bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual Clustering of Transcriptomic Data from Primary and Metastatic Tumors: Dependencies and Novel Pitfalls
Authors: Marquardt Andre , Kollmannsberger Philip , Krebs Markus , Knott Markus , Solimando Antonio Giovanni , Kerscher Alexander
Published: March 2022

Background: Personalized Oncology is a rapidly evolving area and offers cancer patients therapy options more specific than ever. Yet, there is still a lack of understanding regarding transcriptomic similarities or differences of metastases and corresponding primary sites. Methods: Approaching this question, we used two different unsupervised dimension reduction methods – t-SNE and UMAP – on three different metastases datasets – prostate cancer, neuroendocrine prostate cancer, and skin cutaneous melanoma – including 682 different samples, with three different underlying data transformations – unprocessed FPKM values, log10 transformed FPKM values, and log10+1 transformed FPKM values – to visualize potential underlying clusters. Results: The approaches resulted in formation of different clusters that were independent of respective resection sites. Additionally, data transformation critically affected cluster formation in most cases. Of note, our study revealed no tight link between the metastasis resection site and specific transcriptomic features. Instead, our analysis demonstrates the dependency of cluster formation on the underlying data transformation and the dimension reduction method applied. Conclusion: These observations propose data transformation as another key element in the interpretation of visual clustering approaches apart from well-known determinants such as initialization and parameters. Furthermore, the results show the need for further evaluation of underlying data alterations based on the biological question and subsequently used methods and applications.
Strengthening Research Ethics Systems In Liberia: Challenges, Prospects and Implications
Authors: Kennedy Stephen , Mason Gloria , Sherman Lawrence , Tegli Jemee , Taylor Curtis , Morris Cecelia , Bolay Fatorma , Scaramuzz Dario
Published: March 2022

Despite the tremendous growth of Research Ethics systems in resource-limited settings, structural and systematic challenges persist. Therefore, effective ethical frameworks must be cultivated and further implemented to promote the rights of human subjects and vulnerable populations, strengthen the implementation of high quality research, and engage the participation of communities for the sustainable growth of research ethics systems in low and middle income countries (LMICs). To explore those challenges, we conducted a cross-sectional study among prior and current members of research ethics committees in order to determine the facilitators and gaps that are impeding the growth of the research ethical systems in Liberia, a resource-limited country, and subsequently utilize the findings to formulate country-specific ethical and regulatory frameworks. The results revealed plethora of ethical challenges, ranging from the inadequacy of infrastructure to limited, non-inclusive, funder-driven, capacity building initiatives. While the findings have program and policy implications, the results could likely create a platform to support future ethics-based research efforts directed at developing effective ethical frameworks to strengthen and sustain research ethical systems in resource-limited settings.
Exosomal miR-221-3p derived from bone marrow mesenchymal stem cells alleviates asthma progression by targeting FGF2 and inhibiting the ERK1/2 signaling pathway
Authors: Liu Weike , Lin Hui , Nie Wuhui , Wan Jieting , Jiang Qian , Zhang Aimei
Published: March 2022

Exosomes derived from human bone marrow mesenchymal stem cells (BMSCs) play potential protective roles in asthma. However, the underlying mechanisms remain not fully elucidated. Herein, exosomes were isolated from BMSCs, and their morphology, particle size and exosome marker proteins were identified by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) and Western blot, respectively. Then airway smooth muscle cells (ASMCs) were treated with transforming growth factor-β1 (TGF-β1) to construct proliferation model, and then incubated with BMSCs-derived exosomes. We found that exosome incubation increased miR-221-3p expression, and inhibited proliferation, migration, and the levels of extracellular matrix (ECM) proteins including fibronectin and collagen III. Moreover, FGF2 was identified as a target gene of miR-221-3p. FGF2 overexpression reversed the inhibitory effects of exosomal miR-221-3p on ASMC progression. Besides, the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) is inhibited by exosomal miR-221-3p, which was reversed by FGF2 overexpression. And ERK1/2 signaling activator reversed the effects of exosomal miR-221-3p on ASMC progression. Additionally, an ovalbumin (OVA)-induced asthmatic mice model was established, and exosomes treatment alleviated airway hyper-responsiveness (AHR), histopathological damage and ECM deposition in asthmatic mice. Taken together, our findings indicated that exosomal miR-221-3p derived from BMSCs inhibited FGF2 expression and the ERK1/2 signaling, thus attenuating proliferation, migration and ECM deposition in ASMCs and alleviating asthma progression in OVA-induced asthmatic mice. Our findings may provide a novel therapeutic strategy for asthma.
Haplotype-aware modeling of cis-regulatory effects highlights the gaps remaining in eQTL data
Authors: Mohammadi Pejman , Ehsan Nava , Kotis Bence , Castel Stephane , Song Eric , Mancuso Nicholas
Published: March 2022

Expression Quantitative Trait Loci (eQTLs) are critical to understanding the mechanisms underlying disease-associated genomic loci. Nearly all protein-coding genes in the human genome have been associated with one or more eQTLs. Here we introduce a multi-variant generalization of allelic Fold Change (aFC), aFC-n, to enable accurate quantification of the cis-regulatory effects in genes with multiple conditionally independent eQTLs. Applying aFC-n to 458,465 eQTLs in the Genotype-Tissue Expression (GTEx) project data, we demonstrate significant improvement in accuracy over the current tools for estimating the eQTL effect size and predicting genetically regulated gene expression. We characterize some of the empirical properties of the eQTL data and use this framework to assess the current state of eQTL data in terms of characterizing cis-regulatory landscape in individual genomes. Notably, we show that 77.4% of the genes with an allelic imbalance in a sample show 0.5 log2 fold or more of residual imbalance after accounting for the eQTL data underlining the remaining gap in characterizing regulatory landscape in individual genomes. We further contrast this gap across tissue types, and ancestry backgrounds to identify its correlates and guide future studies.
Circular RNA hsa_circ_0023404 promotes the proliferation, migration and invasion in endometrial cancer cells through regulating miR-217/MAPK1 axis
Authors: Chen Zhuoying , Huang Meixiu , You Jiaying , Lin Yanhua , Huang Qiaoyun , He Caiping
Published: March 2022

Aim
Studies indicated that Circular RNA hsa_circ_0023404 play a critical role in cancer progression. The aim of our research is to investigate the functions of hsa_circ_0023404 in endometrial cancer (EC) and the potential molecular mechanism.
Methods
We used RT-qPCR and Western blot approach to detect the expressed levels of related genes in EC cell lines. Transfected siRNAs were applied to knockdown the level of related mRNA in cells. Cell proliferation by CCK-8 assay and colony formation assay were applied to detect cell proliferation. Transwell migration and invasion assay was for detecting the migration and invasion of the cells.
Results
RT-qPCR showed that the level of hsa_circ_0023404 and MARK1 mRNA were upregulated but mirR-217 was decreased in three endometrial cancer cell lines. Knockdown of hsa_circ_0023404 by siRNA markedly increased the level of miR-217 and reduced the proliferation of the Ishikawa cells。 It also inhibited the cell migration and invasion. Anti-miR-217 can reverse the promoted proliferation, migrations and invasion of Ishikawa cells mediated by si-circ_0023404. si-MARK1 restored the inhibited cell proliferation, migration and invasion of the co-transfected Ishikawa cells with si- circ_0023404 and anti-miR-217.
Conclusion
hsa_circ_0023404 exerts a tumor-promoting role in endometrial cancer by regulating miR-217/MARK1 axis. hsa_circ_0023404 inhibit miR-217 as sponge which inhibit endometrial cancer cell growth and metastasis. MARK1 is downstream target of miR217 and upregulated by hsa_circ_0023404/miR-217 axis and involved in the endometrial cancer progression.
Sarcopenia is Associated with Non-motor symptoms in Han Chinese Patients with Parkinson's Disease: A Cross-Sectional Study
Authors: Liu Qiu-wan , Mao Cheng-jie , Lu Zhao-hui , Shi Rong-fang , Zhang Ying-chun , Zhao Ping , Liu Chun-Feng
Published: March 2022

Background: Sarcopenia is commonly seen in the older adults and increases in incidence with age, also in Parkinson’ s Disease (PD). There may be a vicious circle between the development of PD and sarcopenia, but the relationship between the two is not clear. We aimed to investigate the incidence of sarcopenia in patients with PD and the association between non-motor symptoms (NMS) in PD. Methods: The study included 123 patients with PD and 38 age- and sex-matched healthy controls. All participants were evaluated for sarcopenia using the 2019 Asian Sarcopenia Diagnostic Criteria, and patients with PD underwent standard assessments of motor and non-motor symptoms. Multiple logistic regression and receiver operating characteristic (ROC) curve analyses were used to examine the association between sarcopenia and NMS in PD patients.Results: The incidence of sarcopenia was significantly higher in patients with PD than in healthy controls (26.8% vs. 10.4%, p=0.035). Multiple logistic regression analysis revealed that poorer sleep quality (odds ratio [OR]: 1.305; 95% confidence interval [CI]: 1.026–1.622; p=0.030) and fatigue (OR: 1.097, 95% CI: 1.003–1.199, p=0.042) were independently associated with sarcopenia. ROC analysis indicated that the optimal cut-off value for Pittsburgh Sleep Quality Index (PSQI) scores was 10, with 72.7% sensitivity and 74.4% specificity (area under the curve [AUC]=0.776, 95% CI: 0.692–0.846, p<0.001). The optimal cut-off value for Fatigue Severity Scale (FSS) scores was 39, with 87% sensitivity and 50% specificity (AUC=0.725, 95% CI: 0.637 –0.802, p<0.001). joint use of FSS and PSQI increased the predictive value (AUC = 0.804, p<0.001).Conclusion: Patients with PD are more susceptible to sarcopenia than healthy older adults. Combined use of FSS and PSQI scores may be a valuable screening method for identifying sarcopenia in patients with PD.
Weather effects on offspring survival differ between reproductive stages in a Neotropical seabird.
Authors: Ortega Santiago , Rodriguez Cristina , Drummond Hugh
Published: March 2022

Weather conditions can profoundly affect avian reproduction. Thus far, most studies on weather effects have focused on how weather conditions prior to clutch initiation affect laying dates and, ultimately, breeding success. By contrast, little is known of how weather conditions after the onset of reproduction affect birds. Using a 32-year population study of the Blue-footed booby (Sula nebouxii) in Mexico, we show that effects of weather conditions on offspring survival and body condition at independence vary with the reproductive stage at which they occur. During most of the incubation period, warm sea surface temperatures and low to moderate rainfall depressed hatching success; while during the last month of brood care surface temperatures were unimportant but rainfall increased fledging success. In addition, chicks that experienced warm sea surface temperatures in the middle of the brood care stage had lower body condition at fledging. Our results provide insight of how weather effects vary between reproductive stages in a long-lived neotropical seabird.
Musa Acuminata Wastes as New Potential source of Anti-ulcerative Colitis Agents : Pharmacological and Metabolomics Profiles
Authors: Mohammed Mona A. , Ibrahim Bassant M.M. , Abdelatif Yasmin , Hassan Azza H. , Raey Mohamed A. El , Hassan Emad M. , El-Gengaihi Souad E.
Published: March 2022

Musa acuminata is a popular fruit in the world. Non-food parts of the plant have been investigated for their antioxidant and anti-ulcerative colitis activity. Metabolomic approaches was found to be informative as a screening tool. It discovered different metabolites depending on statistical analysis. The antioxidant activity content was measured by colorimetric method. Seventy six investigated metabolites were observed. The identities of some of these markers were confirmed based on their MS2 fragmentation and NMR spectroscopy. These include: Cinnamic acid and its dimer 2-hydroxy-4-(4-methoxyphenyl)-1H-phenalen-1-one beside Gallic acid and flavonoids; Quercetin, Quercetin-3-O-β-D-glucoside, Luteolin-7-O-β-D-glucopyranoside. The leaves, pseudostem and fruit peels extracts were tested for their safety and their antiUlcerative-colitis efficacy in rats. Rats were classified into:Normal, Positive, prednisolone reference group , Musa extracts pretreated groups(250-500mg/kg) for two weeks followed by induction of Ulcerative-colitis by per-rectal infusion of 8% acetic acid. Macroscopic and microscopic examination were done. Inflammatory markers (ANCA, CRP and Ilβ6) were measured in sera. The extracts showed good antioxidant and anti-inflammatory activities as they ameliorated macroscopic and microscopic signs of Ulcerativecolitis and lowered the inflammatory markers compared to untreated group. Musa wastes can be a potential source of bioactive metabolites for industrial use and future employment as promising anti-Ulcerativecolitis food supplements.
Integration of Mentimeter into the Classroom: A Scoping Review
Authors: Madiseh Fatemeh Ranjbaran , Abri Abdullah Al , Sobhanifar Hadi
Published: March 2022

The rapid development in technology and information has inspired educators to explore innovative technological resources and assets to promote the quality of teaching and learning. Student Response Systems (SRS) have been acknowledged as having a significant influence on student engagement, motivation, and overall achievement. This scoping review investigated the integration of Mentimeter in the educational context to determine its effectiveness for both teaching and learning processes. The included studies were screened for only those that investigated the use of Mentimeter in the classroom, while including peer-reviewed journal articles, conference proceedings, short articles, book chapters, and review articles from 2015 to 2022 that were available in English without limitation on discipline. The 57 publications that met the eligibility criteria were coded for various characteristics, the most significant of which are discipline, geographical region, publication type, research method and outcomes. Our results reveal the numerous merits gained from integrating Mentimeter in educational settings, including: 1) benefits not only to enriching student-centered pedagogy, but also encapsulating a diverse audience of cultural backgrounds and competencies; 2) providing immediate feedback for anonymous student responses; 3) enhancing student motivation; 4) engaging students’ active participation. The results of this study provide initiatives for teachers and educational researchers to conduct further research on various educational technology platforms, and highlight the advantages of integrating technology into the educational setting. While teachers and practitioners persevere to transform the learning experience through technology, we emphasize the necessity for continuous research to investigate different learning platforms that considerably improve learning outcomes.
The Efficacy of Casirivimab/Imdevimab in Solid Organ Transplant Recipients with Mild-To-Moderate COVID-19
Authors: Tagaya Etsuko , Kikuchi Ken , Mitsuda Toshihiro , Ebihara Fumiya , Maruyama Takumi , Hamada Yukihiro , Kimura Toshimi , Unagami Kohei , Kanzawa Taichi , Sekiguchi Haruki , Shimamoto Ken , Ishida Hideki , Egawa Hiroto , Tanaka Junji , Tanabe Kazunari , Kawana Masatoshi , Arimura Ken
Published: March 2022

Background: Solid organ transplant recipients (SOTRs) are at high risk for severe coronavirus disease 2019 (COVID-19) due to comorbidities and immunosuppression. Moreover, the treatment for COVID-19 is limited. Neutralizing monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 are used for treating mild-to-moderate COVID-19. However, reports comparing the efficacy of COVID-19 treatment with and without neutralizing mAbs in SOTRs are limited. Here, we assessed the efficacy of casirivimab/imdevimab as neutralizing mAbs against mild-to-moderate COVID-19 in SOTRs. Methods: Forty-one patients hospitalized from September 2020 to September 2021 at Tokyo Women’s Medical University Hospital were included. The duration until antifebrile and of hospitalization, requirement of oxygen (O2) ≥ 5 L, and neutralizing antibody levels were compared in SOTRs with COVID-19 who received and those who did not receive casirivimab/imdevimab therapy.Results: Casirivimab/imdevimab therapy correlated with less duration until antifebrile and of hospitalization and non-requirement of O2 ≥ 5 L in SOTRs with COVID-19 [mean days without vs. with casirivimab/imdevimab: 6 vs. 2; P = 0.0002, hazard ratio (HR) = 0.3333, 95% confidence interval (CI) = 0.1763–0.6301; mean days: 15 vs. 8; P < 0.0001, HR = 0.5333, 95% CI = 0.2878–0.9883; P = 0.0377, HR = 0.1502, 95% CI = 0.02511–0.8980, respectively]. Further, casirivimab/imdevimab therapy was associated with early antifebrile after adjusting for sex and age (P = 0.013, HR = 0.412, 95% CI = 0.205–0.826). Although no significant difference was observed in neutralizing antibody levels between patients without and with casirivimab/imdevimab therapy on the day of hospitalization (P = 0.1055), including 13 SOTRs who had received vaccination. Neutralizing antibody levels were higher in patients with casirivimab/imdevimab therapy at 3–5 days after hospitalization including such patients in whom the levels tended to stay lower despite vaccination than in those without casirivimab/imdevimab at 7–9 days after hospitalization (P < 0.0001, mean antibody without vs. with, 414.9 vs. 40000). Conclusion: Casirivimab/imdevimab therapy was effective and increased the neutralizing antibody levels in SOTRs with mild-to-moderate COVID-19. Therefore, casirivimab/imdevimab therapy could contribute to preventing the progression of mild-to-moderate COVID-19 in SOTRs.
Diminazene aceturate attenuates hepatic ischemia/reperfusion injury in mice
Authors: Yoon So Hye , Kang Hye Bin , Kim Jongwan , Han Sang Jun
Published: March 2022

Hepatic ischemia/reperfusion (I/R) injury is one of the leading causes of mortality following partial hepatectomy, liver transplantation, hypovolemic shock, and trauma; however, effective therapeutic targets for the treatment of hepatic I/R injury are lacking. Recent studies have shown that diminazene aceturate (DIZE) has protective effects against inflammation, oxidative stress, and cell death, which are the main pathogenetic mechanisms associated with hepatic I/R injury. However, the mechanistic effects DIZE exerts on hepatic I/R remain unknown. C57BL/6 male mice were pretreated with either 15 mg/kg DIZE or vehicle control (saline) and subjected to partial liver ischemia for 60 min. One day after induction of hepatic I/R, liver damage, inflammatory responses, oxidative stress and apoptosis were analyzed. By evaluating plasma alanine aminotransferase levels and histology, we found that DIZE treatment attenuated liver failure and was associated with a reduction in histologically-apparent liver damage. We also found that DIZE-treated mice had milder inflammatory responses, less reactive oxidative damage, and less apoptosis following hepatic I/R compared to vehicle-treated mice. Taken together, our study demonstrates that DIZE protects against ischemic liver injury by attenuating inflammation and oxidative damage and may be a potential therapeutic agent for the prevention and treatment of ischemic liver failure.
Predictors of Research Subject retention - Repetitive non-adherence or socioeconomic factors: Insights from a urological clinical trial
Authors: Liss Michael A. , Wheeler Allison J. , Garg Harshit , Kaushik Dharam , Mansour Ahmed , Pruthi Deepak
Published: March 2022

Background:To investigate various patient level variables, specifically socioeconomic status, as risk factors for withdrawal in a recently completed clinical study. We specifically investigate a recent study in men on adherence to an observational prostate cancer imaging and biomarkers study. Methods: We performed a retrospective study to investigate risk factors for withdrawal in a prostate cancer imaging study that enrolled men on active surveillance from January 2016 to June 2019. For each subject, we assessed their retention status and collected demographic data. We compared values between the two retention groups using T-test, Chi-Squared, and logistic regression. Results:Out of 273 men screened, 123 men were enrolled and included in the results of this study. Of those, 106 (86%) were retained in the study and 17 (14%) were withdrawn. While we found no significant relationship between low socioeconomic status and retention, we did find that the number of non-adherences was a significant factor in withdrawal from the study (OR 2.5, 95% CI 3.5-40.5, p<0.001). Conclusions: Expanding diverse inclusion and limiting withdrawal with real-time non-adherence monitoring will lead to more efficient clinical research and greater generalizability of results.
Sustainable Development Goal 13 and Switching Priorities: Addressing Climate Change in the Context of Pandemic Recovery Efforts
Authors: Filho Walter Leal , Minhas Aprajita , Schmook Birgit , Mardero Sofia , Sharifi Ayyoob , Paz Shlomit , Kovaleva Marina , Albertini Maria Cristina , Skouloudis Antonis
Published: March 2022

The COVID-19 pandemic has had many deep social and economic impacts that go beyond health issues. One consequence is that the pandemic has made it even harder to mobilize the financial resources needed to pursue SDG 13 (Climate Action) as a whole and to fund climate change mitigation and adaptation efforts in particular. This is especially acute in respect of the efforts to achieve the targets set by the Paris Agreement and by the recent decisions in Glasgow. This paper looks at how the COVID-19 pandemic has accelerated poverty and undermined climate change adaptation efforts, as a result of the switches in priorities and funding. Using a review of the recent literature, an analysis of international trends, and a survey among climate scientists, it identifies some of the impacts of the pandemic on climate change mitigation and adaptation efforts and discusses their implications. The findings indicate a decrease in funding to climate change research since the pandemic crisis. The bibliometric analysis reveals that a greater emphasis has been placed on the relationship between COVID-19 and poverty when compared to the interrelations between COVID-19 and climate change. Addressing climate change is as urgent now as it was since the pandemic crisis started, and efforts need to be made to upkeep the levels of funding needed to support research in this field.
Rectal swabs as a viable alternative to faecal sampling for the analysis of gut microbiota functionality and composition
Authors: Mullish Benjamin H , Radhakrishnan Shiva T , Gallagher Kate I , Serrano-Contreras Jose I , Alexander James L , Blanco Jesus Miguens , Danckert Nathan P , Valdivia-Garcia Maria , Hopkins Billy J , Ghai Anik , Li Jia V , Marchesi Julian R , Williams Horace RT
Published: March 2022

Faecal or biopsy samples are frequently used to analyse the gut microbiota, but issues remain with the provision and collection of such samples. Rectal swabs are widely-utilised in clinical practice and previous data demonstrate their potential role in microbiota analyses; however, studies to date have been heterogenous, and there is a particular lack of data concerning the utility of swabs for the analysis of the microbiota’s functionality and metabolome. We compared paired stool and rectal swab samples from healthy individuals to investigate whether rectal swabs are a reliable proxy for faecal sampling. There were no significant differences in alpha and beta diversity measures between swab and faecal samples, and inter-subject variability was preserved. Additionally, no significant differences were demonstrated in abundance of major annotated phyla. Inferred gut functionality using Tax4Fun2 showed excellent correlation between the two sampling techniques (Pearson’s coefficient r = 0.9217, P < 0.0001). Proton nuclear magnetic resonance (1H NMR) spectroscopy enabled the detection of 20 metabolites with good correlation between rectal swab and faecal samples for butyrate, succinate and 5-aminovalerate relative abundances, though more variable degrees of association for other identified metabolites. These data support the utility of rectal swabs in both compositional and functional analyses of the gut microbiota.
Radish (Raphanus sativus L.) responds to exogenous ascorbic acid and irrigation levels
Authors: Henschel Juliane Maciel , Soares Vanessa de Azevedo , Figueiredo Mateus Caldeira , Santos Sabrina Kelly dos , Dias Thiago Jardelino , Batista Diego Silva
Published: March 2022

Plant growth and development depend on water availability and a scarcity or excess can reduce the production of root crops such as radishes. Thus, adequate irrigation levels for radish plants are essential avoid water stress, and to develop strategies to overcome negative stress effects to improve tuber production. Here, we aimed to determine the effects of exogenous ascorbic acid (AA) and irrigation levels on radish growth, biomass allocation and gas exchange. Radish plants were irrigated with a water holding capacity (WHC) of 100% (W100), 70% (W70) and 50% (W50) and foliar sprayed with 0 and 2 mM AA. Growth parameters (root diameter, length and volume; and leaf number and area), biomass accumulation (shoot and root fresh weight; shoot, root and total dry weight), biomass allocation (shoot/root ratio and organ mass fractions) and gas exchange (carbon assimilation rate, stomatal conductance, transpiration, intercellular CO2 concentration and instantaneous carboxylation efficiency) were evaluated. The growth of radish plants was impaired when irrigated with W100, probably due to waterlogging the soil, which reduced shoot and root growth and the carbon assimilation rate (A) compared with W50 and W70. Ascorbic acid affected biomass allocation and instantaneous carboxylation efficiency (A/Ci), but not growth and biomass accumulation. W70 was the optimal condition for radish growth and biomass accumulation, regardless of exogenous AA.
Purple BB#10 development in ×Brassicoraphanus koranhort using turnip-intercalated radish chromosomes
Authors: Lee Soo-Seong
Published: March 2022

The nidomi cultivar (introduction number 166) of Brassica rapa ssp. rapifera (turnip) was crossed, after emasculation, with Raphanus sativus var. rafinistrum lr. (landrace) gaetmoo (radish no. 45) to breed a fine-root variety. One seed was harvested. The turnip had already been intercalated with B-genome (166*) and one seed was not crossed and delivered chromosome pieces of Raphanus (166**). The intercalation and absence of hybridization were confirmed by marker and chromosome investigations at the C2F2 generation, when two plants of CMSBB#1-11 × 166**-1-1 (C1F2) produced only one and two seeds in a cross with BB#1. When cultivated, CMSBB#1-7 × 166**-1-2 (C2F2) produced seeds at 21.7% and 20.0% the amount of standard BB#1, and some purple plants were present in the 21.7% line. The purple plants presumably reflect intercalation with radish chromosomes at the pollination stage of the intergeneric hybrid. Three selected purple plants exhibited abundant pollen and were fertile, although they had previously been crossed with CMS-BB#1. Therefore, the pedigree method could be carried out for these plants (C2F2), and the seed production showed great improvement at the C2F4 generation. The purple plant was named BB#10; the pigment, glucoraphenin and glucoraphasatin, and chromosome constitution (C2F5) were analyzed. Purple BB#10 was registered in 2019 (C2F6).
Biotechnological interventions in Orchids: Recent updates, Translational success, and Commercial outcomes
Authors: Tiwari Pragya , Sharma Abhishek , Bose Subir Kumar , Gautam Ashutosh
Published: March 2022

Orchids constitute the largest and most diverse group of flowering plants and are classified in Orchidaceae. Exhibiting significance as the most exotic and ubiquitous flowering plants, the cultivation of orchids on a commercial level, is gaining momentum worldwide. In addition to its ornamental and aesthetic value, the orchid industry has been successful in generating employment for people in developing countries. Recent advances in biotechnological interventions in orchids have substantially contributed to the development of exotic varieties with novel traits, not to forget the inputs of traditional plant breeding methods and tissue culture approaches. In addition, the scientific developments in orchid biology have remarkably improved the knowledge in areas of orchid biology, classification, phytochemistry, and cultivation strategies, among other areas. This has facilitated the commercialization of novel varieties, opening new avenues in the orchid industry, witnessed as cultivation of different varieties and globally marketed as a cut flower and artificially propagated plants. The orchids constitute the first floriculture crops, which revolutionized the orchid industry, however, it also withholds several challenges in natural propagation, several species facing extinction. International organizations like CITES have come forward to address challenges associated with illegal global trade and indiscriminate use of orchid varieties, aiming towards conservation and legal commercial goals. This thematic review is one of a kind in providing comprehensive insights on the emerging momentum of orchid biology and how its globalization projects to considerably impact the orchid industry in the coming time. Together with traditional breeding approaches and plant tissue culture, advances in biotechnological interventions continues to make substantial progress in the development of exotic varieties, with multi-faceted attributes. However, it is imperative to understand the challenges in the cultivation and conservation of orchid varieties and ensure legislative guidelines both on domestic and global levels to ensure a multipronged approach for the conservation and commercialization of orchids.
Ectopic expression of sericin enables efficient production of ancient silk with structural changes in silkworm
Authors: Chen Xuedong , Wang Yongfeng , Wang Yujun , Li Qiuying , Liang Xinyin , Wang Guang , Sima Yang-Hu , Xu Shiqing
Published: March 2022

Bombyx mori silk is a super-long natural protein fiber with a unique structure and excellent performance. Innovative silk structures with high performance are in great demand, thus resulting in an industrial bottleneck. Herein, a transgenic method was used in which the outer layer sericin SER3 in silk is secreted into the inner fibroin layer, thus generating a new structural fiber with non-fibrous sericin microsomes dispersed in fibroin fibrils. The water-soluble SER3 protein secreted by the posterior silk gland causes P25’s detachment from the fibroin unit of the Fib-H/Fib-L/P25 polymer and accumulation on the fibroin surface. Moreover, the water solubility and stability of the fibroin-colloid in the silk glandular cavity are increased, thus significantly improving the β-sheet content of fibroin, as well as the mechanical properties, moisture absorption and moisture liberation of the silk fiber. Our silkworm mutant system circumvents the problems of low vitality and abnormal silk gland development, and enables higher production efficiency of cocoon silk than that of the wild type. We describe a silk gland transgenic target protein selection strategy to alter the ancient silk fiber structure and to innovate the properties of silk protein materials. This study thus provides an efficient, green method to produce new silk fibers.
MHCII Contributes to Bone Cancer Pain via Activating the NLRP3 Inflammasome in Microglia of the Medial Prefrontal Cortex
Authors: Li Xin , Wang Wei , Zhang Xiaoxuan , Gong Zhihao , Tian Mi , Zhang Yuxin , Wu Jingxiang , You Xingji
Published: March 2022

As one of the causes of bone cancer pain (BCP), central hyperalgesia has more and more supporting evidences recently. The medial prefrontal cortex (mPFC) is implicated in emotional disorders associated with BCP. Major histocompatibility complex II (MHCII) is a key component in regulating anti-inflammatory response and antigen presentation. This study aims to investigate whether MHCII of the mPFC participates in the BCP. Rat model of BCP was established by injecting Walker 256 cells into the tibia. BCP-induced decreased pain threshold, increased the expression of MHCII and the downstream protein CTSS, CD74 and upstream protein CIITA in mPFC, and the upregulation of MHCII in the mPFC of BCP rats was restricted in microglia. Furthermore, pharmacological inhibition of MHCII by intraperitoneal injecting minocycline provides relief from BCP. Importantly, the upregulation of MHCII is accompanied by significant NLRP3 inflammasome activated and inflammatory factors (IL-1β, IL-18 and TNF-α) released in the mPFC of BCP rats. Taken together, our data suggest that MHCII participates in BCP by activating inflammasome in microglia of the mPFC.
Neural mechanisms underlying state mental fatigue: a systematic review and activation likelihood estimation meta-analysis
Authors: Salihu Abubakar Tijjani , Hill Keith D , Jaberzadeh Shapour
Published: March 2022

Sustained performance of cognitive tasks could lead to the development of state mental fatigue characterized by subjective sensation of mental weariness and decrease in cognitive performance. In addition to the occupational hazards associated with mental fatigue, it can also affect physical performance reducing endurance, balance, and sport-specific technical skills. Similarly, mental fatigue is a common symptom in certain chronic health conditions such as multiple sclerosis affecting quality of life of the patients. Despite its widely acknowledged negative impact, the neural mechanisms underlining this phenomenon are still not fully understood. We conducted a systematic review and activation likelihood estimation (ALE) meta-analysis of functional neuroimaging studies investigating the effect of mental fatigue due to time-on-task (TOT) on brain activity to elucidate the possible underlying mechanisms. Studies were included if they examined change in brain activity induced by experimental mental fatigue (TOT effect) or investigated the relationship between brain activity and subjective mental fatigue due to TOT. 33 studies met the review’s inclusion criteria, 13 of which were included in meta-analyses. Results of the meta-analyses revealed a decrease in activity with TOT in brain areas that constitute the cognitive control network. Additionally, an increased activity with TOT, as well as negative relationship with subjective mental fatigue was found in parts of the default mode network of the brain. The changes in cognitive control and the default mode networks of the brain due to state mental fatigue observed in this study can be explained based on the “neurotoxic waste disposal” theory of mental fatigue.
A Dual-Center Cohort Study on The Association Between Early Deep Sedation and Clinical Outcomes in Mechanically Ventilated Patients During the COVID-19 Pandemic: the COVID-SED Study
Authors: Stephens Robert J. , Evans Erin M. , Pajor Michael J. , Pappal Ryan D. , Egan Haley M. , Wei Max , Hayes Hunter , Morris Jason A. , Becker Nicholas , Roberts Brian W. , Kollef Marin H. , Mohr Nicholas M. , Fuller Brian M.
Published: March 2022

Background: Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes.Study Design and Methods: Dual-center, retrospective cohort study conducted over six months (March – August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 hours were collected. Deep sedation was defined as Richmond Agitation-Sedation Scale of -3 to -5 or Riker Sedation-Agitation Scale of 1 – 3. To examine impact of early sedation depth on hospital mortality (primary outcome) we used a multivariable logistic regression model. Secondary outcomes included ventilator-, ICU-, and hospital-free days.Results: 391 patients were studied, and 283 (72.4%) experienced early deep sedation. Deeply sedated patients received higher cumulative doses of fentanyl, propofol, midazolam, and ketamine when compared to light sedation. Deep sedation patients experienced fewer ventilator-, ICU-, and hospital-free days, and greater mortality (30.4% versus 11.1%) when compared to light sedation (p < 0.01 for all). After adjusting for confounders, early deep sedation remained significantly associated with higher mortality (adjusted OR 3.44; 95% CI 1.65 – 7.17; p <0.01). These results were stable in the subgroup of patients with COVID-19. Conclusions: The management of sedation for mechanically ventilated patients in the ICU has changed during the COVID pandemic. Early deep sedation is common and independently associated with worse clinical outcomes. A protocol-driven approach to sedation, targeting light sedation as early as possible, should continue to remain the default approach.Clinical Trial Registration: Not applicable.
A Heterophil/lymphocyte Selected Population Reveals the Phosphatase PTPRJ is Associated with Immune Defense in Chickens
Authors: Wang Jie , Zhang Jin , Wang Qiao , Zhang Qi , Thiam Mamadou , Zhu Bo , Ying Fan , Zheng Maiqing , Wen Jie , Li Qinghe , Zhao Guiping
Published: March 2022

Quantification of leukocyte profiles is among the simplest measures of animal immune function. In particular, the heterophil to lymphocyte ratio (H/L) has been extensively studied as a measure of stress in chickens. However, the relationship between H/L ratio and innate immunity and the measure’s utility as an index for heterophil function remains to be analyzed. We raised a chicken line (Jingxing yellow chickens) selected for ten generations on H/L ratio.Genome profiling of 227 chickens from the selection and control lines revealed selection signatures. Variants associated with H/L ratio were then further fine-mapped based on the resequencing of 249 chickens of different generations and an F2 segregating population generated by crossing selection and control lines. H/L ratio in the selection line was associated with a selective sweep of mutations in protein tyrosine phosphatase, receptor type J (PTPRJ), which affects proliferation and differentiation of heterophils through its downstream regulatory genes. The SNP downstream of PTPRJ (rs736799474) have a universal effect on H/L, with CC homozygotes exhibiting improved heterophil function because of downregulated PTPRJ expression. In short, we systematically elucidated the genetic basis of the change in heterophil function resulting from H/L selection by identifying the regulatory gene (PTPRJ) and causative SNP.
Metagenome-wide Association Study of Gut Microbiome Features for Myositis
Authors: Li Yimin , Xu Jun , Li Zijun , Guo Yixue , Xing Xiaoyan , Zhufeng Yunzhi , Wang Ziye , Li Ruoxi , Lu Dan , Liu Xu , He Jing , Li Yuhui , Sun Xiaolin
Published: March 2022

Background: The clinical relevance and pathogenic role of gut microbiome in both myositis and its associated interstitial lung disease (ILD) are still unclear.The purpose of this study was to investigate the role of gut microbiome in myositis through comprehensive metagenomic-wide association studies (MWAS).Results We conducted MWAS of the myositis gut microbiome in a Chinese cohort by using whole-genome shotgun sequencing of high depth, including 30 myositis patients and 31 healthy controls (HC). Among the myositis patients, 11 developed rapidly progressive interstitial lung disease (RP-ILD) and 10 had chronic ILD (C-ILD).Apparent discrepancy in β diversities of metagenome was found in the comparison of myositis and HC, RP-ILD and C-ILD in myositis. Analysis for overall distribution level of the bacteria showed Alistipes onderdonkii, Parabacteroides distasonis and Escherichia coli were upregulated, Lachnospiraceae bacterium GAM79, Roseburia intestinalis, and Akkermansia muciniphila were downregulated in patients with myositis compared to HC. Bacteroides thetaiotaomicron, Parabacteroides distasonis and Escherichia coli were upregulated, Bacteroides A1C1 and Bacteroides xylanisolvens were downregulated in RP-ILD cases compared with C-ILD cases. A variety of biological pathways related to metabolism were enriched in the myositis and HC, RP-ILD and C-ILD comparison. And in the analyses for microbial contribution in metagenomic biological pathways, we have found that E. coli played an important role in the pathway expression in both myositis group and myositis-associated RP-ILD group. Anti-PL-12 antibody, anti-Ro-52 antibody, and anti-EJ antibody were found to have positive correlation with bacterial diversity (Shannon-wiener diversity index and Chao1, richness estimator) between myositis group and control groups. The combination of E. coli and R. intestinalis could distinguish myositis group from Healthy controls effectively. R. intestinalis can also be applied in the distinguishment of RP-ILD group vs. C-ILD group in myositis patients.Conclusion Our MWAS study first revealed the link between gut microbiome and pathgenesis of myositis, which may help us understand the role of gut microbiome in the etiology of myositis and myositis-associated RP-ILD.
Striving for Sufficient Milk to Have a Healthy Late Preterm Baby: a Grounded Theory Study
Authors: Choijorhor Rungtawan , Kantaruksa Kannika , Chotibang Jutamas , Chaloumsuk Nonglak
Published: March 2022

Background: Late preterm infants are at risk for more health problems than full-term infants. They require good nutrition for growth, and breast milk is the gold standard because it contains valuable nutrients. Currently, the population of late preterm infants is increasing as exclusive breastfeeding rates decrease. Hence, this study explored exclusive breastfeeding experiences among Thai first-time mothers of late preterm infants. Methods: Participants were recruited from the family planning unit of a university hospital in Northern Thailand. A grounded theory study design was adopted, and an interview guideline was used to interview seventeen first-time mothers who exclusively breastfed their late preterm infants for the first six weeks of life. Results: “Striving for sufficient milk to have a healthy baby” emerged as the core category. It was defined as a process in which mothers of late preterm infants had to exert great effort to produce sufficient milk for their infants. The following three phases supported the core category: preparing for breastfeeding, overcoming the problem of insufficient milk supply, and managing to continue breastfeeding. Conclusion: Perceived insufficient milk supply in first-time mothers is a threat to achieving exclusive breastfeeding of their late preterm infants. However, the desire to have a healthy baby results in mothers’ effort to achieve a sufficient milk supply. Nurse midwives could apply the management process of exclusive breastfeeding as a guideline when providing support for these mothers throughout the sequence of antenatal, intrapartum, and postpartum care.Trial registration: Permission to conduct the study was obtained from the Institutional Review Board Committee, Faculty of Nursing, and the Faculty of Medicine, Chiang Mai University, No. 2561-EXP065 and No. 2561-05865.
Metal-organic framework [H2NMe2]3 [Tb(PDA)3] induces cytotoxic effects and changes DNA methylation-related gene expression in a human fibroblast cell line
Authors: Carrilo-Cocom Leydi Maribel , Juárez-Méndez Lucia , Rincon Susana , Rivera-Villanueva José María , Nic-Can Geovanny Iran , Zepeda Alejandro
Published: March 2022

The lanthanide metal-organic frameworks (lanthanide MOFs) may be utilized for a variety of environmental and human health applications due to its luminescent properties and high thermal and water stability. However, the cytotoxic and epigenetic effects that these produce in human cells are not known. Therefore, we evaluated the cytotoxic effects, internalization and changes in DNA methylation-associated gene expression induced by exposing human fibroblast cells to a Terbium-based MOF (Tb-MOF). For this purpose, cells were exposed to six concentrations (0.05 to 1.6 mg/mL) of [H2NMe2]3 [Tb(PDA)3] for 48 h. SEM, Confocal microscopy and EDS analysis were performed. Cytotoxicity was determined with the Crystal violet and MTT assays. The results demonstrated the internalization of Tb-MOF at concentrations as low as 0.05 mg/mL, as well as dose-dependent toxicity. Additionally, we detected significant changes in the gene expression levels of DNA methyltransferases and demethylases (important regulators of cell development) due to the presence of Tb-MOF, suggesting that Tb-MOF could generate epigenetic changes even at low concentrations. Results of our study may establish a foundation for future research attempting to develop and apply secure nanomaterials (e.g., MOFs) to minimize damage to the environment and human health.
Vision restoration in photoreceptor-degenerated mice and macaque monkeys using nanowires
Authors: Yang Ruyi , Zhao Peng , Wang Liyang , Feng Chenli , Peng Chen , Wang Zhexuan , Zhang Yingying , Shen Minqian , Shi Kaiwen , Weng Shi-Jun , Dong Chunqiong , Chen Yuqing , Zeng Fu , Zhang Tianyun , Fu Luoyin , Ma Ruoxi , Wang Fei , Jiang Su , Xu Wendong , Wang Gang , Zheng Gengfeng , Chen Aihua , Yuan Fei , Yuan Yuanzhi , Yan Biao , Zhang Jiayi
Published: March 2022

Photoreceptor degeneration diseases, such as retinitis pigmentosa and age-related macular degeneration, are major causes of blindness. Photovoltaic devices or materials activates retinal cells in response to light, hence are promising retinal prosthesis in treating blind patients. The restoration of image-forming vision with high sensitivity is the key. Here we demonstrated that Au nanoparticle-coated titania (TiO2-x) nanowire (NW) arrays can restore vision in blind mice and non-human primates with photoreceptor degeneration. We first showed that blind mice with subretinal implant of NW arrays were capable of detecting static, moving and flashing objects with low light intensity threshold for 22 months, having a visual acuity of 0.3 cpd (0.4 cpd in normal mice). Results in chronic in vivo calcium imaging in primary visual cortex (V1) collectively suggested the plastic change in V1 neurons as well as the improvement in visual information encoding for natural images after NW implant. What’s more, macaque monkeys with subretinal implant of NW arrays were capable of detecting an LED of 0.5º in diameter at 10 μW·mm-2 in visually-guided saccade experiments. Our findings opened up the possibility to utilize nanomaterials as artificial photoreceptors to ameliorate visual deficits of patients with photoreceptor degeneration.