bluuebunny/crossref_metadata_2025 huggingface dataset:
Rheumatic diseases and coronavirus infection: levilimab use experience
Authors: Kalinina E. V. , Lekareva I. V. , Zvonorenko M. S. , Emelianova A. L. , Kostryukova I. V. , Scherbinina E. V. , Babaeva A. R.
Published: August 2021

Background. Rheumatic diseases (RD) of autoimmune origin are considered as an important risk factor for infectious processes due to characteristic native immune system disorder, as well as due to the adverse effect of immunosuppressants and glucocorticoids on the mechanisms of anti-infective protection.

Aim. To highlight the problem of RD and concomitant viral infection which becomes critical in the era of COVID‑19.

Results. According to the current national guidelines for the management of patients with COVID‑19, patients with RD represent an increased risk group for the adverse course of coronavirus infection. Presented article provides basic information on the use of interleukin‑6 (IL‑6) inhibitors in patients with COVID‑19 focusing on the benefit of this therapeutic option in those with prior RD. The article presents an analysis of two clinical cases demonstrating high efficacy and good tolerability of levilimab (Ilsira®) in the treatment of coronavirus pneumoniae in the setting of autoimmune diseases: polymyositis (PM) and rheumatoid arthritis (RA).

Conclusion. Our own clinical experience confirms the feasibility of including an IL‑6 receptor inhibitor in the treatment regimen for coronavirus pneumonia in patients with RD characterized of immune inflammation.
Advances in Biosensors for Continuous Glucose Monitoring Towards Wearables
Authors: Johnston Lucy , Wang Gonglei , Hu Kunhui , Qian Chungen , Liu Guozhen
Published: August 2021

Continuous glucose monitors (CGMs) for the non-invasive monitoring of diabetes are constantly being developed and improved. Although there are multiple biosensing platforms for monitoring glucose available on the market, there is still a strong need to enhance their precision, repeatability, wearability, and accessibility to end-users. Biosensing technologies are being increasingly explored that use different bodily fluids such as sweat and tear fluid, etc., that can be calibrated to and therefore used to measure blood glucose concentrations accurately. To improve the wearability of these devices, exploring different fluids as testing mediums is essential and opens the door to various implants and wearables that in turn have the potential to be less inhibiting to the wearer. Recent developments have surfaced in the form of contact lenses or mouthguards for instance. Challenges still present themselves in the form of sensitivity, especially at very high or low glucose concentrations, which is critical for a diabetic person to monitor. This review summarises advances in wearable glucose biosensors over the past 5 years, comparing the different types as well as the fluid they use to detect glucose, including the CGMs currently available on the market. Perspectives on the development of wearables for glucose biosensing are discussed.
Current Pharmacological Strategies for Duchenne Muscular Dystrophy
Authors: Yao Shanshan , Chen Zihao , Yu Yuanyuan , Zhang Ning , Jiang Hewen , Zhang Ge , Zhang Zongkang , Zhang Baoting
Published: August 2021

Duchenne muscular dystrophy (DMD) is a lethal, X-linked neuromuscular disorder caused by the absence of dystrophin protein, which is essential for muscle fiber integrity. Loss of dystrophin protein leads to recurrent myofiber damage, chronic inflammation, progressive fibrosis, and dysfunction of muscle stem cells. There is still no cure for DMD so far and the standard of care is principally limited to symptom relief through glucocorticoids treatments. Current therapeutic strategies could be divided into two lines. Dystrophin-targeted therapeutic strategies that aim at restoring the expression and/or function of dystrophin, including gene-based, cell-based and protein replacement therapies. The other line of therapeutic strategies aims to improve muscle function and quality by targeting the downstream pathological changes, including inflammation, fibrosis, and muscle atrophy. This review introduces the important developments in these two lines of strategies, especially those that have entered the clinical phase and/or have great potential for clinical translation. The rationale and efficacy of each agent in pre-clinical or clinical studies are presented. Furthermore, a meta-analysis of gene profiling in DMD patients has been performed to understand the molecular mechanisms of DMD.
Construction and Analysis of a Colorectal Cancer Prognostic Model Based on N6-Methyladenosine-Related lncRNAs
Authors: Zeng Hanqian , Xu Yiying , Xu Shiwen , Jin Linli , Shen Yanyan , Rajan K. C. , Bhandari Adheesh , Xia Erjie
Published: August 2021

Given the relatively poor understanding of the expression and functional effects of the N6-methyladenosine (m6A) RNA methylation on colorectal cancer (CRC), we attempted to measure its prognostic value and clinical significance. We comprehensively screened 37 m6A-related prognostic long non-coding RNAs (lncRNAs) with significant differences in expression based on 21 acknowledged regulators of m6A modification and data on 473 colorectal cancer tissues and 41 para-cancer tissues obtained from the TCGA database. Accordingly, we classified 473 CRC patients into two clusters by consensus clustering on the basis of significantly different survival outcomes. We also found a potential correlation between m6A-related prognostic lncRNAs and BRAF-KRAS expression, as well as immune cell infiltration. Then, we established a prognostic model by selecting 16 m6A-related prognostic lncRNAs via LASSO Cox analysis and grouped the CRC patients into low- and high-risk groups to calculate risk scores. Then, we performed stratified sampling to validate and confirm our model by categorising the 473 samples into a training group (N = 208) and a testing group (N = 205) in a 1:1 ratio. The survival curve showed a distinct clinical outcome in the low- and high-risk subgroups. We reconfirmed the reliability and independence of the prognostic model through various measures: risk curve, heat map and univariate and multivariate Cox analyses. To ensure that the outcomes were applicable to clinical settings, we performed stratified analyses on different clinical features, such as age, lymph node status and clinical stage. CRC patients with downregulated m6A-related gene expression, lower immune score, distant metastasis, lymph node metastasis or more advanced clinical staging had higher risk scores, indicating less-desirable outcomes. Moreover, we explored the immunology of colorectal cancer cells. The risk score showed positive correlations with eosinophils, M2 macrophages and neutrophils. In summary, our effort revealed the significance of m6A RNA methylation regulators in colorectal cancer, and the prognostic model we constructed may be used as an essential reference for predicting the outcome of CRC patients.
The SIX Family of Transcription Factors: Common Themes Integrating Developmental and Cancer Biology
Authors: Meurer Logan , Ferdman Leonard , Belcher Beau , Camarata Troy
Published: August 2021

Thesine oculis(SIX) family of transcription factors are key regulators of developmental processes during embryogenesis. Members of this family control gene expression to promote self-renewal of progenitor cell populations and govern mechanisms of cell differentiation. When the function ofSIXgenes becomes disrupted, distinct congenital defects develops both in animal models and humans. In addition to the embryonic setting, members of the SIX family have been found to be critical regulators of tumorigenesis, promoting cell proliferation, epithelial-to-mesenchymal transition, and metastasis. Research in both the fields of developmental biology and cancer research have provided an extensive understanding of SIX family transcription factor functions. Here we review recent progress in elucidating the role ofSIXfamily genes in congenital disease as well as in the promotion of cancer. Common themes arise when comparing SIX transcription factor function during embryonic and cancer development. We highlight the complementary nature of these two fields and how knowledge in one area can open new aspects of experimentation in the other.
ZDHHC11 Positively Regulates NF-κB Activation by Enhancing TRAF6 Oligomerization
Authors: Liu Enping , Sun Jiawei , Yang Jing , Li Lin , Yang Qili , Zeng Jiuqin , Zhang Jiayu , Chen Dahua , Sun Qinmiao
Published: August 2021

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a RING domain ubiquitin ligase that plays an important role in nuclear factor-κB (NF-κB) signaling by regulating activation of the TAK1 and IKK complexes. However, the molecular mechanisms that regulate TRAF6 E3 activity remain unclear. Here, we found that ZDHHC11, a member of the DHHC palmitoyl transferase family, functions as a positive modulator in NF-κB signaling. ZDHHC11 overexpression activated NF-κB, whereas ZDHHC11 deficiency impaired NF-κB activity stimulated by IL-1β, LPS, and DNA virus infection. Furthermore, Zdhhc11 knockout mice had a lower level of serum IL6 upon treatment with LPS and D-galactosamine or HSV-1 infection than control mice. Mechanistically, ZDHHC11 interacted with TRAF6 and then enhanced TRAF6 oligomerization, which increased E3 activity of TRAF6 for synthesis of K63-linked ubiquitination chains. Collectively, our study indicates that ZDHHC11 positively regulates NF-κB signaling by promoting TRAF6 oligomerization and ligase activity, subsequently activating TAK1 and IKK complexes.
Impact of Gut Microbiota and Microbiota-Related Metabolites on Hyperlipidemia
Authors: Jia Xiaokang , Xu Wen , Zhang Lei , Li Xiaoyan , Wang Ruirui , Wu Shuisheng
Published: August 2021

Hyperlipidemia, defined as the presence of excess fat or lipids in the blood, has been considered as a high-risk factor and key indicator of many metabolic diseases. The gut microbiota has been reported playing a vital role in regulating host lipid metabolism. The pathogenic role of gut microbiota in the development of hyperlipidemia has been revealed through fecal microbiota transplantation experiment to germ-free mice. The effector mechanism of microbiota-related metabolites such as bile acids, lipopolysaccharide, and short-chain fatty acids in the regulation of hyperlipidemia has been partially unveiled. Moreover, studies on gut-microbiota-targeted hyperlipidemia interventions, including the use of prebiotics, probiotics, fecal microbiota transplantation, and natural herbal medicines, also have shown their efficacy in the treatment of hyperlipidemia. In this review, we summarize the relationship between gut microbiota and hyperlipidemia, the impact of gut microbiota and microbiota-related metabolites on the development and progression of hyperlipidemia, and the potential therapeutic management of hyperlipidemia targeted at gut microbiota.
Time to Detection of Growth for Mycobacterium tuberculosis in a Low Incidence Area
Authors: Vongthilath-Moeung Rechana , Poncet Antoine , Renzi Gesuele , Schrenzel Jacques , Janssens Jean-Paul
Published: August 2021

Background

Diagnosis of Mycobacterium tuberculosis (MTB) infection can be confirmed by Xpert assays within hours. However, when sample size does not allow performing both culture and Xpert, or if Xpert is negative, then formal diagnosis of MTB relies on culture and time to detection of growth (TDG) becomes critical for clinical management.

Objectives

To determine TDG in Xpert negative samples, or in samples in which Xpert could not be performed, in a low-incidence area for MTB.

Methods

Retrospective analysis (2015-2020) of a database including all cultures for mycobacteria in a University Hospital covering approximately 500’000 inhabitants. Analysis was restricted to culture positive (C+) samples for MTB for which 1/Xpert was negative or could not be performed because of limited sample volume, and 2/collected from subjects treated less than 24 hours. TDG was analyzed according to microscopy, origin of sample (pulmonary or not) and presence of cavitation.

Results

Among 837 C+ samples for MTB, 236 samples (80% of respiratory origin) from 147 patients fulfilled study criteria; 78 samples (49 patients, 33%) were acid-fast bacilli (AFB) positive. Median (IQR) TDG was 25 (17; 40) days for all samples. TDG exceeded 28 days in 43% of samples and was significantly shorter in AFB+ vs AFB- samples, and samples from cavitary vs non cavitary or extra-thoracic disease.

Conclusions

In Xpert negative samples, or samples for which Xpert could not be performed, TDG exceeded 4 weeks in 43% of samples. AFB+ and samples from cavitary lung disease had a significantly shorter TDG.
Preclinical Testing of Living Tissue-Engineered Heart Valves for Pediatric Patients, Challenges and Opportunities
Authors: Movileanu Ionela , Harpa Marius , Al Hussein Hussam , Harceaga Lucian , Chertes Alexandru , Al Hussein Hamida , Lutter Georg , Puehler Thomas , Preda Terezia , Sircuta Carmen , Cotoi Ovidiu , Nistor Dan , Man Adrian , Cordos Bogdan , Deac Radu , Suciu Horatiu , Brinzaniuc Klara , Casco Megan , Sierad Leslie , Bruce Margarita , Simionescu Dan , Simionescu Agneta
Published: August 2021

Introduction: Pediatric patients with cardiac congenital diseases require heart valve implants that can grow with their natural somatic increase in size. Current artificial valves perform poorly in children and cannot grow; thus, living-tissue-engineered valves capable of sustaining matrix homeostasis could overcome the current drawbacks of artificial prostheses and minimize the need for repeat surgeries.

Materials and Methods: To prepare living-tissue-engineered valves, we produced completely acellular ovine pulmonary valves by perfusion. We then collected autologous adipose tissue, isolated stem cells, and differentiated them into fibroblasts and separately into endothelial cells. We seeded the fibroblasts in the cusp interstitium and onto the root adventitia and the endothelial cells inside the lumen, conditioned the living valves in dedicated pulmonary heart valve bioreactors, and pursued orthotopic implantation of autologous cell-seeded valves with 6 months follow-up. Unseeded valves served as controls.

Results: Perfusion decellularization yielded acellular pulmonary valves that were stable, no degradable in vivo, cell friendly and biocompatible, had excellent hemodynamics, were not immunogenic or inflammatory, non thrombogenic, did not calcify in juvenile sheep, and served as substrates for cell repopulation. Autologous adipose-derived stem cells were easy to isolate and differentiate into fibroblasts and endothelial-like cells. Cell-seeded valves exhibited preserved viability after progressive bioreactor conditioning and functioned well in vivo for 6 months. At explantation, the implants and anastomoses were intact, and the valve root was well integrated into host tissues; valve leaflets were unchanged in size, non fibrotic, supple, and functional. Numerous cells positive for a-smooth muscle cell actin were found mostly in the sinus, base, and the fibrosa of the leaflets, and most surfaces were covered by endothelial cells, indicating a strong potential for repopulation of the scaffold.

Conclusions: Tissue-engineered living valves can be generated in vitro using the approach described here. The technology is not trivial and can provide numerous challenges and opportunities, which are discussed in detail in this paper. Overall, we concluded that cell seeding did not negatively affect tissue-engineered heart valve (TEHV) performance as they exhibited as good hemodynamic performance as acellular valves in this model. Further understanding of cell fate after implantation and the timeline of repopulation of acellular scaffolds will help us evaluate the translational potential of this technology.
Evaluation of the Safety and Efficacy of Coronary Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Stenoses: Evidence From the Serial Disrupt CAD Trials
Authors: Liang Bo , Gu Ning
Published: August 2021

Background: Previous understanding holds that rotational atherectomy and modified balloons remain the default strategy for severely calcified coronary stenoses. In recent years, coronary intravascular lithotripsy (IVL) provides new ideas. This study was conducted to evaluate the safety and efficacy of IVL for the treatment of severely calcified coronary stenoses.

Methods: The serial Disrupt CAD trials (Disrupt CAD I, Disrupt CAD II, Disrupt CAD III, and Disrupt CAD IV) were included in this study. The safety endpoint was freedom from major adverse cardiovascular events (MACE) in hospital, at 30 days, and at 6 months following the index procedure. The efficacy endpoints included procedural success and angiographic success. Optical coherence tomography (OCT) was used to evaluate the mechanism of action of IVL quantifying the coronary artery calcification (CAC) characteristics and calcium plaque fracture.

Results: We enrolled a total of 628 patients with a mean age of 71.8 years, 77.1% males. In these patients, the left anterior descending artery and right coronary artery were the most vulnerable vessels. The diameter stenosis was 64.6 ± 11.6% and the lesion length was 24.2 ± 11.4 mm. IVL had a favorable efficacy (93.0% procedural success, 97.5% angiographic success, and 100.0% stent delivery). Among the 628 patients, 568, 568, and 60 reported MACE endpoints in hospital, at 30 days, and at 6 months, respectively. The results showed that 528, 514, and 55 patients were free from MACE in hospital, at 30 days, and at 6 months, respectively. OCT measurements demonstrated that calcium fracture was the underlying mechanism of action for coronary IVL.

Conclusions: IVL is safe and efficient for severely calcified coronary stenoses, and, importantly, calcium fracture facilitated increased vessel compliance and favorable stent expansion.
Successful Multi-Level HPV Vaccination Intervention at a Rural Healthcare Center in the Era of COVID-19
Authors: Kepka Deanna , Christini Kaila , McGough Emily , Wagner Anna , Del Fiol Guilherme , Gibson Bryan , Ayres Shauna , Brandt Heather M. , Mann Sara , Petrik Amanda F. , Coronado Gloria D.
Published: August 2021

Objectives: To develop and test a human papillomavirus (HPV) vaccination intervention that includes healthcare team training activities and patient reminders to reduce missed opportunities and improves the rate of appointment scheduling for HPV vaccination in a rural medical clinic in the United States.

Methods: The multi-level and multi-component intervention included healthcare team training activities and the distribution of patient education materials along with technology-based patient HPV vaccination reminders for parents/caregivers and young adult patients. Missed vaccination opportunities were assessed pre- and post-intervention (n = 402 and n = 99, respectively) by retrospective chart review and compared using Pearson χ2. The patient parent/caregiver and young adult patient population (n = 80) was surveyed following the reminder messages and penalized logistic regression quantified unadjusted odds of scheduling a visit.

Results: Missed opportunities for HPV vaccination declined significantly from the pre-intervention to the post-intervention period (21.6 vs. 8.1%, respectively, p = 0.002). Participants who recalled receipt of a vaccination reminder had 7.0 (95% CI 2.4–22.8) times higher unadjusted odds of scheduling a visit compared with those who did not recall receiving a reminder. The unadjusted odds of confirming that they had scheduled or were intending to schedule a follow-up appointment to receive the HPV vaccine was 4.9 (95% CI 1.51–20.59) times greater among those who had not received the vaccine for themselves or for their child.

Conclusions: Results from this intervention are promising and suggest that vaccination interventions consisting of provider and support staff education and parent/caregiver and patient education materials, and reminders can reduce missed opportunities for vaccinations in rural settings.
Student-Reported Classroom Climate Pre and Post Teacher Training in Restorative Practices
Authors: Weber Constanze , Rehder Merle , Vereenooghe Leen
Published: August 2021

Restorative practices (RP) offer a means to establish positive and caring relationships and could thus foster the mental and scholastic development of students by improving classroom climate. This could benefit both students with and without special educational needs and disabilities (SEND), yet to date no studies evaluated these practices in inclusive educational settings. Here we report the findings of two consecutive studies: a pilot single-group pre-post (Study 1) and a non-randomised controlled study of RP training vs no-intervention control condition (Study 2). Across both studies, 531 students (46.5% female) with a mean age of 11.43 years (SD= 1.27) enrolled in the study at pre-test, of which 13.9% had a confirmed diagnosis of SEND and a further 5.7% were considered by teachers to likely have SEND. School and classroom climate, as well as victimisation experiences, emotional well-being and social inclusion of students were assessed using self-report questionnaires. Easy enrolment of schools and students at pre-test indicated that studies investigating the effects of RP training could be feasible. However, in part due to COVID-19 related school closures, student attrition rates of 90 and 77% were observed, for Study 1 and Study 2 respectively. In spite of observed improvements in classroom climate for the intervention group in Study 2, statistical analyses yielded no significant effects of the intervention and there were no moderation effects of students’ perceived inclusion and victimisation experiences. Together, these studies provide the first quantitative student data on implementing RP in an inclusive educational setting. We discuss our findings in light of the need for ideas on how to reduce attrition and also consider longer school-wide and single-class implementations of RP.
ACE Gene Variants Rise the Risk of Severe COVID-19 in Patients With Hypertension, Dyslipidemia or Diabetes: A Spanish Pilot Study
Authors: Íñiguez María , Pérez-Matute Patricia , Villoslada-Blanco Pablo , Recio-Fernandez Emma , Ezquerro-Pérez Diana , Alba Jorge , Ferreira-Laso M. Lourdes , Oteo José A.
Published: August 2021

Coronavirus disease 19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to scale and threaten human health and public safety. It is essential to identify those risk factors that lead to a poor prognosis of the disease. A predisposing host genetic background could be one of these factors that explain the interindividual variability to COVID-19 severity. Thus, we have studied whether the rs4341 and rs4343 polymorphisms of the angiotensin converting enzyme (ACE) gene, key regulator of the renin-aldosterone-angiotensin system (RAAS), could explain the different outcomes of 128 COVID-19 patients with diverse degree of severity (33 asymptomatic or mildly symptomatic, 66 hospitalized in the general ward, and 29 admitted to the ICU). We found that G allele of rs4341 and rs4343 was associated with severe COVID-19 in hypertensive patients, independently of gender (p<0.05). G-carrier genotypes of both polymorphisms were also associated with higher mortality (p< 0.05) and higher severity of COVID-19 in dyslipidemic (p<0.05) and type 2 diabetic patients (p< 0.01). The association of G alleles with disease severity was adjusted for age, sex, BMI and number of comorbidities, suggesting that both the metabolic comorbidities and the G allele act synergistically on COVID-19 outcome. Although we did not find a direct association between serum ACE levels and COVID-19 severity, we found higher levels of ACE in the serum of patients with the GG genotype of rs4341 and rs4343 (p<0.05), what could explain the higher susceptibility to develop severe forms of the disease in patients with the GG genotype, in addition to hypertension and dyslipidemia. In conclusion, our preliminary study suggests that the G-containing genotypes of rs4341 and rs4343 confer an additional risk of adverse COVID-19 prognosis. Thus, rs4341 and rs4343 polymorphisms of ACE could be predictive markers of severity of COVID-19 in those patients with hypertension, dyslipidemia or diabetes. The knowledge of these genetic data could contribute to precision management of SARS-CoV-2 infected patients when admitted to hospital.
The Impact of the Triglyceride-Glucose Index on Poor Prognosis in NonDiabetic Patients Undergoing Percutaneous Coronary Intervention
Authors: Yang Jie , Tang Yi-Da , Zheng Yitian , Li Chen , Zhou Qing , Gao Jun , Meng Xiangbin , Zhang Kuo , Wang Wenyao , Shao Chunli
Published: August 2021

Background

The triglyceride-glucose index (TyG index) is a valuable marker for predicting adverse cardiovascular events in diabetic patients. However, for nondiabetic patients, whether the TyG index is independently related to poor prognosis remains unclear. This cohort study assessed the association of the TyG index with future cardiovascular risk in nondiabetic subjects who received percutaneous coronary intervention (PCI).

Methods

We consecutively enrolled 5,489 nondiabetic patients who underwent PCI. All experimental subjects were divided into three groups based on their TyG index, which was determined by the equation ln (fasting triglyceride (mg/dl) × fasting blood glucose (mg/dl)/2). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, and target vessel revascularization (TVR).

Results

A total of 386 MACCE were documented during a median 29-month follow-up. The Kaplan–Meier survival results indicated that among the three groups, there was no obvious difference in any endpoints. Further Cox regression analyses suggested that the TyG index was not independently related to adverse cardiovascular outcomes for nondiabetic patients who underwent PCI (HR: 0.77, 95% CI 0.56–1.16, P = 0.210 for MACCE). Subgroup analysis suggested that the TyG index was independently relevant to MACCE for patients with low-density lipoprotein cholesterol (LDL-C) lower than 1.8 mmol/L.

Conclusion

The TyG index is not an effective predictive factor for adverse cardiovascular prognosis in nondiabetic patients who underwent PCI. However, in subjects with LDL-C lower than 1.8mmol/L, it may predict future cardiovascular risk.
A New Two-Stage Approach with Boosting and Model Averaging for Interval-Valued Crude Oil Prices Forecasting in Uncertainty Environments
Authors: Huang Bai , Sun Yuying , Wang Shouyang
Published: August 2021

In view of the intrinsic complexity of the oil market, crude oil prices are influenced by numerous factors that make forecasting very difficult. Recognizing this challenge, numerous approaches have been introduced, but little work has been done concerning the interval-valued prices. To capture the underlying characteristics of crude oil price movements, this paper proposes a two-stage forecasting procedure to forecast interval-valued time series, which generalizes point-valued forecasts to incorporate uncertainty and variability. The empirical results show that our proposed approach significantly outperforms all the benchmark models in terms of both forecasting accuracy and robustness analysis. These results can provide references for decision-makers to understand the trends of crude oil prices and improve the efficiency of economic activities.
Behavioral and Acoustic Responses of the Oriental Reed Warbler (Acrocephalus orientalis), at Egg and Nestling Stages, to the Common Cuckoo (Cuculus canorus)
Authors: Wang Jiaojiao , Ma Laikun , Chen Xiangyang , Yang Canchao
Published: August 2021

Cuckoo nest parasites lay eggs in host nests and thereby transfer all reproduction costs to the hosts. This greatly reduces host fitness. Parasitism has selected for the evolution of anti-parasitic strategies in hosts, including nest defense. The dynamic risk assessment hypothesis holds that nest parasitism only threatens the nests during the egg stage, so hosts should reduce the level of defense against nest parasites after the egg stage. We studied the behavioral and acoustic responses of oriental reed warblers (Acrocephalus orientalis), during both the egg and nestling stages, toward the common cuckoo (Cuculus canorus), sparrowhawks (Accipiter nisus) and oriental turtle doves (Streptopelia orientalis).A. orientaliscan visually distinguish cuckoos from sparrowhawks and doves, indicating that hawk mimicry did not work for the cuckoos. The behavioral response of hosts in the nestling stage was stronger than in the egg stage, which supports the offspring value hypothesis and suggests that cuckoos may also act as nest predators. However, there was no difference in the alarm callsA. orientalisproduce in response to different invaders, indicating that different types of alarm calls may not contain specific information.
A Methodological Approach Using rAAV Vectors Encoding Nanobody-Based Biologics to Evaluate ARTC2.2 and P2X7 In Vivo
Authors: Gondé Henri , Demeules Mélanie , Hardet Romain , Scarpitta Allan , Junge Marten , Pinto-Espinoza Carolina , Varin Rémi , Koch-Nolte Friedrich , Boyer Olivier , Adriouch Sahil
Published: August 2021

On murine T cells, mono-ADP ribosyltransferase ARTC2.2 catalyzes ADP-ribosylation of various surface proteins when nicotinamide adenine dinucleotide (NAD+) is released into the extracellular compartment. Covalent ADP-ribosylation of the P2X7 receptor by ARTC2.2 thereby represents an additional mechanism of activation, complementary to its triggering by extracellular ATP. P2X7 is a multifaceted receptor that may represents a potential target in inflammatory, and neurodegenerative diseases, as well as in cancer. We present herein an experimental approach using intramuscular injection of recombinant AAV vectors (rAAV) encoding nanobody-based biologics targeting ARTC2.2 or P2X7. We demonstrate the ability of thesein vivogenerated biologics to potently and durably block P2X7 or ARTC2.2 activitiesin vivo, or in contrast, to potentiate NAD+- or ATP-induced activation of P2X7. We additionally demonstrate the ability of rAAV-encoded functional heavy chain antibodies to elicit long-term depletion of T cells expressing high levels of ARTC2.2 or P2X7. Our approach of using rAAV to generate functional nanobody-based biologicsin vivoappears promising to evaluate the role of ARTC2.2 and P2X7 in murine acute as well as chronic disease models.
Obesity Attenuates Ventilator-Induced Lung Injury by Modulating the STAT3–SOCS3 Pathway
Authors: Wu Shih-Wei , Peng Chung-Kan , Wu Shu-Yu , Wang Yu , Yang Sung-Sen , Tang Shih-En , Huang Kun-Lun
Published: August 2021

Background

Ventilator-induced lung injury (VILI) is characterized by vascular barrier dysfunction and suppression of alveolar fluid clearance (AFC). Obesity itself leads to chronic inflammation, which may initiate an injurious cascade to the lungs and simultaneously induce a protective feedback. In this study, we investigated the protective mechanism of obesity on VILI in a mouse model.

Methods

The VILI model was set up via 6-h mechanical ventilation with a high tidal volume. Parameters including lung injury score, STAT3/NFκB pathway, and AFC were assessed. Mice with diet-induced obesity were obtained by allowing free access to a high-fat diet since the age of 3 weeks. After a 9-week diet intervention, these mice were sacrificed at the age of 12 weeks. The manipulation of SOCS3 protein was achieved by siRNA knockdown and pharmaceutical stimulation using hesperetin. WNK4 knockin and knockout obese mice were used to clarify the pathway of AFC modulation.

Results

Obesity itself attenuated VILI. Knockdown of SOCS3 in obese mice offset the protection against VILI afforded by obesity. Hesperetin stimulated SOCS3 upregulation in nonobese mice and provided protection against VILI. In obese mice, the WNK4 axis was upregulated at the baseline, but was significantly attenuated after VILI compared with nonobese mice. At the baseline, the manipulation of SOCS3 by siRNA and hesperetin also led to the corresponding alteration of WNK4, albeit to a lesser extent. After VILI, WNK4 expression correlated with STAT3/NFκB activation, regardless of SOCS3 status. Obese mice carrying WNK4 knockout had VILI with a severity similar to that of wild-type obese mice. The severity of VILI in WNK4-knockin obese mice was counteracted by obesity, similar to that of wild-type nonobese mice only.

Conclusions

Obesity protects lungs from VILI by upregulating SOCS3, thus suppressing the STAT3/NFκB inflammatory pathway and enhancing WNK4-related AFC. However, WNK4 activation is mainly from direct NFκB downstreaming, and less from SOCS3 upregulation. Moreover, JAK2–STAT3/NFκB signaling predominates the pathogenesis of VILI. Nevertheless, the interaction between SOCS3 and WNK4 in modulating VILI in obesity warrants further investigation.
Integrating High-Resolution Coastal Acidification Monitoring Data Across Seven United States Estuaries
Authors: Rosenau Nicholas A. , Galavotti Holly , Yates Kimberly K. , Bohlen Curtis C. , Hunt Christopher W. , Liebman Matthew , Brown Cheryl A. , Pacella Stephen R. , Largier John L. , Nielsen Karina J. , Hu Xinping , McCutcheon Melissa R. , Vasslides James M. , Poach Matthew , Ford Tom , Johnston Karina , Steele Alex
Published: August 2021

Beginning in 2015, the United States Environmental Protection Agency’s (EPA’s) National Estuary Program (NEP) started a collaboration with partners in seven estuaries along the East Coast (Barnegat Bay; Casco Bay), West Coast (Santa Monica Bay; San Francisco Bay; Tillamook Bay), and the Gulf of Mexico (GOM) Coast (Tampa Bay; Mission-Aransas Estuary) of the United States to expand the use of autonomous monitoring of partial pressure of carbon dioxide (pCO2) and pH. Analysis of high-frequency (hourly to sub-hourly) coastal acidification data including pCO2, pH, temperature, salinity, and dissolved oxygen (DO) indicate that the sensors effectively captured key parameter measurements under challenging environmental conditions, allowing for an initial characterization of daily to seasonal trends in carbonate chemistry across a range of estuarine settings. Multi-year monitoring showed that across all water bodies temperature and pCO2 covaried, suggesting that pCO2 variability was governed, in part, by seasonal temperature changes with average pCO2 being lower in cooler, winter months and higher in warmer, summer months. Furthermore, the timing of seasonal shifts towards increasing (or decreasing) pCO2 varied by location and appears to be related to regional climate conditions. Specifically, pCO2 increases began earlier in the year in warmer water, lower latitude water bodies in the GOM (Tampa Bay; Mission-Aransas Estuary) as compared with cooler water, higher latitude water bodies in the northeast (Barnegat Bay; Casco Bay), and upwelling-influenced West Coast water bodies (Tillamook Bay; Santa Monica Bay; San Francisco Bay). Results suggest that both thermal and non-thermal influences are important drivers of pCO2 in Tampa Bay and Mission-Aransas Estuary. Conversely, non-thermal processes, most notably the biogeochemical structure of coastal upwelling, appear to be largely responsible for the observed pCO2 values in West Coast water bodies. The co-occurrence of high salinity, high pCO2, low DO, and low temperature water in Santa Monica Bay and San Francisco Bay characterize the coastal upwelling paradigm that is also evident in Tillamook Bay when upwelling dominates freshwater runoff and local processes. These data demonstrate that high-quality carbonate chemistry observations can be recorded from estuarine environments using autonomous sensors originally designed for open-ocean settings.
Oral Hydrogen-Rich Water Alleviates Oxalate-Induced Kidney Injury by Suppressing Oxidative Stress, Inflammation, and Fibrosis
Authors: Si Yachen , Liu Lulu , Cheng Jin , Zhao Tingting , Zhou Qi , Yu Jianpeng , Chen Wei , Ding Jiarong , Sun Xuejun , Lu Hongtao , Guo Zhiyong
Published: August 2021

Objective: To explore the theraputic effects and potential mechanisms of hydrogen-rich water (HRW) against oxalate-induced kidney injury.

Methods: The mouse model of Calcium oxalate (CaOx) crystallization was established by feeding a soluble oxalate diet. Crystal deposition, tubular injury, fibrosis and reactive oxygen species (ROS) production in kidneys were examined by histology. Serum indexes of renal injury, inflammation and oxidative stress were detected by commercial kits. RNA sequencing (RNA-seq) was performed to screen potential pathways and the expressions of key molecules in these pathways were determined by western blotting and immunohistochemistry.

Results: Crystal deposition, tubular injury, fibrosis and increased ROS production in kidneys of mice induced by oxalate diet were improved with HRW administration. The indexes of renal injury, inflammation and oxidative stress in serum of mice were upregulated by oxalate diet, which were reduced by HRW. A total of 3,566 differential genes were screened by RNA-seq and these genes were analyzed by pathway enrichment and PI3K/AKT, NF-κB, and TGF-β pathways were selected for further verification. The expressions of molecules related to PI3K-AKT pathway (PI3K, AKT, and p-AKT), NF-κB pathway (NF-κB p65, p- NF-κB p65, NLRP3, and IL-1β) and TGF-β pathway (TGF-β, TGF-βRI, TGF-βRII, p-Smad2, and p-Smad3) in renal tissues were increased by oxalate diet, which were reduced by HRW administration.

Conclusion: HRW may alleviate oxalate-induced kidney injury with its anti-oxidative, anti-inflammatory and anti-fibrotic effects via inhibiting PI3K/AKT, NF-κB, and TGF-β pathways.
The Risk of Neuraxial Anesthesia-Related Hypotension in COVID-19 Parturients Undergoing Cesarean Delivery: A Multicenter, Retrospective, Propensity Score Matched Cohort Study
Authors: Zhang Yuan , Chen Rong , Cao Chen , Gong Yuan , Zhou Qin , Wei Min , Xia ZhongYuan , Chen XiangDong , Meng QingTao
Published: August 2021

Background: SARS-CoV-2 infection was referred to sympathetic hyperactivity, which might increase the susceptibility of neuraxial anesthesia-related hypotension resulted from sympathetic inhibition. We conducted a multicenter, retrospective, propensity score matched (PSM) cohort study to determine whether COVID-19 parturients have an increased risk of hypotension after neuraxial anesthesia for cesarean delivery.

Methods: Clinical data of COVID-19 parturients were collected from the electronic medical records from 1th January to 31th May, 2020 in three hospitals of Hubei Province, China. Information of Control parturients (without COVID-19) were obtained at the same institutions over a similar period in 2019. All American Society of Anaesthesiologists (ASA) Physical Status II full termed pregnant women who received cesarean delivery under neuraxial anesthesia were included. The primary objective was to obtain and compare the incidence of neuraxial anesthesia-related hypotension. Secondary objectives were the analysis of anesthetic implementation and administration, intraoperative maternal vital signs and adverse reactions, and neonatal Apgar scores at 1 and 5 min after delivery. The clinical characteristics of COVID-19 parturients were also analyzed. PSM was derived to balance the predictors for neuraxial anesthesia-related hypotension based on previous studies.

Results: In present study, 101 COVID-19 parturients and 186 Control parturients were derived from 1,403 cases referenced to propensity score matching. The incidence of neuraxial anesthesia-related hypotension was 57.4% in COVID-19 parturients and 41.9% in Control parturients with an incidence risk ratio (IRR) of 1.37 (95% CI 1.08–1.74; P = 0.012; post-hoc Cramér's V = 0.15) in the PSM cohort. The incidences of nausea, vomiting, dizziness, and shaking were significantly higher in the COVID-19 group than Control group (48.5 vs. 17.2%, P < 0.001; 10.9 vs. 4.3%, P = 0.03; 18.8 vs. 3.2%, P < 0.001; 51.5 vs. 18.3%, P < 0.001; respectively). The Apgar scores at 1 min was significantly lower in newborns from COVID-19 parturients than that in Control babies (P = 0.04).

Conclusions: An increased risk of neuraxial anesthesia-related hypotension in COVID-19 parturients undergoing cesarean delivery should be stressed.
Intraocular Pressure Changes Are Predictive of Ocular Hypertension Onset After Fluocinolone Acetonide Implant: Significant Cutoffs and the Role of Previous DEX Implant
Authors: Arrigo Alessandro , Aragona Emanuela , Capone Luigi , Di Biase Carlo , Lattanzio Rosangela , Bandello Francesco
Published: August 2021

Background: Fluocinolone acetonide (FAc) implant represents a long-term strategy for the management of diabetic macular edema (DME). Because of the 3-year duration, the careful monitoring of the intraocular pressure (IOP) is necessary. The main aim of the study was to provide quantitative IOP cutoffs associated with the onset of IOP increases.

Methods: The study was retrospectively conducted with 2-year of follow-up. We separately considered eyes with good IOP control (Group 1), eyes requiring IOP-lowering medications (Group 2) and eyes undergoing IOP-lowering surgery (Group 3). The statistical analysis assessed Delta% IOP changes over the 2-year follow-up. ROC analysis was performed to detect significant cutoffs associated with Group 2 and Group 3. IOP changes occurring after a previously administered dexamethasone (DEX) implant were also evaluated.

Results: We included 48 eyes (48 patients), stratified as follows: Group 1 (25/48; 52%), Group 2 (19/48; 40%) and Group 3 (4/48; 8%). ROC analysis performed on IOP values detected 2-months later DEX implant showed a mean Delta IOP increase>24% significantly associated with IOP-lowering medications after FAc implant, whereas a mean Delta IOP increase>35% was significantly associated with IOP-lowering surgery after FAc implant. With respect to IOP changes occurred after FAc implant, our ROC analysis showed a mean Delta IOP increase>8% significantly associated with IOP-lowering medications, whereas a mean Delta IOP increase>15% was significantly associated with IOP-lowering surgery. DEX-related IOP changes showed 52% sensitivity and 100% specificity of FAc-related IOP increases.

Conclusions: IOP changes provides clinically relevant cutoffs associated with the onset of FAc-related IOP increases.
Species Diversity and Chemotypes of Fusarium Species Associated With Maize Stalk Rot in Yunnan Province of Southwest China
Authors: Xi Kaifei , Shan Liuying , Yang Yini , Zhang Guoqing , Zhang Jun , Guo Wei
Published: August 2021

Maize stalk rot caused by Fusarium species is one of the most important fungal diseases of maize throughout the world. The disease is responsible for considerable yield losses and has also been associated with mycotoxin contamination of the crop. In this study, a survey of maize stalk rot was performed in seven locations of Yunnan Province in China during the cropping season of 2015 and 2016. Based on morphological and molecular characteristics, 204 isolates belonging to 12 Fusarium spp. from symptomatic stalks of maize were identified. Among the isolated strains, 83 were identified as Fusarium meridionale (40.5%), 46 as Fusarium boothii (22.5%), 34 as Fusarium temperatum (16.5%), 12 as Fusarium equiseti (5.9%), 10 as Fusarium asiaticum (4.9%), six as Fusarium proliferatum (3.0%), four as Fusarium verticillioides (2.0%), four as Fusarium incarnatum (2.0%), two as Fusarium avenaceum (1.0%), one as Fusarium cerealis (0.5%), one as Fusarium graminearum (0.5%), and one as Fusarium cortaderiae (0.5%). Fusarium cortaderiae was the first report on the causal agent of maize stalk rot disease in China. These isolates were divided into five chemotypes: nivalenol (NIV), deoxynivalenol (DON), beauvericin (BEA), zearalenone (ZEN), and fumonisin (FUM). Phylogenetic analysis based on partial sequences of the translation elongation factor 1α (TEF1-α) showed a high degree of interspecific polymorphisms among the isolates. Pathogenicity analysis on maize stalks indicated that all the 12 species of Fusarium were able to cause the disease symptoms with different aggressiveness. This study on population, pathogenicity, and toxigenic chemotypes of Fusarium species associated with maize stalk rot in Yunnan Province of southwest China, will help design an effective integrated control strategy for this disease.
The Small RNA ErsA Impacts the Anaerobic Metabolism of Pseudomonas aeruginosa Through Post-Transcriptional Modulation of the Master Regulator Anr
Authors: Ferrara Silvia , Carrubba Riccardo , Santoro Silvia , Bertoni Giovanni
Published: August 2021

Pseudomonas aeruginosa is one of the most critical opportunistic pathogens in humans, able to cause both lethal acute and chronic lung infections. In previous work, we indicated that the small RNA ErsA plays a role in the regulatory network of P. aeruginosa pathogenicity in airways infection. To give further insight into the lifestyle functions that could be either directly or indirectly regulated by ErsA during infection, we reanalyzed the categories of genes whose transcription appeared dysregulated in an ersA knock-out mutant of the P. aeruginosa PAO1 reference strain. This preliminary analysis indicated ErsA as a candidate co-modulator of denitrification and in general, the anaerobiosis response, a characteristic physiologic state of P. aeruginosa during chronic infection of the lung of cystic fibrosis (CF) patients. To explain the pattern of dysregulation of the anaerobic-lifestyle genes in the lack of ErsA, we postulated that ErsA regulation could target the expression of Anr, a well-known transcription factor that modulates a broad regulon of anoxia-responsive genes, and also Dnr, required for the transcription activation of the denitrification machinery. Our results show that ErsA positively regulates Anr expression at the post-transcriptional level while no direct ErsA-mediated regulatory effect on Dnr was observed. However, Dnr is transcriptionally downregulated in the absence of ErsA and this is consistent with the well-characterized regulatory link between Anr and Dnr. Anr regulatory function is critical for P. aeruginosa anaerobic growth, both through denitrification and fermentation of arginine. Interestingly, we found that, differently from the laboratory strain PAO1, ErsA deletion strongly impairs the anaerobic growth by both denitrification and arginine fermentation of the RP73 clinical isolate, a multi-drug resistant P. aeruginosa CF-adapted strain. This suggests that P. aeruginosa adaptation to CF lung might result in a higher dependence on ErsA for the transduction of the multiple signals to the regulatory network of key functions for survivance in such a complex environment. Together, our results suggest that ErsA takes an upper place in the regulatory network of airways infection, transducing host inputs to biofilm-related factors, as underlined in our previous reports, and to functions that allow P. aeruginosa to thrive in low-oxygen conditions.