bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of macrophage scavenger receptor MSR1 in the progression of non-alcoholic steatohepatitis
Authors: Sheng Wei , Ji Guang , Zhang Li
Published: December 2022

Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD), and the dysregulation of lipid metabolism and oxidative stress are the typical features. Subsequent dyslipidemia and oxygen radical production may render the formation of modified lipids. Macrophage scavenger receptor 1 (MSR1) is responsible for the uptake of modified lipoprotein and is one of the key molecules in atherosclerosis. However, the unrestricted uptake of modified lipoproteins by MSR1 and the formation of cholesterol-rich foamy macrophages also can be observed in NASH patients and mouse models. In this review, we highlight the dysregulation of lipid metabolism and oxidative stress in NASH, the alteration of MSR1 expression in physiological and pathological conditions, the formation of modified lipoproteins, and the role of MSR1 on macrophage foaming and NASH development and progression.
A new framework for host-pathogen interaction research
Authors: Yu Hong , Li Li , Huffman Anthony , Beverley John , Hur Junguk , Merrell Eric , Huang Hsin-hui , Wang Yang , Liu Yingtong , Ong Edison , Cheng Liang , Zeng Tao , Zhang Jingsong , Li Pengpai , Liu Zhiping , Wang Zhigang , Zhang Xiangyan , Ye Xianwei , Handelman Samuel K. , Sexton Jonathan , Eaton Kathryn , Higgins Gerry , Omenn Gilbert S. , Athey Brian , Smith Barry , Chen Luonan , He Yongqun
Published: December 2022

COVID-19 often manifests with different outcomes in different patients, highlighting the complexity of the host-pathogen interactions involved in manifestations of the disease at the molecular and cellular levels. In this paper, we propose a set of postulates and a framework for systematically understanding complex molecular host-pathogen interaction networks. Specifically, we first propose four host-pathogen interaction (HPI) postulates as the basis for understanding molecular and cellular host-pathogen interactions and their relations to disease outcomes. These four postulates cover the evolutionary dispositions involved in HPIs, the dynamic nature of HPI outcomes, roles that HPI components may occupy leading to such outcomes, and HPI checkpoints that are critical for specific disease outcomes. Based on these postulates, an HPI Postulate and Ontology (HPIPO) framework is proposed to apply interoperable ontologies to systematically model and represent various granular details and knowledge within the scope of the HPI postulates, in a way that will support AI-ready data standardization, sharing, integration, and analysis. As a demonstration, the HPI postulates and the HPIPO framework were applied to study COVID-19 with the Coronavirus Infectious Disease Ontology (CIDO), leading to a novel approach to rational design of drug/vaccine cocktails aimed at interrupting processes occurring at critical host-coronavirus interaction checkpoints. Furthermore, the host-coronavirus protein-protein interactions (PPIs) relevant to COVID-19 were predicted and evaluated based on prior knowledge of curated PPIs and domain-domain interactions, and how such studies can be further explored with the HPI postulates and the HPIPO framework is discussed.
The diagnosis of anti-LGI1 encephalitis varies with the type of immunodetection assay and sample examined
Authors: Muñoz-Sánchez Guillermo , Planagumà Jesús , Naranjo Laura , Couso Rocío , Sabater Lidia , Guasp Mar , Martínez-Hernández Eugenia , Graus Francesc , Dalmau Josep , Ruiz-García Raquel
Published: December 2022

Detection of Leucine-rich glioma inactivated 1 (LGI1) antibodies in patients with suspected autoimmune encephalitis is important for diagnostic confirmation and prompt implementation of immunomodulatory treatment. However, the clinical laboratory diagnosis can be challenging. Previous reports have suggested that the type of test and patient’s sample (serum or CSF) have different clinical performances, however, there are no studies comparing different diagnostic tests on paired serum/CSF samples of patients with anti-LGI1 encephalitis. Here, we assessed the clinical performance of a commercial and an in house indirect immunofluorescent cell based assays (IIF-CBA) using paired serum/CSF of 70 patients with suspected anti-LGI1 encephalitis and positive rat brain indirect immunohistochemistry (IIHC). We found that all (100%) patients had CSF antibodies when the in house IIF-CBA was used, but only 88 (83%) were positive if the commercial test was used. In contrast, sera positivity rate was higher with the commercial test (94%) than with the in house assay (86%). If both serum and CSF were examined with the commercial IIFA-CBA, 69/70 (98.5%) patients were positive in at least one of the samples. These findings are clinically important for centers in which rat brain IIHC and in house IIFA-CBA are not available. Moreover, the observation that all patients with anti-LGI1 encephalitis have antibodies in CSF is in line with the concept that these antibodies are pathogenic.
Oral administration of hepcidin and chitosan benefits growth, immunity, and gut microbiota in grass carp (Ctenopharyngodon idella)
Authors: Zhou Jiancheng , Feng Mengzhen , Zhang Weixiang , Kuang Rui , Zou Qi , Su Jianguo , Yuan Gailing
Published: December 2022

Intensive high-density culture patterns are causing an increasing number of bacterial diseases in fish. Hepcidin links iron metabolism with innate immunity in the process of resisting bacterial infection. In this study, the antibacterial effect of the combination of hepcidin (Cihep) and chitosan (CS) against Flavobacterium columnare was investigated. The dosing regimen was also optimized by adopting a feeding schedule of every three days and every seven days. After 56 days of feeding experiment, grass carp growth, immunity, and gut microbiota were tested. In vitro experiments, Cihep and CS can regulate iron metabolism and antibacterial activity, and that the combination of Cihep and CS had the best protective effect. In vivo experiments, Cihep and CS can improve the growth index of grass carp. After challenge with Flavobacterium columnare, the highest survival rate was observed in the Cihep+CS-3d group. By serum biochemical indicators assay and Prussian blue staining, Cihep and CS can increase iron accumulation and decrease serum iron levels. The contents of lysozyme and superoxide dismutase in Cihep+CS-3d group increased significantly. Meanwhile, Cihep and CS can significantly reduce the pathological damage of gill tissue. The 16S rRNA sequencing results showed that Cihep and CS can significantly increase the abundance and diversity of grass carp gut microbiota. These results indicated that the protective effect of consecutive 3-day feeding followed by a 3-day interval was better than that of consecutive 7-day feeding followed by a 7-day interval, and that the protective effect of Cihep in combination with chitosan was better than that of Cihep alone. Our findings optimize the feeding pattern for better oral administration of Cihep in aquaculture.
Immune-related adverse events: A bibliometric analysis
Authors: Jiang Shi-Tao , Liu Yao-Ge , Zhang Lei , Sang Xin-Ting , Xu Yi-Yao , Lu Xin
Published: December 2022

Background

Despite providing clinical benefit, immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) in a number of patients. This study explored the development pattern in irAEs research from a bibliometric perspective.

Methods

We obtained articles and reviews related to irAEs from the Web of Science Core Collection (WoSCC) (retrieved on September 13, 2022). Using the R package “Bibliometrix”, the main bibliometric features were calculated, and a three-filed plot was generated to show the relationship between authors, institutions, and topics. VOSviewer was used for co-authorship and keyword co-occurrence analysis and visualization. CiteSpace was used to detect burst references and keywords.

Results

A total of 3995 publications on irAEs were included. The United States (US), Japan, and China had the highest publications. The Journal for ImmunoTherapy of Cancer had the highest number of publications. In addition to “immune-related adverse events”, “immune checkpoint inhibitors”, “immunotherapy”, and “nivolumab” were the most frequently used keywords.

Conclusions

A bibliometric analysis of 17 years of irAEs research was conducted to map a basic knowledge structure including countries, institutions, authors, journals, and publications. The findings provided a comprehensive perspective on the broad future of this research area.
Infiltration of LPAR5+ macrophages in osteosarcoma tumor microenvironment predicts better outcomes
Authors: He Yi , Zhou Haiting , Huang Xiaojian , Qu Yunkun , Wang Yingguang , Pei Wenbin , Zhang Rui , Chen Sheng , You Hongbo
Published: December 2022

Introduction

Tumor microenvironment (TME) has been shown to be extensively involved in tumor development. However, the dynamic change of TME components and their effects are still unclear. Here, we attempted to identify TME-related genes that could help predict survival and may be potential therapeutic targets.

Methods

Data was collected from UCSC Xena and GEO database. ESTIMATE and CIBERSORT algorithms were applied to estimate the components and the proportions of TIICs in TME. We analyzed the gene expression differences of immune components and stromal components, respectively, and finally got the overlapped DEGs. Through protein-protein interaction (PPI) network and univariate Cox regression analysis based on shared DEGs, we screened out and validated the TME-related genes. Focusing on this gene, we analyzed the expression and prognostic value of this gene, and investigated its relationship with immune cells by correlation analysis, single cell analysis, immunohistochemistry and immunofluorescence analysis.

Results

Through a series analysis, we found that the proportion of immune and stromal components was an important prognostic factor, and screened out a key gene, LPAR5, which was highly correlated with prognosis and metastasis. And the expression of LPAR5 was positively correlated with immune cells, especially macrophages, indicating LPAR5+ macrophages played an important role in tumor microenvironment of osteosarcoma. Meanwhile, the genes in LPAR5 high expression group were enriched in immune-related activities and pathways, and differentially expressed genes between LPAR5+ macrophages and LPAR5- macrophages were enriched in the biological processes associated with phagocytosis and antigen presentation. What’ more, we found that LPAR5 was mainly expressed in TME, and high LPAR5 expression predicting a better prognosis.

Conclusion

We identified a TME-related gene, LPAR5, which is a promising indicator for TME remodeling in osteosarcoma. Particularly, LPAR5+ macrophages might have great potential to be a prognostic factor and therapeutic target for osteosarcoma.
Regulatory policy and pharmaceutical innovation in the United Kingdom after Brexit: Initial insights
Authors: Hofer Matthias P. , Criscuolo Paola , Shah Nilay , Wal Anne L. J. ter , Barlow James
Published: December 2022

Brexit was presented as an opportunity to promote innovation by breaking free from the European Union regulatory framework. Since the beginning of 2021 the Medicines and Healthcare products Regulatory Agency (MHRA) has operated as the independent regulatory agency for the United Kingdom. The MHRA's regulatory activity in 2021 was analyzed and compared to that of other international regulatory bodies. The MHRA remained reliant on EU regulatory decision-making for novel medicines and there were significant regulatory delays for a small number of novel medicines in the UK, the reasons being so far unclear. In addition, the MHRA introduced innovation initiatives, which show early promise for quicker authorization of innovative medicines for cancer and other areas of unmet need. Longer-term observation and analysis is needed to show the full impact of post-Brexit pharmaceutical regulatory policy.
Evaluation of procalcitonin elevation during ICU stay and its relationship with mortality in ICU patients for COVID-19 with respiratory involvement. A multicenter prospective cohort study
Authors: Rivera-Fernandez Ricardo , Yáguez-Mateos Luis , Guerrero-Marin María , Pérez-Manrique Rosa María , Rojas-Amezcua María , Pontes-Moreno Antonio Jesús , Ríos-Toro Juan José , Vela-Colmenero Rosa , Ruiz-Garcia María Isabel , Colmenero-Aguilar Crispín , Castillo-Rivera Ana , Pola-Gallego de Guzmán María Dolores , Aguilar-Alonso Eduardo
Published: December 2022

Introduction

A multicenter prospective cohort study studied patients admitted to the intensive care unit (ICU) by coronavirus-19 (COVID-19) with respiratory involvement. We observed the number of occasions in which the value of procalcitonin (PCT) was higher than 0.5 ng/ml.

Objective

Evaluation of PCT elevation and influence on mortality in patients admitted to the ICU for COVID-19 with respiratory involvement.

Measurements and main results

We studied 201 patients. On the day of admission, acute physiology and chronic health evaluation (APACHE)-II was 13 (10–16) points. In-hospital mortality was 36.8%. During ICU stay, 104 patients presented 1 or more episodes of PCT elevation and 60 (57.7%) died and 97 patients did not present any episodes of PCT elevation and only 14 (14.4%) died (p < 0.001). Multivariable analysis showed that mortality was associated with APACHE-II: [odds ratio (OR): 1.13 (1.04–1.23)], acute kidney injury [OR: 2.21 (1.1–4.42)] and with the presentation of one or more episodes of escalating PCT: [OR: 5.07 (2.44–10.53)]. Of 71 patients who died, 59.2% had an elevated PCT value on the last day, and of the 124 patients who survived, only 3.2% had an elevated PCT value on the last day (p < 0.001). On the last day of the ICU stay, the sequential organ failure assessment (SOFA) score of those who died was 9 (6–11) and 1 (0–2) points in survivors (p < 0.001). Of the 42 patients who died and in whom PCT was elevated on the last day, 71.4% were considered to have a mainly non-respiratory cause of death.

Conclusion

In patients admitted to the ICU by COVID-19 with respiratory involvement, numerous episodes of PCT elevation are observed, related to mortality. PCT was elevated on the last day in more than half of the patients who died. Serial assessment of procalcitonin in these patients is useful because it alerts to situations of high risk of death. This may be useful in the future to improve the treatment and prognosis of these patients.
Bacteroides fragilis participates in the therapeutic effect of methotrexate on arthritis through metabolite regulation
Authors: Zhou Bailing , Dong Chunyan , Zhao Binyan , Lin Ke , Tian Yaomei , Zhang Rui , Zhu Lixin , Xu Hueng , Yang Li
Published: December 2022

Methotrexate (MTX) is a preferred disease-modifying anti-rheumatic drug in the management of rheumatoid arthritis (RA). However, the toxicity and inefficiency of MTX limit its clinical application. Gut microbiota has been implicated in the side effects and efficacy of MTX. In this study, the analysis of the gut microbiota in RA patients revealed that the abundances of intestinal Bacteroides fragilis was reduced after MTX treatment. We observed that MTX has no obvious therapeutic effect in the absence of B. fragilis, while transplantation of B. fragilis restored the efficacy of MTX in antibiotics-pretreated collagen-induced arthritis (CIA) mice. In addition, B. fragilis gavage was accompanied by an increase in butyrate. Supplementation of butyrate restored the response to MTX in gut microbiota-deficient mice, to a similar level achieved by B. fragilis gavage. These results show that gut microbiota-regulated butyrate plays an essential role in the efficacy of MTX, which will provide new strategies to improve the effectiveness of methotrexate in RA treatment.
Functions and evolution of FAM111 serine proteases
Authors: Welter Allison L. , Machida Yuichi J.
Published: December 2022

Proteolysis plays fundamental and regulatory roles in diverse cellular processes. The serine protease FAM111A (FAM111 trypsin-like peptidase A) emerged recently as a protease involved in two seemingly distinct processes: DNA replication and antiviral defense. FAM111A localizes to nascent DNA and plays a role at the DNA replication fork. At the fork, FAM111A is hypothesized to promote DNA replication at DNA-protein crosslinks (DPCs) and protein obstacles. On the other hand, FAM111A has also been identified as a host restriction factor for mutants of SV40 and orthopoxviruses. FAM111A also has a paralog, FAM111B, a serine protease with unknown cellular functions. Furthermore, heterozygous missense mutations in FAM111A and FAM111B cause distinct genetic disorders. In this review, we discuss possible models that could explain how FAM111A can function as a protease in both DNA replication and antiviral defense. We also review the consequences of FAM111A and FAM111B mutations and explore possible mechanisms underlying the diseases. Additionally, we propose a possible explanation for what drove the evolution of FAM111 proteins and discuss why some species have two FAM111 proteases. Altogether, studies of FAM111 proteases in DNA repair, antiviral defense, and genetic diseases will help us elucidate their functions and the regulatory mechanisms.
Effectiveness of a multicomponent exercise training program for the management of delirium in hospitalized older adults using near-infrared spectroscopy as a biomarker of brain perfusion: Study protocol for a randomized controlled trial
Authors: Lozano-Vicario Lucía , Zambom-Ferraresi Fabiola , Zambom-Ferraresi Fabricio , de la Casa-Marín Antón , Ollo-Martínez Iranzu , Sáez de Asteasu Mikel L. , Cedeño-Veloz Bernardo Abel , Fernández-Irigoyen Joaquín , Santamaría Enrique , Romero-Ortuno Román , Izquierdo Mikel , Martínez-Velilla Nicolás
Published: December 2022

Delirium is an important cause of morbidity and mortality in older adults admitted to hospital. Multicomponent interventions targeting delirium risk factors, including physical exercise and mobilization, have been shown to reduce delirium incidence by 30–40% in acute care settings. However, little is known about its role in the evolution of delirium, once established. This study is a randomized clinical trial conducted in the Acute Geriatric Unit of Hospital Universitario de Navarra (Pamplona, Spain). Hospitalized patients with delirium who meet the inclusion criteria will be randomly assigned to the intervention or the control group. The intervention will consist of a multicomponent exercise training program, which will be composed of supervised progressive resistance and strength exercise over 3 consecutive days. Functional Near-Infrared Spectroscopy (NIRS) will be used for assessing cerebral and muscle tissue blood flow. The objective is to assess the effectiveness of this intervention in modifying the following primary outcomes: duration and severity of delirium and functional status. This study will contribute to determine the effectiveness of physical exercise in the management of delirium. It will be the first study to evaluate the impact of a multicomponent intervention based on physical exercise in the evolution of delirium.

Clinical trial registration

ClinicalTrials.gov. identifier: NCT05442892 (date of registration June 26, 2022).
A hybrid learning-based stochastic noise eliminating method with attention-Conv-LSTM network for low-cost MEMS gyroscope
Authors: Liu Yaohua , Cui Jinqiang , Liang Wei
Published: December 2022

Low-cost inertial measurement units (IMUs) based on microelectromechanical system (MEMS) have been widely used in self-localization for autonomous robots due to their small size and low power consumption. However, the low-cost MEMS IMUs often suffer from complex, non-linear, time-varying noise and errors. In order to improve the low-cost MEMS IMU gyroscope performance, a data-driven denoising method is proposed in this paper to reduce stochastic errors. Specifically, an attention-based learning architecture of convolutional neural network (CNN) and long short-term memory (LSTM) is employed to extract the local features and learn the temporal correlation from the MEMS IMU gyroscope raw signals. The attention mechanism is appropriately designed to distinguish the importance of the features at different times by automatically assigning different weights. Numerical real field, datasets and ablation experiments are performed to evaluate the effectiveness of the proposed algorithm. Compared to the raw gyroscope data, the experimental results demonstrate that the average errors of bias instability and angle random walk are reduced by 57.1 and 66.7%.
Volume electron microscopy reveals age-related circuit remodeling in the auditory brainstem
Authors: Chequer Charan Daniela , Hua Yunfeng , Wang Haoyu , Huang Wenqing , Wang Fangfang , Elgoyhen Ana Belén , Boergens Kevin M. , Di Guilmi Mariano N.
Published: December 2022

The medial nucleus of the trapezoid body (MNTB) is an integral component of the auditory brainstem circuitry involved in sound localization. The giant presynaptic nerve terminal with multiple active zones, the calyx of Held (CH), is a hallmark of this nucleus, which mediates fast and synchronized glutamatergic synaptic transmission. To delineate how these synaptic structures adapt to reduced auditory afferents due to aging, we acquired and reconstructed circuitry-level volumes of mouse MNTB at different ages (3 weeks, 6, 18, and 24 months) using serial block-face electron microscopy. We used C57BL/6J, the most widely inbred mouse strain used for transgenic lines, which displays a type of age-related hearing loss. We found that MNTB neurons reduce in density with age. Surprisingly we observed an average of approximately 10% of poly-innervated MNTB neurons along the mouse lifespan, with prevalence in the low frequency region. Moreover, a tonotopy-dependent heterogeneity in CH morphology was observed in young but not in older mice. In conclusion, our data support the notion that age-related hearing impairments can be in part a direct consequence of several structural alterations and circuit remodeling in the brainstem.
Ramsay Hunt syndrome and mandibular alveolar bone necrosis following herpes zoster: A case report and literature review
Authors: Yin Maojia , Huang Panchuan , Yang Sen , Wang Wuchao
Published: December 2022

Background

Reactivation of latent varicella-zoster virus (VZV) can induce herpes zoster (HZ). Ramsay Hunt syndrome (RHS) occurs through the reactivation and proliferation of VZV in the geniculate ganglion, which can lead to vesicular rash in the ear or oral mucosa, accompanied by neurological disorders.

Materials and methods

A 50-year-old man sought a remedy for pain in the right ear and face. Within 1 week, all his lower right teeth fell out, and in the following 3 months, his lower right mandibular alveolar bone gradually became necrotic. In the past 20 days, he experienced blister rash, hearing and taste loss, and slight facial paralysis.

Results

After ruling out tumors and other infectious diseases, he was diagnosed with trigeminal HZ and RHS.

Conclusion

Ramsay Hunt syndrome with tooth loss and alveolar osteonecrosis is rare. It requires long-term treatment of pain, and prevention and treatment of tooth loss and alveolar bone necrosis are difficult and warrant further study.
Effects of voluntary contraction on the soleus H-reflex of different amplitudes in healthy young adults and in the elderly
Authors: Batista-Ferreira Leandra , Rabelo Natielle Ferreira , Cruz Gabriel Menezes da , Costa Juliana Nunes de Almeida , Elias Leonardo Abdala , Mezzarane Rinaldo André
Published: December 2022

A number of H-reflex studies used a moderate steady voluntary contraction in an attempt to keep the motoneuron pool excitability relatively constant. However, it is not clear whether the voluntary muscle activation itself represents a confounding factor for the elderly, as a few ongoing mechanisms of reflex modulation might be compromised. Further, it is well-known that the amount of either inhibition or facilitation from a given conditioning depends on the size of the test H-reflex. The present study aimed at evaluating the effects of voluntary contraction over a wide range of reflex amplitudes. A significant reflex facilitation during an isometric voluntary contraction of the soleus muscle (15% of the maximal voluntary isometric contraction–MVC) was found for both young adults and the elderly (p < 0.05), regardless of their test reflex amplitudes (considering the ascending limb of the H-reflex recruitment curve–RC). No significant difference was detected in the level of reflex facilitation between groups for all the amplitude parameters extracted from the RC. Simulations with a computational model of the motoneuron pool driven by stationary descending commands yielded qualitatively similar amount of reflex facilitation, as compared to human experiments. Both the experimental and modeling results suggest that possible age-related differences in spinal cord mechanisms do not significantly influence the reflex modulation during a moderate voluntary muscle activation. Therefore, a background voluntary contraction of the ankle extensors (e.g., similar to the one necessary to maintain upright stance) can be used in experiments designed to compare the RCs of both populations. Finally, in an attempt to elucidate the controversy around changes in the direct motor response (M-wave) during contraction, the maximum M-wave (Mmax) was compared between groups and conditions. It was found that the Mmax significantly increases (p < 0.05) during contraction and decreases (p < 0.05) with age arguably due to muscle fiber shortening and motoneuron loss, respectively.
A case report: Dual-lead deep brain stimulation of the posterior subthalamic area and the thalamus was effective for Holmes tremor after unsuccessful focused ultrasound thalamotomy
Authors: Maesawa Satoshi , Torii Jun , Nakatsubo Daisuke , Noda Hiroshi , Mutoh Manabu , Ito Yoshiki , Ishizaki Tomotaka , Tsuboi Takashi , Suzuki Masashi , Tanei Takafumi , Katsuno Masahisa , Saito Ryuta
Published: December 2022

Holmes tremor is a symptomatic tremor that develops secondary to central nervous system disorders. Stereotactic neuromodulation is considered when the tremors are intractable. Targeting the ventral intermediate nucleus (Vim) is common; however, the outcome is often unsatisfactory, and the posterior subthalamic area (PSA) is expected as alternative target. In this study, we report the case of a patient with intractable Holmes tremor who underwent dual-lead deep brain stimulation (DBS) to stimulate multiple locations in the PSA and thalamus. The patient was a 77-year-old female who complained of severe tremor in her left upper extremity that developed one year after her right thalamic infarction. Vim-thalamotomy using focused ultrasound therapy (FUS) was initially performed but failed to control tremor. Subsequently, we performed DBS using two leads to stimulate four different structures. Accordingly, one lead was implanted with the aim of targeting the ventral oralis nucleus (Vo)/zona incerta (Zi), and the other with the aim of targeting the Vim/prelemniscal radiation (Raprl). Electrode stimulation revealed that Raprl and Zi had obvious effects. Postoperatively, the patient achieved good tremor control without any side effects, which was maintained for two years. Considering that she demonstrated resting, postural, and intention/action tremor, and Vim-thalamotomy by FUS was insufficient for tremor control, complicated pathogenesis was presumed in her symptoms including both the cerebellothalamic and the pallidothalamic pathways. Using the dual-lead DBS technique, we have more choices to adjust the stimulation at multiple sites, where different functional networks are connected. Intractable tremors, such as Holmes tremor, may have complicated pathology, therefore, modulating multiple pathological networks is necessary. We suggest that the dual-lead DBS (Vo/Raprl and Vim/Zi) presented here is safe, technically feasible, and possibly effective for the control of Holmes tremor.
Microenvironment changes in arteriovenous malformations after stereotactic radiation
Authors: Ung Timothy H. , Belanger Katherine , Hashmi Ayesha , Sekar Vashisht , Meola Antonio , Chang Steven D.
Published: December 2022

Cerebral arteriovenous malformations are dysplastic vascular tangles with aberrant vascular dynamics and can result significant morbidity and mortality. A myriad of challenges are encountered when treating these lesions and are largely based on nidal size, location, and prior hemorrhage. Currently, stereotactic radiosurgery is an accepted form of treatment for small to medium sized lesions and is especially useful in the treatment of lesions in non-surgically assessable eloquent areas of the brain. Despite overall high rates of nidal obliteration, there is relatively limited understand on the mechanisms that drive the inflammatory and obliterative pathways observed after treatment with stereotactic radiosurgery. This review provides an overview of arteriovenous malformations with respect to stereotactic radiosurgery and the current understanding of the mechanisms that lead to nidal obliteration.
Changes in socioeconomic inequalities in food consumption among Brazilian adults in a 10-years period
Authors: Louzada Maria Laura da Costa , Costa Janaína Calu , Costa Caroline dos Santos , Wendt Andrea , Azeredo Catarina Machado
Published: December 2022

Objective

To evaluate changes in socioeconomic inequalities in food consumption in Brazil over a 10-year period.

Methods

Data on 24-h recalls of adults (aged 20 years or more) from the 2008/9 (n = 26,327) and 2017/8 (n = 37,689). Brazilian Dietary Survey were analyzed. We used the Nova classification system to group food items and estimate the percentage of total energy from ultra-processed foods and plant-based natural or minimally processed foods. For sex and area of residence, we calculated the percentage points (p.p.) difference between the estimates for women and men, and rural and urban populations. Negative values indicate higher consumption among men or urban residents, positive values indicate higher consumption among women or rural residents, and zero indicates equality. For education and wealth levels we calculated the slope index of inequality (SII). The SII varies from −100 to 100, with positive values indicating higher consumption among more educated or wealthiest groups, negative values indicating higher consumption among less educated or poorest groups, and zero equality.

Results

Over the period, we observed a reduction in the percentage of total energy from plant-based natural/minimally processed foods from 13.0 to 12.2% and an increase in that of ultra-processed foods from 17.0 to 18.3%. The urban population and those in the wealthier and more educated groups presented higher consumption of ultra-processed foods and lower consumption of plant-based natural/minimally processed foods in both survey years. Over the 10-year period, there was an overall reduction of the socioeconomic inequalities, mainly explained by the greater increase in ultra-processed food consumption by the rural population and those from the poorest and less educated groups (difference for area −7.2 p.p. in 2008/9 and −5.9 p.p. in 2017/8; SII for education 17.7 p.p. in 2008/9 and 13.8 p.p. in 2017/8; SII for wealth 17.0 p.p. in 2008/9 and 11.2 p.p. in 2017/8).

Conclusion

Socioeconomic inequalities in food consumption decreased in Brazil, but it may lead to the overall deterioration of the dietary quality of the more vulnerable groups.
Effects of simulated in vitro gastrointestinal digestion on antioxidant activities and potential bioaccessibility of phenolic compounds from K. coccinea fruits
Authors: Luo Xiaochen , Tian Miaomiao , Cheng Yingying , Ji Caizhe , Hu Shende , Liu Hongnan , Lu Jun , Ren Jiali
Published: December 2022

The changes of bioactive substances in peels and sarcocarps of three different varieties of Kadsura coccinea (Dahong, Fenhong, and Zihei) were evaluated by an in vitro simulation model. In this study, three varieties of K. coccinea fruits were digested in vitro to compare the changes and differences in antioxidant activity (DPPH, ABTS, FRAP) and bioaccessibility. The results showed that before digestion the highest content of total phenolics (TPC) (2.265 ± 0.127 mg GAE/g DW) and the highest content of flavonoids contents (TFC) (10.379 ± 0.093 mg GAE/g DW) were found in Fenhong fruit. The highest release of TPC and TFC after simulated gastric digestion was observed in the Dahong and Zihei sarcocarp, which increased by 98.7 and 20%, respectively. During oral and intestinal digestion, the content of bioactive compounds showed a decreasing trend. The radical scavenging ability of 1, 1-diphenyl-2-picrylhydrazyl (DPPH), [2,2-azino-bis(3-ethylbenzothiazoline) (ABTS)] sulfonic acid free radical scavenging ability, and ferric ion reducing antioxidant power (FRAP) results showed that the antioxidant capacity of K. coccinea fruits increased most significantly (26.9∼181%) in gastric digestion stage and then decreased after intestinal digestion stage. The recoveries of TPC and TFC were all increased after whole simulated digestion, as well as their bioaccessibility in sarcocarps was higher than those in peels, especially for the bioaccessibility of TPC and TFC in Dahong reached 50.53 and 48.19%, respectively. These results indicated that the peel and sarcocarp of K. coccinea had good antioxidant activity, with high bioaccessibility of phenolics could be a promising antioxidant source for the food industry.
Transcriptome analysis of fat accumulation in 3T3-L1 adipocytes induced by chlorantraniliprole
Authors: Chen Ge , Wang Ge , Xu Weidong , Xiao Ying , Peng Ye
Published: December 2022

Introduction

Chlorantraniliprole is a diamide insecticide widely used in agriculture. Chlorantraniliprole has been previously found to increase the accumulation of triglycerides (fats) in adipocytes, however, the underlying molecular mechanism is unknown. The present study aimed to explore the molecular mechanisms of chlorantraniliprole-induced fat accumulation in 3T3-L1 adipocytes.

Methods

We measured the triglyceride content in chlorantraniliprole-treated 3T3-L1 adipocytes, and collected cell samples treated with chlorantraniliprole for 24 h and without any treatment for RNA sequencing.

Results

Compared with the control group, the content of triglyceride in the treatment group of chlorantraniliprole was significantly increased. The results of RNA sequencing (RNA-seq) showed that 284 differentially expressed genes (DEGs) were identified after treatment with chlorantraniliprole, involving 39 functional groups of gene ontology (GO) and 213 KEGG pathways. Moreover, these DEGs were significantly enriched in several key genes that regulate adipocyte differentiation and lipogenesis including Igf1, Rarres2, Nr1h3, and Psmb8.

Discussion

In general, these results suggest that chlorantraniliprole-induced lipogenesis is attributed to a whole-gene transcriptome response, which promotes further understanding of the potential mechanism of chlorantraniliprole-induced adipogenesis.
Comparing the diagnostic value of 18F-FDG PET/CT scan and bone marrow biopsy in newly diagnosed pediatric neuroblastoma and ganglioneuroblastoma
Authors: Fu Zheng , Ren Jiazhong , Zhou Jing , Shen Junkang
Published: December 2022

Objective

This study aims to compare the diagnostic value of 18F-fluorodeoxyglucose (18-FDG) positron emission tomography (PET)/computed tomography (CT) (18F-FDG PET/CT) scan and bone marrow biopsy (BMB) for evaluating bone marrow infiltration (BMI) in newly diagnosed pediatric neuroblastoma (NB) and ganglioneuroblastoma (GNB).

Methods

We retrospectively reviewed 51 patients with newly diagnosed NB and GNB between June 1, 2019 and May 31, 2022. Each patient had undergone 18F-FDG PET/CT and BMB within 1 week and received no treatment. Clinical data were collected and statistically analyzed, including age, sex, pathologic type, and laboratory parameters. 18F-FDG PET/CT and BMB revealed the result of bone lesions.

Results

A concordance analysis showed that, in this study population, 18F-FDG PET/CT and BMB were in moderate agreement (Cohen’s Kappa = 0.444; p = 0.001), with an absolute agreement consistency of 72.5% (37 of 51). The analysis of the receiver operating characteristic (ROC) curve determined that the areas under the ROC curve (AUCs) of SUVBM and SUV/HE-SUVmax were 0.971 (95% CI: 0.911–1.000; p < 0.001) and 0.917 (95% CI: 0.715–1.000; p < 0.001) to predict bone–bone marrow involvement (BMI), respectively.

Conclusion

18F-FDG PET/CT detects BMI with good diagnostic accuracy and can reduce unnecessary invasive inspections in newly diagnosed pediatric NB and GNB, especially patterns C and D. The analysis of the semi-quantitative uptake of 18F-FDG, including SUVBM and SUVBM/HE-SUVmax, enables an effective differentiation between patterns A and B.
Predicting incomplete cytoreduction in patients with advanced ovarian cancer
Authors: Egger Eva K. , Buchen Marie Antonia , Recker Florian , Stope Matthias B. , Strunk Holger , Mustea Alexander , Marinova Milka
Published: December 2022

Purpose

The most important prognostic factor for survival in ovarian cancer patients is complete cytoreduction. The preoperative prediction of suboptimal cytoreduction, considered as any residual disease at the end of surgery, could prevent futile surgery and morbidity. Here, we aimed to identify markers in the preoperative abdominal CT scans of an unselected cohort of patients with ovarian cancer that are predictive of incomplete cytoreduction.

Methods

This is a single-institution retrospective analysis of 105 epithelial ovarian cancer (EOC) patients treated with surgical cytoreduction between 2010 and 2020. Twenty-two variables on preoperative abdominal CT scans were compared to the intraoperative macroscopic findings by Fisher’s exact test. Parameters with a significant correlation between intraoperative findings and imaging were analyzed by multivariate binary logistic regression analysis regarding the surgical outcome of complete versus incomplete cytoreduction.

Results

Complete cytoreduction (CC), indicated by the absence of macroscopic residual disease, was achieved in 79 (75.2%) of 105 patients and 46 (63.9%) of 72 International Federation of Gynecology and Obstetrics (FIGO) stage III and IV patients. Twenty patients (19%) were incompletely cytoreduced due to miliary carcinomatosis of the small bowel, and six patients (5.7%) had various locations of residual disease. Thirteen variables showed a significant correlation between imaging and surgical findings. Large-volume ascites, absence of numerically increased small lymph nodes at the mesenteric root, and carcinomatosis of the transverse colon in FIGO stage III and IV patients decreased the rate of CC to 26.7% in the multivariate analysis.

Conclusion

Large-volume ascites, the absence of numerically increased small lymph nodes at the mesenteric root, and carcinomatosis of the transverse colon are markers in preoperative CT scans predicting a low chance for complete cytoreduction in unselected ovarian cancer patients in a real-world setting.
Interstitial brachytherapy combined with PARP inhibitors in the treatment of chemoresistant recurrent epithelial ovarian cancer: A case report
Authors: Bian Yuan , Guan Ping , Li Dan , Tan Longjing , Pang Haowen , Wen Qinglian , Chen Ping , Zhang Zhenhua
Published: December 2022

Background

Chemoresistance generally develops in patients with advanced epithelial ovarian cancer, and the prognosis is still very poor, with an expected survival time of less than one year. For this population of individuals, there is currently no standard protocol for clinical benefit.

Case presentation

We report a case of an elderly woman diagnosed with stage IIIC high-grade serous ovarian cancer (HGSOC). During a follow-up time of 6 years, the patient initially received multiple sequential courses of chemotherapy with platinum-based regimens and with no maintenance therapy. Similar to most patients with advanced HGSOC, she developed platinum resistance and experienced poor treatment results with a short progression-free survival (PFS). Ultimately, we gave the patient traditional non-platinum-based chemotherapy with bevacizumab and high-dose-rate interstitial brachytherapy followed by olaparib as a maintenance therapy. Up to now, the patient did response well to the treatment, and the PFS had exceeded 12 months.

Conclusion

High-dose-rate interstitial brachytherapy combination with PARP inhibitors may be an option for isolated chemoresistant recurrent epithelial ovarian cancer.
An autophagy-related long non-coding RNA prognostic model and related immune research for female breast cancer
Authors: Chen Jiafeng , Li Xinrong , Yan Shuixin , Li Jiadi , Zhou Yuxin , Wu Minhua , Ding Jinhua , Yang Jiahui , Yuan Yijie , Zhu Ye , Wu Weizhu
Published: December 2022

Introduction

Breast cancer (BRCA) is the most common malignancy among women worldwide. It was widely accepted that autophagy and the tumor immune microenvironment play an important role in the biological process of BRCA. Long non-coding RNAs (lncRNAs), as vital regulatory molecules, are involved in the occurrence and development of BRCA. The aim of this study was to assess the prognosis of BRCA by constructing an autophagy-related lncRNA (ARlncRNA) prognostic model and to provide individualized guidance for the treatment of BRCA.

Methods

The clinical data and transcriptome data of patients with BRCA were acquired from the Cancer Genome Atlas database (TCGA), and autophagy-related genes were obtained from the human autophagy database (HADb). ARlncRNAs were identified by conducting co‑expression analysis. Univariate and multivariate Cox regression analysis were performed to construct an ARlncRNA prognostic model. The prognostic model was evaluated by Kaplan–Meier survival analysis, plotting risk curve, Independent prognostic analysis, clinical correlation analysis and plotting ROC curves. Finally, the tumor immune microenvironment of the prognostic model was studied.

Results

10 ARlncRNAs(AC090912.1, LINC01871, AL358472.3, AL122010.1, SEMA3B-AS1, BAIAP2-DT, MAPT-AS1, DNAH10OS, AC015819.1, AC090198.1) were included in the model. Kaplan–Meier survival analysis of the prognostic model showed that the overall survival(OS) of the low-risk group was significantly better than that of the high-risk group (p< 0.001). Multivariate Cox regression analyses suggested that the prognostic model was an independent prognostic factor for BRCA (HR = 1.788, CI = 1.534–2.084, p < 0.001). ROCs of 1-, 3- and 5-year survival revealed that the AUC values of the prognostic model were all > 0.7, with values of 0.779, 0.746, and 0.731, respectively. In addition, Gene Set Enrichment Analysis (GSEA) suggested that several tumor-related pathways were enriched in the high-risk group, while several immune‑related pathways were enriched in the low-risk group. Patients in the low-risk group had higher immune scores and their immune cells and immune pathways were more active. Patients in the low-risk group had higher PD-1 and CTLA-4 levels and received more benefits from immune checkpoint inhibitors (ICIs) therapy.

Discussion

The ARlncRNA prognostic model showed good performance in predicting the prognosis of patients with BRCA and is of great significance to guide the individualized treatment of these patients.
Impact of type 2 diabetes mellitus on the prognosis of patients with hepatocellular carcinoma after laparoscopic liver resection: A multicenter retrospective study
Authors: Yang Shi-Ye , Yan Mao-Lin , Feng Jin-Kai , Duan Yun-Fei , Ye Jia-Zhou , Liu Zong-Han , Guo Lei , Xue Jie , Shi Jie , Lau Wan Yee , Cheng Shu-Qun , Guo Wei-Xing
Published: December 2022

Background

The effect of type 2 diabetes mellitus (T2DM) on survival of patients with hepatocellular carcinoma (HCC) after laparoscopic liver resection (LLR) has not been reported. This study aimed to explore the relationship between preoperative T2DM and long-term prognosis in HCC patients undergoing LLR.

Methods

HCC patients receiving LLR as initial treatment at four cancer centers were retrospectively included in this study. Clinicopathological factors associated with the prognosis of HCC patients were identified using univariate and multivariate Cox regression analysis. Recurrence-free survival (RFS) and overall survival (OS) curves between different cohorts of patients were generated using the Kaplan-Meier method and compared using the log-rank test.

Results

Of 402 HCC patients included, 62 patients had T2DM and 340 patients did not have T2DM. The OS and RFS of patients with T2DM were significantly worse compared to those without T2DM (P = 0.001 and 0.032, respectively). In Cox multivariate analysis, T2DM was identified as an independent risk factors for OS (HR = 2.31, 95% CI = 1.38–3.85, P = 0.001) and RFS (HR = 1.66, 95% CI = 1.08–2.55, P = 0.020).

Conclusions

Following laparoscopic surgical approach, HCC patients with T2DM had poorer prognoses than those without T2DM. Preoperative T2DM was an independent risk factor for HCC patients. Thus, patients with concurrent HCC and T2DM should be closely monitored after LLR.
Evaluation of drug-drug interaction between rilpivirine and rifapentine using PBPK modelling
Authors: Grañana-Castillo Sandra , Montanha Maiara Camotti , Bearon Rachel , Khoo Saye , Siccardi Marco
Published: December 2022

Tuberculosis remains the leading cause of death among people living with HIV. Rifapentine is increasingly used to treat active disease or prevent reactivation, in both cases given either as weekly or daily therapy. However, rifapentine is an inducer of CYP3A4, potentially interacting with antiretrovirals like rilpivirine. This in silico study investigates the drug-drug interaction (DDI) magnitude between daily oral rilpivirine 25 mg with either daily 600 mg or weekly 900 mg rifapentine. A physiologically based pharmacokinetic (PBPK) model was built in Simbiology (Matlab R2018a) to simulate the drug-drug interaction. The simulated PK parameters from the PBPK model were verified against reported clinical data for rilpivirine and rifapentine separately, daily rifapentine with midazolam, and weekly rifapentine with doravirine. The simulations of concomitant administration of rifapentine with rilpivirine at steady-state lead to a maximum decrease on AUC0-24 and Ctrough by 83% and 92% on day 5 for the daily rifapentine regimen and 68% and 92% for the weekly regimen on day 3. In the weekly regimen, prior to the following dose, AUC0-24 and Ctrough were still reduced by 47% and 53%. In both simulations, the induction effect ceased 2 weeks after the interruption of rifapentine’s treatment. A daily double dose of rilpivirine after initiating rifapentine 900 mg weekly was simulated but failed to compensate the drug-drug interaction. The drug-drug interaction model suggested a significant decrease on rilpivirine exposure which is unlikely to be corrected by dose increment, thus coadministration should be avoided.