bluuebunny/crossref_metadata_2025 huggingface dataset:
Fixel-Based Analysis of White Matter Degeneration in Patients With Progressive Supranuclear Palsy or Multiple System Atrophy, as Compared to Parkinson's Disease
Authors: Nguyen Thanh-Thao , Cheng Jur-Shan , Chen Yao-Liang , Lin Yu-Chun , Tsai Chih-Chien , Lu Chin-Song , Weng Yi-Hsin , Wu Yi-Ming , Hoang Ngoc-Thanh , Wang Jiun-Jie
Published: March 2021

Introduction: White matter degeneration may contribute to clinical symptoms of parkinsonism.

Objective: We used fixel-based analysis (FBA) to compare the extent and patterns of white matter degeneration in different parkinsonian syndromes—including idiopathic Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP).

Methods: This is a retrospective interpretation of prospectively acquired data of patients recruited in previous studies during 2008 and 2019. Diffusion-weighted images were acquired on a 3-Tesla scanner (diffusion weighting b = 1000 s/mm2–applied along either 64 or 30 non-collinear directions) from 53 patients with PD (men/women: 29/24; mean age: 65.06 ± 5.51 years), 47 with MSA (men/women: 20/27; mean age: 63.00 ± 7.19 years), and 50 with PSP men/women: 20/30; mean age: 65.96 ± 3.14 years). Non-parametric permutation tests were used to detect intergroup differences in fixel-related indices—including fiber density, fiber cross-section, and their combination.

Results: Patterns of white matter degeneration were significantly different between PD and atypical parkinsonisms (MSA and PSP). Compared with patients with PD, those with MSA and PSP showed a more extensive white matter involvement—noticeably descending tracts from primary motor cortex to corona radiata and cerebral peduncle. Lesions of corpus callosum were specific to PSP and absent in both MSA and PD.

Discussion: FBA identified specific patterns of white matter changes in MSA and PSP patients compared to PD. Our results proved the utility of FBA in evaluation of implied biological processes of white matter changes in parkinsonism. Our study set the stage for future applications of this technique in patients with parkinsonian syndromes.
Registry of Compartmental Ephrin-B3 Guidance Patterns With Respect to Emerging Multimodal Midbrain Maps
Authors: Stinson Jeremiah P. C. , Brett Cooper A. , Carroll Julianne B. , Gabriele Mark L.
Published: March 2021

Guidance errors and unrefined neural map configurations appear linked to certain neurodevelopmental conditions, including autism spectrum disorders. Deficits in specific multisensory tasks that require midbrain processing are highly predictive of cognitive and behavioral phenotypes associated with such syndromes. The lateral cortex of the inferior colliculus (LCIC) is a shell region of the mesencephalon that integrates converging information from multiple levels and modalities. Mature LCIC sensory maps are discretely-organized, mimicking its compartmental micro-organization. Intermittent modular domains receive patchy somatosensory connections, while inputs of auditory origin terminate in the encompassing extramodular matrix.Eph-ephrin signaling mechanisms instruct comparable topographic arrangements in a variety of other systems. Whether Eph-ephrin interactions also govern the assembly of LCIC multimodal maps remains unaddressed. Previously, we identified EphA4 and ephrin-B2 as key mediators, with overlapping expression patterns that align with emerging LCIC modules. Here, we implicate another member of this guidance family, ephrin-B3, and quantify its transient expression with respect to neurochemically-defined LCIC compartments. Multiple-labeling studies in GAD67-GFP knock-in mice reveal extramodular ephrin-B3 expression, complementary to that of EphA4 and ephrin-B2. This distinctive pattern sharpens over the early postnatal period (birth to P8), prior to ephrin-B3 downregulation once multimodal LCIC inputs are largely segregated (P12). Channel-specific sampling of LCIC ROIs show ephrin-B3 signal periodicities that are out-of-phase with glutamic acid decarboxylase (GAD;modular marker) signal fluctuations, and match calretinin (CR) waveforms (matrix marker). Taken together, the guidance mosaic registry with emerging LCIC compartments and its interfacing afferent streams suggest a prominent role for Eph-ephrins in ordering behaviorally significant multisensory midbrain networks.
Resting State Functional Connectivity Associated With Sahaja Yoga Meditation
Authors: Barrós-Loscertales Alfonso , Hernández Sergio Elías , Xiao Yaqiong , González-Mora José Luis , Rubia Katya
Published: March 2021

Neuroscience research has shown that meditation practices have effects on brain structure and function. However, few studies have combined information on the effects on structure and function in the same sample. Long-term daily meditation practice produces repeated activity of specific brain networks over years of practice, which may induce lasting structural and functional connectivity (FC) changes within relevant circuits. The aim of our study was therefore to identify differences in FC during the resting state between 23 Sahaja Yoga Meditation experts and 23 healthy participants without meditation experience. Seed-based FC analysis was performed departing from voxels that had shown structural differences between these same participants. The contrast of connectivity maps yielded that meditators showed increased FC between the left ventrolateral prefrontal cortex and the right dorsolateral prefrontal cortex but reduced FC between the left insula and the bilateral mid-cingulate as well as between the right angular gyrus and the bilateral precuneus/cuneus cortices. It thus appears that long-term meditation practice increases direct FC between ventral and dorsal frontal regions within brain networks related to attention and cognitive control and decreases FC between regions of these networks and areas of the default mode network.
Discovering Effective Connectivity in Neural Circuits: Analysis Based on Machine Learning Methodology
Authors: Pozo-Jimenez Pedro , Lucas-Romero Javier , Lopez-Garcia Jose A.
Published: March 2021

As multielectrode array technology increases in popularity, accessible analytical tools become necessary. Simultaneous recordings from multiple neurons may produce huge amounts of information. Traditional tools based on classical statistics are either insufficient to analyze multiple spike trains or sophisticated and expensive in computing terms. In this communication, we put to the test the idea that AI algorithms may be useful to gather information about the effective connectivity of neurons in local nuclei at a relatively low computing cost. To this end, we decided to explore the capacity of the algorithm C5.0 to retrieve information from a large series of spike trains obtained from a simulated neuronal circuit with a known structure. Combinatory, iterative and recursive processes using C5.0 were built to examine possibilities of increasing the performance of a direct application of the algorithm. Furthermore, we tested the applicability of these processes to a reduced dataset obtained from original biological recordings with unknown connectivity. This was obtained in house from a mouse in vitro preparation of the spinal cord. Results show that this algorithm can retrieve neurons monosynaptically connected to the target in simulated datasets within a single run. Iterative and recursive processes can identify monosynaptic neurons and disynaptic neurons under favorable conditions. Application of these processes to the biological dataset gives clues to identify neurons monosynaptically connected to the target. We conclude that the work presented provides substantial proof of concept for the potential use of AI algorithms to the study of effective connectivity.
The Role of Canalization and Plasticity in the Evolution of Musical Creativity
Authors: Podlipniak Piotr
Published: March 2021

Creativity is defined as the ability to generate something new and valuable. From a biological point of view this can be seen as an adaptation in response to environmental challenges. Although music is such a diverse phenomenon, all people possess a set of abilities that are claimed to be the products of biological evolution, which allow us to produce and listen to music according to both universal and culture-specific rules. On the one hand, musical creativity is restricted by the tacit rules that reflect the developmental interplay between genetic, epigenetic and cultural information. On the other hand, musical innovations seem to be desirable elements present in every musical culture which suggests some biological importance. If our musical activity is driven by biological needs, then it is important for us to understand the function of musical creativity in satisfying those needs, and also how human beings have become so creative in the domain of music. The aim of this paper is to propose that musical creativity has become an indispensable part of the gene-culture coevolution of our musicality. It is suggested that the two main forces of canalization and plasticity have been crucial in this process. Canalization is an evolutionary process in which phenotypes take relatively constant forms regardless of environmental and genetic perturbations. Plasticity is defined as the ability of a phenotype to generate an adaptive response to environmental challenges. It is proposed that human musicality is composed of evolutionary innovations generated by the gradual canalization of developmental pathways leading to musical behavior. Within this process, the unstable cultural environment serves as the selective pressure for musical creativity. It is hypothesized that the connections between cortical and subcortical areas, which constitute cortico-subcortical circuits involved in music processing, are the products of canalization, whereas plasticity is achieved by the means of neurological variability. This variability is present both at the level of an individual structure’s enlargement in response to practicing (e.g., the planum temporale) and within the involvement of neurological structures that are not music-specific (e.g., the default mode network) in music processing.
Sex-Determining Region Y Controls the Effects of Fetal Alcohol Exposure on Proopiomelanocortin Gene Expression
Authors: Gangisetty Omkaram , Mead Edward A. , Sarkar Dipak K.
Published: March 2021

Fetal alcohol exposure (FAE) causes various neurodevelopmental deficits in offspring, including reduced expression of the stress regulatory proopiomelanocortin (Pomc) gene and an elevated stress response for multiple generations via the male germline. Male germline-specific effects of FAE on the Pomc gene raises the question if the sex-determining region Y (SRY) may have a role in regulating Pomc gene expression. Using a transgenerational model of FAE in Fischer 344 rats, we determined the role of SRY in the regulation of the Pomc gene. FAEs, like on the Pomc gene, reduced Sry gene expression in sperm and the mediobasal hypothalamus (MBH) in male adult offspring. Fetal alcohol-induced inhibition of Sry gene expression was associated with increased Sry promoter DNA methylation. Additionally, fetal alcohol effects on the Sry gene persisted for three generations in the male germline but not in the female germline. Sry gene knockdown reduced the Pomc gene expression. Sry recruitment onto the Pomc promoter was found to be reduced in the hypothalamus of fetal alcohol-exposed rats compared to control rats. Pomc promoter luciferase activity was increased following Sry overexpression. A site-directed mutagenesis study revealed that SRY binding sites are required for POMC promoter transcription activity. Overall, these findings suggest that SRY plays a stimulatory role in the regulation of Pomc gene expression and may potentially contribute to the fetal alcohol-induced changes in the level of Pomc gene expression for multiple generations.
Case Report: Two Cases of Metastatic Pancreatoblastoma in Adults: Efficacy of Folfirinox and Implication of the Wnt/β-Catenin Pathway in Genomic Analysis
Authors: Raoul Jean-Luc , Oziel-Taieb Sandrine , Lecomte Thierry , Adelaide José , Guille Arnaud , Chaffanet Max , Poizat Flora , Heymann Marie-Françoise , Barbier Louise , Bertucci François
Published: March 2021

Pancreatoblastomas are unfrequent tumors usually found in children. We report two cases of metastatic pancreatoblastomas observed in young women. A systemic chemotherapy (FOLFIRINOX regimen) was associated with a disease control in one case and a partial response in the second with an improvement of general status for both. A high-throughput sequencing of the tumor described in both cases alteration in the Wnt/β-catenin pathway: a mutation in CTNNB1 (exon 3, c.110C>G, p.S37C, reported as a hotspot in COSMIC) in one case and a homozygous loss associated with breakage targeting APC (5q22.2) in the second.
Using Deep Neural Network to Diagnose Thyroid Nodules on Ultrasound in Patients With Hashimoto’s Thyroiditis
Authors: Hou Yiqing , Chen Chao , Zhang Lu , Zhou Wei , Lu Qinyang , Jia Xiaohong , Zhang Jingwen , Guo Cen , Qin Yuxiang , Zhu Lifeng , Zuo Ming , Xiao Jing , Huang Lingyun , Zhan Weiwei
Published: March 2021

Objective

The aim of this study is to develop a model using Deep Neural Network (DNN) to diagnose thyroid nodules in patients with Hashimoto’s Thyroiditis.

Methods

In this retrospective study, we included 2,932 patients with thyroid nodules who underwent thyroid ultrasonogram in our hospital from January 2017 to August 2019. 80% of them were included as training set and 20% as test set. Nodules suspected for malignancy underwent FNA or surgery for pathological results. Two DNN models were trained to diagnose thyroid nodules, and we chose the one with better performance. The features of nodules as well as parenchyma around nodules will be learned by the model to achieve better performance under diffused parenchyma. 10-fold cross-validation and an independent test set were used to evaluate the performance of the algorithm. The performance of the model was compared with that of the three groups of radiologists with clinical experience of <5 years, 5–10 years, >10 years respectively.

Results

In total, 9,127 images were collected from 2,932 patients with 7,301 images for the training set and 1,806 for the test set. 56% of the patients enrolled had Hashimoto’s Thyroiditis. The model achieved an AUC of 0.924 for distinguishing malignant and benign nodules in the test set. It showed similar performance under diffused thyroid parenchyma and normal parenchyma with sensitivity of 0.881 versus 0.871 (p = 0.938) and specificity of 0.846 versus 0.822 (p = 0.178). In patients with HT, the model achieved an AUC of 0.924 to differentiate malignant and benign nodules which was significantly higher than that of the three groups of radiologists (AUC = 0.824, 0.857, 0.863 respectively, p < 0.05).

Conclusion

The model showed high performance in diagnosing thyroid nodules under both normal and diffused parenchyma. In patients with Hashimoto’s Thyroiditis, the model showed a better performance compared to radiologists with various years of experience.
High Expression of Interleukin-3 Receptor Alpha Chain (CD123) Predicts Favorable Outcome in Pediatric B-Cell Acute Lymphoblastic Leukemia Lacking Prognosis-Defining Genomic Aberrations
Authors: Li Zhiheng , Chu Xinran , Gao Li , Ling Jing , Xiao Peifang , Lu Jun , Wang Yi , He Hailong , Li Jianqin , Hu Yixin , Li Jie , Pan Jian , Xiao Sheng , Hu Shaoyan
Published: March 2021

Background

Aberrant expression of CD123 (IL-3Rα) was observed in various hematological malignancies including acute lymphoblastic leukemia (ALL), which is the most common malignancy in childhood. Although widely used for minimal residual disease (MRD) monitoring, the prognostic value of CD123 has not been fully characterized in pediatric B-ALL. This retrospective study aims to evaluate the association between the CD123 expression of leukemic blasts and the outcomes of the pediatric B-ALL patients.

Methods

A total of 976 pediatric B-ALL, including 328 treated with CCLG-ALL-2008 protocol and 648 treated with CCCG-ALL-2015 protocol, were recruited in this retrospective study. CD123 expression was evaluated by flow cytometry. Patients with >50, 20–50, or <20% of CD123 expressing blasts were grouped into CD123high, CD123low, and CD123neg, respectively. The correlation between CD123 expression and the patients’ clinical characteristics, overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were studied statistically.

Results

Of 976 pediatric B-ALL, 53.4% from the CCLG-ALL-2008 cohort and 49.2% from the CCCG-ALL-2015 cohort were CD123high. In the CCLG-ALL-2008 cohort, CD123high was significantly associated with chromosome hyperdiploidy (p < 0.0001), risk stratification (p = 0.004), and high survival rate (p = 0.005). By comparing clinical outcomes, patients with CD123high displayed favorable prognosis, with a significantly better OS (p = 0.005), EFS (p = 0.017), and RFS (p = 0.045), as compared to patients with CD123low and CD123neg. The prognostic value of CD123 expression was subsequently confirmed in the CCCG-ALL-2015 cohort. Univariate and multivariate cox regression model analysis showed that high CD123 expression was independently associated with favorable EFS (OR: 0.528; 95% CI: 0.327 to 0.853; p = 0.009) in this cohort. In patients without prognosis-defining genomic abnormalities, high CD123 expression strongly indicated superior survival rates and was identified as an independent prognosis factor for EFS and RFS in both cohorts.

Conclusions

A group of B-ALL lacks prognosis-defining genomic aberrations, which proposes a challenge in risk stratification. Our findings revealed that high CD123 expression of leukemic blasts was associated with favorable clinical outcomes in pediatric B-ALL and CD123 could serve as a promising prognosis predictor, especially in patients without prognosis-defining genetic aberrations.
Tumor Immunometabolism Characterization in Ovarian Cancer With Prognostic and Therapeutic Implications
Authors: Yang Miner , Chen Gaowen , Gao Kunjie , Wang Yifeng
Published: March 2021

Metabolic dysregulation in the tumor microenvironment has significant impact on immune infiltration and immune responses. However, interaction between immunity and metabolism in the ovarian microenvironment requires further exploration. We constructed an immunometabolism gene set and ovarian cancer cohort from The Cancer Genome Atlas (TCGA) and classified these into three immunometabolism subtypes. We explored the relationships between immune infiltration and metabolic reprogramming. Additionally, we built risk score and nomogram as prognostic signatures. Three distinctive immunometabolism subtypes were identified with therapeutic and prognostic implications. Subtype 1, the “immune suppressive-glycan metabolism subtype,” featured high levels of immunosuppressive cell infiltration and glycan metabolism activation; Subtype 2, the “immune inflamed-amino acid metabolism subtype,” showed abundant adaptive immune cell infiltration and amino acid metabolism activation; Subtype 3, the “immune desert-endocrine subtype,” was characterized by low immune cell infiltration and upregulation of hormone biosynthesis. Furthermore, we found that epinephrine biosynthesis displayed a significantly negative correlation with MHC molecules, which may result in defective antigen presentation. We proposed immunometabolism subtypes with prognostic implications and provided new perspectives for the ovarian cancer microenvironment.
Case Report: The Complete Remission of a Mixed Germ Cell Tumor With Somatic Type Malignancy of Sarcoma Type With a GCT-Oriented Therapy: Clinical Findings and Genomic Profiling
Authors: Pantaleo Maria A. , Mandruzzato Marcella , Indio Valentina , Urbini Milena , Nannini Margherita , Gatto Lidia , Schipani Angela , Fiorentino Michelangelo , Franceschini Tania , Ambrosini Valentina , Di Scioscio Valerio , Saponara Maristella , Ianni Manuela , Concetti Sergio , Altimari Annalisa , Ardizzoni Andrea , Astolfi Annalisa
Published: March 2021

Somatic malignant transformation in a germ cell tumor (GCT) is the development of non-germ malignancies; much of available literature refers to teratoma with malignant transformation (TMT). There are various transformation histologies such as sarcoma, adenocarcinoma, primitive neuroectodermal tumors, and more rarely carcinoid tumors, hemangioendothelioma, lymphoma, or nephroblastoma. The treatments of these entities include surgery and/or chemotherapy. A standard approach in choosing chemotherapy in TMT cases has not yet been established. Many authors suggest using chemotherapeutic agents based on the transformed histology, while others recommend GCT-oriented therapy combined with surgery as the primary treatment, reserving histology-driven chemotherapies for metastatic relapse. We report the clinical findings and the genomic profile of a mixed GCT case with somatic-type malignancy of sarcoma type. We achieved a complete radiological response with GCT-oriented chemotherapy performed as salvage therapy after sarcoma-histology therapy. In addition, molecular profiles with RNA-sequencing and exome sequencing analyses of the primary tumor and the tumor with somatic-type malignancy of sarcoma type were explored.
Peritoneal Metastases From Colorectal Cancer: Defining and Addressing the Challenges
Authors: Kranenburg Onno , Speeten Kurt van der , Hingh Ignace de
Published: March 2021

The presence of peritoneal metastases (PM) in patients with colorectal cancer (CRC) is associated with an extremely poor prognosis. The diagnosis of PM is challenging, resulting in an underestimation of their true incidence. While surgery can be curative in a small percentage of patients, effective treatment for non-operable PM is lacking, and clinical and pre-clinical studies are relatively sparse. Here we have defined the major clinical challenges in the areas of risk assessment, detection, and treatment. Recent developments in the field include the application of organoid technology, which has generated highly relevant pre-clinical PM models, the application of diffusion-weighted MRI, which has greatly improved PM detection, and the design of small clinical proof-of-concept studies, which allows the efficient testing of new treatment strategies. Together, these developments set the stage for starting to address the clinical challenges. To help structure these efforts, a translational research framework is presented, in which clinical trial design is based on the insight gained from direct tissue analyses and pre-clinical (organoid) models derived from CRC patients with PM. This feed-forward approach, in which a thorough understanding of the disease drives innovation in its clinical management, has the potential to improve outcome in the years to come.
A Randomized Phase II Trial Comparing the Efficacy and Safety of Pioglitazone, Clarithromycin and Metronomic Low-Dose Chemotherapy with Single-Agent Nivolumab Therapy in Patients with Advanced Non-small Cell Lung Cancer Treated in Second or Further Line (ModuLung)
Authors: Heudobler Daniel , Schulz Christian , Fischer Jürgen R. , Staib Peter , Wehler Thomas , Südhoff Thomas , Schichtl Thomas , Wilke Jochen , Hahn Joachim , Lüke Florian , Vogelhuber Martin , Klobuch Sebastian , Pukrop Tobias , Herr Wolfgang , Held Swantje , Beckers Kristine , Bouche Gauthier , Reichle Albrecht
Published: March 2021

Background: Most non-small cell lung cancers occur in elderly and frequently comorbid patients. Therefore, it is necessary to evaluate the efficacy of biomodulatory active therapy regimen, concertedly interfering with tumor-associated homeostatic pathways to achieve tumor control paralleled by modest toxicity profiles.

Patients and Methods: The ModuLung trial is a national, multicentre, prospective, open-label, randomized phase II trial in patients with histologically confirmed stage IIIB/IV squamous (n = 11) and non-squamous non-small cell (n = 26) lung cancer who failed first-line platinum-based chemotherapy. Patients were randomly assigned on a 1:1 ratio to the biomodulatory or control group, treated with nivolumab. Patients randomized to the biomodulatory group received an all-oral therapy consisting of treosulfan 250 mg twice daily, pioglitazone 45 mg once daily, clarithromycin 250 mg twice daily, until disease progression or unacceptable toxicity.

Results: The study had to be closed pre-maturely due to approval of immune checkpoint inhibitors (ICi) in first-line treatment. Thirty-seven patients, available for analysis, were treated in second to forth-line. Progression-free survival (PFS) was significantly inferior for biomodulation (N = 20) vs. nivolumab (N = 17) with a median PFS (95% confidence interval) of 1.4 (1.2–2.0) months vs. 1.6 (1.4–6.2), respectively; with a hazard ratio (95% confidence interval) of 1.908 [0.962; 3.788]; p = 0.0483. Objective response rate was 11.8% with nivolumab vs. 5% with biomodulation, median follow-up 8.25 months. The frequency of grade 3–5 treatment related adverse events was 29% with nivolumab and 10% with biomodulation. Overall survival (OS), the secondary endpoint, was comparable in both treatment arms; biomodulation with a median OS (95% confidence interval) of 9.4 (6.0–33.0) months vs. nivolumab 6.9 (4.6–24.0), respectively; hazard ratio (95% confidence interval) of 0.733 [0.334; 1.610]; p = 0.4368. Seventy-five percent of patients in the biomodulation arm received rescue therapy with checkpoint inhibitors.

Conclusions: This trial shows that the biomodulatory therapy was inferior to nivolumab on PFS. However, the fact that OS was similar between groups gives rise to the hypothesis that the well-tolerable biomodulatory therapy may prime tumor tissues for efficacious checkpoint inhibitor therapy, even in very advanced treatment lines where poor response to ICi might be expected with increasing line of therapy.
Biochanin A Attenuates Ovariectomy-Induced Cognition Deficit via Antioxidant Effects in Female Rats
Authors: Zhou Yanmeng , Xu Bingbing , Yu Haiyang , Zhao Wei , Song Xinxin , Liu Yan , Wang Kainan , Peacher Nikoli , Zhao Xiaomin , Zhang Han-Ting
Published: March 2021

Background: Impairment of memory and cognition is one of the major symptoms in women with postmenopausal disorders due to estrogen deficiency, which accounts for the much higher prevalence of Alzheimer’s disease in females. Biochanin A (BCA), a natural phytoestrogen, has been reported to protect neurons against ischemic brain injury. However, the neuroprotective effects of BCA in the postmenopausal-like model of ovariectomized (OVX) rats remain to be investigated.

Methods: All the rats except for the sham group underwent the resection of bilateral ovaries. Seven days after the OVX surgery, rats were randomly divided into six groups: sham, OVX, OVX + BCA (5 mg/kg), OVX + BCA (20 mg/kg), OVX + BCA (60 mg/kg), and OVX + estradiol (E2; 0.35 mg/kg), which were administrated daily by gavage for 12 weeks. Learning and memory were examined using the Morris water-maze test before the end of the experiment. Morphological changes of the rat hippocampus were observed by HE staining and electron microscopy. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in the hippocampus were measured. The effect of BCA on cell viability was measured in the presence of hydrogen peroxide (H2O2) using CCK8. Flow cytometry was used to measure neuronal apoptosis and reactive oxygen species (ROS) induced by H2O2. Expression of Bcl-2, Bax, and Caspase-3 was determined by Western blotting using hippocampal tissues and primary cultures of hippocampal neurons.

Results: Chronic treatment with BCA mimicked the ability of E2 to reverse the deficit of learning and memory in the Morris water-maze test in OVX rats. BCA normalized OVX-induced morphological changes as revealed by HE staining and electron microscopy. In addition, BCA significantly decreased the levels of MDA, the biomarker of oxidative damage, and increased the activity of the intracellular antioxidant enzymes SOD and GSH-Px in OVX rats. Further, in primary cultures of hippocampal neurons, BCA reversed H2O2-induced decreases in cell viability and accumulation of ROS. Finally, BCA reversed OVX- or H2O2-induced increases in Bax and Caspase-3 and decreases in Bcl-2 in the hippocampus and primary cultures of hippocampal neurons.

Conclusion: These results suggest that BCA improves memory through its neuroprotective properties in the brain under the circumstance of estrogen deficiency and can be used for treatment of memory loss in postmenopausal women.
Neuroprotective and Neurorescue Mode of Action of Bacopa monnieri (L.) Wettst in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinson’s Disease: An In Silico and In Vivo Study
Authors: Singh Babita , Pandey Shivani , Rumman Mohammad , Kumar Shashank , Kushwaha Prem Prakash , Verma Rajesh , Mahdi Abbas Ali
Published: March 2021

Ethnopharmacological Relevance:Parkinson’s disease (PD) is characterized by progressive death of dopaminergic neurons. The presently used medicines only tackle the symptoms of PD, but none makes a dent on the processes that underpin the disease’s development. Herbal medicines have attracted considerable attention in recent years.Bacopa monnieri(L.)Wettst(Brahmi) has been used in Indian Ayurvedic medicine to enhance memory and intelligence. Herein, we assessed the neuroprotective role ofBacopa monnieri(L.)Wettston Parkinson’s disease.

Aim of the Study:Bacopa monnieri(L.)Wettst, a medicinal herb, is widely used as a brain tonic. We investigated the neuroprotective and neurorescue properties ofBacopa monnieri(L.)Wettstextract (BME) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of PD.

Materials and Methods:The mice model of MPTP-induced PD is used in the study. In the neuroprotective (BME + MPTP) and neurorescue (MPTP + BME) experiments, the animals were administered 40 mg/kg body weight BME orally before and after MPTP administration, respectively. Effect of BME treatment was evaluated by accessing neurobehavioral parameters and levels of dopamine, glutathione, lipid peroxide, and nitrites. Anin silicostudy was performed using AutoDock Tools 1.5.6 (ADT).

Results:A significant recovery in behavioral parameters, dopamine level, glutathione level, lipid peroxides, and nitrite level was observed in BME-treated mice. Treatment with BME before or after MPTP administration has a protective effect on dopaminergic neurons, as evidenced by a significant decrease in GFAP immunostaining and expression of inducible nitric oxide synthase (iNOS) in the substantia nigra region; however, the degree of improvement was more prominent in mice receiving BME treatment before MPTP administration. Moreover, thein silicostudy revealed that the constituents of BM, including bacosides, bacopasides, and bacosaponins, can inactivate the enzyme monoamine oxidase B, thus preventing the breakdown of MPTP to MPP+.

Conclusion:Our results showed that BME exerts both neuroprotective and neurorescue effects against MPTP-induced degeneration of the nigrostriatal dopaminergic neurons. Moreover, BME may slow down the disease progression and delay the onset of neurodegeneration in PD.
Aqueous Tuber Extracts of Tylosema fassoglense (Kotschy ex Schweinf.) Torre and Hillc. (Fabaceae). Possess Significant In-Vivo Antidiarrheal Activity and Ex-Vivo Spasmolytic Effect Possibly Mediated by Modulation of Nitrous Oxide System, Voltage-Gated Calcium Channels, and Muscarinic Receptors
Authors: Mapesa Washika Amos , Waweru Mwangi Peter , Bukachi Frederick , Wafula Kayaja David
Published: March 2021

Tylosema fassoglense (TFG) is used as an antidiarrheal traditional medicine in Western Kenya. This study aimed to investigate the antidiarrheal activity of its aqueous extracts in-vivo and the putative mechanism (s) of action ex-vivo using Sprague-Dawley rats and New Zealand white rabbits respectively. The in-vivo antidiarrheal effects of the extract were evaluated in castor oil-induced diarrhea, the castor oil-induced enteropooling, and phenol red gastric motility tests. On the other hand, isolated rabbit’s jejunal segments were used to evaluate the spasmolytic effect of TFG on spontaneous contraction, in acetylcholine-induced contraction, in presence of 80mMK+, calcium chloride-induced contraction as well as in presence of the following antagonists: naloxone, methylene blue, L-NAME, prazosin, and propranolol in the ex-vivo studies. The data were express as Mean ± S.E.M and analyzed by one-way ANOVA and Tukey’s post hoc test in cases of significance which was set at p < 0.05. The extract was phytochemically characterized using Liquid chromatography Mass spectroscopy (LC-MS).The extract possessed significant inhibitory effect in the in-vivo experiments. The extract exhibited significant spasmolytic effect on both spontaneous contraction and in jejunal segment pre-contracted acetylcholine as well as in presence of 80mMK+ solution. It also attenuated the spasmogenic effect of various concentration of calcium chloride. The extract’s spasmolytic effect was, however, significantly attenuated in presence of several antagonists (methylene blue and L-NAME) but the adrenergic blockers (prazosin and propranolol) had no significant effect in the ex-vivo studies. LC-MS identified thirty compounds where Proathocyanidin (11.54%), Syringic acid (7.30%), and 4-Hydroxybenzoic acid (6.19%) had the highest percentage abundance. In conclusion, the results obtained in this study partially validate the traditional uses of the tubers of this plant species as an antidiarrheal. These antidiarrheal effects are probably mediated via modulation of nitrous oxide pathway, voltage gated calcium channels, and muscarinic receptors.
Design, Implementation and Characterization of Cavity for Absolute Radiometer
Authors: Carlesso Franciele , Vieira Luis E. A. , Berni Luiz A. , Savonov Graziela da S.
Published: March 2021

Absolute radiometers are based on electrical substitution radiometers, which compare optical and electrical power. The same physical principle applies to standard reference detectors operating at cryogenic temperatures and room temperature radiometers for total solar irradiance (TSI) measurements. Both types rely on the cavity with an internal low-reflectance coating to absorb incident radiation similar to a black body. The cavity shape design requires an analysis of the coating reflection properties. Like many materials, ultra-black Ni-P exhibits a mixture of diffuse and specular reflection that depends on the angle of incidence of light in the pores. We employed ray-tracing software to study the impact of the geometry on the absorptivity and distribution of the scattered rays. We describe the scattering model of the black coating in terms of the bidirectional reflectance distribution function. Also, we examined the difficulties of Ni-P electroless deposition and blackening inside the cavity. The measured absorptance of the cavity showed some discrepancies of the simulated absorptance mostly probably due to Ni-P non-uniformity coating.
Comparative Analysis of Plastid Genomes in the Non-photosynthetic Genus Thismia Reveals Ongoing Gene Set Reduction
Authors: Yudina Sophia V. , Schelkunov Mikhail I. , Nauheimer Lars , Crayn Darren , Chantanaorrapint Sahut , Hroneš Michal , Sochor Michal , Dančák Martin , Mar Shek-Shing , Luu Hong Truong , Nuraliev Maxim S. , Logacheva Maria D.
Published: March 2021

Heterotrophic plants provide intriguing examples of reductive evolution. This is especially evident in the reduction of their plastid genomes, which can potentially proceed toward complete genome loss. Several milestones at the beginning of this path of degradation have been described; however, little is known about the latest stages of plastome reduction. Here we analyze a diversity of plastid genomes in a set of closely related non-photosynthetic plants. We demonstrate how a gradual loss of genes shapes the miniaturized plastomes of these plants. The subject of our study, the genus Thismia, represents the mycoheterotrophic monocot family Thismiaceae, a group that may have experienced a very ancient (60–80 mya) transition to heterotrophy. In all 18 species examined, the plastome is reduced to 14–18 kb and is highly AT-biased. The most complete observed gene set includes accD, seven ribosomal protein genes, three rRNA, and two tRNA genes. Different clades of Thismia have undergone further gene loss (complete absence or pseudogenization) compared to this set: in particular, we report two independent losses of rps2 and rps18.
Comprehensive Characterization and Validation of Chromosome-Specific Highly Polymorphic SSR Markers From Pomegranate (Punica granatum L.) cv. Tunisia Genome
Authors: Patil Prakash Goudappa , Singh Nripendra Vikram , Bohra Abhishek , Raghavendra Keelara Puttaswamy , Mane Rushikesh , Mundewadikar Dhananjay M. , Babu Karuppannan Dhinesh , Sharma Jyotsana
Published: March 2021

The simple sequence repeat (SSR) survey of ‘Tunisia’ genome (296.85 Mb) identified a total of 365,279 perfect SSRs spanning eight chromosomes, with a mean marker density of 1,230.6 SSRs/Mb. We found a positive trend in chromosome length and the SSR abundance as marker density enhanced with a shorter chromosome length. The highest number of SSRs (60,708) was mined from chromosome 1 (55.56 Mb), whereas the highest marker density (1,294.62 SSRs/Mb) was recorded for the shortest chromosome 8 (27.99 Mb). Furthermore, we categorized all SSR motifs into three major classes based on their tract lengths. Across the eight chromosomes, the class III had maximum number of SSR motifs (301,684, 82.59%), followed by the class II (31,056, 8.50%) and the class I (5,003, 1.37%). Examination of the distribution of SSR motif types within a chromosome suggested the abundance of hexanucleotide repeats in each chromosome followed by dinucleotides, and these results are consistent with ‘Tunisia’ genome features as a whole. Concerning major repeat types, AT/AG was the most frequent (14.16%), followed by AAAAAT/AAAAAG (7.89%), A/C (7.54%), AAT/AAG (5.23%), AAAT/AAAG (4.37%), and AAAAT/AAAAG (1.2%) types. We designed and validated a total of 3,839 class I SSRs in the ‘Tunisia’ genome through electronic polymerase chain reaction (ePCR) and found 1,165 (30.34%) SSRs producing a single amplicon. Then, we selected 906 highly variable SSRs (> 40 nt) from the ePCR-verified class I SSRs and in silico validated across multiple draft genomes of pomegranate, which provided us a subset of 265 highly polymorphic SSRs. Of these, 235 primers were validated on six pomegranate genotypes through wet-lab experiment. We found 221 (94%) polymorphic SSRs on six genotypes, and 187 of these SSRs had ≥ 0.5 PIC values. The utility of the developed SSRs was demonstrated by analyzing genetic diversity of 30 pomegranate genotypes using 16 HvSSRs spanning eight pomegranate chromosomes. In summary, we developed a comprehensive set of highly polymorphic genome-wide SSRs. These chromosome-specific SSRs will serve as a powerful genomic tool to leverage future genetic studies, germplasm management, and genomics-assisted breeding in pomegranate.
Psychosocial Framework of Resilience: Navigating Needs and Adversities During the Pandemic, A Qualitative Exploration in the Indian Frontline Physicians
Authors: Banerjee Debanjan , Sathyanarayana Rao T. S. , Kallivayalil Roy Abraham , Javed Afzal
Published: March 2021

Introduction

Frontline healthcare workers (HCW) have faced significant plight during the ongoing Coronavirus disease 2019 (COVID-19) pandemic. Studies have shown their vulnerabilities to depression, anxiety disorders, post-traumatic stress, and insomnia. In a developing country like India, with a rising caseload, resource limitations, and stigma, the adversities faced by the physicians are more significant. We attempted to hear their “voices” to understand their adversities and conceptualize their resilience framework.

Methods

A qualitative approach was used with a constructivist paradigm. After an initial pilot, a socio-demographically heterogeneous population of 172 physicians working in COVID-designated centers were purposively sampled from all over India. Following in-depth virtual interviews using a pre-formed semi-structured guide, the data was transcribed and translated verbatim. The interview was focused on their challenges, needs, and processes of coping and support. Charmaz’s grounded theory was used for analysis supplemented by NVivo 10 software.

Results

Fear of infection, uncertainty, stigma, guilt, and social isolation emerged as the main challenges. Simultaneously, their “unmet needs” were flexible work policies, administrative measures for better medical protection, the sensitivity of media toward the image of HCW, effective risk communication for their health, and finally, social inclusion. Their resilience “framework” emerged as a process while navigating these adversities and consisted of three facets: forming a “resilient identity,” managing the resilience, and working through the socio-occupational distress. The role of mental well-being, social network, peer support, problem negotiation, and self-care emerged as the key coping strategies.

Conclusion

The study findings support the global call for better psychosocial health and quality of life of the frontline HCWs. Their “unheard voices” explored in the study can anchor subsequent resilience-enhancing interventions and policies. Guidelines focusing on the psychological wellbeing of frontline HCWs need to be grounded in their unmet needs and lived experiences.
The Principle of Least Effort and Comprehension of Spoken Sentences by Younger and Older Adults
Authors: Ayasse Nicolai D. , Hodson Alana J. , Wingfield Arthur
Published: March 2021

There is considerable evidence that listeners’ understanding of a spoken sentence need not always follow from a full analysis of the words and syntax of the utterance. Rather, listeners may instead conduct a superficial analysis, sampling some words and using presumed plausibility to arrive at an understanding of the sentence meaning. Because this latter strategy occurs more often for sentences with complex syntax that place a heavier processing burden on the listener than sentences with simpler syntax, shallow processing may represent a resource conserving strategy reflected in reduced processing effort. This factor may be even more important for older adults who as a group are known to have more limited working memory resources. In the present experiment, 40 older adults (Mage = 75.5 years) and 20 younger adults (Mage = 20.7) were tested for comprehension of plausible and implausible sentences with a simpler subject-relative embedded clause structure or a more complex object-relative embedded clause structure. Dilation of the pupil of the eye was recorded as an index of processing effort. Results confirmed greater comprehension accuracy for plausible than implausible sentences, and for sentences with simpler than more complex syntax, with both effects amplified for the older adults. Analysis of peak pupil dilations for implausible sentences revealed a complex three-way interaction between age, syntactic complexity, and plausibility. Results are discussed in terms of models of sentence comprehension, and pupillometry as an index of intentional task engagement.
Mediating Effect of Personal Meaning in the Prediction of Life Satisfaction and Mental Health Problems Based on Coronavirus Suffering
Authors: Arslan Gökmen , Yıldırım Murat , Leung Mega M.
Published: March 2021

Research Problem: The onset of the COVID-19 pandemic has triggered a multi-faceted crisis worldwide. Researchers and health authorities in various parts of the world echoed the dire condition of the public's mental health. This study sought to examine the mediating effect of personal meaning on the association between coronavirus (COVID-19)-related suffering, mental health problems, and life satisfaction. Participants included 231 adults (mean age = 46.65 ± 13.98; 68% female) and completed measures of suffering related to COVID-19, meaning, life satisfaction, and mental health problems online.

Results: Findings from mediation analysis showed that suffering had significant associations with personal meaning, mental health, and well-being. Furthermore, personal meaning was significantly associated with adults' mental health and well-being and mediated the negative effect of suffering on mental health and well-being.

Discussion: Overall, results from this study indicate that personal meaning is an important promotive factor that may help to understand the negative effect of coronavirus-related suffering on mental health and well-being amid the public health crisis.
The Legal Vulnerability Model for Same-Sex Parent Families: A Mixed Methods Systematic Review and Theoretical Integration
Authors: Siegel Magdalena , Assenmacher Constanze , Meuwly Nathalie , Zemp Martina
Published: March 2021

Globally, parents and children in same-sex parent families are impacted by many laws related to the parental sexual orientation. These laws vary considerably from one country to another, ranging from full legal recognition to criminalization. The psychological consequences of living in an ambiguous or hostile legal climate likely interfere with parental health, family functioning, and child development. However, a systematic evidence synthesis of the pertinent literature and its placement within a broader psychological model are currently lacking. The aims of this review were thus (1) to systematically review qualitative and quantitative evidence on the impact of sexual orientation laws on same-sex parent families in key domains and (2) to place these findings within a broader model informed by minority stress and family theories. Our review was preregistered and conducted in line with PRISMA guidelines. We searched for qualitative, quantitative, and mixed methods studies on the impact of sexual orientation laws on target outcomes (parental health, family functioning, child outcomes) via systematic database search (PubMed, Scopus, Web of Science) and forward-backward searches. Fifty-five studies published between 1999 and 2020 were eligible for inclusion and were synthesized using a data-based convergent synthesis design. Thirteen descriptive and three overarching analytical themes were identified through thematic synthesis. Linking our findings with minority stress and family theories, we propose a novel legal vulnerability model for same-sex parent families. The model posits that legal vulnerability constitutes an increased risk for parental and child health as well as family functioning through individual and shared pathways between family members. Additionally, the model introduces counteractions that families engage in on the personal, familial, and systemic level to mitigate the impact of legal vulnerability, as well as moderators on the contextual, familial, couple, and individual level that modulate this impact. Implications for research and clinical practice are discussed.