bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastrointestinal Manifestations of COVID-19 Infection: Clinicopathologic Findings in Intestinal Resections Performed at Single Institution
Authors: Burkett Alison E. , Sher Sophia B. , Patel Chirag R. , Ildin-Eltoum Isam , Dhall Deepti , Margaroli Camilla , Peter Shajan , Lee Goo , Bajpai Prachi , Benson Paul V. , Manne Upender , Al Diffalha Sameer
Published: February 2022

It is now known that COVID-19 not only involves the lungs, but other organs as well including the gastrointestinal tract. Although clinic-pathological features are well-described in lungs, the histopathologic features of gastrointestinal involvement in resection specimens are not well characterized. Herein, we describe in detail the clinicopathologic features of intestinal resection specimens in four patients with COVID-19 infection. COVID-19 viral particles by in situ hybridization and immunofluorescence studies are also demonstrated. All four patients were males, aged 28–46 years, with comorbidities. They initially presented with a severe form of pulmonary COVID-19 and showed gastrointestinal symptoms, requiring surgical intervention. Histopathologic examination of resected GI specimens, mostly right colectomies, revealed a spectrum of disease, from superficial mucosal ischemic colitis to frank transmural ischemic colitis and associated changes consistent with pneumatosis cystoides intestinalis. Three patients were African American (75%), and one was Caucasian (25%); three patients died due to complications of their COVID-19 infection (75%), while one ultimately recovered from their GI complications (25%), but experienced prolonged sequela of COVID-19 infection including erectile dysfunction. In conclusion, COVID-19 infection, directly or indirectly, can cause ischemic gastrointestinal complications, with predilection for the right colon.
Dysbiosis of Oral and Gut Microbiomes in SARS-CoV-2 Infected Patients in Bangladesh: Elucidating the Role of Opportunistic Gut Microbes
Authors: Rafiqul Islam S. M. , Foysal Md. Javed , Hoque M. Nazmul , Mehedi H. M. Hamidullah , Rob Md. Abdur , Salauddin Asma , Tanzina Afsana Yeasmin , Biswas Sabuj , Noyon Sajjad Hossain , Siddiki A. M. A. M. Zonaed , Tay Alfred , Mannan Adnan
Published: February 2022

Coronavirus disease-2019 (COVID-19) is an infectious disease caused by SARS-CoV-2 virus. The microbes inhabiting the oral cavity and gut might play crucial roles in maintaining a favorable gut environment, and their relationship with SARS-CoV-2 infection susceptibility and severity is yet to be fully explored. This study investigates the diversity and species richness of gut and oral microbiota of patients with COVID-19, and their possible implications toward the severity of the patient's illness and clinical outcomes. Seventy-four (n = 74) clinical samples (gut and oral) were collected from 22 hospitalized patients with COVID-19 with various clinical conditions and 15 apparently healthy people (served as controls). This amplicon-based metagenomic sequencing study yielded 1,866,306 paired-end reads that were mapped to 21 phyla and 231 classified genera of bacteria. Alpha and beta diversity analyses revealed a distinct dysbiosis of the gut and oral microbial communities in patients with COVID-19, compared to healthy controls. We report that SARS-CoV-2 infection significantly reduced richness and evenness in the gut and oral microbiomes despite showing higher unique operational taxonomic units in the gut. The gut samples of the patients with COVID-19 included 46 opportunistic bacterial genera. Escherichia, Shigella, and Bacteroides were detected as the signature genera in the gut of patients with COVID-19 with diarrhea, whereas a relatively higher abundance of Streptococcus was found in patients with COVID-19 having breathing difficulties and sore throat (BDST). The patients with COVID-19 had a significantly lower abundance of Prevotella in the oral cavity, compared to healthy controls and patients with COVID-19 without diabetes, respectively. The altered metabolic pathways, including a reduction in biosynthesis capabilities of the gut and oral microbial consortia after SARS-CoV-2 infection, were also observed. The present study may, therefore, shed light on interactions of SARS-CoV-2 with resilient oral and gut microbes which might contribute toward developing microbiome-based diagnostics and therapeutics for this deadly pandemic disease.
Case Report: Myocarditis After COVID-19 Vaccination – Case Series and Literature Review
Authors: Nunn Samuel , Kersten Johannes , Tadic Marijana , Wolf Alexander , Gonska Birgid , Hüll Elina , Dietenberger Hanna , Rottbauer Wolfgang , Buckert Dominik
Published: February 2022

Background

The ongoing COVID-19 pandemic demands a series of measures and, above all, the vaccination of a substantial proportion of the population. Acute myocarditis is a rare complication of the widely used mRNA-based vaccines.

Case Presentation

We present a case series of four patients (three men and one woman, 16 to 47 years old) with acute pericarditis/myocarditis 3 to 17 days after mRNA vaccination. They presented with chest pain, fever, and flu-like symptoms. Diagnosis was made based on the synopsis of clinical presentation, elevated levels of troponin T and NT-proBNP, impaired systolic function on echocardiography, and findings in non-invasive tissue characterization by cardiovascular magnetic resonance imaging. Two patients also underwent endomyocardial biopsies. As none of the patients showed signs of cardiogenic shock, they were discharged from ward care only a few days after their initial presentations.

Conclusions

Our data are consistent with other case reports of myocarditis early after mRNA vaccination and demonstrate the need for multimodal diagnostics. In view of its rarity and mild course, the risk–benefit ratio of vaccination remains positive compared to potential SARS-CoV-2 infection.
Soil Nitrogen Treatment Alters Microbiome Networks Across Farm Niches
Authors: Wang XinYue , Reilly Kerri , Heathcott Rosemary , Biswas Ambarish , Johnson Linda J. , Teasdale Suliana , Grelet Gwen-Aëlle , Podolyan Anastasija , Gregorini Pablo , Attwood Graeme T. , Palevich Nikola , Morales Sergio E.
Published: February 2022

Agriculture is fundamental for food production, and microbiomes support agriculture through multiple essential ecosystem services. Despite the importance of individual (i.e., niche specific) agricultural microbiomes, microbiome interactions across niches are not well-understood. To observe the linkages between nearby agricultural microbiomes, multiple approaches (16S, 18S, and ITS) were used to inspect a broad coverage of niche microbiomes. Here we examined agricultural microbiome responses to 3 different nitrogen treatments (0, 150, and 300 kg/ha/yr) in soil and tracked linked responses in other neighbouring farm niches (rumen, faecal, white clover leaf, white clover root, rye grass leaf, and rye grass root). Nitrogen treatment had little impact on microbiome structure or composition across niches, but drastically reduced the microbiome network connectivity in soil. Networks of 16S microbiomes were the most sensitive to nitrogen treatment across amplicons, where ITS microbiome networks were the least responsive. Nitrogen enrichment in soil altered soil and the neighbouring microbiome networks, supporting our hypotheses that nitrogen treatment in soil altered microbiomes in soil and in nearby niches. This suggested that agricultural microbiomes across farm niches are ecologically interactive. Therefore, knock-on effects on neighbouring niches should be considered when management is applied to a single agricultural niche.
Colonization and Interaction of Bacteria Associated With Chinese Chives Affected by Ecological Compartments and Growth Conditions
Authors: Sun Nan , Wang Yuxin , Chen Jianhua , Wang Pingzhi , Song Weitang , Ma Peifang , Duan Yabin , Jiao Ziyuan , Li Yixiao
Published: February 2022

Chinese chive has a long history of planting in China. At present, there are many studies on endophytic bacteria and rhizosphere microorganisms of Chinese chive, but the effects of ecological compartment and growth conditions on bacterial communities in Chinese chives are unclear. Here, we aimed to elucidate the differences in bacterial a-diversity, β-diversity, community structure, core species differences, interaction networks and predicted metabolic functions among bacterial communities in different ecological compartments (the phylloplane, leaf endosphere, stem endosphere, root endosphere, and rhizosphere) in Chinese chives in an open field, a solar greenhouse, an arched shed, and a hydroponic system. Sixty samples were collected from these five ecological compartments under four growth conditions, and we compared the bacterial profiles of these groups using 16S rRNA sequencing. We evaluated the differences in diversity and composition among bacterial communities in these ecological compartments, analyzed the bacterial interaction patterns under the different growth conditions, and predicted the bacterial metabolic pathways in these ecological compartments and growth conditions. The results showed that the effects of ecological compartments on bacterial diversity, community composition, interaction network pattern, and functional expression of Chinese chives were greater than those of growth condition. Ecological compartments (R2 = 0.5292) could better explain bacterial community division than growth conditions (R2 = 0.1056). The microbial interaction networks and indicator bacteria in different ecological compartments showed that most of the bacteria that played the role of key nodes (OTUs) in each ecological compartment were bacteria with high relative abundance in the compartment. However, the bacteria that played the role of key nodes (OTUs) in bulbs were not Proteobacteria with the highest relative abundance in the compartment, but Actinobacteria that were significantly enriched in the root endosphere and rhizosphere ecological compartments. In addition, interactions among bacteria were interrupted in the hydroponic system, and specific bacterial communities and interaction patterns in Chinese chives varied among growth conditions. Prediction of metabolic functions indicated that plant metabolic activity related to stress responses and induction of system resistance was greater in belowground ecological compartments.
The Effects of Immunosuppression on the Lung Microbiome and Metabolites in Rats
Authors: Dong Huiwei , Tan Rong , Chen Zhengshan , Wang Lifang , Song Yuanyuan , Jin Min , Yin Jing , Li Haibei , Li Junwen , Yang Dong
Published: February 2022

Immunosuppressed patients are more likely to suffer from pneumonia, especiallyStreptococcusandEnterobacterpneumonia. Studies have demonstrated the existence of a complex and dynamic microbiota on the surface of human respiratory epithelial cells, both in healthy and diseased states. However, it is not clear whether the pneumonia in immunosuppressed patients is caused by inhaled oropharyngeal pathogens or abnormal proliferation of pulmonary proteobacteria. In this study, immunosuppressed model was made by intraperitoneal injection of cyclophosphamide and oropharyngeal saliva aspiration was simulated by oral and pharyngeal tracheal instillation of sterilized phosphate buffered saline (PBS). Furthermore, the effects of immunosuppression on the lung microbial community and its metabolism were investigated using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis. The 16S rRNA gene sequencing results showed that immunosuppression alone did not change the composition of pulmonary bacteria. Moreover, although the bacteria brought by sterilized PBS from oropharynx to lower respiratory tract changed the composition of the microflora in healthy and immunosuppressed rats, the change in the latter was more obvious. Metabolomic analysis revealed that the levels of pulmonary metabolites were disturbed in the immunosuppressed rats. The altered lung microbiota, includingStreptococcaceaeandEnterobacteriaceae, showed significant positive correlations with pulmonary metabolites. Our study suggested that the source of the pathogens of pneumonia in immunosuppressed rats wasviainhalation and explored the relationship between lung microbiome and metabolites in immunosuppressed rats. Our results provide the basis for the development of prevention and treatment strategies for pneumonia.
CRISPR-Cas13d Exhibits Robust Antiviral Activity Against Seneca Valley Virus
Authors: Zhang Yu-Yuan , Sun Ming-Xia , Lian Yuexiao , Wang Tong-Yun , Jia Mei-Yu , Leng Chaoliang , Chen Meng , Bai Yuan-Zhe , Meng Fandan , Cai Xue-Hui , Tang Yan-Dong
Published: February 2022

In recent years, Seneca Valley virus (SVV) as a newly identified pathogen of porcine vesicular disease spread quickly and has posed a potential threat to the swine industry in several countries resulting in economic losses. Considering the evolution of SVV, attention should be given to controlling SVV epidemics. So far there are no commercial vaccines or drugs available to combat SVV. Therefore, development of strategies for preventing and controlling SVV infection should be taken into account. In the current study, we evaluated whether the CRISPR-Cas13d system could be used as a powerful tool against SVV infection. Besides, selected crRNAs showed different capacity against SVV infection. Our study suggests the CRISPR-Cas13d system significantly inhibited SVV replication and exhibited potent anti-SVV activity. This knowledge may provide a novel alternative strategy to control epidemics of SVV in the future.
Variation of High and Low Nucleic Acid-Content Bacteria in Tibetan Ice Cores and Their Relationship to Black Carbon
Authors: Mao Guannan , Ji Mukan , Xu Baiqing , Liu Yongqin , Jiao Nianzhi
Published: February 2022

Nutrient enrichment caused by black carbon (BC) is a major ecological crisis in glacial ecosystems. The microbiological effects of BC were assessed in this study by using fluorescent fingerprinting assay based on flow cytometry (FCM) of bacterial communities with low (LNA) and high (HNA) nucleic acid-content bacteria. Here, we investigated a high-resolution temporal variation of bacterial abundance and LNA/HNA ratio in Tibetan ice cores. Our results revealed that bacterial abundance was proportional to the atmospheric BC on the glaciers. The shift of LNA functional groups to HNA functional groups in glaciers suggested BC emissions increased the proportion of highly active cells. In addition, distinct number of LNA and HNA functional groups was identified between the monsoon and non-monsoon seasons. Westerly winds with high amounts of BC accounted for high ratio of HNA functional groups during the non-monsoon season. In comparison, high moisture during the monsoon season decreased atmospheric BC loading, which increases the ratio of LNA functional groups. Correlations between BC and functional groups were very strong, showing that two functional groups may serve as early-warning indicators of microbiological effects of BC at low trophic level. Our approach provides a potential early-warning framework to study the influences of atmospheric BC on the glaciological community.
Modulation of Innate Antiviral Immune Response by Porcine Enteric Coronavirus
Authors: Zhang Kunli , Lin Sen , Li Jianhao , Deng Shoulong , Zhang Jianfeng , Wang Sutian
Published: February 2022

Host’s innate immunity is the front-line defense against viral infections, but some viruses have evolved multiple strategies for evasion of antiviral innate immunity. The porcine enteric coronaviruses (PECs) consist of porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), transmissible gastroenteritis coronavirus (TGEV), and swine acute diarrhea syndrome-coronavirus (SADS-CoV), which cause lethal diarrhea in neonatal pigs and threaten the swine industry worldwide. PECs interact with host cells to inhibit and evade innate antiviral immune responses like other coronaviruses. Moreover, the immune escape of porcine enteric coronaviruses is the key pathogenic mechanism causing infection. Here, we review the most recent advances in the interactions between viral and host’s factors, focusing on the mechanisms by which viral components antagonize interferon (IFN)-mediated innate antiviral immune responses, trying to shed light on new targets and strategies effective for controlling and eliminating porcine enteric coronaviruses.
The Prognostic Value of the Developmental Gene FZD6 in Young Saudi Breast Cancer Patients: A Biomarkers Discovery and Cancer Inducers OncoScreen Approach
Authors: Assidi Mourad , Buhmeida Abdelbaset , Al-Zahrani Maryam H. , Al-Maghrabi Jaudah , Rasool Mahmood , Naseer Muhammad I. , Alkhatabi Heba , Alrefaei Abdulmajeed F. , Zari Ali , Elkhatib Razan , Abuzenadah Adel , Pushparaj Peter N. , Abu-Elmagd Muhammad
Published: February 2022

Wnt signalling receptors, Frizzleds (FZDs), play a pivotal role in many cellular events during embryonic development and cancer. Female breast cancer (BC) is currently the worldwide leading incident cancer type that cause 1 in 6 cancer-related death. FZD receptors expression in cancer was shown to be associated with tumour development and patient outcomes including recurrence and survival. FZD6 received little attention for its role in BC and hence we analysed its expression pattern in a Saudi BC cohort to assess its prognostic potential and unravel the impacted signalling pathway. Paraffin blocks from approximately 405 randomly selected BC patients aged between 25 and 70 years old were processed for tissue microarray using an automated tissue arrayer and then subjected to FZD6 immunohistochemistry staining using the Ventana platform. Besides, Ingenuity Pathway Analysis (IPA) knowledgebase was used to decipher the upstream and downstream regulators of FZD6 in BC. TargetScan and miRabel target-prediction databases were used to identify the potential microRNA to regulate FZD6 expression in BC. Results showed that 60% of the BC samples had a low expression pattern while 40% showed a higher expression level. FZD6 expression analysis showed a significant correlation with tumour invasion (p < 0.05), and borderline significance with tumour grade (p = 0.07). FZD6 expression showed a highly significant association with the BC patients’ survival outcomes. This was mainly due to the overall patients’ cohort where tumours with FZD6 elevated expression showed higher recurrence rates (DFS, p < 0.0001, log-rank) and shorter survival times (DSS, p < 0.02, log-rank). Interestingly, the FZD6 prognostic value was more potent in younger BC patients as compared to those with late onset of the disease. TargetScan microRNA target-prediction analysis and validated by miRabel showed that FZD6 is a potential target for a considerable number of microRNAs expressed in BC. The current study demonstrates a potential prognostic role of FZD6 expression in young BC female patients and provides a better understanding of the involved molecular silencing machinery of the Wnt/FZD6 signalling. Our results should provide a better understanding of FZD6 role in BC by adding more knowledge that should help in BC prevention and theranostics.
SARS-CoV-2 Spike Protein Unlikely to Bind to Integrins via the Arg-Gly-Asp (RGD) Motif of the Receptor Binding Domain: Evidence From Structural Analysis and Microscale Accelerated Molecular Dynamics
Authors: Othman Houcemeddine , Messaoud Haifa Ben , Khamessi Oussema , Ben-Mabrouk Hazem , Ghedira Kais , Bharuthram Avani , Treurnicht Florette , Achilonu Ikechukwu , Sayed Yasien , Srairi-Abid Najet
Published: February 2022

The Receptor Binding Domain (RBD) of SARS-CoV-2 virus harbors a sequence of Arg-Gly-Asp tripeptide named RGD motif, which has also been identified in extracellular matrix proteins that bind integrins as well as other disintegrins and viruses. Accordingly, integrins have been proposed as host receptors for SARS-CoV-2. However, given that the microenvironment of the RGD motif imposes a structural hindrance to the protein-protein association, the validity of this hypothesis is still uncertain. Here, we used normal mode analysis, accelerated molecular dynamics microscale simulation, and protein-protein docking to investigate the putative role of RGD motif of SARS-CoV-2 RBD for interacting with integrins. We found, that neither RGD motif nor its microenvironment showed any significant conformational shift in the RBD structure. Highly populated clusters of RBD showed no capability to interact with the RGD binding site in integrins. The free energy landscape revealed that the RGD conformation within RBD could not acquire an optimal geometry to allow the interaction with integrins. In light of these results, and in the event where integrins are confirmed to be host receptors for SARS-CoV-2, we suggest a possible involvement of other residues to stabilize the interaction.
Influence of the Dynamically Disordered N-Terminal Tail Domain on the Amyloid Core Structure of Human Y145Stop Prion Protein Fibrils
Authors: Qi Zhe , Surewicz Krystyna , Surewicz Witold K. , Jaroniec Christopher P.
Published: February 2022

The Y145Stop mutant of human prion protein (huPrP23-144) is associated with a familial prionopathy and provides a convenient in vitro model for investigating amyloid strains and cross-seeding barriers. huPrP23-144 fibrils feature a compact and relatively rigid parallel in-register β-sheet amyloid core spanning ∼30 C-terminal amino acid residues (∼112–141) and a large ∼90-residue dynamically disordered N-terminal tail domain. Here, we systematically evaluate the influence of this dynamic domain on the structure adopted by the huPrP23-144 amyloid core region, by investigating using magic-angle spinning solid-state nuclear magnetic resonance (NMR) spectroscopy a series of fibril samples formed by huPrP23-144 variants corresponding to deletions of large segments of the N-terminal tail. We find that deletion of the bulk of the N-terminal tail, up to residue 98, yields amyloid fibrils with native-like huPrP23-144 core structure. Interestingly, deletion of additional flexible residues in the stretch 99–106 located outside of the amyloid core yields shorter heterogenous fibrils with fingerprint NMR spectra that are clearly distinct from those for full-length huPrP23-144, suggestive of the onset of perturbations to the native structure and degree of molecular ordering for the core residues. For the deletion variant missing residues 99–106 we show that native huPrP23-144 core structure can be “restored” by seeding the fibril growth with preformed full-length huPrP23-144 fibrils.
Thinking Outside the Frame: Impacting Genomes Capacity by Programmed Ribosomal Frameshifting
Authors: Riegger Ricarda J. , Caliskan Neva
Published: February 2022

Translation facilitates the transfer of the genetic information stored in the genome via messenger RNAs to a functional protein and is therefore one of the most fundamental cellular processes. Programmed ribosomal frameshifting is a ubiquitous alternative translation event that is extensively used by viruses to regulate gene expression from overlapping open reading frames in a controlled manner. Recent technical advances in the translation field enabled the identification of precise mechanisms as to how and when ribosomes change the reading frame on mRNAs containing cis-acting signals. Several studies began also to illustrate that trans-acting RNA modulators can adjust the timing and efficiency of frameshifting illuminating that frameshifting can be a dynamically regulated process in cells. Here, we intend to summarize these new findings and emphasize how it fits in our current understanding of PRF mechanisms as previously described.
Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy: New Data and Quantitative Meta-Analysis
Authors: Margraf Nils G. , Jensen-Kondering Ulf , Weiler Caroline , Leypoldt Frank , Maetzler Walter , Philippen Sarah , Bartsch Thorsten , Flüh Charlotte , Röcken Christoph , Möller Bettina , Royl Georg , Neumann Alexander , Brüggemann Norbert , Roeben Benjamin , Schulte Claudia , Bender Benjamin , Berg Daniela , Kuhlenbäumer Gregor
Published: February 2022

Background

To evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the modified Boston criteria in a retrospective multicentric cohort.

Methods

Beta-amyloid 1-40 (Aβ40), beta-amyloid 1-42 (Aβ42), total tau (t-tau), and phosphorylated tau 181 (p-tau181) were measured in 31 patients with probable CAA, 28 patients with Alzheimer’s disease (AD), and 30 controls. Receiver-operating characteristics (ROC) analyses were performed for the measured parameters as well as the Aβ42/40 ratio to estimate diagnostic parameters. A meta-analysis of all amenable published studies was conducted.

Results

In our data Aβ42/40 (AUC 0.88) discriminated best between CAA and controls while Aβ40 did not perform well (AUC 0.63). Differentiating between CAA and AD, p-tau181 (AUC 0.75) discriminated best in this study while Aβ40 (AUC 0.58) and Aβ42 (AUC 0.54) provided no discrimination. In the meta-analysis, Aβ42/40 (AUC 0.90) showed the best discrimination between CAA and controls followed by t-tau (AUC 0.79), Aβ40 (AUC 0.76), and p-tau181 (AUC 0.71). P-tau181 (AUC 0.76), Aβ40 (AUC 0.73), and t-tau (AUC 0.71) differentiated comparably between AD and CAA while Aβ42 (AUC 0.54) did not. In agreement with studies examining AD biomarkers, Aβ42/40 discriminated excellently between AD and controls (AUC 0.92–0.96) in this study as well as the meta-analysis.

Conclusion

The analyzed parameters differentiate between controls and CAA with clinically useful accuracy (AUC > ∼0.85) but not between CAA and AD. Since there is a neuropathological, clinical and diagnostic continuum between CAA and AD, other diagnostic markers, e.g., novel CSF biomarkers or other parameters might be more successful.
A Systematic Review of the Impact of Physical Exercise-Induced Increased Resting Cerebral Blood Flow on Cognitive Functions
Authors: Renke Maria B. , Marcinkowska Anna B. , Kujach Sylwester , Winklewski Paweł J.
Published: February 2022

Brain perfusion declines with aging. Physical exercise represents a low-cost accessible form of intervention to increase cerebral blood flow; however, it remains unclear if exercise-induced amelioration of brain perfusion has any impact on cognition. We aimed to provide a state-of-the art review on this subject. A comprehensive search of the PubMed (MEDLINE) database was performed. On the basis of the inclusion and exclusion criteria, 14 studies were included in the analysis. Eleven of the studies conducted well-controlled exercise programs that lasted 12–19 weeks for 10–40 participants and two studies were conducted in much larger groups of subjects for more than 5 years, but the exercise loads were indirectly measured, and three of them were focused on acute exercise. Literature review does not show a direct link between exercise-induced augmentation of brain perfusion and better cognitive functioning. However, in none of the reviewed studies was such an association the primary study endpoint. Carefully designed clinical studies with focus on cognitive and perfusion variables are needed to provide a response to the question whether exercise-induced cerebral perfusion augmentation is of clinical importance.
Identification, Analysis and Characterization of Base Units of Bird Vocal Communication: The White Spectacled Bulbul (Pycnonotus xanthopygos) as a Case Study
Authors: Marck Aya , Vortman Yoni , Kolodny Oren , Lavner Yizhar
Published: February 2022

Animal vocal communication is a broad and multi-disciplinary field of research. Studying various aspects of communication can provide key elements for understanding animal behavior, evolution, and cognition. Given the large amount of acoustic data accumulated from automated recorders, for which manual annotation and analysis is impractical, there is a growing need to develop algorithms and automatic methods for analyzing and identifying animal sounds. In this study we developed an automatic detection and analysis system based on audio signal processing algorithms and deep learning that is capable of processing and analyzing large volumes of data without human bias. We selected the White Spectacled Bulbul (Pycnonotus xanthopygos) as our bird model because it has a complex vocal communication system with a large repertoire which is used by both sexes, year-round. It is a common, widespread passerine in Israel, which is relatively easy to locate and record in a broad range of habitats. Like many passerines, the Bulbul’s vocal communication consists of two primary hierarchies of utterances, syllables and words. To extract each of these units’ characteristics, the fundamental frequency contour was modeled using a low degree Legendre polynomial, enabling it to capture the different patterns of variation from different vocalizations, so that each pattern could be effectively expressed using very few coefficients. In addition, a mel-spectrogram was computed for each unit, and several features were extracted both in the time-domain (e.g., zero-crossing rate and energy) and frequency-domain (e.g., spectral centroid and spectral flatness). We applied both linear and non-linear dimensionality reduction algorithms on feature vectors and validated the findings that were obtained manually, namely by listening and examining the spectrograms visually. Using these algorithms, we show that the Bulbul has a complex vocabulary of more than 30 words, that there are multiple syllables that are combined in different words, and that a particular syllable can appear in several words. Using our system, researchers will be able to analyze hundreds of hours of audio recordings, to obtain objective evaluation of repertoires, and to identify different vocal units and distinguish between them, thus gaining a broad perspective on bird vocal communication.
Neuroprotective Effects of Exogenous Irisin in Kainic Acid-Induced Status Epilepticus
Authors: Cheng Yao , Cui Yaru , Zhai Yujie , Xin Wenyu , Yu Yan , Liang Jia , Li Shucui , Sun Hongliu
Published: February 2022

Graphical Abstract

Our study confirmed significant anti-oxidative stress and neuroprotective effects of exogenous irisin in KA-induced SE. Moreover, the BDNF/UCP2 pathway may contribute to the mechanism underlying the neuroprotective effects of irisin.
Vav3-Deficient Astrocytes Enhance the Dendritic Development of Hippocampal Neurons in an Indirect Co-culture System
Authors: Wegrzyn David , Zokol Josephine , Faissner Andreas
Published: February 2022

Vav proteins belong to the class of guanine nucleotide exchange factors (GEFs) that catalyze the exchange of guanosine diphosphate (GDP) by guanosine triphosphate (GTP) on their target proteins. Here, especially the members of the small GTPase family, Ras homolog family member A (RhoA), Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division control protein 42 homolog (Cdc42) can be brought into an activated state by the catalytic activity of Vav-GEFs. In the central nervous system (CNS) of rodents Vav3 shows the strongest expression pattern in comparison to Vav2 and Vav1, which is restricted to the hematopoietic system. Several studies revealed an important role of Vav3 for the elongation and branching of neurites. However, little is known about the function of Vav3 for other cell types of the CNS, like astrocytes. Therefore, the following study analyzed the effects of a Vav3 knockout on several astrocytic parameters as well as the influence of Vav3-deficient astrocytes on the dendritic development of cultured neurons. For this purpose, an indirect co-culture system of native hippocampal neurons and Vav3-deficient cortical astrocytes was used. Interestingly, neurons cultured in an indirect contact with Vav3-deficient astrocytes showed a significant increase in the dendritic complexity and length after 12 and 17 days in vitro (DIV). Furthermore, Vav3-deficient astrocytes showed an enhanced regeneration in the scratch wound heal assay as well as an altered profile of released cytokines with a complete lack of CXCL11, reduced levels of IL-6 and an increased release of CCL5. Based on these observations, we suppose that Vav3 plays an important role for the development of dendrites by regulating the expression and the release of neurotrophic factors and cytokines in astrocytes.
RateML: A Code Generation Tool for Brain Network Models
Authors: van der Vlag Michiel , Woodman Marmaduke , Fousek Jan , Diaz-Pier Sandra , Pérez Martín Aarón , Jirsa Viktor , Morrison Abigail
Published: February 2022

Whole brain network models are now an established tool in scientific and clinical research, however their use in a larger workflow still adds significant informatics complexity. We propose a tool, RateML, that enables users to generate such models from a succinct declarative description, in which the mathematics of the model are described without specifying how their simulation should be implemented. RateML builds on NeuroML’s Low Entropy Model Specification (LEMS), an XML based language for specifying models of dynamical systems, allowing descriptions of neural mass and discretized neural field models, as implemented by the Virtual Brain (TVB) simulator: the end user describes their model’s mathematics once and generates and runs code for different languages, targeting both CPUs for fast single simulations and GPUs for parallel ensemble simulations. High performance parallel simulations are crucial for tuning many parameters of a model to empirical data such as functional magnetic resonance imaging (fMRI), with reasonable execution times on small or modest hardware resources. Specifically, while RateML can generate Python model code, it enables generation of Compute Unified Device Architecture C++ code for NVIDIA GPUs. When a CUDA implementation of a model is generated, a tailored model driver class is produced, enabling the user to tweak the driver by hand and perform the parameter sweep. The model and driver can be executed on any compute capable NVIDIA GPU with a high degree of parallelization, either locally or in a compute cluster environment. The results reported in this manuscript show that with the CUDA code generated by RateML, it is possible to explore thousands of parameter combinations with a single Graphics Processing Unit for different models, substantially reducing parameter exploration times and resource usage for the brain network models, in turn accelerating the research workflow itself. This provides a new tool to create efficient and broader parameter fitting workflows, support studies on larger cohorts, and derive more robust and statistically relevant conclusions about brain dynamics.
General Anesthesia vs. Local Anesthesia During Endovascular Treatment for Acute Large Vessel Occlusion: A Propensity Score-Matched Analysis
Authors: Han Hongxing , Wang Yu , Wang Hao , Sun Hongyang , Wang Xianjun , Gong Jian , Huo Xiaochuan , Zhu Qiyi , Che Fengyuan
Published: February 2022

Objective

To date, no consensus still exists on the anesthesia strategy of endovascular treatment (EVT) for acute ischemic stroke (AIS) due to large vessel occlusion (LVO). We aimed to compare the 90-day outcomes, puncture-to-recanalization time (PRT), successful recanalization rate, and symptomatic intracranial hemorrhage (sICH) of patients undergoing general anesthesia (GA) or local anesthesia (LA) ± conscious sedation (CS) during the procedure.

Methods

We selected patients from the Acute Ischemic Stroke Cooperation Group of Endovascular Treatment (ANGEL) registry and divided them into the GA group and the LA ± CS group. The two groups underwent 1:1 matching under propensity score matching (PSM) analysis. Then, we compared the primary outcome including the 90-day modified Rankin Scale (mRS) 0–2, secondary outcome including the 90-day mRS, the 90-day mRS 0–1, the 90-day mRS 0–3, PRT, and successful recanalization rate as well as the safety outcome including sICH, any ICH, and 90-day mRS 6.

Results

Among the 705 enrolled patients, 263 patients underwent GA and 442 patients underwent LA ± CS. After 1:1 PSM according to the baseline characteristics, each group has 216 patients. Patients with GA had the higher median 90-day mRS [3 (1–5) vs. 2 (1–4), p < 0.001], the lower 90-day mRS 0–2 rate (43.5 vs. 56.5%, p = 0.007), higher mortality (19.9 vs.10.2%, p = 0.005), and longer PRT [92 (60–140) vs. 70 (45–103) min, p < 0.001]. There were no differences in sICH and successful recanalization rate between both the groups.

Conclusion

In the real-world setting, LA ± CS might provide more outcomes benefits than GA in patients with AIS-LVO during the procedure.
Orchestration of Ion Channels and Transporters in Neocortical Development and Neurological Disorders
Authors: Bando Yuki , Ishibashi Masaru , Yamagishi Satoru , Fukuda Atsuo , Sato Kohji
Published: February 2022

Electrical activity plays crucial roles in neural circuit formation and remodeling. During neocortical development, neurons are generated in the ventricular zone, migrate to their correct position, elongate dendrites and axons, and form synapses. In this review, we summarize the functions of ion channels and transporters in neocortical development. Next, we discuss links between neurological disorders caused by dysfunction of ion channels (channelopathies) and neocortical development. Finally, we introduce emerging optical techniques with potential applications in physiological studies of neocortical development and the pathophysiology of channelopathies.
Neural Mechanisms of Working Memory Accuracy Revealed by Recurrent Neural Networks
Authors: Xie Yuanqi , Liu Yichen Henry , Constantinidis Christos , Zhou Xin
Published: February 2022

Understanding the neural mechanisms of working memory has been a long-standing Neuroscience goal. Bump attractor models have been used to simulate persistent activity generated in the prefrontal cortex during working memory tasks and to study the relationship between activity and behavior. How realistic the assumptions of these models are has been a matter of debate. Here, we relied on an alternative strategy to gain insights into the computational principles behind the generation of persistent activity and on whether current models capture some universal computational principles. We trained Recurrent Neural Networks (RNNs) to perform spatial working memory tasks and examined what aspects of RNN activity accounted for working memory performance. Furthermore, we compared activity in fully trained networks and immature networks, achieving only imperfect performance. We thus examined the relationship between the trial-to-trial variability of responses simulated by the network and different aspects of unit activity as a way of identifying the critical parameters of memory maintenance. Properties that spontaneously emerged in the artificial network strongly resembled persistent activity of prefrontal neurons. Most importantly, these included drift of network activity during the course of a trial that was causal to the behavior of the network. As a consequence, delay period firing rate and behavior were positively correlated, in strong analogy to experimental results from the prefrontal cortex. These findings reveal that delay period activity is computationally efficient in maintaining working memory, as evidenced by unbiased optimization of parameters in artificial neural networks, oblivious to the properties of prefrontal neurons.
Comprehensive Exploration of Tumor Microenvironment Modulation Based on the ESTIMATE Algorithm in Bladder Urothelial Carcinoma Microenvironment
Authors: Chen Ji , Lv Boyu , Zhan Yating , Zhu Kai , Zhang Rongrong , Chen Bo , Jin Yan , Li Yeping , Zheng Jianjian , Lin Changyong
Published: February 2022

Recently, the tumor microenvironment (TME) has been reported to be closely related to the tumor initiation, progression, and prognosis. Bladder urothelial carcinoma (BLCA), one of the most common subtypes of bladder cancer worldwide, has been associated with increased morbidity and mortality in the past decade. However, whether the TME status of BLCA contributes to the prediction of BLCA prognosis still remains uncertain. In this study, the ESTIMATE algorithms were used to estimate the division of immune and stromal components in 406 BLCA samples downloaded from The Cancer Genome Atlas database (TCGA). Based on the comparison between ESTIMATE scores, the differentially expressed genes (DEGs) were selected. Using the univariate Cox regression analysis, prognosis-related DEGs were further identified (p < 0.05). The LASSO regression analysis was then used to screen 11 genes that were highly related to the TME of BLCA to generate a novel prognostic gene signature. The following survival analyses showed that this signature could effectively predict the prognosis of BLCA. The clinical value of this signature was further verified in an external cohort obtained from the First Affiliated Hospital of Wenzhou Medical University (n = 120). Based on the stage-correlation analysis and differential expression analysis, IGF1 and MMP9 were identified as the hub genes in the signature. Additionally, using CIBERSORT algorithms, we found that both IGF1 and MMP9 were significantly associated with immune infiltration. Collectively, a novel TME-related prognostic signature contributes to accurately predict the prognosis of BLCA.
Cetuximab Combined With Sonodynamic Therapy Achieves Dual-Modal Image Monitoring for the Treatment of EGFR-Sensitive Non-Small-Cell Lung Cancer
Authors: Qiu Guanhua , Xue Lianfang , Zhu Xiaoqi , Lu Xiuxin , Liu Lidong , Wang Zhonghai , Li Xiangdong , Huang Cuiqing , Liu Junjie
Published: February 2022

Background

Blocking signaling by epidermal growth factor receptor (EGFR), can effectively inhibit the proliferation and differentiation of non-small-cell lung cancer (NSCLC). Additionally, an increasing number of NSCLC patients have treatment limitations caused by EGFR overexpression or mutations. Therefore, we constructed a nanotherapy platform consisting of cetuximab (CTX) to target EGFR-sensitive NSCLC with an iron tetroxide core loading the sound-sensitive agent IR780 for dual-mode imaging diagnosis by combining targeting and sonodynamic therapy (SDT) to reshape the tumor microenvironment (TME), enhance the SDT antitumor effects and improve the therapeutic effects of EGFR sensitivity.

Methods

IR780@INPs were prepared by reverse rotary evaporation, CTX was adsorbed/coupled to obtain IR780@INPs-CTX, and the morphology and structure were characterized. Intracellular ROS levels and cell apoptosis first verified its killing effects against tumor cells. Then, a nude mouse lung cancer subcutaneous xenograft model was established with HCC827 cells. A real-time fluorescence IVIS imaging system determined the targeting and live distribution of IR780@INPs-CTX in the transplanted tumors and the imaging effects of the T2 sequence of the INPs by magnetic resonance imaging (MRI) 0 h, 2 h, 4 h and 6 h after administration to confirm drug efficacy.

Results

In vitro, US+IR780@INPs-CTX produced a large amount of ROS after SDT to induce cell apoptosis, and significant cell death after live/dead staining was observed. In vivo fluorescence imaging showed the IR780@INPs-CTX was mainly concentrated in the tumor with a small amount in the liver. MRI displayed rapid enrichment of the IR780@INPs into tumor tissue 0h after injection and the T2 signal intensity gradually decreases with time without obvious drug enrichment in the surrounding tissues. In vivo, at the end of treatment, the US+IR780@INPs-CTX group showed disappearance or a continued decrease in tumor volume, indicating strong SDT killing effects.

Conclusion

The combination of CTX and SDT is expected to become a novel treatment for EGFR-sensitive NSCLC.
Tumor-Associated Macrophages: Key Players in Triple-Negative Breast Cancer
Authors: Qiu Xia , Zhao Tianjiao , Luo Ran , Qiu Ran , Li Zhaoming
Published: February 2022

Triple negative breast cancer (TNBC) refers to the subtype of breast cancer which is negative for ER, PR, and HER-2 receptors. Tumor-associated macrophages (TAMs) refer to the leukocyte infiltrating tumor, derived from circulating blood mononuclear cells and differentiating into macrophages after exuding tissues. TAMs are divided into typical activated M1 subtype and alternately activated M2 subtype, which have different expressions of receptors, cytokines and chemokines. M1 is characterized by expressing a large amount of inducible nitric oxide synthase and TNF-α, and exert anti-tumor activity by promoting pro-inflammatory and immune responses. M2 usually expresses Arginase 1 and high levels of cytokines, growth factors and proteases to support their carcinogenic function. Recent studies demonstrate that TAMs participate in the process of TNBC from occurrence to metastasis, and might serve as potential biomarkers for prognosis prediction.
Cell Division Cycle-Associated Genes Are Potential Immune Regulators in Nasopharyngeal Carcinoma
Authors: Jiang Danxian , Li Yin , Cao Jinxin , Sheng Lianghe , Zhu Xinhai , Xu Meng
Published: February 2022

Background

Cell division cycle-associated (CDCA) gene family is essential to cell cycle regulation. Numerous studies have illuminated that dysfunction of CDCA genes may not only lead to uncontrolled cell proliferation resulting in tumorigenesis but also influence immune cell infiltration in tumors. However, the role of the CDCA gene family on the prognosis and immune infiltration in nasopharyngeal carcinoma (NPC) remains to be unclear.

Methods

SBC human ceRNA array V1.0 was used to measure mRNA expression in three pairs of NPC tissues and nasopharyngitis tissues. The expression of CDCA8 was confirmed in an IHC microarray containing 130 NPC patients. Two external GEO cohorts were enrolled for further analysis. Prognosis analysis was performed using the Kaplan–Meier method. Gene set enrichment analysis (GSEA) was applied to explore the potential mechanism of CDCA genes in NPC. The relationship between CDCA gene family and immune infiltration in NPC was evaluated using the Xcell tool.

Results

CDCA genes were broadly upregulated in NPC tissues compared to nasopharyngitis tissues, and high expression of CDCA3/5/8 indicated worse prognosis in NPC. Besides cell cycle pathways, we found that CDCA3/5/8 were involved in multiple immune-related pathways. Overexpression of CDCA8 was strongly associated with less infiltration of CD8+ T cells and more infiltration of CD4+ Th1 cells and was negatively correlated with immune checkpoint blockade (ICB)-related genes.

Conclusion

CDCA gene family was upregulated in NPC, and their expressions were associated with adverse prognosis. High expression of CDCA8 was associated not only with poor prognosis, but also with less immune infiltration and downregulation of ICB-related genes in NPC.