bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuous theta burst stimulation for drug-resistant epilepsy
Authors: Carrette Sofie , Boon Paul , Klooster Debby , Van Dycke Annelies , Carrette Evelien , Miatton Marijke , Raedt Robrecht , Delbeke Jean , Meurs Alfred , Vonck Kristl
Published: August 2022

Introduction

Repetitive transcranial magnetic stimulation (rTMS) may have anti-epileptic effects, especially in patients with neocortical lesions. Initial clinical trials demonstrated that the duration of the seizure reducing effect is relatively short-lived. In the context of a chronic condition like epilepsy, theta burst stimulation (TBS) may represent a potential solution in optimizing treatment practicality and durability as it was demonstrated to be associated with longer-lasting after-effects. TBS has been studied extensively in diverse neuropsychiatric conditions, but a therapeutic TBS protocol has not previously been applied in epilepsy patients.

Materials and methods

We performed a prospective open-label pilot study of 4-day accelerated continuous TBS (cTBS) treatment in patients with neocortical drug-resistant epilepsy (DRE). A treatment session consisted of 5 cTBS trains, each comprising 600 pulses presented in 50 Hz triplet bursts every 200 ms, delivered at 10-min intertrain-intervals, targeted over the epileptic focus (EF) using a neuronavigation-guided figure-of-8 coil. Safety and feasibility, and seizure frequency were assessed as primary and secondary endpoints, respectively, over a 4-week baseline period, a 1-week treatment period and a 7-week follow-up period, using adverse event logging, electro-encephalography, cognitive, and psychological questionnaires and a seizure diary kept by the patients and/or caregivers.

Results

Seven subjects (4M:3F; median age 48, interquartile ranges 25) underwent the treatment protocol. Adverse events were reported in all subjects but were mild and transient. No clinical or electrographic seizures were evoked during or immediately following stimulation. No deterioration was found in cognition nor in psycho-emotional well-being following treatment. Treatment burden was acceptable, but seems to depend on clinical effect, duration of ongoing effect and stimulation site. Median weekly seizure frequency and ratio of seizure-free weeks did not change significantly in this small patient cohort.

Conclusion

We report the results of the first ever trial of cTBS as a treatment for neocortical DRE. A 4-day accelerated cTBS protocol over the EF appears safe and feasible. Although the design and sample size of this open-label pilot study is unfit to reliably identify a therapeutic effect, results encourage further exploration of cTBS as an anti-epileptic treatment and potential optimization compared to conventional rTMS in a dedicated randomized controlled trial. (clinicaltrials.gov: NCT02635633).
Measuring the effects of mind wandering in people with insomnia: A driving simulator study
Authors: Xu Lin , Yan Yingying , Dong Hongming , Qiao Dandan , Liu Yanyan , Tian Junfang , Ai Zhu , Xue Rong
Published: August 2022

Purpose

Studies have shown that individuals with insomnia experience more frequent and longer episodes of mind wandering (MW) while driving. However, the effect of the interaction between insomnia and MW on driving behavior is not fully understood. This study aimed to gain deeper insights into the relationships among insomnia, MW, and driving behavior.

Patients and methods

Forty-two participants (21 diagnosed with insomnia and 21 controls) were recruited, and subjective sleep quality and cognitive function were assessed. A driving simulator experiment with a within-subject design was performed, involving two distraction tasks (no-distraction task versus MW task) and two driving scenarios (lane-keeping versus lane-changing).

Results

In the lane-keeping scenario, there was no significant between-group difference (people with insomnia and controls) in longitudinal driving performance for the no-distraction task, although the interaction between MW and insomnia significantly increased drivers’ longitudinal control variation. Correlation analysis confirmed that longitudinal driving performance was positively correlated with sleep quality and the cognitive level. Unlike longitudinal driving performance, lateral driving performance was significantly weaker in people with insomnia than in controls under both distraction tasks. In the lane-changing scenario, although there was no between-group difference in driving performance, the MW task led to significant changes in driving performance within each group compared with the no-distraction task, and these findings were associated with cognitive function, but not with sleep quality.

Conclusion

These findings show that insomnia and MW combined can lead to reduced driving performance. Further research is needed to elucidate the factors that influence this phenomenon.
Focal non-invasive deep-brain stimulation with temporal interference for the suppression of epileptic biomarkers
Authors: Acerbo Emma , Jegou Aude , Luff Charlotte , Dzialecka Patrycja , Botzanowski Boris , Missey Florian , Ngom Ibrahima , Lagarde Stanislas , Bartolomei Fabrice , Cassara Antonino , Neufeld Esra , Jirsa Viktor , Carron Romain , Grossman Nir , Williamson Adam
Published: August 2022

Introduction

Neurostimulation applied from deep brain stimulation (DBS) electrodes is an effective therapeutic intervention in patients suffering from intractable drug-resistant epilepsy when resective surgery is contraindicated or failed. Inhibitory DBS to suppress seizures and associated epileptogenic biomarkers could be performed with high-frequency stimulation (HFS), typically between 100 and 165 Hz, to various deep-seated targets, such as the Mesio-temporal lobe (MTL), which leads to changes in brain rhythms, specifically in the hippocampus. The most prominent alterations concern high-frequency oscillations (HFOs), namely an increase in ripples, a reduction in pathological Fast Ripples (FRs), and a decrease in pathological interictal epileptiform discharges (IEDs).

Materials and methods

In the current study, we use Temporal Interference (TI) stimulation to provide a non-invasive DBS (130 Hz) of the MTL, specifically the hippocampus, in both mouse models of epilepsy, and scale the method using human cadavers to demonstrate the potential efficacy in human patients. Simulations for both mice and human heads were performed to calculate the best coordinates to reach the hippocampus.

Results

This non-invasive DBS increases physiological ripples, and decreases the number of FRs and IEDs in a mouse model of epilepsy. Similarly, we show the inability of 130 Hz transcranial current stimulation (TCS) to achieve similar results. We therefore further demonstrate the translatability to human subjects via measurements of the TI stimulation vs. TCS in human cadavers. Results show a better penetration of TI fields into the human hippocampus as compared with TCS.

Significance

These results constitute the first proof of the feasibility and efficiency of TI to stimulate at depth an area without impacting the surrounding tissue. The data tend to show the sufficiently focal character of the induced effects and suggest promising therapeutic applications in epilepsy.
Gut microbiota and host genetics modulate the effect of diverse diet patterns on metabolic health
Authors: Huda M. Nazmul , Salvador Anna C. , Barrington William T. , Gacasan C. Anthony , D'Souza Edeline M. , Deus Ramirez Laura , Threadgill David W. , Bennett Brian J.
Published: August 2022

Metabolic diseases are major public health issues worldwide and are responsible for disproportionately higher healthcare costs and increased complications of many diseases including SARS-CoV-2 infection. The Western Diet (WD) specifically is believed to be a major contributor to the global metabolic disease epidemic. In contrast, the Mediterranean diet (MeD), Ketogenic diet (KD), and Japanese diet (JD) are often considered beneficial for metabolic health. Yet, there is a growing appreciation that the effect of diet on metabolic health varies depending on several factors including host genetics. Additionally, poor metabolic health has also been attributed to altered gut microbial composition and/or function. To understand the complex relationship between host genetics, gut microbiota, and dietary patterns, we treated four widely used metabolically diverse inbred mouse strains (A/J, C57BL/6J, FVB/NJ, and NOD/ShiLtJ) with four human-relevant diets (MeD, JD, KD, WD), and a control mouse chow from 6 weeks to 30 weeks of age. We found that diet-induced alteration of gut microbiota (α-diversity, β-diversity, and abundance of several bacteria including Bifidobacterium, Ruminococcus, Turicibacter, Faecalibaculum, and Akkermansia) is significantly modified by host genetics. In addition, depending on the gut microbiota, the same diet could have different metabolic health effects. Our study also revealed that C57BL/6J mice are more susceptible to altered gut microbiota compared to other strains in this study indicating that host genetics is an important modulator of the diet-microbiota-metabolic health axis. Overall, our study demonstrated complex interactions between host genetics, gut microbiota, and diet on metabolic health; indicating the need to consider both host genetics and the gut microbiota in the development of new and more effective precision nutrition strategies to improve metabolic health.
Liver function parameters aspartate aminotransferase and total protein predict functional outcome in stroke patients with non-cardioembolism
Authors: Xie Jiali , Zhu Yinmeng , Pang Chunyang , Gao Lingfei , Yu Huan , Lv Wenjing , Zhang Wanli , Deng Binbin
Published: August 2022

Stroke, classified as cardioembolism and non-cardioembolism (non-CE), entails a large socioeconomic burden on the elderly. The morbidity and mortality of non-CE are high, whereas studies concerning prognostic factors impacting function outcome remain underdeveloped and understudied. Liver function parameters are convenient approaches to predicting prognosis in cardiovascular diseases, but their clinical significance has not been well characterized in stroke, especially in non-CE. In our study, a total of 576 patients with non-CE at 1 year of follow-up were enrolled in a cohort from a consecutive hospital-based stroke registry, with randomly 387 patients as the development cohort and 189 patients as the validation cohort. The univariate and multivariate analyses revealed the following novel findings: (i) The incidence of unfavorable functional outcomes after non-CE was significantly greater (p < 0.01) in patients with higher age, aspartate aminotransferase (AST), the National Institutes of Health Stroke Scale (NIHSS) score, and depressed total protein (TP); (ii) We established a novel model and nomogram to predict stroke prognosis, in addition to the known factors (age and the NIHSS score). The levels of AST and TP were independently correlated with the incidence of unfavorable outcomes [AST: odds ratio (OR) = 1.026, 95% CI (1.002–1.050); TP: OR = 0.944, 95% CI (0.899–0.991)]; (iii) The results persisted in further subgroup analysis stratified by age, gender, the NIHSS score, and other prespecified factors, especially in males 60 years or older. Overall, this study demonstrates that hepatic parameters (AST and TP) after non-CE are considered to be associated with functional outcomes at 1-year follow-up, especially in males aged ≥ 60 years.
Selinexor inhibits growth of patient derived chordomas in vivo as a single agent and in combination with abemaciclib through diverse mechanisms
Authors: Walker Christopher J. , Chang Hua , Henegar Leah , Kashyap Trinayan , Shacham Sharon , Sommer Josh , Wick Michael J. , Levy Joan , Landesman Yosef
Published: August 2022

Chordoma is a rare cancer that grows in the base of the skull and along the mobile spine from remnants of embryonic notochord tissue. The cornerstone of current treatments is surgical excision with adjuvant radiation therapy, although complete surgical removal is not always possible. Chordomas have high rates of metastasis and recurrence, with no approved targeted agents. Selinexor and eltanexor are selective inhibitors of nuclear export (SINE) that prevent the karyopherin protein exportin-1 (XPO1) from shuttling its cargo proteins through nuclear pore complexes out of the nucleus and into the cytoplasm. As cancer cells overexpress XPO1, and many of its cargos include tumor suppressor proteins and complexes bound to oncogene mRNAs, XPO1 inhibition can suppress oncogene translation and restore tumor suppressor protein activity in different cancer types. SINE compounds have exhibited anti-cancer activity in a wide range of hematological and solid tumor malignancies. Here we demonstrate the preclinical effectiveness of SINE compounds used as single agents or in combination with either the proteasome inhibitor, bortezomib, or the CDK4/6 inhibitor, abemaciclib, against various patient- derived xenograft (PDX) mouse models of chordoma, which included clival and sacral chordomas from adult or pediatric patients with either primary or metastatic disease, with either differentiated or poorly differentiated subtypes. SINE treatment significantly impaired tumor growth in all five tested chordoma models, with the selinexor and abemaciclib combination showing the strongest activity (tumor growth inhibition of 78-92%). Immunohistochemistry analysis of excised tumors revealed that selinexor treatment resulted in marked induction of apoptosis and reduced cell proliferation, as well as nuclear accumulation of SMAD4, and reduction of Brachyury and YAP1. RNA sequencing showed selinexor treatment resulted in differences in activated and repressed signaling pathways between the PDX models, including changes in WNT signaling, E2F pathways and glucocorticoid receptor signaling. This is consistent with SINE-compound mediated XPO1 inhibition exhibiting anti-cancer activity through a broad range of different mechanisms in different molecular chordoma subsets. Our findings validate the need for further investigation into selinexor as a targeted therapeutic for chordoma, especially in combination with abemaciclib.
Downregulation of ZNF280A inhibits proliferation and tumorigenicity of colorectal cancer cells by promoting the ubiquitination and degradation of RPS14
Authors: Tian Binle , Zhou Jingyi , Chen Guiming , Jiang Tao , Li Qi , Qin Jian
Published: August 2022

Colorectal cancer (CRC), one of the cancers with highest mortality, involves complicated molecular mechanisms leading to the onset of malignant phenotypes. ZNF280A, a member of the zinc-finger protein family, was shown to be a promotor of oncogenesis in CRC in this study. ZNF280A was remarkably upregulated in CRC tissues, which was meaningfully associated with tumor progression and poor prognosis in patients with CRC. Loss-of-function studies revealed that ZNF280A knockdown inhibited the development and progression of CRC as evident by the inhibition of cell proliferation, colony formation, cell apoptosis, cell cycle distribution, and cell migration in vitro and the repressed tumorigenesis of CRC cells in vivo. Next, we showed that RPS14 was the downstream target of ZNF280A and ZNF280A knockdown promoted the ubiquitination as well as degradation of RPS14 in CRC. Additionally, we demonstrated that RPS14 regulated the development of CRC via PI3K-Akt signaling pathway. Taken together, our findings provide a novel clear insight into ZNF280A/RPS14/PI3K-Akt axis in CRC for the first time, offering a potential target for early detection, diagnosis and treatment of CRC in future clinical applications.
In vitro elucidation of antioxidant, antiproliferative, and apoptotic potential of yeast-derived β-1,3-glucan particles against cervical cancer cells
Authors: Upadhyay Tarun Kumar , Trivedi Rashmi , Khan Fahad , Al-Keridis Lamya Ahmed , Pandey Pratibha , Sharangi Amit Baran , Alshammari Nawaf , Abdullah Nadiya M. , Yadav Dharmendra Kumar , Saeed Mohd
Published: August 2022

Cancer is the leading cause of mortality worldwide and in particular is the fourth most common cause of mortality in women every year. Conventional treatments for cancer are chemotherapy and radiation therapy, which have various kinds of side effects. Hence, there is a high need to develop alternative, efficient, and safer therapies for cancer treatment. β-Glucan, a novel polysaccharide isolated from baker’s yeast Saccharomyces cerevisiae, shows noteworthy cytotoxicity toward a variety of cancer cell lines in vitro. In this research, we characterized the β-glucan with high-performance thin-layer chromatography (HPTLC) analysis and found that d-glucose units with β-1,3 links are the major component of the extracted β-glucan particles. Fourier transform IR (FTIR) analysis confirmed a β-(1→3)-linked glucan structure. In vitro cell cytotoxicity was evaluated by MTT with IC50 136 μg/ml, and therapeutic potential was assessed by various assays using values below and above the IC50. A significant reactive oxygen species (ROS) generation at 50–150 μg/ml of concentrations indicated the apoptosis of cervical cancer cells. Along with ROS generation, these concentrations were also found to induce morphological changes such as fragmentation in DNA upon staining HeLa cells with DAPI. Mitochondrial membrane potential was significantly reduced after increasing the dose of treatment, assessed with the help of MitoTracker dye. Hence, by all these experimental supports, we observed that β-glucan has the potential to slow down the growth of cervical cancer cells, and it can be further investigated for unfolding its complete anticancer potential.
Circulating cell-free DNA and IL-10 from cerebrospinal fluids aid primary vitreoretinal lymphoma diagnosis
Authors: Zhuang Zhe , Zhang Yan , Zhang Xiao , Zhang Meifen , Zou Dongmei , Zhang Li , Jia Congwei , Zhang Wei
Published: August 2022

Primary vitreoretinal lymphoma (PVRL) is a rare variant of primary central nervous system lymphoma (PCNSL) that presents diagnostic challenges. Here, we focused on circulating cell-free DNA (cfDNA) and interleukin-10 (IL-10) isolated from cerebrospinal fluid. Twenty-three VRL patients (17 PVRL, 2 PCNSL/O, and 4 relapsed VRL, from 10/2018 to 12/2021) and 8 uveitis patients were included in this study. CSF samples from 19 vitreoretinal lymphoma patients had sufficient cfDNA for next-generation sequencing. Of these patients, 73.7% (14/19) had at least one meaningful non-Hodgkin lymphoma-related mutation. The characteristic MYD88L265P mutation was detected in the CSF of 12 VRL patients, with a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 63.2%, 100%, 100%, and 46.2%, respectively. No meaningful lymphoma related mutations were found in CSF samples from uveitis controls with typical intraocular lesions. Meanwhile, CSF IL-10 levels were elevated in 95.7% of the VRL patients, with a sensitivity, specificity, PPV, and NPV of 95.7%, 100%, 100% and 88.9%, respectively. Key somatic mutations like MYD88L265P and CD79B detected from CSF cfDNA and elevated CSF IL-10 levels can be promising adjuncts for primary vitreoretinal lymphoma diagnosis.
Case report: B7-H3 CAR-T therapy partially controls tumor growth in a basal cell carcinoma patient
Authors: Hu Gang , Li Guangchao , Wen Wei , Ding Wen , Zhou Zhao , Zheng Yongwei , Huang Taoyuan , Ren Junnan , Chen Rongyi , Zhu Dingheng , He Renliang , Liang Yunsheng , Luo Min
Published: August 2022

B7-H3 is over-expressed in multiple types of solid tumors, making it an ideal target for chimeric antigen receptor (CAR)-T therapy. Here, we first report a case of multiple basal cell carcinoma (BCC) patient treated with humanized monoclonal anti-B7-H3 CAR-T cells through direct intratumoral injection. After three dose-escalated injections, the lesion in the abdomen decreased by 40% in volume, shrank from bulging to flat, but was not eradicated completely. The large lesion in the forehead became dry from original ulcer and bleeding. The adverse events observed were itching, myalgia, and redness. Immunohistochemistry analysis demonstrated that B7-H3-positive tumor cells and B7-H3 expression intensity were reduced after injections of CAR-T cells. The number of infiltrating CD3 T cells increased significantly but mainly located outside the tumor region. Subsequently, high levels of TGF-β in the tumor area were observed, suggesting that solid tumor microenvironment may hinder the infiltration and effect of CAR-T cells. In summary, in this particular case report, intratumoral injection of B7-H3 CAR-T cells partially controls tumor growth in the BCC patient with minor adverse events. The efficacy and safety of B7-H3 CAR-T therapy need to be further investigated with a larger cohort of patients. Although only one clinical case is reported here, the anti-B7-H3 CAR-T cell therapy should be considered as a treatment option for solid tumors in the future. This clinical trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) with registration number ChiCTR2100044386.
The top 100 most cited papers on endometrial carcinoma: A bibliometric analysis
Authors: Xiao Peichen , Yao Chenchen , Wang Guangxin
Published: August 2022

Objective

This study aimed to analyze the top 100 most cited papers and research trends on endometrial carcinoma via bibliometric methods.

Methods

On the 1st of March 2022, the top 100 most cited papers regarding endometrial carcinoma published from 1971 to 2021 were identified through searching Web of Science Core Collection database and the following data: title, author, journal, publication year, country and institution were extracted. Microsoft Office Excel (2019) was used for descriptive statistical analysis. VOSviewer (1.6.18) was used to perform and visualize co-authorship analysis and co-occurrence analysis.

Results

These 100 papers were cited a total of 45, 685 times, and the mean number of citations was 456.85 (range, 228 to 2487). Most papers were published between 1996 and 2000, and between 2006 and 2010. The Lancet published the largest number of papers (n=12), followed by Gynecologic Oncology (n=11). Most of the papers were from the United States (n=58), followed by Italy (n=8) and Netherlands (n=7). Duke University, Johns Hopkins University, University of California San Francisco and University of Southern California (all in United States) contributed the most papers (n=4, respectively). Nicoletta Colombo contributed the most papers (n=3) as the corresponding author. The co-occurrence keywords were classified into three clusters: cluster 1 (epidemiology study), cluster 2 (molecular biology study) and cluster 3 (clinical treatment study). Early research that was published prior to 2005 in this field was mainly focused on epidemiology and molecular biology; the mean publication year for keywords in cluster 3 was later than other clusters. The keywords “external-beam radiotherapy,” “uterine serous carcinoma,” and “intermediate-risk” showed relatively later mean publication year and lower mean frequency of occurrence.

Conclusions

This study provides medical researchers with bibliometric information relating to endometrial carcinoma. Our results show that the United States is a clear leader in this field. The clinical treatment of endometrial carcinoma has received increasing levels of attention over recent years and is likely to remain a major area of research in the future. Meanwhile, it is recommended to pay attention to potential research hotspots, such as external-beam radiotherapy, uterine serous carcinoma and intermediate-risk.
The role of radiomics with machine learning in the prediction of muscle-invasive bladder cancer: A mini review
Authors: Huang Xiaodan , Wang Xiangyu , Lan Xinxin , Deng Jinhuan , Lei Yi , Lin Fan
Published: August 2022

Bladder cancer is a common malignant tumor in the urinary system. Depending on whether bladder cancer invades muscle tissue, it is classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). It is crucial to accurately diagnose the muscle invasion of bladder cancer for its clinical management. Although imaging modalities such as CT and multiparametric MRI play an important role in this regard, radiomics has shown great potential with the development and innovation of precision medicine. It features outstanding advantages such as non-invasive and high efficiency, and takes on important significance in tumor assessment and laor liberation. In this article, we provide an overview of radiomics in the prediction of muscle-invasive bladder cancer and reflect on its future trends and challenges.
The impacts of the “4+7” pilot policy on the volume, expenditures, and daily cost of Serotonin-Specific Reuptake Inhibitors (SSRIs) antidepressants: A quasi-experimental study
Authors: Wen Xiaotong , Wang Zhaolun , Xu Luxinyi , Luo Jia , Geng Xin , Chen Xiaoze , Yang Ying , Cui Dan , Mao Zongfu
Published: August 2022

Objectives: The purpose of this study was to quantitatively evaluate the impacts of the”4 + 7” pilot policy on purchase volume, purchase expenditures, and daily cost and to find the changes in the use of SSRIs.

Methods: Data was collected covering 31 months, before, during, and after the “4 + 7” pilot policy was implemented in Shenzhen. Interrupted time-series (ITS) analysis was used to examine whether there had been a significant effect with the onset of the “4 + 7” pilot policy in March 2019.

Findings: The daily cost of policy-related drugs had a substantial drop of 2.93 yuan under the “4 + 7” pilot policy. The result has shown a 76.70% increase in volume and a 3.39% decrease in the expenditure on policy-related drugs. This study found that the “4 + 7” pilot policy increased the proportion of purchasing winning drugs, with an increment of 85.60 percent. After the implementation of the “4 + 7” pilot policy, policy-related drugs decreased by 443.55thousand Chinese yuan. The study indicated that volume of winning products significantly increased as shown in the regression with a level coefficient (β2) of -224.17 (p < 0.001) and trend coefficient (β3) of 15.74 (p < 0.001). The result revealed that both volume and expenditures on branded products showed a significant decrease in the regression in the post-intervention period (level coefficient of volume: β2 = -57.65, p < 0.01, trend coefficient of volume: β3 = -3.44, p < 0.01; level coefficient of expenditure: β2 = -712.98, p < 0.01, trend coefficient of expenditure: β3 = -40.10, p < 0.01).

Conclusion: The volume-based procurement has successfully led to price reductions and improved the affordability of medicines, especially for those with chronic diseases. The volume-based procurement has demonstrated initial success in reshaping the composition of the Chinese pharmaceutical market in favor of generics with high quality and low prices.
Enhanced liver fibrosis score as a noninvasive biomarker in hepatitis C virus patients after direct-acting antiviral agents
Authors: Cossiga Valentina , La Civita Evelina , Bruzzese Dario , Guarino Maria , Fiorentino Andrea , Sorrentino Rosanna , Pontillo Giuseppina , Vallefuoco Luca , Brusa Stefano , Montella Emma , Terracciano Daniela , Morisco Filomena , Portella Giuseppe
Published: August 2022

Background: In more than 90% of chronic viral hepatitis C (HCV) patients treated with direct-acting antiviral agents (DAAs), a sustained viral response (SVR) was observed. Unfortunately, there are subgroups of subjects who display enduring liver fibrosis and are at high risk of developing hepatocellular carcinoma (HCC). Thus, liver fibrosis evaluation during the follow-up of these patients plays a pivotal role. The gold standard to evaluate hepatic fibrosis is liver biopsy, which is an invasive procedure. Imaging techniques and serum biomarkers have been proposed as safer and cheaper procedures.

Objectives: In this study, we evaluated the concordance of transient elastography (TE) with ELF score ( enhanced liver fibrosis) in a cohort of patients with HCV before and after direct-acting antiviral (DAAs) treatment. ELF score has been validated in other chronic liver diseases; the evidence is not available in HCV patients treated with DAAs.

Study design: We prospectively recruited all consecutive HCV patient candidates for DAAs therapy at the University of Naples “Federico II” between April 2015 and July 2016. TE and ELF scores were assessed at baseline, at SVR24, and at SVR48.

Results: One-hundred-nineteen patients were treated with DAAs, and 94.1% of them reached SVR. A total of 55.5% of patients were males with a mean age of 64.7 ± 9.6 years. TE results revealed that 12 patients (10%) had F1-2 mild/moderate fibrosis, and 107 (90%) had F3-4 advanced fibrosis. At baseline, SVR24, and SVR48, the concordance between ELF test and TE was poor: 0.11 (p = 0.086), 0.15 (p = 0.124), and 0.034 (p = 0.002), respectively. However, at SVR24 and SVR48, both methods showed a significant amelioration of liver fibrosis compared to baseline (p < 0.001). In addition, both ELF index and TE were significantly associated with portal hypertension at baseline, but not with varices and ascites.

Conclusions: Our findings suggested that ELF test could predict changes in liver fibrosis, independently of TE. In case of TE unavailability, ELF score could represent an appropriate tool. Notably, in the context of the COVID-19 pandemic, ELF testing should be encouraged to reduce unnecessary access to the hospital and prolonged physical contact.
Retinal microglia protect against vascular damage in a mouse model of retinopathy of prematurity
Authors: Liu Jin , Tsang Jessica Kwan Wun , Fung Frederic Khe Cheong , Chung Sookja Kim , Fu Zhongjie , Lo Amy Cheuk Yin
Published: August 2022

Retinopathy of prematurity (ROP) is a common cause of blindness in preterm babies. As a hypoxia-induced eye disease characterized by neovascularization, its association with retinal microglia has been noted but not well documented. We performed a comprehensive analysis of retinal microglia and retinal vessels in mouse oxygen-induced retinopathy (OIR), an animal model of ROP. In combination with a pharmacological inhibitory strategy, the role of retinal microglia in vascular network maintenance was investigated. Postnatal day (P) 7 C57BL/6J mouse pups with their nursing mother were exposed to 75% oxygen for 5 days to induce OIR. Age-matched room air-treated pups served as controls. On P12, P17, P21, P25, and P30, retinal microglia and vessels were visualized and quantified based on their location and activation status. Their relationship with retinal vessels was also analyzed. On P5 or P12, retinal microglia inhibition was achieved by intravitreal injection of liposomes containing clodronate (CLD); retinal vasculature and microglia were examined in P12 and P17 OIR retinae. The number of retinal microglia was increased in the superficial areas of OIR retinae on P12, P17, P21, P25, and P30, and most of them displayed an amoeboid (activated) morphology. The increased retinal microglia were associated with increased superficial retinal vessels in OIR retinae. The number of retinal microglia in deep retinal areas of OIR retinae also increased from P17 to P30 with a ramified morphology, which was not associated with reduced retinal vessels. Intravitreal injection of liposomes-CLD caused a significant reduction in retinal microglia. Loss of retinal microglia before hyperoxia treatment resulted in increased vessel obliteration on P12 and subsequent neovascularization on P17 in OIR retinae. Meanwhile, loss of retinal microglia immediately after hyperoxia treatment on P12 also led to more neovascularization in P17 OIR retinae. Our data showed that activated microglia were strongly associated with vascular abnormalities upon OIR. Retinal microglial activation continued throughout OIR and lasted until after retinal vessel recovery. Pharmacological inhibition of retinal microglia in either hyperoxic or hypoxic stage of OIR exacerbated retinal vascular consequences. These results suggested that retinal microglia may play a protective role in retinal vasculature maintenance in the OIR process.
Shenkang injection improves chronic kidney disease by inhibiting multiple renin-angiotensin system genes by blocking the Wnt/β-catenin signalling pathway
Authors: Wang Yan-Ni , Liu Hong-Jiao , Ren Li-Li , Suo Ping , Zou Liang , Zhang Ya-Mei , Yu Xiao-Yong , Zhao Ying-Yong
Published: August 2022

Chronic kidney disease (CKD) is a major worldwide public health problem. The increase in the number of patients with CKD and end-stage kidney disease requesting renal dialysis or transplantation will progress to epidemic proportions in the next several decades. Although blocking the renin-angiotensin system (RAS) has been used as a first-line standard therapy in patients with hypertension and CKD, patients still progress towards end-stage kidney disease, which might be closely associated with compensatory renin expression subsequent to RAS blockade through a homeostatic mechanism. The Wnt/β-catenin signalling pathway is the master upstream regulator that controls multiple intrarenal RAS genes. As Wnt/β-catenin regulates multiple RAS genes, we inferred that this pathway might also be implicated in blood pressure control. Therefore, discovering new medications to synchronously target multiple RAS genes is necessary and essential for the effective treatment of patients with CKD. We hypothesized that Shenkang injection (SKI), which is widely used to treat CKD patients, might ameliorate CKD by inhibiting the activation of multiple RAS genes via the Wnt/β-catenin signalling pathway. To test this hypothesis, we used adenine-induced CKD rats and angiotensin II (AngII)-induced HK-2 and NRK-49F cells. Treatment with SKI inhibited renal function decline, hypertension and renal fibrosis. Mechanistically, SKI abrogated the increased protein expression of multiple RAS elements, including angiotensin-converting enzyme and angiotensin II type 1 receptor, as well as Wnt1, β-catenin and downstream target genes, including Snail1, Twist, matrix metalloproteinase-7, plasminogen activator inhibitor-1 and fibroblast-specific protein 1, in adenine-induced rats, which was verified in AngII-induced HK-2 and NRK-49F cells. Similarly, our results further indicated that treatment with rhein isolated from SKI attenuated renal function decline and epithelial-to-mesenchymal transition and repressed RAS activation and the hyperactive Wnt/β-catenin signalling pathway in both adenine-induced rats and AngII-induced HK-2 and NRK-49F cells. This study first revealed that SKI repressed epithelial-to-mesenchymal transition by synchronously targeting multiple RAS elements by blocking the hyperactive Wnt/β-catenin signalling pathway.
Effects of propofol on macrophage activation and function in diseases
Authors: Yi Shuyuan , Tao Xinyi , Wang Yin , Cao Qianqian , Zhou Zhixia , Wang Shoushi
Published: August 2022

Macrophages work with monocytes and dendritic cells to form a monocyte immune system, which constitutes a powerful cornerstone of the immune system with their powerful antigen presentation and phagocytosis. Macrophages play an essential role in infection, inflammation, tumors and other pathological conditions, but these cells also have non-immune functions, such as regulating lipid metabolism and maintaining homeostasis. Propofol is a commonly used intravenous anesthetic in the clinic. Propofol has sedative, hypnotic, anti-inflammatory and anti-oxidation effects, and it participates in the body’s immunity. The regulation of propofol on immune cells, especially macrophages, has a profound effect on the occurrence and development of human diseases. We summarized the effects of propofol on macrophage migration, recruitment, differentiation, polarization, and pyroptosis, and the regulation of these propofol-regulated macrophage functions in inflammation, infection, tumor, and organ reperfusion injury. The influence of propofol on pathology and prognosis via macrophage regulation is also discussed. A better understanding of the effects of propofol on macrophage activation and function in human diseases will provide a new strategy for the application of clinical narcotic drugs and the treatment of diseases.
Temozolomide hexadecyl ester targeted plga nanoparticles for drug-resistant glioblastoma therapy via intranasal administration
Authors: Wang Siqi , Yu Yawen , Wang Aiping , Duan Xinliu , Sun Yuchen , Wang Liangxiao , Chu Liuxiang , Lv Yanan , Cui Nan , Fan Xuesong , Sha Chunjie , Xu Lixiao , Sun Kaoxiang
Published: August 2022

Introduction: Temozolomide (TMZ) is the first-line drug for glioblastoma (GBM), but it is limited in clinical use due to the drug resistance, poor brain targeting, and side effects. Temozolomide hexadecyl ester (TMZ16e), a TMZ derivative with high lipophilicity, membrane permeability, and high anti-glioma properties, has the potential to reverse drug resistance. In this study, anti-ephrin type-A receptor 3 (EphA3) modified TMZ16e loaded nanoparticles (NPs) were prepared for targeted GBM therapy via intranasal administration to deliver TMZ16e to the brain, treat drug-resistant glioma effectively, and reduce peripheral toxicity.

Methods: TMZ16e loaded NPs were prepared by emulsion solvent evaporation method followed by modified with anti-EphA3 (anti-EphA3-TMZ16e-NPs). In vitro evaluations were performed by an MTT assay and flow cytometry analysis. The orthotopic nude mice models were used to evaluate the anti-glioma effect in vivo. Additionally, we investigated the anti-drug resistant mechanism by western blot analysis.

Results: The particle size of the prepared NPs was less than 200 nm, and the zeta potential of TMZ16e-NPs and anti-EphA3-TMZ16e-NPs were -23.05 ± 1.48 mV and -28.65 ± 1.20mV, respectively, which is suitable for nasal delivery. In vitro studies have shown that anti-EphA3 modification increased the cellular uptake of nanoparticles in T98G cells. The cytotoxicity in the anti-EphA3-TMZ16e-NPs treated group was significantly higher than that of the TMZ16e-NPs, TMZ16e, and TMZ groups (p < 0.01), and the cell cycle was blocked. Western blotting analysis showed that the TMZ16e-loaded NPs were able to effectively downregulate the expression level of O6-methylguanine-deoxyribonucleic acid-methyltransferase (MGMT) protein in T98G cells and reverse drug resistance. In vivo studies showed that the median survival time of tumor-bearing nude mice in the anti-EphA3-TMZ16e-NPs group was extended to 41 days, which was 1.71-fold higher than that of the saline group and the TUNEL staining results of the brain tissue section indicated that the TMZ16e-loaded NPs could elevate apoptosis in T98G cells.

Conclusion: In conclusion, the TMZ16e-loaded NPs can be effectively delivered to the brain and targeted to gliomas, exhibiting better anti-glioma activity, indicating they possess great potential in the treatment of drug-resistant glioma.
Continuous time series analysis on the effects of induced running fatigue on leg symmetry using kinematics and kinetic variables: Implications for knee joint injury during a countermovement jump
Authors: Gao Zixiang , Zhao Liang , Fekete Gusztáv , Katona Gábor , Baker Julien S. , Gu Yaodong
Published: August 2022

This study investigates the symmetry change in joint angle and joint moment of knee joints following a Running-Induced Fatigue counter movement Jump. Twelve amateur runners volunteered to participate in the study. A prolonged running protocol was used to induce fatigue. Joint angle and moment were recorded during the push and flexion phase of the CMJ before and immediately after fatigue. Borg scale (RPE>17) and real-time heart rate monitoring (HR>90%HRmax) were used to confirm running fatigue. Symmetry function (SF) was used to assess the symmetry of the knee Angle and moment variation parameters over the entire push-off and landing phases based on time series analysis. Paired sample t-test was used to examine changes in SF before and after acute fatigue. The Angle and moment of the knee are asymmetrical in all planes (SF > 0.05), with SF ranging from 5 to 130% in angle and 5–110% in moment. There was a significant increase in knee joint angle asymmetry in the horizontal plane during the push-off and landing stage following the prolonged - Running Protocol implementation. These increases in asymmetry are mainly caused by excessive external rotation of the dominant knee joint. These findings indicate that fatigue-induced changes during CMJ may progress knee movement pattern asymmetry in the horizontal plane.
Effects of short-term heat stress on the activity of three antioxidant enzymes of predatory mite Neoseiulus barkeri (acari, phytoseiidae)
Authors: Li Wei-Zhen , Zhu Tong , Zhou Jing-Jiang , Shang Su-Qin
Published: August 2022

To study the physiological mechanisms of Neoseiulus barkeri in response to short-term heat stress, the eggs and the emerged adults were exposed to 38, 40, and 42°C, 85% ± 5%RH,16 h:8 h (L:D) for 2, 4, and 6 h. The activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) as well as the protein content of N. barkeri were examined. All treatments caused significant different changes compared to the untreated control. The protein content increased as the temperature increased, while it showed different changing trends with the prolongation of exposure duration. The enzymatic activity of SOD, CAT, and POD was significantly affected by the temperature treatment. Both the maximum and minimum level of the three enzymes after a short-term heat stress differed significantly to the control group (p < 0.05). The highest values of three enzymatic activities were all obtained at 40°C-4 h. Person correlation analysis indicates that the high temperature was the primary factor affecting the enzymatic activity, while the exposure duration of the heat stress was the secondary factor. In general, the short-term heat stress increased the protein content of Neoseiulus barkeri and up-regulated the expression of SOD, CAT, and POD activities as well.
Comparison of trunk muscle exercises in supine position during short arm centrifugation with 1 g at centre of mass and upright in 1 g
Authors: Frett Timo , Lecheler Leopold , Speer Martin , Marcos David , Pesta Dominik , Tegtbur Uwe , Schmitz Marie-Therese , Jordan Jens , Green David Andrew
Published: August 2022

Spaceflight is associated with reduced antigravitational muscle activity, which results in trunk muscle atrophy and may contribute to post-flight postural and spinal instability. Exercise in artificial gravity (AG) performed via short-arm human centrifugation (SAHC) is a promising multi-organ countermeasure, especially to mitigate microgravity-induced postural muscle atrophy. Here, we compared trunk muscular activity (mm. rectus abdominis, ext. obliques and multifidi), cardiovascular response and tolerability of trunk muscle exercises performed during centrifugation with 1 g at individual center of mass on a SAHC against standard upright exercising. We recorded heart rate, blood pressure, surface trunk muscle activity, motion sickness and rating of perceived exertion (BORG) of 12 participants (8 male/4 female, 34 ± 7 years, 178.4 ± 8.2 cm, 72.1 ± 9.6 kg). Heart rate was significantly increased (p < 0.001) during exercises without differences in conditions. Systolic blood pressure was higher (p < 0.001) during centrifugation with a delayed rise during exercises in upright condition. Diastolic blood pressure was lower in upright (p = 0.018) compared to counter-clockwise but not to clockwise centrifugation. Target muscle activation were comparable between conditions, although activity of multifidi was lower (clockwise: p = 0.003, counter-clockwise: p < 0.001) and rectus abdominis were higher (clockwise: p = 0.0023, counter-clockwise: < 0.001) during centrifugation in one exercise type. No sessions were terminated, BORG scoring reflected a relevant training intensity and no significant increase in motion sickness was reported during centrifugation. Thus, exercising trunk muscles during centrifugation generates comparable targeted muscular and heart rate response and appears to be well tolerated. Differences in blood pressure were relatively minor and not indicative of haemodynamic challenge. SAHC-based muscle training is a candidate to reduce microgravity-induced inter-vertebral disc pathology and trunk muscle atrophy. However, further optimization is required prior to performance of a training study for individuals with trunk muscle atrophy/dysfunction.
Glomus sp. and Bacillus sp. strains mitigate the adverse effects of drought on maize (Zea mays L.)
Authors: Wilmowicz Emilia , Kućko Agata , Bogati Kalisa , Wolska Magdalena , Świdziński Michał , Burkowska-But Aleksandra , Walczak Maciej
Published: August 2022

Maize (Zea mays L.) is an economically important source of food and feed. This species is highly sensitive to drought, which is the most limiting factor for the biomass yield of a crop. Thus, maize cultivation methods should be improved, especially by environment-friendly agricultural practices, such as microorganisms. Here, we provide evidence that Glomus sp. and Bacillus sp. modulate maize response to drought. Inoculation of maize seeds by these microorganisms restored the proper photosynthetic activity of the plant under drought and stabilized the osmoprotectant content of the leaf. The beneficial effect of Glomus sp. and Bacillus sp. was also related to the stabilization of cell redox status reflected by hydrogen peroxide content, antioxidant enzymes, and malondialdehyde level in leaves. As we revealed by several methods, shaping maize response to drought is mediated by both microorganism-mediated modifications of cell wall composition and structure of leaves, such as downregulating pectin, affecting their methylation degree, and increasing hemicellulose content. Overall, we provide new information about the mechanisms by which Glomus sp. and Bacillus sp. induce drought tolerance in maize, which is a promising approach for mitigating abiotic stresses.
The ferroxidases are critical for Fe(II) oxidation in xylem to ensure a healthy Fe allocation in Arabidopsis thaliana
Authors: Zhu Qing-Yang , Wang Yun , Liu Xing-Xing , Ye Jia-Yuan , Zhou Miao , Jing Xiang-Ting , Du Wen-Xin , Hu Wei-Jie , He Chao , Zhu Ya-Xin , Jin Chong-Wei
Published: August 2022

The long-distance transport of iron (Fe) in the xylem is critical for maintaining systemic Fe homeostasis in plants. The loading form of Fe(II) into the xylem and the long-distance translocation form of Fe(III)–citrate have been identified, but how Fe(II) is oxidized to Fe(III) in the xylem remains unknown. Here, we showed that the cell wall-resided ferroxidases LPR1 and LPR2 (LPRs) were both specifically expressed in the vascular tissues of Arabidopsis thaliana, while disruption of both of them increased Fe(II) in the xylem sap and caused excessive Fe deposition in the xylem vessel wall under Fe-sufficient conditions. As a result, a large amount of Fe accumulated in both roots and shoots, hindering plant growth. Moreover, under low-Fe conditions, LPRs were preferentially induced in old leaves, but the loss of LPRs increased Fe deposition in the vasculature of older leaves and impeded Fe allocation to younger leaves. Therefore, disruption of both LPRs resulted in severer chlorosis in young leaves under Fe-deficient conditions. Taken together, the oxidation of Fe(II) to Fe(III) by LPRs in the cell wall of vasculature plays an important role in xylem Fe allocation, ensuring healthy Fe homeostasis for normal plant growth.