bluuebunny/crossref_metadata_2025 huggingface dataset:
Galvanic Vestibular Stimulation Improves Spatial Cognition After Unilateral Labyrinthectomy in Mice
Authors: Nguyen Thanh Tin , Nam Gi-Sung , Kang Jin-Ju , Han Gyu Cheol , Kim Ji-Soo , Dieterich Marianne , Oh Sun-Young
Published: July 2021

Objectives:To investigate the deficits of spatial memory and navigation from unilateral vestibular deafferentation (UVD) and to determine the efficacy of galvanic vestibular stimulation (GVS) for recovery from these deficits using a mouse model of unilateral labyrinthectomy (UL).

Methods:Thirty-six male C57BL/6 mice were allocated into three groups that comprise a control group and two experimental groups, UVD with (GVS group) and without GVS intervention (non-GVS group). In the experimental groups, we assessed the locomotor and cognitive behavioral function before (baseline) and 3, 7, and 14 days after surgical UL, using the open field (OF), Y maze, and Morris water maze (MWM) tests. In the GVS group, the stimulations were applied for 30 min daily from postoperative day (POD) 0–4viathe electrodes inserted subcutaneously close to both bony labyrinths.

Results:Locomotion and spatial cognition were significantly impaired in the mice with UVD non-GVS group compared to the control group. GVS significantly accelerated recovery of locomotion compared to the control and non-GVS groups on PODs 3 (p< 0.001) and 7 (p< 0.05, Kruskal–Wallis and Mann–WhitneyUtests) in the OF and Y maze tests. The mice in the GVS group were better in spatial working memory assessed with spontaneous alternation performance and spatial reference memory assessed with place recognition during the Y maze test than those in the non-GVS group on POD 3 (p< 0.001). In addition, the recovery of long-term spatial navigation deficits during the MWM, as indicated by the escape latency and the probe trial, was significantly better in the GVS group than in the non-GVS group 2 weeks after UVD (p< 0.01).

Conclusions:UVD impairs spatial memory, navigation, and motor coordination. GVS accelerated recoveries in short- and long-term spatial memory and navigation, as well as locomotor function in mice with UVD, and may be applied to the patients with acute unilateral vestibular failure.
eABR THR Estimation Using High-Rate Multi-Pulse Stimulation in Cochlear Implant Users
Authors: Saeedi Ali , Englert Ludwig , Hemmert Werner
Published: July 2021

We estimated the electrically-evoked auditory brainstem response thresholds (eABR THRs) in response to multi-pulses with high burst rate of 10,000 pulses-per-second (pps). Growth functions of wave eV amplitudes, root mean square (RMS) values, peak of phase-locking value (PLV), and the lowest valid data point (LVDP) were calculated in 1-, 2-, 4-, 8-, and 16-pulses conditions. The growth functions were then fitted and extrapolated with linear and exponential functions to find eABR THRs. The estimated THRs were compared to psychophysical THRs determined for multi-pulse conditions as well as to the clinical THRs measured behaviorally at the rate of 1,000 pps. The growth functions of features showed shallower growth slopes when the number of pulses increased. eABR THRs estimated in 4-, 8-, and 16-pulses conditions were closer to the clinical THRs, when compared to 1- and 2-pulses conditions. However, the smallest difference between estimated eABR THRs and clinical THRs was not always achieved from the same number of pulses. The smallest absolute difference of 30.3 μA was found for the linear fittings on growth functions of eABR RMS values in 4-pulses condition. Pearson’s correlation coefficients (PCCs) between eABR THRs and psychophysical THRs were significant and relatively large in all but 16-pulses conditions. The PCCs between eABR THRs and clinical THRs, however, were smaller and in less cases significant. Results of this study showed that eABRs to multi-pulse stimulation could, to some extent, represent clinical stimulation paradigms, and thus in comparison to single pulses, could estimate clinical THRs with smaller errors.
Information Transmission in Delay-Coupled Neuronal Circuits in the Presence of a Relay Population
Authors: Sánchez-Claros Jaime , Pariz Aref , Valizadeh Alireza , Canals Santiago , Mirasso Claudio R.
Published: July 2021

Synchronization between neuronal populations is hypothesized to play a crucial role in the communication between brain networks. The binding of features, or the association of computations occurring in spatially segregated areas, is supposed to take place when a stable synchronization between cortical areas occurs. While a direct cortico-cortical connection typically fails to support this mechanism, the participation of a third area, a relay element, mediating in the communication was proposed to overcome this limitation. Among the different structures that could play the role of coordination during the binding process, the thalamus is the best placed region to carry out this task. In this paper we study how information flows in a canonical motif that mimics a cortico-thalamo-cortical circuit composed by three mutually coupled neuronal populations (also called the V-motif). Through extensive numerical simulations, we found that the amount of information transferred between the oscillating neuronal populations is determined by the delay in their connections and the mismatch in their oscillation frequencies (detuning). While the transmission from a cortical population is mostly restricted to positive detuning, transmission from the relay (thalamic) population to the cortical populations is robust for a broad range of detuning values, including negative values, while permitting feedback communication from the cortex at high frequencies, thus supporting robust bottom up and top down interaction. In this case, a strong feedback transmission between the cortex to thalamus supports the possibility of robust bottom-up and top-down interactions in this motif. Interestingly, adding a cortico-cortical bidirectional connection to the V-motif (C-motif) expands the dynamics of the system with distinct operation modes. While overall transmission efficiency is decreased, new communication channels establish cortico-thalamo-cortical association loops. Switching between operation modes depends on the synaptic strength of the cortico-cortical connections. Our results support a role of the transthalamic V-motif in the binding of spatially segregated cortical computations, and suggest an important regulatory role of the direct cortico-cortical connection.
Dietary Inflammatory Index and Risk of Asthenozoospermia: A Hospital-Based Case-Controlled Study in China
Authors: Liu Fang-Hua , Wang Xiao-Bin , Wen Zhao-Yan , Wang Han-Yuan , Zhang Meng , Zhang Shuang , Jiang Yu-Ting , Zhang Jia-Yu , Sun Hui , Pan Bo-Chen , Wu Qi-Jun
Published: July 2021

Background: Evidence of associations between a pro-inflammatory diet and asthenozoospermia risk is limited. We therefore performed a case-controlled study to investigate associations between pro-inflammatory diet using dietary inflammatory index (DII) scores and asthenozoospermia risk in China.

Methods: Our hospital-based case-controlled study comprised 549 incident asthenozoospermia men and 581 healthy controls. All were interviewed at the infertility clinic in Shengjing Hospital of China Medical University from June 2020 to December 2020. DII scores were calculated based on dietary intake which were assessed using a validated food frequency questionnaire. Semen parameters were analyzed according to World Health Organization guidelines. An unconditional logistic regression model was used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for asthenozoospermia risk. The lowest tertile served as the reference category for regression analyses.

Results: After adjustment for age in the primary multivariable model, we failed to determine a significant negative association between DII and asthenozoospermia risk (for the highest tertile of DII scores compared to the lowest tertile) (OR = 0.77, 95% CI: 0.57–1.03). Similarly, non-significant associations were also identified in the multivariable model after adjusting for more potential confounders (OR = 0.86; 95% CI: 0.58–1.27). Additionally, in subgroup analyses stratified by age, body mass index, and smoking status, non-significant results were consistent with the main findings.

Conclusions: To our knowledge, this is the first study exploring this particular topic. Our research does not support an association between DII scores and asthenozoospermia risk. Further prospective studies with more DII relevant foods and nutrients are warranted to confirm our findings.
Influence of Tumor Burden on Serum Prostate-Specific Antigen in Prostate Cancer Patients Undergoing Radical Prostatectomy
Authors: Mandel Philipp , Hoeh Benedikt , Preisser Felix , Wenzel Mike , Humke Clara , Welte Maria-Noemi , Jerrentrup Inga , Köllermann Jens , Wild Peter , Tilki Derya , Haese Alexander , Becker Andreas , Roos Frederik C. , Chun Felix K. H. , Kluth Luis A.
Published: July 2021

Objective

We aimed to assess the correlation between serum prostate-specific antigen (PSA) and tumor burden in prostate cancer (PCa) patients undergoing radical prostatectomy (RP), because estimation of tumor burden is of high value, e.g., in men undergoing RP or with biochemical recurrence after RP.

Patients and Methods

From January 2019 to June 2020, 179 consecutive PCa patients after RP with information on tumor and prostate weight were retrospectively identified from our prospective institutional RP database. Patients with preoperative systemic therapy (n=19), metastases (cM1, n=5), and locally progressed PCa (pT4 or pN1, n=50) were excluded from analyses. Histopathological features, including total weight of the prostate and specific tumor weight, were recorded by specialized uro-pathologists. Linear regression models were performed to evaluate the effect of PSA on tumor burden, measured by tumor weight after adjustment for patient and tumor characteristics.

Results

Overall, median preoperative PSA was 7.0 ng/ml (interquartile range [IQR]: 5.41–10) and median age at surgery was 66 years (IQR: 61-71). Median prostate weight was 34 g (IQR: 26–46) and median tumor weight was 3.7 g (IQR: 1.8–7.1), respectively. In multivariable linear regression analysis after adjustment for patients and tumor characteristics, a significant, positive correlation could be detected between preoperative PSA and tumor weight (coefficient [coef.]: 0.37, CI: 0.15–0.6, p=0.001), indicating a robust increase in PSA of almost 0.4 ng/ml per 1g tumor weight.

Conclusion

Preoperative PSA was significantly correlated with tumor weight in PCa patients undergoing RP, with an increase in PSA of almost 0.4 ng/ml per 1 g tumor weight. This might help to estimate both tumor burden before undergoing RP and in case of biochemical recurrence.
Real-World Efficacy and Safety of Anlotinib With and Without Immunotherapy in Advanced Non-Small Cell Lung Cancer
Authors: Xiong Qi , Qin Boyu , Xin Lingli , Yang Bo , Song Qi , Wang Yu , Zhang Sujie , Hu Yi
Published: July 2021

Aims

Combination of anti-angiogenesis therapy and immunotherapy has showed synergistic effects in non-small cell lung cancer (NSCLC). The aim of this retrospective study was to investigate the efficacy and safety of anlotinib with and without immunotherapy in NSCLC.

Methods

Pathologically confirmed NSCLC patients (stage IIIB-IV) receiving anlotinib between November 2018 and February 2020 were enrolled for retrospective analysis. The outcomes and safety of overall patients were evaluated, and the efficacies of anlotinib plus immunotherapy and anlotinib alone was compared. The primary endpoint was progression-free survival (PFS).

Results

A total of 80 patients (median age: 62 years, range: 29-86 years) were included. Overall median PFS was 4.3 months (95% confidence interval (CI): 2.7-5.9 months). In univariate analysis, patients without EGFR mutation, previous EGFR target therapy, and brain metastasis had significantly longer PFS. Cox regression analysis showed that only brain metastasis was an independent predictor of PFS. The median PFS of patients receiving anlotinib plus immunotherapy was slightly longer than that of patients receiving anlotinib alone (4.2 vs 3.1 months); however, the difference was not statistically significant. A tendency of longer median PFS was observed in patients with adenocarcinoma, EGFR wild type, stage IV, no liver metastasis, former smoker, ≥2 previous treatment lines, no previous VEGF or EGFR target therapies in anlotinib plus immunotherapy group. Treatments with anlotinib alone or anlotinib plus immunotherapy were well tolerable. The most common adverse events were fatigue, decreased hemoglobin count, hypertension, hand-foot syndrome, oral mucositis and hoarseness.

Conclusion

Anlotinib is well tolerable and effective in advanced NSCLC patients. Brain metastasis is an independent predictor of PFS in NSCLC patients receiving anlotinib. Future prospective studies with larger sample size and extended follow-up are needed to confirm the clinical benefit in NSCLC patients treated with anlotinib combined with immunotherapy.
Comparable Performance of Deep Learning–Based to Manual-Based Tumor Segmentation in KRAS/NRAS/BRAF Mutation Prediction With MR-Based Radiomics in Rectal Cancer
Authors: Zhang Guangwen , Chen Lei , Liu Aie , Pan Xianpan , Shu Jun , Han Ye , Huan Yi , Zhang Jinsong
Published: July 2021

Radiomic features extracted from segmented tumor regions have shown great power in gene mutation prediction, while deep learning–based (DL-based) segmentation helps to address the inherent limitations of manual segmentation. We therefore investigated whether deep learning–based segmentation is feasible in predicting KRAS/NRAS/BRAF mutations of rectal cancer using MR-based radiomics. In this study, we proposed DL-based segmentation models with 3D V-net architecture. One hundred and eight patients’ images (T2WI and DWI) were collected for training, and another 94 patients’ images were collected for validation. We evaluated the DL-based segmentation manner and compared it with the manual-based segmentation manner through comparing the gene prediction performance of six radiomics-based models on the test set. The performance of the DL-based segmentation was evaluated by Dice coefficients, which are 0.878 ± 0.214 and 0.955 ± 0.055 for T2WI and DWI, respectively. The performance of the radiomics-based model in gene prediction based on DL-segmented VOI was evaluated by AUCs (0.714 for T2WI, 0.816 for DWI, and 0.887 for T2WI+DWI), which were comparable to that of corresponding manual-based VOI (0.637 for T2WI, P=0.188; 0.872 for DWI, P=0.181; and 0.906 for T2WI+DWI, P=0.676). The results showed that 3D V-Net architecture could conduct reliable rectal cancer segmentation on T2WI and DWI images. All-relevant radiomics-based models presented similar performances in KRAS/NRAS/BRAF prediction between the two segmentation manners.
Biological Significance of YAP/TAZ in Pancreatic Ductal Adenocarcinoma
Authors: Hayashi Hiromitsu , Uemura Norio , Zhao Liu , Matsumura Kazuki , Sato Hiroki , Shiraishi Yuta , Baba Hideo
Published: July 2021

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal types of cancer. Despite major advances in defining the molecular mutations driving PDAC, this disease remains universally lethal with an overall 5-year survival rate of only about 7–8%. Genetic alterations in PDAC are exemplified by four critical genes (KRAS, TP53, CDKN2A, and SMAD4) that are frequently mutated. Among these, KRAS mutation ranges from 88% to 100% in several studies. Hippo signaling is an evolutionarily conserved network that plays a key role in normal organ development and tissue regeneration. Its core consists of the serine/threonine kinases mammalian sterile 20-like kinase 1 and 2 (MST1/2) and large tumor suppressor 1 and 2. Interestingly, pancreas-specific MST1/2 double knockout mice have been reported to display a decreased pancreas mass. Many of the genes involved in the Hippo signaling pathway are recognized as tumor suppressors, while the Hippo transducers Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are identified as oncogenes. By dephosphorylation, YAP and TAZ accumulate in the nucleus and interact with transcription factors such as TEA domain transcription factor-1, 2, 3, and 4. Dysregulation of Hippo signaling and activation of YAP/TAZ have been recognized in a variety of human solid cancers, including PDAC. Recent studies have elucidated that YAP/TAZ play a crucial role in the induction of acinar-to-ductal metaplasia, an initial step in the progression to PDAC, in genetically engineered mouse models. YAP and TAZ also play a key role in the development of PDAC by both KRAS-dependent and KRAS-independent bypass mechanisms. YAP/TAZ have become extensively studied in PDAC and their biological importance during the development and progression of PDAC has been uncovered. In this review, we summarize the biological significance of a dysregulated Hippo signaling pathway or activated YAP/TAZ in PDAC and propose a role for YAP/TAZ as a therapeutic target.
Characterization of Histone Deacetylase Mechanisms in Cancer Development
Authors: Hai Rihan , He Liuer , Shu Guang , Yin Gang
Published: July 2021

Over decades of studies, accumulating evidence has suggested that epigenetic dysregulation is a hallmark of tumours. Post-translational modifications of histones are involved in tumour pathogenesis and development mainly by influencing a broad range of physiological processes. Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are pivotal epigenetic modulators that regulate dynamic processes in the acetylation of histones at lysine residues, thereby influencing transcription of oncogenes and tumour suppressor genes. Moreover, HDACs mediate the deacetylation process of many nonhistone proteins and thus orchestrate a host of pathological processes, such as tumour pathogenesis. In this review, we elucidate the functions of HDACs in cancer.
Prognostic Role of Tumor Mutational Burden in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis
Authors: Huang Taobi , Chen Xia , Zhang Huiyun , Liang Yuan , Li Longquan , Wei Hui , Sun Weiming , Wang Yuping
Published: July 2021

Purpose

Immunotherapy is regarded as the most promising treatment for cancer. However, immune checkpoint inhibitors (ICIs) are not effective for all patients. Herein, we conducted a systematic review and meta-analysis to explore whether tumor mutational burden (TMB) can be used as a potential prognostic biomarker for cancer patients treated with ICIs.

Methods

We systematically retrieved relevant literature published in the PubMed, Embase, Web of Science, and Cochrane databases up to December 28, 2020. All cohort studies and clinical trials that reported hazard ratios (HRs) for overall (OS) and progression-free survival (PFS), as well as the corresponding 95% confidence intervals (CIs) of high and low TMB patients, were included. All statistical analyses were performed using the R software.

Results

Pooled results from a total of 32 studies with 6,131 participants showed significantly increased OS (HR: 0.61, 95% CI: 0.53–0.71; P <0.01) and PFS (HR: 0.51, 95% CI: 0.44–0.60; P <0.01) for the high TMB group receiving ICIs as compared to the low TMB group. Particularly, results were found to be more significant in studies with larger sample sizes (≥30), Western patients, higher TMB cutoff values (≥20 mut/Mb), anti–PD-1 therapy, and when the sample source was tissue and tumor type was either melanoma, small cell lung cancer, or gastric cancer.

Conclusion

TMB is a promising independent prognostic biomarker for cancer patients receiving ICIs, which could provide a new potential therapeutic strategy for high TMB patients who have failed traditional therapy. Furthermore, consistency in the key aspects of TMB assessment is expected in the future.

Systematic Review Registration

[https://www.crd.york.ac.uk/PROSPERO], Prospective Register of Systematic Reviews (PROSPERO), identifier: CRD42021229016.
LncRNA FOXD3-AS1 Promotes the Malignant Progression of Nasopharyngeal Carcinoma Through Enhancing the Transcription of YBX1 by H3K27Ac Modification
Authors: Yang Huiyun , Pan Yuliang , Zhang Jun , Jin Long , Zhang Xi
Published: July 2021

Background

Long noncoding RNAs (lncRNAs) can affect the progression of various tumors, including nasopharyngeal carcinoma (NPC). Here, lncRNA FOXD3-AS1 is highly expressed in NPC tissues through bioinformatics analysis and related to the malignant progression of NPC.

Methods

Bioinformatics analysis and real-time reverse transcription quantitative PCR(RT-qPCR) assay were applied to identify the expression of FOXD3-AS1 in NPC tissues and cells. Specific short hairpin RNAs (shRNAs) or overexpression plasmids were used to knockdown or upregulate FOXD3-AS1 in NPC cells. The effect of FOXD3-AS1 on proliferation and metastasis of NPC was confirmed by CCK8, colony formation, transwell assays in vitro and mouse tumor growth and metastasis models in vivo, of which the mechanism was explored by RNA pull down, mass spectrometry (MS), RNA Immunoprecipitation (RIP), chromatin immunoprecipitation (CHIP) and luciferase assays.

Results

FOXD3-AS1 was highly expressed in NPC tissues and cells. Knockdown of FOXD3-AS1 significantly inhibited proliferation, migration, and invasion of NPC cells in vitro and vivo. FOXD3-AS1 could specifically bind to YBX1 and have a positive effect on the expression of YBX1. Bioinformatics analysis showed that the promoter of YBX1 had a high enrichment of H3K27ac, which promote mRNA transcription and protein translation of YBX1. Moreover, overexpression of YBX1 could reverse the proliferation, migration and invasion arrest caused by FOXD3-AS1 knockdown.

Conclusion

LncRNA FOXD3-AS1 is highly expressed and promotes malignant phenotype in NPC, which may provide a new molecular mechanism for NPC.
Erythema Multiforme Major Associated With Community-Acquired Pneumonia: Lessons From a Case Report
Authors: Fan Xiaomei , Luo Yong , Lu Jieluan , Xu Jinji , Chen Qing , Guo Huijuan , Jin Ping
Published: July 2021

Background:Erythema multiforme (EM) is an acute immune-mediated inflammatory mucinous skin disorder. The etiology of pediatric EM involves infections, medications, autoimmune diseases, and genetic factors.

Case Report:An 8-year-old girl withMycoplasma pneumoniae(MP) associated community-acquired pneumonia developed erythema target-like symptoms 1 week after azithromycin administration. The erythema quickly spread throughout the body involving the oral and ocular mucous membranes, the trunk, and the extremities, and eventually developed into erythema multiform major (EMM). Through drug withdrawal and specific treatment including systemic corticosteroids and supportive care, her clinical symptoms were improved. After 31 days, most of the mucocutaneous symptoms were relieved, except pigmentation. Human leukocyte antigen (HLA) gene sequencing was performed and 20 HLA genotypes were identified. The patient follow-up lasted for 18 months. Rashes appeared on her trunk when receiving azithromycin orally after discharge and then disappeared after azithromycin withdrawal.

Conclusions:Pediatric EM is a rare disease and recognition of its etiology is important for EM management. In this case, azithromycin andHLA-DQB1*03:01genotype may contribute to EMM.

Lesson:For drug-induced EM, rapid identification and withdrawal of the causative drugs is critical. Re-exposure to the same drug or exposure to drugs with similar chemical structures should also be avoided. Patient education and rational use of medicines are essential for pediatric patients.
Early Identification of Prolonged QT Interval for Prevention of Sudden Infant Death
Authors: Sarquella-Brugada Georgia , García-Algar Oscar , Zambrano María Dolores , Fernández-Falgueres Anna , Sailer Sebastian , Cesar Sergi , Sebastiani Giorgia , Martí-Almor Julio , Aurensanz Esther , Cruzalegui Jose Carlos , Merchan Erika Fernanda , Coll Mónica , Pérez-Serra Alexandra , Olmo Bernat del , Fiol Victoria , Iglesias Anna , Ferrer-Costa Carles , Puigmulé Marta , Lopez Laura , Pico Ferran , Arbelo Elena , Jordà Paloma , Brugada Josep , Brugada Ramon , Campuzano Oscar
Published: July 2021

Introduction: Long QT syndrome is the main arrhythmogenic disease responsible for sudden death in infants, especially in the first days of life. Performing an electrocardiogram in newborns could enable early diagnosis and adoption of therapeutic measures focused on preventing lethal arrhythmogenic events. However, the inclusion of an electrocardiogram in neonatal screening protocols still remains a matter of discussion. To comprehensively analyse the potential clinical value of performing an electrocardiogram and subsequent follow-up in a cohort of newborns.

Methods: Electrocardiograms were performed in 685 neonates within the first week of life. One year follow-up was performed if QTc > 450 ms identified. Comprehensive genetic analysis using massive sequencing was performed in all cases with QTc > 470 ms.

Results: We identified 54 neonates with QTc > 450 ms/ <470 ms; all normalized QTc values within 6 months. Eight cases had QTc > 480 ms at birth and, if persistent, pharmacological treatment was administrated during follow-up. A rare variant was identified as the potential cause of long QT syndrome in five cases. Three cases showed a family history of sudden arrhythmogenic death.

Conclusions: Our prospective study identifies 0.14% of cases with a definite long QT, supporting implementation of electrocardiograms in routine pediatric protocols. It is an effective, simple and non-invasive approach that can help prevent sudden death in neonates and their relatives. Genetic analyses help to unravel the cause of arrhythmogenic disease in diagnosing neonates. Further, clinical assessment and genetic analysis of relatives allowed early identification of family members at risk of arrhythmias helping to adopt preventive personalized measures.
Supportive Care During Pediatric Hematopoietic Stem Cell Transplantation: Prevention of Infections. A Report From Workshops on Supportive Care of the Paediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Ifversen Marianne , Meisel Roland , Sedlacek Petr , Kalwak Krzysztof , Sisinni Luisa , Hutt Daphna , Lehrnbecher Thomas , Balduzzi Adriana , Diesch Tamara , Jarisch Andrea , Güngör Tayfun , Stein Jerry , Yaniv Isaac , Bonig Halvard , Kuhlen Michaela , Ansari Marc , Nava Tiago , Dalle Jean-Hugues , Diaz-de-Heredia Cristina , Trigoso Eugenia , Falkenberg Ulrike , Hartmann Mihaela , Deiana Marco , Canesi Marta , Broggi Chiara , Bertaina Alice , Gibson Brenda , Krivan Gergely , Vettenranta Kim , Matic Toni , Buechner Jochen , Lawitschka Anita , Peters Christina , Yesilipek Akif , Yalçin Koray , Lucchini Giovanna , Bakhtiar Shahrzad , Turkiewicz Dominik , Niinimäki Riitta , Wachowiak Jacek , Cesaro Simone , Dalissier Arnaud , Corbacioglu Selim , Willasch Andre Manfred , Bader Peter
Published: July 2021

Specific protocols define eligibility, conditioning, donor selection, graft composition and prophylaxis of graft vs. host disease for children and young adults undergoing hematopoietic stem cell transplant (HSCT). However, international protocols rarely, if ever, detail supportive care, including pharmaceutical infection prophylaxis, physical protection with face masks and cohort isolation or food restrictions. Supportive care suffers from a lack of scientific evidence and implementation of practices in the transplant centers brings extensive restrictions to the child's and family's daily life after HSCT. Therefore, the Board of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) held a series of dedicated workshops since 2017 with the aim of initiating the production of a set of minimal recommendations. The present paper describes the consensus reached within the field of infection prophylaxis.
Sex Differences in the Vasodilation Mediated by G Protein-Coupled Estrogen Receptor (GPER) in Hypertensive Rats
Authors: Delgado Nathalie Tristão Banhos , Rouver Wender do Nascimento , Freitas-Lima Leandro Ceotto , Vieira-Alves Ildernandes , Lemos Virgínia Soares , Santos Roger Lyrio dos
Published: July 2021

Background

The protective effect of estrogen on the vasculature cannot be explained only by its action through the receptors ERα and ERβ. G protein-coupled estrogen receptors (GPER)—which are widely distributed throughout the cardiovascular system—may also be involved in this response. However, little is known about GPER actions in hypertension. Therefore, in this study we evaluated the vascular response mediated by GPER using a specific agonist, G-1, in spontaneously hypertensive rats (SHR). We hypothesized that G-1 would induce a relaxing response in resistance mesenteric arteries from SHR of both sexes.

Methods

G-1 concentration-response curves (1 nM-10 μM) were performed in mesenteric arteries from SHR of both sexes (10–12-weeks-old, weighing 180–250 g). The effects of G-1 were evaluated before and after endothelial removal and incubation for 30 min with the inhibitors L-NAME (300 μM) and indomethacin (10 μM) alone or combined with clotrimazole (0.75 μM) or catalase (1,000 units/mL). GPER immunolocalization was also investigated, and vascular hydrogen peroxide (H2O2) and ROS were evaluated using dichlorofluorescein (DCF) and dihydroethidium (DHE) staining, respectively.

Results

GPER activation promoted a similar relaxing response in resistance mesenteric arteries of female and male hypertensive rats, but with the participation of different endothelial mediators. Males appear to be more dependent on the NO pathway, followed by the H2O2 pathway, and females on the endothelium and H2O2 pathway.

Conclusion

These findings show that the GPER agonist G-1 can induce a relaxing response in mesenteric arteries from hypertensive rats of both sexes in a similar way, albeit with differential participation of endothelial mediators. These results contribute to the understanding of GPER activation on resistance mesenteric arteries in essential hypertension.
Can Reactivity of Heart Rate Variability Be a Potential Biomarker and Monitoring Tool to Promote Healthy Aging? A Systematic Review With Meta-Analyses
Authors: Manser Patrick , Thalmann Melanie , Adcock Manuela , Knols Ruud H. , de Bruin Eling D.
Published: July 2021

Background: Monitoring phasic responses of heart rate variability (HRV) in terms of HRV reactivity [i. e., the absolute change from resting state to on-task (i.e., absolute values of HRV measured during exercise)] might provide useful insights into the individual psychophysiological responses of healthy middle-aged to older adults (HOA) to cognitive and physical exercises.

Objectives: To summarize the evidence of phasic HRV responses to cognitive and physical exercises, and to evaluate key moderating factors influencing these responses.

Methods: A systematic review with meta-analyses was performed. Publications up to May 2020 of the databases Medline (EBSCO), Embase, Cochrane Library, CINAHL, Psycinfo, Web of Science, Scopus, and Pedro were considered. Controlled clinical trials and observational studies measuring phasic HRV responses to cognitive and/or physical exercises in HOA (≥50 years) were included.

Results: The initial search identified 6,828 articles, of which 43 were included into the systematic review. Compared to resting state, vagally-mediated HRV indices were significantly reduced during all types of exercises [Hedge's g = −0.608, 95 % CI (−0.999 to −0.218), p = 0.002] indicating a significant parasympathetic withdrawal compared to rest. The key moderating variables of these responses identified included exercise intensity for physical exercises, and participant characteristics (i.e., level of cognitive functioning, physical fitness), task demands (i.e., task complexity and modality) and the individual responses to these cognitive challenges for cognitive exercises. In particular, higher task demands (task complexity and physical exercise intensity) were related to larger HRV reactivities. Better physical fitness and cognition were associated with lower HRV reactivities. Additionally, HRV reactivity appeared to be sensitive to training-induced cognitive and neural changes.

Conclusion: HRV reactivity seems to be a promising biomarker for monitoring internal training load and evaluating neurobiological effects of training interventions. Further research is warranted to evaluate the potential of HRV reactivity as a monitoring parameter to guide cognitive-motor training interventions and/or as a biomarker for cognitive impairment. This may facilitate the early detection of cognitive impairment as well as allow individualized training adaptations that, in turn, support the healthy aging process by optimizing individual exercise dose and progression of cognitive-motor training.
Long-Term Narrowband Lighting Influences Activity but Not Intrinsically Photosensitive Retinal Ganglion Cell-Driven Pupil Responses
Authors: Lou Linjiang , Arumugam Baskar , Hung Li-Fang , She Zhihui , Beach Krista M. , Smith Earl L. , Ostrin Lisa A.
Published: July 2021

Purpose:Light affects a variety of non-image forming processes, such as circadian rhythm entrainment and the pupillary light reflex, which are mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). The purpose of this study was to assess the effects of long- and short-wavelength ambient lighting on activity patterns and pupil responses in rhesus monkeys.

Methods:Infant rhesus monkeys were reared under either broadband “white” light (n= 14), long-wavelength “red” light (n= 20; 630 nm), or short-wavelength “blue” light (n= 21; 465 nm) on a 12-h light/dark cycle starting at 24.1 ± 2.6 days of age. Activity was measured for the first 4 months of the experimental period using a Fitbit activity tracking device and quantified as average step counts during the daytime (lights-on) and nighttime (lights-off) periods. Pupil responses to 1 s red (651 nm) and blue (456 nm) stimuli were measured after approximately 8 months. Pupil metrics included maximum constriction and the 6 s post-illumination pupil response (PIPR).

Results:Activity during the lights-on period increased with age during the first 10 weeks (p< 0.001 for all) and was not significantly different for monkeys reared in white, red, or blue light (p= 0.07). Activity during the 12-h lights-off period was significantly greater for monkeys reared in blue light compared to those in white light (p= 0.02), but not compared to those in red light (p= 0.08). However, blue light reared monkeys exhibited significantly lower activity compared to both white and red light reared monkeys during the first hour of the lights-off period (p= 0.01 for both) and greater activity during the final hour of the lights-off period (p< 0.001 for both). Maximum pupil constriction and the 6 s PIPR to 1 s red and blue stimuli were not significantly different between groups (p> 0.05 for all).

Conclusion:Findings suggest that long-term exposure to 12-h narrowband blue light results in greater disruption in nighttime behavioral patterns compared to narrowband red light. Normal pupil responses measured later in the rearing period suggest that ipRGCs adapt after long-term exposure to narrowband lighting.
Revealing the Introduction History and Phylogenetic Relationships of Passiflora foetida sensu lato in Australia
Authors: Hopley Tara , Webber Bruce L. , Raghu S. , Morin Louise , Byrne Margaret
Published: July 2021

Genomic analysis can be a valuable tool to assistmanagement of non-native invasive species, through determining source and number of introductions as well as clarifying phylogenetic relationships. Here, we used whole chloroplast sequencing to investigate the introduction history of Passiflora foetida sensu lato in Australia and clarify its relationship with other Passiflora species present. Phylogenetic analysis of chloroplast genome data identified three separate genetic lineages of P. foetida s. l. present in Australia, indicating multiple introductions. These lineages had affinities to samples from three separate areas within the native range in Central and South America that represented phylogenetically distinct lineages. These results provide a basis for a targeted search of the native range of P. foetida s. l. for candidate biological control agents that have co-evolved with this species and are thus better adapted to the lineages that are present in Australia. Results also indicated that the Passiflora species native to Australia are in a separate clade to that of P. foetida s. l. and other introduced Passiflora species cultivated in Australia. This knowledge is important to assess the likelihood of finding biological control agents for P. foetida s. l. that will be sufficiently host-specific for introduction in Australia. As P. foetida s. l. is a widespread non-native invasive species across many regions of the world, outcomes from this work highlight the importance of first evaluating the specific entities present in a country before the initiation of a biological control program.
Leaf Epidermis: The Ambiguous Symplastic Domain
Authors: Voitsekhovskaja Olga V. , Melnikova Anna N. , Demchenko Kirill N. , Ivanova Alexandra N. , Dmitrieva Valeria A. , Maksimova Anastasiia I. , Lohaus Gertrud , Tomos A. Deri , Tyutereva Elena V. , Koroleva Olga A.
Published: July 2021

The ability to develop secondary (post-cytokinetic) plasmodesmata (PD) is an important evolutionary advantage that helps in creating symplastic domains within the plant body. Developmental regulation of secondary PD formation is not completely understood. In flowering plants, secondary PD occur exclusively between cells from different lineages, e.g., at the L1/L2 interface within shoot apices, or between leaf epidermis (L1-derivative), and mesophyll (L2-derivative). However, the highest numbers of secondary PD occur in the minor veins of leaf between bundle sheath cells and phloem companion cells in a group of plant species designated “symplastic” phloem loaders, as opposed to “apoplastic” loaders. This poses a question of whether secondary PD formation is upregulated in general in symplastic loaders. Distribution of PD in leaves and in shoot apices of two symplastic phloem loaders, Alonsoa meridionalis and Asarina barclaiana, was compared with that in two apoplastic loaders, Solanum tuberosum (potato) and Hordeum vulgare (barley), using immunolabeling of the PD-specific proteins and transmission electron microscopy (TEM), respectively. Single-cell sampling was performed to correlate sugar allocation between leaf epidermis and mesophyll to PD abundance. Although the distribution of PD in the leaf lamina (except within the vascular tissues) and in the meristem layers was similar in all species examined, far fewer PD were found at the epidermis/epidermis and mesophyll/epidermis boundaries in apoplastic loaders compared to symplastic loaders. In the latter, the leaf epidermis accumulated sugar, suggesting sugar import from the mesophyll via PD. Thus, leaf epidermis and mesophyll might represent a single symplastic domain in Alonsoa meridionalis and Asarina barclaiana.
QTL Mapping for Leaf Area of Tea Plants (Camellia sinensis) Based on a High-Quality Genetic Map Constructed by Whole Genome Resequencing
Authors: An Yanlin , Chen Linbo , Tao Lingling , Liu Shengrui , Wei Chaoling
Published: July 2021

High-quality genetic maps play important roles in QTL mapping and molecular marker-assisted breeding. Tea leaves are not only important vegetative organs but are also the organ for harvest with important economic value. However, the key genes and genetic mechanism of regulating leaf area have not been clarified. In this study, we performed whole-genome resequencing on “Jinxuan,” “Yuncha 1” and their 96 F1 hybrid offspring. From the 1.84 Tb of original sequencing data, abundant genetic variation loci were identified, including 28,144,625 SNPs and 2,780,380 indels. By integrating the markers of a previously reported genetic map, a high-density genetic map consisting of 15 linkage groups including 8,956 high-quality SNPs was constructed. The total length of the genetic map is 1,490.81 cM, which shows good collinearity with the genome. A total of 25 representative markers (potential QTLs) related to leaf area were identified, and there were genes differentially expressed in large and small leaf samples near these markers. GWAS analysis further verified the reliability of QTL mapping. Thirty-one pairs of newly developed indel markers located near these potential QTLs showed high polymorphism and had good discrimination between large and small leaf tea plant samples. Our research will provide necessary support and new insights for tea plant genetic breeding, quantitative trait mapping and yield improvement.
Differential Nutrient Uptake by Saltmarsh Plants Is Modified by Increasing Salinity
Authors: Carmona Raquel , Muñoz Rocío , Niell F. Xavier
Published: July 2021

In Southern European estuaries and associated salt marshes, the anthropogenic nutrient inputs, together with longer drought periods, are leading to increasing eutrophication and salinization of these coastal ecosystems. In this study, uptake kinetics of ammonium, nitrate, and phosphate by three common plants in Palmones salt marsh (Southern Spain), Sarcocornia perennis ssp. alpini, Atriplex portulacoides, and Arthrocnemum macrostachyum were measured in hydroponic cultures. We also determined how these uptakes could be modified by increasing salinity, adding NaCl to the incubation medium (from 170 to 1,025 mM). Kinetic parameters are analyzed to understand the competition of the three species for nutrient resources under realistic most frequent concentrations in the salt marsh. These results may also be useful to predict the possible changes in the community composition and distribution if trends in environmental changes persist. Atriplex portulacoides showed the highest Vmax for ammonium, the most abundant nutrient in the salt marsh, while the highest affinity for this nutrient was observed in A. macrostachyum. Maximum uptake rates for nitrate were much lower than for ammonium, without significant differences among species. The highest Vmax value for phosphate was observed in A. macrostachyum, whereas A. portulacoides presented the highest affinity for this nutrient. High salinity drastically affected the physiological response of these species, decreasing nutrient uptake. Sarcocornia perennis ssp. alpini and A. macrostachyum were not affected by salinity up to 510 mM NaCl, whereas A. portulacoides notably decreased its uptake capacity at 427 mM and even withered at 1,025 mM NaCl. At current most frequent concentrations of ammonium and phosphate in the salt marsh, S. perennis ssp. alpini is the most favored species, from the nutritional point of view. However, A. portulacoides could enhance its presence if the increasing ammonium load continues, although a simultaneous salinization would negatively affect its nutritional physiology.
Plasmodiophora brassicae-Triggered Cell Enlargement and Loss of Cellular Integrity in Root Systems Are Mediated by Pectin Demethylation
Authors: Stefanowicz Karolina , Szymanska-Chargot Monika , Truman William , Walerowski Piotr , Olszak Marcin , Augustyniak Adam , Kosmala Arkadiusz , Zdunek Artur , Malinowski Robert
Published: July 2021

Gall formation on the belowground parts of plants infected with Plasmodiophora brassicae is the result of extensive host cellular reprogramming. The development of these structures is a consequence of increased cell proliferation followed by massive enlargement of cells colonized with the pathogen. Drastic changes in cellular growth patterns create local deformities in the roots and hypocotyl giving rise to mechanical tensions within the tissue of these organs. Host cell wall extensibility and recomposition accompany the growth of the gall and influence pathogen spread and also pathogen life cycle progression. Demethylation of pectin within the extracellular matrix may play an important role in P. brassicae-driven hypertrophy of host underground organs. Through proteomic analysis of the cell wall, we identified proteins accumulating in the galls developing on the underground parts of Arabidopsis thaliana plants infected with P. brassicae. One of the key proteins identified was the pectin methylesterase (PME18); we further characterized its expression and conducted functional and anatomic studies in the knockout mutant and used Raman spectroscopy to study the status of pectin in P. brassicae-infected galls. We found that late stages of gall formation are accompanied with increased levels of PME18. We have also shown that the massive enlargement of cells colonized with P. brassicae coincides with decreases in pectin methylation. In pme18-2 knockout mutants, P. brassicae could still induce demethylation; however, the galls in this line were smaller and cellular expansion was less pronounced. Alteration in pectin demethylation in the host resulted in changes in pathogen distribution and slowed down disease progression. To conclude, P. brassicae-driven host organ hypertrophy observed during clubroot disease is accompanied by pectin demethylation in the extracellular matrix. The pathogen hijacks endogenous host mechanisms involved in cell wall loosening to create an optimal cellular environment for completion of its life cycle and eventual release of resting spores facilitated by degradation of demethylated pectin polymers.
An Affordable Image-Analysis Platform to Accelerate Stomatal Phenotyping During Microscopic Observation
Authors: Toda Yosuke , Tameshige Toshiaki , Tomiyama Masakazu , Kinoshita Toshinori , Shimizu Kentaro K.
Published: July 2021

Recent technical advances in the computer-vision domain have facilitated the development of various methods for achieving image-based quantification of stomata-related traits. However, the installation cost of such a system and the difficulties of operating it on-site have been hurdles for experimental biologists. Here, we present a platform that allows real-time stomata detection during microscopic observation. The proposed system consists of a deep neural network model-based stomata detector and an upright microscope connected to a USB camera and a graphics processing unit (GPU)-supported single-board computer. All the hardware components are commercially available at common electronic commerce stores at a reasonable price. Moreover, the machine-learning model is prepared based on freely available cloud services. This approach allows users to set up a phenotyping platform at low cost. As a proof of concept, we trained our model to detect dumbbell-shaped stomata from wheat leaf imprints. Using this platform, we collected a comprehensive range of stomatal phenotypes from wheat leaves. We confirmed notable differences in stomatal density (SD) between adaxial and abaxial surfaces and in stomatal size (SS) between wheat-related species of different ploidy. Utilizing such a platform is expected to accelerate research that involves all aspects of stomata phenotyping.