bluuebunny/crossref_metadata_2025 huggingface dataset:
A Moving Dune, A Stunning View: Visitors’ Recollections of a Ranger-Led Hike at Indiana Dunes National Park
Authors: Forist Brian E. , Merson Martha , Allen Louise C. , Hristov Nickolay I.
Published: July 2021

Located 50 miles from Chicago, at Indiana Dunes National Park, thousands interact with rangers annually, many taking part in ranger-led hikes. The study focused on visitor recollections of a ranger-led hike that provided opportunities to learn about landscape change, recent events, and associated scientific findings. Interpreters are encouraged to co-construct audience-centered experiences, making space in interactions for visitors’ knowledge, interests, and previous experience. Researchers observed six ranger-led hikes incorporating audience-centered design elements and recruited a convenience sample of twenty-one visitors for participation in a pre-hike survey to gather responses about interest and knowledge before the hike and their willingness to participate in a follow up post-hike phone interview. After ranger-led hikes, researchers conducted fifteen interviews using a phenomenological approach to glean visitors’ recollections of the experience. Our findings confirm that visitors arrive with background knowledge, scientific interests, and curiosity. Months after the park experience, they were able to give examples of dune formation and change over time, the human effect on the landscape, and findings from recent events and scientific study at Mount Baldy. Interviewees recalled and reflected on rangers’ facilitation and use of props, as well as visual details and feelings evoked by the physical conditions. The results offer a rare look at what sticks with visitors after their participation in a ranger-led hike.
Single-Molecule Real-Time and Illumina-Based RNA Sequencing Data Identified Vernalization-Responsive Candidate Genes in Faba Bean (Vicia faba L.)
Authors: Yuan Xingxing , Wang Qiong , Yan Bin , Zhang Jiong , Xue Chenchen , Chen Jingbin , Lin Yun , Zhang Xiaoyan , Shen Wenbiao , Chen Xin
Published: July 2021

Faba bean (Vicia faba L.) is one of the most widely grown cool season legume crops in the world. Winter faba bean normally has a vernalization requirement, which promotes an earlier flowering and pod setting than unvernalized plants. However, the molecular mechanisms of vernalization in faba bean are largely unknown. Discovering vernalization-related candidate genes is of great importance for faba bean breeding. In this study, the whole transcriptome of faba bean buds was profiled by using next-generation sequencing (NGS) and single-molecule, real-time (SMRT) full-length transcriptome sequencing technology. A total of 29,203 high-quality non-redundant transcripts, 21,098 complete coding sequences (CDS), 1,045 long non-coding RNAs (lncRNAs), and 12,939 simple sequence repeats (SSRs) were identified. Furthermore, 4,044 differentially expressed genes (DEGs) were identified through pairwise comparisons. By Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, these differentially expressed transcripts were found to be enriched in binding and transcription factor activity, electron carrier activity, rhythmic process, and receptor activity. Finally, 50 putative vernalization-related genes that played important roles in the vernalization of faba bean were identified; we also found that the levels of vernalization-responsive transcripts showed significantly higher expression levels in cold-treated buds. The expression of VfSOC1, one of the candidate genes, was sensitive to vernalization. Ectopic expression of VfSOC1 in Arabidopsis brought earlier flowering. In conclusion, the abundant vernalization-related transcripts identified in this study will provide a basis for future researches on the vernalization and faba bean breeding and established a reference full-length transcriptome for future studies on faba bean.
Meta-Analyzing Multiple Omics Data With Robust Variable Selection
Authors: Hu Zongliang , Zhou Yan , Tong Tiejun
Published: July 2021

High-throughput omics data are becoming more and more popular in various areas of science. Given that many publicly available datasets address the same questions, researchers have applied meta-analysis to synthesize multiple datasets to achieve more reliable results for model estimation and prediction. Due to the high dimensionality of omics data, it is also desirable to incorporate variable selection into meta-analysis. Existing meta-analyzing variable selection methods are often sensitive to the presence of outliers, and may lead to missed detections of relevant covariates, especially for lasso-type penalties. In this paper, we develop a robust variable selection algorithm for meta-analyzing high-dimensional datasets based on logistic regression. We first search an outlier-free subset from each dataset by borrowing information across the datasets with repeatedly use of the least trimmed squared estimates for the logistic model and together with a hierarchical bi-level variable selection technique. We then refine a reweighting step to further improve the efficiency after obtaining a reliable non-outlier subset. Simulation studies and real data analysis show that our new method can provide more reliable results than the existing meta-analysis methods in the presence of outliers.
Integrated Analysis of lncRNAs, mRNAs, and TFs to Identify Regulatory Networks Underlying MAP Infection in Cattle
Authors: Heidari Maryam , Pakdel Abbas , Bakhtiarizadeh Mohammad Reza , Dehghanian Fariba
Published: July 2021

Johne’s disease is a chronic infection of ruminants that burdens dairy herds with a significant economic loss. The pathogenesis of the disease has not been revealed clearly due to its complex nature. In order to achieve deeper biological insights into molecular mechanisms involved in MAP infection resulting in Johne’s disease, a system biology approach was used. As far as is known, this is the first study that considers lncRNAs, TFs, and mRNAs, simultaneously, to construct an integrated gene regulatory network involved in MAP infection. Weighted gene coexpression network analysis (WGCNA) and functional enrichment analysis were conducted to explore coexpression modules from which nonpreserved modules had altered connectivity patterns. After identification of hub and hub-hub genes as well as TFs and lncRNAs in the nonpreserved modules, integrated networks of lncRNA-mRNA-TF were constructed, and cis and trans targets of lncRNAs were identified. Both cis and trans targets of lncRNAs were found in eight nonpreserved modules. Twenty-one of 47 nonpreserved modules showed significant biological processes related to the immune system and MAP infection. Some of the MAP infection’s related pathways in the most important nonpreserved modules comprise “positive regulation of cytokine-mediated signaling pathway,” “negative regulation of leukocyte migration,” “T-cell differentiation,” “neutrophil activation,” and “defense response.” Furthermore, several genes were identified in these modules, including SLC11A1, MAPK8IP1, HMGCR, IFNGR1, CMPK2, CORO1A, IRF1, LDLR, BOLA-DMB, and BOLA-DMA, which are potentially associated with MAP pathogenesis. This study not only enhanced our knowledge of molecular mechanisms behind MAP infection but also highlighted several promising hub and hub-hub genes involved in macrophage-pathogen interaction.
Structure and Function of Pancreatic Lipase-Related Protein 2 and Its Relationship With Pathological States
Authors: Zhu Guoying , Fang Qing , Zhu Fengshang , Huang Dongping , Yang Changqing
Published: July 2021

Pancreatic lipase is critical for the digestion and absorption of dietary fats. The most abundant lipolytic enzymes secreted by the pancreas are pancreatic triglyceride lipase (PTL or PNLIP) and its family members, pancreatic lipase-related protein 1 (PNLIPRP1or PLRP1) and pancreatic lipase-related protein 2 (PNLIPRP2 or PLRP2). Unlike the family’s other members, PNLIPRP2 plays an elemental role in lipid digestion, especially for newborns. Therefore, if genetic factors cause gene mutation, or other factors lead to non-expression, it may have an effect on fat digestion and absorption, on the susceptibility to pancreas and intestinal pathogens. In this review, we will summarize what is known about the structure and function of PNLIPRP2 and the levels of PNLIPRP2 and associated various pathological states.
Telomerase as a Target for Therapeutic Cancer Vaccines and Considerations for Optimizing Their Clinical Potential
Authors: Ellingsen Espen Basmo , Mangsbo Sara M. , Hovig Eivind , Gaudernack Gustav
Published: July 2021

Telomerase-based therapeutic cancer vaccines (TCVs) have been under clinical investigation for the past two decades. Despite past failures, TCVs have gained renewed enthusiasm for their potential to improve the efficacy of checkpoint inhibition. Telomerase stands as an attractive target for TCVs due to its almost universal presence in cancer and its essential function promoting tumor growth. Herein, we review tumor telomerase biology that may affect the efficacy of therapeutic vaccination and provide insights on optimal vaccine design and treatment combinations. Tumor types possessing mechanisms of increased telomerase expression combined with an immune permissive tumor microenvironment are expected to increase the therapeutic potential of telomerase-targeting cancer vaccines. Regardless, rational treatment combinations, such as checkpoint inhibitors, are likely necessary to bring out the true clinical potential of TCVs.
Association of NRAS Mutation With Clinical Outcomes of Anti-PD-1 Monotherapy in Advanced Melanoma: A Pooled Analysis of Four Asian Clinical Trials
Authors: Zhou Li , Wang Xuan , Chi Zhihong , Sheng Xinan , Kong Yan , Mao Lili , Lian Bin , Tang Bixia , Yan Xieqiao , Bai Xue , Li Siming , Guo Jun , Cui Chuanliang , Si Lu
Published: July 2021

Background

Anti-PD-1 monotherapy is the standard therapy for advanced melanoma patients, including those with NRAS mutations. The influence of NRAS mutation on immunotherapy, especially in noncutaneous melanoma, is largely uncharacterized.

Materials and Methods

We analyzed clinical data of four clinical trials for advanced melanoma patients treated with anti-PD-1 monotherapy between 2016 and 2019. The impact of NRAS mutation on efficacy and outcome of immunotherapy were analyzed in cutaneous and noncutaneous groups separately.

Results

A total of 206 patients were assessed, including 92 cutaneous melanoma patients with 12 NRAS mutations and 114 noncutaneous melanoma patients with 21 NRAS mutations. In cutaneous melanoma, the response rates of NRAS mutant patients were lower than patients without NRAS mutations (9.5% vs. 23.9%), the median progression-free survival (PFS) and median overall survival (OS) were shorter for patients with NRAS mutations, although without significant difference for OS (P=0.081). In noncutaneous melanoma, the response rates were 0 and 13.7% for NRAS mutant and wild-type patients, the median PFS were 3.6 months (95% CI: 0.9-6.3) and 4.3 months (95%CI: 2.9-5.7) (P=0.015), and the median OS were 10.8 months (95% CI: 1.5-20.1) and 15.3 months (95% CI: 13.2-17.4) (P=0.025), respectively. In multivariate analysis, NRAS mutation, along with ECOG performance score and LDH level, was negatively associated with both PFS (HR 1.912, P=0.044) and OS (HR 2.210, P=0.025) in noncutaneous melanoma.

Conclusion

In advanced Asian melanoma treated with anti-PD-1 monotherapy, NRAS mutant patients had lower response rates and poorer prognoses compared to wild-type patients, especially in noncutaneous subtypes.
Deteriorating Habitats and Conservation Strategies to Repopulate the Endangered Indus River Dolphin (Platanista gangetica minor); a Lesson Learned From the Conservation Practices of the Yangtze Finless Porpoise (Neophocaena asiaeorientalis)
Authors: Nabi Ghulam , Ahmad Shahid , McLaughlin Richard William , Hao Yujiang , Khan Suliman , Ahmad Naveed , Ahmad Saeed , Kiani Muhammad Shoaib , Wu Yuefeng , Li Dongming
Published: July 2021

The Indus River dolphin (IRD;Platanista gangetica minor) is an endangered and blind freshwater cetacean, endemic to the Indus River system of Pakistan and India. This review article provides detailed information about the major challenges IRDs are facing, and their possible consequences on the population dynamics of the IRD. Furthermore, we have suggested future conservation strategies for the IRD based on the lesson learned from the conservation of the Yangtze finless porpoise (YFP;Neophocaena asiaeorientalis), a Critically Endangered freshwater cetacean. The major challenges for IRDs are habitat degradation, habitat fragmentation, and several types of industrial and agricultural pollutants. Worsening climatic changes, illegal fishing, and overfishing are additional threats. The construction of several barrages has fragmented the population into several short segments, some of which are too small for the IRDs to survive. In some segments, the population status of the IRD is unknown. In the remaining populations, genetic inbreeding, water shortage, canal entrapment, and altered ecological environment are potent negative factors for the survival of the IRD. Conservation strategies including fishing bans, translocation, and future research (tagging, periodic health assessments, necropsy and virtopsy, understanding the reproductive biology, and genomics) are possible recommendations. Very serious conservation efforts are needed to save the IRD from decline keeping in view the water shortage, pollution, lack of health assessment studies, and habitat degradation and fragmentation.
Perceived Vulnerability and Climate Change Impacts on Small-Scale Fisheries in Davao Gulf, Philippines
Authors: Macusi Edison D. , Camaso Kezia L. , Barboza Anna , Macusi Erna S.
Published: July 2021

The small-scale fisheries play a critical role in food security and income of coastal fishing communities. However, climate variability and its impacts are affecting fishers, their communities, and fishing grounds. This study aimed to determine the perceived impacts of climate change and vulnerability of small-scale fisheries in selected fishing communities around the Davao Gulf. A semi-structured questionnaire was used to gather data on the perceptions of fishers (N= 220) on the impacts of climate change on their livelihood and communities. Seven focus groups corroborated the collected data and conclusions reached (N= 15). Principal component analysis (PCA) was used to reduce the sources of vulnerability and number of impacts of climate change. Regression was used to determine factors influencing the catch per unit effort (CPUE). The PCA results showed that for the vulnerability, the sources, coral bleaching, inadequate food, lack of credit access, changes in weather pattern and hotter temperature contributed highly. For the climate change impacts, the factors, less seasonality, unclear reproductive patterns, diseases in the catch, invasive species, decrease in catch and venturing farther to fish offshore were substantially influential. Further analysis showed that disease and invasive species, decrease in fish catch, fishing farther offshore, and monthly income affected the CPUE of the fisheries. Recommendations for climate change vulnerability reduction based on the conclusions reached in this study include more financial credit access, apprehension of illegal fishers, increased capacity building and technical skills for coastal communities, supplemental livelihoods, and information dissemination on climate change adaptation strategies.
Evolutionary Insights Into Two Widespread Ectomycorrhizal Fungi (Pisolithus) From Comparative Analysis of Mitochondrial Genomes
Authors: Wu Peng , Yao Tian , Ren Yuanhang , Ye Jinghua , Qing Yuan , Li Qiang , Gui Mingying
Published: July 2021

The genus Pisolithus is a group of global ectomycorrhizal fungi. The characterizations of Pisolithus mitochondrial genomes have still been unknown. In the present study, the complete mitogenomes of two Pisolithus species, Pisolithus microcarpus, and Pisolithus tinctorius, were assembled and compared with other Boletales mitogenomes. Both Pisolithus mitogenomes comprised circular DNA molecules with sizes of 43,990 and 44,054 bp, respectively. Comparative mitogenomic analysis showed that the rps3 gene differentiated greatly between Boletales species, and this gene may be subjected to strong pressure of positive selection between some Boletales species. Several plasmid-derived genes and genes with unknown functions were detected in the two Pisolithus mitogenomes, which needs further analysis. The two Pisolithus species show a high degree of collinearity, which may represent the gene arrangement of the ancestors of ectomycorrhizal Boletales species. Frequent intron loss/gain events were detected in Boletales and basidiomycetes, and intron P717 was only detected in P. tinctorius out of the eight Boletales mitogenomes tested. We reconstructed phylogeny of 79 basidiomycetes based on combined mitochondrial gene dataset, and obtained well-supported phylogenetic topologies. This study served as the first report on the mitogenomes of the family Pisolithaceae, which will promote the understanding of the evolution of Pisolithus species.
Expression of the ACE2 Virus Entry Protein in the Nervus Terminalis Reveals the Potential for an Alternative Route to Brain Infection in COVID-19
Authors: Bilinska Katarzyna , von Bartheld Christopher S. , Butowt Rafal
Published: July 2021

Previous studies suggested that the SARS-CoV-2 virus may gain access to the brain by using a route along the olfactory nerve. However, there is a general consensus that the obligatory virus entry receptor, angiotensin converting enzyme 2 (ACE2), is not expressed in olfactory receptor neurons, and the timing of arrival of the virus in brain targets is inconsistent with a neuronal transfer along olfactory projections. We determined whether nervus terminalis neurons and their peripheral and central projections should be considered as a potential alternative route from the nose to the brain. Nervus terminalis neurons in postnatal mice were double-labeled with antibodies against ACE2 and two nervus terminalis markers, gonadotropin-releasing hormone (GnRH) and choline acetyltransferase (CHAT). We show that a small fraction of CHAT-labeled nervus terminalis neurons, and the large majority of GnRH-labeled nervus terminalis neurons with cell bodies in the region between the olfactory epithelium and the olfactory bulb express ACE2 and cathepsins B and L. Nervus terminalis neurons therefore may provide a direct route for the virus from the nasal epithelium, possibly via innervation of Bowman’s glands, to brain targets, including the telencephalon and diencephalon. This possibility needs to be examined in suitable animal models and in human tissues.
Synthetic Birdsongs as a Tool to Induce, and Iisten to, Replay Activity in Sleeping Birds
Authors: Amador Ana , Mindlin Gabriel B.
Published: July 2021

Birdsong is a complex vocal behavior, which emerges out of the interaction between a nervous system and a highly nonlinear vocal device, the syrinx. In this work we discuss how low dimensional dynamical systems, interpretable in terms of the biomechanics involved, are capable of synthesizing realistic songs. We review the experimental and conceptual steps that lead to the formulation of low dimensional dynamical systems for the song system and describe the tests that quantify their success. In particular, we show how to evaluate computational models by comparing the responses of highly selective neurons to the bird’s own song and to synthetic copies generated mathematically. Beyond testing the hypothesis behind the model’s construction, these low dimensional models allow designing precise stimuli in order to explore the sensorimotor integration of acoustic signals.
Heart Rate Variability Changes in Patients With Major Depressive Disorder: Related to Confounding Factors, Not to Symptom Severity?
Authors: Sarlon Jan , Staniloiu Angelica , Kordon Andreas
Published: July 2021

Background

The aim of this study was to assess the electrophysiological and other influencing factors correlating with symptom severity in patients with major depressive disorder (MDD) under three different conditions: baseline, stress exposure, and relaxation following stress exposure.

Methods

Symptom severity was assessed using the Beck Depression Inventory (BDI-II) in 89 inpatients (37 women; mean age 51 years) with MDD. Resting heart rate (RHR), heart rate variability (HRV), respiration rate (RR), skin conductance (SC), and skin temperature (ST) were recorded at baseline for 300 s, under stress exposure for 60 s, and under self-induced relaxation for 300 s. Age, nicotine consumption, body mass index, and blood pressure were evaluated as influencing factors.

Results

The BDI-II mean score was 29.7 points. Disease severity correlated positively with SC elevation under stress exposure and with a higher RR in the relaxed state, but no association was found between HRV and symptom severity. Age and higher blood pressure were both associated with lower HRV and higher RHR.

Conclusion

The results indicate that, in patients with MDD, changes in the autonomic nervous system (ANS) are complex; and the assessment of ANS reactivity to stressors is useful. Elevated blood pressure might be underdiagnosed, although it is already relevant in patients with MDD in their early 50s.
Functional Imaging to Guide Network-Based TMS Treatments: Toward a Tailored Medicine Approach in Alzheimer’s Disease
Authors: Bagattini Chiara , Brignani Debora , Bonnì Sonia , Quattrini Giulia , Gasparotti Roberto , Pievani Michela
Published: July 2021

A growing number of studies is using fMRI-based connectivity to guide transcranial magnetic stimulation (TMS) target identification in both normal and clinical populations. TMS has gained increasing attention as a potential therapeutic strategy also in Alzheimer’s disease (AD), but an endorsed target localization strategy in this population is still lacking. In this proof of concept study, we prove the feasibility of a tailored TMS targeting approach for AD, which stems from a network-based perspective. Based on functional imaging, the procedure allows to extract individual optimal targets meanwhile accounting for functional variability. Single-subject resting-state fMRI was used to extract individual target coordinates of two networks primarily affected in AD, the default mode and the fronto-parietal network. The localization of these targets was compared to that of traditional group-level approaches and tested against varying degrees of TMS focality. The distance between individual fMRI-derived coordinates and traditionally defined targets was significant for a supposed TMS focality of 12 mm and in some cases up to 20 mm. Comparison with anatomical labels confirmed a lack of 1:1 correspondence between anatomical and functional targets. The proposed network-based fMRI-guided TMS approach, while accounting for inter-individual functional variability, allows to target core AD networks, and might thus represent a step toward tailored TMS interventions for AD.
The Metallome as a Link Between the “Omes” in Autism Spectrum Disorders
Authors: Stanton Janelle E. , Malijauskaite Sigita , McGourty Kieran , Grabrucker Andreas M.
Published: July 2021

Metal dyshomeostasis plays a significant role in various neurological diseases such as Alzheimer’s disease, Parkinson’s disease, Autism Spectrum Disorders (ASD), and many more. Like studies investigating the proteome, transcriptome, epigenome, microbiome, etc., for years, metallomics studies have focused on data from their domain, i.e., trace metal composition, only. Still, few have considered the links between other “omes,” which may together result in an individual’s specific pathologies. In particular, ASD have been reported to have multitudes of possible causal effects. Metallomics data focusing on metal deficiencies and dyshomeostasis can be linked to functions of metalloenzymes, metal transporters, and transcription factors, thus affecting the proteome and transcriptome. Furthermore, recent studies in ASD have emphasized the gut-brain axis, with alterations in the microbiome being linked to changes in the metabolome and inflammatory processes. However, the microbiome and other “omes” are heavily influenced by the metallome. Thus, here, we will summarize the known implications of a changed metallome for other “omes” in the body in the context of “omics” studies in ASD. We will highlight possible connections and propose a model that may explain the so far independently reported pathologies in ASD.
Comparative Analysis of Akebia trifoliata Fruit Softening at Different Flesh Ripening Stages Using Tandem Mass Tag Technology
Authors: Niu Juan , Sun Zhimin , Shi Yaliang , Huang Kunyong , Zhong Yicheng , Chen Jing , Chen Jianhua , Luan Mingbao
Published: July 2021

Owing to its medicinal and high nutritional values, Akebia trifoliata can be considered as a new type of medicinal and edible homologous resources, and it has begun to be widely cultivated in many areas of China. Over-softening of fruit would affect the sensorial quality, utilization rate, and consumer acceptance of the fruit postharvest. However, fruit softening has not been characterized and the molecular mechanism underlying A. trifoliata fruit softening during ripening remains unclear. A comparative proteomic analysis was performed on the fruit at three developmental stages using tandem mass tag technology. In total, 2,839 proteins and 302 differentially abundant proteins (DAPs) were identified. Bioinformatics analysis indicated that most DAPs were implicated in oxidoreductase activity, protein domain-specific binding and pyruvate metabolism. Moreover, 29 DAPs associated with cell wall metabolism, plant hormone, and stress and defense response pathways were validated using quantitative PCR. Notably, pectinesterase, pectate lyase, and β-galactosidase, which are involved in cell wall degradation, as well as gibberellin regulated protein, cysteine protease, thaumatin-like protein and heat shock proteins which is involved in plant hormone, and stress and defense response, were significantly up-regulated in softening fruit compared with the levels in non-softening fruit. This indicated that they might play key roles in A. trifoliata fruit softening. Our findings will provide new insights into potential genes influencing fruit softening traits of A. trifoliata, which will help to develop strategies to improve fruit quality and reduce softening-related losses.
Beyond Colonoscopy: Exploring New Cell Surface Biomarkers for Detection of Early, Heterogenous Colorectal Lesions
Authors: Ramezani Saleh , Parkhideh Arianna , Bhattacharya Pratip K. , Farach-Carson Mary C. , Harrington Daniel A.
Published: July 2021

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths among both men and women in the United States. Early detection and surgical removal of high-risk lesions in the colon can prevent disease from developing and spreading. Despite implementation of programs aimed at early detection, screening colonoscopies fail to detect a fraction of potentially aggressive colorectal lesions because of their location or nonobvious morphology. Optical colonoscopies, while highly effective, rely on direct visualization to detect changes on the surface mucosa that are consistent with dysplasia. Recent advances in endoscopy techniques and molecular imaging permit microscale visualization of the colonic mucosa. These technologies can be combined with various molecular probes that recognize and target heterogenous lesion surfaces to achieve early, real-time, and potentially non-invasive, detection of pre-cancerous lesions. The primary goal of this review is to contextualize existing and emergent CRC surface biomarkers and assess each’s potential as a candidate marker for early marker-based detection of CRC lesions. CRC markers that we include were stratified by the level of support gleaned from peer-reviewed publications, abstracts, and databases of both CRC and other cancers. The selected biomarkers, accessible on the cell surface and preferably on the luminal surface of the colon tissue, are organized into three categories: (1) established biomarkers (those with considerable data and high confidence), (2) emerging biomarkers (those with increasing research interest but with less supporting data), and (3) novel candidates (those with very recent data, and/or supportive evidence from other tissue systems). We also present an overview of recent advances in imaging techniques useful for visual detection of surface biomarkers, and discuss the ease with which these methods can be combined with microscopic visualization.
Collision Carcinoma Involving Small Cell Neuroendocrine Carcinoma and Squamous Cell Carcinoma of the Ureter: A Case Report and Review of the Literature
Authors: Xu Sheng , Xu Lei , Cao Peng , Yao Shiyun , Wu Tingming , Hu Xinming , Chen Hualei , Gu Jun , Che Xianping
Published: July 2021

Background

Small cell neuroendocrine carcinoma (SCNEC) of the ureter is a rare tumour, accounting for less than 0.5% of all ureteral tumours. SCNEC tumours are highly aggressive and patients have a poor prognosis. Ureteral SCNEC colliding with other pathological types of tumours is extremely rare. In this paper, we present the case of a patient with ureteral small cell carcinoma colliding with squamous cell carcinoma and review the literature regarding the clinicopathological features, treatment and prognosis of thus tumour. To the best of our knowledge, this is the second identified case of ureteral SCNEC colliding with SCC.

Case Presentation

A 64-year-old male patient presented with a history of 1 month of gross haematuria and 3 months of left flank pain. CT urography revealed a soft tissue mass in the upper ureter, which was slightly enhanced on contrast-enhanced CT. Nephroureterectomy was performed after the patient was diagnosed with a tumour in the left ureter. Microscopy and immunohistochemical examination confirmed the mass to be a SCNEC collision with SCC. Two months after the surgery, the patient received adjuvant chemotherapy (cisplatin/etoposide). After 14 months of follow-up, no local recurrence or distant metastasis was found.

Conclusion

Ureteral collision carcinoma with SCNEC predominantly occurs in Asian individuals, is difficult to diagnose preoperatively and is highly invasive. The current management of ureteral collision carcinoma is a comprehensive treatment based on surgery.
Case Report: Severe Rashes Associated With Fruquintinib in a Patient With Metastatic Colorectal Cancer
Authors: Shu Yefei , Zheng Song
Published: July 2021

Metastatic colorectal cancer (mCRC) is a common and high-risk malignant tumor. Fruquintinib is a novel small-molecule compound with high selective inhibition of vascular endothelial growth factor (VEGF) receptor (VEGFR) for mCRC for which second-line or higher standard chemotherapy has been ineffective. A female patient with mCRC developed severe rashes after 2 weeks of taking fruquintinib. Considering the relationship between fruquintinib and the rashes, she discontinued taking the drug, and her condition improved. Although fruquintinib has shown good safety and manageable toxicity in previous trials, the patient in the present case developed severe rashes after 2 weeks of taking fruquintinib. The common skin reactions of hand and foot are erythema and paresthesia of hand and foot. Because few people have reported a severe rash caused by fruquintinib, which is different from the common hand foot skin reaction. We hope the case attracts the attention of oncologists.
Monoaminergic and Opioidergic Modulation of Brainstem Circuits: New Insights Into the Clinical Challenges of Pain Treatment?
Authors: Tavares Isaura , Costa-Pereira José Tiago , Martins Isabel
Published: July 2021

The treatment of neuropathic pain remains a clinical challenge. Analgesic drugs and antidepressants are frequently ineffective, and opioids may induce side effects, including hyperalgesia. Recent results on brainstem pain modulatory circuits may explain those clinical challenges. The dual action of noradrenergic (NA) modulation was demonstrated in animal models of neuropathic pain. Besides the well-established antinociception due to spinal effects, the NA system may induce pronociception by directly acting on brainstem pain modulatory circuits, namely, at the locus coeruleus (LC) and medullary dorsal reticular nucleus (DRt). The serotoninergic system also has a dual action depending on the targeted spinal receptor, with an exacerbated activity of the excitatory 5-hydroxytryptamine 3 (5-HT3) receptors in neuropathic pain models. Opioids are involved in the modulation of descending modulatory circuits. During neuropathic pain, the opioidergic modulation of brainstem pain control areas is altered, with the release of enhanced local opioids along with reduced expression and desensitization of μ-opioid receptors (MOR). In the DRt, the installation of neuropathic pain increases the levels of enkephalins (ENKs) and induces desensitization of MOR, which may enhance descending facilitation (DF) from the DRt and impact the efficacy of exogenous opioids. On the whole, the data discussed in this review indicate the high plasticity of brainstem pain control circuits involving monoaminergic and opioidergic control. The data from studies of these neurochemical systems in neuropathic models indicate the importance of designing drugs that target multiple neurochemical systems, namely, maximizing the antinociceptive effects of antidepressants that inhibit the reuptake of serotonin and noradrenaline and preventing desensitization and tolerance of MOR at the brainstem.
Weight Status and Body Composition Dynamics in Children and Adolescents During the COVID-19 Pandemic
Authors: Azoulay Erez , Yackobovitch-Gavan Michal , Yaacov Hadar , Gilboa Inbar , Lopez Adar , Sheppes Tamar , Waksman Yarden , Lebenthal Yael , Brener Avivit
Published: July 2021

Introduction: The preventive measures taken in attempt to prevent COVID-19 spread lead to closure of schools and leisure time activities. The impact of the pandemic on pediatric weight status is unclear, reports from around the world predict grave consequences with increasing obesity. We aimed to examine the change in body composition parameters of children and adolescents during the pandemic.

Materials and Methods: An observational study of 220 pediatric subjects (109 boys; mean current age 11.8 ± 3.3 years; 37 with underweight, 123 with normal weight, and 60 with overweight/obesity) who underwent height and body composition measurements by bioelectrical impedance analysis, Tanita MC-780MA, GMON Professional Software before and during the pandemic. Height, body mass index (BMI) and muscle-to-fat ratio (MFR) z-scores were calculated. Data collected from the participants' medical files included home address for socioeconomic position calculation, pubertal stage, and self-reported sleep duration and physical activity performance.

Results: The vast majority of the cohort (81.8%) had stable or improved MFR z-scores during the pandemic. MFR z-scores significantly increased in subjects with underweight (p = 0.05) and normal weight (p = 0.008), but not in subjects with overweight/obesity (p = 0.169). There were significant associations in BMI z-scores (r = 0.961, p < 0.001) and MFR z-scores (r = 0.854, p < 0.001) before and during the pandemic. A multivariate linear regression model identified socioeconomic position, pre-pandemic BMI z-scores, pre-pandemic MFR z-scores, and physical activity levels during the pandemic as predictors for delta MFR z-scores (F = 12.267, p < 0.001). Age, sex, pre-pandemic physical activity, and the time that had elapsed between initiation of the first nationwide lockdown and the BIA assessment during the pandemic did not emerge as predictors for delta MFR z-score.

Conclusions: Our encouraging findings demonstrate improvement in body composition parameters of subjects with underweight and normal weight and stability in subjects with overweight/obesity. Engagement in physical activity during the pandemic predicted improvement, while lower socioeconomic position predicted deterioration.
Geometric Features of the Pial Arteriolar Networks in Spontaneous Hypertensive Rats: A Crucial Aspect Underlying the Blood Flow Regulation
Authors: Lapi Dominga , Di Maro Martina , Serao Nicola , Chiurazzi Martina , Varanini Maurizio , Sabatino Lina , Scuri Rossana , Colantuoni Antonio , Guida Bruna
Published: July 2021

Background

Several studies indicate that hypertension causes major changes in the structure of the vessel wall by affecting the regulation of blood supply to the tissues. Recently, it has been observed that capillary blood flow is also considerably influenced by the structural arrangement of the microvascular networks that undergo rarefaction (reduction of the perfused vessel number). Therefore, this study aimed to assess the geometric arrangements of the pial arteriolar networks and the arteriolar rhythmic diameter changes in spontaneously hypertensive rats (SHRs).

Methods

Fluorescence microscopy was utilized to observe in vivo the pial microcirculation through a closed cranial window. Pial arterioles were classified according to Strahler’s method. The arteriolar rhythmic diameter changes were evaluated by a generalization short-time Fourier transform.

Result

Young SHRs showed four orders of vessels while the adult ones only three orders. The diameter, length, and branching number obeyed Horton’s law; therefore, the vessels were distributed in a fractal manner. Larger arterioles showed more asymmetrical branches than did the smaller ones in young SHRs, while in adult SHRs smaller vessels presented asymmetrical branchings. In adult SHRs, there was a significant reduction in the cross-sectional area compared with the young SHRs: this implies an increase in peripheral resistance. Young and adult age-matched normotensive rats did not show significant alterations in the geometric arteriolar arrangement with advancing age, both had four orders of arteriolar vessels, and the peripheral resistance did not change significantly. Conversely, the frequency components evaluated in arteriolar rhythmic diameter changes of young and adult SHRs showed significant differences because of a reduction in the frequency components related to endothelial activity detected in adult SHRs.

Conclusion

In conclusion, hypertension progressively causes changes in the microarchitecture of the arteriolar networks with a smaller number of vessels and consequent reduced conductivity, characteristic of rarefaction. This was accompanied by a reduction in the formation and release of independent and dependent – endothelial nitric oxide components regulating arterial vasomotion.
Minocycline Treatment Reduces Mass and Force Output From Fast-Twitch Mouse Muscles and Inhibits Myosin Production in C2C12 Myotubes
Authors: Kiriaev Leonit , Perry Ben D. , Mahns David A. , Shortland Peter J. , Redwan Asma , Morley John W. , Head Stewart I.
Published: July 2021

Minocycline, a tetracycline-class of antibiotic, has been tested with mixed effectiveness on neuromuscular disorders such as amyotrophic lateral sclerosis, autoimmune neuritis and muscular dystrophy. The independent effect of minocycline on skeletal muscle force production and signalling remain poorly understood. Our aim here is to investigate the effects of minocycline on muscle mass, force production, myosin heavy chain abundance and protein synthesis. Mice were injected with minocycline (40 mg/kg i.p.) daily for 5 days and sacrificed at day six. Fast-twitch EDL, TA muscles and slow-twitch soleus muscles were dissected out, the TA muscle was snap-frozen and the remaining muscles were attached to force transducer whilst maintained in an organ bath. In C2C12 myotubes, minocycline was applied to the media at a final concentration of 10 μg/mL for 48 h. In minocycline treated mice absolute maximal force was lower in fast-twitch EDL while in slow-twitch soleus there was an increase in the time to peak and relaxation of the twitch. There was no effect of minocycline treatment on the other contractile parameters measured in isolated fast- and slow-twitch muscles. In C2C12 cultured cells, minocycline treatment significantly reduced both myosin heavy chain content and protein synthesis without visible changes to myotube morphology. In the TA muscle there was no significant changes in myosin heavy chain content. These results indicate that high dose minocycline treatment can cause a reduction in maximal isometric force production and mass in fast-twitch EDL and impair protein synthesis during myogenesis in C2C12 cultured cells. These findings have important implications for future studies investigating the efficacy of minocycline treatment in neuromuscular or other muscle-atrophy inducing conditions.
Outlook of Cassava Brown Streak Disease Assessment: Perspectives of the Screening Methods of Breeders and Pathologists
Authors: Ozimati Alfred A. , Esuma Williams , Alicai Titus , Jannink Jean-Luc , Egesi Chiedozie , Kawuki Robert
Published: July 2021

Cassava production and productivity in Eastern, Central, and Southern Africa are ravaged by cassava brown streak disease (CBSD), causing yield losses of up to 100% when susceptible varieties are grown. Efforts to develop CBSD-resistant clones are underway. However, the methods for screening CBSD resistance currently vary between breeders and pathologists, with the limited empirical data to support their choices. In this study, we used the empirical CBSD foliar and root necrosis data from two breeding populations, termed cycle zero (C0) and cycle one (C1), to assess and compare the effectiveness of the CBSD screening methods of breeders vs. pathologists. On the one hand, the estimates of broad-sense heritability (H2) for the CBSD root necrosis assessment of breeder ranged from 0.15 to 0.87, while for the assessment method of pathologists, H2 varied from 0.00 to 0.71 in C0 clones. On the other hand, the marker-based heritability estimates (h2) for C0 ranged from 0.00 to 0.70 for the assessment method of breeders and from 0.00 to 0.63 for the assessment method of pathologists. For cycle one (C1) population, where both foliar and root necrosis data were analyzed for clones assessed at clonal evaluation trials (CETs) and advanced yield trials (AYTs), H2 varied from 0.10 to 0.59 for the assessment method of breeders, while the H2 values ranged from 0.09 to 0.35 for the CBSD computation method of pathologists. In general, higher correlations were recorded for foliar severity from the assessment method of breeders (r = 0.4, p ≤ 0.01 for CBSD3s and r = 0.37, p ≤ 0.01 for CBSD6s) in C1 clones evaluated at both clonal and advanced breeding stages than from the approach of pathologists. Ranking of top 10 C1 clones by their indexed best linear unbiased predictors (BLUPs) for CBSD foliar and root necrosis showed four overlapping clones between clonal and advanced selection stages for the method of breeders; meanwhile, only a clone featured in both clonal and advanced selection stages from the CBSD assessment method of pathologists. Overall, the CBSD assessment method of breeders was more effective than the assessment method of pathologists, and thus, it justifies its continued use in CBSD resistance breeding.
A Sequential Three-Phase Pathway Constitutes Tracheary Element Connection in the Arabidopsis/Nicotiana Interfamilial Grafts
Authors: Deng Zhuying , Wu Huiyan , Jin Tianlin , Cai Tingting , Jiang Mengting , Wang Mi , Liang Dacheng
Published: July 2021

Scion-rootstock union formation is a critical step toward the functional assemblage of heterogeneous plants. Interfamilial scion-rootstock interaction often results in graft incompatibility during the assemblage process, and the underlying mechanisms are largely unknown. In this study, we reported that tracheary element (TE) remodeling, including TE segmentation and deformation, rather than de novo formation from callus or adjacent tissues, took place at the early stage of grafting interface between Arabidopsis thaliana and Nicotiana benthamiana (At/Nb). Following cellular deposits, the short TEs from both partners were overlapping, dependent on the homogeneity of contacting TEs, with each other. Without overlapping, the TEs at the interface would grow laterally, and the TEs above and below the interface would undergo self-fusion to form insulating spiraling bundles. Finally, the overlapping TEs constituted a continuous network through alignment. Our results provide a definitive framework for the critical process of TE behavior in the At/Nb distant grafts, including (1) segmentation and/or deformation, (2) matching, overlapping, and cellular deposits, and (3) aligning or spiraling. These insights might guide us in the future into constructing more compatible distant grafts from the perspective of TE homogeneity.
Convolutional Rebalancing Network for the Classification of Large Imbalanced Rice Pest and Disease Datasets in the Field
Authors: Yang Guofeng , Chen Guipeng , Li Cong , Fu Jiangfan , Guo Yang , Liang Hua
Published: July 2021

The accurate classification of crop pests and diseases is essential for their prevention and control. However, datasets of pest and disease images collected in the field usually exhibit long-tailed distributions with heavy category imbalance, posing great challenges for a deep recognition and classification model. This paper proposes a novel convolutional rebalancing network to classify rice pests and diseases from image datasets collected in the field. To improve the classification performance, the proposed network includes a convolutional rebalancing module, an image augmentation module, and a feature fusion module. In the convolutional rebalancing module, instance-balanced sampling is used to extract features of the images in the rice pest and disease dataset, while reversed sampling is used to improve feature extraction of the categories with fewer images in the dataset. Building on the convolutional rebalancing module, we design an image augmentation module to augment the training data effectively. To further enhance the classification performance, a feature fusion module fuses the image features learned by the convolutional rebalancing module and ensures that the feature extraction of the imbalanced dataset is more comprehensive. Extensive experiments in the large-scale imbalanced dataset of rice pests and diseases (18,391 images), publicly available plant image datasets (Flavia, Swedish Leaf, and UCI Leaf) and pest image datasets (SMALL and IP102) verify the robustness of the proposed network, and the results demonstrate its superior performance over state-of-the-art methods, with an accuracy of 97.58% on rice pest and disease image dataset. We conclude that the proposed network can provide an important tool for the intelligent control of rice pests and diseases in the field.
Recognition Characteristics of Facial and Bodily Expressions: Evidence From ERPs
Authors: Li Xiaoxiao
Published: July 2021

In the natural environment, facial and bodily expressions influence each other. Previous research has shown that bodily expressions significantly influence the perception of facial expressions. However, little is known about the cognitive processing of facial and bodily emotional expressions and its temporal characteristics. Therefore, this study presented facial and bodily expressions, both separately and together, to examine the electrophysiological mechanism of emotional recognition using event-related potential (ERP). Participants assessed the emotions of facial and bodily expressions that varied by valence (positive/negative) and consistency (matching/non-matching emotions). The results showed that bodily expressions induced a more positive P1 component and a shortened latency, whereas facial expressions triggered a more negative N170 and prolonged latency. Among N2 and P3, N2 was more sensitive to inconsistent emotional information and P3 was more sensitive to consistent emotional information. The cognitive processing of facial and bodily expressions had distinctive integrating features, with the interaction occurring in the early stage (N170). The results of the study highlight the importance of facial and bodily expressions in the cognitive processing of emotion recognition.