bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative Predictive Modeling of Metastasis in Melanoma Cancer Based on MicroRNA, mRNA, and DNA Methylation Data
Authors: Kutlay Ayşegül , Aydin Son Yeşim
Published: September 2021

Introduction: Despite the significant progress in understanding cancer biology, the deduction of metastasis is still a challenge in the clinic. Transcriptional regulation is one of the critical mechanisms underlying cancer development. Even though mRNA, microRNA, and DNA methylation mechanisms have a crucial impact on the metastatic outcome, there are no comprehensive data mining models that combine all transcriptional regulation aspects for metastasis prediction. This study focused on identifying the regulatory impact of genetic biomarkers for monitoring metastatic molecular signatures of melanoma by investigating the consolidated effect of miRNA, mRNA, and DNA methylation.

Method: We developed multiple machine learning models to distinguish the metastasis by integrating miRNA, mRNA, and DNA methylation markers. We used the TCGA melanoma dataset to differentiate between metastatic melanoma samples by assessing a set of predictive models. For this purpose, machine learning models using a support vector machine with different kernels, artificial neural networks, random forests, AdaBoost, and Naïve Bayes are compared. An iterative combination of differentially expressed miRNA, mRNA, and methylation signatures is used as a candidate marker to reveal each new biomarker category’s impact. In each iteration, the performances of the combined models are calculated. During all comparisons, the choice of the feature selection method and under and oversampling approaches are analyzed. Selected biomarkers of the highest performing models are further analyzed for the biological interpretation of functional enrichment.

Results: In the initial model, miRNA biomarkers can identify metastatic melanoma with an 81% F-score. The addition of mRNA markers upon miRNA increased the F-score to 92%. In the final integrated model, the addition of the methylation data resulted in a similar F-score of 92% but produced a stable model with low variance across multiple trials.

Conclusion: Our results support the role of miRNA regulation in metastatic melanoma as miRNA markers model metastasis outcomes with high accuracy. Moreover, the integrated evaluation of miRNA with mRNA and methylation biomarkers increases the model’s power. It populates selected biomarkers on the metastasis-associated pathways of melanoma, such as the “osteoclast”, “Rap1 signaling”, and “chemokine signaling” pathways.

Source Code:https://github.com/aysegul-kt/MelonomaMetastasisPrediction/
Mitochondrial Protein PGAM5 Emerges as a New Regulator in Neurological Diseases
Authors: Liang Min-Zong , Ke Ting-Ling , Chen Linyi
Published: September 2021

As mitochondrial dysfunction has increasingly been implicated in neurological diseases, much of the investigation focuses on the response of the mitochondria. It appears that mitochondria can respond to external stimuli speedy fast, in seconds. Understanding how mitochondria sense the signal and communicate with cytosolic pathways are keys to understand mitochondrial regulation in diseases or in response to trauma. It was not until recently that a novel mitochondrial protein, phosphoglycerate mutase family member 5 (PGAM5) has emerged to be a new regulator of mitochondrial homeostasis. Although controversial results reveal beneficial as well as detrimental roles of PGAM5 in cancers, these findings also suggest PGAM5 may have diverse regulation on cellular physiology. Roles of PGAM5 in neuronal tissues remain to be uncovered. This review discusses current knowledge of PGAM5 in neurological diseases and provides future perspectives.
A Zebrafish Model of Metastatic Colonization Pinpoints Cellular Mechanisms of Circulating Tumor Cell Extravasation
Authors: Allen Tyler A. , Cullen Mark M. , Hawkey Nathan , Mochizuki Hiroyuki , Nguyen Lan , Schechter Elyse , Borst Luke , Yoder Jeffrey A. , Freedman Jennifer A. , Patierno Steven R. , Cheng Ke , Eward William C. , Somarelli Jason A.
Published: September 2021

Metastasis is a multistep process in which cells must detach, migrate/invade local structures, intravasate, circulate, extravasate, and colonize. A full understanding of the complexity of this process has been limited by the lack of ability to study these steps in isolation with detailed molecular analyses. Leveraging a comparative oncology approach, we injected canine osteosarcoma cells into the circulation of transgenic zebrafish with fluorescent blood vessels in a biologically dynamic metastasis extravasation model. Circulating tumor cell clusters that successfully extravasated the vasculature as multicellular units were isolated under intravital imaging (n = 6). These extravasation-positive tumor cell clusters sublines were then molecularly profiled by RNA-Seq. Using a systems-level analysis, we pinpointed the downregulation of KRAS signaling, immune pathways, and extracellular matrix (ECM) organization as enriched in extravasated cells (p < 0.05). Within the extracellular matrix remodeling pathway, we identified versican (VCAN) as consistently upregulated and central to the ECM gene regulatory network (p < 0.05). Versican expression is prognostic for a poorer metastasis-free and overall survival in patients with osteosarcoma. Together, our results provide a novel experimental framework to study discrete steps in the metastatic process. Using this system, we identify the versican/ECM network dysregulation as a potential contributor to osteosarcoma circulating tumor cell metastasis.
Disulfiram Alone Functions as a Radiosensitizer for Pancreatic Cancer Both In Vitro and In Vivo
Authors: Xu Ying , Lu Lunjie , Luo Judong , Wang Lili , Zhang Qi , Cao Jianping , Jiao Yang
Published: September 2021

The prognosis of pancreatic cancer remains very poor worldwide, partly due to the lack of specificity of early symptoms and innate resistance to chemo-/radiotherapy. Disulfiram (DSF), an anti-alcoholism drug widely used in the clinic, has been known for decades for its antitumor effects when simultaneously applied with copper ions, including pancreatic cancer. However, controversy still exists in the context of the antitumor effects of DSF alone in pancreatic cancer and related mechanisms, especially in its potential roles as a sensitizer for cancer radiotherapy. In the present study, we focused on whether and how DSF could facilitate ionizing radiation (IR) to eliminate pancreatic cancer. DSF alone significantly suppressed the survival of pancreatic cancer cells after exposure to IR, both in vitro and in vivo. Additionally, DSF treatment alone caused DNA double-strand breaks (DSBs) and further enhanced IR-induced DSBs in pancreatic cancer cells. In addition, DSF alone boosted IR-induced cell cycle G2/M phase arrest and apoptosis in pancreatic cancer exposed to IR. RNA sequencing and bioinformatics analysis results suggested that DSF could trigger cell adhesion molecule (CAM) signaling, which might be involved in its function in regulating the radiosensitivity of pancreatic cancer cells. In conclusion, we suggest that DSF alone may function as a radiosensitizer for pancreatic cancer, probably by regulating IR-induced DNA damage, cell cycle arrest and apoptosis, at least partially through the CAM signaling pathway.
Impact of Adjuvant Therapy on Survival in Surgically Resected Limited-Stage Small Cell Lung Cancer
Authors: Li Di , Deng Chaoqiang , Zheng Qiang , Fu Fangqiu , Wang Shengping , Li Yuan , Chen Haiquan , Zhang Yang
Published: September 2021

Background

Data on efficacy of adjuvant therapy for surgically resected small cell lung cancer are scant. This study was determined to reveal the survival benefits of different adjuvant treatment modalities for limited-stage small cell lung cancer patients following surgical resection.

Methods

Data of patients with histologically confirmed small cell lung cancer after surgical resection were collected from November 2006 to June 2019. Survival analyses were calculated by Kaplan–Meier method, with log-rank test to evaluate statistical significance. Prognostic factors were identified by multivariate analysis using cox proportional hazards model. Further survival analysis and cox regression analysis stratified by clinicopathologic features were conducted to evaluate the survival benefits of different adjuvant treatment modalities.

Results

In total, 153 out of 157 patients were analyzed. Multivariate analysis showed male sex, lymph node metastasis, residual tumor, VPI and non-adjuvant therapy were independently associated with poor prognosis. Subgroup analyses revealed both adjuvant chemotherapy and adjuvant chemoradiotherapy were significantly associated with superior survival for stage pT2-4 (HR=0.176, 95%CI:0.053-0.578, p=0.004; and HR=0.115, 95%CI:0.033-0.405, p=0.001) and pure SCLC patients (HR=0.182, 95%CI:0.067-0.494, p=0.001; and HR=0.181, 95%CI:0.071-0.465, p<0.001). For pN0 patients, adjuvant chemotherapy was associated with better survival (HR=0.219, 95%CI:0.054-0.891, p=0.034), while adjuvant chemoradiotherapy was associated with improved survival for pN+ patients (HR=0.324, 95%CI:0.138-0.760, p=0.010).

Conclusions

For patients without pathologic lymph node metastasis, there is a survival benefit with adjuvant chemotherapy. However, for patients with pathologic lymph node metastasis, adjuvant chemoradiotherapy might achieve a significant survival benefit. Further prospective studies are needed to validate the results.
Actin Beta-Like 2 as a New Mediator of Proliferation and Migration in Epithelial Ovarian Cancer
Authors: Topalov Nicole Elisabeth , Mayr Doris , Scherer Clemens , Chelariu-Raicu Anca , Beyer Susanne , Hester Anna , Kraus Fabian , Zheng Mingjun , Kaltofen Till , Kolben Thomas , Burges Alexander , Mahner Sven , Trillsch Fabian , Jeschke Udo , Czogalla Bastian
Published: September 2021

The impact of Actin beta-like 2 (ACTBL2), a novel described actin isoform, on epithelial ovarian cancer (EOC) biology has not been investigated so far. In this study, we analyzed the prognostic and functional significance of ACTBL2 and its regulatory element Nuclear factor of activated T-cells 5 (NFAT5). The expression of ACTBL2 and NFAT5 was examined in tissue microarrays of 156 ovarian cancer patients by immunohistochemistry. Aiming to assess the molecular impact of ACTBL2 on cellular characteristics, functional assays were executed in vitro upon siRNA knockdown of ACTBL2 and NFAT5. ACTBL2 expression was identified as an independent negative prognostic factor for overall survival of EOC patients. EOC cell lines showed a significantly increased mRNA and protein level of ACTBL2 compared to the benign control. In vitro analyses upon siRNA knockdown of ACTBL2 displayed a significantly reduced cellular viability, proliferation and migration. siRNA knockdown of NFAT5 proved a significant molecular interplay by inducing a downregulation of ACTBL2 with a thus resulting concordant alteration in cellular functions, predominantly reflected in a decreased migratory potential of EOC cells. Our results provide significant evidence on the negative prognostic impact of ACTBL2 in EOC, suggesting its crucial importance in ovarian carcinogenesis by modulating cellular motility and proliferation.
A Different View for an Old Disease: NEDDylation and Other Ubiquitin-Like Post-Translational Modifications in Chronic Lymphocytic Leukemia
Authors: Arenas Víctor , Castaño Jose Luis , Domínguez-García Juan José , Yáñez Lucrecia , Pipaón Carlos
Published: September 2021

Despite the enormous amount of molecular data obtained over the years, the molecular etiology of chronic lymphocytic leukemia (CLL) is still largely unknown. All that information has enabled the development of new therapeutic approaches that have improved life expectancy of the patients but are still not curative. We must increase our knowledge of the molecular alterations responsible for the characteristics common to all CLL patients. One of such characteristics is the poor correlation between mRNA and protein expression, that suggests a role of post-translational mechanisms in CLL physiopathology. Drugs targeting these processes have indeed demonstrated an effect either alone or in combination with other aimed at specific pathways. A recent article unveiled an increment in ubiquitin-like modifications in CLL, with many protein members of relevant pathways affected. Interestingly, the inhibition of the NEDD8-activating protein NAE reverted a substantial number of those modifications. The present review gets the scarce data published about the role of NEDDylation in CLL together and establishes connections to what is known from other neoplasias, thus providing a new perspective to the underlying mechanisms in CLL.
Case Report: Long Progression-Free Survival of Immunotherapy for Lung Adenocarcinoma With Epidermal Growth Factor Receptor Mutation
Authors: Peng Jianfeng , Zhao Xianguang , Zhao Kaikai , Meng Xiangjiao
Published: September 2021

Background

Immune checkpoint inhibitors (ICIs) have been clinically proven to be efficient in non-small cell lung cancer (NSCLC). However, it has also been found that immunotherapy is not effective for all patients. For instance, some patients with epidermal growth factor receptor (EGFR) mutation tumors have a low overall response rate to ICIs. As a result, we retrospectively analyzed the efficacy of anti-programmed death-ligand 1 (anti-PD-L1) blockade (atezolizumab) treatment for a patient with EGFR mutation, and we explored the interaction between immunotherapy and EGFR mutations in NSCLC.

Case Presentation

A patient, 62-year-old non-smoking female, with lung adenocarcinoma was initially misdiagnosed as EGFR wild type and received a third-line treatment with atezolizumab, experiencing partial response (PR) and progression-free survival (PFS) for 23 months. She had later been confirmed with EGFR L858R mutation prior to taking atezolizumab. On top of that, the patient developed T790M mutation after being administered with atezolizumab instead of EGFR tyrosine kinase inhibitors (TKIs). She started with osimertinib, although the lesion continued to progress. Tumor mutational burden (TMB), PD-L1 expression, and tumor-infiltrating lymphocytes (TILs) had been tested for further analysis.

Conclusion

The case report and literature review indicate that ICIs might be more effective for L858R mutation than for other EGFR mutant subtypes, which correlates with certain potential predictors such as TMB and concurrent PD-L1 plus CD8+ TIL expression. However, there is no report on progression from non-primary EGFR T790M mutation to T790M mutation of patients who neither previously suffered from EGFR-TKIs nor responded to osimertinib. This case report will offer some information to guide the investigation on how to identify those who can benefit from immunotherapy and those who do not respond to EGFR-TKIs among the patients with EGFR mutations.
The Role of Urinary Biomarkers as Diagnostic and Prognostic Predictors of Acute Kidney Injury Associated With Vancomycin
Authors: Sampaio de Souza Garms Durval , Cardoso Eid Karina Zanchetta , Burdmann Emmanuel A. , Marçal Lia Junqueira , Antonângelo Leila , Santos Adriano dos , Ponce Daniela
Published: September 2021

Introduction: The incidence of acute kidney injury (AKI) related to vancomycin is variable, and several risk factors related to the treatment and patients may explain the nephrotoxicity. The role of urinary biomarkers in AKI related to vancomycin is unknown.

Objective: The aim of this study was to evaluate the role of urinary IL-18, KIM-1, NGAL, TIMP-2, and IGFBP7 as diagnostic and prognostic predictors of AKI related to vancomycin.

Methods: A prospective cohort study of patients receiving vancomycin and admitted to wards of a public university hospital from July 2019 to May 2020 was performed. We excluded patients that had AKI before starting vancomycin, hemodynamic instability, inability to collect urine, and chronic kidney disease stage 5.

Results: Ninety-four patients were included, and the prevalence of AKI was 24.5%, while the general mortality was 8.7%. AKI occurred 11 ± 2 days after the first vancomycin dose. The most frequent KDIGO stage was 1 (61%). There was no difference between patients who developed and did not develop AKI due to gender, length of hospital stay, dose, and time of vancomycin use. Logistic regression identified age (OR 6.6, CI 1.16–38.22, p = 0.03), plasmatic vancomycin concentrations between 96 and 144 h (OR 1.18, CI 1.04-1.40, p = 0.04), and urinary NGAL levels between 96 and 144 h (OR 1.123, CI 1.096–1.290, p = 0.03) as predictors of AKI. The time of vancomycin use (OR 4.61, CI 1.11–22.02, p = 0.03), higher plasmatic vancomycin concentrations between 192 and 240 h (OR 1.02, CI 0.98–1.06, p = 0.26), and higher cell cycle arrest urinary biomarkers TIMP-2 multiplied by IGFBP-7 between 144 and 192 h (OR 1.33, CI 1.10–1.62, p = 0.02; OR 1.19, CI 1.09–1.39, p = 0.04, respectively) were identified as prognostic factors for non-recovery of kidney function at discharge.

Conclusion: AKI related to vancomycin was frequent in patients hospitalized in wards. Age, plasmatic vancomycin concentrations, and NGAL between 96 and 144 h were identified as predictors of AKI related to vancomycin use. Plasmatic vancomycin concentrations and urinary NGAL were predictors of AKI diagnosis within the next 5 days. The urinary biomarkers of cell cycle arrest TIMP-2 and IGFBP-7 and the duration of vancomycin use were associated with non-recovery of kidney function at hospital discharge moment.
Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis
Authors: Markakis Ioannis , Charitakis Ioannis , Beeton Christine , Galani Melpomeni , Repousi Elpida , Aggeloglou Stella , Sfikakis Petros P. , Pennington Michael W. , Chandy K. George , Poulopoulou Cornelia
Published: September 2021

Voltage-gated Kv1.3 potassium channels are key regulators of T lymphocyte activation, proliferation and cytokine production, by providing the necessary membrane hyper-polarization for calcium influx following immune stimulation. It is noteworthy that an accumulating body of in vivo and in vitro evidence links these channels to multiple sclerosis pathophysiology. Here we studied the electrophysiological properties and the transcriptional and translational expression of T lymphocyte Kv1.3 channels in multiple sclerosis, by combining patch clamp recordings, reverse transcription polymerase chain reaction and flow cytometry on freshly isolated peripheral blood T lymphocytes from two patient cohorts with multiple sclerosis, as well as from healthy and disease controls. Our data demonstrate that T lymphocytes in MS, manifest a significant up-regulation of Kv1.3 mRNA, Kv1.3 membrane protein and Kv1.3 current density and therefore of functional membrane channel protein, compared to control groups (p < 0.001). Interestingly, patient sub-grouping shows that Kv1.3 channel density is significantly higher in secondary progressive, compared to relapsing-remitting multiple sclerosis (p < 0.001). Taking into account the tight connection between Kv1.3 channel activity and calcium-dependent processes, our data predict and could partly explain the reported alterations of T lymphocyte function in multiple sclerosis, while they highlight Kv1.3 channels as potential therapeutic targets and peripheral biomarkers for the disease.
Introgression of Maize Diversity for Drought Tolerance: Subtropical Maize Landraces as Source of New Positive Variants
Authors: Barbosa Pedro Augusto Medeiros , Fritsche-Neto Roberto , Andrade Marcela Carvalho , Petroli César Daniel , Burgueño Juan , Galli Giovanni , Willcox Martha C. , Sonder Kai , Vidal-Martínez Víctor A. , Sifuentes-Ibarra Ernesto , Molnar Terence Luke
Published: September 2021

Current climate change models predict an increased frequency and intensity of drought for much of the developing world within the next 30 years. These events will negatively affect maize yields, potentially leading to economic and social instability in many smallholder farming communities. Knowledge about the genetic resources available for traits related to drought tolerance has great importance in developing breeding program strategies. The aim of this research was to study a maize landrace introgression panel to identify chromosomal regions associated with a drought tolerance index. For that, we performed Genome-Wide Association Study (GWAS) on 1326 landrace progenies developed by the CIMMYT Genetic Resources Program, originating from 20 landraces populations collected in arid regions. Phenotypic data were obtained from early testcross trials conducted in three sites and two contrasting irrigation environments, full irrigation (well-watered) and reduced irrigation (drought). The populations were genotyped using the DArTSeq® platform, and a final set of 5,695 SNPs markers was used. The genotypic values were estimated using spatial adjustment in a two-stage analysis. First, we performed the individual analysis for each site/irrigation treatment combination. The best linear unbiased estimates (BLUEs) were used to calculate the Harmonic Mean of Relative Performance (HMRP) as a drought tolerance index for each testcross. The second stage was a joint analysis, which was performed using the HMRP to obtain the best linear unbiased predictions (BLUPs) of the index for each genotype. Then, GWAS was performed to determine the marker-index associations and the marker-Grain Yield (GY) associations for the two irrigation treatments. We detected two significant markers associated with the drought-tolerance index, four associated with GY in drought condition, and other four associated with GY in irrigated conditions each. Although each of these markers explained less than 0.1% of the phenotypic variation for the index and GY, we found two genes likely related to the plant response to drought stress. For these markers, alleles from landraces provide a slightly higher yield under drought conditions. Our results indicate that the positive diversity delivered by landraces are still present on the backcrosses and this is a potential breeding strategy for improving maize for drought tolerance and for trait introgression bringing new superior allelic diversity from landraces to breeding populations.
Photosynthetic Physiological Characteristics of Water and Nitrogen Coupling for Enhanced High-Density Tolerance and Increased Yield of Maize in Arid Irrigation Regions
Authors: Guo Yao , Yin Wen , Fan Hong , Fan Zhilong , Hu Falong , Yu Aizhong , Zhao Cai , Chai Qiang , Aziiba Emmanuel Asibi , Zhang Xijun
Published: September 2021

To some extent, the photosynthetic traits of developing leaves of maize are regulated systemically by water and nitrogen. However, it remains unclear whether photosynthesis is systematically regulated via water and nitrogen when maize crops are grown under close (high density) planting conditions. To address this, a field experiment that had a split-split plot arrangement of treatments was designed. Two irrigation levels on local traditional irrigation level (high, I2, 4,050 m3 ha−1) and reduced by 20% (low, I1, 3,240 m3 ha−1) formed the main plots; two levels of nitrogen fertilizer at a local traditional nitrogen level (high, N2, 360 kg ha−1) and reduced by 25% (low, N1, 270 kg ha−1) formed the split plots; three planting densities of low (D1, 7.5 plants m−2), medium (D2, 9.75 plants m−2), and high (D3, 12 plants m−2) formed the split-split plots. The grain yield, gas exchange, and chlorophyll a fluorescence of the closely planted maize crops were assessed. The results showed that water–nitrogen coupling regulated their net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), quantum yield of non-regulated non-photochemical energy loss [Y(NO)], actual photochemical efficiency of PSII [Y(II)], and quantum yield of regulated non-photochemical energy loss [Y(NPQ)]. When maize plants were grown at low irrigation with traditional nitrogen and at a medium density (i.e., I1N2D2), they had Pn, Gs, and Tr higher than those of grown under traditional treatment conditions (i.e., I2N2D1). Moreover, the increased photosynthesis in the leaves of maize in the I1N2D2 treatment was mainly caused by decreased Y(NO), and increased Y(II) and Y(NPQ). The coupling of 20%-reduced irrigation with the traditional nitrogen application boosted the grain yield of medium density-planted maize, whose Pn, Gs, Tr, Y(II), and Y(NPQ) were enhanced, and its Y(NO) was reduced. Redundancy analysis revealed that both Y(II) and SPAD were the most important physiological factors affecting maize yield performance, followed by Y(NPQ) and NPQ. Using the 20% reduction in irrigation and traditional nitrogen application at a medium density of planting (I1N2D2) could thus be considered as feasible management practices, which could provide technical guidance for further exploring high yields of closely planted maize plants in arid irrigation regions.
The Formation of Fruit Quality in Cucumis sativus L.
Authors: Zhang Juping , Feng Shengjun , Yuan Jing , Wang Chen , Lu Tao , Wang Huasen , Yu Chao
Published: September 2021

Cucumber is one of the most widely grown vegetables in China and an indispensable fresh fruit in the diet. With the development of society, the demand of people for cucumber quality is higher and higher. Therefore, cultivating high-quality cucumber varieties is one of the main goals of cucumber breeding. With the rapid development of biotechnology such as molecular marker, cucumber quality control network is becoming clear. In this review, we describe the formation mechanism of cucumber fruit quality from three aspects: (1) the commercial quality of cucumber fruit, (2) nutritional quality formation, and (3) flavor quality of cucumber fruit. In addition, the determinants of cucumber fruit quality were summarized from two aspects of genetic regulation and cultivation methods in order to provide ideas for cucumber researchers and cultivators to improve fruit quality.
Pea Breeding for Intercropping With Cereals: Variation for Competitive Ability and Associated Traits, and Assessment of Phenotypic and Genomic Selection Strategies
Authors: Annicchiarico Paolo , Nazzicari Nelson , Notario Tommaso , Monterrubio Martin Cristina , Romani Massimo , Ferrari Barbara , Pecetti Luciano
Published: September 2021

Mixed stand (MS) cropping of pea with small-grain cereals can produce more productive and environment-friendly grain crops relative to pure stand (PS) crops but may require selection to alleviate the pea competitive disadvantage. This study aimed to assess the pea variation for competitive ability and its associated traits and the efficiency of four phenotypic or genomic selection strategies. A set of 138 semi-leafless, semi-dwarf pea lines belonging to six recombinant inbred line populations and six parent lines were genotyped using genotyping-by-sequencing and grown in PS and in MS simultaneously with one barley and one bread wheat cultivar in two autumn-sown trials in Northern Italy. Cereal companions were selected in a preliminary study that highlighted the paucity of cultivars with sufficient earliness for association. Pea was severely outcompeted in both years albeit with variation for pea proportion ranging from nearly complete suppression (<3%) to values approaching a balanced mixture. Greater pea proportion in MS was associated with greater total yield of the mixture (r≥ 0.46). The genetic correlation for pea yield across MS and PS conditions slightly exceeded 0.40 in both years. Later onset of flowering and taller plant height at flowering onset displayed a definite correlation with pea yield in MS (r≥ 0.46) but not in PS, whereas tolerance to ascochyta blight exhibited the opposite pattern. Comparisons of phenotypic selection strategies within or across populations based on predicted or actual yield gains for independent years indicated an efficiency of 52–64% for indirect selection based on pea yield in PS relative to pea yield selection in MS. The efficiency of an indirect selection index including onset of flowering, plant height, and grain yield in PS was comparable to that of pea yield selection in MS. A genome-wide association study based on 5,909 SNP markers revealed the substantial diversity of genomic areas associated with pea yield in MS and PS. Genomic selection for pea yield in MS displayed an efficiency close to that of phenotypic selection for pea yield in MS, and nearly two-fold greater efficiency when also taking into account its shorter selection cycle and smaller evaluation cost.
Leaf Morphogenesis: Insights From the Moss Physcomitrium patens
Authors: Lin Wenye , Wang Ying , Coudert Yoan , Kierzkowski Daniel
Published: September 2021

Specialized photosynthetic organs have appeared several times independently during the evolution of land plants. Phyllids, the leaf-like organs of bryophytes such as mosses or leafy liverworts, display a simple morphology, with a small number of cells and cell types and lack typical vascular tissue which contrasts greatly with flowering plants. Despite this, the leaf structures of these two plant types share many morphological characteristics. In this review, we summarize the current understanding of leaf morphogenesis in the model moss Physcomitrium patens, focusing on the underlying cellular patterns and molecular regulatory mechanisms. We discuss this knowledge in an evolutionary context and identify parallels between moss and flowering plant leaf development. Finally, we propose potential research directions that may help to answer fundamental questions in plant development using moss leaves as a model system.
Performance of Bimanual Finger Coordination Tasks in Speakers Who Stutter
Authors: Toyomura Akira , Fujii Tetsunoshin , Sowman Paul F.
Published: September 2021

Stuttering is a neurodevelopmental speech disorder characterized by the symptoms of speech repetition, prolongation, and blocking. Stuttering-related dysfluency can be transiently alleviated by providing an external timing signal such as a metronome or the voice of another person. Therefore, the existence of a core motor timing deficit in stuttering has been speculated. If this is the case, then motoric behaviors other than speech should be disrupted in stuttering. This study examined motoric performance on four complex bimanual tasks in 37 adults who stutter and 31 fluent controls. Two tasks utilized bimanual rotation to examine motor dexterity, and two tasks used the bimanual mirror and parallel tapping movements to examine timing control ability. Video-based analyses were conducted to determine performance accuracy and speed. The results showed that individuals who stutter performed worse than fluent speakers on tapping tasks but not on bimanual rotation tasks. These results suggest stuttering is associated with timing control for general motor behavior.
Lie for Me: Developmental Trends in Acquiescing to a Blatantly False Statement
Authors: Hritz Amelia Courtney , Ceci Stephen J.
Published: September 2021

A pair of studies demonstrates that simply asking children to make a blatantly false accusation in the guise of helping others can result in both immediate and long-term false claims. In the pilot study, the initial willingness to make a blatantly false statement was associated with some children making false statements a week later despite being told that the first interviewer had made mistakes during the initial interview. On a positive note, the majority of participants accurately stated that they did not have first-hand knowledge of their accusation's accuracy. Across both studies, the rate of false accusation rates was high. The main experiment demonstrated that children who were young, possessed the lowest verbal intelligence or who were from the lowest SES homes made the most accusations. These findings illustrate not only the dangers of encouraging children to make false statements, but the ease and durability of making such false statements.
Consumer Brand Engagement Beyond the “Likes”
Authors: Razmus Wiktor
Published: September 2021

In most consumer brand engagement (CBE) scales, indicators of CBE refer to behaviors that are related to social media or online brand communities. CBE also occurs beyond the Internet context in real-life settings. This paper reports the development and validation process of a CBE scale beyond the Internet behavior context. The results of three studies support the content validity, internal consistency, reliability, and nomological validity of the scale. Moreover, the results indicate that brand engagement measured by the CBE scale affects important aspects of brand-related consumer constructs. Consumers with a high level of brand engagement reflected greater brand loyalty, consumer satisfaction with a product, and perceived value of a brand. The author discusses the usefulness of this scale for marketing and psychological research.
An Iterative and Collaborative End-to-End Methodology Applied to Digital Mental Health
Authors: Boulos Laura Joy , Mendes Alexandre , Delmas Alexandra , Chraibi Kaadoud Ikram
Published: September 2021

Artificial intelligence (AI) algorithms together with advances in data storage have recently made it possible to better characterize, predict, prevent, and treat a range of psychiatric illnesses. Amid the rapidly growing number of biological devices and the exponential accumulation of data in the mental health sector, the upcoming years are facing a need to homogenize research and development processes in academia as well as in the private sector and to centralize data into federalizing platforms. This has become even more important in light of the current global pandemic. Here, we propose an end-to-end methodology that optimizes and homogenizes digital research processes. Each step of the process is elaborated from project conception to knowledge extraction, with a focus on data analysis. The methodology is based on iterative processes, thus allowing an adaptation to the rate at which digital technologies evolve. The methodology also advocates for interdisciplinary (from mathematics to psychology) and intersectoral (from academia to the industry) collaborations to merge the gap between fundamental and applied research. We also pinpoint the ethical challenges and technical and human biases (from data recorded to the end user) associated with digital mental health. In conclusion, our work provides guidelines for upcoming digital mental health studies, which will accompany the translation of fundamental mental health research to digital technologies.
Epistemic Trust and the Emergence of Conduct Problems: Aggression in the Service of Communication
Authors: Talia Alessandro , Duschinsky Robbie , Mazzarella Diana , Hauschild Sophie , Taubner Svenja
Published: September 2021

Fonagy and colleagues have recently proposed that deficits in the capacity for epistemic trust (i. e., the expectation that interpersonal communication is relevant to the addressee) are fundamental to psychopathology. In this paper, we consider the implications of this hypothesis for understanding the role of aggression in conduct disorder and conduct problems more generally. Our main proposal is to view conduct problems not only as reflecting dysregulation, but as an adaptation that allows communication with others who are (or are perceived to be) unreliable. Our formulation hinges on two propositions. The first one is to view aggression as a modality of communication adapted to scenarios in which the communicator expects the audience to have low epistemic trust in the communicator. The second idea is to conceptualize the failed “unlearning of aggression” as reflecting a lack of interest in maintaining one's reputation as a communicator, which in turn stems from a lack of epistemic trust in other communicators. In this paper, we discuss these ideas and examine how they may account for the developmental pathways that lead young people to develop conduct problems.
High Schizotypy Predicts Emotion Recognition Independently of Negative Affect
Authors: Dawes Christopher , Danielmeier Claudia , Haselgrove Mark , Moran Paula M.
Published: September 2021

Introduction: Deficits in Emotion Recognition (ER) contribute significantly to poorer functional outcomes in people with schizophrenia. However, rather than reflecting a core symptom of schizophrenia, reduced ER has been suggested to reflect increased mood disorder co-morbidity and confounds of patient status such as medication. We investigated whether ER deficits are replicable in psychometrically defined schizotypy, and whether this putative association is mediated by increased negative affect.

Methods: Two hundred and nine participants between the ages of 18 and 69 (66% female) were recruited from online platforms: 80% held an undergraduate qualification or higher, 44% were current students, and 46% were in current employment. Participants were assessed on psychometric schizotypy using the O-LIFE which maps onto the same symptoms structure (positive, negative, and disorganised) as schizophrenia. Negative affect was assessed using the Depression Anxiety and Stress Scale (DASS-21). Emotion Recognition of both positive and negative emotions was assessed using the short version of the Geneva Emotion Recognition Task (GERT-S).

Results: Negative schizotypy traits predicted poorer ER accuracy to negative emotions (β = −0.192, p = 0.002) as predicted. Unexpectedly, disorganised schizotypy traits predicted improved performance to negative emotions (β = 0.256, p = 0.007) (primarily disgust). Negative affect was found to be unrelated to ER performance of either valence (both p > 0.591). No measure predicted ER accuracy of positive emotions. Positive schizotypy traits were not found to predict either positive or negative ER accuracy. However, positive schizotypy predicted increased confidence in decisions and disorganised schizotypy predicted reduced confidence in decisions.

Discussion: The replication of ER deficits in non-clinical negative schizotypy suggests that the association between negative symptoms and ER deficits in clinical samples may be independent of confounds of patient status (i.e., anti-psychotic medication). The finding that this association was independent of negative affect further suggests ER deficits in patients may also be independent of mood disorder co-morbidity. This association was not demonstrated for the positive symptom dimension of the O-LIFE, which may be due to low levels of this trait in the current sample.
The Support Person's Preferences and Perspectives of Physical Activity Programs for Older Adults With Cognitive Impairment
Authors: Chong Terence W. H. , You Emily , Ellis Kathryn A. , Cox Kay L. , Harrington Karra D. , Rainey-Smith Stephanie R. , Ames David , Lautenschlager Nicola T. ,   AIBL Research Group
Published: September 2021

Objectives: Physical activity (PA) is beneficial for older adults' cognition. There is limited research investigating perspectives of support persons (SPs) of next-of-kins (NOKs) with cognitive impairment. This exploratory study aimed to investigate perspectives of SPs of older adults with Alzheimer's Dementia (AD) or Mild Cognitive Impairment (MCI).

Methods: A telephone survey of 213 SPs of NOKs from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL) was undertaken to quantitatively assess SPs' beliefs and knowledge about PA benefits, current PA level of their NOK, and PA program preferences. The contribution of age, gender, diagnosis and mental health symptoms was assessed using multiple logistic regression analyses.

Results: Many SPs were aware of PA benefits for memory (64%) and believed it would help their NOK (72%). Older SP age was associated with less awareness of benefits (p = 0.016). SPs caring for male NOKs were more likely to believe that PA would be helpful than those caring for female NOKs (p = 0.049). NOK AD diagnosis (rather than MCI) (p = 0.014), older age (p = 0.005) and female gender (p = 0.043) were associated with lower PA levels. SPs were mixed regarding preference for their NOKs to participate in individual (45%) or group (54%) PA. Many SPs wanted to participate in PA with their NOK (63%).

Conclusions: The results highlight that SPs have high levels of awareness of the cognitive benefits of PA, and describe their preferences regarding PA programs. The findings provide new information to inform targeted public health messaging, PA prescribers and providers, and future research directions.
Integrative Role of Hyperbaric Oxygen Therapy on Healthspan, Age-Related Vascular Cognitive Impairment, and Dementia
Authors: Balasubramanian Priya , Delfavero Jordan , Nyul-Toth Adam , Tarantini Amber , Gulej Rafal , Tarantini Stefano
Published: September 2021

Growing life expectancy will contribute to the on-going shift towards a world population increasingly comprised of elderly individuals. This demographic shift is associated with a rising prevalence of age-related diseases, among all age-related pathologies it has become crucial to understand the age-associated cognitive changes that remain a major risk factor for the development of vascular cognitive impairment and dementia (VCID). Furthermore, age-related Alzheimer’s disease and other neurogenerative diseases with vascular etiology are the most prominent contributing factors for the loss of cognitive function observed in aging. Hyperbaric Oxygen Therapy (HBOT) achieves physiologic effects by increasing oxygen tension (PO2), raising oxygen tissue levels, decreasing intracranial pressure and relieving cerebral edema. Many of the beneficial effects of HBOT exert their protective effects at the level of the microcirculation. Furthermore, the microcirculation’s exquisite pervasive presence across every tissue in the body, renders it uniquely able to influence the local environment of most tissues and organs, including the brain. As such, treatments aimed at restoring aging-induced functional and structural alterations of the cerebral microcirculation may potentially contribute to the amelioration of a range of age-related pathologies including vascular cognitive impairment, Alzheimer’s disease, and vascular dementias. Despite the presented evidence, the efficacy and safety of HBOT for the treatment of age-related vascular cognitive impairment and dementia remains understudied. The present review aims to examine the existing evidence indicative of a potential therapeutic role for HBOT-induced hyperoxia against age-related cerebromicrovascular pathologies contributing to cognitive impairment, dementia and decreased healthspan in the elderly.
Using ICF to Describe Problems With Functioning in Everyday Life for Children Who Completed Treatment for Brain Tumor: An Analysis Based on Professionals' Documentation
Authors: Björklund Ann-Christin , Granlund Mats , Santacroce Sheila Judge , Enskär Karin , Carlstein Stefan , Björk Maria
Published: September 2021

Background:Children treated for brain tumors often experience persistent problems affecting their activity performance and participation in everyday life, especially in school. Linking these problems to the International Classification of Functioning, Disability and Health (ICF) classification system can be described as affecting body function, activity performance, and/or participation. Services involved in the everyday life of the child have different focus and goals when meeting the child in context, which advantage the use of ICF to overcome this impediment to follow-up and provide comprehensive support for children who have completed treatment for a brain tumor.

Aim:The aim of the study was to use the ICF classification system to describe how professionals in healthcare, habilitation, and school document problems with everyday life functioning at body, activity, and participation levels for children who completed treatment for a brain tumor.

Materials and Methods:A retrospective review of records from healthcare, habilitation, and school concerning nine children completed treatment for brain tumor was implemented. Identified problems in everyday life were linked to ICF codes. Descriptive statistics of ICF-linked code frequency supplemented by network visualization diagrams viewing the co-occurrence between codes within the body, activity participation, and environmental components were performed.

Results:Most documented problems were found in healthcare records, whereas the documentation in habilitation and school was sparse. The frequently occurring codes, independent of record source, were linked to the body function component, and ICF-linked problems in habilitation and school were salient in the activity and participation component. To gain a holistic picture of relations between ICF codes and problems, network visualization diagrams were used to illustrate clusters of problems.

Conclusion:Code prevalence likely reflects where healthcare professionals and educators focus their attention when meeting the needs of children treated for a brain tumor in context. To maximize the comprehensive view of functioning and participation of children in everyday life, the full range of difficulties regarding body impairments, activity limitations, and participation restrictions must be identified and linked to each other in patterns of co-occurrence, which the ICF facilitate. However, ICF provides no guidance on how to identify networks of problems within the body, activity, and participation. Identifying such networks is important for building comprehensive interventions for children.
Integrating Pre-Exposure Prophylaxis Delivery in Public Health Family Planning Clinics: Lessons Learned From a Programmatic Implementation Project in Kenya
Authors: Mugwanya Kenneth K. , Kinuthia John
Published: September 2021

Sexually active African women are a priority population for HIV prevention due to the disproportionately high frequency of new HIV infections. Family planning (FP) clinics offer an already trusted platform that can be used to reach women for HIV prevention services, including pre-exposure prophylaxis (PrEP). In the recent PrEP Implementation in Young Women and Adolescent (PrIYA program), we piloted PrEP implementation in FP clinics in Kisumu, Kenya, and demonstrated that it was possible to integrate PrEP provision in FP systems with a program-dedicated staff. In this perspective, we describe experiences and strategies employed to introduce PrEP implementation in FP clinics and lessons learned. We identified the following lessons for PrEP introduction in FP clinics in Kenya: (1) possible to integrate and generate high enthusiasm for PrEP delivery in FP clinics but persistence on PrEP is a challenge, (2) involvement of national and regional stakeholders is critical for buy-in, contextualization, and sustainability, (3) delivery models that do not integrate fully with existing staff and systems are less sustainable, (4) creatinine testing at PrEP initiation may not be necessary, (5) fully integrated HIV and FP data systems need to be developed, and (6) incorporating implementation science evaluation is important to understand and document effective implementation strategies. In summary, integration of HIV prevention and FP services provides an opportunity to promote one-stop women-centered care efficiently. However, a broader focus on delivery models that utilize existing staff and novel strategies to help women identify their own risk for HIV are needed to ensure greater success and sustainability.