bluuebunny/crossref_metadata_2025 huggingface dataset:
New Insights Into the Threshold Values of Multi-Locus Sequence Analysis, Average Nucleotide Identity and Digital DNA–DNA Hybridization in Delineating Streptomyces Species
Authors: Hu Siren , Li Kaiqin , Zhang Yifei , Wang Yinfeng , Fu Li , Xiao Yan , Tang Xinke , Gao Jian
Published: May 2022

Multi-locus sequence analysis (MLSA) has been proved to be a useful method for Streptomyces identification and MLSA distance of 0.007 is considered as the boundary value. However, we found that MLSA distance of 0.007 might be insufficient to act as a threshold according to the correlations among average nucleotide identity based on MuMmer ultra-rapid aligning tool (ANIm), digital DNA–DNA hybridization (dDDH) and MLSA from the 80 pairs of Streptomyces species; in addition, a 70% dDDH value did not correspond to a 95∼96% ANIm value but approximately to 96.7% in the genus Streptomyces. Based on our analysis, it was proposed that when the MLSA distance value between a novel Streptomyces and a reference strain was < 0.008, the novel strain could be considered as a heterotypic synonym of the reference strain; when the MLSA distance value was ≥ 0.014, the novel strain could be regarded as a new Streptomyces species; when the MLSA distance value was between 0.008 and 0.014 (not included), the dDDH or ANIm value between a new strain and a reference strain must be calculated in order to determine the taxonomic status of a novel strain. In this context, a 70% dDDH or 96.7% ANIm value could act as the threshold value in delineating Streptomyces species, but if the dDDH or ANIm value was less than but close to 70 or 96.7% cut-off point, the taxonomic status of a novel strain could only be determined by a combination of phenotypic characteristics, chemotaxonomic characteristics and phylogenomic analysis.
Neuroprotection in Acute Ischemic Stroke: A Battle Against the Biology of Nature
Authors: Ghozy Sherief , Reda Abdullah , Varney Joseph , Elhawary Ahmed Sallam , Shah Jaffer , Murry Kimberly , Sobeeh Mohamed Gomaa , Nayak Sandeep S. , Azzam Ahmed Y. , Brinjikji Waleed , Kadirvel Ramanathan , Kallmes David F.
Published: May 2022

Stroke is the second most common cause of global death following coronary artery disease. Time is crucial in managing stroke to reduce the rapidly progressing insult of the ischemic penumbra and the serious neurologic deficits that might follow it. Strokes are mainly either hemorrhagic or ischemic, with ischemic being the most common of all types of strokes. Thrombolytic therapy with recombinant tissue plasminogen activator and endovascular thrombectomy are the main types of management of acute ischemic stroke (AIS). In addition, there is a vital need for neuroprotection in the setting of AIS. Neuroprotective agents are important to investigate as they may reduce mortality, lessen disability, and improve quality of life after AIS. In our review, we will discuss the main types of management and the different modalities of neuroprotection, their mechanisms of action, and evidence of their effectiveness after ischemic stroke.
The “Primitive Brain Dysfunction” Theory of Autism: The Superior Colliculus Role
Authors: Jure Rubin
Published: May 2022

A better understanding of the pathogenesis of autism will help clarify our conception of the complexity of normal brain development. The crucial deficit may lie in the postnatal changes that vision produces in the brainstem nuclei during early life. The superior colliculus is the primary brainstem visual center. Although difficult to examine in humans with present techniques, it is known to support behaviors essential for every vertebrate to survive, such as the ability to pay attention to relevant stimuli and to produce automatic motor responses based on sensory input. From birth to death, it acts as a brain sentinel that influences basic aspects of our behavior. It is the main brainstem hub that lies between the environment and the rest of the higher neural system, making continuous, implicit decisions about where to direct our attention. The conserved cortex-like organization of the superior colliculus in all vertebrates allows the early appearance of primitive emotionally-related behaviors essential for survival. It contains first-line specialized neurons enabling the detection and tracking of faces and movements from birth. During development, it also sends the appropriate impulses to help shape brain areas necessary for social-communicative abilities. These abilities require the analysis of numerous variables, such as the simultaneous evaluation of incoming information sustained by separate brain networks (visual, auditory and sensory-motor, social, emotional, etc.), and predictive capabilities which compare present events to previous experiences and possible responses. These critical aspects of decision-making allow us to evaluate the impact that our response or behavior may provoke in others. The purpose of this review is to show that several enigmas about the complexity of autism might be explained by disruptions of collicular and brainstem functions. The results of two separate lines of investigation: 1. the cognitive, etiologic, and pathogenic aspects of autism on one hand, and two. the functional anatomy of the colliculus on the other, are considered in order to bridge the gap between basic brain science and clinical studies and to promote future research in this unexplored area.
Associations of the Dietary Magnesium Intake and Magnesium Depletion Score With Osteoporosis Among American Adults: Data From the National Health and Nutrition Examination Survey
Authors: Wang Jie , Xing Fei , Sheng Ning , Xiang Zhou
Published: May 2022

Objectives

The study aimed to explore the associations between dietary magnesium (Mg) intake and magnesium depletion score (MDS) among American adults with osteoporosis.

Methods

The continuous data from the National Health and Nutrition Examination Survey 2005–2006, 2007–2008, 2009–2010, 2013–2014, and 2017–2018 were merged to ensure a large and representative sample and a total of 14,566 participants were enrolled for the analysis. The weighted multivariate linear regression model was performed to assess the linear relationship between dietary Mg intake and osteoporosis. Further, the non-linear relationship was also characterized by smooth curve fitting (SCF) and weighted generalized additive model (GAM). In addition, the odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between the MDS and osteoporosis were assessed by weighted logistic regression models.

Results

After adjusting all covariates, the weighted multivariable linear regression models demonstrated that the dietary Mg intake negatively correlated with osteoporosis, especially in participants aged 55 years or older. In addition, the non-linear relationship characterized by SCF and weighted GAM showed that the dietary Mg intake presented an L-shaped association with osteoporosis among females aged 55 years or older. Moreover, the weighted logistic regression model demonstrated that compared with MDS 0, the OR between MDS ≥3 and osteoporosis was 2.987 (95% CI 1.904, 4.686) in the male-middle intake group. Moreover, compared with MDS 0, the ORs between MDS ≥3 and osteoporosis was 5.666 (95% CI 3.188, 10.069) in the female-low intake group and 1.691 (95% CI 1.394, 2.051) in the female-middle intake group.

Conclusion

The present study indicated that in people with a daily intake of Mg level below the recommended daily intake (RDI), the dietary Mg intake and Mg bioavailability represented by MDS have a negative correlation with osteoporosis. According to the results, the combination of MDS and dietary Mg intake may be more comprehensive and rigorous in screening the population with osteoporosis. Therefore, early monitoring and interventions for osteoporosis may be necessary for those with insufficient dietary Mg intake or high MDS scores.
Probiotics Interact With Lipids Metabolism and Affect Gut Health
Authors: Wu Taoying , Wang Guangqiang , Xiong Zhiqiang , Xia Yongjun , Song Xin , Zhang Hui , Wu Yan , Ai Lianzhong
Published: May 2022

Probiotics have attracted much attention due to their ability to modulate host intestinal microbe, participate in nutrient metabolism or immunomodulatory. Both inflammatory bowel disease (IBD) and bowel cancer are digestive system disease, which have become a global public health problem due to their unclear etiology, difficult to cure, and repeated attacks. Disturbed gut microbiota and abnormal lipid metabolism would increase the risk of intestinal inflammation. However, the link between lipid metabolism, probiotics, and IBD is unclear. In this review, we found that different lipids and their derivatives have different effects on IBD and gut microbes. ω-3 polyunsaturated fatty acids (PUFAs) docosahexaenoic acid, eicosapentaenoic acid, and their derivatives resolvin E1, resolvin D can inhibit oxidative stress and reactive oxygen species activate NFκB and MAPk pathway. While ω-6 PUFAs linoleic acid and arachidonic acid can be derived into leukotrienes and prostaglandins, which will aggravate IBD. Cholesterol can be converted into bile acids to promote lipid absorption and affect microbial survival and colonization. At the same time, it is affected by microbial bile salt hydrolase to regulate blood lipids. Low denstiy lipoprotein (LDL) is easily converted into oxidized LDL, thereby promoting inflammation, while high denstiy lipoprotein (HDL) has the opposite effect. Probiotics compete with intestinal microorganisms for nutrients or ecological sites and thus affect the structure of intestinal microbiota. Moreover, microbial short chain fatty acids, bile salt hydrolase, superoxide dismutase, glutathione, etc. can affect lipid metabolism and IBD. In conclusion, probiotics are directly or indirectly involved in lipids metabolism and their impact on IBD, which provides the possibility to explore the role of probiotics in improving gut health.
A Germline Mutation in ATR Is Associated With Lung Adenocarcinoma in Asian Patients
Authors: Bao Guangyao , Guan Xiaojiao , Liang Jie , Yao Yao , Xiang Yifan , Li Tian , Zhong Xinwen
Published: May 2022

Background

Familial lung cancer (FLC) accounts for 8% of lung adenocarcinoma. It is known that a few germline mutations are associated with risk increasing and may provide new screening and treatment option. The goal of this study is to identify an FLC gene among three members of an FLC family.

Methods

To uncover somatic and embryonic mutations linked with familial lung cancer, whole exome sequencing was done on surgical tissues and peripheral blood from three sisters in a family diagnosed with pulmonary lung adenocarcinoma (LUAD). At the same time, single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data in public databases were enrolled to identify specific gene expression level.

Results

Ataxia Telangiectasia and Rad3-Related Protein (ATR) gene C.7667C >G (p.T2556S) mutation were found in 3 patients with familial lung cancer. Whole-genome sequencing revealed that the three sisters exhibited similar somatic mutation patterns. Besides ATR mutations, common mutated genes (BRCA1, EGFR, and ROS1) that characterize LUAD were also found in 5 tumor samples. Analysis for the ATR expression in LUAD patients by single-cell sequencing data, we found ATR expression of tumor patients at high level in immune cells when compared with normal patients, but the expression of ATR in stromal cells has the opposite result.

Conclusion

We found a germline mutation in the ATR gene in three sisters of a Chinese family affected by familial lung cancer, which may be a genetic factor for lung cancer susceptibility.
Perioperative Outcomes of Video-Assisted Thoracoscopic Surgery Versus Open Thoracotomy After Neoadjuvant Chemoimmunotherapy in Resectable NSCLC
Authors: Zhang Baihua , Xiao Qin , Xiao Haifan , Wu Jie , Yang Desong , Tang Jinming , Li Xu , Wu Zhining , Zhou Yong , Wang Wenxiang
Published: May 2022

Background

Neoadjuvant chemoimmunotherapy becomes more widespread in the treatment of NSCLC, but few studies have reported the details of surgical techniques and perioperative challenges following neoadjuvant chemoimmunotherapy until now. The primary aim of our study was to address the feasibility and safety of pulmonary resection after neoadjuvant chemoimmunotherapy via different surgical approaches, video-assisted thoracoscopic surgery (VATS) and open thoracotomy.

Methods

Patients with an initial diagnosis of clinical stage IB-IIIB(T3-4N2) NSCLC, who received neoadjuvant chemoimmunotherapy and surgery between January 2019 and August 2021 were included. Patients were retrospectively divided into two groups (VATS, and thoracotomy), and differences in perioperative, oncological, and survival outcomes were compared.

Results

In total, there were 131 NSCLC patients included. Surgery was delayed beyond 42 days in 21 patients (16.0%), and radical resection (R0) was achieved in 125 cases (95.4%). Lobectomy was the principal method of pulmonary resection (102 cases, 77.9%) and pneumonectomy was performed in 11 cases (8.4%). Postoperative complications within 30 days occurred in 28 patients (21.4%), and no 90-day mortality was recorded. There were 53 patients (38.5%) treated with VATS, and 78 (59.5%) with open thoracotomy. VATS could achieve similar definitive resection rates, postoperative recovery courses, comparable morbidities, and equivalent RFS rates(p>0.05), with the advantages of reduced operative time (160.1 ± 40.4 vs 177.7 ± 57.7 min, p=0.042), less intraoperative blood loss (149.8 ± 57.9 vs 321.2 ± 72.3 ml, p=0.021), and fewer intensive care unit(ICU) stays after surgery (3.8% vs 20.5%, p=0.006) compared with open thoracotomy. However, the mean number of total lymph nodes resected was lower in the VATS group (19.5 ± 7.9 vs 23.0 ± 8.1, p=0.013). More patients in the thoracotomy group received bronchial sleeve resection/bronchoplasty (53.8% vs 32.1%, p=0.014) and vascular sleeve resection/angioplasty (23.1% vs 3.8%, p=0.003). After propensity score matching (PSM) analysis, VATS still had the advantage of fewer ICU stays after surgery (2.3% vs. 20.5%, p=0.007).

Conclusions

Our results have confirmed that pulmonary resection following neoadjuvant PD-1 inhibitors plus chemotherapy is safe and feasible. VATS could achieve similar safety, definitive surgical resection, postoperative recovery, and equivalent oncological efficacy as open thoracotomy, with the advantage of fewer ICU stays after surgery.
Network Control Models With Personalized Genomics Data for Understanding Tumor Heterogeneity in Cancer
Authors: Yan Jipeng , Hu Zhuo , Li Zong-Wei , Sun Shiren , Guo Wei-Feng
Published: May 2022

Due to rapid development of high-throughput sequencing and biotechnology, it has brought new opportunities and challenges in developing efficient computational methods for exploring personalized genomics data of cancer patients. Because of the high-dimension and small sample size characteristics of these personalized genomics data, it is difficult for excavating effective information by using traditional statistical methods. In the past few years, network control methods have been proposed to solve networked system with high-dimension and small sample size. Researchers have made progress in the design and optimization of network control principles. However, there are few studies comprehensively surveying network control methods to analyze the biomolecular network data of individual patients. To address this problem, here we comprehensively surveyed complex network control methods on personalized omics data for understanding tumor heterogeneity in precision medicine of individual patients with cancer.
Determining Out-of-Field Doses and Second Cancer Risk From Proton Therapy in Young Patients—An Overview
Authors: Romero-Expósito Maite , Toma-Dasu Iuliana , Dasu Alexandru
Published: May 2022

Proton therapy has the potential to provide survival and tumor control outcomes comparable and frequently superior to photon therapy. This has led to a significant concern in the medical physics community on the risk for the induction of second cancers in all patients and especially in younger patients, as they are considered more radiosensitive than adults and have an even longer expected lifetime after treatment. Thus, our purpose is to present an overview of the research carried out on the evaluation of out-of-field doses linked to second cancer induction and the prediction of this risk. Most investigations consisted of Monte Carlo simulations in passive beam facilities for clinical scenarios. These works established that equivalent doses in organs could be up to 200 mSv or 900 mSv for a brain or a craniospinal treatment, respectively. The major contribution to this dose comes from the secondary neutrons produced in the beam line elements. Few works focused on scanned-beam facilities, but available data show that, for these facilities, equivalent doses could be between 2 and 50 times lower. Patient age is a relevant factor in the dose level, especially for younger patients (by means of the size of the body) and, in addition, in the predicted risk by models (due to the age dependence of the radiosensitivity). For risks, the sex of the patient also plays an important role, as female patients show higher sensitivity to radiation. Thus, predicted risks of craniospinal irradiation can range from 8% for a 15-year-old male patient to 58% for a 2-year-old female patient, using a risk model from a radiological protection field. These values must be taken with caution due to uncertainties in risk models, and then dosimetric evaluation of stray radiation becomes mandatory in order to complement epidemiological studies and be able to model appropriate dose–response functions for this dose range. In this sense, analytical models represent a useful tool and some models have been implemented to be used for young patients. Research carried out so far confirmed that proton beam therapy reduces the out-of-field doses and second cancer risk. However, further investigations may be required in scanned-beam delivery systems.
Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Phase 2 Study
Authors: Chen Xiaofeng , Li Wei , Wu Xiaofeng , Zhao Fengjiao , Wang Deqiang , Wu Hao , Gu Yanhong , Li Xiao , Qian Xiaofeng , Hu Jun , Li Changxian , Xia Yongxiang , Rao Jianhua , Dai Xinzheng , Shao Qianwen , Tang Jie , Li Xiangcheng , Shu Yongqian
Published: May 2022

Purpose

Immune checkpoint inhibitors plus antiangiogenic tyrosine kinase inhibitors may offer a first-line treatment for advanced hepatocellular carcinoma (HCC). In this phase 2 trial [registered with clinicaltrials.gov (NCT04052152)], we investigated the safety and efficacy of first-line anti-PD-1 antibody sintilimab plus antiangiogenic TKI anlotinib for advanced HCC.

Methods and Materials

Pathologically-proven advanced HCC patients received sintilimab (200 mg) on day 1 and anlotinib (12 mg) once daily on days 1 to 14 every 3 weeks, with a safety run-in for the first six participants to assess dose-limiting toxicities (DLTs). The primary endpoints were safety and objective response rate (ORR) per RECIST v1.1.

Results

Twenty advanced HCC patients were enrolled. No DLTs occurred in the safety run-in. All patients had treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 8 (40.0%) patients, the most common being decreased platelet count (10.0%) and increased γ-glutamyl transferase (10.0%). No grade 4/5 TRAEs occurred. Five (25%) patients developed immune-related AEs. The ORR was 35.0% (95%CI 15.4%-59.2%) per RECIST v1.1 and 55.0% (95%CI 31.5%-76.9%) per modified RECIST. At data cutoff (March 31, 2021), the median progression-free survival was 12.2 months (95%CI, 3.8 to not reached). The median PFS was significantly longer in patients with lower LDH levels (not reached [NR], 95% CI, 8.7 to NR vs. higher LDH levels 5.2 months, 95% CI 3.4 to NR; P=0.020) and a CONUT score ≤2 (NR, 95% CI 5.1 to NR vs. CONUT score >2 6.2 months, 95% CI 1.8 to NR; P=0.020). Furthermore, patients showing tumor response had a significantly higher median proportion of CD16+CD56+ NK cells than patients who had stable or progressive disease (21.6% vs. 14.6%; P=0.026).

Conclusion

Sintilimab plus anlotinib showed promising clinical activities with manageable toxicity as first-line treatment of advanced HCC.
The Effect of Risk Accumulation on Childhood Stunting: A Matched Case-Control Study in China
Authors: Tang Xiao , Zhao Yanxiang , Liu Qigui , Hu Dongmei , Li Guorong , Sun Jin , Song Guirong
Published: May 2022

Background

Childhood stunting is still a public health issue in developing countries. However, the traditional risk factors in underdeveloped areas are not suitable for developed areas. Moreover, childhood stunting is influenced by several aspects, including genetic factors, perinatal conditions, maternal conditions, and feeding practices, but researchers have not yet clearly determined which aspect of risk accumulation exerts the strongest effect on stunting. A matched case-control study was performed to assess the effect of different aspects of risk accumulation on childhood stunting.

Methods

In total, 173 non-stunted children aged under 7 years were matched in our study from June 2015 to August 2015. The children's heights and weights were measured, and a self-administered questionnaire was used to collect information from the children and their parents. The risk factors were assigned to the following five aspects: genetic factors, family socioeconomic status, perinatal conditions, maternal conditions, and feeding practices. The risk accumulation (cumulative risk score) in each aspect was defined as the total number of risk factors that occurred in a certain aspect. A conditional logistic regression model was used to assess the effect of risk accumulation in different aspects on stunting, and a decision-tree model was used to predict the children's stunting based on the cumulative risk scores.

Results

Risk accumulation in perinatal conditions, genetic factors, maternal conditions, and feeding practices was significant in the conditional logistic regression model (P < 0.05). Perinatal conditions showed the strongest association with stunting in both the regression analysis and the decision-tree model. The risk of stunting increased by 1.199 times if the cumulative risk score for perinatal conditions increased by one, and the probability of stunting was 75.8% if the cumulative risk score for perinatal conditions was ≥1.

Conclusion

Risk accumulation in perinatal conditions, genetic factors, maternal conditions, and feeding practices substantially increased the probability of stunting in childhood. Perinatal conditions were the main aspect associated with stunting. Prevention and intervention measures should be adopted to avoid risk accumulation in stunting.
Case Report: Isolated Epileptic Seizures Associated With Anti-LGI1 Antibodies in a 7-Year-Old Girl With Literature Review
Authors: Wang Ying , Zhang Wei-Hua , Wang Yuan
Published: May 2022

We describe the case of a 7-year-old girl with anti-leucine-rich glioma-inactivated 1 (anti-LGI1) antibodies (Abs) who presented with isolated epileptic seizures. Her refractory focal seizures did not respond to anti-seizure medicines but responded rapidly to immunotherapy. She remained seizure-free at 2 years follow-up. Reviewing the literature, isolated epileptic seizures have not been reported as the phenotype of anti-LGI1 autoimmunity in children. Our study indicated that screening for anti-LGI1 Abs is necessary for children with severe and/or drug-resistant new-onset focal epileptic seizures.
Children's Positive and Negative Emotional Responses to an HIV Disclosure Study in South Africa
Authors: Ramsammy Candice W. , Galvin Lisa , Joyce Celeste , Leshabane Given , Buckley Janice , Otwombe Kennedy , Liberty Afaaf , Violari Avy
Published: May 2022

The benefits of HIV status disclosure to children is widely cited. However, few studies have reported how children respond to the process in a longitudinal fashion. This paper describes children's responses, as documented by healthcare providers (HCPs), during a longitudinal disclosure study conducted at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa. Two HCPs facilitating disclosure recorded observations of 30 participating children (60% female), aged 7-13 years. Participants attended an average of six disclosure counseling sessions over 78 weeks. Observations documented by HCPs included the child's behavior and expressed emotions during the disclosure counseling sessions. The data was analyzed using content analysis. Mixed responses were observed in children who received full disclosure (27/30), with more children responding with strong negative emotions (16/27). However, 10 of those responded well to reassurance, and emotionally improved over subsequent sessions. Improvements were also observed in the communication and relationship between caregivers and children (17/30). Although most children understood the disclosure content (17/30), many were avoidant of the topic of HIV (16/30). With the understanding of the complex range of emotions elicited by HIV disclosure, we can better prepare HCPs on what to anticipate and train caregivers to further manage negative responses post-disclosure. This in turn may lead to more positive experiences of disclosure and the child's healthy acceptance of their HIV status.
Association of Gestational Age at Birth With Subsequent Neurodevelopment in Early Childhood: A National Retrospective Cohort Study in China
Authors: Hua Jing , Barnett Anna L. , Lin Yao , Guan Hongyan , Sun Yuanjie , Williams Gareth J. , Fu Yuxuan , Zhou Yingchun , Du Wenchong
Published: May 2022

Background

The association between preterm birth and neurodevelopmental delays have been well examined, however, reliable estimates for the full range of gestational age (GA) are limited, and few studies explored the impact of post-term birth on child development.

Objective

This study aimed to examine the long-term neuropsychological outcomes of children born in a full range of GA with a national representative sample in China.

Methods

In this retrospective population-based cohort study, a total of 137,530 preschoolers aged 3–5 years old (65,295/47.5% females and 72,235/52.5% males) were included in the final analysis. The Ages and Stages Questionnaires-Third Edition (ASQ-3) was completed by parents to evaluate children's neurodevelopment. The associations between GA and neurodevelopment were analyzed by a generalized additive mixed model with thin plate regression splines. Logistic regression was also conducted to examine the differences in children's development with different GAs.

Results

There was a non-linear relationship between GA and children's neurodevelopmental outcomes with the highest scores at 40 weeks gestational age. The adjusted risks of GAs (very and moderately preterm, late-preterm, early-term, and post-term groups) on suspected developmental delays were observed in communication (OR were 1.83, 1.28, 1.13, and 1.21 respectively, each p < 0.05), gross motor skill (OR were 1.67, 1.38, 1.10, and 1.05 respectively, each p < 0.05), and personal social behavior (OR were 1.01, 1.36, 1.12, and 1.18 respectively, each p < 0.05). The adjusted OR of very and moderately preterm, late-preterm, and early-term were observed in fine motor skills (OR were 1.53, 1.22, and 1.09 respectively, each p < 0.05) and problem-solving (OR were 1.33, 1.12, and 1.06 respectively, each p < 0.05).

Conclusion

GAs is a risk factor for neurodevelopmental delays in preschoolers after controlling for a wide range of covariates, and 40–41 weeks may be the ideal delivery GA for optimal neurodevelopmental outcomes. Close observation and monitoring should be considered for early- and post-term born children as well as pre-term children.
Current Knowledge Regarding Long-Term Consequences of Pediatric Intensive Care: A Staff Survey in Intensive Care Units in German-Speaking Countries
Authors: Von Borell Florian , Engel Juliane , Neunhoeffer Felix , Hoffmann Florian , Michel Jörg
Published: May 2022

Background

The Post Intensive Care Syndrome (PICS) describes new impairments of physical, cognitive, social, or mental health after critical illness. In recent years, prevention and therapy concepts have been developed. However, it is unclear whether and to what extent these concepts are known and implemented in hospitals in German-speaking countries.

Methods

We conducted an anonymous online survey in German-speaking pediatric intensive care units on the current state of knowledge about the long-term consequences of intensive care treatment as well as about already established prevention and therapy measures. The request to participate in the survey was sent to the heads of the PICUs of 98 hospitals.

Results

We received 98 responses, 54% of the responses came from nurses, 43% from physicians and 3% from psychologist, all working in intensive care. As a main finding, our survey showed that for only 31% of the respondents PICS has an importance in their daily clinical practice. On average, respondents estimated that about 42% of children receiving intensive care were affected by long-term consequences after intensive care. The existence of a follow-up outpatient clinic was mentioned by 14% of the respondents. Frequent reported barriers to providing follow-up clinics were lack of time and staff. Most frequent mentioned core outcome parameters were normal developmental trajectory (59%) and good quality of life (52%).

Conclusion

Overall, the concept of PICS seems to be underrepresented in German-speaking pediatric intensive care units. It is crucial to expand knowledge on long-term complications after pediatric critical care and to strive for further research through follow-up programs and therewith ultimately improve long-term outcomes.
Case Report: Ciclosporin A for Refractory Multisystem Inflammatory Syndrome in Children
Authors: Suzuki Takayuki , Suenaga Tomohiro , Sakai Aiko , Sugiyama Masaya , Mizokami Masashi , Mizukami Ayumi , Takasago Satoshi , Hamada Hiromichi , Kakimoto Nobuyuki , Takeuchi Takashi , Ueda Mina , Komori Yuki , Tokuhara Daisuke , Suzuki Hiroyuki
Published: May 2022

Multisystem inflammatory syndrome in children (MIS-C) is a new syndrome involving the development of severe dysfunction in multiple organs after severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Because the pathophysiology of MIS-C remains unclear, a treatment strategy has not yet been established. We experienced a 12-year-old boy who developed MIS-C at 56 days after SARS-CoV-2 infection and for whom ciclosporin A (CsA) was effective as a third-line treatment. He had a high fever on day 1, and developed a rash on the trunk, swelling in the cervical region, and palmar erythema on day 2. On days 3, he developed conjunctivitis and lip redness, and fulfilled the criteria for classical Kawasaki disease (KD). Although intravenous immunoglobulin infusion (IVIG) was started on day 4, fever persisted and respiratory distress and severe abdominal pain developed. On day 5, because he fulfilled the criteria for MIS-C, methylprednisolone pulse was started for 3 days as a second-line treatment. However, he did not exhibit defervescence and the symptoms continued. Therefore, we selected CsA as a third-line treatment. CsA was so effective that he became defervescent and his symptoms disappeared. In order to clarify the relationship with treatment and the change of clinical conditions, we examined the kinetics of 71 serum cytokines to determine their relationships with his clinical course during the three successive treatments. We found that CsA suppressed macrophage-activating cytokines such as, IL-12(p40), and IL-18 with improvement of his clinical symptoms. CsA may be a useful option for additional treatment of patients with MIS-C refractory to IVIG + methylprednisolone pulse.
Softer More Frequent Stools in Infants With Difficult Stooling Fed Hydrolyzed Protein Formula With Added Prebiotics: Randomized Controlled Trial
Authors: Fabrizio Veronica , Harris Cheryl L. , Walsh Kelly R. , Wampler Jennifer L. , Zhuang Weihong , Wu Steven S.
Published: May 2022

Objective

To evaluate stool consistency in infants with reported hard or infrequent stools fed hydrolyzed protein formula with added prebiotics designed to promote stool softening.

Methods

In this multi-center, double-blind, controlled study, eligible infants (28–300 days of age at enrollment) were randomized to: partially hydrolyzed cow’s milk protein formula (PHF, 75% carbohydrate as lactose; 12 mg Mg/100 kcal; n = 49) or routine intact protein cow’s milk-based infant formula (Control, 92% carbohydrate as lactose; 8 mg Mg/100 kcal; n = 51) over a 14-day period. Both formulas had a prebiotic blend (polydextrose and galactooligosaccharides, 4 g/L; 1:1 ratio). Parent-reported stool consistency (hard = 1 through watery = 5) and other daily outcomes were collected by diary. Endpoint stool consistency (mean score over last 3 days of study feeding) was the primary outcome. Adverse events were recorded.

Results

Baseline stool consistency (Control: 1.4 ± 0.1, PHF: 1.4 ± 0.1) and frequency were similar between groups; the majority had hard (n = 61, 64%) or formed (n = 30, 32%) stools. Stool consistency became softer over Day 1–3 (Control: 2.5 ± 0.1, PHF: 2.6 ± 0.1) and remained similar from Day 4 to 6 through study end (post hoc analysis). For PHF vs Control, endpoint stool consistency was significantly softer (3.4 ± 0.1 vs 3.0 ± 0.1; P = 0.019) and frequency significantly higher (1.5 ± 0.1 vs 1.0 ± 0.1; P = 0.002). Crying, fussing, and appearance of pain during stooling decreased from baseline to study end in both groups. Formula intake, infant fussiness and incidence of adverse events were similar between groups.

Conclusion

An infant formula designed to promote stool softening was well-tolerated and associated with softer, more frequent stools in infants with reported hard or infrequent stools.
Enteral Feeding/Total Fluid Intake Ratio Is Associated With Risk of Bronchopulmonary Dysplasia in Extremely Preterm Infants
Authors: Lin Bingchun , Xiong Xiaoyun , Lu Xia , Zhao Jie , Huang Zhifeng , Chen Xueyu
Published: May 2022

Background

Nutrition is an essential factor in preventing and managing bronchopulmonary dysplasia (BPD), a multifactorial chronic respiratory disease in premature infants. This study examined the association between nutritional intakes during the first 2 weeks of life and BPD in extremely preterm infants.

Methods

A retrospective single-center cohort study was performed in infants born <28 weeks' gestational age or with a birth weight <1,000 g. Intake of energy and ratio of enteral feeding/ total fluid intake during the first 2 weeks of life and association with outcome of BPD were examined.

Results

134 infants were included in our study, and 43 infants (32.1%) developed BPD. During the first 2 weeks of life, the average of total caloric intake and the ratio of enteral feeding/ total fluid intake were significantly lower in the BPD group (total caloric intake:91.90 vs. 95.72 kcal/kg/d, p < 0.05, ratio of enteral feeding/total fluid intake: 0.14 vs. 0.18, p < 0.05), while the average of total fluid intake, caloric and protein intake from parenteral nutrition did not differ between the groups. The ratio of enteral feeding/ total fluid intake during the second week were significantly lower in the BPD group (0.21 vs. 0.28, p < 0.05), while this ratio during the first week did not differ between the groups. An increase of 10% in the ratio of enteral feeding/ total fluid intake during the second week of life significantly reduced the risk of BPD (OR 0.444, 95% CI: 0.270–0.731).

Conclusions

A higher ratio of enteral feeding/ total fluid intake was associated with a lower risk for BPD. Early and rapidly progressive enteral nutrition should be encouraged in extremely preterm infants in the absence of feeding intolerance.
Maternal and Neonatal Prognostic Factors for Cardiorespiratory Events in Healthy Term Neonates During Early Skin-to-Skin Contact
Authors: Rodríguez-López Jesús , De la Cruz Bértolo Javier , García-Lara Nadia Raquela , Asla Elorriaga Izaskun , Román Echevarría Lourdes , Vento Máximo , Parra-Llorca Anna , Cabañas Fernando , Lozano Pedro , García-Algar Óscar , Martín-Ancel Ana , Copons Fernández Cristina , González Carrasco Ersilia , Olabarrieta Arnal Iciar , Pellicer Adelina , Marín Huarte Natalia , Pallás-Alonso Carmen Rosa
Published: May 2022

Background

During early skin-to-skin contact (ESSC), alterations in peripheral oxygen saturation (SpO2) and heart rate (HR) have been frequently observed.

Objectives

This study aimed to determine the incidence of cardiorespiratory events (CREs) during ESSC in healthy term newborns (HTNs) and estimate the association of maternal and neonatal prognostic factors with the risk of CREs.

Methods

A pooled analysis of the cohort from a clinical trial involving healthy mother–child dyads during ESSC was performed. Pulse oximetry was employed to continuously monitor SpO2 and HR within 2 h after birth. The individual and combined prognostic relevance of the demographic and clinical characteristics of dyads for the occurrence of a CRE (SpO2 <91% or HR <111 or >180 bpm) was analyzed through logistic regression models.

Results

Of the 254 children assessed, 169 [66.5%; 95% confidence interval (95% CI), 60.5–72.5%] had at least one CRE. The characteristics that increased the risk of CRE were maternal age ≥35 years (odds ratio, 2.21; 95% CI, 1.19–4.09), primiparity (1.96; 1.03–3.72), gestational body mass index (BMI) >25 kg/m2 (1.92; 1.05–3.53), and birth time between 09:00 p.m. and 08:59 a.m. (2.47; 1.02–5.97).

Conclusion

CREs were more frequent in HTNs born during nighttime and in HTNs born to first-time mothers, mothers ≥35 years, and mothers with a gestational BMI >25 kg/m2. These predictor variables can be determined during childbirth. Identification of neonates at higher risk of developing CREs would allow for closer surveillance during ESSC.
Aerobic Exercise Inhibited P2X7 Purinergic Receptors to Improve Cardiac Remodeling in Mice With Type 2 Diabetes
Authors: Wang Ting , Li Jianmin , Li Hui , Zhong Xin , Wang Luya , Zhao Shujue , Liu Xuesheng , Huang Zhouqing , Wang Yonghua
Published: May 2022

Background: Diabetic cardiomyopathy (DCM), the main complication of diabetes mellitus, presents as cardiac dysfunction by ventricular remodeling. In addition, the inhibition of P2X7 purinergic receptors (P2X7R) alleviates cardiac fibrosis and apoptosis in Type 1 diabetes. However, whether exercise training improves cardiac remodeling by regulating P2X7R remains unknown.

Methods: Db/db mice spontaneously induced with type 2 diabetes and high-fat diet (HFD) and mice with streptozotocin (STZ)-induced type 2 diabetes mice were treated by 12-week treadmill training. Cardiac functions were observed by two-dimensional echocardiography. Hematoxylin-eosin staining, Sirius red staining and transmission electron microscopy were respectively used to detect cardiac morphology, fibrosis and mitochondria. In addition, real-time polymerase chain reaction and Western Blot were used to detect mRNA and protein levels.

Results: Studying the hearts of db/db mice and STZ-induced mice, we found that collagen deposition and the number of disordered cells significantly increased compared with the control group. However, exercise markedly reversed these changes, and the same tendency was observed in the expression of MMP9, COL-I, and TGF-β, which indicated cardiac fibrotic and hypertrophic markers, including ANP and MyHC expression. In addition, the increased Caspase-3 level and the ratio of Bax/Bcl2 were reduced by exercise training, and similar results were observed in the TUNEL test. Notably, the expression of P2X7R was greatly upregulated in the hearts of db/db mice and HFD + STZ-induced DM mice and downregulated by aerobic exercise. Moreover, we indicated that P2X7R knock out significantly reduced the collagen deposition and disordered cells in the DM group. Furthermore, the apoptosis levels and TUNEL analysis were greatly inhibited by exercise or in the P2X7R−/− group in DM. We found significant differences between the P2X7R−/− + DM + EX group and DM + EX group in myocardial tissue apoptosis and fibrosis, in which the former is significantly milder. Moreover, compared with the P2X7R−/− + DM group, the P2X7R−/− + DM + EX group represented a lower level of cardiac fibrosis. The expression levels of TGF-β at the protein level and TGF-β and ANP at the genetic level were evidently decreased in the P2X7R−/− + DM + EX group.

Conclusion: Aerobic exercise reversed cardiac remodeling in diabetic mice at least partly through inhibiting P2X7R expression in cardiomyocytes.
Why can Mozambique Tilapia Acclimate to Both Freshwater and Seawater? Insights From the Plasticity of Ionocyte Functions in the Euryhaline Teleost
Authors: Inokuchi Mayu , Hiroi Junya , Kaneko Toyoji
Published: May 2022

In teleost fishes, ionocytes in the gills are important osmoregulatory sites in maintaining ionic balance. During the embryonic stages before the formation of the gills, ionocytes are located in the yolk-sac membrane and body skin. In Mozambique tilapia embryos, quintuple-color immunofluorescence staining allowed us to classify ionocytes into four types: type I, showing only basolateral Na+/K+-ATPase (NKA) staining; type II, basolateral NKA and apical Na+, Cl− cotransporter 2; type III, basolateral NKA, basolateral Na+, K+, 2Cl− cotransporter 1a (NKCC1a) and apical Na+/H+ exchanger 3; and type IV, basolateral NKA, basolateral NKCC1a and apical cystic fibrosis transmembrane conductance regulator Cl− channel. The ionocyte population consisted mostly of type I, type II and type III in freshwater, while type I and IV dominated in seawater. In adult tilapia, dual observations of whole-mount immunocytochemistry and scanning electron microscopy showed morphofunctional alterations in ionocytes. After transfer from freshwater to seawater, while type-II ionocytes closed their apical openings to suspend ion absorption, type-III ionocytes with a concave surface were transformed into type IV with a pit via a transitory surface. The proposed model of functional classification of ionocytes can account not only for ion uptake in freshwater and ion secretion in seawater, but also for plasticity in ion-transporting functions of ionocytes in tilapia.
Identification of Silencing Suppressor Protein Encoded by Strawberry Mottle Virus
Authors: Fan Lingjiao , He Chengyong , Gao Dehang , Xu Tengfei , Xing Fei , Yan Jiaqi , Zhan Binhui , Li Shifang , Wang Hongqing
Published: May 2022

Strawberry mottle virus (SMoV) is associated with strawberry decline disease, causing losses to fruit yield and quality. In this study, using a screening system that enables detection of both local and systemic plant host (RNA silencing) defense responses, we found that Pro2Glu and P28, encoded by SMoV RNA2 genome, functioned to suppress local and systemic RNA silencing triggered by single- but not double-stranded GFP RNA. Subcellular localization assay revealed that both Pro2Glu and P28 were localized to nucleus and cytoplasm. The deletion of 11 amino acid residues at the C-terminus destabilized Pro2Glu protein, and the disruption of two conserved GW motifs deprived Pro2Glu of ability to suppress RNA silencing. Additionally, SMoV Pro2Glu and P28 enhanced the accumulation of potato virus X (PVX) in Nicotiana benthamiana 22 days post-infiltration, and P28 exacerbated significantly the symptoms of PVX. Collectively, these data indicate that the genome of SMoV RNA2 encodes two suppressors of RNA silencing. This is the first identification of a stramovirus suppressor of RNA silencing.
QTLs Identification for Iron Chlorosis in a Segregating Peach–Almond Progeny Through Double-Digest Sequence-Based Genotyping (SBG)
Authors: Guajardo Verónica , Martínez-García Pedro José , Solís Simón , Calleja-Satrustegui Aitziber , Saski Christopher , Moreno María Ángeles
Published: May 2022

Linkage maps are highly appreciated tools for cultivar and rootstock breeding programs because they are suitable for genetic and genomic studies. In this study, we report on using sequence-based genotyping (SBG) approach to simultaneously discover and genotype SNPs from two peach-based rootstocks (“Adafuel” and “Flordaguard”) and their progeny (n= 118): from a initial mapping population composed of 131 seedlings. The plant material was developed at the EEAD–CSICPrunusrootstocks breeding program, aiming to obtain a segregating progeny for a range of characters of agronomical interest to rootstock breeding (iron-chlorosis and root-asphyxia tolerance, nematode resistance, vigor traits, and other effects on scion cultivars). Sequence reads obtained from double-digest SBG were aligned to theP. persicareference genome (Peach v2.0). While eight linkage groups were constructed for “Adafuel,” only four linkage groups were constructed for “Flordaguard,” given the low heterozygosity of this last genotype. High synteny and co-linearity were observed between obtained maps and Peach v2.0. On the other hand, this work aimed to elucidate the genetic basis of leaf chlorosis tolerance using the phenotypic segregation of the progeny to iron-chlorosis tolerance, along with the QTLs responsible for leaf chlorosis. The F1 mapping population, composed initially of 131 seedlings, was growing in four field trials established on calcareous soils at the experimental field of the EEAD-CSIC in Zaragoza, Spain. From the initial mapping population, 131 individuals were selected for their phenotypical characterization with SPAD measurements of plants grown in the field, exhibiting a great variability. Significant QTLs associated with tolerance to iron chlorosis were found in LG1, LG5, LG7, and LG8. The significant QTLs detected in LG5 and LG7 have not been associated with this abiotic stress before inPrunus. Several candidate genes such as Prupe.1G541100, predicted as glutamyl-tRNA reductase 1, Prupe.1G468200, encoding a 2-oxoglutarate (2OG), and Fe(II)-dependent oxygenase superfamily protein or Prupe.1G577000 (ppa011050.m), a NIFU-like protein 2 (NIFU2) were detected. The exact biological function of some of these genes should be verified for the future development of marker-assisted selection for peach iron chlorosis tolerance.
The Association of Salivary Serotonin With Mood and Cardio-Autonomic Function: A Preliminary Report
Authors: Karbownik Michał Seweryn , Hicks Steven Daniel
Published: May 2022

Background

Serotonin plays an important role in mood regulation and depression. However, it is not clear whether the levels of serotonin in saliva are related to current mood.

Aim

To test the association of salivary serotonin concentrations with mood, as well as cardiovascular and autonomic parameters.

Materials and Methods

Saliva samples were obtained from collegiate runners and output parameters were examined before and after physical activity.

Results

Salivary serotonin concentration was negatively associated with current mood (β = −0.32, 95%CI −0.62 to −0.02, p = 0.037, analysis adjusted for potential confounders), but insignificantly with measured cardiovascular and autonomic parameters.

Conclusions

Salivary serotonin may reflect current mood. The results are preliminary and require further evaluation.