bluuebunny/crossref_metadata_2025 huggingface dataset:
The association between sugar-sweetened beverages and milk intake with emotional and behavioral problems in children with autism spectrum disorder
Authors: Tan Si , Pan Ning , Xu Xiaoyu , Li Hailin , Lin Lizi , Chen Jiajie , Jin Chengkai , Pan Shuolin , Jing Jin , Li Xiuhong
Published: August 2022

Background

Emotional and behavioral problems are common in children with autism spectrum disorder (ASD). It's still unclear whether children with ASD have abnormal sugar-sweetened beverages (SSBs) and milk intake and whether this abnormality will affect their emotions and behavior remains unclear. The current study aims to investigate the association of SSBs and milk intake with emotional and behavioral problems in children with autism spectrum disorder (ASD).

Methods

107 children with ASD and 207 typical developing (TD) children aged 6-12 years old were recruited for the study. The frequency of SSBs and milk intake was assessed by a self-designed questionnaire. Emotional and behavioral problems were assessed by Strength and Difficulties Questionnaire (SDQ). Then, the linear regression model was produced to evaluate the association of SSBs and milk intake with emotional and behavioral problems.

Results

In the current study, there was no difference in frequency of SSBs intake between children with ASD and TD children (p > 0.05), and children with ASD consumed less milk compared to TD children (p < 0.05). After adjusting sex, age, maternal and paternal education, and monthly family income, we found a significant difference in each subscale score of SDQ in the two groups (p < 0.05). In children with ASD, higher frequent SSBs intake was positively associated with the scores of the emotional problem (p for trend <0.05), and lower frequent milk intake was inversely associated with the scores of prosocial behavior (p for trend <0.05). No interactive effects were found on SSBs and milk intake with emotional and behavioral problems (p for trend > 0.05).

Conclusion

In children with ASD, frequency of SSBs and milk intake was associated with the emotional problem and prosocial behavior, respectively. Children with ASD should increase the frequency of milk intake and decrease the frequency of SSBs intake.
Obesity in male volcano mice Neotomodon alstoni affects the daily rhythm of metabolism and thermoregulation
Authors: Herrera-García Andrea , Pérez-Mendoza Moisés , Arellanes-Licea Elvira del Carmen , Gasca-Martínez Deisy , Carmona-Castro Agustín , Díaz-Muñoz Mauricio , Miranda-Anaya Manuel
Published: August 2022

The mouseN. alstonispontaneously develops the condition of obesity in captivity when fed regular chow. We aim to study the differences in metabolic performance and thermoregulation between adult lean and obese male mice. The experimental approach included indirect calorimetry using metabolic cages for VO2intake and VCO2production. In contrast, the body temperature was measured and analyzed using intraperitoneal data loggers. It was correlated with the relative presence of UCP1 protein and its gene expression from interscapular adipose tissue (iBAT). We also explored in this tissue the relative presence of Tyrosine Hydroxylase (TH) protein, the rate-limiting enzyme for catecholamine biosynthesis present in iBAT. Results indicate that obese mice show a daily rhythm persists in estimated parameters but with differences in amplitude and profile. Obese mice presented lower body temperature, and a low caloric expenditure, together with lower VO2intake and VCO2than lean mice. Also, obese mice present a reduced thermoregulatory response after a cold pulse. Results are correlated with a low relative presence of TH and UCP1 protein. However, qPCR analysis of Ucp1 presents an increase in gene expression in iBAT. Histology showed a reduced amount of brown adipocytes in BAT. The aforementioned indicates that the daily rhythm in aerobic metabolism, thermoregulation, and body temperature control have reduced amplitude in obese miceNeotomodon alstoni.
Impact of agro-forestry systems on the aroma generation of coffee beans
Authors: Xu Su , Liu Yuze , Ma Fengwei , Yang Ni , Virginio Filho Elias de Melo , Fisk Ian Denis
Published: August 2022

A long experiment has been established since 2000 at CATIE (Tropical Agricultural Research and Higher Education Center), Turrialba, Costa Rica. Twenty agro-forestry systems with different shade types and managements (organic and non-organic) consisting of an incomplete randomized block-design with shade tree as main effect and subplots represented by management were set up. The effects of different managements and shade types on the aroma and color generation of roasted coffee beans were investigated. The total protein content was significantly higher (P < 0.05) under the intensive conventional (IC) (168 g/Kg) and intensive organic (IO) (167 g/Kg) managements than under the moderate conventional (MC) (153 g/Kg in IC vs. MC group, 157 g/Kg in MC vs. IO group). Comparing with the moderate conventional (MC) management, the intensive organic (IO) management had a stronger ability to generate more flavor and color. The total protein content was significantly higher (P < 0.05) under the full sun system (172 g/Kg) than under the shaded (159 g/Kg) and Erythrina system (155 g/Kg), under the service system (165 g/Kg) than under the timber system (146 g/Kg), under the legume timber system (170 g/Kg) than under the non-legume timber system (152 g/Kg). The full sun system had a greater flavor generation and color after roasting. Comparing with the timber system, the service system produced roasted beans with the more flavor and color. Comparing with the non-legume shade tree, the legume shade tree improved the performance of flavor and color in the roasted coffee beans.
Effect of ancient wheat pasta on gut microbiota composition and bacteria-derived metabolites: A randomized controlled trial
Authors: Baldi Simone , Dinu Monica , Pagliai Giuditta , Colombini Barbara , Di Gloria Leandro , Curini Lavinia , Pallecchi Marco , Ramazzotti Matteo , Bartolucci Gianluca , Benedettelli Stefano , Amedei Amedeo , Sofi Francesco
Published: August 2022

Background and aim

In recent years, many studies have suggested that ancient wheat products might have beneficial effects on cardiometabolic risk profile, but little is known about their effect on gut microbiota (GM). The aim of the present study was to evaluate whether a replacement diet with pasta made from ancient wheat (AD) could influence the GM composition and its metabolites’ production compared to a replacement diet with pasta made from modern wheat (CD).

Methods

A randomized, double-blinded crossover trial with two intervention phases was conducted on 20 clinically healthy adults (9 females; 11 males; mean age 43.1 ± 12.5 years). Study participants were assigned to consume pasta made using semi-whole flour from organic wheat that was either from ancient or modern control wheat for 8 weeks in a random order. An 8-week washout period was implemented between the interventions. Stool samples were collected from all subjects at the beginning and at the end of each intervention period. GM composition, and short- (SCFAs) and medium- chain fatty acids (MCFAs) production was evaluated.

Results

Dietary interventions did not produce significant diversity in the GM composition at higher ranks (phylum, class, order and family), but only at genus level. In detail, the AD significantly (adj. p < 0.05) changed the abundance of Erysipelatoclostridium spp., Bacteroides_pectinophilus_group spp., CAG-873 spp., and Holdemanella spp. The CD significantly affected the abundance of Akkermansia spp., CAG-873 spp., Hungatella spp., Lachnospiraceae_UCG-008 spp., NK4A214_group spp., Frisingicoccus spp., Megasphaera spp., Synergistes spp., and Tyzzerella spp. Regarding the production of SCFAs and MCFAs, AD resulted in a significant increase of fecal acetic (+0.7%), isobutyric (+30.1%), 2-methylbutyric (+64.2%), and isovaleric (+22.5%) acids. On the other hand, CD resulted in increased levels of isobutyric (+71.4%), 2-methylbutyric (+116.2%), isovaleric (+99%), and valeric (+21.4%) acids, and a reduction of butyric (-31.6%) and hexanoic (-66.4%) acids.

Conclusion

A short-term replacement diet with both ancient and modern wheat pasta determined significant changes in GM composition at the genus level but notably the AD resulted in a greater beneficial impact on anti-inflammatory SCFAs.
Identification and validation of four photodynamic therapy related genes inhibiting MAPK and inducing cell cycle alteration in squamous cell carcinoma
Authors: Zhao Yingchao , Dong Jianxiang , Liao Yuxuan , Wang Hongyi , Zhou Dawei , Kang Jian , Chen Xiang
Published: August 2022

Introduction

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, and photodynamic therapy (PDT) is a promising modality against cSCC. This study investigated the impact of PDT on the MAPK pathway and cell cycle alternation of cSCC as well as the related molecular mechanisms.

Method

Expressing mRNA profile data sets GSE98767, GSE45216, and GSE84758 were acquired from the GEO database. The functions of differently expressed genes (DEGs) were enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Least absolute shrinkage and selection operator (Lasso) analysis were used to establish a diagnosis model based on GSE98767. A correlation analysis and a protein–protein interaction (PPI) network were used to evaluate the relationship between cSCC-PDT-related genes and the MAPK pathway. Single-sample gene set enrichment analysis (ssGSEA) was performed on GSE98767 to estimate MAPK activation and cell cycle activity. Finally, the effect of MAPK activation on the cell cycle was explored in vitro.

Result

Four cSCC-PDT-related genes, DUSP6, EFNB2, DNAJB1, and CCNL1, were identified as diagnostic markers of cSCC, which were upregulated in cSCC or LC50 PDT-protocol treatment and negatively correlated with the MAPK promoter. Despite having a smaller MAPK activation score, cSCC showed higher cell cycle activity. The PDT treatment suppressed the G1 to G2/M phase in JNK overexpressed A431 cells.

Conclusion

CCNL1, DNAJB1, DUSP6, and EFNB2 were identified as potential PDT target genes in cSCC treatment, whose potential therapeutic mechanism was inhibiting the MAPK pathway and inducing cell cycle alternation.
Discovery of spirooxindole-derived small-molecule compounds as novel HDAC/MDM2 dual inhibitors and investigation of their anticancer activity
Authors: Zhao Qian , Xiong Shan-Shan , Chen Can , Zhu Hong-Ping , Xie Xin , Peng Cheng , He Gu , Han Bo
Published: August 2022

Simultaneous inhibition of more than one target is considered to be a novel strategy in cancer therapy. Owing to the importance of histone deacetylases (HDACs) and p53-murine double minute 2 (MDM2) interaction in tumor development and their synergistic effects, a series of MDM2/HDAC bifunctional small-molecule inhibitors were rationally designed and synthesized by incorporating an HDAC pharmacophore into spirooxindole skeletons. These compounds exhibited good inhibitory activities against both targets. In particular, compound 11b was demonstrated to be most potent for MDM2 and HDAC, reaching the enzyme inhibition of 68% and 79%, respectively. Compound 11b also showed efficient antiproliferative activity towards MCF-7 cells with better potency than the reference drug SAHA and Nutlin-3. Furthermore, western blot analysis revealed that compound 11b increased the expression of p53 and Ac-H4 in MCF-7 cells in a dose-dependent manner. Our results indicate that dual inhibition of HDAC and MDM2 may provide a novel and efficient strategy for the discovery of antitumor drug in the future.
Lidocaine and Ketamine Infusions as Adjunctive Pain Management Therapy: A Retrospective Analysis of Clinical Outcomes in Hospitalized Patients Admitted for Pain Related to Sickle Cell Disease
Authors: Zavala Nicolas A. , Knoebel Randall W. , Anitescu Magdalena
Published: August 2022

Objective

In this study, we aim to evaluate the efficacy of adjunctive lidocaine and ketamine infusions for opioid reduction in the treatment of sickle cell disease in patients with vaso-occlusive crisis (VOC).

Design

We retrospectively reviewed a cohort of 330 adult sickle-cell crisis hospital encounters with 68 patients admitted to our institution from July 2017 to August 2018.

Methods

Upon institutional IRB approval, we obtained initial data from billing records and performed chart reviews to obtain pain scores and confirm total opioid consumption. If provided by the acute pain consultation service, the patients received either a lidocaine or a ketamine infusion of 0.5–2 mg/min or 2–3 mcg/kg, respectively, for a maximum of 24–48 h. We compared the change in opioid consumption before and after infusion therapy to patients that did not receive ketamine or lidocaine.

Results

Compared to patients that did not receive infusion therapy, ketamine and lidocaine accounted for respective relative decreases of 28 and 23% in average daily morphine consumption (p = 0.02). Patients that received either infusion were 3 to 4 times more likely to decrease their opioid consumption independent of treatment length or baseline opioid doses (p < 0.01). Ketamine and lidocaine therapies were not associated with change in pain scores. When a patient had multiple admissions, opioid reduction was strongly correlated with initiation of infusions in the later visits.

Conclusion

Both ketamine and lidocaine infusion therapies are effective in reducing opioid consumption for patients with vaso-occlusive crisis. Lidocaine infusion is emerging as an agent for stabilizing opioid doses in VOC for patients with high daily MME.
Machine learning early prediction of respiratory syncytial virus in pediatric hospitalized patients
Authors: Tso Chak Foon , Lam Carson , Calvert Jacob , Mao Qingqing
Published: August 2022

Respiratory syncytial virus (RSV) causes millions of infections among children in the US each year and can cause severe disease or death. Infections that are not promptly detected can cause outbreaks that put other hospitalized patients at risk. No tools besides diagnostic testing are available to rapidly and reliably predict RSV infections among hospitalized patients. We conducted a retrospective study from pediatric electronic health record (EHR) data and built a machine learning model to predict whether a patient will test positive to RSV by nucleic acid amplification test during their stay. Our model demonstrated excellent discrimination with an area under the receiver-operating curve of 0.919, a sensitivity of 0.802, and specificity of 0.876. Our model can help clinicians identify patients who may have RSV infections rapidly and cost-effectively. Successfully integrating this model into routine pediatric inpatient care may assist efforts in patient care and infection control.
Using intranasal dexmedetomidine with buccal midazolam for magnetic resonance imaging sedation in children: A single-arm prospective interventional study
Authors: Li Bi Lian , Luo Hao , Huang Jun Xiang , Zhang Huan Huan , Paquin Joanna R. , Yuen Vivian M. , Song Xing Rong
Published: August 2022

Objective

Although numerous intravenous sedative regimens have been documented, the ideal non-parenteral sedation regimen for magnetic resonance imaging (MRI) has not been determined. This prospective, interventional study aimed to investigate the efficacy and safety of buccal midazolam in combination with intranasal dexmedetomidine in children undergoing MRI.

Methods

Children between 1 month and 10 years old requiring sedation for MRI examination were recruited to receive buccal midazolam 0.2 mg⋅kg–1 with intranasal dexmedetomidine 3 μg⋅kg–1. The primary outcome was successful sedation following the administration of the initial sedation regimens and the completion of the MRI examination.

Results

Sedation with dexmedetomidine–midazolam was administered to 530 children. The successful sedation rate was 95.3% (95% confidence interval: 93.5–97.1%) with the initial sedation regimens and 97.7% (95% confidence interval: 96.5–99%) with a rescue dose of 2 μg⋅kg–1 intranasal dexmedetomidine. The median sedation onset time was 10 min, and a significant rising trend was observed in the onset time concerning age (R = 0.2491, P < 0.001). The wake-up and discharge times significantly correlated with the duration of the procedure (R = 0.323, P < 0.001 vs. R = 0.325, P < 0.001). No oxygen deficiency nor medication intervention due to cardiovascular instability was observed in any of the patients. History of a prior failed sedation was considered a statistically significant risk factor for failed sedation in the multivariate logistic regression model [odds ratio = 4.71 (95% confidence interval: 1.24–17.9), P = 0.023].

Conclusion

In MRI examinations, the addition of buccal midazolam to intranasal dexmedetomidine is associated with a high success rate and a good safety profile. This non-parenteral sedation regimen can be a feasible and convenient option for short-duration MRI in children between 1 month and 10 years.
Whole Exome Sequencing in a Population With Severe Congenital Anomalies of Kidney and Urinary Tract
Authors: Harris Meredith , Schuh Meredith P. , McKinney David , Kaufman Kenneth , Erkan Elif
Published: August 2022

Fetal and neonatal interventions (e.g., amnioinfusions, amniotic shunting, and infant dialysis) have increased survival of infants with severe Congenital Anomalies of the Kidney and Urinary Tract (CAKUT), however, outcomes vary dramatically. Our aim was to perform Whole Exome Sequencing (WES) in a unique severe CAKUT population with the goal to identify new variants that will enhance prediction of postnatal outcomes. We performed trio WES on five infants with severe CAKUT (undergoing fetal interventions and/or those who initiated renal replacement therapy (RRT) within 1 month of life) and their parents as well as three singletons. We identified three potential candidate gene variants (NSUN7, MTMR3, CEP162) and validated two variants in known CAKUT genes (GATA3 and FRAS1) showing strong enrichment in this severe phenotype population. Based on our small pilot study of a unique severe CAKUT population, WES appears to be a potential tool to help predict the course of infants with severe CAKUT prenatally.
Stunting among kindergarten children in China in the context of COVID-19: A cross-sectional study
Authors: Ma Xueyan , Yang Xiangzheng , Yin Hongzhi , Wang Yang , Tian Yuanshuo , Long Chaojun , Bai Chen , Dong Fei , Wang Zhendong , Liu Tiegang , Gu Xiaohong
Published: August 2022

Background

The impact of COVID-19 has most likely increased the prevalence of stunting. The study aimed to determine the prevalence of stunting among kindergarten children in the context of coronavirus disease 2019 (COVID-19) in Longgang District, Shenzhen, China, and its risk factors.

Methods

A cross-sectional study was conducted to identify children from 11 sub districts of 481 kindergartens in the Longgang District of Shenzhen City from May to July 2021. In the context of COVID-19, an online survey was conducted to gather demographic information, height, birth information, and lifestyle. The prevalence of stunting was calculated, and the risk factors were analyzed using binary logistic regression with three stepwise models.

Results

A total of 118,404 subjects were included from May to July 2021, with a response and questionnaire effective rates of 85.75% and 95.03%, respectively. The prevalence of stunting and severe stunting were 3.3% and 0.8%, respectively. Model 3 showed that risk factors for stunting were male sex [odds ratio (OR) = 1.07], low birth weight (OR = 2.02), insufficient sleep time (OR = 1.08), less food intake than their peers (OR = 1.66), slower eating than their peers (OR = 1.16), accompanied by grandparents alone or non-lineal relatives (reference: parents accompanying) (OR = 1.23, 1.51), and children induced to eat (OR = 1.17). Protective factors included only-child status (OR = 0.66), reported high activity (OR = 0.37, 0.26, 0.23), parents with high education levels (father: OR = 0.87, 0.69; mother: OR = 0.69, 0.58), high monthly income per capita of the family (OR = 0.88, 0.74, 0.68), and allowing children to make food choices (OR = 0.82).

Conclusion

The stunting rate of children in kindergartens in Longgang District is 3.3%, close to the level of developed countries but higher than the average level of developed cities in China. The relatively high stunting rate in children under 3 years old in 2021 may be associated with the influence of COVID-19. Appropriate policies should be formulated for individuals and families with children to help children establish good living habits and reduce stunting.
Video recording emergency care and video-reflection to improve patient care; a narrative review and case-study of a neonatal intensive care unit
Authors: Heesters Veerle , Witlox Ruben , van Zanten Henriette A. , Jansen Sophie J. , Visser Remco , Heijstek Veerle , Te Pas Arjan B.
Published: August 2022

As the complexity of emergency care increases, current research methods to improve care are often unable to capture all aspects of everyday clinical practice. Video recordings can visualize clinical care in an objective way. They can be used as a tool to assess care and to reflect on care with the caregivers themselves. Although the use of video recordings to reflect on medical interventions (video-reflection) has increased over the years, it is still not used on a regular basis. However, video-reflection proved to be of educational value and can improve teams’ management and performance. It has a positive effect on guideline adherence, documentation, clinical care and teamwork. Recordings can also be used for video-reflexivity. Here, caregivers review recordings together to reflect on their everyday practice from new perspectives with regard to context and conduct in general. Although video-reflection in emergency care has proven to be valuable, certain preconditions have to be met and obstacles need to be overcome. These include gaining trust of the caregivers, having a proper consent-procedure, maintaining confidentiality and adequate use of technical equipment. To implement the lessons learned from video-reflection in a sustainable way and to continuously improve care, it should be integrated in regular simulation training or education. This narrative review will describe the development of video recording in emergency care and how video-reflection can improve patient care and safety in new ways. On our own department, the NICU at the LUMC, video-reflection has already been implemented and we want to further expand this. We will describe the use of video-reflection in our own unit. Based on the results of this narrative review we will propose options for future research to increase the value of video-reflection.
In silico genome-scale metabolic modeling and in vitro static time-kill studies of exogenous metabolites alone and with polymyxin B against Klebsiella pneumoniae
Authors: Chung Wan Yean , Abdul Rahim Nusaibah , Mahamad Maifiah Mohd Hafidz , Hawala Shivashekaregowda Naveen Kumar , Zhu Yan , Wong Eng Hwa
Published: August 2022

Multidrug-resistant (MDR) Klebsiella pneumoniae is a top-prioritized Gram-negative pathogen with a high incidence in hospital-acquired infections. Polymyxins have resurged as a last-line therapy to combat Gram-negative “superbugs”, including MDR K. pneumoniae. However, the emergence of polymyxin resistance has increasingly been reported over the past decades when used as monotherapy, and thus combination therapy with non-antibiotics (e.g., metabolites) becomes a promising approach owing to the lower risk of resistance development. Genome-scale metabolic models (GSMMs) were constructed to delineate the altered metabolism of New Delhi metallo-β-lactamase- or extended spectrum β-lactamase-producing K. pneumoniae strains upon addition of exogenous metabolites in media. The metabolites that caused significant metabolic perturbations were then selected to examine their adjuvant effects using in vitro static time–kill studies. Metabolic network simulation shows that feeding of 3-phosphoglycerate and ribose 5-phosphate would lead to enhanced central carbon metabolism, ATP demand, and energy consumption, which is converged with metabolic disruptions by polymyxin treatment. Further static time–kill studies demonstrated enhanced antimicrobial killing of 10 mM 3-phosphoglycerate (1.26 and 1.82 log10 CFU/ml) and 10 mM ribose 5-phosphate (0.53 and 0.91 log10 CFU/ml) combination with 2 mg/L polymyxin B against K. pneumoniae strains. Overall, exogenous metabolite feeding could possibly improve polymyxin B activity via metabolic modulation and hence offers an attractive approach to enhance polymyxin B efficacy. With the application of GSMM in bridging the metabolic analysis and time–kill assay, biological insights into metabolite feeding can be inferred from comparative analyses of both results. Taken together, a systematic framework has been developed to facilitate the clinical translation of antibiotic-resistant infection management.
Cardiac Safety in Breast Cancer Patients Receiving Pegylated Liposome Doxorubicin Sequential Anti-HER2 Monoclonal Antibody Therapy
Authors: Huang Ping , Huang Jia-huan , Zheng Ya-bing , Cao Wen-ming , Shao Xi-ying , Chen Jun-qing , Huang Yuan , Li Guang-liang , Sharma K , Zhou Huan-huan , Wang Xiao-jia , Jin Hong-chuan , Chen Zhan-hong
Published: August 2022

Background: Cardiotoxicity associated with the sequential use of anthracyclines followed by trastuzumab is common in adjuvant therapy of patients with HER2-positive early breast cancer (eBC). However, the cardiac safety of trastuzumab concurrent with pegylated liposomal doxorubicin (PLD) is relatively less studied.

Method: Clinical data of patients with HER2-positive eBC treated with PLD and cyclophosphamide (PLD-C) followed by taxanes plus trastuzumab ± pertuzumab (TH or TPH) who then completed standard anti-HER2 treatment for 12 months from June 2012 to August 2021 were retrospectively collected. The primary endpoints were clinical and subclinical cardiotoxicity.

Result: In total, 70 eligible patients were enrolled. Among them, 55 patients (78.6%) received PLD-C → TH and 15 patients (21.4%) received PLD-C → TPH. The median follow-up time was 41.8 months. Until August 2021, only two patients had recurrent or metastatic diseases, with 2-year and 5-year disease-free survivals of 98.6% and 96.8%, respectively. Clinical cardiotoxicity occurred in six patients (8.6%), and all of them had an absolute decline of ≥16% from baseline left ventricular ejection fraction (LVEF) but not below the lower limit of normal (LLN = 50%). Subclinical cardiotoxicity events occurred in 17 patients (24.3%), and all of them had absolute declines of ≥10% and <16% from baseline LVEF but not below the LLN. No patients were interrupted from treatment, and all patients completed anti-HER2 treatment for 12 months. The sharpest decrease in LVEF was observed at 18 months after the start of PLD treatment. The cumulative incidences of clinical and subclinical cardiotoxicity were 9.8% and 28.3%, respectively. In the univariate analysis, body mass index, age, left chest wall radiotherapy, and ongoing cardiovascular risk factors were not significantly associated with clinical or subclinical cardiotoxicity (p > 0.05). No patients had congestive heart failure or death caused by PLD or anti-HER2 treatment.

Conclusion: The sequential use of PLD and trastuzumab showed a lower incidence of clinical cardiotoxicity, presented as asymptomatic decreased LVEF, compared with the results obtained in previous clinical studies using conventional anthracycline, taxanes and trastuzumab. The study regimen demonstrated good cardiac tolerance and is an alternative strategy for cardioprotection in patients with HER2-positive eBC.
Polydatin activates the Nrf2/HO-1 signaling pathway to protect cisplatin-induced hearing loss in guinea pigs
Authors: Li Dafei , Zhao Haiyan , Xu Piao , Lin Qiongping , Zhao Tingting , Li Chubing , Cui Zhong-Kai , Tian Guangyong
Published: August 2022

Irreversible sensorineural hearing loss is one of the most common side effects after cisplatin treatment. Prevention and reversal of hearing loss caused by cisplatin are of great importance for cancer patients, especially children. Oxidative stress is an important cause of hearing loss resulted from cisplatin, unfortunately, there is no drug yet available that can completely prevent and reverse the ototoxicity from cisplatin. Polydatin (PD) possesses excellent antioxidant and anti-inflammatory effects, however, its role in the cisplatin-induced hearing loss has not been investigated. Herein, we have explored the preventive and therapeutic effects of PD on cisplatin-induced hearing loss and the possible underlying mechanisms. In the in vivo setting with guinea pigs, we have demonstrated that PD can reduce the threshold shift of auditory brainstem response (ABR) caused by cisplatin, promote the nuclear translocation of Nuclear factor erythroid-2 related factor 2 (Nrf2), increase the expression of Nrf2 and heme oxygenase-1 (HO-1), and thus reduce the loss of outer hair cells (OHCs). PD can ameliorate cisplatin-induced hearing loss through activating the Nrf2/HO-1 signaling pathway. This study provides a potential strategy for preventing and improving hearing loss resulted from cisplatin treatment in clinics.
Contribution of patient registries to regulatory decision making on rare diseases medicinal products in Europe
Authors: Jonker Carla J. , Bakker Elisabeth , Kurz Xavier , Plueschke Kelly
Published: August 2022

Between 2000 and 2021, the European Medicines Agency (EMA) assigned the orphan designation to over 1,900 medicines. Due to their small target populations, leading to challenges regarding clinical trial recruitment, study design and little knowledge on the natural history of the disease, the overall clinical evidence submitted at the time of marketing authorisation application for these medicines is often limited. Patient registries have been recognised as important sources of data on healthcare practices, drug utilisation and clinical outcomes. They may help address these challenges by providing information on epidemiology, standards of care and treatment patterns of rare diseases. In this review, we illustrate the utility of patient registries across the different stages of development of medicinal products, including orphans, to provide evidence in the context of clinical studies and to generate post-authorisation long term data on their effectiveness and safety profiles. We present important initiatives leveraging the role of registries for orphan medicinal products’ development and monitoring to ultimately improve patients’ lives.
Therapeutic effect and mechanism of Anemarrhenae Rhizoma on Alzheimer’s disease based on multi-platform metabolomics analyses
Authors: Wang Hui , Dai Jian-Ying , He Yu-Zhen , Xia Zhe-Wei , Chen Xiao-Fei , Hong Zhan-Ying , Chai Yi-Feng
Published: August 2022

Anemarrhenae Rhizoma (AR) has multiple pharmacological activities to prevent and treat Alzheimer’s disease (AD). However, the effect and its molecular mechanism are not elucidated clear. This study aims to evaluate AR’s therapeutic effect and mechanism on AD model rats induced by D-galactose and AlCl3 with serum metabolomics. Behavior study, histopathological observations, and biochemical analyses were applied in the AD model assessment. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-QTOF/MS) were combined with multivariate statistical analysis to identify potential biomarkers of AD and evaluate the therapeutic effect of AR on AD from the perspective of metabolomics. A total of 49 biomarkers associated with the AD model were identified by metabolomics, and pathway analysis was performed to obtain the metabolic pathways closely related to the model. With the pre-treatment of AR, 32 metabolites in the serum of AD model rats were significantly affected by AR compared with the AD model group. The regulated metabolites affected by AR were involved in the pathway of arginine biosynthesis, arginine and proline metabolism, ether lipid metabolism, glutathione metabolism, primary bile acid biosynthesis, and steroid biosynthesis. These multi-platform metabolomics analyses were in accord with the results of behavior study, histopathological observations, and biochemical analyses. This study explored the therapeutic mechanism of AR based on multi-platform metabolomics analyses and provided a scientific basis for the application of AR in the prevention and treatment of AD.
Preclinical models of congestive heart failure, advantages, and limitations for application in clinical practice
Authors: Saura Marta , Zamorano Jose Luis , Zaragoza Carlos
Published: August 2022

Congestive heart failure (CHF) has increased over the years, in part because of recent progress in the management of chronic diseases, thus contributing to the maintenance of an increasingly aging population. CHF represents an unresolved health problem and therefore the establishment of animal models that recapitulates the complexity of CHF will become a critical element to be addressed, representing a serious challenge given the complexity of the pathogenesis of CHF itself, which is further compounded by methodological biases that depend on the animal species in use. Animal models of CHF have been developed in many different species, with different surgical procedures, all with promising results but, for the moment, unable to fully recapitulate the human disease. Large animal models often provide a more promising reality, with all the difficulties that their use entails, and which limit their performance to fewer laboratories, the costly of animal housing, animal handling, specialized facilities, skilled methodological training, and reproducibility as another important limiting factor when considering a valid animal model versus potentially better performing alternatives. In this review we will discuss the different animal models of CHF, their advantages and, above all, the limitations of each procedure with respect to effectiveness of results in terms of clinical application.
Environment predicts seagrass genotype, phenotype, and associated biodiversity in a temperate ecosystem
Authors: Alotaibi Nahaa M , Kenyon Emma J , Bertelli Chiara M , Al-Qthanin Rahmah N , Mead Jessica , Parry Mark , Bull James C
Published: August 2022

Coastal vegetative ecosystems are among the most threatened in the world, facing multiple anthropogenic stressors. A good example of this is seagrass, which supports carbon capture, coastal stabilization, and biodiversity, but is declining globally at an alarming rate. To understand the causes and consequences of changes to these ecosystems, we need to determine the linkages between different biotic and abiotic components. We used data on the seagrass, Zostera marina, collected by citizen scientists across 300 km of the south coast of the United Kingdom as a case study. We assembled data on seagrass genotype, phenotype, infauna, and associated bathymetry, light, sea surface temperature, and wave and current energy to test hypotheses on the distribution and diversity of this temperate sub-tidal ecosystem. We found spatial structure in population genetics, evident through local assortment of genotypes and isolation by distance across a broader geographic scale. By integrating our molecular data with information on seagrass phenotype and infauna, we demonstrate that these ecosystem components are primarily linked indirectly through the effects of shared environmental factors. It is unusual to examine genotypic, phenotypic, and environmental data in a single study, but this approach can inform both conservation and restoration of seagrass, as well as giving new insights into a widespread and important ecosystem.
Degradation reduces the diversity of nitrogen-fixing bacteria in the alpine wetland on the Qinghai-Tibet Plateau
Authors: Li Chengyi , Li Xilai , Yang Yuanwu , Shi Yan , Li Honglin
Published: August 2022

Biological nitrogen fixation is a key process in the nitrogen cycle and the main source of soil available nitrogen. The number and diversity of nitrogen-fixing bacteria directly reflect the efficiency of soil nitrogen fixation. The alpine wetland on the Qinghai-Tibet Plateau (QTP) is degrading increasingly, with a succession toward alpine meadows. Significant changes in soil physicochemical properties accompany this process. However, it is unclear how does the soil nitrogen-fixing bacteria change during the degradation processes, and what is the relationship between these changes and soil physicochemical properties. In this study, the nifH gene was used as a molecular marker to further investigate the diversity of nitrogen-fixing bacteria at different stages of degradation (none, light, and severe degeneration) in the alpine wetland. The results showed that wetland degradation significantly reduced the diversity, altered the community composition of nitrogen-fixing bacteria, decreased the relative abundance of Proteobacteria, and increased the relative abundance of Actinobacteria. In addition to the dominant phylum, the class, order, family, and genus of nitrogen-fixing bacteria had significant changes in relative abundance. Analysis of Mantel test showed that most soil factors (such as pH, soil water content (SWC), the organic carbon (TOC), total nitrogen (TN), and soil C:P ratio) and abundance had a significant positive correlation. TOC, TN, total phosphorus (TP), soil C:P ratio and Shannon had a significant positive correlation with each other. The RDA ranking further revealed that TOC, SWC, and TN were the main environmental factors influencing the community composition of nitrogen-fixing bacteria. It is found that the degradation of the alpine wetland inhibited the growth of nitrogen-fixing bacteria to a certain extent, leading to the decline of their nitrogen-fixing function.
Integrating transcriptome and chemical analyses to reveal the anti-Alzheimer’s disease components in Verbena officinalis Linn
Authors: Peng Shuhuan , Li Fangyi , Yu Kuo , Zhou Fengshu , Yu Heshui , Liu Hui , Guo Jialiang , Li Guoqiang , Wang Chunhua , Yan Xiaohui , Li Zheng
Published: August 2022

Verbena officinalis Linn. is a kind of traditional Chinese medicine, which has a long history of application and shows good effects on neuroprotection. Therefore, we consider that V. officinalis may be a potential drug for treating Alzheimer’s disease (AD). First, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) pointed out that the main chemical components in V. officinalis were iridoid glycosides, phenylethanoid glycosides, and flavonoids. These compounds were used for molecular docking and the results showed that these compounds had good anti-AD activity. To explore the biosynthetic pathway of anti-AD components in V. officinalis, UPLC and ultraviolet (UV) spectrophotometry were used for contents determination and the result was leaf > stem > root. At the same time, 92,867 unigenes were annotated in V. officinalis transcriptome; 206, 229, 115 related unigenes were, respectively, annotated in iridoid glycoside, phenylethanoid glycoside, and flavonoid pathway, of which 61, 73, and 35 were differential expression genes. The components had relatively high expression in leaves, which was consistent with the quantitative results. In addition, the tissue distribution particularity of verbenalin may be related to the branching of pathways. Meanwhile transcription factors VoWRKY6 and VoWRKY7 may be involved in the regulation of iridoid glycoside biosynthesis. Further, VoWRKY3, VoWRKY9, and VoWRKY12 may be related to flavonoid biosynthesis. The above research is helpful to explore the biosynthetic pathway of anti-AD components and the regulation mechanism of active components and to further explore the anti-AD effect of V. officinalis.
Genotypic-specific hormonal reprogramming and crosstalk are crucial for root growth and salt tolerance in bermudagrass (Cynodon dactylon)
Authors: Yang Yong , Wassie Misganaw , Liu Ning-fang , Deng Hui , Zeng Yi-bing , Xu Qian , Hu Long-xing
Published: August 2022

Salt stress is one of the major abiotic factors limiting the productivity of bermudagrass (Cynodon dactylon). However, the role of hormonal reprogramming and crosstalk in regulating root growth and salt tolerance in bermudagrass was not reported. Here, we examined the physiological and hormonal responses of two contrasting bermudagrass genotypes; ‘C43,’ salt-tolerant ‘C198’ salt-sensitive. Under salt stress, ‘C43’ had better membrane stability and higher photosynthetic activity than the ‘C198.’ Salt stress promoted root growth and improved root/shoot ratio and root activity in ‘C43,’ but the root growth of ‘C198’ was inhibited by salt stress, leading to diminished root activity. The two bermudagrass genotypes also showed critical differences in hormonal responses, especially in the roots. The root contents of indole-3-acetic acid (IAA), cytokinin derivatives, such as trans-zeatin riboside (tZR) and dihydrozeatin riboside (DHZR) were increased in ‘C43,’ but decreased in ‘C198’ when exposed to salt stress. The root growth rate was positively correlated with the root IAA, tZR and DHZR, indicating their crucial role in root growth under salt stress. The expressions of TAA/YUCCA and CYP735A involved in IAA and tZR biosynthesis were induced by salt stress in ‘C43,’ but inhibited in ‘C198,’ leading to reduced hormone accumulations. Salt stress decreased the iP, tZ, and DHZ content in the roots of both genotypes, and no significant difference was observed between the two genotypes. Salt stress reduced the content of GA3 in both genotypes by inhibiting GA20ox and GA2ox genes, which could be attributed to the reduced shoot growth in both genotypes. The increased ABA level by salt stress was significantly higher in ‘C198’ than ‘C43.’ Furthermore, there were positive and negative correlations between different hormones and root growth, suggesting that root growth could be regulated by complex hormonal reprogramming and crosstalk. This study provides a foundation for understanding the underlying mechanisms of hormonal-mediated root growth and salt tolerance in bermudagrass.
Combining spectral and wavelet texture features for unmanned aerial vehicles remote estimation of rice leaf area index
Authors: Zhou Cong , Gong Yan , Fang Shenghui , Yang Kaili , Peng Yi , Wu Xianting , Zhu Renshan
Published: August 2022

Estimating the crop leaf area index (LAI) accurately is very critical in agricultural remote sensing, especially in monitoring crop growth and yield prediction. The development of unmanned aerial vehicles (UAVs) has been significant in recent years and has been extensively applied in agricultural remote sensing (RS). The vegetation index (VI), which reflects spectral information, is a commonly used RS method for estimating LAI. Texture features can reflect the differences in the canopy structure of rice at different growth stages. In this research, a method was developed to improve the accuracy of rice LAI estimation during the whole growing season by combining texture information based on wavelet transform and spectral information derived from the VI. During the whole growth period, we obtained UAV images of two study areas using a 12-band Mini-MCA system and performed corresponding ground measurements. Several VI values were calculated, and the texture analysis was carried out. New indices were constructed by mathematically combining the wavelet texture and spectral information. Compared with the corresponding VIs, the new indices reduced the saturation effect and were less sensitive to the emergence of panicles. The determination coefficient (R2) increased for most VIs used in this study throughout the whole growth period. The results indicated that the estimation accuracy of LAI by combining spectral information and texture information was higher than that of VIs. The method proposed in this study used the spectral and wavelet texture features extracted from UAV images to establish a model of the whole growth period of rice, which was easy to operate and had great potential for large-scale auxiliary rice breeding and field management research.
Transcriptomic and metabolomic reveals silicon enhances adaptation of rice under dry cultivation by improving flavonoid biosynthesis, osmoregulation, and photosynthesis
Authors: Jiang Hao , Song Ze , Su Qing-Wang , Wei Zhi-Heng , Li Wan-Chun , Jiang Zi-Xian , Tian Ping , Wang Zhen-Hui , Yang Xue , Yang Mei-Ying , Wei Xiao-Shuang , Wu Zhi-Hai
Published: August 2022

Dry cultivation is a new rice crop mode used to alleviate water shortage and develop water-saving agriculture. There is obvious genetic difference compared with drought-tolerant rice. Silicon (Si) plays an important role in plant adaptation to adverse environmental conditions and can significantly improve the drought tolerance and yield of rice. However, the regulatory mechanism via which Si provides plant tolerance or adaptation under dry cultivation is not well understood. The present study investigated the changes in plant growth, photosynthetic gas exchange, and oxidative stress of the rice cultivar “Suijing 18” under dry cultivation. Si improved photosynthetic performance and antioxidant enzyme activity and subsequently reduced lipid peroxidation of rice seedlings, promoted LAI and promoted leaf growth under dry cultivation. Further, transcriptomics combined with quasi-targeted metabolomics detected 1416 and 520 differentially expressed genes (DEGs), 38 and 41 differentially accumulated metabolites (DAMs) in the rice leaves and roots, respectively. Among them, 13 DEGs were involved in flavonoid biosynthesis, promoting the accumulation of flavonoids, anthocyanins, and flavonols in the roots and leaves of rice under dry cultivation. Meanwhile, 14 DEGs were involved in photosynthesis, promoting photosystem I and photosystem II responses, increasing the abundance of metabolites in leaves. On the other hand, 24 DAMs were identified involved in osmoregulatory processes, significantly increasing amino acids and carbohydrates and their derivatives in roots. These results provide new insight into the role of Si in alleviating to adverse environmental, Si enhanced the accumulation of flavonoids and osmoregulatory metabolites, thereby alleviating drought effect on the roots. On the other hand, improving dehydration resistance of leaves, guaranteeing normal photosynthesis and downward transport of organic matter. In conclusion, Si promoted the coordinated action between the above-ground and below-ground plant parts, improved the root/shoot ratio (R/S) of rice and increased the sugar content and enhancing rice adaptability under dry cultivation conditions. The establishment of the system for increasing the yield of rice under dry cultivation provides theoretical and technical support thereby promoting the rapid development of rice in Northeast China, and ensuring national food security.
Classification of plug seedling quality by improved convolutional neural network with an attention mechanism
Authors: Du Xinwu , Si Laiqiang , Jin Xin , Li Pengfei , Yun Zhihao , Gao Kaihang
Published: August 2022

The classification of plug seedling quality plays an active role in enhancing the quality of seedlings. The EfficientNet-B7-CBAM model, an improved convolutional neural network (CNN) model, was proposed to improve classification efficiency and reduce high cost. To ensure that the EfficientNet-B7 model simultaneously learns crucial channel and spatial location information, the convolutional block attention module (CBAM) has been incorporated. To improve the model’s ability to generalize, a transfer learning strategy and Adam optimization algorithm were introduced. A system for image acquisition collected 8,109 images of pepper plug seedlings, and data augmentation techniques improved the resulting data set. The proposed EfficientNet-B7-CBAM model achieved an average accuracy of 97.99% on the test set, 7.32% higher than before the improvement. Under the same experimental conditions, the classification accuracy increased by 8.88–20.05% to classical network models such as AlexNet, VGG16, InceptionV3, ResNet50, and DenseNet121. The proposed method had high accuracy in the plug seedling quality classification task. It was well-adapted to numerous types of plug seedlings, providing a reference for developing a fast and accurate algorithm for plug seedling quality classification.