bluuebunny/crossref_metadata_2025 huggingface dataset:
Geography, niches, and transportation influence bovine respiratory microbiome and health
Authors: Chai Jianmin , Liu Xinting , Usdrowski Hunter , Deng Feilong , Li Ying , Zhao Jiangchao
Published: September 2022

Bovine respiratory disease (BRD), one of the most common and infectious diseases in the beef industry, is associated with the respiratory microbiome and stressors of transportation. The impacts of the bovine respiratory microbiota on health and disease across different geographic locations and sampling niches are poorly understood, resulting in difficult identification of BRD causes. In this study, we explored the effects of geography and niches on the bovine respiratory microbiome and its function by re-analyzing published metagenomic datasets and estimated the main opportunistic pathogens that changed after transportation. The results showed that diversity, composition, structure, and function of the bovine nasopharyngeal microbiota were different across three worldwide geographic locations. The lung microbiota also showed distinct microbial composition and function compared with nasopharyngeal communities from different locations. Although different signature microbiota for each geographic location were identified, a module with co-occurrence of Mycoplasma species was observed in all bovine respiratory communities regardless of geography. Moreover, transportation, especially long-distance shipping, could increase the relative abundance of BRD-associated pathogens. Lung microbiota from BRD calves shaped clusters dominated with different pathogens. In summary, geography, sampling niches, and transportation are important factors impacting the bovine respiratory microbiome and disease, and clusters of lung microbiota by different bacterial species may explain BRD pathogenesis, suggesting the importance of a deeper understanding of bovine respiratory microbiota in health.
Materializing the abstract: Understanding AI by game jamming
Authors: Falk Jeanette , Inie Nanna
Published: September 2022

In this article, we argue that game jam formats are uniquely suited to engage participants in learning about artificial intelligence (AI) as a design material because of four factors which are characteristic of game jams: 1) Game jams provide an opportunity for hands-on, interactive prototyping, 2) Game jams encourage playful participation, 3) Game jams encourage creative combinations of AI and game development, and 4) Game jams offer understandable goals and evaluation metrics for AI. We support the argument with an interview study conducted with three AI experts who had all organized game jams with a focus on using AI in game development. Based on a thematic analysis of the expert interviews and a theoretical background of Schön's work on educating the reflective practitioner, we identified the four abovementioned factors as well as four recommendations for structuring and planning an AI-focused game jam: 1) Aligning repertoires, 2) Supporting playful participation, 3) Supporting ideation, and 4) Facilitating evaluation and reflection. Our contribution is motivated by the recent discourse on general challenges and recommendations of teaching AI identified by related literature, here under the long and intertwined history of games and AI in general. The article presents an initial discussion of the value of game jam formats for learning about AI and which factors need to be considered in regard to this specific learning goal.
Detecting illegal wildlife trafficking via real time tomography 3D X-ray imaging and automated algorithms
Authors: Pirotta Vanessa , Shen Kaikai , Liu Sheldon , Phan Ha Tran Hong , O’Brien Justine K. , Meagher Phoebe , Mitchell Jessica , Willis Joel , Morton Ed
Published: September 2022

Wildlife trafficking is a global problem involving the deliberate and illegal transport of wildlife across international borders. Animals are either removed directly from their natural environment or bred specifically to fuel demand driven by activities such as the illegal pet trade or for purported medicinal reasons. In Australia, wildlife trafficking poses a serious environmental and biosecurity risk through the removal of native species and the introduction of exotic invasive wildlife. This has the potential to impact the natural ecosystem and Australia’s multibillion-dollar agricultural industry. To help detect and restrict this activity, innovative technologies such as 3D X-ray CT technology using Real Time Tomography has been trialed to create wildlife detection algorithms for deployment across Australian mail/traveller luggage pathways. Known species of trafficked Australian wildlife and additional model species of exotics were scanned to create an image reference library for algorithm detection. A total of 294 scans from 13 species of lizards, birds and fish were used to develop initial wildlife algorithms with a detection rate of 82% with a false alarm rate at 1.6%. In combination with human and biosecurity dog detection, this innovative technology is a promising complementary platform for wildlife detection at Australian international borders, with potential worldwide applications.
Impact of concomitant COVID-19 on the outcome of patients with acute myocardial infarction undergoing coronary artery angiography
Authors: Terlecki Michał , Wojciechowska Wiktoria , Klocek Marek , Olszanecka Agnieszka , Bednarski Adam , Drożdż Tomasz , Pavlinec Christopher , Lis Paweł , Zając Maciej , Rusinek Jakub , Siudak Zbigniew , Bartuś Stanisław , Rajzer Marek
Published: September 2022

Background

The impact of COVID-19 on the outcome of patients with MI has not been studied widely. We aimed to evaluate the relationship between concomitant COVID-19 and the clinical course of patients admitted due to acute myocardial infarction (MI).

Methods

There was a comparison of retrospective data between patients with MI who were qualified for coronary angiography with concomitant COVID-19 and control group of patients treated for MI in the preceding year before the onset of the pandemic. In-hospital clinical data and the incidence of death from any cause on 30 days were obtained.

Results

Data of 39 MI patients with concomitant COVID-19 (COVID-19 MI) and 196 MI patients without COVID-19 in pre-pandemic era (non-COVID-19 MI) were assessed. Compared with non-COVID-19 MI, COVID-19 MI was in a more severe clinical state on admission (lower systolic blood pressure: 128.51 ± 19.76 vs. 141.11 ± 32.47 mmHg, p = 0.024), higher: respiratory rate [median (interquartile range), 16 (14–18) vs. 12 (12–14)/min, p < 0.001], GRACE score (178.50 ± 46.46 vs. 161.23 ± 49.74, p = 0.041), percentage of prolonged (>24 h) time since MI symptoms onset to coronary intervention (35.9 vs. 15.3%; p = 0.004), and cardiovascular drugs were prescribed less frequently (beta-blockers: 64.1 vs. 92.8%, p = 0.009), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers: 61.5 vs. 81.1%, p < 0.001, statins: 71.8 vs. 94.4%, p < 0.001). Concomitant COVID-19 was associated with seven-fold increased risk of 30-day mortality (HR 7.117; 95% CI: 2.79–18.14; p < 0.001).

Conclusion

Patients admitted due to MI with COVID-19 have an increased 30-day mortality. Efforts should be focused on infection prevention and implementation of optimal management to improve the outcomes in those patients.
Neutrophil-to-lymphocyte Ratio is Associated with LV Diastolic Dysfunction in the Overt Hyperthyroid Patients
Authors: Zhang Huan , Zhang Jiaoyue , Li Huan , Bi Yaqiong , Wang Linfang , Li Yuming
Published: September 2022

Background

Recent studies have shown that the neutrophil-to-lymphocyte ratio (NLR) has gradually been identified as a more reliable marker of inflammation, with predictive value for the development of many diseases. However, its association with left ventricular (LV) diastolic dysfunction in overt hyperthyroid patients is unclear. Here, we aimed to explore the relationship between NLR and LV diastolic dysfunction in overt hyperthyroid patients.

Methods

For this study, we retrospected the consecutive medical files of 350 overt hyperthyroid patients. Their medical data and laboratory findings were recorded. According to the presence or absence of LV diastolic dysfunction, the patients with overt hyperthyroidism were divided into two groups. One group with LV diastolic dysfunction included 104 patients and another group with non-LV diastolic dysfunction included 246 patients. The NLR values between the two groups were compared, and the relationship between NLR levels and the prevalence of LV diastolic dysfunction was also explored.

Results

The NLR value in LV diastolic dysfunction group in the overt hyperthyroid subjects was significantly higher than that in non-LV diastolic dysfunction group [1.100 (0.907-1.580) vs 1.000 (0.761-1.405), P=0.016]. The prevalence of LV diastolic dysfunction in Low- (NLR<0.879), Medium- (0.879< NLR<1.287), and High- (NLR >1.287) NLR level groups were 20.9%, 32.5% and 35.7% respectively. Moreover, increased NLR is associated with increased prevalence of LV diastolic dysfunction, and after adjustment for potential associated factors, NLR remained significantly associated with LV diastolic dysfunction. (OR = 11.753, 95%CI = 1.938-71.267, P = 0.007).

Conclusions

Our findings demonstrated that the NLR was associated with LV diastolic dysfunction in the overt hyperthyroid patients, and the prevalence of LV diastolic dysfunction may be positively correlated with NLR levels.
Latent Autoimmune Diabetes in Adults (LADA): From Immunopathogenesis to Immunotherapy
Authors: Hu Jingyi , Zhang Rong , Zou Hailan , Xie Lingxiang , Zhou Zhiguang , Xiao Yang
Published: September 2022

Latent autoimmune diabetes in adults (LADA) is a type of diabetes characterized by slow autoimmune damage of pancreatic β cells without insulin treatment in the early clinical stage. There are differences between LADA and classical type 1 diabetes (T1D) and type 2 diabetes (T2D) in genetic background, autoimmune response, rate of islet function decline, clinical metabolic characteristics, and so on. The disease progression and drug response of patients with LADA are closely related to the level of islet autoimmunity, thus exploring the pathogenesis of LADA is of great significance for its prevention and treatment. Previous studies reported that adaptive immunity and innate immunity play a critical role in the etiology of LADA. Recent studies have shown that the intestinal microbiota which impacts host immunity hugely, participates in the pathogenesis of LADA. In addition, the progression of autoimmune pancreatic β cell destruction in LADA is slower than in classical T1D, providing a wider window of opportunities for intervention. Therefore, therapies including antidiabetic drugs with immune-regulation effects and immunomodulators could contribute to promising interventions for LADA. We also shed light on potential interventions targeting the gut microbiota and gut-associated immunity, which may be envisaged to halt or delay the process of autoimmunity in LADA.
The willingness to pay for agricultural irrigation water and the influencing factors in the Dujiangyan irrigation area: An empirical double-hurdle model analysis
Authors: Tang Hong , Yang Zhongjian , Guo Zepeng , Yang Chuan , Huang Feng , Ran Ruiping
Published: September 2022

Water prices are an efficient way to manage and allocate water resources. A scientific and reasonable water price standard can assist farmers to optimize their water allocations and ensure an efficient agricultural water system. However, under the current agricultural water pricing policy, it is difficult for water resource management departments to achieve sustainable operation because of unreasonable water price standards and the unwillingness of farmers to pay for agricultural irrigation water. Therefore, to ensure the sustainable management of agricultural water departments, it is important to design scientific and reasonable water price mechanisms that give full play to the regulatory role of agricultural water prices and encourage farmers to pay agricultural water fees. Based on survey data from 335 farming households in the Dujiangyan Irrigation Area, Sichuan, China, in 2019, a double-hurdle model was used to assess the willingness to pay for agricultural irrigation water. The willingness to pay was positively impacted by age, education level, willingness to participate, the arable land area, the water fee proportion, and water-saving awareness but negatively impacted by the water price standard and the farmers’ perceptions of the water price standard. Based on these results, to encourage farmers to participate in and afford agricultural water payments and to give full play to the water price adjustment function and other countermeasures, it is proposed that 1) water-saving awareness training be strengthened; 2) agricultural modernization be promoted; and 3) water price standards be scientifically and rationally formulated.
Variation in TAS2R receptor genes explains differential bitterness of two common antibiotics
Authors: Nolden Alissa A. , Hayes John E. , Feeney Emma L.
Published: September 2022

For pharmaceuticals to deliver their full benefits with maximum efficacy, patients need to follow recommended dosing schedules, in terms of amount and frequency. Unfortunately, the aversive taste of many drugs, especially bitterness, can reduce patient compliance in oral liquid formulations. Given common genetic differences in bitter taste receptor genes (TAS2Rs), some individuals may be at increased risk for poor compliance due to heightened bitterness that becomes a barrier to proper use. Here we report on the sensory profile of two antibiotics, chloramphenicol and ofloxacin, investigating whether bitterness intensity associates with nominally functional TAS2R variants. Participants (n = 143) rated suprathreshold intensity on a general Labeled Magnitude Scale (gLMS) for chloramphenicol and ofloxacin; propylthiouracil (PROP) was included as a control, given robust prior associations with TAS2R38 variants. The dominant sensation from chloramphenicol and ofloxacin was bitterness, falling just below “moderate” on a gLMS. TAS2R38 diplotype associated with variable bitterness of chloramphenicol and PROP, but not ofloxacin. The bitterness of ofloxacin associated with a TAS2R9 SNP (V187A). This pilot study provides novel evidence on differences in the bitterness from two antibiotics, which are associated with TAS2R variants. Improved understanding of individualized barriers to patient compliance, especially for oral formulations, can guide future efforts to optimize delivery systems for improved compliance.
Endoscopic ultrasound guided therapy of gastric varices: Initial experience in the Arab world (with video)
Authors: Alali Ali A. , Hashim Ahmad , Alkandari Asma
Published: September 2022

Background and objectives

Gastric varices (GV) bleeding is a catastrophic complication of portal hypertension and is associated with significant morbidity and mortality. There are limited effective therapeutic interventions for the management of bleeding GV. Recently, EUS-guided therapy has been shown to be effective and safe intervention for such patients. However, there are no data to describe the feasibility and safety of EUS-guided therapy for GV in Arab population. The aim of this study is to describe our initial experience of EUS-guided therapy for GV in Kuwait.

Methods

A case-series of patients that underwent EUS-guided therapy for clinically significant GV. All patients underwent EUS-guided therapy including Cyanoacrylate (CYA) injection with or without coil embolization. Patients were followed post procedure to document GV obliteration and monitor for any adverse events.

Results

In total, 15 patients were included in this study (80% male) with mean age of 58 ± 12 years. The main indication for therapy was active GV bleeding (53.3%) followed by secondary prophylaxis (33.3%). Most patients had GOV-2 (80%) with mean GV size of 24.9 ± 7.9 mm. Combined EUS coil-CYA was used in most patients (80%), mean volume of CYA injected was 1.5 ± 0.74ml and mean number coils used of 1.5 ± 1.4. The technical success rate was 100% and all patients achieved GV obliteration after a median of 1 session (range 1-2). There were no major adverse events.

Conclusion

Among Arab population with portal hypertension, EUS-guided therapy is highly effective and safe option for the managements of clinically significant GV.
Evidence of maternal transfer of antigen-specific antibodies in serum and breast milk to infants at high-risk of S. pneumoniae and H. influenzae disease
Authors: Martinovich Kelly M. , Seppanen Elke J. , Bleakley Amy S. , Clark Sharon L. , Andrews Ross M. , Richmond Peter C. , Binks Michael J. , Thornton Ruth B. , Kirkham Lea-Ann S.
Published: September 2022

Introduction

Children in low-mid income countries, and First Nations children in high-income countries, experience disproportionately high rates of Streptococcus pneumoniae and Haemophilus influenzae infections and diseases including pneumonia and otitis media. We previously observed that infants from Papua New Guinea had no evidence of waning maternal immunity for H. influenzae-specific antibodies. In this study, we assessed S. pneumoniae and H. influenzae antibody titres in Australian First Nation mothers and infants to determine antigen-specific antibody ontogenies and whether H. influenzae antibody titres in infants were due to low maternal antibody titres or lack of placental transfer.

Methods

Breast milk, infant nasopharyngeal swabs and ear assessment data were collected 1-, 2-, 7-months post-birth as well as maternal, cord and 7-month-old infant sera, from 85 Australian Aboriginal and Torres Strait Islander mother-infant pairs. Serum IgG and breast milk IgG and IgA antibody titres to S. pneumoniae antigens (PspA1, PspA2, CbpA, Ply) and H. influenzae antigens (PD, ChimV4, OMP26, rsPilA) were measured.

Results

IgG titres in maternal and cord sera were similar for all antigens, except Ply (higher in cord; p=0.004). Sera IgG titres at 7-months of age were lower than cord sera IgG titres for all S. pneumoniae antigens (p<0.001). Infant sera IgG titres were higher than cord sera for H. influenzae PD (p=0.029), similar for OMP26 (p=0.817) and rsPilA (p=0.290), and lower for ChimV4 (p=0.004). Breast milk titres were similar for all antigens at 1, 2 and 7-months except OMP26 IgA (lower at 7-months than 1-month; p=0.035), PspA2 IgG (p=0.012) and Ply IgG that increased by 7-months (p=0.032). One third of infants carried nontypeable Haemophilus influenzae (NTHi), 45% carried S. pneumoniae and 52% had otitis media (OM) observed at least once over the 7-months. 73% of infants who carried either S. pneumoniae or NTHi, also had otitis media observed.

Conclusions

Similarities between maternal and cord IgG titres, and absence of waning, support a lack of maternal H. influenzae IgG antibodies available for cross-placental transfer. Increased maternal anti-PD IgG could offer some protection from early carriage with NTHi, and maternal immunisation strategies should be considered for passive-active immunisation of infants to protect against S. pneumoniae and H. influenzae diseases.

Trial registration

ClinicalTrials.gov NCT00714064 and NCT00310349.
Inactivated vaccine Covaxin/BBV152: A systematic review
Authors: Ahmed Tousief Irshad , Rishi Saqib , Irshad Summaiya , Aggarwal Jyoti , Happa Karan , Mansoor Sheikh
Published: September 2022

We systematically reviewed and summarized studies focusing on Bharat Biotech’s Whole Virion Inactivated Corona Virus Antigen BBV152 (Covaxin), which is India’s indigenous response to fighting the SARS-CoV-2 pandemic. Studies were searched for data on the efficacy, immunogenicity, and safety profile of BBV152. All relevant studies published up to March 22, 2022, were screened from major databases, and 25 studies were eventually inducted into the systematic review. The studies focused on the virus antigen (6 μg) adjuvanted with aluminium hydroxide gel and/or Imidazo quinolin gallamide (IMDG), aTLR7/8 agonist. Pre-clinical, phase I, and II clinical trials showed appreciable immunogenicity. Both neutralizing and binding antibody titers were significant and T cell responses were Th1-biased. Phase III trials on the 6 μg +Algel-IMDG formulation showed a 93.4% efficacy against severe COVID-19. Data from the trials revealed an acceptable safety profile with mostly mild-moderate local and systemic adverse events. No serious adverse events or fatalities were seen, and most studies reported milder and lesser adverse events with Covaxin when compared with other vaccines, especially Oxford-Astra Zeneca’s AZD1222 (Covishield). The immunogenicity performance of Covaxin, which provided significant protection only after the second dose, was mediocre and it was consistently surpassed by Covishield. One study reported adjusted effectiveness against symptomatic infection to be just 50% at 2 weeks after the second dose. Nonetheless, appreciable results were seen in previously infected individuals administered both doses. There was some evidence of coverage against the Alpha, Beta, and Delta variants. However, neither Covaxin nor Covishield showed sufficient protection against the Omicron variant. Two studies reported super-additive results on mixing Covaxin with Covishield. Further exploration of heterologous prime-boost vaccination with a combination of an inactivated vaccine and an adenoviral vector-based vaccine for tackling future variants may be beneficial.
Multiplex protein profiling of bronchial aspirates reveals disease-, mortality- and respiratory sequelae-associated signatures in critically ill patients with ARDS secondary to SARS-CoV-2 infection
Authors: Molinero Marta , Gómez Silvia , Benítez Iván D. , Vengoechea J. J. , González Jessica , Polanco Dinora , Gort-Paniello Clara , Moncusí-Moix Anna , García-Hidalgo María C. , Perez-Pons Manel , Belmonte Thalía , Torres Gerard , Caballero Jesús , Barberà Carme , Ayestarán Rota Jose Ignacio , Socías Crespí Lorenzo , Ceccato Adrián , Fernández-Barat Laia , Ferrer Ricard , Garcia-Gasulla Dario , Lorente-Balanza Jose Ángel , Menéndez Rosario , Motos Ana , Peñuelas Oscar , Riera Jordi , Torres Antoni , Barbé Ferran , de Gonzalo-Calvo David
Published: September 2022

Introduction

Bronchial aspirates (BAS) obtained during invasive mechanical ventilation (IMV) constitutes a useful tool for molecular phenotyping and decision making.

Aim

To identify the proteomic determinants associated with disease pathogenesis, all-cause mortality and respiratory sequelae in BAS samples from critically ill patients with SARS-CoV-2-induced ARDS

Methods

Multicenter study including 74 critically ill patients with COVID-19 and non-COVID-19 ARDS. BAS were obtained by bronchoaspiration after IMV initiation. Three hundred sixty-four proteins were quantified using proximity extension assay (PEA) technology. Random forest models were used to assess predictor importance.

Results

After adjusting for confounding factors, CST5, NADK, SRPK2 and TGF-α were differentially detected in COVID-19 and non-COVID-19 patients. In random forest models for COVID-19, CST5, DPP7, NADK, KYAT1 and TYMP showed the highest variable importance. In COVID-19 patients, reduced levels of ENTPD2 and PTN were observed in nonsurvivors of ICU stay, even after adjustment. AGR2, NQO2, IL-1α, OSM and TRAIL showed the strongest associations with in-ICU mortality and were used to construct a protein-based prediction model. Kaplan-Meier curves revealed a clear separation in mortality risk between subgroups of PTN, ENTPD2 and the prediction model. Cox regression models supported these findings. In survivors, the levels of FCRL1, NTF4 and THOP1 in BAS samples obtained during the ICU stay correlated with lung function (i.e., DLCO levels) 3 months after hospital discharge. Similarly, Flt3L and THOP1 levels were correlated with radiological features (i.e., TSS). These proteins are expressed in immune and nonimmune lung cells. Poor host response to viral infectivity and an inappropriate reparative mechanism seem to be linked with the pathogenesis of the disease and fatal outcomes, respectively.

Conclusion

BAS proteomics identified novel factors associated with the pathology of SARS-CoV-2-induced ARDS and its adverse outcomes. BAS-based protein testing emerges as a novel tool for risk assessment in the ICU.
CXCL11 Correlates with Immune Infiltration and Impacts Patient Immunotherapy Efficacy: A Pan-Cancer Analysis
Authors: Li Yang , Han Shukun , Wu Baokang , Zhong Chongli , Shi Yu , Lv Chao , Fu Lei , Zhang Yizhou , Lang Qi , Liang Zhiyun , Yu Yang , Tian Yu
Published: September 2022

Background

Immunotherapy has achieved great success in cancer. Nevertheless, many patients cannot benefit from immune checkpoint blockade therapy because of the scantiness of CD8+ T cell infiltration in the tumor microenvironment (TME). CXCL11 is known as a regulator that influences T-cell infiltration into tumors. However, the role of CXCL11 in pan-cancer is still unclear.

Methods

In this study, we investigated the expression and function of CXCL11 across 33 types of cancers based on datasets from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database. We analyzed the CXCL11 differential expression in tumor tissue and nontumoral tissue and in different stages of cancers. Moreover, the correlations among CXCL11 expression, prognosis, mismatch repair, tumor mutation burden (TMB), microsatellite instability (MSI), tumor microenvironment, and immune-related genes were evaluated.

Results

CXCL11 expression was significantly higher in tumoral tissue than in nontumoral tissue for most types of cancer. Improved CXCL11 expression was related to an inconsistent prognosis in different cancers. CXCL11 was positively associated with CD8+ T cells and T follicular helper cells in the TME. High expression of CXCL11 was positively related to TMB in BLCA, BRCA, CESC, COAD, LGG, LUAD, OV, SKCM, STAD, THYM, and UCEC. A positive correlation between CXCL11 and MSI was found in COAD and UVM. Moreover, functional analysis of CXCL11 showed that high CXCL11 expression was significantly related to immune-relevant pathways.

Conclusions

CXCL11 might function as a prognostic and immunotherapy marker across cancers. Further investigation into CXCL11 might provide promising insights to improve cancer therapy.
Pathogenic roles and diagnostic utility of interleukin-18 in autoinflammatory diseases
Authors: Shimizu Masaki , Takei Syuji , Mori Masaaki , Yachie Akihiro
Published: September 2022

Interleukin (IL)-18 is a pleiotropic, pro-inflammatory cytokine involved in the regulation of innate and adaptive immune responses. IL-18 has attracted increasing attention as a key mediator in autoinflammatory diseases associated with the development of macrophage activation syndrome (MAS) including systemic juvenile idiopathic arthritis and adult-onset Still’s disease. In these diseases, dysregulation of inflammasome activity and overproduction of IL-18 might be associated with the development of MAS by inducing natural killer cell dysfunction. Serum IL-18 levels are high in patients with these diseases and therefore are useful for the diagnosis and monitoring of disease activity. In contrast, a recent study revealed the overproduction of IL-18 was present in cases of autoinflammation without susceptibility to MAS such as pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. The pathogenic and causative roles of IL-18 remain unclear in these autoinflammatory diseases. Further investigations are necessary to clarify the role of IL-18 and its importance as a therapeutic target in the pathogenesis of autoinflammatory diseases.
Maternal gut microbiota during pregnancy and the composition of immune cells in infancy
Authors: Gao Yuan , O’Hely Martin , Quinn Thomas P. , Ponsonby Anne-Louise , Harrison Leonard C. , Frøkiær Hanne , Tang Mimi L. K. , Brix Susanne , Kristiansen Karsten , Burgner Dave , Saffery Richard , Ranganathan Sarath , Collier Fiona , Vuillermin Peter
Published: September 2022

Background

Preclinical studies have shown that maternal gut microbiota during pregnancy play a key role in prenatal immune development but the relevance of these findings to humans is unknown. The aim of this prebirth cohort study was to investigate the association between the maternal gut microbiota in pregnancy and the composition of the infant’s cord and peripheral blood immune cells over the first year of life.

Methods

The Barwon Infant Study cohort (n=1074 infants) was recruited using an unselected sampling frame. Maternal fecal samples were collected at 36 weeks of pregnancy and flow cytometry was conducted on cord/peripheral blood collected at birth, 6 and 12 months of age. Among a randomly selected sub-cohort with available samples (n=293), maternal gut microbiota was characterized by sequencing the 16S rRNA V4 region. Operational taxonomic units (OTUs) were clustered based on their abundance. Associations between maternal fecal microbiota clusters and infant granulocyte, monocyte and lymphocyte subsets were explored using compositional data analysis. Partial least squares (PLS) and regression models were used to investigate the relationships/associations between environmental, maternal and infant factors, and OTU clusters.

Results

We identified six clusters of co-occurring OTUs. The first two components in the PLS regression explained 39% and 33% of the covariance between the maternal prenatal OTU clusters and immune cell populations in offspring at birth. A cluster in which Dialister, Escherichia, and Ruminococcus were predominant was associated with a lower proportion of granulocytes (p=0.002), and higher proportions of both central naïve CD4+ T cells (CD4+/CD45RA+/CD31−) (p<0.001) and naïve regulatory T cells (Treg) (CD4+/CD45RA+/FoxP3low) (p=0.02) in cord blood. The association with central naïve CD4+ T cells persisted to 12 months of age.

Conclusion

This birth cohort study provides evidence consistent with past preclinical models that the maternal gut microbiota during pregnancy plays a role in shaping the composition of innate and adaptive elements of the infant’s immune system following birth.
Application of fluorescence correlation spectroscopy to investigate the dynamics of a ribosome-associated trigger factor in Escherichia coli
Authors: Niwa Tatsuya , Nakazawa Koki , Hoshi Kensuke , Tadakuma Hisashi , Ito Koichi , Taguchi Hideki
Published: September 2022

Co-translational protein folding is one of the central topics in molecular biology. In Escherichia coli, trigger factor (TF) is a primary chaperone that facilitates co-translational folding by directly interacting with nascent polypeptide chains on translating ribosomes. In this study, we applied fluorescence correlation spectroscopy (FCS), which can analyze the diffusion properties of fluorescent molecules by measuring the fluctuations of the fluorescent intensity, to investigate the interaction between TF and a nascent chain on translating ribosomes both in vitro and in vivo. The FCS analysis with a reconstituted cell-free translation system revealed that the interaction of fluorescently labeled TF with a nascent chain depended on the emergence of the nascent chain from the ribosome exit tunnel, and this interaction was not inhibited by excess amounts of other chaperones. Furthermore, the translation-dependent interaction between GFP-fused TFs and nascent chains was also observed in living E. coli cells. The FCS-based approach established here could be an effective method to investigate the dynamics of other ribosome-associated chaperones besides TF.
Characteristics of Cognitive Impairment and Their Relationship With Total Cerebral Small Vascular Disease Score in Parkinson’s Disease
Authors: Hou Miaomiao , Hou Xiaojun , Qiu Yiqing , Wang Jiali , Zhang Mingyang , Mao Xiaowei , Wu Xi
Published: September 2022

Background

This study aimed to investigate the characteristics of cognitive dysfunctions and their relationship with total cerebral small vascular disease (CSVD) in Parkinson’s disease (PD).

Methods

A total of 174 idiopathic PD patients who underwent brain magnetic resonance imaging (MRI) were recruited. Demographic information, vascular disease risk factors, motor function (MDS-UPDRS III score), and cognitive level (MoCA, MMSE) were collected for these patients. The total CSVD burden was scored based on lacunes, enlarged perivascular spaces (EPVS), high-grade white matter hyperintensities (WMH), and cerebral microbleeds (CMBs) for each subject.

Results

Cognitive scores on MoCA for language, delayed recall, and orientation were significantly reduced in PD patients with CSVD burden ≥ 1 than in those with CSVD burden = 0. Educational level, PDQ 39, and CSVD burden were significantly associated with MoCA scores in individuals with PD. For the whole group, the full model accounted for 33.6% variation in total MoCA scores. In which, CSVD burden explained 2.7% of the results, and the detection of lacunes, WMH, EPVS, and strictly lobar CMBs were significantly correlated with MoCA scores. The stability of the outcomes was confirmed by sensitivity analysis.

Conclusion

CSVD can independently contribute to cognitive decline in PD and cause damage in specific cognitive domains. Promoting neurovascular health may help preserve cognitive functions in PD.
Genetically predicted circulating levels of glycine, glutamate, and serotonin in relation to the risks of three major neurodegenerative diseases: A Mendelian randomization analysis
Authors: Li Ruizhuo , Deng Mengjuan , Lin Yuhong , Gao Wenjing , Liu Bohao , Xia Huimin
Published: September 2022

It has been previously postulated that blood neurotransmitters might affect risks of neurodegenerative diseases. Here, a Mendelian Randomization (MR) study was conducted to explore whether genetically predicted concentrations of glycine, glutamate and serotonin were associated with risks of Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). From three genome-wide association studies of European ancestry, single nucleotide polymorphisms strongly associated with glycine, glutamate and serotonin were selected as genetic instrumental variables. Corresponding summary statistics were also obtained from the latest genome-wide association meta-analyses of AD, PD and ALS. The inverse-variance weighted MR and multiple sensitivity analyses were performed to evaluate causal effects of genetically predicted levels of neurotransmitters on risks of neurodegenerative diseases. The statistical significance threshold was set at P < 0.0056 using the Bonferroni-correction, while 0.0056 < P < 0.05 was considered suggestive evidence for a causal association. There was a causal association of elevated blood glutamate levels with higher AD risks. The odds ratio (OR) of AD was 1.311 [95% confidence interval (CI), 1.087–1.580; P = 0.004] per one standard deviation increase in genetically predicted glutamate concentrations. There was suggestive evidence in support of a protective effect of blood serotonin on AD (OR = 0.607; 95% CI, 0.396–0.932; P = 0.022). Genetically predicted glycine levels were not associated with the risk of AD (OR = 1.145; 95% CI, 0.939–1.396; P = 0.180). Besides, MR analyses indicated no causal roles of three blood neurotransmitters in PD or ALS. In conclusion, the MR study provided evidence supporting the association of elevated blood glutamate levels with higher AD risks and the association of increased blood serotonin levels with lower AD risks. Triangulating evidence across further study designs is still warranted to elucidate the role of blood neurotransmitters in risks of neurodegenerative diseases.
Dynamic coupling between the central and autonomic cardiac nervous systems in patients with refractory epilepsy: A pilot study
Authors: Melo Eline , Fiel José , Milhomens Rodrigo , Ribeiro Thaynara , Navegantes Raphael , Gomes Francinaldo , Duarte Gomes Bruno , Pereira Antonio
Published: September 2022

The heart and brain are reciprocally interconnected and engage in two-way communication for homeostatic regulation. Epilepsy is considered a network disease that also affects the autonomic nervous system (ANS). The neurovisceral integration model (NVM) proposes that cardiac vagal tone, indexed by heart rate variability (HRV), can indicate the functional integrity of cognitive neural networks. ANS activity and the pattern of oscillatory EEG activity covary during the transition of arousal states and associations between cortical and autonomic activity are reflected by HRV. Cognitive dysfunction is one of the common comorbidities that occur in epilepsy, including memory, attention, and processing difficulties. Recent studies have shown evidence for the active involvement of alpha activity in cognitive processes through its active role in the control of neural excitability in the cortex through top-down modulation of cortical networks. In the present pilot study, we evaluated the association between resting EEG oscillatory behavior and ANS function in patients with refractory epilepsy. Our results show: (1) In patients with refractory epilepsy, there is a strong positive correlation between HRV and the power of cortical oscillatory cortical activity in all studied EEG bands (delta, theta, alpha, and beta) in all regions of interest in both hemispheres, the opposite pattern found in controls which had low or negative correlation between these variables; (2) higher heartbeat evoked potential amplitudes in patients with refractory epilepsy than in controls. Taken together, these results point to a significant alteration in heart-brain interaction in patients with refractory epilepsy.
Ferulic acid attenuates high-fat diet-induced hypercholesterolemia by activating classic bile acid synthesis pathway
Authors: Luo Zhixin , Li Mengqian , Yang Jiachuan , Li Jia , Zhang Yao , Liu Fang , El-Omar Emad , Han Lin , Bian Ji , Gong Lan , Wang Min
Published: September 2022

Ferulic acid (FA), a natural phenolic phytochemical abundantly present in whole grains, displays promising therapeutic effects on hypercholesterolemia while its underlying mechanism not fully elucidated. This study aimed to investigate the cholesterol-lowering effect of FA in high-fat diet (HFD)-fed mice and its potential molecular mechanism. FA supplementation alleviated HFD-induced hypercholesterolemia (–13.2%, p < 0.05), along with increased excretion of bile acids (BAs) in feces (37.0%, p < 0.05). Mechanism studies showed that FA activated the expression of cholesterol 7α hydroxylase (CYP7A1), a rate-limiting enzyme in BA biosynthesis in the liver, which increased the BAs biosynthesis from cholesterol. Surprisingly, increased excretion of BAs in feces is a consequence, not a cause, of CYP7A1 activation. Furthermore, enterohepatic farnesoid X receptor (FXR) signaling is not involved in the activation of hepatic CYP7A1 by FA. In conclusion, FA activates CYP7A1 through non-FXR signaling, which on the one hand effectively prevents hypercholesterolemia, and on the other hand leads to secondary BAs elevation in plasma. The latter may be the key to the anti-obesity and hypoglycemic effects of FA.
Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma
Authors: Lorusso Domenica , Danesi Romano , Locati Laura Deborah , Masi Gianluca , De Giorgi Ugo , Gadducci Angiolo , Pignata Sandro , Sabbatini Roberto , Savarese Antonella , Valabrega Giorgio , Zamagni Claudio , Colombo Nicoletta
Published: September 2022

Introduction

The combination of lenvatinib plus pembrolizumab demonstrated a relevant clinical benefit in patients with endometrial carcinoma. The safety profile was consistent with the established profiles of each drug in monotherapy, with the most frequent adverse events being hypertension, an on-target effect, hypothyroidism, diarrhea, nausea, vomiting, loss of appetite, fatigue, and weight loss.

Areas covered

We first review the rationale based on the combination of a VEGFR inhibitor and an immune checkpoint inhibitor, highlighting the main pharmacokinetic and pharmacodynamic features of lenvatinib. Next, we focus on the common adverse events associated with lenvatinib and guide how to optimally prevent, detect, and manage them, while minimizing interruptions during lenvatinib treatment.

Discussion

The side effects profile of lenvatinib is very well known, being similar across different tumor types. Most toxicities can be preventable. An appropriate, proactive, and thorough management of lenvatinib toxicities during treatment is required to maximize potential lenvatinib efficacy. Adverse events should be detected as early as possible, by both carefully monitoring the patient from lenvatinib initiation and preventing their occurrence. Patients should be followed also during treatment as some adverse events, e.g., cardiac dysfunction might appear later. Increased awareness on risk to benefit ratio among clinicians would be helpful to avoid dose interruptions or discontinuation of lenvatinib, with preferring other medical interventions and supportive care.
Future insights of pharmacological prevention for AKI post cardiopulmonary bypass surgery (based on PK/PD approach)
Authors: Permeisari Dias
Published: September 2022

The incidence of acute kidney injury (AKI) post-cardiopulmonary bypass (CPB) can cause an increase in the rate of renal replacement therapy (RRT) and mortality rate. Compared to brain and liver damage post-CPB, AKI has the highest incidence of 83%. Based on this phenomenon, various efforts have been made to reduce the incidence of AKI post-CPB, both pharmacologically and non-pharmacologically interventions. The purpose of this review is to emphasize several renal protector agents which under optimal conditions can provide significant benefits in reducing the incidence of AKI post-CPB. This article was obtained by conducting a study on several kinds of literature, including the original article, RCT study, systematic review and meta-analysis, and other review articles. There are five renal protector agents that are the focus of this article, those are fenoldopam which effectively works to prevent the incidence of AKI post-CPB, while furosemide has shown satisfactory results in patients with decreased renal function when administered in the Renal Guard (RG) system, mannitol, and nitric oxide, both of these can also effectively reduce the incidence of AKI post‐CPB by controlling its blood concentration and timing of administration, and another form of N-Acetylcysteine, namely N‐Acetylcysteine amide has better activity as a renoprotective agent than N‐Acetylcysteine itself. The benefits of these agents can be obtained by developing devices that can control drug levels in the blood and create optimal conditions for drugs during the use of a CPB machine.
Expression of group II and III mGluRs in the carotid body and its role in the carotid chemoreceptor response to acute hypoxia
Authors: Zhao Chenlu , Li Chaohong , Zhao Baosheng , Liu Yuzhen
Published: September 2022

The carotid body (CB) contributes significantly to oxygen sensing. It is unclear, however, whether glutamatergic signaling is involved in the CB response to hypoxia. Previously, we reported that ionotropic glutamate receptors (iGluRs) and multiple glutamate transporters are present in the rat CB. Except for iGluRs, glutamate receptors also include metabotropic glutamate receptors (mGluRs), which are divided into the following groups: Group I (mGluR1/5); group II (mGluR2/3); group III (mGluR4/6/7/8). We have studied the expression of group I mGluRs in the rat CB and its physiological function response to acute hypoxia. To further elucidate the states of mGluRs in the CB, this study’s aim was to investigate the expression of group II and III mGluRs and the response of rat CB to acute hypoxia. We used reverse transcription-polymerase chain reaction (RT-PCR) to observed mRNA expression of GRM2/3/4/6/7/8 subunits by using immunostaining to show the distribution of mGluR2 and mGluR8. The results revealed that the GRM2/3/4/6/7/8 mRNAs were expressed in both rat and human CB. Immunostaining showed that mGluR2 was localized in the type I cells and mGluR8 was localized in type I and type II cells in the rat CB. Moreover, the response of CB to acute hypoxia in rats was recorded byin vitrocarotid sinus nerve (CSN) discharge. Perfusion of group II mGluRs agonist or group III mGluRs agonist (LY379268 or L-SOP) was applied to examine the effect of group II and III mGluRs on rat CB response to acute hypoxia. We found that LY379268 and L-SOP inhibited hypoxia-induced enhancement of CSN activity. Based on the above findings, group II and III mGluRs appear to play an inhibitory role in the carotid chemoreceptor response to acute hypoxia.
Taxation strategies for the governance of digital business model—An example of China
Authors: Guo Yi , Zou Tingting , Shan Ziwei
Published: September 2022

The digital business model emerges as a new business model and gradually penetrates global industries, and countries are putting in place various digital strategies to support their development. As one of the important tools, taxation strategies are highly expected by countries, which not only describe the economic development pattern of a country but also show the digital leadership of a country. Some countries have introduced their own unilateral digital services tax to govern their digital business models, while others have looked more to the global minimum tax, resulting in the current situation of both a unilateral digital services tax and a global minimum tax. However, both of them are of great reference value for the tax governance of digital business models. This paper compares the development history of digital tax strategies, categorizes, and analyzes the design logic of existing digital tax strategies, and takes China, one of the major digital economy countries, as an example to propose China’s digital tax strategies by drawing on international experience. We set an example for the design of digital economy tax strategies for countries around the world so that they can manage digital business models more efficiently.
Examining the moderating role of technostress and compatibility in EFL Learners’ mobile learning adoption: A perspective from the theory of planned behaviour
Authors: Wang Qiong , Zhao Guoqing , Cheng Zhuo
Published: September 2022

Mobile English learning has multiple advantages and brings enormous benefits to EFL learners. However, not everyone adopts it, and the determinants of learners’ adoption intention have not yet been investigated fully. This study aimed to better understand learners’ adoption by employing the theory of planned behaviour (TPB) in conjunction with the influences of technostress and compatibility. Based on existing literature, a research model was proposed and verified with a sample of 409 undergraduates from a Chinese university. The results indicated that in the context of mobile English learning: (a) Individuals with higher adoption intention are more likely to engage in mobile English learning with higher frequency (b = 0.473, P < 0.001) and longer duration (b = 0.330, P < 0.001); (b) Individuals’ attitude toward mobile English learning (b = 0.171, P < 0.05), perceived behavioural control (b = 0.221, P < 0.001), subjective norms (b = 0.237, P < 0.05), and compatibility (b = 0.443, P < 0.001) are significantly positively associated with their adoption intention; (c) Compatibility is the strongest predictor of adoption intention (b = 0.443, P < 0.001) and negatively moderates the effect of subjective norms on adoption intention (b = –0.103, P < 0.005); (d) The influence of technostress on the adoption intention of mobile English learning is not significant (b = –0.041, P > 0.05). Practical implications related to mobile English learning were discussed.