bluuebunny/crossref_metadata_2025 huggingface dataset:
THE ROLE OF SURFICIAL BIOTURBATION IN THE LATEST EDIACARAN: A QUANTITATIVE ANALYSIS OF TRACE FOSSIL INTENSITY IN THE TERMINAL EDIACARAN–LOWER CAMBRIAN OF CALIFORNIA
Authors: O'NEIL GRETCHEN R. , TACKETT LYDIA S. , MEYER MICHAEL B.
Published: December 2022

Bioturbating activities have played a vital role in shaping the marine ecosystem throughout metazoan history, influencing the abundance and preservation potential of body fossil-producing taxa and driving major environmental and geochemical changes. The earliest trace making behaviors arose during the late Ediacaran Period (∼ 560–541 Ma), disrupting the substrate previously occupied by dominantly sessile organisms. Simple dwelling and grazing behaviors exploited the organic-rich matgrounds, expanding into the underutilized microbial mat ecosystem. In the western United States, trace assemblages from Ediacaran–Cambrian boundary-spanning deposits document a thriving trace-maker ecosystem. One boundary-spanning deposit in this region, the lower member of the Wood Canyon Formation, crops out along the California-Nevada boundary and contains both trace and body fossil assemblages. The Chicago Pass section of the lower Wood Canyon Formation contains a suite of dominantly simple Ediacaran traces, which become commonplace in the upper part of the stratigraphic section, documenting the onset of prevalent trace-making behaviors in this region. While traces have been previously described from this locality, the addition of the complex trace Lamonte trevallis and quantification of trace fossil density of simple Ediacaran traces provides a more comprehensive ichnological view of the Chicago Pass section. Although Chicago Pass does not yield abundant tubicolous body fossils, as are found elsewhere in the region, the low diversity ichnoassemblages document both burgeoning surficial trace making groups and mat-targeted mining in the latest Ediacaran. The behaviors present at Chicago Pass are similar to those of the Dengying Formation in South China, and highlight the need for petrographic-based trace fossil studies. Additionally, studies of Nama Group trace fossils of the same age from Namibia report higher diversity and complexity in trace-making activities than what has been observed at Chicago Pass, but with similar, low Ediacara biota body fossil diversity. If Ediacara biota diversity is anticorrelated with trace-making behaviors, Chicago Pass represents a low-complexity end-member of the same phenomenon observed in Namibia. The effect of surface sediment disruption on the sessile Ediacaran communities may have been decoupled from complexity of the traces, more so influenced by the presence of general trace-making behaviors in aggregate, including simple traces.
GRAIN-SIZE CONTROLS ON THE SILURO-DEVONIAN COLONIZATION OF NON-MARINE SUBSTRATES BY INFAUNAL INVERTEBRATES
Authors: SHILLITO ANTHONY P. , DAVIES NEIL S.
Published: December 2022

Throughout the history of life on Earth, sedimentary environments have placed controls on the trajectory of evolutionary innovations. To survive and thrive in newly colonized sedimentary environments, organisms have needed to develop novel behaviors: often evidenced in the rock record as architectural innovation and diversification in trace fossil morphology. This study focuses on ichnological diversification as a response to challenges presented by different sediment grain sizes during the late Silurian to Early Devonian colonization of the continents by invertebrate life. The ichnodiversity and ichnodisparity from this interval reveal details of the biological response to newly adopted sedimentary and environmental conditions.

Characteristics of ichnofaunas from terrestrial and emergent settings are compared across the Silurian-Devonian boundary, within both sand and mud dominated successions, to identify differences associated with different substrate compositions. Two trends are revealed: 1) Successions dominated by mudrock contain a lower ichnodiversity than sandstone-dominated successions of similar age, potentially due to the different challenges associated with burrowing in cohesive versus non-cohesive media. Alternatively, this could be due to preference of the tracemakers for the broader environmental conditions that lead to sand or mud deposition. 2) The maximum size of trace fossils within a given formation is larger in sandstone dominated strata than in mudrock dominated strata. Together, these suggest that the availability of substrates with different grain sizes was one factor determining the constitution of early animal communities and behavioral styles during the colonization of the continents.
Lithology of the Upper Triassic Sedimentary Rocks of Chukotka and Wrangel Island and Their Relationship with Coeval Rocks of the Eastern Arctic
Authors: Tuchkova M.I. , Sokolov S.D. , Moiseev A.V. , Verzhbitskii V.E. , Kostyleva V.V. , Vatrushkina E.V.
Published: December 2022

—The correlation between the sedimentologic characteristics of the Upper Triassic deposits of Wrangel Island and the Chukchi Peninsula (Chukotka) is discussed. These deposits are similar in isotopic, petrographic, and geochemical features. It has been established that the Upper Triassic sand strata accumulated at different sites of a single sedimentary basin, in shallow-water prodeltas of Wrangel Island and in deeper-water environments of Chukotka. In the latest Triassic, the portion of the sand component in the sections increased. At the same time, the average size of the sand grains decreased, which indicates weakening of the tectonic factor in some zones of the provenance and its general peneplanation with the formation of a weathering crust. The eroded complexes are composed of granitoid, metamorphic, and metavolcanic rocks. They stayed on land for a long time, being subjected to chemical weathering. The depth intervals with the large amount of sandy material in the section of Wrangel Island and Chukotka are correlated with those in the sections of the Sverdrup Basin and the northern slope of Alaska.
Increasingly unfit new parkrunners and a narrowing gender gap in attendance suggest parkrun is becoming more inclusive
Authors: Gilburn Andre S.
Published: December 2022

Background: parkrun is a weekly mass participation event that encourages people to exercise. All finishes are recorded with the parkrun results database likely to contain a wealth of potentially important public health information on the fitness benefits from attending and the participation patterns of different groups. The aim was to conduct the first quantitative assessment of performance and attendance of participants at parkrun using general linear mixed models to identify characteristics of events that might help overcome barriers to participation and to identify if there are changing patterns in the demographics of parkrun participants.
Study design: The study conducted linear and binomial mixed models of age-graded performance, gender ratio and age of participants at every parkrun event held in Scotland. Predictor variables included age, gender, parkrun ID number, number of runs, date of event, elevation gain, surface type and travelling time to the next nearest parkrun event venue.
Results: There was a decline in the mean performance of participants at events, however individual performances showed a trend towards improvement. The gender ratio shows higher male participation although the gender gap is narrowing. Events in the most remote parts of Scotland had the lowest age graded performance scores and the highest proportion of female participants with more females than males attending the remotest events. Events on slower surfaces had a higher proportion of female participants.
Conclusion: This study reports that parkrun events are becoming more inclusive with new participants increasingly being poor performing and female. In remoter parts of Scotland more females participate in parkrun than males revealing parkrun has seemingly overcome traditional barriers to female participation in sport. Events with slower surfaces had more female participants. Prioritising the creation of events at more remote locations and on slower surfaces could increase inclusivity and widen participation further. These findings could also help general practitioners prescribe those events that are most likely to benefit new participants making the parkrun practice initiative more effective. For example, women might be encouraged to attend traditionally slower events than men. It is concluded that parkrun is not only a highly successful public health initiative but it is also increasing its attractiveness to those who would benefit most from physical activity.
The Cu/Nb ratio influencing microstructure, mechanical and electrical properties in as-cast Al3CuxNb alloys.
Authors: Mendes Gabriel , Azevedo Hugo , Dillon Thiago , Rodrigues Helder , Hoffmann Evaldo , Rocha Otávio
Published: December 2022

In this work, solidification experiments were performed with Al-3CuxNb alloys (x = 0.5, 3 and 5wt.%). The role of the Cu/Nb ratio was investigated on thermal parameters such as growth and cooling rates (VL and TR), structure, microhardness (HV) and electrical properties such as electrical resistance, resistivity and conductivity (R, ρ, and σ, respectively). A columnar to equiaxed grain transition (CET) was observed for lower Cu/Nb ratios. The typical solidification microstructure was quantified by means of secondary dendritic spacings (λ2). It was observed that the decrease of the Cu/Nb ratio with the increase of the Nb content increased the HV, R, and ρ values, but the σ values decreased. It was deduced that the harder particles of the Al3Nb and Al2Cu intermetallic phases contributed to the increase of HV, while the Al3Nb phase influenced the decrease of electrical conductivity with the increase of Nb content.
X-photon laser direct write 3D nanolithography
Authors: Skliutas Edvinas , Samsonas Danielius , Čiburys Arūnas , Kontenis Lukas , Gailevičius Darius , Berzinš Jonas , Narbutis Donatas , Jukna Vytautas , Vengris Mikas , Juodkazis Saulius , Malinauskas Mangirdas
Published: December 2022

Polymerized voxels by focusing ultrashort pulses varying wavelength over three-octaves wide range for femtosecond laser direct write 3D nanoprinting are studied. A possibility to use any color of spectrum from 500-nm-to-1200-nm with a controlled pulse width of 100-fs reveals a delicate interplay of photo-physica mechanisms more than just two-photon absorption inducing localized photo-polymerization. None of the applied exposure conditions ensured signicantly higher spatial definition than 200-nm in width using SZ2080TM photosensitized and pure materials, yet it allowed tuning the voxel aspect ratio and greatly influenced dynamic fabrication window determined by the resolution bridges method. An efective order of absorption, i.e., the nef -photon process of absorption, and exposure per pulse (energy, fluence, intensity) was assessed for ultra-short pulses varying wavelengths as it has the paramount influence on the established multi-photon polymerization (MPP) process. Here an evolution of the polymerized volume via different energy delivery mechanisms: one-/two-/three-photon absorption, avalanche ionization, and thermal diffusion leading to controlled photo-polymerization are revealed. The results can be used to tailor polymerized volume for increasing the 3D nano-printing performance. A non-trivial energy deposition by X-photon absorption was observed with an onset of a strong lateral size increase at the higher pulse energy at longer wavelengths and can be understood as due to reaching epsilon-near-zero conditions. Findings are valuable for developing MPP technology to reduce the footprint size and increase its efficiency. Understanding mechanisms and appearance of λ-tunable commercial lasers are benefiting broad applications in advanced optical additive manufacturing areas of micro-optics, nano-photonic devices, meta-materials, and integrated-chips, and tissue engineering.
Charectarization of Groundwater Level Zones Using Innovative Trend & Regression Analysis: Case Study at Rechna Doab-pakistan
Authors: Abbas Muhammad , Arshad Muhammad , Shahid Muhammad Adnan
Published: December 2022

The authors have requested that this preprint be removed from Research Square.
Trade in global value chains as a driver for economic growth in ECOWAS: The complementary role of regional trade agreement Review of World Economics
Authors: Mamba Essotanam
Published: December 2022

The research analyzes the effects of global value chains (GVCs) on economic growth in the Economic Community of West African States (ECOWAS) during 1990–2020 by highlighting the complementarity role of the regional trade agreement (RTA). Unlike previous studies at the ECOWAS level, this research focuses on the specific aspect of trade in GVCs. This research also investigates the complementary role of RTA and uses a continuous index of RTA rather than dummy variables which are often employed. To control for the endogeneity issue, the research applies the instrumental variables approach. The findings indicate the positive effect of GVCs on growth but the effect of forward GVC participation is greater than that of backward GVCs. They also show the differentiated effects of agricultural, manufacturing, and services GVCs. Finally, the findings reveal that the effect of GVCs on growth increases with RTA. These findings have important policy implications.
JEL Classification: E61, F1, O47
Appropriateness of Computed Tomography Scan in Mild Traumatic Head Injury Among Adult Patients in Mulago National Referral Hospital, Uganda: a Cross-sectional Hospital Based Study
Authors: Babirye Deborah , Kisembo Harriet , Muyinda Zeridah , Sekabunga Juliet Nalwanga , Jonathan Walubembe , Miriam Nakku , Mubuuke Aloysius Gonzaga
Published: December 2022

Background
Computed Tomographic (CT) scanning of the head can detect acute intracranial injury and help to identify patients requiring neurosurgical intervention. The inappropriate utilization of CT scan strains meagre imaging resources especially in resource-constrained settings and risks the patients to unnecessary radiation. The Canadian CT head rule (CCHR) is a validated clinical tool used to predict mild head injury patients that will have a clinically significant intracranial injury on head CT scan. This reduces the number of requested CT scans while at the same time ensuring that those who would benefit from it are easily identified. However, this tool has not been previously applied in many low income settings where it would be very useful.
Objective
To determine the appropriateness of head CT scans performed among patients with mild traumatic head injury based on the Canadian CT head rule (CCHR).
Methods
This was a cross sectional study conducted at the emergency department of Mulago Hospital involving 259 adults clinically diagnosed with mild head injury with a head CT scan performed. They were assessed using the CCHR for a prediction of whether a head CT scan was appropriate or inappropriate. The proportion of appropriate head CT scans was obtained. The participants were followed up to assess their health status.
Results
The common abnormal CT scan findings were comminuted and depressed skull fractures. The proportion of appropriate head CT scans performed based on the CCHR was 70.7%. Most participants with positive CT scan findings were classified as appropriate when the CCHR was applied. 81.6% (n = 62) of the participants whose CT scans were classified as inappropriate had normal findings. There was a statistically significant association between categories of CCHR classification (appropriate vs inappropriate) and CT scan findings (normal vs neurologically insignificant).
Conclusion
About one-third of head CT scans performed in this study were inappropriate by applying the CCHR. Avoidance of CT scan in such patients is unlikely to miss any important injuries. Findings from the study can guide the adoption and adaptation of CCHR use in emergency departments.
Prevalence, components and consequences of moral injury: preliminary validation of a new brief measure
Authors: LeClaire Michele , Poplau Sara , Freese Rebecca L. , Porta Carolyn M. , Sullivan Erin , Linzer Mark
Published: December 2022

Aim
The aim of this study was to design and use a parsimonious survey tool to use in real time to assess moral injury and describe how moral injury relates to burnout and intent to leave the job. The Moral Injury Quotient (MIQ) is derived from this 6-item tool.
Findings
The MIQ metric has good performance characteristics and captures a substantiative portion of moral injury. It is related to clinically meaningful changes; each 10-point increase in the MIQ was associated with 125% increased odds of burnout (p < 0.001) and 50% increased odds of intending to leave the job (p < 0.001).
Conclusions
Measuring and addressing moral injury has major workforce implications. This metric is an “off the shelf” tool that may be helpful in busy clinical settings to assess, implement improvements, and reassess for reductions in moral injury.
Differential transcriptome analysis of Dunaliella salina during flagellar assembly
Authors: Zhu Liqiang , Hu Lina , Li Aifang , Li Shuxuan , Li Yalan , Wang Qianqian , Huang Yu , Feng Yanxia , Li Qinghua , Feng Shuying
Published: December 2022

Background
Eukaryotic flagellum is highly conserved in basic structure and biogenesis, and defects in ciliary assembly or function lead to a wide range of human disease symptoms. The alga Dunaliella salina (D. salina), provides an excellent model for investigating flagellar/ciliary system. However, the genomes it carries is unpublished.
Results
In this study, using high-throughput illumina RNA sequencing, the transcriptomes from flagella-assembling D. salina were analyzed firstly at an unprecedented depth. About 4 gigabases of raw sequence data were generated and 197,295 unigenes were annotated with gene descriptions, conserved protein domains, or gene ontology terms against public databases. Among the annotated unigenes, 25,412 unigenes were differentially expressed during flagella regeneration, including 9,988 up-regulated unigenes and 15,407 down-regulated unigenes. Moreover, to functionally categorize the D. salina unigenes, the differentially expressed unigenes distributed into the category of biological process, molecular function and cellular component. These transcriptome datasets might reveal the mechanism of flagella assembly in D. salina cells, and serve as a public information platform for D. salina functional genomics and proteomics analysis. Furthermore, the differentially expressed unigenes involved in different signaling pathways of D. salina flagella assembly and human diseases were screened respectively.
Conclusion
These pathway-based results not only provide a further understanding to specific processes of ciliogenesis and ciliopathies, but also offer a cue to mechanism of human diseases.
Flooding in Freetown's urban coastal settlements: a community-based course of action
Authors: Turay Bashiru
Published: December 2022

The Sierra Leone government and its partners have been working hard to find a solution to the devastating flooding in Portee and Rokupa. However, information for understanding community-based actions in flood containment is limited, particularly at the household and organisation levels of coastal slum settlements. Consequently, there is insufficient knowledge to implement projects to change the current condition. In light of these concerns, this paper aims to present current information on this subject using a mixed methodology, with purposive and snowballing sampling techniques, to investigate 204 slum households and 12 community-based organisations. The findings show that word-of-mouth is the primary source of flood information for most household respondents (53%). This method of disseminating flood news is inefficient and indicates the widespread lack of flood information in the study sites. In their situation, a majority (83.2%) of household respondents and community-based organisations (58%) do not get support for flood management. The author recommends the urgent implementation of a people-centred early warning system. Also, future statistical studies are advised to use correlation and other relevant tests to assess the relationships between household characteristics and the potential to take or not take a particular flood management action. Such studies should look into the relative advantages and disadvantages of these actions. A comparative analysis of flood response and management strategies among the country's various coastal slum settlements is also recommended. Further investigation is required into the feasibility, socio-ecological and economic costs, and opportunities for transforming these slum settlements into modern flood-resistant structures.
A ferroptosis-related lncRNAs signature for prognosis prediction and its relationship with immune microenvironment in colon adenocarcinoma
Authors: Xu Zijie , Chen Yi , Yu Yue , Yu Ting , Wang Yiwen , Chen Tao , Zhu Lingjun , Shu Yongqian
Published: December 2022

Objective
The present study aimed to develop a prognostic ferroptosis-related long noncoding RNAs (lncRNAs) signature and to investigate its potential relationship with clinical characteristics and immune microenvironment in patients with colon adenocarcinoma (COAD).
Methods
Clinical information and RNA sequencing data were downloaded from The Cancer Genome Atlas (TCGA) database. Genes associated with ferroptosis were retrieved from the FerrDb database. Pearson’s correlation analysis was performed for the retrieved data, and differentially expressed ferroptosis-related lncRNAs (frlncRNAs) were screened out. A prognostic frlncRNAs signature was established based on the results of univariate Cox regression analysis and the least absolute shrinkage and selection operator algorithm. Survival analysis and receiver operating characteristic curve analysis were conducted to evaluate the prognostic efficacy of this signature. Gene set enrichment analysis (GSEA), somatic mutation analysis, drug sensitivity analysis, and immune analysis were performed. Quantitative real-time PCR was then used to confirm the expression of lncRNAs, and the regulatory functions of the screened lncRNAs LINC01138 and LINC01857 in ferroptosis were assessed.
Results
Eleven frlncRNAs were identified from the databases. A prognostic signature was constructed, and the risk score was calculated. Patients were classified into high-and low-risk groups according to their risk score. The prognostic signature showed a high efficacy for survival prediction, and the risk score was confirmed as an independent prognostic factor. GSEA showed differences between the two groups in terms of specific pathways involved in immune response, cell adhesion, mitochondrial function, and energy metabolism. Moreover, the high- and low-risk groups showed a significant difference in somatic mutation status such as that of TP53 gene. Patients in the high-risk group exhibited lower half-inhibitory concentration (IC50) values for cisplatin, bleomycin, gefitinib, veliparib, rapamycin, AZD8055, MK-2206, and Bay61-3606 and a higher IC50 value for sorafenib. Immune status and response of the patients to immunotherapy were also associated with the risk signature. The experiments also showed that LINC01138 and LINC01857 regulated ferroptosis processes in COAD.
Conclusion
The prognostic signature of frlncRNAs developed in this study facilitate the clinical diagnosis and treatment of patients with COAD and may enable to study the deeper functional mechanisms of frlncRNAs in immune microenvironment in COAD.
A literature review of methods for assessment of reproducibility in science
Authors: Nordling Torbjörn , Peralta Tomas Melo
Published: December 2022

Introduction: In response to the US Congress petition, the National Academies of Sciences, Engineering, and Medicine investigated the status of reproducibility and replicability in science. A piece of work is reproducible if the same results can be obtained while following the methods under the same conditions and using the same data. Unavailable data, missing code, and unclear or incomplete method descriptions are common reasons for failure to reproduce results. Objectives: The motivation behind this review is to investigate the current methods for reproducibility assessment and analyze their strengths and weaknesses so that we can determine where there is room for improvement. Methods: We followed the PRISMA 2020 standard and conducted a literature review to find the current methods to assess the reproducibility of scientific articles. We made use of three databases for our search: Web of Science, Scopus, and Engineering Village. Our criteria to find relevant articles was to look for methods, algorithms, or techniques to evaluate, assess, or predict reproducibility in science. We discarded methods that were specific to a single study, or that could not be adapted to scientific articles in general.
Results: We found ten articles describing methods to evaluate reproducibility, and classified them as either a prediction market, a survey, a machine learning algorithm, or a numerical method. A prediction market requires participants to bet on the reproducibility of a study. The surveys are simple and straightforward, but their performance has not been assessed rigorously. Two types of machine learning methods have been applied: handpicked features and natural language processing.
Conclusion: While the machine learning methods are promising because they can be scaled to reduce time and cost for researchers, none of the models reviewed achieved an accuracy above 75%. Given the prominence of transformer models for state-of-the-art natural language processing (NLP) tasks, we believe a transformer model can achieve better accuracy.
Epigenetics and Familial Hypercholesterolemia: a methylation study on the three canonical genes
Authors: RA Zorzo , VMM Suen , JE Santos , Silva-Jr  , VK Suazo , ALSC Honorato , RD Santos , CE Jannes , Pereira A , JE Krieger , Liberatore-Jr
Published: December 2022

Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein cholesterol (LDL-C) levels and a high risk of early coronary heart disease. Structural alterations in theLDLR,APOB, andPCSK9genes were not found in 20–40% of patients diagnosed using the Dutch Lipid Clinic Network (DCLN) criteria. We hypothesized that methylation in canonical genes could explain the origin of the phenotype in these patients. This study included 62 DNA samples from patients with a clinical diagnosis of FH according to the DCLN criteria, who previously tested negative for structural alterations in the canonical genes, and 47 DNA samples from patients with normal blood lipids (control group). All DNA samples were tested for methylation in the CpG islands of the three genes. The prevalence of FH relative to each gene was determined in both groups and the respective prevalence ratios (PRs) were calculated. The methylation analysis ofAPOBandPCSK9was negative in both groups, showing no relationship between methylation in these genes and the FH phenotype. Asthe LDLRgene has two CpG islands, we analyzed each island separately. The analysis ofLDLR-island1 showed PR = 0.982 (CI 0.33–2.95), also suggesting no relationship between methylation and the FH phenotype. Analysis ofLDLR-island2 showed a PR of 4.12 (CI 1.43–11.88), indicating a possible association between methylation on this island and the FH phenotype.
Optimizing the flash extraction process for total flavonoids from Edgeworthia gardneri (Wall) Meissn and antioxidant activity of the extracts
Authors: Ma Xinyu , Zhang Junwei , Liu Jiahao , Zhang Zhongtao , Liu Lu , Tian Jiahui , Guan Jiayu , Lu Zhao , Chen Huiyu
Published: December 2022

In order to efficiently extract natural medicines, response surface methodology (RSM)were used for the modeling and optimization of flash extraction of total flavonoids to determine the antioxidant activity of the extracts obtained from Edgeworthia gardneri (Wall). For the optimal combination of the comprehensive yield of total flavonoids (Y), the Box-Behnken design (BBD) was used to improve extract voltage (X1), extraction time (X2), ethanol concentration (X3), and liquid-solid ratio (X4). Based on the results of single factor test, the amount of total flavonoids extracted from Edgeworthia gardneri (Wall) Meissn was used as the evaluation index. The Box-Behnken experimental design was used to optimize the flash extraction process and to investigate the antioxidant activity in vitro. The results showed that the optimal extraction conditions were as follows: extraction voltage 150 V, flash extraction time 100 s, ethanol volume fraction 70%, solid-liquid ratio 1:30 mL/g, and total flavonoids extraction amount of 18.91 (mg/g). The total flavonoids of Edgeworthia gardneri (Wall) Meissn had significant scavenging ability against 2,2-diphenyl-1-picrylhydrazyl (DPPH), O2- and OH free radicals, and had good antioxidant activity. Furthermore, the HPLC separation conditions of total flavonoids of Edgeworthia gardneri (Wall) were explored. Under the set HPLC conditions (Hanbon benatach C18 250 mm × 4.6 mm, 5 μm, A: acetonitrile-B: 0.2% formic acid aqueous solution, 0→10→50→65→85 min, 5%→10%→30%→45%→90% A gradient elution, 1 mL/min, 314 nm, Column temperature: 25 ℃), the main components of total flavonoids of Edgeworthia gardneri (Wall) could achieve a good separation, which provide the separation conditions and basis for the identification of total flavonoids from Edgeworthia gardneri (Wall) Meissn.
Effectiveness and Safety of Normoxic Allogenic Umbilical Cord Mesenchymal Stem Cells Administered as Adjunctive Treatment in Patients with Severe COVID-19
Authors: Malueka Rusdy Ghazali , Nurudhin Arief , Purwoko Purwoko , Sumardi Sumardi , Wisaksana Rudi , Adhiputri Artrien , Sudadi Sudadi , Soeroto Arto Yuwono , Sidharta Brigitte Rina Aninda , Thobari Jarir At , Murni Tri Wahyu , Soewondo Widiastuti , Herningtyas Elizabeth Henny , Sudjud Reza Widianto , Trisnawati Ika , Ananda Nur Rahmi , Faried Ahmad , Soetjahjo Bintang
Published: December 2022

Inflammatory response in COVID-19 contributes greatly to disease severity. Mesenchymal Stem Cells (MSCs) have the potential to alleviate inflammation and reduce mortality and length of stay in COVID-19 patients. We investigated the safety and effectiveness of normoxic-allogenic umbilical cord (NA-UC)-MSCs as an adjunctive treatment in severe COVID-19 patients. A double-blind, multicentric, randomized, placebo-controlled trial involving severe COVID-19 patients was performed from January–June 2021 in three major hospitals across Java, Indonesia. Eligible participants (n = 42) were randomly assigned to two groups (1:1), namely the intervention (n = 21) and control (n = 21) groups. Either NA-UC-MSCs or NaCl placebo were administered daily. The primary outcome was the duration of hospitalization. Meanwhile, the secondary outcomes were radiographical progression (Brixia score), respiratory and oxygenation parameters, and inflammatory markers, in addition to the safety profile of NA-UC-MSCs. NA-UC-MSC administration did not affect the length of hospital stay of severe COVID-19 patients, nor did it improve the Brixia score or mMRC dyspnoea scale better than placebo. Nevertheless, NA-UC-MSCs led to a better recuperation in oxygenation index (120.80 ± 72.70 baseline vs 309.63 ± 319.30 D + 22, p = 0.038) and oxygen saturation (97.24 ± 4.10% vs 96.19 ± 3.75% in placebo, p = 0.028). Additionally, compared to the placebo group, the treatment group had a significantly smaller increase in PCT level at D + 22 (1.43 vs. 12.76, p = 0.011). No adverse effects, including serious ones, were recorded until D + 91. NA-UC-MSC therapy is a very safe adjunct for COVID-19 patients. It improves the oxygenation profile and carries potential to suppress inflammation.
The Role of Neutrophil - Lymphocyte ratio and Platelet - Lymphocyte ratio with High Sensitivity C-Reactive Protein level in patients on hemodialysis
Authors: Raji Sara , Rad Fatemeh Javadi , Mottaghi Mahdi , Kazerani Marzieh
Published: December 2022

Background: Hemodialysis (HD) is the most common treatment for chronic kidney insufficiency that can increase inflammation and mortality in these patients. We aimed to compare the relationship of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) with high sensitivity C-reactive protein (hs-CRP) levels in predicting inflammatory conditions in HD patients.
Methods: This cross-sectional study included end-stage renal disease (ESRD) patients on regular HD in the Islamic Republic of Iran. Based on patients’ records, demographic and clinical data, and inflammatory markers, including NLR, PLR, and hs-CRP, were obtained.
Results: One hundred patients were enrolled, of which 46% were female. The mean age was 37.96 ± 10.29, and the mean HD time was 54.32 ± 50 months. The mean hs-CRP levels, NLR, and PLR were 6.08 ± 5.70mg/l, 2.79 ± 1.18, and 125.80 ± 57.14, respectively. Our results showed a statistically significant and direct relationship between PLR and hs-CRP levels (P = 0.01) but no correlation between NLR and hs-CRP levels (P = 0.8). In addition, PLR was correlated inversely with hs-CRP in hypertensive patients (r = -0.283, P = 0.04) and had significant relationships in the female population (r = 0.3, P = 0.04) and time of HD below five years (r = 0.3, P = 0.001).
PLR is a suitable and inexpensive inflammatory marker in HD patients with ESRD, correlating with hs-CRP. Further investigations emphasizing accuracy establishment are mandated to certify its application in clinical workups.
Differences and biocontrol potential of haustorial endophytic fungi from Taxillus Chinensis on different host plants
Authors: Song Li-sha , Huo Juan , Wan Lingyun , Pan Limei , Jiang Ni , Fu Jine , Wei Shugen , He Lili
Published: December 2022

Background
In order to explore the community composition and diversity of the endophytic fungi in Taxillus chinensis, samples of the parasites growing on seven different hosts, Morus alba, Prunus salicina, Phellodendron chinense, Bauhinia purpurea, Dalbergia odorifera, Diospyros kaki and Dimocarpus longan, were isolated. The strains were identified by their morphological characteristics and their internal transcribed spacer (ITS) sequences were analyzed.
Results
150 different endophytic fungi were isolated from the haustorial roots of the seven hosts, and the total isolation rate was 61.24%. These were found to belong to 1 phylum, 2 classes, 7 orders, 9 families, 11 genera and 8 species. Pestalotiopsis, Neopestalotiopsis and Diaporthe were the dominant genera, accounting for 26.67, 17.33 and 31.33% of the total number of strains, respectively. Diversity and similarity analyses showed that the endophytic fungi isolated from D. longan (H'=1.60) had the highest diversity index. The highest richness indexes were found in M. alba and D. odorifera (both 2.23). The evenness index of D. longan was the highest (0.82). The similarity coefficient of D. odorifera was the most similar to D. longan and M. alba (33.33%), while the similarity coefficient of P. chinense was the lowest (7.69%) with M. alba and D. odorifera. Nine strains showed antimicrobial activities. Among them, Pestalotiopsis sp., N. parvum and H. investiens showed significant antifungal activity against three fungal phytopathogens of medicinal plants. At the same time, the crude extracts from the metabolites of the three endophytic fungi had strong inhibitory effect on the three pathogens. Pestalotiopsis sp., N. parvum and H. investiens had the strongest inhibitory effects of S. cucurbitacearum, with inhibitory rates of 100%, 100% and 81.51%, respectively. Secondly, N. parvum had a strong inhibitory effect on D. glomerata and C. cassicola, with inhibitory rates of 82.35% and 72.80%, respectively.
Conclusions
These results indicate that the species composition and diversity of endophytic fungi in the branches of T. chinensis were varied in the different hosts and showed good antimicrobial potential in the control of plant pathogens.
WITHDRAWN: Prediction of fruit quality parameters using peel color in Citrus Reticulata L. fruit by multiple linear regression and artificial neural network approach
Authors: Ghanghas Sachin , Singh Vijay Kumar , Kumar Sunil , Kumar Nitin , Garg Mukesh Kumar
Published: December 2022

Kinnow mandarin fruit color changes from deep green to completely orange during the period of peak maturity, which indicates if the fruit should be harvested. On the basis of the peel color, fifteen fruits were being selected for harvest, and their colors were measured with the chromameter which measures color in CIE-Lab color space. Green to Orange color fruits were divided into five regions (Green, Green-Yellow, Yellow, Yellow-Orange, Orange). The fruit samples in triplicate were used for all the laboratory analysis. The effects of color parameters i.e. L-value, a-value and b-value in different color regions on chemical parameters i.e. total soluble solids (TSS), titratable acidity (TA), fruit juice content (Juice %), maturity index (MI), ascorbic acid content (AA) and pH value of the fruit were studied using descriptive and correlation analysis. The model approaches i.e. multiple linear regression (MLR) and artificial neural network (multi-layer perceptron) (MLP-ANN) were implemented on the fruit sample data to predict the important fruit quality parameters which were prominent in determining the fruit color. The predicted data was plotted against the actual data using boxplot and scatter plot for both the models, the linearly best fitted and statistical significance was determined using R2, RMSE. Green and Green-Yellow colored region fruits have high in titratable acidity, ascorbic acid content and lower soluble sugars, maturity index and pH value. There was a steeper transition visible in TSS, juice content, maturity index, AA and pH value for the color shift from Yellow region to Yellow-Orange region. The better and optimal predictions were made with MLP-ANN for total soluble solids, titratable acidity and fruit juice content. The ANN model could be used in future for prediction of maturity indices of kinnow fruit in different maturity regions as per the consumer and market preferences.
The Low expression of PAI-1 increasing MC3T3-E1 cell proliferation by promoting glucose metabolism and activating BMP/TGF-β/Smad and Wnt/β-catenin pathways: a downstream regulatory role of PAI-1 in osteoblasts
Authors: aikebaier aobulikasimu , Chen Hongtao , Jiang Luoyong , zhuang Qianzheng , You Wei , Zhai Rihong , Sun Wei
Published: December 2022

PAI-1 is a marker of aging and a mediator of aging induction. Our previous study showed that PAI-1 is highly expressed in bone tissues of osteoporosis patients. Gavage of osteoporosis model mice with PAI-1 inhibitor resulted in increased Osteoblasts and bone mineral density. Inhibition of PAI-1 expression in MC3T3-E1 cells found that the altered transcription factors were mainly enriched in zf-C2H2 (12.38%) and HMG (10.48%), and Zinc finger related proteins were significantly increased in the differential proteins. Transcription factors use the energy provided by ATP to regulate the transcription and translation of downstream genes. The low expression of PAI-1 in MC3T3-E1 cells promotes ATP synthesis, cell cycle progression through cellular ATP binding and cellular metabolic process, and as a result, Osteoblast proliferation. Runx1 is expressed at different stages of Chondrocyte and Osteoblast differentiation and promotes Chondrogenesis by regulating the BMP/TGF-β/Smad and Wnt/β-catenin signaling pathways. The low expression of PAI-1 in MC3T3-E1 cells promotes Runx1 expression. This may imply that the low expression of PAI-1 may promote Osteoblast proliferation by activating the BMP/TGF-β/Smad and Wnt/β-catenin pathways by Runx1.
Molecular Characterisation of Human Respiratory Adeno Viruses in Uganda
Authors: Ukuli Qouilazoni Aquino , Erima Bernard , Mubiru Andrew , Atim Gladys , Tugume Titus , Kibuuka Hannah , Mworozi Edison , Ducatez Mariette F. , Wabwire-Mangeni Fred , Byarugaba Denis K.
Published: December 2022

Human adenoviruses (HAdV) are a diverse group of viruses causing a broad range of infections of the respiratory, urogenital and gastrointestinal tracts, and keratoconjunctivitis. There are seven species of human adenoviruses with over 51 serotypes and 69 genotypes which may contain multiple genetic variants. This study characterised the genotypes of human respiratory adenoviruses and associated factors in samples collected from selected hospitals in Uganda. A total of 2,298 nasopharyngeal samples were collected from patients seeking health care at tertiary hospitals for influenza-like illness. They were screened by Polymerase Chain Reaction (PCR) to determine the prevalence of HAdV. HAdV was isolated in A549 cell lines and the Hexon gene from the HAdV isolates was sequenced by sanger sequencing method using the BigDye Terminator v3.1. Of the 2,298 samples tested, 225 (9.8%) were adenovirus positive by PCR. Age and HAdV infection were found to be significantly associated (p = 0.028) with 98% (220/225) of the positives in children below 6 years and none in adults above 25 years of age. The sequenced isolates belonged to species HAdV B and HAdV C with most isolates identified as genotype B3. The results showed a high prevalence and HAdV genetic diversity in respiratory HAdV circulating in Ugandan population. Children aged between 0 to 5 years were more likely to get infected with HAdV than other age groups. Deeper genomic characterization based on whole genome sequencing is necessary to further elucidate possible transmission and impact of current adeno-vectored vaccines in Africa.
Comparison of multimodel ensembles of global and regional climate models projections for extreme precipitation over four major river basins in southern Africa. Part II: Future changes under 1.5°C, 2.0°C and 3.0°C warming levels
Authors: Samuel Sydney , Dosio Alessandro , Mphale Kgakgamatso , Faka Dieudonne Nsadisa , ni Modise
Published: December 2022

We compare the consistency of the future response of extreme precipitation to 1.5°C, 2.0°C, and 3.0°C global warming levels (GWLs) above the pre-industrial period (1850–1900) over four major basins in southern Africa. In particular, we compare the results from large ensembles of global climate models (GCMs) and regional climate models (RCMs) from the Coupled Model Intercomparison Project (CMIP5 and CMIP6) and the COordinated Regional-climate Downscaling EXperiment (CORDEX and CORE). The results show that the signal of the changes under all GWLs is generally consistent across the ensembles, particularly for the spatially averaged medians over each basin. Generally, all the ensembles project an increase in maximum consecutive dry days (CDD) and simple daily rainfall intensity (SDII) and a decrease in maximum consecutive wet days (CWD) and the total number of rainy days (RR1) over the basins under all GWLs. However, there are differences in the signal and robustness of the projected changes among the ensembles. For instance, CORDEX projects a robust increase in heavy precipitation days over most of the Zambezi basin under 2.0°C and 3.0°C GWLs, while CORE projects a robust decrease over most of the basins. Additionally, the projected decrease in RR1 is robust over most parts of the basins in CMIP5, CORDEX, and CORE under all GWLs, but uncertain over most parts in CMIP6. Overall, CORE projects larger areas of robust changes in extreme precipitation compared to other ensembles, with uncertain changes over most parts of the basins in CMIP6. For the avoided impacts by limiting global warming at 1.5°C, all the ensembles agree that the impacts of extreme precipitation will be reduced in general over basins under 1.5°C GWLs compared to 2.0°C and 3.0°C GWLs.
Thyroid function in opium users: A Cross-Sectional Study on PERSIAN Cohort of Fasa, 2017
Authors: Pezeshki Babak , Pourmontaseri Hossein , Homayounfar Reza , Moghaddam Maryam Talebi , Dehghan Azizallah
Published: December 2022

Background
Addiction increases the risk of different lifelong disorders. However, there are limited studies evaluating the effects of opium use on thyroid. The present study aimed to compare the thyroid function of opium users and non-users.
Methods
This cross-sectional study was conducted on 700 participants of the Persian Cohort of Fasa, Iran. Pregnant women and participants with false or missing data were excluded from the study. Frozen plasma samples of the cohort bank were used to determine the levels of T3, T4, and thyroid-stimulating hormone (TSH). The thyroid function was compared between the two groups using Mann-Whitney test (P < 0.05).
Results
The mean age of the study population (n = 648) was 54.0 ± 9.8 years, including 336 men (49.1%) and 197 opium users (28.8%). The median levels of TSH, T4, and T3 were 2.91 ± 4.61, 9.26 ± 3.65, and 1.22 ± 0.49, respectively. The opium users had significantly higher TSH (3.72 ± 6.2 vs. 2.58 ± 3.75) and lower T4 (8 ± 3.6 vs. 9.8 ± 3.5) levels (P < 0.001). Also, T3 was slightly lower in opium users (1.1 ± 0.5 vs. 1.3 ± 0.5; P = 0.369), although this association was only significant in female opium users (P < 0.001).
Conclusions
The present findings revealed that opium use causes a reduction in T4, while increasing TSH. Therefore, opium use may lead to the development of primary hypothyroidism, which needs to be investigated in future studies.
Uncovering the relationship between YTHDF1 related to immune cells and prognosis and diagnosis in lung adenocarcinoma
Authors: Han Lei , Liu Yan , Wu Jia , Fan Bin , Wang Lei , Li Genshan , Yao Zhihong , Ye Lijuan , Li Dongqi , Yang Zuozhang
Published: December 2022

The authors have requested that this preprint be removed from Research Square.
Characterization of the Complete Mitochondrial Genome of Cucurbita maxima Duch
Authors: Liu Zefa , Jiang Yanfang , Zhu Hongye , Gong Yihui , Yusop Mohd Rafii , Abdullah Shamsiah
Published: December 2022

Cucurbita maxima Duch is a widely cultivated and consumed vegetable with high economic and nutritional value. The complete mitochondrial (mt) genome of C. maxima was characterized by Illumina paired-end sequencing and is reported here. The size of the complete mt genome was 640,814 bp, and its GC content was 43.37%. Sequence analyses showed that the mt genome encoded 68 genes, consisting of 38 mRNA, 27 tRNA, and 3 rRNA genes. Phylogenetic analysis indicated that C. maxima was most closely related to Cucurbita pepo (NC-014050.1). This study provides useful genetic information for further studies on the genetic structure and evolutionary patterns of C. maxima for species identifications. The genome can be accessed on GenBank with the accession number (OL350846.1).