bluuebunny/crossref_metadata_2025 huggingface dataset:
The Prognostic Value of ctDNA and bTMB on Immune Checkpoint Inhibitors in Human Cancer
Authors: Wei Jiayan , Feng Jia , Weng Yiming , Xu Zexi , Jin Yao , Wang Peiwei , Cui Xue , Ruan Peng , Luo Ruijun , Li Na , Peng Min
Published: October 2021

Background

Circulating tumor DNA (ctDNA) levels and blood tumor mutation burden (bTMB) have a significant impact on the prognosis of tumor patients. However, their prognostic role in immune checkpoint inhibitors (ICIs) in cancer patients is still unclear.

Methods

We used the Review Manager software (version 5.3) to perform a meta-analysis based on the published literature to explore the prognostic value of ctDNA and bTMB in patients receiving immunotherapy. We extracted the hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS) for each included study and their respective 95% confidence intervals (CIs) and p-values for analysis.

Results

Thirteen studies were included in the meta-analysis. Higher ctDNA levels were significantly associated with shorter OS (HR = 3.35, 95%CI = 2.49–4.51, p < 0.00001) and PFS (HR = 3.28, 95%CI = 2.47–4.35, p < 0.00001). The results of ctDNA subgroup analysis showed that high posttreatment ctDNA levels significantly correlated with shorter OS in cancer patients receiving ICIs (HR = 5.09, 95%CI = 1.43–18.07, p = 0.01). Moreover, patients with ctDNA clearance had better OS (HR = 4.94, 95%CI = 2.96–8.26, p < 0.00001). Patients with high posttreatment ctDNA levels had shorter PFS (HR = 3.00, 95%CI = 2.02–4.46, p < 0.00001) and those with ctDNA clearance had longer PFS (HR = 4.61, 95%CI = 2.78–7.65, p < 0.00001). However, there was no statistically significant difference in the OS benefits between a high and a low bTMB after ICI therapy (HR = 0.68, 95%CI = 0.33–1.37, p = 0.28).

Conclusions

The host immune system and tumor burden together determine whether cancer patients can benefit from ICI therapy. Our systematic review and meta-analysis revealed for the first time that the levels of pretreatment and posttreatment ctDNA and the clearance of ctDNA can independently be used as prognostic factors for antitumor immunotherapy, while bTMB cannot. In conclusion, ctDNA levels have great potential as an assistant tool for radiological assessments to make clinical therapeutic decisions. The prognostic utility of bTMB still requires further exploration.
A Fully Automatic Artificial Intelligence System Able to Detect and Characterize Prostate Cancer Using Multiparametric MRI: Multicenter and Multi-Scanner Validation
Authors: Giannini Valentina , Mazzetti Simone , Defeudis Arianna , Stranieri Giuseppe , Calandri Marco , Bollito Enrico , Bosco Martino , Porpiglia Francesco , Manfredi Matteo , De Pascale Agostino , Veltri Andrea , Russo Filippo , Regge Daniele
Published: October 2021

In the last years, the widespread use of the prostate-specific antigen (PSA) blood examination to triage patients who will enter the diagnostic/therapeutic path for prostate cancer (PCa) has almost halved PCa-specific mortality. As a counterpart, millions of men with clinically insignificant cancer not destined to cause death are treated, with no beneficial impact on overall survival. Therefore, there is a compelling need to develop tools that can help in stratifying patients according to their risk, to support physicians in the selection of the most appropriate treatment option for each individual patient. The aim of this study was to develop and validate on multivendor data a fully automated computer-aided diagnosis (CAD) system to detect and characterize PCas according to their aggressiveness. We propose a CAD system based on artificial intelligence algorithms that a) registers all images coming from different MRI sequences, b) provides candidates suspicious to be tumor, and c) provides an aggressiveness score of each candidate based on the results of a support vector machine classifier fed with radiomics features. The dataset was composed of 131 patients (149 tumors) from two different institutions that were divided in a training set, a narrow validation set, and an external validation set. The algorithm reached an area under the receiver operating characteristic (ROC) curve in distinguishing between low and high aggressive tumors of 0.96 and 0.81 on the training and validation sets, respectively. Moreover, when the output of the classifier was divided into three classes of risk, i.e., indolent, indeterminate, and aggressive, our method did not classify any aggressive tumor as indolent, meaning that, according to our score, all aggressive tumors would undergo treatment or further investigations. Our CAD performance is superior to that of previous studies and overcomes some of their limitations, such as the need to perform manual segmentation of the tumor or the fact that analysis is limited to single-center datasets. The results of this study are promising and could pave the way to a prediction tool for personalized decision making in patients harboring PCa.
A Large Real-World Study on the Effectiveness of the Combined Inhibition of EGFR and MET in EGFR-Mutant Non-Small-Cell Lung Cancer After Development of EGFR-TKI Resistance
Authors: Liu Li , Qu Jingjing , Heng Jianfu , Zhou Chunhua , Xiong Yi , Yang Haiyan , Jiang Wenjuan , Zeng Liang , Zhu Songlin , Zhang Yongchang , Tan Jiarong , Hu Chengping , Deng Pengbo , Yang Nong
Published: October 2021

Background

MET proto-oncogene amplification (amp) is an important mechanism underlying acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the optimal treatment strategy after acquiring MET-amp-mediated EGFR-TKI resistance remains controversial. Our study compared three treatment strategies for patients with EGFR-mutant non-small-cell lung cancer (NSCLC) who were detected with MET-amp at EGFR-TKI progression using next-generation sequencing.

Methods

Of the 70 patients included in the study, 38 received EGFR-TKI + crizotinib, 10 received crizotinib monotherapy, and 22 received chemotherapy. Clinical outcomes and molecular profiles were analyzed.

Results

The objective response rate was 48.6% for EGFR-TKI + crizotinib group, 40.0% for crizotinib monotherapy group, and 18.2% for chemotherapy group. Patients who received EGFR-TKI + crizotinib had significantly longer progression-free survival than those who received crizotinib or chemotherapy (5.0 vs. 2.3 vs. 2.9 months, p = 0.010), but overall survival was comparable (10.0 vs. 4.1 vs. 8.5 months, p = 0.088). TP53 mutation (58.5%) and EGFR-amp (42.9%) were frequent concurrent mutations of the cohort. Progression-free survival was significantly longer for patients with either concurrent TP53 mutation (n = 17) (6.0 vs. 2.3 vs. 2.9 months, p = 0.009) or EGFR-amp (n = 13) (5.0 vs. 1.2 vs. 2.4 months, p = 0.016) in the EGFR-TKI + crizotinib group than the other two regimen. Potential acquired resistance mechanisms to EGFR-TKI + crizotinib included EGFR-T790M (n = 2), EGFR-L718Q (n = 1), EGFR-S645C (n = 1), MET-D1228H (n = 1), BRAF-V600E (n = 1), NRAS-Q61H (n = 1), KRAS-amp (n = 1), ERBB2-amp (n = 1), CDK4-amp (n = 1), and MYC-amp (n = 1).

Conclusion

Our study provides real-world clinical evidence from a large cohort that simultaneous inhibition of EGFR and MET could be a more effective therapeutic strategy for patients with MET-amp acquired from EGFR-TKI therapy.
CALR-TLR4 Complex Inhibits Non-Small Cell Lung Cancer Progression by Regulating the Migration and Maturation of Dendritic Cells
Authors: Chen Ruo , Huang Min , Yang Xu , Chen Xiao-Hong , Shi Ming-Yan , Li Zhuo-Fan , Chen Zhi-Nan , Wang Ke
Published: October 2021

Background

Lung cancer is a common malignant tumor that threatens human life and is associated with high morbidity and mortality rates. Calreticulin (CALR) is a antigen characteristic of immunogenic cell death in non-small cell lung cancer (NSCLC), which is closely related to anti-tumor immunity, but its specific mechanism in anti-tumor immunity remains unclear.

Methods

Immunohistochemical staining was performed to detect the expression of CALR and dendritic cell-lysosome-associated membrane glycoprotein (DC-LAMP) in NSCLC tissues. The cell supernatant was used to induce migration and maturation of dendritic cells (DCs). Western blot and real-time PCR were used to investigate the corresponding molecule expression in the CALR-Toll-like receptor 4 (TLR4)-MyD88 signaling pathway. In vivo experiments were conducted to evaluate the role of mCALR in lung cancer progression.

Results

The expression of CALR on NSCLC cell membrane (mCALR) and DC infiltration in NSCLC were positively correlated and were closely related to the prognosis of NSCLC patients. Moreover, mCALR facilitated the migration and maturation of DCs by activating CALR-TLR4-MyD88 signaling and increasing the secretion of TNFα and CCL19, which was inhibited by the loss of TLR4. In vivo experiments demonstrated that mCALR inhibited lung cancer progression by facilitating DC infiltration in lung cancer tissues.

Conclusion

Our study explores the function and mechanism of the CALR-TLR4 complex in DC migration and maturation and investigates the inhibitory effect of the CALR-TLR4 complex on lung cancer progression, providing a theoretical basis and ideas for immunotherapy of NSCLC.
Development and Validation of an Autophagy-Related LncRNA Prognostic Signature in Head and Neck Squamous Cell Carcinoma
Authors: Shen Lin , Li Na , Zhou Qin , Li Zhanzhan , Shen Liangfang
Published: October 2021

Head and neck squamous cell carcinoma (HNSCC) is one of the greatest public challenges because of delayed diagnosis and poor prognosis. In this study, we established an autophagy-associated long non-coding (Lnc)RNA prognostic signature to assess the prognosis of HNSCC patients. The LncRNA expression profiles and clinical information of 499 HNSCC samples were available in The Cancer Genome Atlas. Autophagic LncRNAs were analyzed using Pearson correlation. A co-expression network showed the interactions between autophagic genes and LncRNAs. An autophagic LncRNAs prognostic signature, consisting of MYOSLID, AL139287.1, AC068580.1, AL022328.2, AC104083.1, AL160006.1, AC116914.2, LINC00958, and AL450992.2, was developed through uni- and multivariate Cox regressions. High- and low-risk groups were classified based on the median risk scores. The high-risk group had significantly worse overall survival according to Kaplan–Meier curve analysis. Multivariate Cox regression demonstrated that risk scores were a significant independent prognostic factor (hazard ratio = 1.739, 95% confidence interval: 1.460–2.072), with an area under the curve of 0.735. Principal component analysis distinguished two categories based on the nine-LncRNA prognostic signature. In conclusion, this novel autophagic LncRNA signature is an independent prognostic factor and may suggest novel therapeutic targets for HNSCC.
Case Report: Progressive Cholestasis: Severe Phenotype of MEGDEL Syndrome With SATB2-Associated Syndrome
Authors: Su Yajie , Zhang Hui , Wang Huijun , Wu Bingbing , Yang Jiao , Zhou Wenhao , Li Long
Published: October 2021

MEGDEL syndrome and SATB2-associated syndrome (SAS) are both rare congenital disorders with poor prognoses caused by gene mutations. We present the case of a 2-day-old girl with an unexplained abnormal liver function, feeding problem, and dystonia. Using next-generation sequencing, we identified two novel mutations in SERAC1 and a mutation in SATB2. Now, she is 15 months old and has the characteristics of SAS, such as downslanting palpebral fissures and delayed primary dentition. Besides the typical phenotypes of MEGDEL syndrome, such as hypertonia, failure to thrive, deafness, and motor regression, she has progressive cholestasis and is prone to high serum lactate after rehabilitation training and hypoglycemia with low ketone under starving conditions. These phenotypes substantially differ from the transient liver function abnormalities and hypoglycemia reported in the literature.
Prophylactic Use of Fluconazole in Very Premature Infants
Authors: Zhang Deshuang , Xie Dongke , He Na , Wang Xiaoling , Dong Wenbin , Lei Xiaoping
Published: October 2021

Objective: To evaluate the efficacy, safety, and fungal sensitivity of prophylactic fluconazole use in very premature infants.

Methods: We performed a retrospective historical comparative analysis of 196 very premature infants (113 in the prophylaxis group and 83 in the rescue group). The incidence of nosocomial fungal infection (NCFI) and pathogenic fungi, their drug sensitivity, and the minimum inhibitory concentration (MIC) of fluconazole were compared between the two groups. We also analyzed differences in short-term adverse outcomes, such as drug-induced liver or renal function disruption, fungal-attributable death, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), and necrotizing enterocolitis (NEC), between the groups. The effects of the prophylactic fluconazole strategy on NCFI and short-term adverse outcomes were assessed by multivariate logistic regression.

Results:Candida albicans (46.7%) and Candida glabrata (43.3%) were the main culprit pathogens causing NCFI. The incidence of NCFI was significantly lower in the prophylaxis group than in the rescue group (15.9 vs. 45.8%, P < 0.001). However, fewer fungi were completely sensitive to fluconazole (40 vs. 85%, P < 0.05) and the MIC of fluconazole was higher [16.0 (3.5 ~ 16.0) vs. 3.0 (1.0 ~ 8.0) μg/ml, P < 0.001] in the prophylaxis group than in the rescue group. Compared with the rescue group, the prophylaxis group had a lower risk of NCFI (adjusted OR 0.25; 95% CI 0.11, 0.55). Additionally, the prophylaxis group had significantly lower risks of combined outcomes (one or more complications, such as BPD, ROP needing interventions, PVL/IVH (grade > 2), NEC stage ≥2, and fungal-attributable death) (adjusted OR 0.44; 95% CI 0.21, 0.92). There was no significant difference in serum alanine transferase (ALT), aspartate transaminase (AST), creatinine (Cr), or direct bilirubin (DBIL) levels between the two groups.

Conclusions: Fluconazole prophylaxis reduced NCFI and improved combined clinical outcomes in very premature infants, with no increased risks of serious short-term adverse side effects; however, the MIC of fluconazole showed significant increases. Therefore, further optimization of preventive strategies is necessary to maintain the sensitivity of fluconazole against fungal isolates.
External Validation of BMT-i Computerized Test Battery for Diagnosis of Learning Disabilities
Authors: Billard Catherine , Jung Camille , Munnich Arnold , Gassama Sahawanatou , Touzin Monique , Mirassou Anne , Willig Thiébaut-Noël
Published: October 2021

Background: Learning disabilities (LDs) are a major public health issue, affecting cognitive functions and academic performance for 8% of children. If LDs are not detected early and addressed through appropriate interventions, they have a heavy impact on these children in the social, educational, and professional spheres, at great cost to society. The BMT-i (Batterie Modulable de Tests informatisée, or “computerized Adaptable Test Battery”) enables fast, easy, reliable assessments for each cognitive domain. It has previously been validated in children ages 4–13 who had no prior complaints. The present study demonstrates the sensitivity of the BMT-i, relative to reference test batteries, for 191 children with cognitive difficulties.

Materials and Methods: These 191 subjects were included in the study by the 14 pediatricians treating them for complaints in five cognitive domains: written language [60 (cases)]; mathematical cognition (40); oral language (60); handwriting, drawing, and visuospatial construction (45); and attention and executive functioning (45). In accordance with a predefined protocol, the children were administered BMT-i tests first, by their pediatricians, and reference tests later, by specialists to whom the BMT-i test results were not disclosed. Comparison of BMT-i and reference test results made it possible to evaluate sensitivity and agreement between tests.

Results: For each of the five domains, the BMT-i was very sensitive (0.91–1), and normal BMT-i results were highly predictive of normal results for specialized reference tests [negative likelihood ratio (LR–): 0–0.16]. There was close agreement between BMT-i and reference tests in all domains except attention and executive functioning, for which only moderate agreement was observed.

Conclusion: The BMT-i offers rapid, reliable, simple computerized assessments whose sensitivity and agreement with reference test batteries make it a suitable first-line instrument for LD screening in children 4–13 years old.
Demographic and Clinical Features of Small-for-Gestational-Age Infants Born to Mothers With Gestational Diabetes Mellitus
Authors: Chen Juncao , Xiao Huimin , Yang Yong , Tang Yaping , Yang Xiaoqi , Zhang Zhe , Lu Weineng , Yao Jie , Huang Longguang , Liu Xiaoping , Zhou Wei
Published: October 2021

We studied the demographic and clinical characteristic, risk factors, outcomes of full-term small-for-gestational-age (SGA) infants born to mothers with gestational diabetes mellitus (GDM) in China. A retrospective case-control study that included 1981 SGA infants was conducted; the demographic and clinical data between SGA infants born to mothers with and without GDM were compared. Of 383 SGA infants born to mothers with GDM, 221 (57.7%) were female, and the incidence of these infants was 1 in 155 live births. The risk of SGA siblings (RR, 1.88; 95% CI, [1.23–2.86]), low 1- and 5-min Apgar scores (RR,2.04 and 4.21; 95%CI [1.05–4.00] and [1.05–16.89], respectively), early thrombocytopenia (RR, 3.39; 95%CI, [1.33–8.64]), hypoglycemia(RR, 2.49; 95%CI, [1.55–3.98]), and hypoxic-ischemic encephalopathy (RR,5.61; 95%CI, [1.25–25.18]) were increased in SGA infants born to mothers with GDM compared to SGA infants born to mothers without GDM. SGA girls born to mothers with GDM had a significantly higher ratio of catch-up growth (CUG) (RR, 1.73; 95%CI, [1.18–2.54]) in the first year of life. These results show that genetic factors may be one of the etiologies of SGA infants born to mothers with GDM; and these infants have more adverse perinatal outcomes compared to SGA infants born to mothers without GDM. SGA girls born to mothers with GDM had accelerated CUG in the first year of life.
A Novel Self-Assembled Gel for Gastric Endoscopic Submucosal Dissection-Induced Ulcer: A Preclinical Study in a Porcine Model
Authors: Li Meng , Jin Haifeng , Shi Changpei , Lyu Bin , Ying Xiao , Shi Yuan
Published: October 2021

Endoscopic submucosal dissection (ESD) is a routine procedure for the management of early gastrointestinal neoplasia, but it results in large ulcers. This study aims to examine the feasibility and effectiveness of a newly developed self-assembled gel on the ulcer healing process after ESD. Sixteen 2.0-cm (diameter) gastric ulcers were created by ESD in five pigs. All ulcers were randomized: control group (n = 7, routine ulcer management) and gel-treated group (n = 9). The gel was applied to cover the whole ulcer bed through the endoscope immediately after ESD. The feasibility of this endoscopic treatment modality was macroscopically accessed by endoscopy. The effectiveness was evaluated based on the ulcer area and histology changes at 14 days after ESD. The gel-treated group showed higher healing activity compared with the control ulcers on day 14 after ESD. The percentage of healing was higher for the gel-treated ulcers than in control ones (96.2 ± 2.2% vs. 91.9 ± 4.5%, p = 0.035). The extent of the new epithelium covering the ulcer was greater in the gel group than in controls. One delayed overt bleeding occurred in the control group (14.3%). This novel gel might promote the speed of ulcer healing after ESD, leading to higher epithelium formation.
Effects of Terlipressin on Management of Hypotensive Brain-Dead Patients Who are Potential Organ Donors: A Retrospective Study
Authors: Zheng Donghua , Liu Genglong , Chen Li , Xie Wenfeng , Sun Jiaqi , Wang Siqi , Tai Qiang
Published: October 2021

Background: Administration of terlipressin can reverse hypotension in potential organ donors with norepinephrine-resistance. The aim of this study was to determine the effects of terlipressin on the hemodynamics, liver function, and renal function of hypotensive brain-dead patients who were potential organ donors.

Methods: A retrospective study was conducted by using the ICU database of one hospital. 18 patients in a total of 294 brain-dead cases were enrolled and administered terlipressin intravenously. All physiological parameters of recruited patients were obtained at baseline, 24 and 72 h after administration, and immediately before organ procurement.

Results: Terlipressin induced significant increases in mean arterial pressure (MAP) from 69.56 ± 10.68 mm Hg (baseline) to 101.82 ± 19.27 mm Hg (immediately before organ procurement) and systolic blood pressure (SBP) from 89.78 ± 8.53 mm Hg (baseline) to 133.42 ± 26.11 mm Hg (immediately before organ procurement) in all patients. The increases in MAP were accompanied by significant decreases in heart rate (HR) from 113.56 ± 28.43 bpm (baseline) to 83.89 ± 11.70 bpm (immediately before organ procurement), which resulted in the decrease of norepinephrine dose over time from 0.8 ± 0.2 μg/kg/min (baseline) to 0.09 ± 0.02 μg/kg/min (immediately before organ procurement). There were no changes in central venous pressure, liver function including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin. Renal function, assessed by serum creatinine (SCr), urine output (UOP), creatinine clearance rate (CCr), and estimated glomerular filtration rate (eGFR), improved significantly.

Conclusion: Our analysis of brain-dead patients with hypotension indicates that administration of terlipressin can significantly increases MAP, SBP, UOP, CCr, and eGFR, while decreases HR and Scr. Terlipressin appears to help maintain hemodynamic stability, reduce vasoactive support, and improve renal function.
A Dual PI3K/HDAC Inhibitor Downregulates Oncogenic Pathways in Hematologic Tumors In Vitro and In Vivo
Authors: Yan Zheng , Zhang Kehui , Ji Ming , Xu Heng , Chen Xiaoguang
Published: October 2021

Purpose: To investigate the efficacy and mechanism of compound 23, a PI3K/HDAC dual-target inhibitor, on hematologic tumor cells in vitro and in vivo. Methods: The MTS Kit was used to study the antiproliferative effects in vitro. Western blot was used to analyze the involved signaling pathways. Flow cytometry was used to analyze apoptosis and the cell cycle. The antiproliferative effects were evaluated in vivo using EL4 and A20 xenograft models. The CCLE database was used to analyze gene expression. Results: Compound 23 significantly inhibited the proliferation of hematologic tumors; it simultaneously regulated PI3K/HDAC pathways and induced apoptosis and G1-phase arrest in EL4, NB4, and A20 cells in vitro. When tested in vivo, compound 23 significantly inhibited the proliferation of EL4 and A20. The expression levels of ErbB2 and ErbB3 decreased in hematologic tumors compared with it in solid tumors. Conclusion: Compound 23 modulates the PI3K/HDAC pathway, which results in significant inhibition of hematologic tumor proliferation in vivo and in vitro. The differential levels of ERBB2 and ERBB3 might be related to the difference in the effect of compound 23 on hematologic tumors and solid tumors.
Formation of Magnetic Flux Rope During Solar Eruption. I. Evolution of Toroidal Flux and Reconnection Flux
Authors: Jiang Chaowei , Chen Jun , Duan Aiying , Bian Xinkai , Wang Xinyi , Li Jiaying , Zou Peng , Feng Xueshang
Published: October 2021

Magnetic flux ropes (MFRs) constitute the core structure of coronal mass ejections (CMEs), but hot debates remain on whether the MFR forms before or during solar eruptions. Furthermore, how flare reconnection shapes the erupting MFR is still elusive in three dimensions. Here we studied a new MHD simulation of CME initiation by tether-cutting magnetic reconnection in a single magnetic arcade. The simulation follows the whole life, including the birth and subsequent evolution, of an MFR during eruption. In the early phase, the MFR is partially separated from its ambient field by a magnetic quasi-separatrix layer (QSL) that has a double-J shaped footprint on the bottom surface. With the ongoing of the reconnection, the arms of the two J-shaped footprints continually separate from each other, and the hooks of the J shaped footprints expand and eventually become closed almost at the eruption peak time, and thereafter the MFR is fully separated from the un-reconnected field by the QSL. We further studied the evolution of the toroidal flux in the MFR and compared it with that of the reconnected flux. Our simulation reproduced an evolution pattern of increase-to-decrease of the toroidal flux, which is reported recently in observations of variations in flare ribbons and transient coronal dimming. The increase of toroidal flux is owing to the flare reconnection in the early phase that transforms the sheared arcade to twisted field lines, while its decrease is a result of reconnection between field lines in the interior of the MFR in the later phase.
Vascular Health Triad in Humans With Hypertension—Not the Usual Suspects
Authors: Ranadive Sushant M. , Dillon Gabrielle A. , Mascone Sara E. , Alexander Lacy M.
Published: October 2021

Hypertension (HTN) affects more than one-third of the US population and remains the top risk factor for the development of cardiovascular disease (CVD). Identifying the underlying mechanisms for developing HTN are of critical importance because the risk of developing CVD doubles with ∼20 mmHg increase in systolic blood pressure (BP). Endothelial dysfunction, especially in the resistance arteries, is the primary site for initiation of sub-clinical HTN. Furthermore, inflammation and reactive oxygen and nitrogen species (ROS/RNS) not only influence the endothelium independently, but also have a synergistic influence on each other. Together, the interplay between inflammation, ROS and vascular dysfunction is referred to as the vascular health triad, and affects BP regulation in humans. While the interplay of the vascular health triad is well established, new underlying mechanistic targets are under investigation, including: Inducible nitric oxide synthase, hydrogen peroxide, hydrogen sulfide, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor activated T cells. This review outlines the role of theseunusual suspectsin vascular health and function in humans. This review connects the dots using theseunusual suspectsunderlying inflammation, ROS and vascular dysfunction especially in individuals at risk of or with diagnosed HTN based on novel studies performed in humans.
XAP5 CIRCADIAN TIMEKEEPER Affects Both DNA Damage Responses and Immune Signaling in Arabidopsis
Authors: Kumimoto Roderick W. , Ellison Cory T. , Toruño Tania Y. , Bak Aurélie , Zhang Hongtao , Casteel Clare L. , Coaker Gitta , Harmer Stacey L.
Published: October 2021

Numerous links have been reported between immune response and DNA damage repair pathways in both plants and animals but the precise nature of the relationship between these fundamental processes is not entirely clear. Here, we report that XAP5 CIRCADIAN TIMEKEEPER (XCT), a protein highly conserved across eukaryotes, acts as a negative regulator of immunity in Arabidopsis thaliana and plays a positive role in responses to DNA damaging radiation. We find xct mutants have enhanced resistance to infection by a virulent bacterial pathogen, Pseudomonas syringae pv. tomato DC3000, and are hyper-responsive to the defense-activating hormone salicylic acid (SA) when compared to wild-type. Unlike most mutants with constitutive effector-triggered immunity (ETI), xct plants do not have increased levels of SA and retain enhanced immunity at elevated temperatures. Genetic analysis indicates XCT acts independently of NONEXPRESSOR OF PATHOGENESIS RELATED GENES1 (NPR1), which encodes a known SA receptor. Since DNA damage has been reported to potentiate immune responses, we next investigated the DNA damage response in our mutants. We found xct seedlings to be hypersensitive to UV-C and γ radiation and deficient in phosphorylation of the histone variant H2A.X, one of the earliest known responses to DNA damage. These data demonstrate that loss of XCT causes a defect in an early step of the DNA damage response pathway. Together, our data suggest that alterations in DNA damage response pathways may underlie the enhanced immunity seen in xct mutants.
Elevated CO2 Enhances Dynamic Photosynthesis in Rice and Wheat
Authors: Kang Huixing , Zhu Ting , Zhang Yan , Ke Xinran , Sun Wenjuan , Hu Zhenghua , Zhu Xinguang , Shen Haihua , Huang Yao , Tang Yanhong
Published: October 2021

Crops developed under elevated carbon dioxide (eCO2) exhibit enhanced leaf photosynthesis under steady states. However, little is known about the effect of eCO2 on dynamic photosynthesis and the relative contribution of the short-term (substrate) and long-term (acclimation) effects of eCO2. We grew an Oryza sativa japonica cultivar and a Triticum aestivum cultivar under 400 μmol CO2 mol−1 air (ambient, A) and 600 μmol CO2 mol−1 air (elevated, E). Regardless of growth [CO2], the photosynthetic responses to the sudden increase and decrease in light intensity were characterized under 400 (a) or 600 μmol CO2 mol−1 air (e). The Aa1, Ae2, Ea3, and Ee4 treatments were employed to quantify the acclimation effect (Ae vs. Ee and Aa vs. Ea) and substrate effect (Aa vs. Ae and Ea vs. Ee). In comparison with the Aa treatment, both the steady-state photosynthetic rate (PN) and induction state (IS) were higher under the Ae and Ee treatments but lower under the Ea treatment in both species. However, IS reached at the 60 sec after the increase in light intensity, the time required for photosynthetic induction, and induction efficiency under Ae and Ee treatment did not differ significantly from those under Aa treatment. The substrate effect increased the accumulative carbon gain (ACG) during photosynthetic induction by 45.5% in rice and by 39.3% in wheat, whereas the acclimation effect decreased the ACG by 18.3% in rice but increased it by 7.5% in wheat. Thus, eCO2, either during growth or at measurement, enhances the dynamic photosynthetic carbon gain in both crop species. This indicates that photosynthetic carbon loss due to an induction limitation may be reduced in the future, under a high-CO2 world.
Effect of Cotton Leafroll Dwarf Virus on Physiological Processes and Yield of Individual Cotton Plants
Authors: Parkash Ved , Sharma Divya Bhanu , Snider John , Bag Sudeep , Roberts Phillip , Tabassum Afsha , West Dalton , Khanal Sameer , Suassuna Nelson , Chee Peng
Published: October 2021

Cotton leafroll dwarf disease (CLRDD) caused by cotton leafroll dwarf virus (CLRDV) is an emerging threat to cotton production in the United States. The disease was first reported in Alabama in 2017 and subsequently has been reported in 10 other cotton producing states in the United States, including Georgia. A field study was conducted at field sites near Tifton, Georgia in 2019 and 2020 to evaluate leaf gas exchange, chlorophyll fluorescence, and leaf temperature responses for a symptomatic cultivar (diseased plants observed at regular frequency) at multiple stages of disease progression and for asymptomatic cultivars (0% disease incidence observed). Disease-induced reductions in net photosynthetic rate (An, decreased by 63–101%), stomatal conductance (gs, decreased by 65–99%), and efficiency of the thylakoid reactions (32–92% decline in primary photochemistry) were observed, whereas leaf temperature significantly increased by 0.5–3.8°C at advanced stages of the disease. Net photosynthesis was substantially more sensitive to disease-induced declines in gs than the thylakoid reactions. Symptomatic plants with more advanced disease stages remained stunted throughout the growing season, and yield was reduced by 99% by CLRDD due to reductions in boll number per plant and declines in boll mass resulting from fewer seeds per boll. Asymptomatic cultivars exhibited more conservative gas exchange responses than apparently healthy plants of the symptomatic cultivar but were less productive. Overall, it is concluded that CLRDV limits stomatal conductance and photosynthetic activity of individual leaves, causing substantial declines in productivity for individual plants. Future studies should evaluate the physiological contributors to genotypic variation in disease tolerance under controlled conditions.
Downregulation of Barley Regulator of Telomere Elongation Helicase 1 Alters the Distribution of Meiotic Crossovers
Authors: Barakate Abdellah , Arrieta Mikel , Macaulay Malcolm , Vivera Sebastian , Davidson Diane , Stephens Jennifer , Orr Jamie , Schreiber Miriam , Ramsay Luke , Halpin Claire , Waugh Robbie
Published: October 2021

Programmed meiotic DNA double-strand breaks (DSBs), necessary for proper chromosomal segregation and viable gamete formation, are repaired by homologous recombination (HR) as crossovers (COs) or non-crossovers (NCOs). The mechanisms regulating the number and distribution of COs are still poorly understood. The regulator of telomere elongation helicase 1 (RTEL1) DNA helicase was previously shown to enforce the number of meiotic COs in Caenorhabditis elegans but its function in plants has been studied only in the vegetative phase. Here, we characterised barley RTEL1 gene structure and expression using RNA-seq data previously obtained from vegetative and reproductive organs and tissues. Using RNAi, we downregulated RTEL1 expression specifically in reproductive tissues and analysed its impact on recombination using a barley 50k iSelect SNP Array. Unlike in C. elegans, in a population segregating for RTEL1 downregulated by RNAi, high resolution genome-wide genetic analysis revealed a significant increase of COs at distal chromosomal regions of barley without a change in their total number. Our data reveal the important role of RTEL1 helicase in plant meiosis and control of recombination.
The Tea Plant Leaf Cuticle: From Plant Protection to Tea Quality
Authors: Chen Mingjie
Published: October 2021

Camellia sinensis (tea tree) is a perennial evergreen woody crop that has been planted in more than 50 countries worldwide; its leaves are harvested to make tea, which is one of the most popular nonalcoholic beverages. The cuticle is the major transpiration barrier to restrict nonstomatal water loss and it affects the drought tolerance of tea plants. The cuticle may also provide molecular cues for the interaction with herbivores and pathogens. The tea-making process almost always includes a postharvest withering treatment to reduce leaf water content, and many studies have demonstrated that withering treatment-induced metabolite transformation is essential to shape the quality of the tea made. Tea leaf cuticle is expected to affect its withering properties and the dynamics of postharvest metabolome remodeling. In addition, it has long been speculated that the cuticle may contribute to the aroma quality of tea. However, concrete experimental evidence is lacking to prove or refute this hypothesis. Even though its relevance to the abiotic and biotic stress tolerance and postharvest processing properties of tea tree, tea cuticle has long been neglected. Recently, there are several studies on the tea cuticle regarding its structure, wax composition, transpiration barrier organization, environmental stresses-induced wax modification, and structure–function relations. This review is devoted to tea cuticle, the recent research progresses were summarized and unresolved questions and future research directions were also discussed.
Phenoloxidases in Plants—How Structural Diversity Enables Functional Specificity
Authors: Blaschek Leonard , Pesquet Edouard
Published: October 2021

The metabolism of polyphenolic polymers is essential to the development and response to environmental changes of organisms from all kingdoms of life, but shows particular diversity in plants. In contrast to other biopolymers, whose polymerisation is catalysed by homologous gene families, polyphenolic metabolism depends on phenoloxidases, a group of heterogeneous oxidases that share little beyond the eponymous common substrate. In this review, we provide an overview of the differences and similarities between phenoloxidases in their protein structure, reaction mechanism, substrate specificity, and functional roles. Using the example of laccases (LACs), we also performed a meta-analysis of enzyme kinetics, a comprehensive phylogenetic analysis and machine-learning based protein structure modelling to link functions, evolution, and structures in this group of phenoloxidases. With these approaches, we generated a framework to explain the reported functional differences between paralogs, while also hinting at the likely diversity of yet undescribed LAC functions. Altogether, this review provides a basis to better understand the functional overlaps and specificities between and within the three major families of phenoloxidases, their evolutionary trajectories, and their importance for plant primary and secondary metabolism.
Cross-Sectional and Longitudinal Associations Among Children’s Interpersonal Trust, Reputation for Trustworthiness, and Relationship Closeness
Authors: Li Qinggong , Li Zhuocheng , Zhang Wenyu , Wang Yang , Heyman Gail D.
Published: October 2021

Interpersonal trust plays a crucial role in the formation and maintenance of social relationships. The present cross-sectional and longitudinal research examines the development of interpersonal trust judgments with reference to (1) the trustee’s reputation for trustworthiness, and (2) the nature of the trustor’s relationship closeness with the trustee. There were 194 7- to 13-year-olds who participated in the first wave of the study, and 107 of those individuals also participated in two subsequent waves across a 2-year period. Both cross-sectional and longitudinal results showed that with age, reputation for trustworthiness becomes less important and relationship closeness become more important. We also found that relationship closeness played a greater role in interpersonal trust evaluations for girls than for boys. These findings indicate that the way children make trust evaluations becomes increasingly relationship-specific over time and is more relationship-specific for girls than for boys.
Validating the General Extended Technology Acceptance Model for E-Learning: Evidence From an Online English as a Foreign Language Course Amid COVID-19
Authors: Jiang Michael Yi-chao , Jong Morris Siu-yung , Lau Wilfred Wing-fat , Meng Yan-li , Chai Ching-sing , Chen Mengyuan
Published: October 2021

The present study validated the general extended technology acceptance model for e-learning (GETAMEL) with the survey data from the English as a foreign language (EFL) online class during the novel coronavirus lockdown period. A total of 678 undergraduates participated in the survey. Structural equation modeling was employed to analyze the data. The results showed that the influence of perceived usefulness of students on their intentional behavior to use the online learning system was not mediated by their attitude, indicating a very limited role of attitude toward technology in the model. Enjoyment and self-efficacy had no significant effects on the internal constructs, raising theoretical concerns on the applicability of this general model into specific contexts. In addition, we found that experience might be a moderator rather than an antecedent of the internal constructs in the model.
Impact of Supportive Leadership During Covid-19 on Nurses' Well-Being: The Mediating Role of Psychological Capital
Authors: Um-e-Rubbab  , Farid Tahir , Iqbal Sadaf , Saeed Imran , Irfan Shahid , Akhtar Tanvir
Published: October 2021

The corona virus disease (Covid-19) has significantly affected the social, physical, and psychological health of workers, specifically the nurses working in the healthcare sectors. Studies have been conducted on the impact of Covid-19 on employees' well-being, organizational structure, and job design; however, limited studies have been conducted focusing on the impact of leadership on employee's well-being during the Covid-19 pandemic. Drawing on job demands resources model and social exchange theory, we examined the impact of supportive leadership on employees' physical, social, and psychological well-being during the Covid-19 pandemic. In addition, we examined the mediating role of psychological capital in examining the relationship between supportive leadership and employees' physical, social, and psychological well-being. Based on three wave time-lagged design, the data were collected from 214 nurses' linear regression analysis and Hayes Process for mediation to test the proposed hypothesis. As hypothesized, supportive leadership predicted employees' physical, social, and psychological well-being. In addition, psychological capital mediated the relationship between supportive leadership and employees' physical, social, and psychological well-being. Implications for research, theory, and practice are discussed.
Skill Differences in a Discrete Motor Task Emerging From the Environmental Perception Phase
Authors: Hasegawa Yumiko , Okada Ayako , Fujii Keisuke
Published: October 2021

Because of the challenges associated with measuring human perception and strategy, the process of human performance from perception to motion to results is not fully understood. Therefore, this study clarifies the phase at which errors occur and how differences in skill level manifest in a motor task requiring an accurate environmental perception and fine movement control. We assigned a golf putting task and comprehensively examined various errors committed in five phases of execution. Twelve tour professionals and twelve intermediate amateur golfers performed the putting task on two surface conditions: flat and a 0.4-degree incline. The participants were instructed to describe the topographical characteristics of the green before starting the trials on each surface (environmental perception phase). Before each attempt, the participants used the reflective markers to indicate their aim point from which the ball would be launched (decision-making phase). We measured the clubface angle and impact velocity to highlight the pre-motion and motion errors (pre-motion and motion phase). In addition, mistakes in the final ball position were analyzed as result errors (post-performance phase). Our results showed that more than half of the amateurs committed visual–somatosensory errors in the perception phase. Moreover, their aiming angles in the decision-making phase differed significantly from the professionals, with no significant differences between slope conditions. In addition, alignment errors, as reported in previous studies, occurred in the pre-motion phase regardless of skill level (i.e., increased in the 0.4-degree condition). In the motion phase, the intermediate-level amateurs could not adjust their clubhead velocity control to the appropriate level, and the clubhead velocity and clubface angle control were less reproducible than those of the professionals. To understand the amateur result errors in those who misperceived the slopes, we checked the individual results focusing on the final ball position. We found that most of these participants had poor performance, especially in the 0.4-degree condition. Our results suggest that the amateurs’ pre-motion and strategy errors depended on their visual–somatosensory errors.
Advances in Behavioral Remote Data Collection in the Home Setting: Assessing the Mother-Infant Relationship and Infant’s Adaptive Behavior via Virtual Visits
Authors: Shin Eunkyung , Smith Cynthia L. , Howell Brittany R.
Published: October 2021

Psychological science is struggling with moving forward in the midst of the COVID-19 pandemic, especially due to the halting of behavioral data collection in the laboratory. Safety barriers to assessing psychological behavior in person increased the need for remote data collection in natural settings. In response to these challenges, researchers, including our team, have utilized this time to advance remote behavioral methodology. In this article, we provide an overview of our group’s strategies for remote data collection methodology and examples from our research in collecting behavioral data in the context of psychological functioning. Then, we describe the design and development of our strategies for remote data collection of mother-infant interactions, with the goal being to assess maternal sensitivity and intrusiveness, as well as infants’ adaptive behaviors in several developmental domains. During these virtual visits over Zoom, mother-infant dyads watched a book-reading video and were asked to participate in peek-a-boo, toy play, and toy removal tasks. After the behavioral tasks, a semi-structured interview (Vineland Adaptive Behavior Scale – VABS III) was conducted to assess the infant’s adaptive behavior in communication, socialization, daily living skills, and motor domains. We delineate the specific strategies we applied to integrate laboratory tasks and a semi-structured interview into remote data collection in home settings with mothers and infants. We also elaborate on issues encountered during remote data collection and how we resolved these challenges. Lastly, to inform protocols for future remote data collection, we address considerations and recommendations, as well as benefits and future directions for behavioral researchers in developmental psychology research.
Ontological Security, Trauma and Violence, and the Protection of Women: Polygamy Among Minority Communities
Authors: Harel-Shalev Ayelet , Kook Rebecca
Published: October 2021

In this article, we examine the special challenges posed by the practice of polygamy to minority women, focusing on the ways that the state and the women confront the related experiences of violence and trauma associated with this practice. Based on analysis of both policy and interviews with women, we demonstrate the tension between the different mechanisms adopted by the state as opposed to those adopted by the women themselves. We suggest that the concept of ontological security is valuable for a deeper understanding of the range of state motivations in cases related to minority women, violence, and the right for protection. Our case study is the Bedouin community in Israel. We explore the relationship between individual and state-level conceptions of violence and trauma and the complex relationship between these two. We examine state discourses of ontological security through a gendered lens, as frameworks of belonging and mechanisms of exclusion.