bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of critical protein-protein interactions of SARS-CoV-2 capping and proofreading molecular machineries towards designing dual target inhibitory peptides
Authors: Arabi-Jeshvaghani Fatemeh , Javadi‐Zarnaghi Fatemeh , Ganjalikhany Mohamad Reza
Published: August 2022

Coronaviruses (CoVs) have been the cause of human respiratory syndromes for many years. In recent years, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as the cause of the coronavirus disease (COVID-19) global pandemic has imposed enormous health care issues and economic burden. The recent emerging SARS-CoV-2 variants with higher transmissibility and substantial immune evasion, have highlighted the importance of sustainable and imperative solutions to develop novel therapeutics other than vaccination to combat CoVs infections. In the search for promising antivirals for coronaviruses, besides receptor recognition and virus entry, efforts have concentrated on targeting other molecular machineries of the virus, such as the replication/transcription complex (RTC). Here, the key interacting residues that mediate the protein-protein interactions (PPIs) of nsp10 with nsp16 and nsp14 have been comprehensively analyzed. Consequently, the key residues' interaction maps, interaction energies, structural networks, and dynamics were investigated. Nsp10 stimulates nsp14's exoribonuclease (ExoN) as well as nsp16's 2′O-methyltransferase (2′O-MTase). Nsp14 ExoN is an RNA proofreading enzyme that supports replication fidelity. Nsp16 2′O-MTase is responsible for completion of the RNA capping to ensure efficient replication and translation and escape from the host cell's innate immune system. The results of PPIs analysis proposed crucial information which was applicable to anti SARS-CoV-2 drug design. Based on the PPIs analysis, a set of dual-target peptide inhibitors were designed on the basis of the predicted shared protein-protein interfaces of the nsp16-nsp10 and nsp14-nsp10 interactions. The peptides were evaluated by molecular docking, peptide-protein interaction analysis, and molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) calculations, and then were further optimized by in silico saturation mutagenesis. According to the predicted evolutionary conservation among CoVs for the target residues that interact with the designed peptides, the designed peptides have the potential to be developed as dual target pan-coronavirus inhibitors.
High parenteral carbohydrate intakes in patients with chronic intestinal failure are associated with accumulation of advanced glycation end products.
Authors: Tetard Candice , Poullenot Florian , Pellet Gauthier , Clouzeau Haude , Rebouissoux Laurent , Wilsius Eva , Kerlogot Laurianne , Chevrier Constance , Laharie David , Lamireau Thierry , Enaud Raphaël
Published: August 2022

Advanced glycation end-products (AGE) are the product of non-enzymatic reactions between reduced carbohydrates, peptides, lipids, nucleic acids. AGE accumulate over time, they are considered as the metabolic memory. In certain pathologies such as diabetes mellitus, AGE accumulation is increased and correlated with vascular complications. Patients with chronic intestinal failure dependent on parenteral nutritional have long-term intravenous carbohydrate intakes. The assessment of AGE levels in this population has never been performed. We measured skin AGE levels by auto-fluorescence in 23 adults followed in a tertiary center for chronic intestinal insufficiency and treated with home parenteral nutrition that we compared to the values of the general population. We also analyzed factors associated with elevated AGE. More than half (n=13) had elevated AGE. The presence of elevated AGE was significantly associated with higher parenteral carbohydrate intakes. Patients with elevated AGE had higher intravenous carbohydrate intakes (median 3.3g/kg/day [1.84;3.62]), compared to patients with normal AGE (1.79g/kg/d [1.45;2.26], p=0.03). The presence of chronic renal failure was also associated with elevated AGE. This preliminary study suggests that AGE accumulation is increased in subjects on prolonged parenteral nutrition. Studies with larger numbers will be necessary to confirm this hypothesis and to evaluate the association with cardiovascular events.
Predictive value of TRPV2 expression from peripheral blood mononuclear cells on the early recurrence of atrial fibrillation after radiofrequency catheter ablation
Authors: Ling Xuebin , Wang Jun , Qin Xue , Lin Chufen , Jie Wei , Chen Yane , Fu Dajia , Yang Yang , Meng Qingwen , Lin Jing , Liu Hui , Li Tianfa , Guo Junli
Published: August 2022

Background:: Recent study has shown that the transient receptor potential vanilloid 2 (TRPV2) channel was exclusively upregulated in patients with atrial fibrillation (AF), and that this overexpression might be detrimental for occurrence and maintenance of AF. We aimed to characterize the expression levels of TRPV2 mRNA in peripheral blood mononuclear cells (PBMCs) with/without early recurrence of atrial fibrillation (ERAF) after radiofrequency catheter ablation (RFCA), and to find a reliable predictor for ERAF. Methods: 65 patients of AF, who underwent RFCA successfully, then divided into two groups according to ERAF during following 3 months. PBMCs were isolated from whole blood by Ficoll gradient centrifugation before and after RFCA. Gene set enrichment analysis (GSEA) was performed to evaluate TRPV channels expression levels and KEGG mapping was used for pathway enrichment analysis. Results: There was no significant difference in the TRPV2 mRNA expression level between the two groups before RFCA, while without ERAF group of TRPV2 expression was markedly reduced compared to ERAF group after RFCA. Moreover, the number of TRPV2 expression was confirmed as an independent predictor for the first time through receiver operation characteristic (ROC) and Kaplan-Meier survival curve analysis. It should be pointed out that the above results were only used to predict ERAF, and have no predictive significance for late recurrence of atrial fibrillation (LRAF) according to the current data. Additionally, ERAF was inversely correlated with P wave dispersion (PWD). KEGG mapping further clustered 41 pathways, revealing that ‘‘cGMP-PKG signaling pathway’’ was significantly enriched. Conclusions: We firstly assume that downregulated expression of peripheral TRPV2 appear in patients without ERAF after RFCA. TRPV2 may thus represent a novel predictor of early phase after successful radiofrequency ablation.
Investigating nicotine pathway-related long noncoding RNAs in Nicotiana tabacum
Authors: Xie Xiaodong , Jin Jingjing , Wang Chen , Lu Peng , Li Zefeng , Tao Jiemeng , Cao Peijian , Xu Yalong
Published: August 2022

Background
Long noncoding RNAs (lncRNAs) are transcripts longer than 200bp with low or no protein-coding ability, which play essential roles in various biological processes in plants. Tobacco is an ideal model plant for studying nicotine biosynthesis and metabolism, and there is little research on lncRNAs in this field. Therefore, how to take advantage of the mature tobacco system to profoundly investigate the lncRNAs involved in the nicotine pathway is intriguing.
Results
By exploiting 549 public RNA-Seq datasets of tobacco, 30,212 lncRNA candidates were identified, including 24,084 large intervening noncoding RNAs (lincRNAs) and 5,778 natural antisense transcripts (NATs), and 350 intronic noncoding RNAs (incRNAs). Compared with protein-coding genes, lncRNAs have distinct properties in terms of exon number, sequence length, A/U content, and tissue-specific expression pattern. incRNAs showed an asymmetric evolutionary pattern, with a higher proportion (68.71%) expressed from N.sylvestris (S) subgenome. We predicted the potential cis/trans-regulatory effects on protein-coding genes. One hundred four lncRNAs were detected as precursors of 30 known miRNA family members, and 110 lncRNAs were expected to be the potential endogenous target mimic for 39 miRNAs. By combining the results of weighted gene co-expression network analysis with the differential expressed gene analysis of topping RNA-seq data, we constructed a sub-network containing eight lncRNAs and 25 nicotine-related coding genes. We confirmed that seven lncRNAs could be affected by MeJA treatment and transcription factor NtMYC2 using a quantitative PCR assay.
Conclusions
Nicotine pathway-related lncRNA candidates were predicted and investigated in our study. We verified that seven lncRNAs could be affected by MeJA treatment and the transcription factor NtMYC2. Results suggested that they are involved in the nicotine pathway. Our findings further deepened the understanding of the features and functions of lncRNAs and provided new candidates for regulating nicotine biosynthesis in tobacco.
Templing and Temple Search-Same Height Hashing
Authors: Tripathi Rajeev Ranjan Kumar , Singh Pradeep Kumar , Singh Sarvpal
Published: August 2022

In the current computing era, data are generating in exponential manner. These data are processed to extract information. This processing demands many query operations which in-turn requires the application of hashing for fast process of query operations. Cuckoo hashing is more efficient than conventional hashing techniques like open addressing, chaining and coalesced hashing. Because of simplicity and ease of use Cuckoo hashing has been used in real-world applications. Inherent problem associated with hashing is data collision and Cuckoo hashing also experiences the same. Cuckoo hashing uses endless loops,that results into high insertion latency and rehash operations. The idea behind Templing and Temple Search is to develop a robust hashing technique based on B-Tree that can efficiently handle the problem of data collisions without any changes in its underlying structure. In each bucket a separate B-Tree of same height is maintained to store the keys. Comprehensive analysis of experimental results demonstrate the potential of Templing and Temple Search. Templing and Temple Search addresses all challenges associated with Cuckoo hashing: intensive data migration, inefficient memory usages and high insertion latency.In future,Templing and Temple Search technique has great potential of its applications in the area of distributed hashing and in parallel hashing.
Adjunctive Nd:YAG laser irradiation in the treatment of stage III/IV periodontitis. A 12-month, randomized, controlled trial
Authors: Markou Nikolaos , Papadelli Anastasia , Nikolidakis Dimitris , Pepelassi Eudoxie , Madianos Phoebus , Karoussis Ioannis K.
Published: August 2022

Objectives: The aim of this triple-arm parallel prospective, randomized controlled 12-month trial was to evaluate in stage III/IV periodontitis the clinical efficacy of the adjunctive use of Nd:YAG laser, applied with two different protocols, to full-mouth scaling and root planing (FMS), compared to FMS alone. Materials and methods: Sixty healthy stage III/IV periodontitis patients were treated with FMS (control) or combined FMS/single Nd:YAG laser irradiation (3 W, 150 mJ, 20 Hz with Micro Short Pulse 100 µs) (Laser 1) or combined FMS/ double Nd:YAG laser irradiation (1 week interval, 2.0 W, 200 mJ, 10 Hz with Micro Short Pulse 100 µs) (Laser 2). Clinical parameters were evaluated at baseline, 6 weeks, 3, 6 and 12 months after treatment. Patient-reported parameters were also evaluated 1 week after treatment.Results: All groups presented significant (p<0.0001) clinical improvement for a 12-month period, except for clinical attachment level gain for Laser 2 at 12 months. Clinical improvement was similar among groups at all time points. The reported analgesic consumption was significantly higher for Laser 1.Conclusions: The combined FMS/Nd:YAG laser was significantly clinically effective for 12 months. The adjunctive use of Nd:YAG laser irradiation to FMS, applied with two different approaches, was similarly clinically effective to FMS for a 12-month period. A single post-FMS application of Nd:YAG laser for pocket epithelium removal and coagulation might non-statistically significantly further improve the PD reduction achieved with FMS alone. Clinical relevance: When Nd:YAG laser is used for sulcular epithelium removal and coagulation, it may provide minor improvements compared to FMS and Laser 2 long-term. The sense of discomfort seems to be more pronounced in Laser 1.
Social return on investment economic evaluation of supportive care for lung cancer patients in acute care settings in Australia
Authors: Hyatt Amelia , Chung Holly , Aston Ruth , Gough Karla , Krishnasamy Meinir
Published: August 2022

Background
Unmanaged consequences of cancer and its treatment are high among patients with lung cancer and their informal carers, resulting in avoidable healthcare use and financial burden. Provision of cancer supportive care has demonstrated efficacy in mitigating these consequences; however, globally, there is a lack of investment in these services. Paucity of robust economic evidence regarding benefit of cancer supportive care has limited policy impact and allocation of resources. In response to this, this study utilised a Social Return on Investment (SROI) methodology to conduct a forecast evaluation of lung cancer supportive care services, to ascertain social value and return on investment.
Methods
An SROI economic evaluation model was developed using qualitative stakeholder consultations synthesised with published evidence to compare the inputs, outcomes and financial value associated with the delivery of quality lung cancer supportive care services. SROI ratios were generated to determine the social value and cost savings associated per every $1AUD invested in cancer supportive care for both the healthcare system and patients. Deadweight, displacement, drop off and attribution were calculated, and sensitivity analysis was performed to confirm the stability of the model.
Results
The value generated from modelled supportive care service investments in a one-year period resulted in an SROI ratio of 1:9; that is, for every dollar invested in supportive care, AUD$9.00 return is obtained when savings to the healthcare system and benefits to the patients are combined. At five-years, these same investments resulted in greater cumulative value generated for both the patient and the healthcare system, with a SROI ratio of 1:11.
Conclusions
Our study provides strong evidence for policy makers, clinicians and consumers to advocate for further investment in cancer supportive care, as demonstrated cost savings can be achieved through implementation of the proposed supportive care service model, with these accruing over a five-year period. The SROI model provides a comprehensive framework detailing supportive care services and the health workforce necessary to achieve value-based outcomes for patients and the healthcare system.
Development and Validation of a duplex real-time PCR for the rapid detection and quantitation of HTLV-1
Authors: Ji Huimin , Chang Le , Yan Ying , Wang Lunan
Published: August 2022

Background
The HTLV-1 prevalence in China varies geographically, while HTLV-2 infection has rarely been found so far. Proviral load is one of the determining factors of pathogenesis and progression of HTLV-1 related diseases. However, neither molecular assays nor commercial kits are available for HTLV-1 diagnosis in China. The purpose of the present study was to develop and validate a TaqMan qPCR assay for HTLV-1 proviral load quantification.
Results
A plasmid containing both the HTLV-1 of interest and a fragment of the RNase P (RPPH1) gene was constructed and used to establish the standard curves. The assay has a wide dynamic range (2.5×108 copies/reaction ~ 25 copies/reaction) and sensitive to 1 copy for HTLV-1 and RPPH1. The limit of detection for Hut102 cell concentration was 0.0218% (95% confidence interval 0.0179 ~ 0.0298%). The assay gave coefficient of variation (CV) for both the HTLV-1 and RPPH1 Ct values. All of the HTLV-1 sero-negative samples and MOT cell line (infected with HTLV-2) amplified only the RPPH1 gene by our method, presenting 100% specificity. 85 Samples confirmed positive or indeterminate by LIA were performed by established qPCR assay and WB. 90.0% (27/30) of LIA-HTLV-1-positive, 33% (2/6) of LIA-untypeable and 2% (1/49) of LIA-indeterminate samples were defined as qPCR-positive. The median PVL of LIA-positive samples (n = 27, 1.780 copies/100 cells) was much higher than that of LIA-untypeable and (n = 2, 0.271 copies/100 cells) indeterminate samples (n = 1, 0.017 copies/ 100 cells). Additionally, the duplex qPCR confirmed more positive samples than WB, indicating a higher sensitivity than the later.
Conclusion
The duplex qPCR developed here with high sensitivity, good specificity and reproducibility could accurately and quantitatively detect the HTLV-1 PVLs, which can not only be used to confirm the initial reactive samples for a better cost/benefit ratio, but also to monitor the clinical progression and efficacy of therapy in patients with HTLV-1 related disease.
Cumulative Exposure to Oxidized Low-Density Lipoprotein is a Potential Predictor for Prognosis in Acute Ischemic Stroke: A Cohort Study
Authors: Kaili Cheng , Chen Xiuqi , Luo Yufan , Sun Wenbo , Yang Xiaoli , Huang Shengwen , Wang Yuanyuan , Wu Danhong
Published: August 2022

Background
Oxidized low-density lipoprotein (ox-LDL) is closely related to the recrudescence and prognosis of acute ischemic stroke (AIS). However, there are limited studies about the effect of a long-term elevation of ox-LDL in AIS. In this research, our porpose was to explore the relevence between cumulative ox-LDL exposure and the short-term prognosis of AIS.
Methods
This study recruited patients with AIS. AIS severity was evaluated by infarct volumes and National Institute of Health Stroke Scale (NIHSS) scores at admission. AIS prognosis was assessed by Modified Rankin Scale (mRS) scores at 90 days and the difference between NIHSS scores at admission and discharge. Cumulative ox-LDL exposure was defined as ox-LDL level (pg/mL) multiplied by age (y). A multivariate logistic regression model was employed to investigate the correlation between exposure factors and the prognosis of AIS. The predictive ability of cumulative ox-LDL exposure for the prognosis of AIS was compared with cumulative LDL exposure by the receiver operating characteristic curve (ROC).
Results
A total of 175 AIS patients were included with an average age of 66.00 (61.00, 73.00). Patients with higher cumulative ox-LDL exposure tended to manifest worse prognosis, including neurological worsening at discharge (NIHSS increasing more than 2 points) (OR = 3.02, 95% CI, 1.30–6.98, P = 0.01) and poor functional prognosis at 90 days (mRS ≥ 3) (OR = 21.21, 95% CI, 4.72–95.36, P < 0.001). After adjusting for potential confounders, multivariate regression analysis showed significantly increased cumulative ox-LDL exposure was elated to poor functional prognosis at 90 days (OR = 9.92, 95% CI, 1.23–79.76, P = 0.031), but not with neurological worsening at discharge (OR = 1.74, 95% CI, 0.46–6.55, P = 0.414). ROC curve revealed that ox-LDL cumulative exposure had higher predictive value (AUC = 0.843, P < 0.001) for the functional prognosis of AIS than cumulative LDL exposure (AUC = 0.629, P = 0.023).
Conclusion
High cumulative ox-LDL exposure is related to the poor prognosis at 3-month of AIS, and its predictive accuracy is better than cumulative LDL exposure.
Curiosity in wild orangutans: ecological, social, and intrinsic effects assessed during a field experiment
Authors: Schuppli Caroline , Nellissen Lara , Carvajal Luz , Ashbury Alison , Oliver-Caldwell Natalie , Rahmaeti Tri , Laumer Isabelle , Haun Daniel
Published: August 2022

The readiness to interact with, and explore, novel stimuli – i.e., curiosity – are cornerstones of innovation. Great apes show the broadest and most complex innovation repertoires. However, little is known about the factors that affect curiosity in wild apes. To shed light on wild apes’ curiosity, we measured the reactions of wild Sumatran orangutans (Pongo abelii) to an experimental apparatus. Compared to adults, immatures showed higher tendencies to visually explore and approach the apparatus but were more likely to show signs of agitation. The presence of conspecifics who approached the apparatus increased exploration and approach tendencies. Prevailing habitat food availability positively affected exploration but had a negative effect on approach tendencies. These findings show that intrinsic, social, and ecological factors affect reactions to novelty in wild orangutans and suggest that exploration, neophobia and neophilia are independently regulated. Therefore, to understand the evolution of innovative tendency, factors acting on different elements of curiosity must be considered.
Design of Double Functionalized Carbon Nanotube for Amphotericin B and Genetic Material Delivery
Authors: Yazdani Sara , Mozaffarian Mehrdad , Pazuki Gholamreza , Hadidi Naghmeh , Gallego Idoia , Puras Gustavo , Pedraz Jose Luis
Published: August 2022

In the present work, single wall carbon nanotubes (SWCNT) were functionalized with phospholipid DSPE-PEG carboxylic acid, and then, with ethylenediamine (EDA), to obtain double functionalized single wall carbon nanotube (DFSWCNT). We applied DFSWCNT as a carrier for delivering amphotericin B (Amb) and EGFP plasmid. FSWCNT’s concentration obtained via UV-visible analysis was 0.99 mg/mL. The TGA analysis results provided the lost weights of DSPE-PEG-COOH, EDA, Amb and SWCNT impurities. XPS results showed that carbon atoms’ percentage decreased during the functionalization process from 97.2% (SWCNT) to 76.4% (FSWCNT) and 69.9% (DFSWNCT). Additionally, the oxygen atoms’ percentage increased from 2.3% (SWCNT) to 21% and 22.5% for FSWCNT and DFSWCNT, respectively. New bonds such as C-N and N-C = O appeared in the synthesized nanocarrier. The IG/ID ratio in Raman analysis decrease from 7.15 (SWCNT) to 4.08 (FSWCNT). The amount of Amb released to phosphate buffer saline medium was about 33% at pH = 5.5 and 75% at pH = 7.4 after 48 h. CCK8 results confirmed that the toxicity of functionalized SWCNT decreased. In a 2:1 ratio of DFSWCNT/EGFP plasmid, the cell viability (87%) and live transfected cells (56%) were at their maximum values. processes indicate that carbon nanotubes have the potential to be applied as both drug/gene delivery systems with outstanding properties such as high loading capacity and easy penetration to the cell membrane.
Ecogeographic patterns of macrophyte metacommunities in the Hengduan Mountain Region
Authors: Fu Hui , Guo Jingjing , Ge Yili , Wu Aiping , Li Wei , Liu Huanyao , Yuan Guixiang , Jeppesen Erik
Published: August 2022

Biological communities exhibit multiple distribution patterns at metacommunity scale and assessing the major drivers of these patterns is a key issue in community ecology. Here we aimed to investigate how the environmental and geographic gradients shape the distribution patterns of macrophytes at metacommunity level.We applied the framework of the elements of metacommunity structure (EMS) to identify the distinct types of 48 macrophyte metacommunities in the Hengduan Mountain Region (HDMR) of China. Then we used generalized linear model and model selection approaches to determine which variables contributed to the variations of EMS, and linear discriminant function analysis to evaluate how well the tested variables in predicting the metacommunity patterns.We found wide variations of the three elements of metacommunity structure (i.e., coherence, range turnover, and range boundary clumping). Latitude and alpha diversity were most important in determining coherence, nestedness followed by spatial extent was mostly related to turnover, while sampling depth was significantly associated with boundary clumping. Seven metacommunity types were identified in HDMR and most metacommunities fitted best the Gleasonian (continuous community boundaries) and Clementsian (discrete community boundaries) patterns as well as their quasi-structures. These metacommunity types were best discriminated by nestedness, altitude, and latitude. Our results provide strong evidences of the impact of geographic patterns on macrophyte metacommunities, with the Gleasonian patterns being dominant at the two ends of latitude/altitude gradients and the Clementsian patterns being common in the middle of the gradients.
In Silico Deterministic Assessment on TdP Risks of Drug-drug Interactions under CiPA Paradigm
Authors: Qauli Ali Ikhsanul , Marcellinus Aroli , Setiawan Muhammad Aldo , Zain Andi Faiz Naufal , Pinandito Azka Muhammad , Lim Ki Moo
Published: August 2022

Researchers have recently proposed the Comprehensive In-vitro Proarrhythmia Assay (CiPA) to analyze medicines’ TdP risks. Using the TdP metric known as qNet, numerous single-drug effects have been studied to classify the medications as low, intermediate, and high-risk. Furthermore, multiple medication therapies are recognized as a potential method for curing patients, mainly when a limited number of drugs are available. This work expands the TdP risk assessment of drugs by introducing a CiPA-based in silico analysis of the TdP risk of combined drugs. The cardiac cell model was simulated using the population of models approach incorporating drug-drug interactions (DDIs) models for various two-drug combinations. Action potential duration (APD90), qNet, and calcium duration (CaD90) were computed and analyzed as features. The drug combination maps were also utilized to illustrate the impact of DDIs on the TdP risk of combined medicines. We found that the DDIs of the combined drugs alter cell responses in terms of biomarkers such as APD90, qNet, and CaD90 in a highly nonlinear manner. The results also revealed that combinations of high-risk with low-risk and intermediate-risk with low-risk drugs could result in compounds with varying TdP risks depending on the drug concentrations.
Detailed statistical analysis plan for a randomised controlled trial of the effects of a modified muscle sparing posterior technique (SPAIRE) in hip hemiarthroplasty for displaced intracapsular fractures on post-operative function compared to a standard lateral approach: HemiSPAIRE
Authors: Ball Susan , McAndrew Amy , Aylward Alex , Cockcroft Emma , Gordon Elizabeth , Kerridge Alison , Morgan-Trimmer Sarah , Powell Roy , Rhodes Shelley , Timperley Andrew John , Wickins Robert , Charity John
Published: August 2022

Background: The HemiSPAIRE trial is being conducted to determine whether a modified muscle sparing technique (SPAIRE - “Save Piriformis and Internus, Repairing Externus”) in hip hemiarthroplasty brings clinical benefits compared to the standard lateral technique in adults aged 60 years or older, with a displaced intracapsular hip fracture. This article describes the detailed statistical analysis plan for the trial.Methods and design: HemiSPAIRE is a definitive, pragmatic, superiority, multicentre, randomised controlled trial (with internal pilot) with two parallel groups. Participants, ward staff and all research staff involved in post-operative assessments are blinded to allocation. This article describes in detail (1) the primary and secondary outcomes, (2) the statistical analysis principles, including: a survivor average causal effect (SACE) method chosen specifically to address the issue of potential bias from differential survival between trial arms, which was seen from data review by the Trial Steering Committee; the participants that will be included in each analysis; the covariates that will be included in each analysis, and how the results will be presented, (3) planned main analysis of the primary outcome; (4) planned analyses of the secondary outcomes, (5) planned additional analyses of the primary and secondary outcomes.Trial registration: ClinicalTrials.gov NCT04095611. Registered on 19 September 2019.
Phase singularities of tightly focused high-order axially symmetric polarized beams in the focal region
Authors: Zhou Zhehai
Published: August 2022

Phase singularities of tight focused high-order axially symmetric polarized beams are studied theoretically based on vector diffraction theory. The phase distributions of focused fields are analyzed based on the mathematical expressions of focused fields which are derived using Richards & Wolf diffraction theory, and the numerical simulation results are presented further for beams with different polarization orders. We find that the phase singularities of the tightly focused fields are related with several parameters, such as numerical-aperture of objective lens, polarization order of incident beams, pupil filling factor and so on, which means the phase distributions including singularities properties of the focused fields can be modulated by changing these parameters, and provide some unique applications in optical trapping, microscopy and near-field optics.
Science governs the future of the mesopelagic zone
Authors: Schadeberg Amanda , Kraan Marloes , Groeneveld Rolf , Trilling Damian , Bush Simon
Published: August 2022

Scientists have studied the open ocean’s mesopelagic zone, extending from 200m-1000m depth, for more than 70 years. As renewed interest in this global ecosystem grows, divergent proposals and knowledge claims are being made on its current and future role in supporting human life. We use automated content analysis to identify 13 latent topics about the mesopelagic zone from 2,226 scientific abstracts and 4,066 tweets. Two dominant ideas emerge: (1) the exploitation of fish resources and (2) the potential of the mesopelagic zone as a carbon sink. We find that, in the absence of national or international governing institutions, science plays ade factogoverning role by shaping how the ecosystem is known to the public and policymakers alike. These results indicate the need for new knowledge and governance arrangements that can broaden the range of meanings and knowledge needed to anticipate future uses of deeply uncertain ecosystems and resources.
The Construction of a Novel Ferroptosis-Related LncRNA Model to Predict Prognosis in Colorectal Cancer Patients
Authors: Chen Weihong , Deng Jianzhi , Zhou Yuehan
Published: August 2022

Colorectal cancer (CRC) is the most common gastrointestinal tumor with poor prognosis. Ferroptosis is a pivotal form of programmed iron-dependent cell death different from autophagy and apoptosis, and long non-coding RNA (lncRNA) can influence the prognosis of CRC via regulating ferroptosis. Nowadays, artificial intelligence (AI) driven solutions, especially machine learning (ML) methodologies, are becoming effective tools in increasing the likelihood of the development of new prognostic and predictive biomarkers of diseases. In this study, with ML-associated tools, a prognostic model was constructed and validated by screening ferroptosis-related lncRNAs associated with prognosis based on the transcriptome data and survival data of CRC patients in TCGA database. Regarding the established prognostic models, differences in signaling pathways and immune infiltration, as well as differences in immune function, immune checkpoints, and m6A-related genes were also analyzed. We obtained a total of 6 ferroptosis-related lncRNAs, and found that the prognostic model could accurately predict the prognosis of CRC patients. Significant differences were found in multiple signaling pathways, as well as immune infiltration, immune function, immune checkpoints, and m6A-related genes between high and low risk groups. Our study provides an efficient prediction tool for CRC patients and contributes to guide the personalized treatment.
Compositional time-use and psychosocial health in young children: a longitudinal study
Authors: Taylor Rachael W , Haszard Jillian J , Meredith-Jones Kim A , Azeem Anita A , Galland Barbara C , Heath Anne-Louise M , Taylor Barry J , Healey Dione
Published: August 2022

BackgroundGood quality sleep, regular physical activity, and limited time spent sedentary are all considered individually important in promoting good mental health in children. However, few studies have examined the influence of each behaviour simultaneously, using compositional analysis which accounts for the closed nature of the 24-hour day. Our aim was to determine how compositional time use in early childhood is related to mental and psychosocial health at five years of age.Methods392 children wore Actical accelerometers 24-hours a day for one week at 2, 3.5 and 5 years of age to examine time in sleep, physical activity, and sedentary behaviour. Psychosocial and mental health were assessed at age 5 using both laboratory based (researcher-assessed) and questionnaire (parental-report) measures. Associations were estimated using regression models with isometric log-ratios of time-use components as predictors.ResultsCross-sectionally, 5-year old children who spent 10% (64 minutes) more time asleep than average had better inhibitory control (standardised mean difference; 95% CI: 0.19; 0.02, 0.36 for Statue test and 0.16; -0.01, 0.33 for Heads, Toes, Knees, Shoulders task). A greater proportion of time spent active (10%, 31 minutes) was associated with poorer inhibitory control (Statue: -0.07; -0.13, -0.02, Head, Toes, Knees, Shoulders task: -0.06; -0.11, -0.01). By contrast, differences in time-use were not meaningfully associated with any measure of self-regulation or mental health at 5 years of age, nor were any significant longitudinal relationships apparent.Conclusions24-hour time use in the preschool years was not significantly associated with any measure of psychosocial or mental health at 5 years of age, although some relationships with inhibitory control were observed cross-sectionally.Trial registration: ClinicalTrials.gov number NCT00892983
An analytical model of grinding force for ultrasonic processing of Cf/SiC composites
Authors: Zhang Menghua , Pang Zixuan , Xia Ziwen , Jia Yunxiang , Shan Chenwei , Luo Ming
Published: August 2022

Ultrasonic-assisted machining of silicon carbide (SiC) ceramic matrix composites (CMCs) has the ability to decrease grinding force and improve processing quality. The machining process often produces large cutting forces that cause defects, such as delamination and burrs, due to the brittleness and high hardness of the material. Therefore, it is significant to precisely simulate the grinding force. In published literature, the modelling of cutting force has been investigated based on brittle removal assumption. However, a ductile flow phenomenon exists simultaneously during the micro-grinding of CMCs. Hence, in this paper, we present an analytical model of grinding force with the consideration of ductile-brittle transition. Additionally, the critical cutting depth for removal mode transition can be applied to distinguish the ductile and brittle fracture removal processes. The establishment of the analytical model was on the basis of the research of single abrasive grain, including motion trajectory, micromechanical analysis, cutting time, and removal volume in ductile and brittle fracture processes during one cutting cycle. Thereafter, the final model was proposed with respect to the quantity of active abrasive grains in the cutting area. The trend of the experiment results was in good agreement with the predicted values of the analytical model.
Impact Driven Cavitation Bubble Dynamics
Authors: Bao Hengzhu , Reuter Fabian , Zhang Hongchao , Lu Jian , Ohl Claus-Dieter
Published: August 2022

The dynamics of a single cavitation bubble exposed to a transient acceleration is studied experimentally. A single cavitation bubble is seeded with a pulsed laser in a free falling and impacting water-filled test tube. After impact, a pressure wave containing compression and rarefaction phases is generated and interacts with the bubble. The bubble dynamics is studied with high-speed imaging and compared to numerical simulations using the Keller-Miksis model. The timing of bubble seeding with respect to the pressure wave is varied and a regime of enhanced collapse strength is found.
Comparative Evaluation of Machine Learning Methods for the Detection of the Eccentricity Faults of Induction Motors by Using Vibration Signals
Authors: Irgat Eyüp , Unsal Abdurrahman
Published: August 2022

One of the most critical tasks to ensure continuous operation in most industrial applications is electric machines' fault and condition monitoring. Induction motors are widely used electrical machines. They are more prone to eccentricity faults due to the short air-gap length. Recently, machine learning techniques have been developed to diagnose the faults of induction motors. This study presents an experimental comparison of the performance of four commonly used machine learning techniques in detecting eccentricity faults of induction motors. The detection of the eccentricity faults is conducted by using vibration signals. The three-axis vibration signals were collected for two cases, healthy and faulty, under different loading levels of a three-phase, 3-kW, two-pole induction motor. The performance of each machine learning method in detecting eccentricity was tested with the vibration signals and compared with each other. The purpose of the study is to assess the performance of each machine learning method and find the most effective features. The results show that rms and p2p features of the vibration signals provide the highest accuracy rates in all four ML methods.
Reconstruction of Incomplete X-Ray Diffraction Pole Figures Using Deep Learning
Authors: Meier David , Ragunathan Rishan , Degener Sebastian , Liehr Alexander , Vollmer Malte , Niendorf Thomas , Sick Bernhard
Published: August 2022

X-ray diffraction crystallography allows non-destructive examination of crystal structures. Furthermore, it has low requirements regarding the surface preparation, especially compared to electron backscatter diffraction. However, up to now, X-ray diffraction is highly time-consuming in standard laboratory conditions since we have to record intensities on multiple lattice planes by rotating and tilting the sample. In this article, we propose a method based on deep learning that allows faster experimentation due to accurate reconstructions of pole figure regions, which we did not probe experimentally. To speed up the development of our proposed method and further machine learning algorithms, we introduce a GPU-based simulation for data generation. Furthermore, we present a pole widths standardization technique using a custom deep learning architecture that makes algorithms more robust against influences from the experiment setup and material.
The Effects of Different Conditioning Contraction Protocols of Post-activation Potentiation on Variables of Eccentric Phases and Concentric Phase of Countermovement Jump
Authors: Živanović Vladimir
Published: August 2022

Purpose Investigation of the influence of different conditioning contraction protocols on the eccentric variables: depth of descent of body centre of mass (CMJ) and capacity of muscle force, power, and velocity (CMJ), i.e., height of jump. Methods In a sample of 28-students (age: pretest 19.5 ± 1.0; posttest 19.7 ± 1.1), 1 RM was determined by estimating 10 RM, to be stratified in a six-week workout: static-hold back squat at 120°, dynamic-back squat at 120° (x8), combined-2 back squat at 120° and 2 seconds endurance (x2) [for 12 seconds], and control group-6 to 8 hours of activity per week. After the pre-contractions, they continuously performed shock-plyometrics (50 cm box), triple jump and 5-meter sprint. Training load was 80% 1 RM. Results A statistically significant increase (13.3%) was found in variable of power unlike variable (CMJ) V ecc and static i.e., dynamic groups where significant differences between pretest and posttest performance from 12.9 and 5.9% were found. Concentric variable (CMJ) H exhibits significance for ED and EC groups (6.8, 8.9%, p ≤ 0.05). Conclusion The most indicated increases (CMJ) H, by practicing contrast sessions i.e., conditioning contraction (CC) or post-activation potentiation, were observed after the application of combined i.e., dynamic conditioning contractions, referring to sublimated eccentric manifestation and concentric muscular effect.
Effect of autofluorescence monitoring on postoperative permanent hypoparathyroidism after total thyroidectomy
Authors: Tzikos Georgios , Moysidis Moysis , Pliakos Ioannis , Bakkar Sohail , Giannoulis Kleanthis , Papaioannou Maria , Michalopoulos Antonios , Papavramidis Theodosios
Published: August 2022

Purpose: Post-operative hypoparathyroidism (POHP), permanent or temporary, is the commonest complication of thyroidectomy. To avoid hypoparathyroidism after thyroidectomy a few centers including ours have explored the use of parathyroid autofluorescent properties intra-operatively (AFI). The present supplementary study aimed to determine the rates of permanent POHP in patients undergoing total thyroidectomy (TT) 12 months after surgery and whether the introduction of AFI resulted in the reduction of its incidence. Methods: This was a supplementary prospective observational single-center study including the patients presenting postoperative temporary hypoparathyroidism after having undergone a scheduled TT and been randomly allocated into: (i) patients operated without near-infrared imaging (non-NIR group) and (ii) patients operated with near-infrared imaging (NIR group). These patients were re-evaluated, regarding albumin, 25-hydroxy-vitamin D, serum calcium, phosphorus, and PTH 12 months postoperatively.Results: In the NIR group were significantly fewer patients experiencing permanent POHP compared to the non-NIR group (0.00% versus 9.09%, p<0.001). Consequently, the level of PTH and serum total calcium were significantly lower in the non-NIR group 12 months after TT (p<0.001 and p=0.033 respectively).Conclusion: The ability of AFI to demonstrate parathyroid glands with high accuracy during TT decreases significantly the incidence of permanent POHP resulting in better outcomes after thyroid surgery.
Etiology And Perinatal Outcomes Between Early And Late-Onset Non-Immune Hydrops Fetalis
Authors: Ergani Seval Yılmaz , İban Müjde Can , Çakır Ayberk , Örgül Gökcen , Tonyalı Nazan Vanlı , Çelik Özge Yücel , Şahin Dilek
Published: August 2022

Purpose We aimed to compare the etiology, and perinatal outcomes of non-immune hydrops fetalis (NIHF) diagnosed early and late-onset at our hospital.Methods The records of the patients who applied to our department were reviewed, and we reached 42 NIHF cases retrospectively and examined the medical records. Hydrops diagnosis week, birth week, accompanying anomalies, and we compared perinatal outcomes as <=12 weeks (early-onset) and >12 weeks (late-onset).Results The median diagnosis week for hydrops was 18 weeks. A statistically significant difference was found between the distribution of birth week according to the diagnosis week (p=0.029). 66.7% of those diagnosed before 12 weeks and 23.3% of those diagnosed after 12 weeks gave birth before 24 weeks.Conclusions In this study, most fetuses diagnosed with early-onset NIHF were born in the first 24 weeks. In addition, it was observed that live birth rates were higher in the late-onset NIHF.
Postoperative radiotherapy for supraglottic cancer on real- word data: Can we reduce dose to lymph node levels?
Authors: Xu Yi , Wei Yumei , Wang Jingbo , Zhang Jianghu , Chen Xuesong , Wu Runye , Liu Qingfeng , Qu Yuan , Wang Kai , Huang Xiaodong , Luo Jingwei , Xu Wei , Zhang Ye , Yi Junlin
Published: August 2022

Purpose: To evaluate prognosis for reducing postoperative radiotherapy (PORT) dose to lymph node levels of supraglottic cancer (SC) on real-word data.Method and materials: Patients were derived from two cancer centers. In center 1, the involved nodal levels (high-risk levels, HRL) and the next level received a dose of 60.06Gy/1.82Gy per fraction, while the other uninvolved levels (low-risk levels, LRL) received 50.96Gy/1.82Gy per fraction. In center 2, all received 50Gy/2Gy per fraction. The rates of high-risk levels control (HRC), regional control (RC), overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated by Kaplan-Meier method. Result: Totally, 124 patients were included (62 in center 1, 62 in center 2). Most patients (106, 85.5%) had a stage T3/N+ tumor. The median follow-up was 45 months (range 1-163 months). There were no significant differences in terms of OS (p=0.126), RC (p=0.514), PFS (p=0.195) and DMFS (p=0.834). Most regional recurrences (4, 80%) occurred within three years of treatment, and all occurred within the target volumes. No regional failure occurred in HRL in center 1, while three (3/4) failures occurred in center 2. Dose reduction prescription to HRL led to a lower HRC rate (100% vs. 90.6%, p=0.009). While the rates of LRL control (98.4%) were equal between the two centers.Conclusion: Compared with a standard dose, the reduced dose to involved nodal levels showed inferior regional control for PORT, while uninvolved nodal levels showed equal outcomes. A dose of 50Gy for HRL may be an unfavorable treatment option for SC.
Identification of pivotal genes with prognostic evaluation value in lung adenocarcinoma by bioinformatics analysis
Authors: Wang Yushan , Zhao Yanhui , Wang Yizhen , Ma Cuiping , Gu Yuchao , Peng Xiufa , Zhang Chunling , Wang Ye
Published: August 2022

Lung cancer remains the leading cause of cancer morbidity and mortality worldwide, and over diagnosis causes various unnecessary losses in patients' lives and health. How to more effectively screen lung cancer patients and their potential prognostic risk become the focus of our current study. By analyzing the LUAD expression profile in The Cancer Genome Atlas (TCGA), we constructed a weighted gene co-expression network using differentially expressed genes (DEGs) to find the key modules and pivotal genes. A COX proportional risk regression model based on the least absolute shrinkage and selection operator (LASSO) was used to assess the predictive value of the model for the prognosis of LUAD patients. A total of 4107 up-regulated DEGs and 2022 down-regulated DEGs were identified in this study, and enrichment analysis showed that these analyzes were associated with the extracellular matrix of cells and adhesion. Ten gene markers consisting of LDHA, TOP2A, UBE2C, TYMS, TRIP13, EXO1, TTK, TPX2, ZWINT, and UHRF1 were established by extracting the central genes in the key modules, and the upregulation of these genes was accompanied by an increased prognostic risk of patients. Among them, high expression of LDHA, TRIP13, TTK in LUAD was associated with shorter overall survival and could be used as independent prognostic factors to participate in metabolic processes such as tumor NAD. The present study provides a powerful molecular target for the study of LUAD prognosis and provides a theoretical basis for the diagnosis and treatment of LUAD and the development of targeted inhibitors.