai Zhengli , Xu Menglong , Mei Ying , Hu Tuo , Zhang Panpan , Chen Manman , Lv Wenxiu , Lu Chenchen , Tan Shuhua
Published: October 2021

Inhibition of Proprotein convertase subtilisin/kexin type 9 (PCSK9) has become an attractive therapeutic strategy for lowering low-density lipoprotein cholesterol (LDL-C). In this study, a novel high affinity humanized IgG1 mAb (named h5E12-L230G) targeting the catalytic domain of human PCSK9 (hPCSK9) was generated by using CDR-grafting, alanine-scanning mutagenesis, and saturated site-directed mutagenesis. To eliminate the cytotoxic effector functions and mitigate the heterogeneity, the heavy-chain constant region of h5E12-L230G was modified with L234A/L235A/N297G mutations and C-terminal lysine deletion. The biolayer interferometry (BLI) binding assay and molecular docking study revealed that h5E12-L230G binds to the catalytic domain of hPCSK9 with nanomolar affinity (KD =1.72 nM) and an extremely slow dissociation rate (koff, 4.84 × 10−5 s−1), which interprets its quite low binding energy (-54.97 kcal/mol) with hPCSK9. Additionally, h5E12-L230G elevated the levels of LDLR and enhanced the LDL-C uptake in HepG2 cells, as well as reduced the serum LDL-C and total cholesterol (TC) levels in hyperlipidemic mouse model with high potency comparable to Alirocumab. Our data suggest that h5E12-L230G is a highly potent antibody binding to PCSK9 catalytic domain with slow dissociation rate which may be utilized as a therapeutic candidate for treating hypercholesterolemia and relevant cardiovascular diseases.
Clinical Characteristics and Outcomes of Exertional Rhabdomyolysis after Indoor Spinning: A Systematic Review
Authors: Masuda Yoshio , Wam Rachel , Paik Benjamin , Ngoh Clara L.Y. , Choong Andrew M.T.L , Ng Jun Jie
Published: October 2021

ObjectivesMore patients are being diagnosed with exertional rhabdomyolysis secondary to indoor spinning. We conducted a systematic review to characterize the clinical characteristics of this new clinical entity.MethodsWe conducted a thorough literature search on PubMed, Embase, Web of Science, Scopus and The Cumulative Index to Nursing and Allied Health Literature (CINAHL). Articles published from inception till 23rd June 2021 were considered for inclusion. A two-stage article selection process was performed. Articles that reported clinical characteristics and outcomes for patients with SIER were included. Quality assessment was performed using the Joanna Briggs Institute checklists.ResultsThere was a total of 22 articles and 97 patients with SIER. Most patients were healthy females who had attended their first spinning session. The average time to clinical presentation was 3.1 ± 1.5 days. The most common presenting symptoms were myalgia, dark urine and muscle weakness involving the thigh. Seven patients (7.2%) developed acute kidney injury, and two patients (2.1%) required temporary inpatient haemodialysis. Four patients (4.1%) developed thigh compartment syndrome and required fasciotomies. There were no long-term sequelae or mortality observed. The average length of stay was 5.6 ± 2.9 days.ConclusionsHealthcare professionals must have a high index of suspicion of SIER if any patient presents with myalgia, dark urine or weakness after a recent episode of indoor spinning. Fitness centre owners, spinning instructors and participants should also be better educated about the clinical characteristics and manifestations of SIER.
Insight into the structure of black coatings of ancient Egyptian mummies by advanced EPR spectroscopy of vanadyl complexes.
Authors: Dutoit Charles-Emmanuel , Binet Laurent , Vezin Hervé , Anduze Océane , Lattuati-Derieux Agnès , Gourier Didier
Published: October 2021

Advanced EPR techniques such as ENDOR and pulsed EPR are used to investigate the enigmatic black coatings of ancient Egyptian mummies, consisting in a complex and heterogeneous mixtures of conifer resins, wax, fat and oil with variable amounts of bitumen. Natural bitumen always contains traces of vanadyl porphyrin complexes that we used here as internal probes to explore the nanoscale environment of V4+ ions in these black coatings by hyperfine spectroscopy. Four types of vanadyl porphyrins were identified from the analysis of 14N hyperfine interactions. Three types (referred to as VO-P1, VO-P2 and VO-P3) are present in natural bitumen from the Dead Sea, among which VO-P1 and VO-P2 are also present in black coatings of mummies. The absence of VO-P3 in mummies, which is replaced by another complex VO-P4, may be due to its transformation during preparation of the black matter for embalming. Analysis of 1H hyperfine interaction shows that bitumen and other natural substances are intimately mixed in these black coatings, with bitumen aggregate sizes not larger than a few nanometres.
Construction of Immune-gene-pairs and Prognostic Model and its Immune Cell Infiltrationin in Glioblastoma — A Study based on TCGA and GTEx
Authors: Wei Yongxiang , Shi Jixin
Published: October 2021

Background: Gliomas are the most common primary intracranial tumor, containing 81% of brain malignant carcinoma. Glioblastoma is a primary brain tumor with a very poor prognosis. Existing treatment methods have many limitations, so more in-depth researches are urgently needed. Results: To screen key genes and build models, we made full use of RNA sequencing (RNA-seq) data from TCGA and GTEx and perform immune infiltration analysis in multiple immune-related databases. Finally, we screened key genes and build the model. Meanwhile, we explored immune cell infiltration. KEGG and GO analysis prompted us COVID-2019 may have potential relation with GBM. Further selection of immune-related differential genes and gene-pairs were then explored. The prognosis model built by lasso regression was tested to have great effect. Key genes were all found to have quite diverse expression level compared with normal samples. Moreover, their co-expression analysis reminded us more attention could be paid to WNT and NOTCH signaling. Immune infiltration suggests that most immune cells are differentially expressed in tumor samples, and the interaction reminded us B cells may play a critical role. Conclusion: This study is the first to build immune-gene-pairs and used lasso regression to construct the model and screen critical pairs. Key genes were then selected and observed their role in GBM.
Comparison Between Fasting and Non-Fasting Cut-Off Values of Triglyceride in Diagnosing High Triglyceride in Chinese Hypertensive Outpatients
Authors: Xie Yingying , Qu Peiliu , Wen Tie , Liu Ling , Du Xiao , Zhang Shilan , Guo Liling , Xiang Qunyan , Lin Qiuzhen , Xu Jin , Zhu Liyuan , Tan Yangrong , Fu Yan , Zhang Miao , Zang Xueyan
Published: October 2021

Background: Hypertension (HBP) often occurs together with hypertriglyceridemia that indicates elevated triglyceride (TG) and remnant cholesterol (RC) levels. Non-fasting (i.e. postprandial) blood lipid test after a daily meal has been recommended by the European Atherosclerosis Society (EAS). However, little is known about the difference between fasting and non-fasting cut-off values in assessing high TG (HTG) and high RC (HRC) in HBP outpatients.Methods: Two hundred and twenty-five Chinese outpatients with HBP were enrolled in this study. According to the time of blood lipid test, they were divided into two groups, i.e. the fasting group (n=119) and the non-fasting group (n=139). Non-fasting levels of blood lipids at 2 h after a daily breakfast were also tested in 33 patients among the fasting group. Venous blood samples were collected. Serum levels of blood lipids were measured by the enzymatic and direct methods on a HITACHI 7170A analyzer or estimated via related formulas. Results: The non-fasting group had significantly higher levels of TG and RC while lower levels of total cholesterol, low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol than the fasting group (P＜0.05). According to TG and RC cut-off values of the EAS, the percentages of HTG and HRC in the non-fasting group were 67.6% and 65.6%, respectively, while those in the fasting group were 57.1% and 52.9%, respectively. However, the percentages of HTG in the fasting state and at 2 h after a daily breakfast in 33 outpatients did not reach statistical significance (57.6% v.s. 51.5%). So did the fasting and at 2 h non-fasting percentages of HRC in them.Conclusion: Non-fasting blood lipid test could find more HBP outpatients with HTG in Chinese outpatients with HBP. However, the percentage of HTG at 2h after a daily breakfast seemed to be close to that in the fasting state.
Generation of Genome-Edited Dogs by Somatic Cell Nuclear Transfer
Authors: Kim Dong-Ern , Lee Ji-Hye , Ji Kuk-Bin , Park Kang-Sun , Kil Tae-Young , Koo Okjae , Kim Min-Kyu
Published: October 2021

Background: Canine cloning technology based on somatic cell nuclear transfer (SCNT) combined with genome editing tools, such as CRISPR/Cas9, can be used to correct pathogenic mutations in purebred dogs or to generate animal models of disease.Results: In this study, we constructed a CRISPR/Cas9 vector construct targeting the canine DJ-1 gene. Genome-edited canine fibroblasts were established by transfection of the vector following antibiotic selection. We performed canine SCNT using genome-edited fibroblasts and successfully produced two genome-edited dogs. Both genome-edited dogs had indel mutations at the target locus, and expression of the DJ-1 gene was downregulated or completely repressed.Conclusion: In conclusion, SCNT successfully produced genome-edited dogs using the CRISPR/Cas9 system for the first time.
Correlation of Diabetes and Cancers: A Survey of Hospitalized Patients in the United State, 2005-2015
Authors: Mirahmadizadeh Alireza , Sharifi Mohammad Hossein , Aryaie Mohammad , Gheibi Zahra , Rezvani Alireza , Zeighami Shahryar , Heiran Alireza , Seifi Ali
Published: October 2021

BackgroundIn recent decades, there is a growing body of literature that recognizes the relationship between diabetes and cancers. However, there is limited and contradictory evidence regarding whether diabetes is associated with an increased or decreased risk of some cancers.MethodIn this survey, data from 44,262,443 patients aged ≥50 years from 2005 to 2015 were obtained from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) database. Univariate analysis and multivariate logistic regression between diabetes and 33 selected cancers among hospitalized patients were calculated from data extracted from the database.ResultsThis study revealed that out of 44,262,443 discharges, 13,048,961 patients had diabetes for a prevalence of 29.48%, and 11,752,871 cases of 33 different cancers existed among 9,103,889 patients. Data revealed that the proportion of patients hospitalized with diabetes increased from 25.79% to 32.31% in uncomplicated diabetes (mean age: 70.11±11.07 years) and from 4.47% to 7.14% in complicated diabetes (mean age: 68.71±10.72 years). The univariate analysis and multivariate logistic regression analysis revealed that diabetes, including uncomplicated and complicated, had a protective role for 33 selected cancers as the 1st–30th diagnosis except for pancreatic cancer (OR 1.415, 95% CI: 1.40–1.43), and liver and intrahepatic cancer (OR 1.199, 95% CI: 1.184–1.213).ConclusionThis study presents new information on the likelihood of a protective role of diabetes in certain cancers using a large amount of individual data. Continued efforts and research are needed to provide detailed and probable biological mechanisms linking diabetes and the development and progression of cancer.
Utility and Its Relationship With Disease Activity and Physical Disability of Patients With Psoriatic Arthritis in Thailand
Authors: Sawangjit Ratree , Dilokthornsakul Piyameth , Chiowchanwisawakit Praveena , Louthrenoo Worawit , Osiri Manathip , Sucheewasilp Jeeranun , Nampuan Sawanya , Permsuwan Unchalee
Published: October 2021

Physical disability and severity of skin disease are important factors for evaluating healthy utility in psoriatic arthritis (PsA) patient. This study aims to estimate health utility and its related factors incorporating both rheumatologic and dermatologic factors in PsA. This cross-sectional study performed in PsA patients in Thailand. EQ-5D-5L, Health Assessment Questionnaire Disability Index (HAQ-DI), and Psoriasis Area and Severity Index (PASI) tools were used to collect health utility, physical disability, and severity of psoriatic skin lesions by face-to-face interviewed. Linear regression analysis was performed to relate health utility and its related factors. Of 84 patients enrolled, 49 (58.3%) were female, 67 (79.8%) had remission or low disease activity. Eighty-three patients (98.8%) received conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologic DMARDs (bDMARDs). The mean±SD overall utility was 0.87±0.15. The utility score of patients with low disease activity was significantly greater than those with moderate to severe disease activity (0.89±0.12 vs 0.72±0.19, p<0.001). The HAQ-DI (unstandardized β = -0.167, 95%CI; -0.218 to -0.116, p<0.001) and PASI (unstandardized β = -0.006, 95%CI; -0.009 to -0.003, p<0.001) were found to be significant related factors for utility. These results indicated that Thai patients with PsA had relatively high health utility. However, most included patients were in remission or had low disease activity. The HAQ-DI and PASI showed a strong predictors of patients’ health utility.
Climate Change and Equestrian Empires in the Eastern Steppes: New Insights from a High-resolution Lake Core in Central Mongolia
Authors: Struck Julian , Bliedtner Marcel , Strobel Paul , Taylor William Timothy Treal , Biskop Sophie , Plessen Birgit , Klaes Björn , Bittner Lucas , Jamsranjav Bayarsaikhan , Salazar Gary , Szidat Sönke , Brenning Alexander , Bazarradnaa Enkhtuya , Glaser Bruno , Zech Michael , Zech Roland
Published: October 2021

The repeated expansion of East Asian steppe cultures was a key driver of Eurasian history, forging new social, economic, and biological links across the continent. Climate has been suggested as important driver of these poorly understood cultural expansions, but paleo-climate records from the Mongolian Plateau often suffer from poor age control or ambiguous proxy interpretation. Here, we use a combination of geochemical analyses and comprehensive radiocarbon dating to establish the first robust and detailed record of paleo-hydrological conditions for Lake Telmen, Mongolia, covering the past ~4000 years. Our record shows that humid conditions coincided with solar minima, and hydrological modelling confirms the high sensitivity of the lake to paleo-climate changes. Careful comparisons with archaeological and historical records suggest that in the vast semi-arid grasslands of eastern Eurasia, solar minima led to reduced temperatures, less evaporation, and high biomass production, expanding the power base for pastoral economies and horse cavalry. Our findings suggest a crucial link between temperature dynamics in the Eastern Steppe and key social developments, such as the emergence of pastoral empires, and fuel concerns that global warming enhances water scarcity in the semi-arid regions of interior Eurasia.
Development of a Clinical 3D Modeling Program to Guide Pediatric Cardiothoracic Surgery and Intervention
Authors: Ghosh Reena Maria , Jolley Matthew A , Mascio Christopher E , Chen Jonathan M , Fuller Stephanie , Rome Jonathan J , Silvestro Elizabeth , Whitehead Kevin K
Published: October 2021

Background. Surgical and catheter-based interventions for congenital heart disease require precise understanding of complex anatomy. The use of three-dimensional (3D) visualization techniques to enhance visuospatial understanding has been well documented, but integration of these methods into routine clinical practice has not been well described. We report the growth and development of a clinical 3D modeling service to inform procedural planning within a high-volume pediatric heart center.Methods. Clinical 3D modeling was performed using cardiac magnetic resonance (CMR) or computed tomography (CT) derived data. Image segmentation and post-processing was performed using FDA-approved software. Patient-specific anatomy was visualized using 3D printed models, digital flat screen models and virtual reality. Surgical repair options were digitally designed using proprietary and open-source computer aided design (CAD) based modeling tools. Results. From 2018 to 2020 there were 112 individual 3D modeling cases performed, 16 for educational purposes and 96 clinically utilized for procedural planning. Over the 3-year period, demand for clinical modeling tripled and in 2020, 3D modeling was requested in more than one-quarter of STAT category 3, 4 and 5 cases. The most common indications for modeling were complex biventricular repair (n = 30, 31%) and repair of multiple ventricular septal defects (VSD) (n=11, 12%). Conclusions. Using a multidisciplinary approach, clinical application of 3D modeling can be seamlessly integrated into pre-procedural care for patients with congenital heart disease. Rapid expansion and increased demand for utilization of these tools within a high-volume center demonstrate the high value conferred on these techniques by surgeons and interventionalists alike.
Chondroitin Sulphate and Glucosamine Sulphate Synergistically Reduced DRG Proinflammatory Molecules and Improved Axonal Function in Sciatic Nerve Ligated Rats.
Authors: Owoyele Bamidele Victor , Olaseinde Olutayo Folajimi
Published: October 2021

Neuropathic pain (NP) is a sickness of the somatosensory nervous system. It is linked to defective quality of life and often poorly managed. Due to the limited number of approved drugs, limited efficacy and side effects associated with them, drugs or drug combinations with great efficacy and very minimal or no side effects will be of great advantage in managing NP. This study aimed at investigating the synergistic antinociceptive effects of the combination of glucosamine sulphate (GS) (240mg/kg) and chondroitin sulphate (CS) (900mg/kg) in chronic constriction injury (CCI)-induced neuropathy in rat. Forty-two Wistar rats were randomly distributed into seven groups (n=6). Sciatic nerve was ligated with four loose ligatures to induce NP. Effects of drugs were examined on stimulus and non-stimulus evoked potentials, expression of dorsal root ganglia (DRG) pain modulators and structural architecture of DRG. Oral administration of GS and CS for 21 days reduced hyperalgesia, allodynia, sciatic nerve functional aberration and DRG pain modulators. Histopathology and immunohistochemistry revealed restoration of structural integrity of DRG. Our result showed that the combination of GS and CS produced antinociceptive effects by attenuating hyperalgesia, allodynia and downregulation of NP mediators. GS and CS additionally produced synergistic analgesic effect than its individual components.
Analysis of Furrow Irrigation Design Parameters On Sugarcane Growth And Yield Parameters Under Wonji Shoa Climatic Condition
Authors: Negera Belay Yadeta , Ayana Mekonen , Yitayew Muluneh , Hordofa Tilahun
Published: October 2021

Sugarcane is one of the important industrial crops produced all over the tropical areas. Sugarcane production is highly expanding in developing countries like Ethiopia. However, sugarcane is characterized by very high crop requirements. But sugarcane is produced mostly in Ethiopia using furrow irrigation methods in which more losses of irrigation water is most common due to many factors. Even if there are high losses of water in furrow irrigation, in which its performance influenced by many factors, to improve its performance or reduces the losses of irrigation water proper furrow irrigation decision variables combination is very important. In line with this the current study focused on three main furrow irrigation design parameters. The main purpose of the current study was to analyse effect of furrow irrigation design on sugarcane growth and yield parameters under Wonji Shoa Sugar Estate conditions. The field experiment was conducted using Split-split plot design with three factorial experiments replicated three times. All required data on growth and yield of sugarcane parameters were collected and analysed using SAS 9.4 version statistical software. The effect of furrow slope showed statistically significance variation at 5% significance on growth parameters (cane height, cane weight, cane diameter and number of cane internode per stalk), but non significance variation on yield components of sugarcane (moisture percent, dry substance, number of millable cane stalk and sugarcane yield). But the effect of furrow length showed statistically significance variation on almost all growth and yield parameters of sugarcane at 5% significance level except sugarcane yield. Finally, the effect of furrow discharge rate on all growth and yield parameters considered were showed statistically significance variation at 5% significance level except number of millable cane stalk. In general, the highest sugarcane yield was obtained from furrow slope three, furrow length three and furrow discharge rate as compared to the other factors level. Therefore, this result it can be recommended that slightly slope, longer furrow length and less properly applied discharge rate resulted in more yield of sugarcane.
Antimicrobial Resistance and Genetic Characteristics that Might be Related to Antibiotic Resistance of 112 Helicobacter Pylori Shanghai Isolates
Authors: Liu Yixin , Wang Su , Yang Feng , Chi Wenjing , Ding Li , Liu Tao , Zhu Feng , Ji Danian , Zhou Jun , Fang Yi , Zhang Jinghao , Xiang Ping , Zhang Yanmei , Zhao Hu
Published: October 2021

Background

Shanghai, east China has one of the world’s highest burdens of Helicobacter pylori infection. While multidrug regimens can effectively eradicate H. pylori, antibiotic-resistant (AR) H. pylori has been recognized by the WHO as ‘high priority’ for urgent need of new therapies. Moreover, the genetic characteristics of H. pylori AR in Shanghai is under-reported. The purpose of this study was to determine the resistance prevalence, re-substantiate resistance-conferring mutations, and investigate novel genetic elements might be related to H. pylori AR.
Results

We performed a whole-genomic and phenotypic analysis of 112 H. pylori isolated from gastric biopsy specimens from a population with different gastric diseases and residing in Shanghai. No strains were resistant to amoxicillin. Levofloxacin, metronidazole and clarithromycin resistance was observed in 39, 73 and 18 isolates, respectively. There was no association between gastroscopy diagnosis and resistance phenotypes. We reported the presence or absence of several subsystem proteins including hopE, hofF, spaB, cagY and pflA, and a combination of CRISPRs, which were potentially correlated with resistance phenotypes. The H. pylori isolates were also annotated for AR genes to define a resistome containing 80 genes. A resistome-wide association study (RWAS) was performed for the three antibiotics by correlating the phenotypes with the variation data. The RWAS correctly identified the well-known intrinsic resistance associated mutations for levofloxacin (N87T/I and/or D91G/Y mutations in gyrA), metronidazole (I38V mutation in fdxB), and clarithromycin (A2143G and/or A2142G mutations in 23S rRNA), and added 174 novel variations, with 23 nsSNPs and 48 fsIndels significantly enriched in resistant or susceptible populations. The variant-level linkage disequilibrium analysis demonstrated a series of variations with strong co-occurring correlation with known mutations, and highlighted the underlying role of a protease Lon.
Conclusion

Our study indicated H. pylori isolates from Shanghai exhibit multidrug antibiotic resistance, and identified specific genomic characteristics in relation to H. pylori AR in Shanghai. Continued surveillance of H. pylori AR in Shanghai is warranted in order to establish appropriate eradication treatment regimens for this population.
Parallel m-Dimensional Relative Ant Colony Optimization (mDRACO) For the Costas-Array Problem
Authors: Vulakh David , Finkel Raphael
Published: October 2021

The Costas-array problem is a combinatorial constraint-satisfaction problem (CSP) that remains unsolved for many array sizes greater than 30. In order to reduce the time required to solve large instances, we present an Ant Colony Optimization algorithm called m-Dimensional Relative Ant Colony Optimization (mDRACO) for combinatorial CSPs, focusing specifically on the Costas-array problem. This paper introduces the optimizations included in mDRACO, such as map-based association of pheromone with arbitrary-length component sequences and relative path storage. We assess the quality of the resulting mDRACO framework on the Costas-array problem by computing the efficiency of its processor utilization and comparing its run time to that of an ACO framework without the new optimizations. mDRACO gives promising results; it has efficiency greater than 0.5 and reduces time-to-first-solution for the m = 16 Costas-array problem by a factor of over 300.
Are We Aiming for Cure or Lifelong Treatment of Hypertension? All Doctors Need To Be Aware of Primary Aldosteronism. A Nationwide Study With Up To 8-Year Follow-Up
Authors: Gunnarsdóttir Hrafnhildur , Jonsdottir Gudbjorg , Birgisson Gudjon , Gudmundsson Jon , Sigurjonsdottir Helga Agusta
Published: October 2021

Purpose

Long term follow-up studies on primary aldosteronism (PA) diagnosis, treatment response and comparison of the two major subgroups – unilateral (UD) and bilateral disease (BD) – are lacking. While adrenalectomy for UD is considered effective, less is known about long-term effects of specialized treatment for BD. We present the results from our nationwide observational study, executed at Landspitali University Hospital, tertiary referral center. We aim to review results of diagnostic procedures and histopathology for PA patients diagnosed in 2012-2016 in Iceland, compare UD and BD and assess treatment response.
Methods

A total of 32 PA patients aged 28-88 years were diagnosed and treated according to current guidelines. Adrenalectomy was used for AVS-confirmed UD and mineralocorticoid receptor antagonists for BD.
Results

The majority of patients had BD, roughly half of them had a unilateral nodule. With specialized treatment, a reduction was seen in UD and BD in systolic blood pressure (BP) (p<0,001, both groups), antihypertensive drug count (p=0,002 and p=0,04, respectively) and need for potassium supplementation (p<0,001, both groups). Diastolic BP decreased significantly in UD (p<0,001).
Conclusion

Our results show similarly good treatment response in both subgroups. Ratio of hypokalemia and number of cases indicates severe PA underdiagnosis in Iceland. Adrenal nodules diagnosed using CT can be misleading and AVS is mandatory in diagnosing unilateral vs bilateral PA.
FTO-Mediated N6-Methyladenosine Modification of KLF3 Promotes Osteosarcoma Progression
Authors: Shan Hong-Jian , Gu Wen-Xiang , Duan Gang , Zhu Zhi-Man , Chen Hong-Liang
Published: October 2021

N6-methyladenosine (m6A) methylation is the most common and abundant methylation modification of eukaryotic mRNAs, which is involved in tumor initiation and progression. This study aims to explore the functional role and regulatory mechanism of FTO in osteosarcoma progression. In this study, we detected the expressions of KLF3 in OS cells and tissues by qRT-PCR and western blot, and found that the mRNA and protein expressions of KLF3 were increased in OS cells and tissues and significantly related to tumor size, metastasis, and TNM stage and poor prognosis of OS patients. FTO promoted the proliferation and invasion and suppressed apoptosis of OS cells through CCK-8, Transwell and apoptosis assays. Further mechanism dissection revealed that FTO and YTHDF2 enforced the decay of KLF3 mRNAs and decreased its expression. Knockdown of FTO led to elevate m6A and mRNA levels. FTO-mediated m6A modification regulated KLF3 expression in the YTHDF2-dependent manner. Moreover, KLF3 overexpression abrogated FTO-induced oncogenic effects on the proliferation and invasion of OS cells. Overall, our findings showed that FTO-mediated m6A modification of KLF3 promoted OS progression, which may provide a therapeutic target for osteosarcoma.
Study on the Interpretation Method of Low Resistivity Contrast Oil Reservoir Based on Support Vector Machine—Taking the Chang 8 Tight Sandstone Reservoir of Yanchang Formation in Huanxian Area, Ordos Basin as an Example
Authors: Bai Ze , Tan Maojin , Shi Yujiang , Guan Xingning
Published: October 2021

Low resistivity contrast oil reservoirs are subtle reservoirs that have no obvious difference in physical and electrical properties from water layers. It is difficult to identify based on the characteristics of the geophysical well logging response. Especially in tight sandstone reservoirs with low porosity and low permeability, the log interpretation effect of low resistivity contrast oil layers is worse. In recent years, data mining technology has been increasingly applied in oil exploration and development, especially for some complex reservoirs with unclear logging response characteristics, and how to use data mining technology to effectively solve some complex problems is of great significance in oilfields. Therefore, support vector machine (SVM) technology was applied to interpret the low resistivity contrast oil layer in this paper. First, the input data sequences of logging curves were selected by analyzing the relationship between reservoir fluid types and logging data. Then, the SVM classification model for fluid identification and SVR regression model for reservoir parameter prediction were constructed. Finally, the two models were applied to the logging interpretation of the Chang 8 tight sandstone reservoir of the Yanchang Formation in the Huanxian area, Ordos Basin. The application results show that the fluid recognition accuracy of the SVM classification model is higher than that of the logging cross plot method and BP neural network method. The calculation accuracy of permeability and water saturation predicted by the SVR regression model is higher than that based on the experimental fitting model, which indicates that it is feasible to carry out logging interpretation and evaluation of the low resistivity contrast oil layer by the SVM method. The research results not only provide an important reference and basis for the review of old wells but also provide technical support for the exploration and development of new strata.
An Experimental Investigation on Micro Drilling of Cold Work Steel X153CrMoV12 By EDM
Authors: CERİTBİNMEZ FERHAT , Kanca Erdoğan
Published: October 2021

In this study, it was aimed to analyze the effects of machining parameters on the process quality by drilling holes in heat treated cold work tool steel with a hardness of 60-62 HRC using the electrical discharge machining (EDM) method and Ø2 mm diameter brass electrodes. In this context, drilling was performed using three different current values ​​(5, 6, 7 A), three different voltage values ​​(1, 2, 3 V), three different discharge pulse frequency Ton (23, 26, 29 µs) as well as Toff (3, 5 µs) respectively, and the effects of these machining parameters on the machining time, material removal rate (MRR), electrode wear rate (EWR), surface roughness (SR) and hardness of around the white layer were analyzed using micro, macro and analytical measurements, especially with Scanning Electron Microscopy (SEM) and Energy Dispersive X-Ray Analysis (EDX). As a result of the analysis, ıt was observed that current, voltage, Ton and Toff had an effect on machining time, MRR, EWR, SR and hardness, but current was the most effective parameter, and also worn electrode as well as workpiece residues affected the process quality. Increasing the machining current increased sparking between the workpiece and the electrode, resulting in increased point melting and evaporation, resulting in increased average surface roughness, metal removal rate, and electrode wear rate. As a result of the high metal removal rate, the machining time was greatly reduced and the thermal effect time was reduced, which led to a decrease in the hardness variation on the machined surfaces.
Multi-point Sources Continuous Release Inversion Based on Improved Four-Dimensional Variation Method
Authors: CHAOSHUAI HAN , Zhu Xuezheng , Gu Jin , Zuo Qinwen
Published: October 2021

the continuous release of multi-point sources is one of the most common cases in the field of air pollution. In order to solve the problem of multi-point sources continuous release inversion, a source intensity and location estimation method based on improved Four-Dimensional Variation is proposed. Firstly, by constructing the diffusion equation of multi-point sources continuous release and the monitoring concentration matrix, the source term inversion model of multi-point sources continuous release is formed. Secondly, the joint transformation method and Taylor series upwind difference method are used to solve the convection-diffusion equation of multi-point sources continuous release, and the numerical solution format of the forward problem is formed through simulation analysis. Furthermore, based on the numerical solution scheme of the forward problem, a four-dimensional variation inversion algorithm for multi-point sources continuous release is constructed, and the flower pollination algorithm is used to improve the inversion accuracy and computational efficiency. Finally, the applicability, feasibility, advantages and disadvantages of the improved four-dimensional variation algorithm are verified by numerical simulation analysis. It is found that the improved four-dimensional variation algorithm can realize the source term inversion under three conditions: the location is known and the intensity is unknown, the intensity is known and the location is unknown, the intensity and the location are all unknown, which the accuracy and computational efficiency can basically meet the actual needs.
Kinetic and Thermodynamic Control in Rare Earth Cyamelurates Synthesis
Authors: Isbjakowa Albina S. , Chernyshev Vladimir V. , Tafeenko Victor A. , Aslanov Leonid A
Published: October 2021

If various compounds exist in the metal cation – C6N7O33– – H2O system, the synthesis temperature can affect the isolation of a particular product. Low temperatures favor the release of metastable kinetic products, and high temperatures, on the contrary, of thermodynamic ones. It is found that several structural types exist in the row of rare-earth cyamelurates. Room temperature synthesis leads to the formation of [Ln(H2O)7C6N7O3] (Ln=Y, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er), an increase in temperature yields thermodynamically more stable [Ln(H2O)4C6N7O3]n·nH2O (Ln=Y, Ho, Er, Tm, Yb, Lu) and [Ln(H2O)5C6N7O3]n (Ln = Pr, Nd). The change in the synthesis temperature did not affect the structures of Sm, Eu, Gd, Tb, Dy cyamelurates, as well as the structure of lanthanum cyamelurate [La(H2O)6C6N7O3]·H2O.In synthesized at increased temperature [Ln(H2O)4C6N7O3]n·nH2O and [Ln(H2O)5C6N7O3]n cyamelurates polymeric chains exist due to the fact that the cyamelurate anion acts as a bridging ligand. Kinetically trapped Y, Pr, Nd, Ho, Er cyamelurates, in contrast, consist of individual complex molecules [Ln(H2O)7C6N7O3]. Probably, steric difficulties caused a decrease in the coordination number of Y, Ho, Er from 9 to 8 in the thermodynamic product. The coordination number of Pr and Nd remains equal to 9 in both types of compounds.
Laying the foundations of meaningful community engagement in Aboriginal health research: Establishing a community reference group and terms of reference in a novel research field.
Authors: O'Brien Penny , Prehn Ryan , Rind Naz , Lin Ivan , Choong Peter FM , Bessarab Dawn , Coffin Juli , Mason Toni , Dowsey Michelle M , Bunzli Samantha
Published: October 2021

The authors have requested that this preprint be removed from Research Square.