bluuebunny/crossref_metadata_2025 huggingface dataset:
A Modified Lysimeter Study for Phyto-Treatment of Moderately Saline Wastewater Using Plant-Derived Filter Bedding Materials
Authors: Marathe Deepak , Raghunathan Karthik , Singh Anshika , Thawale Prashant , Kumari Kanchan
Published: December 2021

The present study focuses on determining the phyto-treatment efficiency for treatment of moderately saline wastewater using organic raw materials, such as rice husk, coconut husk, rice straw, and charcoal. The moderately saline wastewater with total dissolved solids (TDS) concentration up to 6143.33 ± 5.77 mg/L was applied to the lysimeters at the rate of 200 m3ha–1day–1in five different lysimeter treatments planted withEucalyptus camaldulensis(T1, T2, T3, T4, and T5). T1 was a control without any filter bedding material, whereas rice straw, rice husk, coconut husk, and charcoal were used as filter bedding materials in the T2, T3, T4, and T5 treatment systems, respectively. Each treatment showed significant treatment efficiency wherein T3 had the highest removal efficiency of 76.21% followed by T4 (67.57%), T5 (65.18%), T2 (46.46%), and T1 (45.5%). T3 and T4 also showed higher salt accumulation, such as sodium (Na) and potassium (K). Further, the pollution load in terms of TDS and chemical and biological oxygen demand significantly reduced from leachate in the T3 and T4 treatments in comparison with other treatments. Parameters of the soil, such as electrical conductivity, exchangeable sodium percentage, and cation exchange capacity did not show values corresponding to high salinity or sodic soils, and therefore, no adverse impact on soil was observed in the present study. Also,Eucalyptus camaldulensisplant species showed good response to wastewater treatment in terms of growth parameters, such as root/shoot weight and nitrogen, phosphorus, and potassium (NPK) uptake, plant height, biomass, and chlorophyll content. Root and shoot dry weight were in the order T3 (51.2 and 44.6 g)>T4 (49.3 and 43.5 g) > T5 (47.6 and 40.5 g) > T2 (46.9 and 38.2 g) > T1 (45.6 and 37.1 g). Likewise, the total chlorophyll content was highest in T3 (12.6 μg/g) followed by T4 (12.3 μg/g), T5 (11.9 μg/g), T2 (11.5 μg/g), and the control, that is, T1 (11.0 μg/g). However, the most promising results were obtained for T3 and T4 treatments in comparison with the control (T1), which implies that, among all organic raw materials, coconut and rice husks showed the highest potential for salt accumulation and thereby wastewater treatment. Conclusively, the findings of the study suggest that organic raw material–based amendments are useful in managing the high salts levels in both plants and leachates.
An Update on Antioxidative Stress Therapy Research for Early Brain Injury After Subarachnoid Hemorrhage
Authors: Lin Fa , Li Runting , Tu Wen-Jun , Chen Yu , Wang Ke , Chen Xiaolin , Zhao Jizong
Published: December 2021

The main reasons for disability and death in aneurysmal subarachnoid hemorrhage (aSAH) may be early brain injury (EBI) and delayed cerebral ischemia (DCI). Despite studies reporting and progressing when DCI is well-treated clinically, the prognosis is not well-improved. According to the present situation, we regard EBI as the main target of future studies, and one of the key phenotype-oxidative stresses may be called for attention in EBI after laboratory subarachnoid hemorrhage (SAH). We summarized the research progress and updated the literature that has been published about the relationship between experimental and clinical SAH-induced EBI and oxidative stress (OS) in PubMed from January 2016 to June 2021. Many signaling pathways are related to the mechanism of OS in EBI after SAH. Several antioxidative stress drugs were studied and showed a protective response against EBI after SAH. The systematical study of antioxidative stress in EBI after laboratory and clinical SAH may supply us with new therapies about SAH.
Production and Characterization of Cellulose Nanofiber Slurries and Sheets for Biomedical Applications
Authors: Carter Nicklaus , Grant Isabelle , Dewey Marley , Bourque Mary , Neivandt David J.
Published: December 2021

Cellulose nanomaterials are produced employing a multitude of methodologies including electrospinning, bacterial generation, acid digestion, and a variety of mechanical defibrillation techniques; the morphology of the nanomaterial produced is specific to the production process. Feedstocks range from various forms of woody biomass, to fungi, and have a great impact on the resulting product. The mechanical defibrillation technique, such as that employed in the present work, continuously breaks down cellulose fibers suspended in water via segmentation and defibrillation through grinding and refining. The process is typically operated until a desired level of fines is achieved in the resultant slurry of cellulose nanofiber (CNF), alternatively known as cellulose nanofibril. Mechanical defibrillation processes can be built to produce several liters in a small batch system or up to tons per day in a continuous pilot scale refiner system. In the present work a continuous system was developed with the capacity to produce 14 L of cellulose nanofiber slurry with consistent specifications and in a manner compliant with GMP/GLP protocols in order to be amenable to biomedical applications. The system was constructed within an ISO class 7 cleanroom and refining was performed on bleached softwood pulp suspension in purified water. This manuscript details the continuous grinding system, the processes employed to produce cellulose nanofiber, and characterizes the resultant cellulose nanofiber slurry and sheets formed from the slurry.
Neural Progenitor Cells Expressing Herpes Simplex Virus-Thymidine Kinase for Ablation Have Differential Chemosensitivity to Brivudine and Ganciclovir
Authors: Lou Zijian , Post Alexander , Rodgers Christopher E. , Chamankhah Mahmood , Hong James , Ahuja Christopher S. , Khazaei Mohamad , Fehlings Michael G.
Published: December 2021

Neural progenitor cell (NPC) transplants are a promising therapy for treating spinal cord injury (SCI), however, their long-term role after engraftment and the relative contribution to ongoing functional recovery remains a key knowledge gap. Selective human cell ablation techniques, currently being developed to improve the safety of progenitor cell transplant therapies in patients, may also be used as tools to probe the regenerative effects attributable to individual grafted cell populations. The Herpes Simplex Virus Thymidine Kinase (HSV-TK) and ganciclovir (GCV) system has been extensively studied in the context of SCI and broader CNS disease. However, the efficacy of brivudine (BVDU), another HSV-TK prodrug with potentially reduced bystander cytotoxic effects and in vivo toxicity, has yet to be investigated for NPC ablation. In this study, we demonstrate successful generation and in vitro ablation of HSV-TK-expressing human iPSC-derived NPCs with a >80% reduction in survival over controls. We validated an HSV-TK and GCV/BVDU synergistic system with iPSC-NPCs using an efficient gene-transfer method and in vivo ablation in a translationally relevant model of SCI. Our findings demonstrate enhanced ablation efficiency and reduced bystander effects when targeting all rapidly dividing cells with combinatorial GCV and BVDU treatment. However, for use in loss of function studies, BVDU alone is optimal due to reduced nonselective cell ablation.
Corticothalamic Projections Gate Alpha Rhythms in the Pulvinar
Authors: Cortes Nelson , Abbas Farishta Reza , Ladret Hugo J. , Casanova Christian
Published: December 2021

Two types of corticothalamic (CT) terminals reach the pulvinar nucleus of the thalamus, and their distribution varies according to the hierarchical level of the cortical area they originate from. While type 2 terminals are more abundant at lower hierarchical levels, terminals from higher cortical areas mostly exhibit type 1 axons. Such terminals also evoke different excitatory postsynaptic potential dynamic profiles, presenting facilitation for type 1 and depression for type 2. As the pulvinar is involved in the oscillatory regulation between intercortical areas, fundamental questions about the role of these different terminal types in the neuronal communication throughout the cortical hierarchy are yielded. Our theoretical results support that the co-action of the two types of terminals produces different oscillatory rhythms in pulvinar neurons. More precisely, terminal types 1 and 2 produce alpha-band oscillations at a specific range of connectivity weights. Such oscillatory activity is generated by an unstable transition of the balanced state network’s properties that it is found between the quiescent state and the stable asynchronous spike response state. While CT projections from areas 17 and 21a are arranged in the model as the empirical proportion of terminal types 1 and 2, the actions of these two cortical connections are antagonistic. As area 17 generates low-band oscillatory activity, cortical area 21a shifts pulvinar responses to stable asynchronous spiking activity and vice versa when area 17 produces an asynchronous state. To further investigate such oscillatory effects through corticothalamo-cortical projections, the transthalamic pathway, we created a cortical feedforward network of two cortical areas, 17 and 21a, with CT connections to a pulvinar-like network with two cortico-recipient compartments. With this model, the transthalamic pathway propagates alpha waves from the pulvinar to area 21a. This oscillatory transfer ceases when reciprocal connections from area 21a reach the pulvinar, closing the CT loop. Taken together, results of our model suggest that the pulvinar shows a bi-stable spiking activity, oscillatory or regular asynchronous spiking, whose responses are gated by the different activation of cortico-pulvinar projections from lower to higher-order areas such as areas 17 and 21a.
Real-Time Detection of Freezing Motions in Parkinson's Patients for Adaptive Gait Phase Synchronous Cueing
Authors: Dvorani Ardit , Waldheim Vivian , Jochner Magdalena C. E. , Salchow-Hömmen Christina , Meyer-Ohle Jonas , Kühn Andrea A. , Wenger Nikolaus , Schauer Thomas
Published: December 2021

Parkinson's disease is the second most common neurodegenerative disease worldwide reducing cognitive and motoric abilities of affected persons. Freezing of Gait (FoG) is one of the severe symptoms that is observed in the late stages of the disease and considerably impairs the mobility of the person and raises the risk of falls. Due to the pathology and heterogeneity of the Parkinsonian gait cycle, especially in the case of freezing episodes, the detection of the gait phases with wearables is challenging in Parkinson's disease. This is addressed by introducing a state-automaton-based algorithm for the detection of the foot's motion phases using a shoe-placed inertial sensor. Machine-learning-based methods are investigated to classify the actual motion phase as normal or FoG-affected and to predict the outcome for the next motion phase. For this purpose, spatio-temporal gait and signal parameters are determined from the segmented movement phases. In this context, inertial sensor fusion is applied to the foot's 3D acceleration and rate of turn. Support Vector Machine (SVM) and AdaBoost classifiers have been trained on the data of 16 Parkinson's patients who had shown FoG episodes during a clinical freezing-provoking assessment course. Two clinical experts rated the video-recorded trials and marked episodes with festination, shank trembling, shuffling, or akinesia. Motion phases inside such episodes were labeled as FoG-affected. The classifiers were evaluated using leave-one-patient-out cross-validation. No statistically significant differences could be observed between the different classifiers for FoG detection (p>0.05). An SVM model with 10 features of the actual and two preceding motion phases achieved the highest average performance with 88.5 ± 5.8% sensitivity, 83.3 ± 17.1% specificity, and 92.8 ± 5.9% Area Under the Curve (AUC). The performance of predicting the behavior of the next motion phase was significantly lower compared to the detection classifiers. No statistically significant differences were found between all prediction models. An SVM-predictor with features from the two preceding motion phases had with 81.6 ± 7.7% sensitivity, 70.3 ± 18.4% specificity, and 82.8 ± 7.1% AUC the best average performance. The developed methods enable motion-phase-based FoG detection and prediction and can be utilized for closed-loop systems that provide on-demand gait-phase-synchronous cueing to mitigate FoG symptoms and to prevent complete motoric blockades.
Higher Cerebral Blood Flow Predicts Early Hematoma Expansion in Patients With Intracerebral Hemorrhage: A Clinical Study
Authors: Wang Weijing , Jin Weitao , Feng Hao , Wu Guoliang , Wang Wenjuan , Jia Jiaokun , Ji Ruijun , Wang Anxin , Zhao Xingquan
Published: December 2021

The early hematoma expansion of intracerebral hemorrhage (ICH) indicates a poor prognosis. This paper studies the relationship between cerebral blood flow (CBF) around the hematoma and hematoma expansion (HE) in the acute stage of intracerebral hemorrhage. A total of 50 patients with supratentorial cerebral hemorrhage were enrolled in this study. They underwent baseline whole-brain CTP within 6 h after intracerebral hemorrhage, and non-contrast CT within 24 h. Absolute hematoma growth and relative hematoma growth were calculated, respectively. A relative growth of Hematoma volume >33% was considered to be hematoma expansion. The Ipsilateral peri-edema CBF and Ipsilateral edema CBF were calculated by CTP maps in patients with and without hematoma expansion, respectively. In this study the incidence of hematoma expansion in the early stage of supratentorial cerebral hemorrhage was 32%; The CBF of the hematoma expansion group was higher than that of the patients without hematoma expansion (23.5 ± 12.5 vs. 15.1 ± 7.4, P = 0.004). After adjusting for age, gender, Symptom onset to NCCT and Baseline hematoma volume, ipsilateral peri-edema CBF was still an independent risk factor for early HE (or = 1.095, 95% CI = 1.01–1.19, P = 0.024). Here, we concluded that higher cerebral blood flow predicts early hematoma expansion in patients with intracerebral hemorrhage.
The Effect of Isotonic Saline Nasal Lavages in Improving Symptoms in SARS-CoV-2 Infection: A Case-Control Study
Authors: Spinato Giacomo , Fabbris Cristoforo , Costantini Giulio , Conte Federica , Scotton Pier Giorgio , Cinetto Francesco , De Siati Rosalba , Matarazzo Alessandro , Citterio Marco , Contro Giacomo , De Filippis Cosimo , Agostini Carlo , Emanuelli Enzo , Boscolo-Rizzo Paolo , Frezza Daniele
Published: December 2021

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mainly colonizes nasopharynx. In upper airways acute infections, e.g., the common cold, saline nasal irrigations have a significant efficacy in reducing symptoms. The present study aimed to test the efficacy of nasal lavages in upper airways symptoms of Coronavirus Disease 2019 (COVID-19).

Methods: A series of consecutive adult subjects who tested positive for SARS-CoV-2 from December 2020 to February 2021 performed daily nasal lavages with saline solution (Lavonase®—Purling, Lugo di Romagna, Italy) for 12 days, starting on the day after the SARS-CoV-2 positive swab. A control group included a historical series of patients who were infected in February-March 2020 and who did not perform lavages. An ad hoc questionnaire regarding symptoms was administered to each subjects at base-line and 10 days after diagnosis (i.e., on the same day of the control swab) in both cases and controls.

Results: A total of 140 subjects were enrolled. 68 participants in the treatment group and 72 in the control group were included. 90% of respondents declared the lavages were simple to use and 70% declared they were satisfied. Symptoms of blocked nose, runny nose, or sneezing decreased by an average of 24.7% after the treatment. Blocked nose and sneezing increased in the same period of time in the control group. Ears and eyes symptoms, anosmia/ageusia symptoms, and infection duration (10.53 days in the treatment group and 10.48 days in the control group) didn't vary significantly among the two groups.

Conclusion: Nasal lavages resulted to significantly decrease nasal symptoms in newly diagnosed SARS-CoV-2 patients. These devices proved to be well-tolerated and easy to be used. Further studies on a larger number of subjects are needed in order to possibly confirm these preliminary results.
Developmental Exposure to a Human-Relevant Polychlorinated Biphenyl Mixture Causes Behavioral Phenotypes That Vary by Sex and Genotype in Juvenile Mice Expressing Human Mutations That Modulate Neuronal Calcium
Authors: Sethi Sunjay , Keil Stietz Kimberly P. , Valenzuela Anthony E. , Klocke Carolyn R. , Silverman Jill L. , Puschner Birgit , Pessah Isaac N. , Lein Pamela J.
Published: December 2021

Polychlorinated biphenyls (PCBs) are putative environmental risks for neurodevelopmental disorders. Here, we tested two hypotheses: (1) developmental exposure to a human-relevant PCB mixture causes behavioral phenotypes relevant to neurodevelopmental disorders; and (2) expression of human mutations that dysregulate neuronal Ca2+ homeostasis influence sensitivity to behavioral effects of developmental PCB exposures. To test these hypotheses, we used mice that expressed a gain-of-function mutation (T4826I) in ryanodine receptor 1 (RYR1), the X-linked fragile X mental retardation 1 (FMR1) CGG repeat expansion or both mutations (double mutant; DM). Transgenic mice and wildtype (WT) mice were exposed to the MARBLES PCB mix at 0, 0.1, 1, and 6 mg/kg/day in the maternal diet throughout gestation and lactation. The MARBLES PCB mix simulates the relative proportions of the 12 most abundant PCB congeners found in the serum of pregnant women at increased risk for having a child with a neurodevelopmental disorder. We assessed ultrasonic vocalizations at postnatal day 7 (P7), spontaneous repetitive behaviors at P25-P30, and sociability at P27-P32. Developmental PCB exposure reduced ultrasonic vocalizations in WT litters in all dose groups, but had no effect on ultrasonic vocalizations in transgenic litters. Developmental PCB exposure significantly increased self-grooming and decreased sociability in WT males in the 0.1 mg/kg dose group, but had no effect on WT females in any dose group. Genotype alone influenced ultrasonic vocalizations, self-grooming and to a lesser extent sociability. Genotype alone also influenced effects of PCBs on sociability. PCB levels in the brain tissue of pups increased in a dose-dependent manner, but within any dose group did not differ between genotypes. In summary, developmental PCB exposure phenocopied social behavior phenotypes observed in mice expressing human mutations that modify intracellular Ca2+ dynamics, and expression of these mutations alleviated PCB effects on ultrasonic vocalizations and repetitive behavior, and modified the dose-response relationships and sex-dependent effects of PCB effects on social behavior. These findings suggest that: (1) developmental PCB exposure causes behavioral phenotypes that vary by sex and genotype; and (2) sex-specific responses to environmental factors may contribute to sex biases in the prevalence and/or severity of neurodevelopmental disorders.
Altered Static and Dynamic Interhemispheric Resting-State Functional Connectivity in Patients With Thyroid-Associated Ophthalmopathy
Authors: Chen Wen , Hu Hao , Wu Qian , Chen Lu , Zhou Jiang , Chen Huan-Huan , Xu Xiao-Quan , Wu Fei-Yun
Published: December 2021

Purpose: Thyroid-associated ophthalmopathy (TAO) is a debilitating and sight-threatening autoimmune disease that severely impairs patients’ quality of life. Besides the most common ophthalmic manifestations, the emotional and psychiatric disturbances are also usually observed in clinical settings. This study was to investigate the interhemispheric functional connectivity alterations in TAO patients using resting-state functional magnetic resonance imaging (rs-fMRI).

Methods: Twenty-eight TAO patients and 22 healthy controls (HCs) underwent rs-fMRI scans. Static and dynamic voxel-mirrored homotopic connectivity (VMHC) values were calculated and compared between the two groups. A linear support vector machine (SVM) classifier was used to examine the performance of static and dynamic VMHC differences in distinguishing TAOs from HCs.

Results: Compared with HCs, TAOs showed decreased static VMHC in lingual gyrus (LG)/calcarine (CAL), middle occipital gyrus, postcentral gyrus, superior parietal lobule, inferior parietal lobule, and precuneus. Meanwhile, TAOs demonstrated increased dynamic VMHC in orbitofrontal cortex (OFC). In TAOs, static VMHC in LG/CAL was positively correlated with visual acuity (r = 0.412, P = 0.036), whilst dynamic VMHC in OFC was positively correlated with Hamilton Anxiety Rating Scale (HARS) score (r = 0.397, P = 0.044) and Hamilton Depression Rating Scale (HDRS) score (r = 0.401, P = 0.042). The SVM model showed good performance in distinguishing TAOs from HCs (area under the curve, 0.971; average accuracy, 94%).

Conclusion: TAO patients had altered static and dynamic VMHC in the occipital, parietal, and orbitofrontal areas, which could serve as neuroimaging prediction markers of TAO.
The High Level of Xylooligosaccharides Improves Growth Performance in Weaned Piglets by Increasing Antioxidant Activity, Enhancing Immune Function, and Modulating Gut Microbiota
Authors: Pang Jiaman , Zhou Xingjian , Ye Hao , Wu Yujun , Wang Zhenyu , Lu Dongdong , Wang Junjun , Han Dandan
Published: December 2021

The aim of this study was to investigate the effects of the high level of xylooligosaccharides (XOS) on growth performance, antioxidant capability, immune function, and fecal microbiota in weaning piglets. The results showed that 28 d body weight exhibited linear and quadratic increases (P < 0.05) with increasing dietary XOS level, as well as average daily feed intake (ADFI) on d 15–28, average daily gain (ADG) on d 15–28 and 1–28. There was a linear decrease (P < 0.05) between XOS levels and feed conversion rate (FCR) on d 1–14 and 1–28. Additionally, glutathione peroxidase (GSH-Px) showed a linear increase (P < 0.05), while the malondialdehyde (MDA) level decreased linearly and quadratically (P < 0.05) with the increasing dietary level of XOS. Moreover, the XOS treatments markedly increased the levels of immunoglobulin A (Ig A) (linear, P < 0.05; quadratic, P < 0.05), IgM (quadratic, P < 0.05), IgG (linear, P < 0.05), and anti-inflammatory cytokine interleukin-10 (IL-10) (quadratic, P < 0.05) in serum, while the IL-1β (linear, P < 0.05; quadratic, P < 0.05) and IL-6 (linear, P < 0.05) decreased with increasing level of XOS. Microbiota analysis showed that dietary supplementation with 1.5% XOS decreased (P < 0.05) the α-diversity and enriched (P < 0.05) beneficial bacteria including Lactobacillus, Bifidobacterium, and Fusicatenibacter at the genus level, compared with the control group. Importantly, linearly increasing responses (P < 0.05) to fecal acetate, propionate, butyrate, and total short-chain fatty acids (SCFAs) were observed with increasing level of XOS. Spearman correlation analyses found that Lactobacillus abundance was positively correlated with ADG, acetate, propionate, and IgA (P < 0.05), but negatively correlated with IL-1β (P < 0.05). Bifidobacterium abundance was positively related with ADFI, total SCFAs, IgG, and IL-10 (P < 0.05), as well as g_Fusicatenibacter abundance with ADFI, total SCFAs, and IL-10. However, Bifidobacterium and Fusicatenibacter abundances were negatively associated with MDA levels (P < 0.05). In summary, dietary supplementation with XOS can improve the growth performance in weaning piglets by increasing antioxidant capability, enhancing immune function, and promoting beneficial bacteria counts.
Recent Insights Into Processing Approaches and Potential Health Benefits of Goat Milk and Its Products: A Review
Authors: Nayik Gulzar Ahmad , Jagdale Yash D. , Gaikwad Sailee A. , Devkatte Anupama N. , Dar Aamir Hussain , Dezmirean Daniel Severus , Bobis Otilia , Ranjha Muhammad Modassar A. N. , Ansari Mohammad Javed , Hemeg Hassan A. , Alotaibi Saqer S.
Published: December 2021

Goat milk is considered to be a potential source of various macro- and micro-nutrients. It contains a good proportion of protein, fat, carbohydrates, and other nutritional components which help in promoting nutritional and desirable health benefits. Goat milk is considered to be superior in terms of numerous health benefits, and lower risk of allergy, when compared to the milk of other species. Several processing techniques such as pasteurization, ultrafiltration, microfiltration, and ultrasound have been employed to enhance the quality and shelf life of goat milk and its products. The diverse range of goat milk-based products such as yogurt, cheese, fermented milk, goat milk powder, and others are available in the market and are prepared by the intervention of advanced processing technologies. Goats raised in pasture-based feeding systems are shown to have a better milk nutritional composition than its counterpart. Goat milk contains potential bioactive components, which aids in the maintenance of the proper metabolism and functioning of the human body. This review gives insight into the key nutritional ingredients and bioactive constituents present in goat milk and their potential role in the development of various functional foods using different processing technologies. Goat milk could be considered as a significant option for milk consumption in infants, as compared to other milk available.
Case Report: Long-Term Response to Radiotherapy Combined With Targeted Therapy in Histiocytic Sarcoma Harboring Mutations in MAPK and PI3K/AKT Pathways
Authors: Liu Zijian , Xiao Yin , Liu Xinxiu , Li Qiuhui , Liu Tao , Zhu Fang , Wu Gang , Zhang Liling
Published: December 2021

Background

Histiocytic sarcoma (HS) is a rare hematopoietic malignancy with an aggressive clinical presentation associated with a poor overall survival. To date, surgical resection, radiation therapy, and chemotherapy were often utilized for HS, but curative effects are rather disappointing.

Case Presentation

A 19-year-old female was referred to our hospital with a pathologic diagnosis of HS in December 2017. The patient had a severe airway obstruction resulting from a large mass (6.0 cm × 4.4 cm) arising from the left parapharyngeal space. She did not respond to cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOEP) chemotherapy, then she was switched to radiotherapy and crizotinib according to next-generation sequencing (NGS) results (mutations in MET and MAP2K1). The patient got a partial response after radiotherapy and crizotinib, then she switched to imatinib combined with thalidomide treatment. The patient got a long-term complete response from the treatment and is alive 44 months after initial diagnosis without disease progression. Further KEGG pathway enrichment analysis of NGS results from patient’s tissue revealed that phosphatidylinositol 3′ kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) pathways were activated in this HS patient. We further performed experiments in vitro in a canine histiocytic sarcoma cell line DH82, in order to explore the possible mechanism of imatinib plus thalidomide in HS. Results of cell counting kit-8 (CCK8) assays showed that the proliferation activity of DH82 was significantly inhibited by imatinib but not thalidomide. Combined thalidomide and imatinib treatment did not improve the inhibitory effects of imatinib to DH82. Results of Western blot confirmed the inhibitory effects of imatinib on DH82 by targeting activation of MAPK and PI3K/AKT pathways.

Conclusion

Radiotherapy combined with targeted therapy guided by NGS may be promising, and further perspective clinical trial is warranted for the localized HS.
Efficacy and Safety of Immune Checkpoint Blockades in the Treatment of Ocular Melanoma: A Systematic Review and Meta-Analysis
Authors: Zhao Lu , Xia Wenwen , Zhang Yan , Zou Peng , Zhu Qiwen , Zhang Rong
Published: December 2021

Aim

This meta-analysis aimed to compare the efficacy and safety of immune checkpoint blockade for the treatment of ocular melanoma.

Methods

We searched the PubMed, EMBASE, and Cochrane Library databases up to July 2021. Effect sizes (ESs) and corresponding 95% confidence intervals (CIs) were used to compare the outcomes. Efficacy outcomes included complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR), overall survival (OS), progression free survival (PFS). Safety outcomes included adverse events (AEs) and serious adverse event (SAEs).

Results

A total of 16 eligible articles with 848 ocular melanoma patients were included. ICB treatment significantly improved CR (ES=0.02, 95%CI: 0.00-0.03, P=0.023), PR (ES=0.07, 95%CI: 0.05-0.09, P=0.000), SD (ES=0.31, 95%CI: 0.17-0.46, P=0.000), PD (ES=0.69, 95%CI: 0.61-0.77, P=0.000), ORR (ES=0.10, 95%CI: 0.04-0.15, P=0.000), OS (ES=9.68, 95%CI: 7.28-12.07, P=0.000) and PFS (ES=2.88, 95%CI: 2.69-3.07, P=0.000) in patients with ocular melanoma. Moreover, ICB therapies were associated with reduced AEs (ES=0.48, 95%CI: 0.30-0.67, P=0.000) and SAEs (ES=0.31, 95%CI: 0.18-0.45, P=0.000).

Conclusions

ICB therapy showed good efficacy and safety in treating patients with ocular melanoma.
Venetoclax Shows Low Therapeutic Activity in BCL2-Positive Relapsed/Refractory Peripheral T-Cell Lymphoma: A Phase 2 Study of the Fondazione Italiana Linfomi
Authors: Ballotta Laura , Zinzani Pier Luigi , Pileri Stefano , Bruna Riccardo , Tani Monica , Casadei Beatrice , Tabanelli Valentina , Volpetti Stefano , Luminari Stefano , Corradini Paolo , Lucchini Elisa , Tisi Maria Chiara , Merli Michele , Re Alessandro , Varettoni Marzia , Pesce Emanuela Anna , Zaja Francesco
Published: December 2021

Patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) have a poor prognosis, with an expected survival of less than 1 year using standard salvage therapies. Recent advances in our understanding of the biology of PTCL have led to identifying B-Cell Lymphoma 2 (BCL2) protein as a potential therapeutic target. BLC2 inhibitor venetoclax was investigated in a prospective phase II trial in patients with BCL2-positive R/R PTCL after at least one previous standard line of treatment (NCT03552692). Venetoclax given alone at a dosage of 800 mg/day resulted in one complete response (CR) and two stable diseases (SDs) among 17 enrolled patients. The majority of patients (88.2%) interrupted the treatment due to disease progression. No relationship with BCL2 expression was documented. At a median follow-up of 8 months, two patients are currently still on treatment (one CR and one SD). No case of tumor lysis syndrome was registered. Therefore, venetoclax monotherapy shows activity in a minority of patients whose biological characteristics have not yet been identified.

Clinical Trial Registration

www.clinicaltrials.gov (NCT03552692, EudraCT number 2017-004630-29).
Roles of Lung Ultrasound Score in the Extubation Failure From Mechanical Ventilation Among Premature Infants With Neonatal Respiratory Distress Syndrome
Authors: Liang Zhenyu , Meng Qiong , You Chuming , Wu Bijun , Li Xia , Wu Qianmei
Published: December 2021

Objective: To investigate the predictive value of lung ultrasound score (LUS) in the extubation failure from mechanical ventilation (MV) among premature infants with neonatal respiratory distress syndrome (RDS).

Methods: The retrospective cohort study was conducted with a total of 314 RDS newborns who received MV support for over 24 h. After extubation from MV, infants were divided into extubation success and extubation failure groups. Extubation failure was defined as re-intubation within 48 h after extubation. Univariate and multivariate logistic regression analyses were used to identify the predictors of the extubation failure. The predictive effectiveness of the combined model and LUS in the extubation failure was assessed by receiver operating characteristic curve, area under curve (AUC), and internal validation.

Results: 106 infants failed extubation from MV. The combined model for predicting the extubation failure was performed according to the predictors of gestational age, body length, birth weight, and LUS. The AUC of this combined model was 0.871 (sensitivity: 86.67%, specificity: 74.31%). The AUC of LUS was 0.858 (sensitivity: 84.00%, specificity: 80.69%), and the cutoff value was 18. There was no statistical difference in the predictive power between the combined model and LUS (Z = 0.880, P = 0.379). The internal validation result showed that the AUC of LUS was 0.855.

Conclusions: LUS presented a good ability in predicting the extubation failure among RDS newborns after MV.
The Association of Maternal Emotional Status With Child Over-Use of Electronic Devices During the COVID-19 Pandemic
Authors: Guo Xiangrong , Zhou Yulai , Xu Jian , Hu Yuelai , Liu Zhiwei
Published: December 2021

The quarantine during the COVID-19 pandemic may generate high levels of maternal depression/anxiety, and maternal emotional status may affect child behavioral development. Online education during the pandemic may induce child over-use of electronic-devices. However, child electronic-device over-use (especially among children under 12 who are immature in physical and mental development) during the pandemic has not attracted sufficient attention, and the association of child over-use with maternal emotional status remains unknown. Therefore, this study aims to assess the characteristics of child electronic-device over-use and the association between maternal emotional status and child over-use among 1,300 children from nurseries (<3 years), kindergartens (3–6 years), and primary schools (6–12 years) in Shanghai and Wuhan during COVID-19. Mothers completed an online questionnaire (including the Self-Rating-Depression/Anxiety-Scales and Family-Environment-Scale). The use of electronic devices (mobile-phones, iPads, computers, and televisions) and online courses taken by the children were investigated. Associations of maternal emotional status with electronic-device-use by child age were analyzed. The proportions of children in nurseries, kindergartens and primary schools were 8.5, 44.5, and 47.0%, their percentages following online-courses were 24.5, 48.4, and 99.0%, and their rates of electronic-device over-use were 34.2, 62.2, and 93.4%, respectively. Significant associations were observed between higher maternal anxiety/depression levels and higher risks of mobile-phone/iPad over-use among preschoolers and primary-school students. Lower family intimacy and higher conflict levels were associated with higher maternal depression/anxiety levels and higher risks of electronic-device over-use. Our findings suggested that over-use of electronic-devices among children under 12 was common during COVID-19, especially among children ≥6 years, and online-teaching may exacerbate over-use. Maternal anxiety/depression levels were associated with over-use of portable internet-devices (mobile-phone/iPad), especially among preschoolers and school-aged students, and family environment may mediate the association. These findings may contribute to a better understanding of factors leading to over-use of electronic-device and developing strategies to decrease over-use during COVID-19.
Resting Energy Expenditure Prediction Equations in the Pediatric Population: A Systematic Review
Authors: Fuentes-Servín Jimena , Avila-Nava Azalia , González-Salazar Luis E. , Pérez-González Oscar A. , Servín-Rodas María Del Carmen , Serralde-Zuñiga Aurora E. , Medina-Vera Isabel , Guevara-Cruz Martha
Published: December 2021

Background and Aims: The determination of energy requirements is necessary to promote adequate growth and nutritional status in pediatric populations. Currently, several predictive equations have been designed and modified to estimate energy expenditure at rest. Our objectives were (1) to identify the equations designed for energy expenditure prediction and (2) to identify the anthropometric and demographic variables used in the design of the equations for pediatric patients who are healthy and have illness.

Methods: A systematic search in the Medline/PubMed, EMBASE and LILACS databases for observational studies published up to January 2021 that reported the design of predictive equations to estimate basal or resting energy expenditure in pediatric populations was carried out. Studies were excluded if the study population included athletes, adult patients, or any patients taking medications that altered energy expenditure. Risk of bias was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.

Results: Of the 769 studies identified in the search, 39 met the inclusion criteria and were analyzed. Predictive equations were established for three pediatric populations: those who were healthy (n = 8), those who had overweight or obesity (n = 17), and those with a specific clinical situation (n = 14). In the healthy pediatric population, the FAO/WHO and Schofield equations had the highest R2 values, while in the population with obesity, the Molnár and Dietz equations had the highest R2 values for both boys and girls.

Conclusions: Many different predictive equations for energy expenditure in pediatric patients have been published. This review is a compendium of most of these equations; this information will enable clinicians to critically evaluate their use in clinical practice.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=226270, PROSPERO [CRD42021226270].
Evaluations and Mechanistic Interrogation of Natural Products Isolated From Paeonia suffruticosa for the Treatment of Inflammatory Bowel Disease
Authors: Wu Kun-Chang , Lee Der-Yen , Hsu Jeh-Ting , Cheng Chi-Fang , Lan Joung-Liang , Chiu Shao-Chih , Cho Der-Yang , Hsu Jye-Lin
Published: December 2021

Mu Dan Pi (MDP), a traditional Chinese medicine derived from the root bark of Paeonia suffruticosa Andrews, is used to treat autoimmune diseases due to its anti-inflammatory properties. However, the impact of MDP on inflammatory bowel disease (IBD) and its principal active compounds that contribute to the anti-inflammatory properties are uncertain. Thus, this study systemically evaluated the anti-inflammatory effects of fractionated MDP, which has therapeutic potential for IBD. MDP fractions were prepared by multistep fractionation, among which the ethyl acetate-fraction MDP5 exhibited the highest potency, with anti-inflammatory activity screened by the Toll-like receptor (TLR)-2 agonist, Pam3CSK4, in a cell-based model. MDP5 (at 50 μg/ml, p < 0.001) significantly inhibited nuclear factor kappa-B (NF-κB) reporters triggered by Pam3CSK4, without significant cell toxicity. Moreover, MDP5 (at 10 μg/ml) alleviated proinflammatory signaling triggered by Pam3CSK4 in a dose-dependent manner and reduced downstream IL-6 and TNF-α production (p < 0.001) in primary macrophages. MDP5 also mitigated weight loss, clinical inflammation, colonic infiltration of immune cells and cytokine production in a murine colitis model. Index compounds including paeoniflorin derivatives (ranging from 0.1 to 3.4%), gallic acid (1.8%), and 1,2,3,4,6-penta-O-galloyl-β-D-glucose (1.1%) in MDP5 fractions were identified by LC-MS/MS and could be used as anti-inflammatory markers for MDP preparation. Collectively, these data suggest that MDP5 is a promising treatment for IBD patients.
Effects of Donepezil and Medroxyprogesterone Versus Placebo on Weaning in Adult Patients With Non-Pulmonary Etiologies Receiving Invasive Mechanical Ventilation: A triple‐blind Randomized Clinical Trial
Authors: Alizadeh Zahra , Sahebnasagh Adeleh , Hadadzadegan Navid , Mohammadi Farhad , Saghafi Fatemeh
Published: December 2021

Background: Medroxyprogesterone and donepezil could be used as respiratory stimulants in ventilated patients. However, no randomized placebo-controlled trial is available to confirm this approach and compare these drugs. The aim of the current study was to evaluate the effects of donepezil or medroxyprogesterone compared to the placebo in improvement in respiratory status and weaning facilitation in critically ill adult patients receiving mechanical ventilation.

Material and Methods: This randomized, triple-blind trial was conducted on 78 ventilated patients in intensive care units (ICU). Patients who were intubated due to pulmonary disorders were ruled out. Patients were randomized in a 1:1:1 ratio to receive 5 mg donepezil (n = 23) or 5 mg medroxyprogesterone (n = 26), or placebo (n = 24) twice a day until weaning (maximum 10 days). The primary endpoints were weaning duration, and duration of invasive mechanical ventilation. Secondary endpoints included rate of successful weaning, changes in arterial blood gas (ABG) parameters, GCS and sequential organ failure assessment (SOFA) score, hemoglobin (Hgb), ICU-mortality, and duration of ICU stay, were measured before and after the intervention and if successful weaning was recorded.

Results: Of 78 studied patients who were randomized, 59 weaned successfully. 87% patients in donepezil and 88.5% patients in medroxyprogesterone groups were successfully weaned compared to 66.7% patients in the placebo group. However, this difference was not statistically significant (p-Value = 0.111). Changes in pH, mean duration of intubation, and weaning duration were statistically different in donepezil compared with the control group (p-Value < 0.05). No significant difference in ABG, Hgb, GCS and SOFA score, and duration of intubation were seen in the medroxyprogesterone group, but weaning duration was significantly reduced to 1.429 days compared with the control group (p-Value = 0.038).

Conclusion: The results of this clinical trial have demonstrated that the administered dose of medroxyprogesterone and donepezil can expedite the weaning process by reducing the weaning duration compared to placebo. Furthermore, the total duration of invasive ventilation was significantly lower in the donepezil group compared to the control group. Future clinical trials with a larger sample size will determine the exact role of medroxyprogesterone and donepezil in mechanically ventilated patients.

Clinical Trial Registration:https://irct.ir/IRCT20190810044500N2 (April 1, 2020).
The Extracellular Matrix Enriched With Exosomes for the Treatment on Pulmonary Fibrosis in Mice
Authors: Yu Yanzhen , Liu Xingzhi , Zhao Zhe , Xu Zhongjuan , Qiao Yong , Zhou Yuanshuai , Qiao Hong , Zhong Junjie , Dai Jianwu , Suo Guangli
Published: December 2021

Pulmonary fibrosis (PF) is a severe respiratory disease caused by lung microenvironment changes. TGF-β/Smad3 signaling pathway plays a critical role in the fibrotic process. MicroRNA-29 (miR-29) has proved to alleviate the occurrence of PF by downregulating TGF-β/Smad3 signaling pathway. The miRNA application encounters obstacles due to its low stability in body and no targeting to lesions. Exosomes can be used for therapeutic delivery of miRNA due to their favorable delivery properties. However, low efficiency of separation and production impedes the therapeutic application of exosomes. In this study, we developed a liquid natural extracellular matrix (ECM) enriched with miR-29-loaded exosomes for PF treatment. The collagen-binding domain (CBD)-fused Lamp2b (CBD-Lamp2b) and miR-29 were overexpressed in human foreskin fibroblast (HFF) host cells for the entrapment of miR-29-loaded exosomes in ECM of the cells. The repeated freeze-thaw method was performed to prepare the liquid ECM enriched with exosomes without destroying the exosomal membrane. In summary, this study developed a novel functional ECM biomaterial for therapy of PF, and also provided a promising gene therapy platform for different diseases by treatment with liquid ECM that is, enriched with exosomes loaded with different functional miRNAs.
Platinum and Taxane Based Adjuvant and Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer: A Narrative Review
Authors: Tian Hao , Ma Dandan , Tan Xuanni , Yan Wenting , Wu Xiujuan , He Cheng , Zhong Ling , Zhang Yan , Yu Bingjie , Zhang Yi , Qi Xiaowei
Published: December 2021

Platinum (Pt) derivatives such as cisplatin and carboplatin are the class of drugs with proven activity against triple-negative breast cancer (TNBC). This is due to the ability of Pt compounds to interfere with the DNA repair mechanisms of the neoplastic cells. Taxanes have been efficacious against estrogen receptor-negative tumors and act by disruption of microtubule function. Due to their distinct mechanisms of action and routes of metabolism, the combination of the Pt agents and taxanes results in reduced systemic toxicity, which is ideal for treating TNBC. Also, the sensitivity ofBRCA1-mutated cells to taxanes remains unsolved asin vitroevidence indicates resistance against taxanes due toBRCA1mutations. Recent evidence suggests that the combination of carboplatin and paclitaxel resulted in better pathological complete response (pCR) in patients with TNBC, both in neoadjuvant and adjuvant settings.In vitrostudies showed sequential dependency and optimal time scheduling of Pt- and taxane-based chemotherapy. Also, combining carboplatin with docetaxel in the NAC regimen yields an excellent pCR in patients withBRCA-associated and wild-type TNBC. TNBC is a therapeutic challenge that can be tackled by identifying new therapeutic sub-targets and specific cross-sections that can be benefitted from the addition of Pt- and taxane-based chemotherapy. This review summarizes the merits as well as the mechanism of Pt- and taxane-based adjuvant and neoadjuvant chemotherapies in early TNBC from the available and ongoing clinical studies.
Protective Effects and Mechanisms of Polyethylene Glycol Loxenatide Against Hyperglycemia and Liver Injury in db/db diabetic Mice
Authors: Zhang Yu , Li Yufeng , Zhao Junjun , Wang Cong , Deng Bin , Zhang Qilin , Shi Chen
Published: December 2021

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disorder with insulin resistance and impaired insulin secretion that can cause complications, including liver injury. Polyethylene glycol loxenatide (PEG-Loxe), a glucagon-like peptide-1 (GLP-1) analog, is widely used to treat T2DM. However, its specific glucose-lowering and hepatoprotective mechanisms of action have not been established yet.

METHODS: Using a high glucose-induced hepatocyte injury model and a type 2 diabetic db/db mouse model, we assessed PEG-Loxe’s impact on reducing blood glucose and improving liver injury in T2DM and revealed its mechanism.

RESULTS: PEG-Loxe treatment significantly reduced body weight and fasting glucose, increased glucose tolerance, improved serum and liver biochemical parameters (glycated hemoglobin, serum insulin, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate aminotransferase), and attenuated hepatic steatosis and liver and pancreatic tissue damages in db/db mice. Additionally, PEG-Loxe considerably inhibited oxidative stress, decreased pro-inflammatory factor (TNF-α, IL-6, and MCP-1) levels, and increased anti-inflammatory factor IL-10 levels. PEG-Loxe possibly inhibits hepatic lipid synthesis, oxidative stress, and inflammatory response by upregulating Sirt1, p-AMPK, and p-ACC expressions in the Sirt1/AMPK/ACC pathway of lipid metabolism, thereby improving T2DM liver injury. PEG-Loxe most likely also promotes GLP-1R expression by inhibiting β-cell apoptosis, which in turn activates the insulin PI3K/AKT pathway to promote insulin synthesis and secretion, thereby exerting hypoglycemic effects. In vitro cellular experiments further confirmed that PEG-Loxe possibly exerts hypoglycemic effects by activating the insulin PI3K/AKT pathway.

Conclusion: PEG-Loxe improved liver injury in T2DM probably by activating Sirt1/AMPK/ACC lipid metabolism pathway, and exerted hypoglycemic effects through activation of insulin PI3K/AKT pathway.