bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the binding behavior and functional properties of soybean protein isolate and β-carotene
Authors: Zhang Yating , Zhao Wenqi , Xing Zhuqing , Zhu Beibei , Hou Ruiyang , Zhang Junxi , Li Taoran , Zhang Zifan , Wang Hongwu , Li Zheng
Published: September 2022

This study focused on the non-covalent interaction between soybean protein isolate (SPI) and β-carotene (BC). The conformational changes of SPI with β-carotene in varying proportions (BC/SPI: 2%, 4%, 6%, 8%, and 10%) were investigated by multi-spectroscopy and molecular docking. Results showed that the quenching mode is static quenching and binding affinity increased with temperature. The stoichiometry was 1:1, indicating there was only one binding site in SPI. The binding was based on entropy and primarily driven by hydrophobic interactions and its binding constant was in the order of 104 L⋅mol–1. The addition of the β-carotene affected the secondary structure of SPI resulting in an increase in α-Helix and a decrease in random coil and β-turn content, indicating protein aggregated and hydrophobic interactions occurred. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) verified that no new larger molecular weight substance was formed and no covalent interaction existed. Molecular docking corroborated that electrostatic and hydrophobic interactions were both involved in the formation of complexes, where hydrophobic interaction was the dominant one. Moreover, β-carotene improved 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, foaming capacity, and emulsifying stability of SPI. These findings provide useful information about the interaction mechanism of SPI and β-carotene, which contributes to the further development and application of SPI products rich in β-carotene in the food industry.
Gastric adenocarcinoma: 1-year overall survival, disability-adjusted life years, years of life lost, and prognostic factors—a single-institution experience
Authors: Tiengo Tatiane , Fernandes Gisele Aparecida , Curado Maria Paula
Published: September 2022

Objective

To analyze factors affecting 1-year overall survival and burden of gastric adenocarcinoma in a single-institution cohort.

Methods

A prospective cohort study of gastric adenocarcinoma patients from a cancer center in São Paulo, Brazil, was conducted between February 2016 and July 2019. Overall survival was analyzed at 12 months post-diagnosis using the Kaplan–Meier method. A log-rank test was applied to compare curves. Sociodemographic and clinicopathological features were assessed to detect prognostic factors using univariate and multivariable Cox regression analyses to calculate hazard ratio (HR) and its confidence intervals (CIs). Disability-adjusted life years (DALY) constituted the sum of years of life lost (YLL) plus years lived with disability (YLD). YLL represented the sum of years lost before the age of 76.6 years. YLD was calculated as the number of cases multiplied by the duration and burden of the disease. YLL per death was calculated as the mean YLL for each individual.

Results

Overall survival at 1-year follow-up was 80.8%. The multivariable model adjusted for age and sex identified cerebrovascular disease (HR 8.5, 95% CI 3.3–21.8), stage III/IV (HR 5.7, 95% CI 2.3–13.7), diabetes (HR 3.2, 95% CI 1.5–6.6), and<9 years of education (HR 2.9, 95% CI 1.5–5.8) as prognostic factors. Out of the 214 treated cases, there was 700.72 DALY during the first year, of which 90.55% corresponded to YLL and 9.45% to YLD. The average YLL per death was 15.48 and was higher among women (19.24 YLL per death).

Conclusion

At a single cancer center, 1-year overall survival probability was approximately 80% in patients with gastric adenocarcinoma. Patients with a higher risk of death had cerebrovascular disease, advanced clinical staging, diabetes, and/or lower educational level. Approximately 700 years of DALY was documented, with women having the highest YLL per death. Because this study was conducted at a single cancer center, the results might not be representative of a general population. To the best of our knowledge, this study was the first to assess gastric adenocarcinoma DALY, YLL, and YLL per death in the first year of follow-up in a hospital cohort in Brazil.
Role of reactive thrombocytosis after primary cytoreductive surgery in advanced ovarian cancer
Authors: Kim Myeong-Seon , Baek Seung Hun , Noh Joseph J. , Shim Jung In , Kang Jun Hyeok , Jeong Soo Young , Choi Chel Hun , Kim Tae-Joong , Lee Jeong-Won , Lee Yoo-Young
Published: September 2022

We investigated the incidence of reactive thrombocytosis after maximal cytoreductive surgery in advanced epithelial ovarian cancer (EOC) and its role in patient survival. We retrospectively reviewed the electronic medical records of patients who underwent primary cytoreductive surgery for advanced EOC from 1 January 2012 to 31 December 2017. We analyzed the serum platelet counts at various time points from before surgery, during the peri-operative period, and after each cycle of adjuvant chemotherapy. A total of 474 patients were eligible for the analysis. Among them, 401 patients (84.6%) had FIGO stage III disease status. The most common histology type was serous adenocarcinoma (405 patients, 85.4%). Seventy-nine patients (22.6%) received splenectomy, and optimal cytoreduction was achieved in 326 patients (68.8%). A week after surgery, thrombocytosis was observed in 165 patients (34.8%) in the entire cohort. Higher platelet counts were observed in patients with splenectomy compared with patients without splenectomy. In particular, thrombocytosis on the fifth cycle of adjuvant chemotherapy showed the most significant effects on overall survival in multivariate analysis. In a logistic regression model, splenectomy was significantly attributed to thrombocytosis on the fifth cycle of chemotherapy. Reactive thrombocytosis after primary cytoreductive surgery is associated with poor survival in advanced EOC, particularly when thrombocytosis is observed during adjuvant chemotherapy.
Severe radiation-induced lymphopenia during postoperative radiotherapy or chemoradiotherapy has poor prognosis in patients with stage IIB-III after radical esophagectomy: A post hoc analysis of a randomized controlled trial
Authors: Ni Wenjie , Xiao Zefen , Zhou Zongmei , Chen Dongfu , Feng Qinfu , Liang Jun , Lv Jima
Published: September 2022

Objective

To investigate whether radiation-induced lymphopenia (RIL) affects survival and identify the predictors of RIL in postoperative esophageal cancer.

Materials and methods

Post hoc analysis was conducted on data from 116 patients with esophageal cancer from a randomized controlled trial comparing adjuvant therapy with surgery alone. Doses of 54 Gy in 27 fractions was delivered in the postoperative radiotherapy (PORT) group and 50.4 Gy in 28 fractions combined with chemotherapy was delivered in postoperative concurrent chemoradiotherapy (POCRT) group. Blood counts were obtained before, during, and at first follow-up after treatment. Lymphopenia was graded per version 4.03 of the Common Terminology Criteria for Adverse Events. Disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method, and compared between groups using the log-rank test. Receiver operating characteristic curves identified thresholds for preventing grade 4 (G4) lymphopenia.

Results

Median follow-up duration was 56.0 months. During treatment, 16 patients (13.8%) had G4 lymphopenia. All cases of G4 lymphopenia occurred in group PORT (30.2% vs 0.0%, p<0.001). Baseline absolute lymphocyte count was comparable between G1-3 and G4 patients (2.0 ± 0.8 *109/L vs 1.7 ± 0.5 *109/L; p=0.101). The 3-year DFS was significantly lower in group G4 lymphopenia than that in group G1-3 (31.3% vs 57.6%, p=0.036). The 3-year OS was comparable between both groups (50.0% vs 66.5%, p=0.095). Logistic regression analysis revealed that exposed more thoracic marrow (TM V20 ≥75%; TVB V20 ≥71%), heart (V15 ≥40%) and PTV (volume ≥507 ml) were associated with G4 lymphopenia (p<0.05).

Conclusions

G4 RIL had poor disease-free survival, which may be related to more dose exposure of thoracic marrow and heart due to larger PTV. Reasonably reducing the radiation field combined with concurrent chemotherapy, or radiation dose constraints for these normal tissues may be sufficient to decrease the incidence of G4 lymphopenia, but further prospective trials are needed to verify the results.

Clinical Trial Registration

clinicaltrials.gov, identifier NCT02279134
Phenformin suppresses angiogenesis through the regulation of exosomal microRNA-1246 and microRNA-205 levels derived from oral squamous cell carcinoma cells
Authors: Zhuang Dexuan , Wang Shuangshuang , Liu Guanyi , Liu Panpan , Deng Huiting , Sun Jianfeng , Liu Chang , Leng Xue , Zhang Qun , Bai Fuxiang , Mi Jun , Wu Xunwei
Published: September 2022

Exosomes secreted by cancer cells are important components in the tumor microenvironment, enabling cancer cells to communicate with each other and with noncancerous cells to play important roles in tumor progression and metastasis. Phenformin, a biguanide antidiabetic drug, has been reported to have a strong antitumor function in multiple types of cancer cells, however little research has been reported about whether phenformin can regulate the secretion of exosomes by cancer cells to regulate the tumor microenvironment and contribute to its antitumor function. Here we found that exosomes (Phen-Exo) derived from phenformin-treated oral squamous cell carcinoma (OSCC) cells significantly suppress the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. The inhibition of angiogenesis by Phen-Exo was verified in vivo by matrigel plug angiogenesis assays and by chick chorioallantoic membrane assays. Mechanistically, we discovered that the expression of microRNA-1246 (miR-1246) and microRNA-205 (miR-205) was significantly increased in exosomes secreted by OSCC cells treated with phenformin, while high expression levels of miR-1246 or miR-205 in vascular endothelial cells inhibited their angiogenic effects and decreased expression of the angiogenic factor VEGFA. In conclusion, these results reveal that phenformin can inhibit angiogenesis by regulating the levels of miR-1246 and miR-205 in exosomes secreted by OSCC cells, suggesting that phenformin has the potential to alter the tumor microenvironment to antagonize the growth of OSCCs, which provides a theoretical basis for developing new strategies to treat OSCCs in the future.
Systemic treatment for primary malignant sarcomas arising in craniofacial bones
Authors: Bielack Stefan S.
Published: September 2022

Introduction

Craniofacial bones may be the site of origin of various sarcomas. We review the various malignancies affecting this region of the body and attempt to put systemic treatment approaches into perspective.

Material and methods

Non-systematic literature review

Results

Conventional types of osteosarcoma, Ewing sarcoma, and chondrosarcoma are the most frequent bone sarcomas occurring in craniofacial region, but variants may occur. The tumors’ biologies and the resulting treatment strategies vary distinctly. As a general rule, local control remains paramount regardless of histology. The efficacy of antineoplastic chemotherapy varies by type of malignancy. It is clearly indicated in Ewing sarcoma and related tumors, potentially of benefit in high-grade osteosarcoma, undifferentiated pleomorphic sarcoma, dedifferentiated and mesenchymal chondrosarcoma, and of no proven benefit in the others.

Conclusions

Various histologies demand various and distinct treatment approaches, with local control remaining paramount in all. The efficacy of systemic treatments varies by type of tumor. Prospective trials would help in all of these to better define systemic treatment strategies.
Lymphoma tumor burden before chimeric antigen receptor T-Cell treatment: RECIL vs. Lugano vs. metabolic tumor assessment
Authors: Winkelmann Michael , Bücklein Veit L. , Blumenberg Viktoria , Rejeski Kai , Ruzicka Michael , Unterrainer Marcus , Schmidt Christian , Dekorsy Franziska J. , Bartenstein Peter , Ricke Jens , von Bergwelt-Baildon Michael , Subklewe Marion , Kunz Wolfgang G.
Published: September 2022

Purpose

High tumor burden has emerged as a negative predictor of efficacy in chimeric antigen receptor T-cell therapy (CART) in patients with refractory or relapsed large B-cell lymphoma. This study analyzed the deviation among imaging-based tumor burden (TB) metrics and their association with progression-free (PFS) and overall survival (OS).

Materials and methods

In this single-center observational study, we included all consecutively treated patients receiving CD19 CART with available baseline PET-CT imaging. Imaging-based TB was determined based on response evaluation criteria in lymphoma (RECIL), the Lugano criteria, and metabolic tumor volume. Total, nodal and extranodal TB were represented, according to the respective criteria, by sum of longest diameters (TBRECIL), sum of product of perpendicular diameters (TBLugano), and metabolic tumor volume (TBMTV). Correlation statistics were used for comparison. Proportional Cox regression analysis studied the association of TB metrics with PFS and OS.

Results

34 consecutive patients were included (median age: 67 years, 41% female) with total median baseline TBRECIL of 12.5 cm, TBLugano of 4,030 mm2 and TBMTV of 330 mL. The correlation of TBRECIL and TBLugano with TBMTV was strong (ρ=0.744, p<0.001 and ρ=0.741, p<0.001), with lowest correlation for extranodal TBRECIL with TBMTV (ρ=0.660, p<0.001). Stratification of PFS was strongest by total TBMTV>50% (HR=2.915, p=0.042), whereas total TBRECIL>50% and total TBLugano>50% were not significant (both p>0.05). None of the total TB metrics were associated with OS (all p>0.05).

Conclusion

Pre-CART TB metrics vary significantly based on the assessment method, impacting their association with survival outcomes. The correlation between TBRECIL, TBLugano and TBMTV was influenced by disease phenotype and prior bridging therapy. TB method of assessment must be considered when interpreting the impact of TB on outcomes in clinical trials. Considering the heterogeneity, our results argue for standardization and harmonization across centers.
Association of methylenetetrahydrofolate reductase gene polymorphisms and maternal folic acid use with the risk of congenital heart disease
Authors: Zhong Taowei , Song Xinli , Liu Yiping , Sun Mengting , Zhang Senmao , Chen Letao , Diao Jingyi , Li Jinqi , Li Yihuan , Shu Jing , Wei Jianhui , Zhu Ping , Wang Tingting , Qin Jiabi
Published: September 2022

Background

To systematically evaluate the association of MTHFR genetic polymorphisms, maternal folic acid intake, and the time when folic acid intake was started with the risk of congenital heart disease (CHD) and investigated the role of their interaction on infant CHD risk in Chinese populations.

Methods

A case–control study involving 592 CHD cases, 617 health controls, and their mothers was performed. The exposures of interest were single nucleotide polymorphisms (SNPs) of the MTHFR gene, maternal folic acid use, and the time when folic acid use was started. We applied the logistic regression model to explore the strength of association.

Results

Our findings showed that mothers lacking folic acid intake had a significantly higher risk of CHD in offspring (aOR = 2.00; 95%CI: 1.34–2.98). Mothers who started to use folic acid from the first trimester of the fetation (aOR = 1.65; 95% CI: 1.22–2.23) or from the second trimester of the fetation (aOR = 7.77; 95% CI: 2.52–23.96), compared with those starting to use folic acid from 3 months previous to the conception, were at a significantly higher risk of CHD in offspring. Genetic variants at rs2066470 (AA vs. GG: aOR = 5.09, 95%CI: 1.99–13.03), rs1801133 (AA vs. GG: aOR = 2.49, 95%CI: 1.58–3.93), and rs1801131 (TG vs. TT: aOR = 1.84, 95%CI: 1.36–2.50; GG vs. TT: aOR = 3.58, 95%CI: 1.68–7.63) were significantly associated with the risk of CHD based on the multivariate analysis. Additionally, statistically significant interactions between maternal folic acid intake and genetic variants of the MTHFR gene at rs1801133 and rs1801131 were observed.

Conclusion

An association of maternal folic acid intake and the time when intake was started with the risk of CHD in offspring was found. What's more, maternal folic acid fortification may help counteract partial of the risks of CHD in offspring attributable to MTHFR genetic mutations.

Registration number

http://www.chictr.org.cn/edit.aspx?pid=28300&htm=4, identifier: ChiCTR1800016635.
Effects of uteroplacental insufficiency on growth-restricted rats with altered lung development: A metabolomic analysis
Authors: Yuliana Merryl Esther , Huang Zheng-Hao , Chou Hsiu-Chu , Chen Chung-Ming
Published: September 2022

Background

Intrauterine growth restriction (IUGR) is among the most challenging problems in antenatal care. Several factors implicated in the pathophysiology of IUGR have been identified. We aimed to investigate the effect of UPI on lung development by identifying metabolic changes during the first seven days of postnatal life.

Materials and methods

On gestation day 17, four time-dated pregnant Sprague Dawley rats were randomized to a IUGR group or a control group, which underwent an IUGR protocol comprising bilateral uterine vessel ligation and sham surgery, respectively. On gestation day 22, 39 control and 26 IUGR pups were naturally delivered. The rat pups were randomly selected from the control and IUGR group on postnatal day 7. The pups' lungs were excised for histological, Western blot, and metabolomic analyses. Liquid chromatography mass spectrometry was performed for metabolomic analyses.

Results

UPI induced IUGR, as evidenced by the IUGR rat pups having a significantly lower average body weight than the control rat pups on postnatal day 7. The control rats exhibited healthy endothelial cell healthy and vascular development, and the IUGR rats had a significantly lower average radial alveolar count than the control rats. The mean birth weight of the 26 IUGR rats (5.89 ± 0.74 g) was significantly lower than that of the 39 control rats (6.36 ± 0.55 g; p < 0.01). UPI decreased the levels of platelet-derived growth factor-A (PDGF-A) and PDGF-B in the IUGR newborn rats. One-way analysis of variance revealed 345 features in the pathway, 14 of which were significant. Regarding major differential metabolites, 10 of the 65 metabolites examined differed significantly between the groups (p < 0.05). Metabolite pathway enrichment analysis revealed significant between-group differences in the metabolism of glutathione, arginine–proline, thiamine, taurine–hypotaurine, pantothenate, alanine–aspartate–glutamate, cysteine–methionine, glycine–serine–threonine, glycerophospholipid, and purine as well as in the biosynthesis of aminoacyl-tRNA, pantothenate, and CoA.

Conclusions

UPI alters lung development and metabolomics in growth-restricted newborn rats. Our findings may elucidate new metabolic mechanisms underlying IUGR-induced altered lung development and serve as a reference for the development of prevention and treatment strategies for IUGR-induced altered lung development.
The burden of hospital-attended influenza in Norwegian children
Authors: Bøås Håkon , Bekkevold Terese , Havdal Lise Beier , Kran Anne-Marte Bakken , Rojahn Astrid Elisabeth , Størdal Ketil , Debes Sara , Døllner Henrik , Nordbø Svein Arne , Barstad Bjørn , Haarr Elisebet , Vázquez Fernández Liliana , Nakstad Britt , Leegaard Truls Michael , Hungnes Olav , Flem Elmira ,   Norwegian Enhanced Pediatric Immunisation Surveillance (NorEPIS) Network
Published: September 2022

Background

Norwegian health authorities do not recommend universal pediatric vaccination against seasonal influenza. We aimed to estimate the incidence of influenza by age and underlying medical conditions in hospitalized Norwegian children aged <18 years.

Methods

Active surveillance for influenza in children <18 years was implemented in five hospitals during 2015–18. Children with respiratory symptoms and/or fever were prospectively enrolled and tested for influenza. Surveillance data were linked to health registry data to estimate the national burden of influenza in hospitals.

Results

In 309 (10%) out of 3,010 hospital contacts, the child tested positive for influenza, corresponding to an average incidence of 0.96 hospital-attended influenza cases per 1,000 children <18 years of age. Children <1 year of age (3.8 per 1,000 children) and children with underlying medical conditions (17 per 1,000 children with bronchopulmonary dysplasia) had the highest average incidence. Among <1 year old children, 3% tested positive for influenza, compared to 25% for children aged 6–17. Few children were vaccinated against influenza.

Conclusions

Children <1 year of age and children with underlying medical conditions had a higher incidence of influenza requiring hospital treatment compared to the general population. Effective interventions against seasonal influenza for children in Norway should be considered.
Case report: Microcirculatory leukocytes in a pediatric patient with severe SARS-CoV-2 pneumonia. Findings of leukocytes trafficking beyond the lungs
Authors: Bottari Gabriella , Ince Can , Confalone Valerio , Perdichizzi Salvatore , Casamento Tumeo Chiara , Nunziata Joseph , Bernardi Stefania , Calò Carducci Francesca , Lancella Laura , Bernaschi Paola , Russo Cristina , Perno Carlo Federico , Cecchetti Corrado , Villani Alberto
Published: September 2022

Background

SARS-CoV-2 can lead to excessive coagulation and thrombo-inflammation with deposition of microthrombi and microvascular dysfunction. Several studies in human and animal models have already evidenced biomarkers of endothelial injury during SARS-CoV-2 infection. Real-time observation of sublingual microcirculation using an handheld vital microscopy with an Incident Dark Field (IDF) technique could represent a non-invasive way to assess early signs of microvascular dysfunction and endothelial inflammation in patients with severe COVID-19 infection.

Clinical case

We report for the first time in a pediatric patient with severe SARS-CoV-2 pneumonia findings about microcirculatory leukocytes in the sublingual microcirculation of a 7 month-old patient admitted to our PICU using handheld vital microscopy with IDF technique.

Results

Sublingual microcirculation analysis revealed the presence of microcirculatory alterations and an extensive presence of leukocytes in the patient’s sublingual microcirculation. It’s significant to underline how the patient didn’t show a contextual significant increase in inflammatory biomarkers or other clinical signs related to an inflammatory response, beyond the presence of severe hypoxic respiratory failure.

Conclusion

Leukocyte activation in multiple organs can occur at the endothelial lining of the microvasculature where a surge of pro-inflammatory mediators can result in accumulation of activated leukocytes and degradation of the endothelium. The introduction of a method to assess in a non-invasive, real-time manner the extent of inflammation in a patient with COVID19 could lead to potential clinical and therapeutic implications. However, more studies are required to prove that studying leukocytes microcirculation using sublingual microcirculation analysis could be useful as a bedside point of care monitor to predict the presence of systemic inflammation associated with the impact of COVID-19, leading in a late phase of severe SARS-CoV-2 infection to a microvascular dysfunction and micro-thrombosis.
The protective activity of genistein against bone and cartilage diseases
Authors: Wu Zhenyu , Liu Luying
Published: September 2022

Genistein, a natural isoflavone rich in soybean and leguminous plants, has been shown various biological effects, such as anti-inflammation, anti-oxidation, anti-cancer, and bone/cartilage protection. Due to the structural similarity to estrogen, genistein exhibits estrogen-like activity in protecting against osteoporosis and osteoarthritis. Furthermore, genistein has been considered as an inhibitor of tyrosine kinase, which has been found to be dysregulated in the pathological development of osteoporosis, osteoarthritis, and intervertebral disc degeneration (IDD). Many signaling pathways, such as MAPK, NF-κB, and NRF2/HO-1, are involved in the regulatory activity of genistein in protecting against bone and cartilage diseases. The potential molecular mechanisms of genistein in therapeutic management of bone and cartilage diseases have been investigated, but remain to be fully understood. In this article, we mainly discuss the current knowledge of genistein in protecting against bone and cartilage diseases, such as osteoporosis, osteoarthritis, rheumatoid arthritis (RA), and IDD.
Exploring the recent trends in perturbing the cellular signaling pathways in cancer by natural products
Authors: Rahman Md. Mominur , Sarker Md. Taslim , Alam Tumpa Mst. Afroza , Yamin Md. , Islam Tamanna , Park Moon Nyeo , Islam Md. Rezaul , Rauf Abdur , Sharma Rohit , Cavalu Simona , Kim Bonglee
Published: September 2022

Cancer is commonly thought to be the product of irregular cell division. According to the World Health Organization (WHO), cancer is the major cause of death globally. Nature offers an abundant supply of bioactive compounds with high therapeutic efficacy. Anticancer effects have been studied in a variety of phytochemicals found in nature. When Food and Drug Administration (FDA)-approved anticancer drugs are combined with natural compounds, the effectiveness improves. Several agents have already progressed to clinical trials based on these promising results of natural compounds against various cancer forms. Natural compounds prevent cancer cell proliferation, development, and metastasis by inducing cell cycle arrest, activating intrinsic and extrinsic apoptosis pathways, generating reactive oxygen species (ROS), and down-regulating activated signaling pathways. These natural chemicals are known to affect numerous important cellular signaling pathways, such as NF-B, MAPK, Wnt, Notch, Akt, p53, AR, ER, and many others, to cause cell death signals and induce apoptosis in pre-cancerous or cancer cells without harming normal cells. As a result, non-toxic “natural drugs” taken from nature’s bounty could be effective for the prevention of tumor progression and/or therapy of human malignancies, either alone or in combination with conventional treatments. Natural compounds have also been shown in preclinical studies to improve the sensitivity of resistant cancers to currently available chemotherapy agents. To summarize, preclinical and clinical findings against cancer indicate that natural-sourced compounds have promising anticancer efficacy. The vital purpose of these studies is to target cellular signaling pathways in cancer by natural compounds.
Insula deep rTMS and varenicline for smoking cessation: A randomized control trial study protocol
Authors: Ibrahim Christine , Malik Saima , Barr Mera S. , Blumberger Daniel M. , Daskalakis Zafiris J. , Le Foll Bernard
Published: September 2022

Background: Current approved therapies for smoking cessation have modest long-term effects for abstinence. The insular cortex has been identified by preclinical and clinical studies as a critical target for addiction treatment. Insula functions can be modulated non-invasively using brain stimulation. It is unknown if deep repetitive transcranial magnetic stimulation (rTMS) of the insula can improve smoking cessation of smokers trying to quit using varenicline.

Methods: This will be a randomized, double-blind, sham-controlled clinical trial with 50 nicotine dependent smokers looking to quit. They will be randomly assigned to receive either active (10 Hz) or sham insula deep rTMS. Deep rTMS will be administered for 4 weeks (5 days/week). All participants will receive open label varenicline for 12 weeks. The primary outcome measure will be the 7-day point prevalence abstinence at the end of 12 weeks. The secondary outcomes will be Fagerström Test of Nicotine Dependence, Minnesota Nicotine Withdrawal Scale, Tiffany Questionnaire of Smoking Urges, expired carbon monoxide measurements, cigarettes smoked per day, point prevalence abstinence at end of 4 weeks, prolonged and continuous abstinence at 6 months. The measures will be collected throughout the 3-month treatment period as well as at the 6-month follow up.

Discussion: This trial will test for the first time the impact of deep insula rTMS on smoking cessation in smokers treated with varenicline. This trial will use an H-coil specific to the insula, while previous studies have targeted both the insula and prefrontal cortex. This trial will inform on the utility to combine insula deep rTMS with varenicline to improve smoking abstinence rates.

Clinical Trial Registration: Trial registered at https://clinicaltrials.gov/ct2/show/NCT04083144 (Identifier: NCT04083144).
The genetic mechanisms underlying the convergent evolution of pollination syndromes in the Neotropical radiation of Costus L.
Authors: Valderrama Eugenio , Landis Jacob B. , Skinner Dave , Maas Paul J. M. , Maas-van de Kramer Hiltje , André Thiago , Grunder Nikolaus , Sass Chodon , Pinilla-Vargas Maria , Guan Clarice J. , Phillips Heather R. , Almeida Ana Maria Rocha de , Specht Chelsea D.
Published: September 2022

Selection together with variation in floral traits can act to mold floral form, often driven by a plant’s predominant or most effective pollinators. To investigate the evolution of traits associated with pollination, we developed a phylogenetic framework for evaluating tempo and mode of pollination shifts across the genusCostusL., known for its evolutionary toggle between traits related to bee and bird pollination. Using a target enrichment approach, we obtained 957 loci for 171 accessions to expand the phylogenetic sampling of NeotropicalCostus. In addition, we performed whole genome resequencing for a subset of 20 closely related species with contrasting pollination syndromes. For each of these 20 genomes, a high-quality assembled transcriptome was used as reference for consensus calling of candidate loci hypothesized to be associated with pollination-related traits of interest. To test for the role these candidate genes may play in evolutionary shifts in pollinators, signatures of selection were estimated asdN/dSacross the identified candidate loci. We obtained a well-resolved phylogeny for NeotropicalCostusdespite conflict among gene trees that provide evidence of incomplete lineage sorting and/or reticulation. The overall topology and the network of genome-wide single nucleotide polymorphisms (SNPs) indicate that multiple shifts in pollination strategy have occurred acrossCostus, while also suggesting the presence of previously undetected signatures of hybridization between distantly related taxa. Traits related to pollination syndromes are strongly correlated and have been gained and lost in concert several times throughout the evolution of the genus. The presence of bract appendages is correlated with two traits associated with defenses against herbivory. Although labellum shape is strongly correlated with overall pollination syndrome, we found no significant impact of labellum shape on diversification rates. Evidence suggests an interplay of pollination success with other selective pressures shaping the evolution of theCostusinflorescence. Although most of the loci used for phylogenetic inference appear to be under purifying selection, many candidate genes associated with functional traits show evidence of being under positive selection. Together these results indicate an interplay of phylogenetic history with adaptive evolution leading to the diversification of pollination-associated traits in NeotropicalCostus.
Genetic mapping and genome-wide association study identify BhYAB4 as the candidate gene regulating seed shape in wax gourd (Benincasa hispida)
Authors: Luo Chen , Yan Jinqiang , Liu Wenrui , Xu Yuanchao , Sun Piaoyun , Wang Min , Xie Dasen , Jiang Biao
Published: September 2022

Wax gourd is an important vegetable crop of the Cucurbitaceae family. According to the shape and structure of the seed coat, the seeds of the wax gourd can be divided into bilateral and unilateral. Bilateral seeds usually germinate quickly and have a high germination rate than unilateral seeds. Thereby, wax gourd varieties with bilateral seeds are more welcomed by seed companies and growers. However, the genetic basis and molecular mechanism regulating seed shape remain unclear in the wax gourd. In this study, the genetic analysis demonstrated that the seed shape of wax gourd was controlled by a single gene, with bilateral dominant to unilateral. Combined with genetic mapping and genome-wide association study, Bhi04G000544 (BhYAB4), encoding a YABBY transcription factor, was identified as the candidate gene for seed shape determination in the wax gourd. A G/A single nucleotide polymorphism variation of BhYAB4 was detected among different germplasm resources, with BhYAB4G specifically enriched in bilateral seeds and BhYAB4A in unilateral seeds. The G to A mutation caused intron retention and premature stop codon of BhYAB4. Expression analysis showed that both BhYAB4G and BhYAB4A were highly expressed in seeds, while the nuclear localization of BhYAB4A protein was disturbed compared with that of BhYAB4G protein. Finally, a derived cleaved amplified polymorphic sequence marker that could efficiently distinguish between bilateral and unilateral seeds was developed, thereby facilitating the molecular marker-assisted breeding of wax gourd cultivars.
A CRISPR/Cas12a-based portable platform for rapid detection of Leptosphaeria maculans in Brassica crops
Authors: Lei Rong , Li Yuan , Li Limei , Wang Jingyi , Cui Zhenhai , Ju Rui , Jiang Li , Liao Xiaoling , Wu Pinshan , Wang Xinyi
Published: September 2022

Establishing a portable diagnostic method for identifying plant pathogens is essential to prevent the spread of plant disease, especially in field and customs inspections. Leptosphaeria maculans (L. maculans) is an aggressive fungus, which causes severe phoma stem canker of Brassica napus, responsible for major yield losses of oilseed rape worldwide. In this study, CRISPR/Cas12a-based detection system and recombinase polymerase amplification (RPA) technique were employed to develop a rapid and sensitive detection method for identifying L. maculans. The involved RPA pre-amplification and CRISPR/Cas12a cleavage confer considerable sensitivity and selectivity, which can be finished within 45 min with a LOD of 4.7 genomic DNA copies. This detection system was further developed to two portable platforms, i.e., one-pot lateral flow detection and all-in-one chip lateral flow assay (AOCLFA), which integrates the lyophilized recombinase polymerase amplification (RPA) reagents and lyophilized Cas12a cleavage reagents in one tube or chip. The developed portable platforms have flexible portability and simple operation for the detection of L. maculans from plant tissues in the field. The proposed portable suitcase containing the minimum equipment, regents, and AOCLFA meets the practical needs of rapid on-site disease screening of plant fungi, port quarantine, or pathogen spreading control.
Effects of limited water supply on metabolite composition in tomato fruits (Solanum lycopersicum L.) in two soils with different nutrient conditions
Authors: Kim Yangmin X. , Son Su Young , Lee Seulbi , Lee Yejin , Sung Jwakyung , Lee Choong Hwan
Published: September 2022

Effect of water supply to metabolites in tomato fruit was compared in two soils with different nutrient conditions, i.e., either limited or excess. Two types of soil nutrient condition, type A: nutrient-limited and type B: nutrient-excess, were prepared as follows; type A is a low nutrient-containing soil without a replenishment of starved nitrogen and phosphorous, type B is a high nutrient-containing soil exceeding the recommended fertilization. Soil water was adjusted either at −30 kPa (sufficient) or −80 kPa (limited). For harvested tomato fruits, we examined primary and secondary metabolites using non-targeted mass spectrometry based metabolomics. The fruit production and leaf SPAD were greatly dependent on soil nutrient levels, by contrast, the level of lycopene remained unchanged by different levels of water and nutrient supply. The perturbation of metabolites by water supply was clear in the nutrient-excess soil. In particular, limited water supply strongly decreased primary metabolites including sugars and amino acids. We demonstrated that water stress differently shifted primary metabolites of tomato fruits in two soils with different nutrient conditions via non-targeted mass spectrometry-based metabolomics. In conclusion, we suggest that the limited water supply in soils with surplus nutrient is not a recommendable way for tomato ‘cv. Super Dotaerang’ production if fruit nutritional quality such as sugars and amino acids is in the consideration, although there was no disadvantage in fruit yield.
A suitable organic fertilizer substitution ratio could improve maize yield and soil fertility with low pollution risk
Authors: He Hao , Peng Mengwen , Ru Sibo , Hou Zhenan , Li Junhua
Published: September 2022

Organic fertilizer substitution (OFS) is an effective strategy for reducing the chemical fertilizer usage; however, the effects of different OFS ratios (OFSRs) on maize yield, soil fertility, and heavy metal pollution risk are still unclear. Therefore, determining a suitable OFSR is important. Through the pot experiment, no fertilizer (CK) and organic fertilizer substituting 0% (CF, chemical fertilizer alone), 8% (OF8), 16% (OF16), and 24% (OF24) of the chemical N fertilizer were set to investigate the effects of different OFSRs on maize growth and yield, soil properties (available nutrients, carbon fractions, and carbon pool indices), and nutrients and heavy metals in grain and soil. The results showed that OF8, OF16, and OF24 improved soil fertility by increasing soil organic carbon (SOC, by 10.05–16.26%) and its fractions, most middle- and micro-nutrients content, and carbon pool management index (CPMI, by 17.45–30.31%) compared with CF, while improving grain nutritional quality. However, they increased heavy metals content in grain and soil and their Nemerow comprehensive pollution index (NCPI, by 4.06–16.56% in grain and 2.55–5.57% in soil) but did not cause pollution. Among them, throughout the growth period, only OF8 treatment increased soil available nitrogen (AN), phosphorus (AP), and potassium (AK) content by 3.04–11.15%, 7.11–8.05%, and 0.12–6.05%, respectively, compared with CF, which thus significantly promoted maize growth and increased yield (by 35.65%); the NCPI of grain and soil was however lower than that OF16 and OF24. In conclusion, substitution ratio of 8% was considered ideal for promoting maize growth, improving yield and soil fertility, with a low pollution risk. The results of this study would aid in guiding the scientific application of OFS technology to agricultural production, thereby contributing to resource utilization of organic waste and sustainable agricultural development.
Optimized methods for random and targeted mutagenesis in field pea (Pisum sativum L.)
Authors: Pandey Prashant Kumar , Bhowmik Pankaj , Kagale Sateesh
Published: September 2022

Field pea is an important pulse crop for its dense nutritional profile and contribution to sustainable agricultural practices. Recently, it has received extensive attention as a potential leading source of plant-based proteins. However, the adoption of peas as a mainstream source of proteins is affected by a relatively moderate protein content, anti-nutritional factors and high levels of off-flavor components that reduce protein quality. Availability of genetic variation for desirable seed quality traits is the foundation for the sustainable development of pea varieties with improved protein content and quality. Mutagenesis has been an important tool in gene functional characterization studies and creating genetic variability for crop breeding. Large-scale mutagenesis of a crop using physical and chemical agents requires diligent selection of the mutagen and optimization of its dose to increase the frequency of mutations. In this study, we present detailed optimized protocols for physical and chemical mutagenesis of pea using gamma irradiation and ethyl methanesulfonate (EMS), respectively. Gamma radiation and EMS titration kill curves were established to identify optimal doses of the two mutagenic agents. Based on germination, survival rate and growth phenotypes, a gamma radiation dose of 225 Gy and EMS concentration of 5 mm were selected as optimal dosages for mutagenesis in field pea. The presented protocol has been modified from previously established mutagenesis protocols in other crop plants. Our results indicate that the optimal mutagen dosage is genotype dependent. CRISPR/Cas-based gene editing provides a precise and rapid method for targeted genetic manipulation in plants. With the recent success of gene editing in pea using CRISPR/Cas, this innovative technology is expected to become an integral component of the gene discovery and crop improvement toolkit in pea. Here, we describe an optimized methods for targeted mutagenesis of pea protoplasts, including mesophyll protoplast extraction, PEG-mediated transformation and gene editing of a LOX gene using CRISPR/Cas system. The general strategies and methods of mutagenesis described here provide an essential resource for mutation breeding and functional genomics studies in pea. These methods also provide a foundation for similar studies in other crops.
Latent growth curve modeling for the investigation of emotional factors in L2 in longitudinal studies: A conceptual review
Authors: Zhang Fang
Published: September 2022

With the advent of Complex dynamic systems theory (CDST) in the field of second language question (SLA), the need for suitable CDST compatible methods for the investigation of temporal change in L2 affective variables has been felt more than before. One of the innovative methods for this purpose is latent growth curve modeling (LGCM), which has recently drawn the attention of SLA scholars. However, the application of this method is still a burgeoning demand in SLA. In response to this demand, the present study provides a review of the conceptualization, significance, and technical features of the implementation of LGCM. In doing so, this review suggests a number of practices via which LGCM has been introduced in SLA. Additionally, some practical implications are provided for SLA researchers to enhance their literacy of LGCM. Finally, future research suggestions for the progress of the use of this method in SLA are discussed.
Stress can lead to an increase in smartphone use in the context of texting while walking
Authors: Alcaraz Maria Lilian , Labonté-LeMoyne Élise , Lupien Sonia , Sénécal Sylvain , Cameron Ann-Frances , Bellavance François , Léger Pierre-Majorique
Published: September 2022

Texting while walking (TWW) is a dangerous behavior that can lead to injury and even death. While several studies have examined the relationship between smartphone use and stress, to our knowledge no studies have yet investigated the relationship between stress and TWW. The objective of the present study was to investigate this relationship by examining the effects of stress on TWW, the effects of TWW on subsequent stress, and the effect of stress on multitasking performance. A total of 80 participants completed two sequential tasks in a laboratory while they walked on a treadmill and responded to a biological motion stimulus imitating the movement of another pedestrian. In the unrestricted task, participants were given the choice to use their personal phones. In the controlled task, they carried a text conversation with a research assistant while they walked and responded to the stimulus. Stress was measured via questionnaire and saliva collection for measure of cortisol (a stress hormone) before and after each task. Results show that greater psychological stress and cortisol variations were associated with a greater number of phone uses during the unrestricted task. Greater phone use during the unrestricted task was associated with lower subsequent psychological stress in women and total time of phone use was correlated with subsequent cortisol levels. Stress measured before the controlled task had no effect on multitasking performance, but participants with moderate performance were those with the highest cortisol levels. Our results suggest that stress could be a precursor to TWW and that it could affect a pedestrian’s ability to stay safe when using their smartphone.
Context matters during pick-and-place in VR: Impact on search and transport phases
Authors: Lukashova-Sanz Olga , Agarwala Rajat , Wahl Siegfried
Published: September 2022

When considering external assistive systems for people with motor impairments, gaze has been shown to be a powerful tool as it is anticipatory to motor actions and is promising for understanding intentions of an individual even before the action. Up until now, the vast majority of studies investigating the coordinated eye and hand movement in a grasping task focused on single objects manipulation without placing them in a meaningful scene. Very little is known about the impact of the scene context on how we manipulate objects in an interactive task. In the present study, it was investigated how the scene context affects human object manipulation in a pick-and-place task in a realistic scenario implemented in VR. During the experiment, participants were instructed to find the target object in a room, pick it up, and transport it to a predefined final location. Thereafter, the impact of the scene context on different stages of the task was examined using head and hand movement, as well as eye tracking. As the main result, the scene context had a significant effect on the search and transport phases, but not on the reach phase of the task. The present work provides insights into the development of potential supporting intention predicting systems, revealing the dynamics of the pick-and-place task behavior once it is realized in a realistic context-rich scenario.