bluuebunny/crossref_metadata_2025 huggingface dataset:
Bio-organic fertilizers improve Dendrocalamus farinosus growth by remolding the soil microbiome and metabolome
Authors: Li Shangmeng , Fan Wei , Xu Gang , Cao Ying , Zhao Xin , Hao Suwei , Deng Bin , Ren Siyuan , Hu Shanglian
Published: February 2023

Organic and microbial fertilizers have potential advantages over inorganic fertilizers in improving soil fertility and crop yield without harmful side-effects. However, the effects of these bio-organic fertilizers on the soil microbiome and metabolome remain largely unknown, especially in the context of bamboo cultivation. In this study, we cultivated Dendrocalamus farinosus (D. farinosus) plants under five different fertilization conditions: organic fertilizer (OF), Bacillus amyloliquefaciens bio-fertilizer (Ba), Bacillus mucilaginosus Krassilnikov bio-fertilizer (BmK), organic fertilizer plus Bacillus amyloliquefaciens bio-fertilizer (OFBa), and organic fertilizer plus Bacillus mucilaginosus Krassilnikov bio-fertilizer (OFBmK). We conducted 16S rRNA sequencing and liquid chromatography/mass spectrometry (LC–MS) to evaluate the soil bacterial composition and soil metabolic activity in the different treatment groups. The results demonstrate that all the fertilization conditions altered the soil bacterial community composition. Moreover, the combination of organic and microbial fertilizers (i.e., in the OFBa and OFBmK groups) significantly affected the relative abundance of soil bacterial species; the largest number of dominant microbial communities were found in the OFBa group, which were strongly correlated with each other. Additionally, non-targeted metabolomics revealed that the levels of soil lipids and lipid-like molecules, and organic acids and their derivatives, were greatly altered under all treatment conditions. The levels of galactitol, guanine, and deoxycytidine were also markedly decreased in the OFBa and OFBmK groups. Moreover, we constructed a regulatory network to delineated the relationships between bamboo phenotype, soil enzymatic activity, soil differential metabolites, and dominant microbial. The network revealed that bio-organic fertilizers promoted bamboo growth by modifying the soil microbiome and metabolome. Accordingly, we concluded that the use of organic fertilizers, microbial fertilizers, or their combination regulated bacterial composition and soil metabolic processes. These findings provide new insights into how D. farinosus-bacterial interactions are affected by different fertilization regiments, which are directly applicable to the agricultural cultivation of bamboo.
Acupuncture on mild cognitive impairment: A systematic review of neuroimaging studies
Authors: Yin Zihan , Zhou Jun , Xia Manze , Chen Zhenghong , Li Yaqin , Zhang Xinyue , Li Xiang , Yan Hang , Wang Lu , Sun Mingsheng , Zhao Ling , Liang Fanrong , Wang Ziwen
Published: February 2023

Mild cognitive impairment (MCI) is a multifactorial and complex central neurodegenerative disease. Acupuncture appears to be an effective method for cognitive function improvement in MCI patients. Neural plasticity remaining in the MCI brain implies that acupuncture-associated benefits may not be limited to the cognitive function. Instead, neurological alternations in the brain play a vital role in corresponding to the cognitive improvement. However, previous studies have mainly focused on the effects of cognitive function, leaving neurological findings relatively unclear. This systematic review summarized existing studies that used various brain imaging techniques to explore the neurological effect regarding acupuncture use for MCI treatment. Potential neuroimaging trials were searched, collected, and identified independently by two researchers. Four Chinese databases, four English databases, and additional sources were searched to identify studies reporting the use of acupuncture for MCI from the inception of databases until 1 June 2022. Methodological quality was appraised using the Cochrane risk-of-bias tool. In addition, general, methodological, and brain neuroimaging information was extracted and summarized to investigate the potential neural mechanisms by which acupuncture affects patients with MCI. In total, 22 studies involving 647 participants were included. The methodological quality of the included studies was moderate to high. The methods used included functional magnetic resonance imaging, diffusion tensor imaging, functional near-infrared spectroscopy, and magnetic resonance spectroscopy. Acupuncture-induced brain alterations observed in those patients with MCI tended to be observable in the cingulate cortex, prefrontal cortex, and hippocampus. The effect of acupuncture on MCI may play a role in regulating the default mode network, central executive network, and salience network. Based on these studies, researchers could extend the recent research focus from the cognitive domain to the neurological level. Future researches should develop additional relevant, well-designed, high-quality, and multimodal neuroimaging researches to detect the effects of acupuncture on the brains of MCI patients.
Potential roles of the endoplasmic reticulum stress pathway in amyotrophic lateral sclerosis
Authors: Jeon Yu-Mi , Kwon Younghwi , Lee Shinrye , Kim Hyung-Jun
Published: February 2023

The endoplasmic reticulum (ER) is a major organelle involved in protein quality control and cellular homeostasis. ER stress results from structural and functional dysfunction of the organelle, along with the accumulation of misfolded proteins and changes in calcium homeostasis, it leads to ER stress response pathway such as unfolded protein response (UPR). Neurons are particularly sensitive to the accumulation of misfolded proteins. Thus, the ER stress is involved in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, prion disease and motor neuron disease (MND). Recently, the complex involvement of ER stress pathways has been demonstrated in experimental models of amyotrophic lateral sclerosis (ALS)/MND using pharmacological and genetic manipulation of the unfolded protein response (UPR), an adaptive response to ER stress. Here, we aim to provide recent evidence demonstrating that the ER stress pathway is an essential pathological mechanism of ALS. In addition, we also provide therapeutic strategies that can help treat diseases by targeting the ER stress pathway.
Recent trends in wearable device used to detect freezing of gait and falls in people with Parkinson’s disease: A systematic review
Authors: Huang Tinghuai , Li Meng , Huang Jianwei
Published: February 2023

Background

The occurrence of freezing of gait (FOG) is often observed in moderate to last-stage Parkinson’s disease (PD), leading to a high risk of falls. The emergence of the wearable device has offered the possibility of FOG detection and falls of patients with PD allowing high validation in a low-cost way.

Objective

This systematic review seeks to provide a comprehensive overview of existing literature to establish the forefront of sensors type, placement and algorithm to detect FOG and falls among patients with PD.

Methods

Two electronic databases were screened by title and abstract to summarize the state of art on FOG and fall detection with any wearable technology among patients with PD. To be eligible for inclusion, papers were required to be full-text articles published in English, and the last search was completed on September 26, 2022. Studies were excluded if they; (i) only examined cueing function for FOG, (ii) only used non-wearable devices to detect or predict FOG or falls, and (iii) did not provide sufficient details about the study design and results. A total of 1,748 articles were retrieved from two databases. However, only 75 articles were deemed to meet the inclusion criteria according to the title, abstract and full-text reviewed. Variable was extracted from chosen research, including authorship, details of the experimental object, type of sensor, device location, activities, year of publication, evaluation in real-time, the algorithm and detection performance.

Results

A total of 72 on FOG detection and 3 on fall detection were selected for data extraction. There were wide varieties of the studied population (from 1 to 131), type of sensor, placement and algorithm. The thigh and ankle were the most popular device location, and the combination of accelerometer and gyroscope was the most frequently used inertial measurement unit (IMU). Furthermore, 41.3% of the studies used the dataset as a resource to examine the validity of their algorithm. The results also showed that increasingly complex machine-learning algorithms had become the trend in FOG and fall detection.

Conclusion

These data support the application of the wearable device to access FOG and falls among patients with PD and controls. Machine learning algorithms and multiple types of sensors have become the recent trend in this field. Future work should consider an adequate sample size, and the experiment should be performed in a free-living environment. Moreover, a consensus on provoking FOG/fall, methods of assessing validity and algorithm are necessary.

Systematic Review Registration: PROSPERO, identifier CRD42022370911.
Connectomics underlying motor functional outcomes in the acute period following stroke
Authors: Bian Rong , Huo Ming , Liu Wan , Mansouri Negar , Tanglay Onur , Young Isabella , Osipowicz Karol , Hu Xiaorong , Zhang Xia , Doyen Stephane , Sughrue Michael E. , Liu Li
Published: February 2023

Objective

Stroke remains the number one cause of morbidity in many developing countries, and while effective neurorehabilitation strategies exist, it remains difficult to predict the individual trajectories of patients in the acute period, making personalized therapies difficult. Sophisticated and data-driven methods are necessary to identify markers of functional outcomes.

Methods

Baseline anatomical T1 magnetic resonance imaging (MRI), resting-state functional MRI (rsfMRI), and diffusion weighted scans were obtained from 79 patients following stroke. Sixteen models were constructed to predict performance across six tests of motor impairment, spasticity, and activities of daily living, using either whole-brain structural or functional connectivity. Feature importance analysis was also performed to identify brain regions and networks associated with performance in each test.

Results

The area under the receiver operating characteristic curve ranged from 0.650 to 0.868. Models utilizing functional connectivity tended to have better performance than those utilizing structural connectivity. The Dorsal and Ventral Attention Networks were among the top three features in several structural and functional models, while the Language and Accessory Language Networks were most commonly implicated in structural models.

Conclusions

Our study highlights the potential of machine learning methods combined with connectivity analysis in predicting outcomes in neurorehabilitation and disentangling the neural correlates of functional impairments, though further longitudinal studies are necessary.
Subdural evacuating port system with subdural thrombolysis for the treatment of chronic subdural hematoma in patients older than 80 years
Authors: Liu Tianqing , Gao Zhenwen , Zhou Jianjun , Lai Xiaoyan , Chen Xiaomei , Rao Qiong , Guo Dongbin , Zheng Jinliang , Lin Fuxin , Lin Yuanxiang , Lin Zhiqin
Published: February 2023

Objective

The subdural evacuating port system (SEPS) is a minimally invasive approach that can be performed under local anesthesia for the treatment of chronic subdural hematoma (CSDH). Subdural thrombolysis has been described as an exhaustive drainage strategy and found to be safe and effective for improving drainage. We aim to analyze the effectiveness of SEPS with subdural thrombolysis in patients older than 80 years.

Method

Consecutive patients aged ≥80 years old who presented with symptomatic CSDH and underwent SEPS followed by subdural thrombolysis between January 2014 and February 2021 were retrospectively studied. Outcome measures included complications, mortality, recurrence, and modified Rankin Scale (mRS) scores at discharge and 3 months.

Results

In total, 52 patients with CSDH in 57 hemispheres were operated on, with a mean age of 83.9 ± 3.3 years, and 40 (76.9%) patients were men. The preexisting medical comorbidities were observed in 39 patients (75.0%). Postoperative complications occurred in nine patients (17.3%), with two having significant complications (3.8%). The complications observed included pneumonia (11.5%), acute epidural hematoma (3.8%), and ischemic stroke (3.8%). One patient experienced contralateral malignant middle cerebral artery infarction and died of subsequent severe herniation, contributing to a perioperative mortality rate of 1.9%. Discharge and 3 months of favorable outcomes (mRS score 0–3) were achieved in 86.5% and 92.3% of patients, respectively. CSDH recurrence was observed in five patients (9.6%), and repeat SEPS was performed.

Conclusion

As an exhaustive drainage strategy, SEPS followed by thrombolysis is safe and effective with excellent outcomes among elderly patients. It is a technically easy and less invasive procedure with similar complications, mortality, and recurrence rates compared with burr-hole drainage in the literature.
Glymphatic system impairment in nonathlete older male adults who played contact sports in their youth associated with cognitive decline: A diffusion tensor image analysis along the perivascular space study
Authors: Morita Yuichi , Kamagata Koji , Andica Christina , Takabayashi Kaito , Kikuta Junko , Fujita Shohei , Samoyeau Thomas , Uchida Wataru , Saito Yuya , Tabata Hiroki , Naito Hitoshi , Someya Yuki , Kaga Hideyoshi , Tamura Yoshifumi , Miyata Mari , Akashi Toshiaki , Wada Akihiko , Taoka Toshiaki , Naganawa Shinji , Watada Hirotaka , Kawamori Ryuzo , Abe Osamu , Aoki Shigeki
Published: February 2023

Background and purpose

Exposure to contact sports in youth causes brain health problems later in life. For instance, the repetitive head impacts in contact sports might contribute to glymphatic clearance impairment and cognitive decline. This study aimed to assess the effect of contact sports participation in youth on glymphatic function in old age and the relationship between glymphatic function and cognitive status using the analysis along the perivascular space (ALPS) index.

Materials and methods

A total of 52 Japanese older male subjects were included in the study, including 12 who played heavy-contact sports (mean age, 71.2 years), 15 who played semicontact sports (mean age, 73.1 years), and 25 who played noncontact sports (mean age, 71.3 years) in their youth. All brain diffusion-weighted images (DWIs) of the subjects were acquired using a 3T MRI scanner. The ALPS indices were calculated using a validated semiautomated pipeline. The ALPS indices from the left and right hemispheres were compared between groups using a general linear model, including age and years of education. Furthermore, partial Spearman's rank correlation tests were performed to assess the correlation between the ALPS indices and cognitive scores (Mini-Mental State Examination and the Japanese version of the Montreal Cognitive Assessment [MoCA-J]) after adjusting for age years of education and HbA1c.

Results

The left ALPS index was significantly lower in the heavy-contact and semicontact groups than that in the noncontact group. Although no significant differences were observed in the left ALPS index between the heavy-contact and semicontact groups and in the right ALPS index among groups, a trend toward lower was found in the right ALPS index in individuals with semicontact and heavy-contact compared to the noncontact group. Both sides' ALPS indices were significantly positively correlated with the MoCA-J scores.

Conclusion

The findings indicated the potential adverse effect of contact sports experience in youth on the glymphatic system function in old age associated with cognitive decline.
N6-methyladenosine RNA is modified in the rat hippocampus following traumatic brain injury with hypothermia treatment
Authors: Cheng Jin , Lin Lian , Yu Jiangtao , Zhu Xiaolu , Ma Haoli , Zhao Yan
Published: February 2023

Recent studies have suggested a role for N6-methyladenosine (m6A) modification in neurological diseases. Hypothermia, a commonly used treatment for traumatic brain injury, plays a neuroprotective role by altering m6A modifications. In this study, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) was applied to conduct a genome-wide analysis of RNA m6A methylation in the rat hippocampus of Sham and traumatic brain injury (TBI) groups. In addition, we identified the expression of mRNA in the rat hippocampus after TBI with hypothermia treatment. Compared with the Sham group, the sequencing results of the TBI group showed that 951 different m6A peaks and 1226 differentially expressed mRNAs were found. We performed cross-linking analysis of the data of the two groups. The result showed that 92 hyper-methylated genes were upregulated, 13 hyper-methylated genes were downregulated, 25 hypo-methylated genes were upregulated, and 10 hypo-methylated genes were downregulated. Moreover, a total of 758 differential peaks were identified between TBI and hypothermia treatment groups. Among these differential peaks, 173 peaks were altered by TBI and reversed by hypothermia treatment, including Plat, Pdcd5, Rnd3, Sirt1, Plaur, Runx1, Ccr1, Marveld1, Lmnb2, and Chd7. We found that hypothermia treatment transformed some aspects of the TBI-induced m6A methylation landscape of the rat hippocampus.
Design and implementation of informatization for unified management of stroke rehabilitation in urban multi-level hospitals
Authors: Huang Lihua , Jiang Lan , Xu Yiming , Ma Yanhong
Published: February 2023

Background

With the aging of the population, the prevalence and incidence of stroke in China are increasing every year. China advocates the establishment of a three-level medical service system for stroke rehabilitation, but it lacks uniform information management among all levels of medical institutions.

Objective

To achieve unified management of stroke patient rehabilitation in multilevel hospitals in the region through informatization construction.

Methods

The need for informatization of three-level stroke rehabilitation management was analyzed. Then, network connections were established, and a common rehabilitation information management system (RIMS) was developed for all levels of hospitals to enable daily stroke rehabilitation management, inter-hospitals referral, and remote video consultation. Finally, the impact on the efficiency of daily rehabilitation work, the functioning and satisfaction of stroke patients were investigated after implementing the three-level rehabilitation network.

Results

One year after implementation, 338 two-way referrals and 56 remote consultations were completed using RIMS. The stroke RIMS improved the efficiency of doctors’ orders, reduced therapists’ time to write medical documents, simplified statistical analysis of data and made referrals and remote consultations more convenient compared to the traditional model. The curative effect of stroke patients managed by RIMS is better than that of traditional management. Patient satisfaction with rehabilitation services in the region has increased.

Conclusion

The three-level stroke rehabilitation informatization has enabled the unified management of stroke rehabilitation in multilevel hospitals in the region. The developed RIMS improved the efficiency of daily work, improved the clinical outcomes of stroke patients, and increased patient satisfaction.
Disease-associated oligodendrocyte signatures are spatiotemporally dysregulated in spinocerebellar ataxia type 3
Authors: Schuster Kristen H. , DiFranco Danielle M. , Putka Alexandra F. , Mato Juan P. , Jarrah Sabrina I. , Stec Nicholas R. , Sundararajan Vikram O. , McLoughlin Hayley S.
Published: February 2023

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease caused by a CAG repeat expansion in the ATXN3 gene. Though the ATXN3 protein is expressed ubiquitously throughout the CNS, regional pathology in SCA3 patients is observed within select neuronal populations and more recently within oligodendrocyte-rich white matter tracts. We have previously recapitulated these white matter abnormalities in an overexpression mouse model of SCA3 and demonstrated that oligodendrocyte maturation impairments are one of the earliest and most progressive changes in SCA3 pathogenesis. Disease-associated oligodendrocyte signatures have recently emerged as significant contributors to several other neurodegenerative diseases, including Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease, but their role in regional vulnerability and disease progression remains unexplored. Here, we are the first to comparatively assess myelination in human tissue in a region-dependent manner. Translating these findings to SCA3 mouse models of disease, we confirmed endogenous expression of mutant Atxn3 leads to regional transcriptional dysregulation of oligodendrocyte maturation markers in Knock-In models of SCA3. We then investigated the spatiotemporal progression of mature oligodendrocyte transcriptional dysregulation in an overexpression SCA3 mouse model and how it relates to the onset of motor impairment. We further determined that regional reduction in mature oligodendrocyte cell counts in SCA3 mice over time parallels the onset and progression of brain atrophy in SCA3 patients. This work emphasizes the prospective contributions of disease-associated oligodendrocyte signatures to regional vulnerability and could inform timepoints and target regions imperative for biomarker assessment and therapeutic intervention in several neurodegenerative diseases.
Association between dietary habits and incident thyroid cancer: A prospective cohort study
Authors: Nguyen Linh Thi Dieu , Gunathilake Madhawa , Lee Jeonghee , Kim Jeongseon
Published: February 2023

Background

In addition to the thyroid cancer (TC) risk from lifestyle and environmental factors such as radiation exposure, some studies have indicated that diet may affect TC development; however, previous findings are inconsistent. The objective of our study was to investigate the association between dietary habits and TC risk in a Korean population.

Materials and methods

A total of 13,973 participants were selected after excluding ineligible subjects from the Cancer Screenee Cohort at National Cancer Center in Korea from October 2007 to December 2021. Participants were followed until May 2022 to identify incident TC cases. Information on dietary habits and general characteristics was collected using a self-report questionnaire administered at enrollment without keeping track of changes in eating habits during the follow-up period. A Cox proportional hazards model was used to determine the hazard ratio (HR) and 95% confidence interval (CI) of TC risk for each dietary factor.

Results

A total of 138 incident TC cases were identified during the median follow-up period of 7.6 years. Of the 12 dietary habits evaluated, only two habits showed significant associations with TC. A significantly decreased TC risk was found among participants who consumed milk and/or dairy products 5 or more days a week [adjusted HR (aHR), 0.58; 95% CI, 0.39–0.85]. Notably, a stronger protective effect of dairy consumption was observed in participants aged ≥ 50 years (aHR, 0.44; 95% CI, 0.26–0.75), in women (aHR, 0.53; 95% CI, 0.35–0.81), and in non-smokers (aHR, 0.60; 95% CI, 0.39–0.92). There was a reduced risk of TC in participants with meal durations longer than 10 min (aHR, 0.58; 95% CI, 0.41–0.83). However, this association was limited to individuals aged ≥ 50 years (aHR, 0.49; 95% CI, 0.31–0.79), women (aHR, 0.61; 95% CI, 0.41–0.90), and non-smokers (aHR, 0.62; 95% CI, 0.41–0.92).

Conclusion

Our findings suggest that consuming milk and/or dairy products 5 or more days a week and having a meal duration longer than 10 min could be protective factors against TC, especially in individuals aged ≥ 50 years, women and non-smokers. Further prospective studies are needed to investigate the association of dietary intake with specific types of TC.
Classic ketogenic diet in parenteral nutrition in a GLUT1DS patient: Doing more with less in an acute surgical setting
Authors: De Giorgis Valentina , Ferraris Cinzia , Brena Mario Leo , Farris Giorgio , Gentilino Valerio , Guglielmetti Monica , Marazzi Claudia , Pasca Ludovica , Trentani Claudia , Tagliabue Anna , Varesio Costanza
Published: February 2023

Ketogenic Dietary Treatments (KDTs) are to date the gold-standard treatment for glucose transporter type 1 (GLUT1) deficiency syndrome. Administration of KDTs is generally per os; however, in some conditions including the acute gastro-enteric post-surgical setting, short-term parenteral (PN) administration might be needed. We report the case of a 14-year-old GLUT1DS patient, following classic KDT for many years, who underwent urgent laparoscopic appendectomy. PN-KDT was required, after 1 day of fasting. No ad hoc PN-KDTs products were available and the patient received infusions of OLIMEL N4 (Baxter). On the sixth day postoperatively enteral nutrition was progressively reintroduced. The outcome was optimal with rapid recovery and no exacerbation of neurological manifestations. Our patient is the first pediatric patient with GLUT1DS in chronic treatment with KDT efficiently treated with exclusive PN for five days. This case reports on real-word management and the ideal recommendations for PN-KDT in an acute surgical setting.
Unveiling the therapeutic potential of cabozantinib-loaded poly D,L-lactic-co-glycolic acid and polysarcosine nanoparticles in inducing apoptosis and cytotoxicity in human HepG2 hepatocellular carcinoma cell lines and in vivo anti-tumor activity in SCID female mice
Authors: Bhattacharya Sankha , Parihar Vipan Kumar , Prajapati Bhupendra G.
Published: February 2023

Introduction

The study aimed to develop a nano-based drug delivery system for the treatment of hepatocellular carcinoma (HCC), a type of liver cancer that accounts for 90% of all liver malignancies. The study focused on the use of cabozantinib (CNB), a potent multikinase inhibitor that targets the VEGF receptor 2, as the chemotherapeutic drug. We developed CNB-loaded nanoparticles made from Poly D, L-lactic-co-glycolic acid, and Polysarcosine (CNB-PLGA-PSar-NPs) for use in human HepG2 cell lines.

Methods

By O/W solvent evaporation method, the polymeric nanoparticles were prepared. The various techniques, such as photon correlation spectroscopy, scanning electron microscopy, and transmission electron microscopy were used, to determine the formulation's particle size, zeta potential, and morphology. SYBR Green/ROX qPCR Master Mix and RT-PCR equipment used to measure liver cancer cell line and tissue mRNA expression and MTT assay to test HepG2 cell cytotoxicity. Cell cycle arrest analysis, annexin V assay, and ZE5 Cell Analyzer apoptosis assay were also performed.

Results

The results of the study showed that the particle diameters were 192.0 ± 3.67 nm with 0.128 PDI and -24.18 ± 3.34 mV zeta potential. The antiproliferative and proapoptotic effects of CNB-PLGA-PSar-NPs were evaluated using MTT and flow cytometry (FCM). The IC50 value of CNB-PLGA-PSar-NPs was 45.67 µg/mL, 34.73 µg/mL, and 21.56 µg/mL for 24, 48, and 72 h, respectively. The study also found that 11.20% and 36.77% of CNB-PLGA-PSar-NPs-treated cells were apoptotic at 60 µg/mL and 80 µg/mL, respectively, suggesting that the nanoparticles were effective in inducing apoptosis in the cancer cells. It can also conclude that, CNB-PLGA-PSar-NPs inhibit human HepG2 hepatocellular carcinoma cells and kill them by upregulating the tumour suppressor genes MT1F, MT1X, and downregulating MTTP, APOA4. Further in vivo antitumor activity was well reported in SCID female mice.

Discussion

Overall, this study suggests that the CNB-PLGA-PSar-NPs are a promising drug delivery system for the treatment of HCC, and further research is needed to investigate their potential in clinical treatment.
Lamivudine 24-month-long prophylaxis is a safe and efficient choice for the prevention of hepatitis B virus reactivation in HBsAg-negative/HBcAb-positive patients with advanced DLBCL undergoing upfront R-CHOP-21
Authors: Giordano Claudia , Picardi Marco , Pugliese Novella , Vincenzi Annamaria , Abagnale Davide Pio , De Fazio Laura , Giannattasio Maria Luisa , Fatigati Carmina , Ciriello Mauro , Salemme Alessia , Muccioli Casadei Giada , Vigliar Elena , Mascolo Massimo , Troncone Giancarlo , Pane Fabrizio
Published: February 2023

Introduction

Occult hepatitis B infection (OBI) is a condition where replication-competent hepatitis B virus-DNA (HBV-DNA) is present in the liver, with or without HBV-DNA in the blood [<200 international units (IU)/ml or absent] in HB surface antigen (HBsAg)-negative/HB core antibody (HBcAb)-positive individuals. In patients with advanced stage diffuse large B-cell lymphoma (DLBCL) undergoing 6 cycles of R-CHOP-21+2 additional R, OBI reactivation is a frequent and severe complication. There is no consensus among recent guidelines on whether a pre-emptive approach or primary antiviral prophylaxis is the best solution in this setting of patients. In addition, questions still unresolved are the type of prophylactic drug against HBV and adequate prophylaxis duration.

Methods

In this case-cohort study, we compared a prospective series of 31 HBsAg−/HBcAb+ patients with newly diagnosed high-risk DLBCL receiving lamivudine (LAM) prophylaxis 1 week before R-CHOP-21+2R until 18 months after (24-month LAM series) versus 96 HBsAg−/HBcAb+ patients (from January 2005 to December 2011) undergoing a pre-emptive approach (pre-emptive cohort) and versus 60 HBsAg−/HBcAb+ patients, from January 2012 to December 2017, receiving LAM prophylaxis [1 week before immunochemotherapy (ICHT) start until 6 months after] (12-month LAM cohort). Efficacy analysis focused primarily on ICHT disruption and secondarily on OBI reactivation and/or acute hepatitis.

Results

In the 24-month LAM series and in the 12-month LAM cohort, there were no episodes of ICHT disruption versus 7% in the pre-emptive cohort (P = 0.05). OBI reactivation did not occur in any of the 31 patients in the 24-month LAM series versus 7 out of 60 patients (10%) in the 12-month LAM cohort or 12 out of 96 (12%) patients in the pre-emptive cohort (P = 0.04, by χ2 test). No patients in the 24-month LAM series developed acute hepatitis compared with three in the 12-month LAM cohort and six in the pre-emptive cohort.

Discussion

This is the first study collecting data regarding a consistent and homogeneous large sample of 187 HBsAg−/HBcAb+ patients undergoing standard R-CHOP-21 for aggressive lymphoma. In our study, 24-month-long prophylaxis with LAM appears to be the most effective approach with a null risk of OBI reactivation, hepatitis flare-up, and ICHT disruption.
Predicting complications in pediatric Crohn's disease patients followed in CEDATA-GPGE registry
Authors: Klamt Juliane , de Laffolie Jan , Wirthgen Elisa , Stricker Sebastian , Däbritz Jan ,   the CEDATA-GPGE study group
Published: February 2023

Background

Complications of Crohn's disease (CD) often impair patients' quality of life. It is necessary to predict and prevent these complications (surgery, stricturing [B2]/penetrating [B3] disease behavior, perianal disease, growth retardation and hospitalization). Our study investigated previously suggested and additional predictors by analyzing data of the CEDATA-GPGE registry.

Methods

Pediatric patients (< 18 years) diagnosed with CD with follow up data in the registry were included in the study. Potential risk factors for the selected complications were evaluated by performing Kaplan-Meier survival curves and cox regression models.

Results

For the complication surgery, the potential risk factors older age, B3 disease, severe perianal disease and initial therapy with corticosteroids at the time of diagnosis were identified. Older age, initial therapy with corticosteroids, low weight-for-age, anemia and emesis predict B2 disease. Low weight-for-age and severe perianal disease were risk factors for B3 disease. Low weight-for-age, growth retardation, older age, nutritional therapy, and extraintestinal manifestations (EIM) of the skin were identified as risk factors for growth retardation during the disease course. High disease activity and treatment with biologicals were predictors for hospitalization. As risk factors for perianal disease, the factors male sex, corticosteroids, B3 disease, a positive family history and EIM of liver and skin were identified.

Conclusion

We confirmed previously suggested predictors of CD course and identified new ones in one of the largest registries of pediatric CD patients. This may help to better stratify patients’ according to their individual risk profile and choose appropriate treatment strategies.
Platelet and ferritin as early predictive factors for the development of macrophage activation syndrome in children with Kawasaki disease: A retrospective case-control study
Authors: Zhang Hua-yong , Xiao Min , Zhou Dan , Yan Fan , Zhang Yong
Published: February 2023

Objective

To investigate the early predictive factors for Kawasaki disease complicated with macrophage activation syndrome (KD-MAS)

Methods

We performed a retrospective case-control study in children with KD from August 2017 to August 2022, involving 28 cases with KD-MAS and 112 cases not developing KD-MAS. Based on the univariate analysis, binary logistic regression was used to identify the early predictive factors for KD-MAS development, and the receiver operating characteristic curve (ROC) analysis was carried out to obtain the optimal cut-off value.

Results

Two predictive factors were associated with the development of KD-MAS, which were PLT (OR = 1.013, 95%CI, 1.001–1.026), and serum ferritin (OR = 0.991, 95%CI, 0.982–0.999). The cut-off value of PLT was 110 × 109/L, and the cut-off value of serum ferritin was 548.4 ng/ml.

Conclusion

Children with KD who had a PLT count under 110 × 109/L, and a serum ferritin level over 548.4 ng/ml are more likely to develop KD-MAS.
Avatrombopag for the treatment of thrombocytopenia in children's patients following allogeneic hematopoietic stem-cell transplantation: A pilot study
Authors: Ruan Yongsheng , Cao Wei , Luo Tingting , Liu Xuan , Liu Qiujun , Xiao Yuhua , Wu Cuiling , Xie Danfeng , Ren Yuqiong , Wu Xuedong , Feng Xiaoqin
Published: February 2023

Thrombocytopenia following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a common and life-threatening complication. Thus, new prevention and treatment strategies for post-HSCT thrombocytopenia are urgently required. In recent studies, thrombopoietin receptor agonists (TPO-RA) for treating post-HSCT thrombocytopenia indicated efficiency and safety. The improved effect of post-HSCT thrombocytopenia in adults was found in the administration of avatrombopag which was a new TPO-RA. However, there was no relevant study in the children's cohort. Herein, we retrospectively analyzed the effect of avatrombopag in post-HSCT thrombocytopenia in children. As a result, the overall response rate (ORR) and complete response rate (CRR) were 91% and 78%, respectively. Furthermore, both cumulative ORR and CRR were significantly lower in the poor graft function (PGF)/secondary failure of platelet recovery (SFPR) group compared to the engraftment-promotion group (86.7% vs. 100%, p = 0.002 and 65.0% vs. 100%, p < 0.001, respectively). Achieving OR required a median of 16 days in the PGF/SFPR group while 7 days in the engraftment-promotion group (p = 0.003). Grade III–IV acute graft vs. host disease and inadequate megakaryocytes were identified as risk factors of CRR only in univariate analysis (p = 0.03 and p = 0.01, respectively). No severe adverse events were documented. Conclusively, avatrombopag is an alternatively efficient and safe agent for treating post-HSCT thrombocytopenia in children.
Effects of a mobile health nutrition intervention on dietary intake in children who have autism spectrum disorder
Authors: Kral Tanja V. E. , O’Malley Lauren , Johnson Kelsey , Benvenuti Teresa , Chittams Jesse , Quinn Ryan J. , Thomas J. Graham , Pinto-Martin Jennifer A. , Levy Susan E. , Kuschner Emily S.
Published: February 2023

Background

Children who have Autism Spectrum Disorder (ASD) show preferences for processed foods, such as salty and sugary snacks (SSS) and sugar-sweetened beverages (SSB), while healthier foods, such as fruits and vegetables (FV), are consumed less. Innovative tools are needed that can efficiently disseminate evidence-based interventions and engage autistic children to improve their diet.

Aim

The aim of this 3-month randomized trial was to test the initial efficacy of a mobile health (mHealth) nutrition intervention on changing consumption of targeted healthy (FV) and less healthy foods/beverages (SSS, SSB) in children who have ASD, ages 6–10, who were picky eaters.

Methods

Thirty-eight parent-child dyads were randomly assigned to either an intervention (technology) group or a wait list control (education) group. The intervention included behavioral skills training, a high level of personalization for dietary goals, and involved parents as “agents of change.” Parents in the education group received general nutrition education and the dietary goals but did not receive skills training. Children's intake was assessed at baseline and at 3 months using 24-hour dietary recalls.

Results

While there were no significant group-by-time interactions (P > 0.25) for any of the primary outcomes, we found a significant main effect of time for FV intake (P = 0.04) indicating that both groups consumed more FV at 3 months (2.58 ± 0.30 servings/day) than at baseline (2.17 ± 0.28 servings/day; P = 0.03). Children in the intervention group who consumed few FV at baseline and showed high engagement with the technology increased their FV intake by 1.5 servings/day (P < 0.01). Children's taste/smell sensitivity significantly predicted their FV intake (P = 0.0446); for each unit of lower taste/smell sensitivity (indicating greater sensory processing abnormalities), FV intake increased by 0.13 ± 0.1 servings/day.

Discussion

This mHealth intervention did not yield significant between-group differences for changing consumption of targeted foods/beverages. Only children who consumed few FV at baseline and highly engaged with the technology increased their FV intake at 3 months. Future research should test additional strategies to expand the intervention's impact on a wider range of foods while also reaching a broader group of children who have ASD. This trial was registered at clinicaltrials.gov as NCT03424811.

Clinical Trial Registration: This study was registered at clinicaltrials.gov as NCT03424811.
Association of newer definitions of bronchopulmonary dysplasia with pulmonary hypertension and long-term outcomes
Authors: Hwang Jae Kyoon , Shin Seung Han , Kim Ee-Kyung , Kim Seh Hyun , Kim Han-Suk
Published: February 2023

Background

The definition of bronchopulmonary dysplasia (BPD) has been evolved recently from definition by the National Institute of Child Health and Human Development in 2001 (NICHD 2001) to the definition reported in 2018 (NICHD 2018) and that proposed by Jensen et al. in 2019 (NICHD 2019). The definition was developed based on the evolution of non-invasive respiratory support and to achieve better prediction of later outcomes. Our objective was to evaluate the association between different definitions of BPD and occurrence of pulmonary hypertension (PHN) and long term outcomes.

Methods

This retrospective study enrolled preterm infants born at < 32 weeks of gestation between 2014 and 2018. The association between re-hospitalization owing to a respiratory illness until a corrected age (CA) of 24 months, neurodevelopmental impairment (NDI) at a CA of 18–24 months, and PHN at a postmenstrual age (PMA) of 36 weeks was evaluated, with the severity of BPD defined based on these three definitions.

Results

Among 354 infants, the gestational age and birth weight were the lowest in severe BPD based on the NICHD 2019 definition. In total, 14.1% of the study population experienced NDI and 19.0% were re-hospitalized owing to a respiratory illness. At a PMA of 36 weeks, PHN was identified in 9.2% of infants with any BPD. Multiple logistic regression analysis showed that the adjusted odds ratio (OR) for re-hospitalization was the highest for Grade 3 BPD of the NICHD 2019 criteria (5.72, 95% confidence interval [CI]: 1.37–23.92), while the adjusted OR of Grade 3 BPD was 4.96 (95% CI: 1.73–14.23) in the NICHD 2018 definition. Moreover, no association of the severity of BPD was found in the NICHD 2001 definition. The adjusted ORs for NDI (12.09, 95% CI: 2.52–58.05) and PHN (40.37, 95% CI: 5.15–316.34) were also the highest for Grade 3 of the NICHD 2019 criteria.

Conclusion

Based on recently suggested criteria by the NICHD in 2019, BPD severity is associated with long-term outcomes and PHN at a PMA of 36 weeks in preterm infants.
TRPV1: A promising therapeutic target for skin aging and inflammatory skin diseases
Authors: Xiao Tengfei , Sun Mingzhong , Zhao Chuanxiang , Kang Jingjing
Published: February 2023

TRPV1 is a non-selective channel receptor widely expressed in skin tissues, including keratinocytes, peripheral sensory nerve fibers and immune cells. It is activated by a variety of exogenous or endogenous inflammatory mediators, triggering neuropeptide release and neurogenic inflammatory response. Previous studies have shown that TRPV1 is closely related to the occurrence and/or development of skin aging and various chronic inflammatory skin diseases, such as psoriasis, atopic dermatitis, rosacea, herpes zoster, allergic contact dermatitis and prurigo nodularis. This review summarizes the structure of the TRPV1 channel and discusses the expression of TRPV1 in the skin as well as its role of TRPV1 in skin aging and inflammatory skin diseases.
In vitro metabolic characterization of the SARS-CoV-2 papain-like protease inhibitors GRL0617 and HY-17542
Authors: Cho Hyunki , Kim Young Jun , Chae Jung-Woo , Meyer Markus R. , Kim Sang Kyum , Ryu Chang Seon
Published: February 2023

The SARS-CoV-2 pandemic requires a new therapeutic target for viral infection, and papain-like protease (Plpro) has been suggested as a druggable target. This in-vitro study was conducted to examine the drug metabolism of the GRL0617 and HY-17542, Plpro inhibitors. Metabolism of these inhibitors was studied to predict the pharmacokinetics in human liver microsomes. The hepatic cytochrome P450 (CYP) isoforms responsible for their metabolism were identified using recombinant enzymes. The drug–drug interaction potential mediated by cytochrome P450 inhibition was estimated. In human liver microsomes, the Plpro inhibitors had phase I and phase I + II metabolism with half-lives of 26.35 and 29.53 min, respectively. Hydroxylation (M1) and desaturation (-H2, M3) of the para-amino toluene side chain were the predominant reactions mediated with CYP3A4 and CYP3A5. CYP2D6 is responsible for the hydroxylation of the naphthalene side ring. GRL0617 inhibits major drug-metabolizing enzymes, including CYP2C9 and CYP3A4. HY-17542 is structural analog of GRL0617 and it is metabolized to GRL0617 through non-cytochrome P450 reactions in human liver microsomes without NADPH. Like GRL0617 and HY-17542 undergoes additional hepatic metabolism. The in-vitro hepatic metabolism of the Plpro inhibitors featured short half-lives; preclinical metabolism studies are needed to determine therapeutic doses for these inhibitors.
Association between statin use and the risk of gout in patients with hyperlipidemia: A population-based cohort study
Authors: Lin Guan-Ling , Lin Hsiu-Chen , Lin Hsiu-Li , Keller Joseph Jordan , Wang Li-Hsuan
Published: February 2023

Objective: To investigate the association between statin use and risk of gout in patients with hyperlipidemia.

Methods: In this population-based retrospective cohort study, patients ≥20 years and diagnosed as having incident hyperlipidemia between 2001 and 2012 were identified from the 2000 Longitudinal Generation Tracking Database in Taiwan. Regular statin users (incident statin use, having 2 times and ≥90 days of prescription for the first year) and two active comparators [irregular statin use and other lipid-lowering agent (OLLA) use] were compared; the patients were followed up until the end of 2017. Propensity score matching was applied to balance potential confounders. Time-to-event outcomes of gout and dose- and duration-related associations were estimated using marginal Cox proportional hazard models.

Results: Regular statin use non-significantly reduced gout risk compared with irregular statin use (aHR, 0.95; 95% CI, 0.90–1.01) and OLLA use (aHR, 0.94; 95% CI, 0.84–1.04). However, a protective effect was noted for a cumulative defined daily dose (cDDD) of >720 (aHR, 0.57; 95% CI, 0.47–0.69 compared with irregular statin use and aHR, 0.48; 95% CI, 0.34–0.67 compared with OLLA use) or a therapy duration of >3 years (aHR, 0.76; 95% CI, 0.64–0.90 compared with irregular statin use and aHR, 0.50; 95% CI, 0.37–0.68 compared with OLLA use). Dose- and duration-dependent associations were consistent in the 5-year sensitivity analyses.

Conclusion: Although statin use was not associated with a reduction in gout risk, the protective benefit was observed in those receiving higher cumulative doses or with a longer therapy duration.
Inhibitory effect of Selaginella doederleinii hieron on human cytochrome P450
Authors: Lin Fei , Lin Xinhua , Wang Xuewen , Mei Guanghui , Chen Bing , Yao Hong , Huang Lingyi
Published: February 2023

Introduction:Selaginella doederleinii Hieron is a traditional Chinese herbal medicine, the ethyl acetate extract from Selaginella doederleinii (SDEA) showed favorable anticancer potentials. However, the effect of SDEA on human cytochrome P450 enzymes (CYP450) remains unclear. To predict the herb-drug interaction (HDI) and lay the groundwork for further clinical trials, the inhibitory effect of SDEA and its four constituents (Amentoflavone, Palmatine, Apigenin, Delicaflavone) on seven CYP450 isoforms were investigated by using the established CYP450 cocktail assay based on LC-MS/MS.

Methods: Appropriate substrates for seven tested CYP450 isoforms were selected to establish a reliable cocktail CYP450 assay based on LC-MS/MS. The contents of four constituents (Amentoflavone, Palmatine, Apigenin, Delicaflavone) in SDEA were determined as well. Then, the validated CYP450 cocktail assay was applied to test the inhibitory potential of SDEA and four constituents on CYP450 isoforms.

Results: SDEA showed strong inhibitory effect on CYP2C9 and CYP2C8 (IC50 ≈ 1 μg/ml), moderate inhibitory effect against CYP2C19, CYP2E1 and CYP3A (IC50 < 10 μg/ml). Among the four constituents, Amentoflavone had the highest content in the extract (13.65%) and strongest inhibitory effect (IC50 < 5 μM), especially for CYP2C9, CYP2C8 and CYP3A. Amentoflavone also showed time-dependent inhibition on CYP2C19 and CYP2D6. Apigenin and Palmatine both showed concentration-dependent inhibition. Apigenin inhibited CYP1A2, CYP2C8, CYP2C9, CYP2E1 and CYP3A. Palmatine inhibited CYP3A and had a weak inhibitory effect on CYP2E1. As for Delicaflavone, which has the potential to develop as an anti-cancer agent, showed no obvious inhibitory effect on CYP450 enzymes.

Conclusion: Amentoflavone may be one of the main reasons for the inhibition of SDEA on CYP450 enzymes, the potential HDI should be considered when SDEA or Amentoflavone were used with other clinical drugs. On the contrast, Delicaflavone is more suitable to develop as a drug for clinical use, considering the low level of CYP450 metabolic inhibition.