bluuebunny/crossref_metadata_2025 huggingface dataset:
The First Case of Familiar Anti-leucine-rich Glioma-Inactivated1 Autoimmune Encephalitis: A Case Report and Literature Review
Authors: Ding Chuhan , Sun Qibing , Li Ran , Li Hanli , Wang Yu
Published: April 2022

Anti-leucine-rich glioma-inactivated1 (Anti-LGI1) autoimmune encephalitis is a rare autoimmune disease discovered in recent years. It is generally not defined as an inherited disease, though its etiology is still unclear. Herein, we report the first case of adult patients with familial anti-LGI1 encephalitis. Two biological siblings who worked in different regions were successively diagnosed with anti-LGI1 encephalitis in their middle age. The two patients had similar clinical manifestations including imaging results. Their clinical symptoms improved after immunotherapy and antiepileptic therapy. Given that some unique human leukocyte antigen (HLA) subtypes appear at a high frequency, multiple recent studies have revealed that anti-LGI1 encephalitis is associated with genetic susceptibility. One of the patients underwent HLA genotyping and whole-exome sequencing (WES), revealing the same HLA typing as in previous studies and two rare HLA variants. Therefore, further studies involving larger samples and more populations should be conducted to explore the possibility of other influencing factors such as environmental impacts.
Time-Frequency Representations of Brain Oscillations: Which One Is Better?
Authors: Bârzan Harald , Ichim Ana-Maria , Moca Vasile Vlad , Mureşan Raul Cristian
Published: April 2022

Brain oscillations are thought to subserve important functions by organizing the dynamical landscape of neural circuits. The expression of such oscillations in neural signals is usually evaluated using time-frequency representations (TFR), which resolve oscillatory processes in both time and frequency. While a vast number of methods exist to compute TFRs, there is often no objective criterion to decide which one is better. In feature-rich data, such as that recorded from the brain, sources of noise and unrelated processes abound and contaminate results. The impact of these distractor sources is especially problematic, such that TFRs that are more robust to contaminants are expected to provide more useful representations. In addition, the minutiae of the techniques themselves impart better or worse time and frequency resolutions, which also influence the usefulness of the TFRs. Here, we introduce a methodology to evaluate the “quality” of TFRs of neural signals by quantifying how much information they retain about the experimental condition during visual stimulation and recognition tasks, in mice and humans, respectively. We used machine learning to discriminate between various experimental conditions based on TFRs computed with different methods. We found that various methods provide more or less informative TFRs depending on the characteristics of the data. In general, however, more advanced techniques, such as the superlet transform, seem to provide better results for complex time-frequency landscapes, such as those extracted from electroencephalography signals. Finally, we introduce a method based on feature perturbation that is able to quantify how much time-frequency components contribute to the correct discrimination among experimental conditions. The methodology introduced in the present study may be extended to other analyses of neural data, enabling the discovery of data features that are modulated by the experimental manipulation.
Mathematical Abilities in School-Aged Children: A Structural Magnetic Resonance Imaging Analysis With Radiomics
Authors: Pina Violeta , Campello Víctor M. , Lekadir Karim , Seguí Santi , García-Santos Jose M. , Fuentes Luis J.
Published: April 2022

Structural magnetic resonance imaging (sMRI) studies have shown that children that differ in some mathematical abilities show differences in gray matter volume mainly in parietal and frontal regions that are involved in number processing, attentional control, and memory. In the present study, a structural neuroimaging analysis based on radiomics and machine learning models is presented with the aim of identifying the brain areas that better predict children’s performance in a variety of mathematical tests. A sample of 77 school-aged children from third to sixth grade were administered four mathematical tests: Math fluency, Calculation, Applied problems and Quantitative concepts as well as a structural brain imaging scan. By extracting radiomics related to the shape, intensity, and texture of specific brain areas, we observed that areas from the frontal, parietal, temporal, and occipital lobes, basal ganglia, and limbic system, were differentially related to children’s performance in the mathematical tests. sMRI-based analyses in the context of mathematical performance have been mainly focused on volumetric measures. However, the results for radiomics-based analysis showed that for these areas, texture features were the most important for the regression models, while volume accounted for less than 15% of the shape importance. These findings highlight the potential of radiomics for more in-depth analysis of medical images for the identification of brain areas related to mathematical abilities.
Assessment of Dietary and Lifestyle Responses After COVID-19 Vaccine Availability in Selected Arab Countries
Authors: Cheikh Ismail Leila , Osaili Tareq M. , Mohamad Maysm N. , Al Marzouqi Amina , Habib-Mourad Carla , Abu Jamous Dima O. , Ali Habiba I. , Al Sabbah Haleama , Hasan Hayder , Hassan Hussein , Stojanovska Lily , Hashim Mona , AlHaway Muna , Qasrawi Radwan , Shaker Obaid Reyad R. , Al Daour Rameez , Saleh Sheima T. , Al Dhaheri Ayesha S.
Published: April 2022

Background

The COVID-19 pandemic has been consistently associated with unhealthy lifestyle behaviors and dietary practices. This study aimed to assess the dietary and lifestyle behaviors of adults after COVID-19 vaccine availability and their attitude toward the vaccine in selected Arab countries.

Methods

A cross-sectional survey-based study was conducted between October 2021 and December 2021 using Google Forms (n = 2259). A multi-component questionnaire was used to collect socio-demographic characteristics, attitudes toward the COVID-19 vaccine, and behavioral, dietary, and lifestyle responses after easing the restriction. Participants were given a score based on the sum of positive dietary and lifestyle changes. The generalized linear models were used to identify the association between positive dietary and lifestyle changes score and sociodemographic characteristics.

Results

Weight gain during the pandemic was reported by 39.5% of the participants, 36.1% reported ever getting infected with the COVID-19 virus, and 85% received at least one dose of the vaccine. The key adverse reactions of the COVID-19 vaccine were fatigue, headache, and joint pain, and the main reason for vaccination was protection against infection. Most participants were concerned about the vaccine side effects (45.8%) and inadequate testing (50.7%). After easing of restriction, 54.3% of the participants reduced the frequency of disinfecting objects, and 58.3% joined social events. Most dietary and lifestyle behaviors remained unchanged after vaccine availability but there was an increase in the time spent behind the screen for work (50.1%) and entertainment (42.9%). The results of the multivariate regression analyses revealed that older participants (p = 0.001), those with higher education (p = 0.010), and those working from home (p = 0.040) were more likely to have higher positive dietary and lifestyle changes scores.

Conclusion

Although most participants were concerned about vaccine safety, low vaccine hesitancy rates were observed among the study sample. The availability of the COVID-19 vaccines resulted in loosening some of the safety social measures among Arab adults but the negative impact of the pandemic on dietary and lifestyle behaviors remained unaltered.
A Novel Hyaluronic Acid-Black Rice Anthocyanins Nanocomposite: Preparation, Characterization, and Its Xanthine Oxidase (XO)-Inhibiting Properties
Authors: Liu Ya , Peng Bangzhu
Published: April 2022

To promote the normal metabolism of human uric acid, high-performance hyaluronic acid-black rice anthocyanins (HAA) nanocomposite particles were successfully prepared by a simple crosslinking method as a novel xanthine oxidase inhibitor. Its structure and properties were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectrometry (FT-IR), and X-ray diffraction (XRD). SEM and TEM electron microscopy showed an obvious double-layer spherical structure with a particle size of ~298 nm. FT-IR and XRD analysis confirmed that black rice anthocyanins (ATC) had been successfully loaded into the hyaluronic acid (HA) structure. Nanocomposite particles (embedded form) showed higher stability in different environments than free black rice ATC (unembedded form). In addition, the preliminary study showed that the inhibition rate of the nanocomposite particles on Xanthine oxidase (XO) was increased by 40.08%. These results indicate that HAA nanocomposite particles can effectively improve black rice ATC's stability and activity, creating an ideal new material for inhibiting XO activity that has a broad application prospect.
Feasibility for Using Thermography Throughout an Exercise Program in Mastectomized Patients
Authors: das Virgens Aquino Maria Jane , dos Santos Leite Paula Michele , Lima Rodrigues Ingrid Kyelli , DeSantana Josimari Melo
Published: April 2022

Introduction

Breast cancer is the most common in the female population. Physical training is safe and indicated after surgical treatment for breast cancer. During exercise, body temperature changes due to tissue metabolic activity; in this sense, infrared thermography is used to map the thermal patterns of the body surface.

Objective

This study aimed to evaluate the feasibility of using thermography during a physical rehabilitation program in mastectomized patients by analyzing the change in body temperature caused by physical exercise in the breast region.

Methodology

This is a simple and covert clinical trial, in which the sample was constituted for convenience. The women were submitted to a supervised physical exercise protocol, three times a week, for 20 sessions. They were evaluated in the first, tenth, and twentieth sessions in relation to changes in body temperature in the breast region (infrared thermography).

Results

Twenty patients who underwent mastectomy surgery were recruited. No patient had drain infection, scar dehiscence, or lymphedema, and only one patient had seroma removed. The mean age was 50.45 ± 2.00 years, and the body mass index (BMI) was 28.95 ± 1.11 kg/m2. In the body thermography of the patients’ breast region, no significant difference was observed when comparing the thermograms of the plastron region of the patients in the first, tenth, and twentieth sessions (p = 0.201). However, when comparing the plastron region with the control breast, a reduction in temperature was observed in the operated region in the first (p = 0.012) and tenth sessions (p = 0.004).

Conclusion

Through this study, we can conclude that the use of infrared thermography is viable for the analysis of the body temperature of mastectomized patients during a supervised physical exercise protocol and, therefore, suggest that this instrument is increasingly used in the cancer public.
Extrachromosomal Circular DNA: A New Target in Cancer
Authors: Wu Pan , Liu Yuhang , Zhou Ruijia , Liu Lingyun , Zeng Hongli , Xiong Fang , Zhang Shanshan , Gong Zhaojian , Zhang Wenling , Guo Can , Wang Fuyan , Zhou Ming , Zu Xuyu , Zeng Zhaoyang , Li Yong , Li Guiyuan , Huang He , Xiong Wei
Published: April 2022

Genomic instability and amplification are intrinsically important traits determining the development and heterogeneity of tumors. The role of extrachromosomal circular DNA (eccDNA) in tumors has recently been highlighted. EccDNAs are unique genetic materials located off the chromosomal DNA. They have been detected in a variety of tumors. This review analyzes the mechanisms involved in the formation of eccDNAs and their genetic characteristics. In addition, the high-copy number and transcriptional levels of oncogenes located in eccDNA molecules contribute to the acceleration of tumor evolution and drug resistance and drive the development of genetic heterogeneity. Understanding the specific genomic forms of eccDNAs and characterizing their potential functions will provide new strategies for tumor therapy. Further research may yield new targets and molecular markers for the early diagnosis and treatment of human cancer.
Time Trends and Income Inequalities in Cancer Incidence and Cancer-Free Life Expectancy – a Cancer Site-Specific Analysis of German Health Insurance Data
Authors: Tetzlaff Fabian , Hoebel Jens , Epping Jelena , Geyer Siegfried , Golpon Heiko , Tetzlaff Juliane
Published: April 2022

Cancer represents a major burden of morbidity and mortality globally. So far, however, little is known on time trends and inequalities in the lengths of life spent free of any cancer. This study steps into this gap by analyzing time trends and income inequalities in cancer-free life expectancy (CFLE). For this retrospective cohort study, data of a large German health insurer were used (N = 3,405,673individuals, 2006–2018). Income inequalities were assessed using individual income (<60% of German average income (GAI) and ≥60% of GAI). Trends in incidence risks were analysed employing proportional-hazard regression models by splitting the observation time into three periods of 52 months. Trends in CFLE in total and for the most common site-specific cancers were calculated based on multiple decrement life tables. Incidence rates declined in almost all cancers and CFLE increased substantially over time (49.1 (95% CI 48.8-49.4) to 51.9 (95% CI 51.6-52.2) years for men, 53.1 (95% CI 52.7-53.5) to 55.4 (95% CI 55.1-55.8) years for women at age 20 for total cancer) and income groups. Considerable income inequalities in cancer risks were evident in both sexes, but were more pronounced in men (total cancer HR 0.86 (95% CI 0.85-0.87)), with higher-income individuals having lower risks. The highest income inequalities were found in colon (HR 0.90 (95% CI 0.87-0.93)), stomach (HR 0.78 (95% CI 0.73-0.84)), and lung cancer (HR 0.58 (95% CI 0.56-0.60)) in men. A reverse gradient was found for skin (HR 1.39 (95% CI 1.30-1.47) men; HR 1.27 (95% CI 1.20-1.35) women) and prostate cancer (HR 1.13 (95% CI 1.11-1.15)). The proportion of CFLE in total life expectancy declined for lung, skin and cervical cancer in women, indicating a relative shortening of lifetime spent cancer-free. In contrast, increasing proportions were found in breast and prostate cancer. To our knowledge, this is the first study analysing trends and income inequalities in CFLE. The life span free of cancer increased clearly over time. However, not all cancer types contributed equally to this positive development. Income inequalities persisted or tended to widen, which underlines the need for increased public health efforts in socioeconomically vulnerable groups.
Effect of the Nipple-Excising Breast-Conserving Therapy in Female Breast Cancer: A Competing Risk Analysis and Propensity Score Matching Analysis of Results Based on the SEER Database
Authors: Li Shouyu , Zhao Yuting , Yan Lutong , Yang Zejian , Qiu Pei , Chen Heyan , Zhou Yudong , Niu Ligang , Yan Yu , Zhang Wei , Zhang Huimin , He Jianjun , Zhou Can
Published: April 2022

Introduction

Due to the lack of randomized controlled trial, the effectiveness and oncological safety of nipple-excising breast-conserving therapy (NE-BCT) for female breast cancer (FBC) remains unclear. We aimed to explore and investigate the prognostic value of NE-BCT versus nipple-sparing breast-conserving therapy (NS-BCT) for patients with early FBC.

Methods

In this cohort study, data between NE-BCT and NS-BCT groups of 276,661 patients diagnosed with tumor–node–metastasis (TNM) stage 0–III FBC from 1998 to 2015 were retrieved from the Surveillance, Epidemiology, and End Results database. Propensity score matching analysis, Kaplan–Meier, X-tile, Cox proportional hazards model, and competing risk model were performed to evaluate the effectiveness and oncological safety for patients in NE-BCT and NS-BCT groups.

Results

A total of 1,731 (0.63%) patients received NE-BCT (NE-BCT group) and 274,930 (99.37%) patients received NS-BCT (NS-BCT group); 44,070 subjects died after a median follow-up time of 77 months (ranging from 1 to 227 months). In the propensity score matching (PSM) cohort, NE-BCT was found to be an adversely independent prognostic factor affecting overall survival (OS) [hazard ratio (HR), 1.24; 95% CI, 1.06–1.45, p=0.0078]. Subjects in NE-BCT group had similar breast-cancer-specific survival (BCSS) (HR, 1.15; 95%CI, 0.88–1.52, p=0.30) and worse other-causes-specific death (OCSD) (HR, 1.217; 95%CI, 1.002–1.478, p=0.048<0.05) in comparison with those in the NS-BCT group.

Conclusions

Our study demonstrated that the administration of NE-BCT is oncologically safe and reliable and can be widely recommended in clinics for women with non-metastatic breast cancer.
Chk1 Inhibition Hinders the Restoration of H3.1K56 and H3.3K56 Acetylation and Reprograms Gene Transcription After DNA Damage Repair
Authors: Ding Nan , Shao Zhiang , Yuan Fangyun , Qu Pei , Li Ping , Lu Dong , Wang Jufang , Zhu Qianzheng
Published: April 2022

H3K56 acetylation (H3K56Ac) was reported to play a critical role in chromatin assembly; thus, H3K56ac participates in the regulation of DNA replication, cell cycle progression, DNA repair, and transcriptional activation. To investigate the influence of DNA damage regulators on the acetylation of histone H3 and gene transcription, U2OS cells expressing SNAP-labeled H3.1 or SNAP-labeled H3.3 were treated with ATM, ATR, or a Chk1 inhibitor after ultraviolet (UV) radiation. The levels of H3.1K56ac, H3.3K56ac, and other H3 site-specific acetylation were checked at different time points until 24 h after UV radiation. The difference in gene transcription levels was also examined by mRNA sequencing. The results identified Chk1 as an important regulator of histone H3K56 acetylation in the restoration of both H3.1K56ac and H3.3K56ac. Moreover, compromising Chk1 activity via chemical inhibitors suppresses gene transcription after UV radiation. The study suggests a previously unknown role of Chk1 in regulating H3K56 and some other site-specific H3 acetylation and in reprograming gene transcription during DNA damage repair.
Progress in Radiotherapy for Cholangiocarcinoma
Authors: Wang Ningyu , Huang Ai , Kuang Bohua , Xiao Yu , Xiao Yong , Ma Hong
Published: April 2022

Cholangiocarcinoma (CCA) originates from the epithelium of the bile duct and is highly malignant with a poor prognosis. Radical resection is the only treatment option to completely cure primary CCA. Due to the insidious onset of CCA, most patients are already in an advanced stage at the time of the initial diagnosis and may lose the chance of radical surgery. Radiotherapy is an important method of local treatment, which plays a crucial role in preoperative neoadjuvant therapy, postoperative adjuvant therapy, and palliative treatment of locally advanced lesions. However, there is still no unified and clear recommendation on the timing, delineating the range of target area, and the radiotherapy dose for CCA. This article reviews recent clinical studies on CCA, including the timing of radiotherapy, delineation of the target area, and dose of radiotherapy. Further, we summarize large fraction radiotherapy (stereotactic body radiotherapy [SBRT]; proton therapy) in CCA and the development of immunotherapy and the use of targeted drugs combined with radiotherapy.
Contralateral Axillary Lymph Node Metastasis of Breast Cancer: Retrospective Analysis and Literature Review
Authors: Zhang Liang , Wang Xin zhao , Li Chao , Yu Qian , Liu Zhaoyun , Yu Zhi yong
Published: April 2022

Background

Contralateral axillary lymph node metastasis (CAM) is classified as distant metastasis in guidelines, but the prognosis is better than that of stage IV patients. It is controversial to classify CAM as a distant metastasis or a regional metastasis, and the optimal treatment strategy for CAM is unknown.

Patients and Methods

Breast cancer patients who were confirmed by pathology and treated at Shandong Cancer Hospital between January 2012 and July 2021 were included in our study. We retrospectively reviewed the medical records of the patients for their clinical features, pathological diagnosis, treatment strategy, and follow-up data. Survival analysis was calculated by Kaplan–Meier analysis, and patient matching was performed by case–control matching.

Results

A total of 60 patients were included, and there were 49 metachronous CAM cases and 11 synchronous CAM cases. The prognosis of isolated CAM patients was better than that of patients with other distant metastases in terms of CAM-OS and PFS with significant differences (median CAM-OS 71.0 vs. 30.0 months, P=0.022; median PFS 42.0 vs. 11.0 months, P=0.009) and OS without significant differences (median OS 126.0 vs. 79.0 months, P=0.111). The five-year survival rate of isolated CAM patients was 67.4%, and the five-year disease-free survival (DFS) rate was 52.9%. The prognosis of CAM patients was similar to that of N3M0 patients in terms of OS (mean OS 82.4 vs. 65.6 months, P=0.537) and DFS (mean PFS 54.5 vs. 52.6 months, P=0.888). Axillary lymph node dissection (ALND) or low-middle level ALND significantly improved the OS (mean OS 237.4 vs. 111.0 months, P=0.011), CAM-OS (mean CAM-OS 105.2 vs. 46.6 months, P = 0.002), and PFS (mean PFS 92.3 vs. 26.9 months, P = 0.001) of isolated CAM patients. Axillary radiotherapy improved PFS, CAM-OS, and OS but without significant differences (mean PFS 80.0 vs. 46.6 months, P = 0.345; mean CAM-OS 86.8 vs. 72.1 months, P = 0.338; mean OS 147.6 vs. 133.0 months, P = 0.426).

Conclusion

CAM should be diagnosed as local recurrence and treated with aggressive and curative rather than palliative strategies. Contralateral axillary surgery and radiotherapy are recommended for isolated CAM patients.
Axillary Lymph Node Dissection Can Be Omitted in Breast Cancer Patients With Mastectomy and False-Negative Frozen Section in Sentinel Lymph Node Biopsy
Authors: Si Jing , Guo Rong , Pan Huan , Lu Xiang , Guo Zhiqin , Han Chao , Xue Li , Xing Dan , Wu Wanxin , Chen Caiping
Published: April 2022

Background

The IBCSG 23-01 and AMAROS trials both reported that axillary lymph node dissection (ALND) did not change survival rates in breast cancer patients with positive nodes detected by sentinel lymph node biopsy (SLNB). The aim of this study was to determine whether breast cancer patients with mastectomy and false-negative frozen section (FS) in SLNB could forgo ALND.

Materials and Methods

This was a retrospective study of cN0 patients diagnosed with primary invasive breast cancer treated by mastectomy and SLNB at our institute between January 2010 and December 2014. Patients with false-negative FS in SLNB were separated by the following management of axillary lymph node dissection in the non-ALND group (nonprocess or axillary radiation only) and ALND group (with or without radiation).

Results

A total of 212 patients were included, 86 and 126 patients in the non-ALND and ALND groups, respectively. The positive rate of non-sentinel lymph nodes (SLNs) was 15.87% (20/126) in the ALND group. In multivariate analysis, we found that patients with larger tumor size (>2 cm) (OR, 1.989; p = 0.030) and multifocal lesions (OR, 3.542; p = 0.029) tended to receive ALND. The positivity of non-SLNs in the ALND group was associated with SLN macrometastasis (OR, 3.551; p = 0.043) and lymphovascular invasion (OR, 6.158; p = 0.003). Also, removing more SLNs (≥3) was related to negativity in non-SLNs (OR, 0.255; p = 0.016). After a median follow-up of 59.43 months, RFS and OS of the two groups were similar (p = 0.994 and 0.441). In subgroup analysis, we found that 97 patients who met the inclusive criteria of the IBCSG 23-01 trial had similar RFS and OS between the non-ALND and ALND groups (p = 0.856 and 0.298). The positive rate of non-SLNs was 9.62% (5/52). Also, in 174 patients who met the criteria of the AMAROS trial, RFS and OS in the non-ALND and ALND groups were similar (p = 0.930 and 0.616). The positive rate of non-SLNs was 18.27% (19/104).

Conclusion

ALND can be carefully omitted in selected breast cancer patients with mastectomy and false-negative FS in SLNB. SLNB is relatively sufficient in the IBCSG 23-01-eligible patients, and axillary radiation was an effective option in the AMAROS-eligible patients.
BIGDATA: A Protocol to Create and Extend a 25-Year Clinical Trial and Observational Data Asset to Address Key Knowledge Gaps in Otitis Media and Hearing Loss in Australian Aboriginal and Non-Aboriginal Children
Authors: Beissbarth Jemima , Smith-Vaughan Heidi C. , Cheng Allen C. , Morris Peter S. , Leach Amanda J.
Published: April 2022

Introduction

Otitis media (OM) is a common childhood illness, often resolving without intervention and acute and long-term complications are rare. However, Australian Aboriginal and Torres Strait Islander infants and children experience a high burden of OM and are at high risk of complications (tympanic membrane perforation and chronic infections). Bacterial OM is commonly associated with Streptococcus pneumoniae, non-typeable Haemophilus influenzae, and Moraxella catarrhalis. BIGDATA is a data asset combining over 25 years of microbiology and OM surveillance research from the Ear Health Research Program at Menzies School of Health Research (Northern Territory, Australia), including 11 randomized controlled trials, four cohort studies, eight surveys in over 30 remote communities (including data from Western Australia), and five surveys of urban childcare centers including Aboriginal and Torres Strait Islander and non-Indigenous children. Outcome measures include clinical examinations (focusing on OM), antibiotic prescriptions, pneumococcal vaccination, modifiable risk factors such as smoking and household crowding, and nasopharyngeal and ear discharge microbiology including antimicrobial resistance testing.

Methods and Analysis

The initial series of projects are planned to address the following key knowledge gaps: (i) otitis media prevalence and severity over pre pneumococcal conjugate vaccines (PCVs) and three eras of increasing PCV valency; (ii) impact of increasing valency PCVs on nasopharyngeal carriage dynamics of pneumococcal serotypes, and antimicrobial resistance; (iii) impact of increasing valency PCVs on nasopharyngeal carriage dynamics and antimicrobial resistance of other otopathogens; and (iv) serotype specific differences between children with acute OM and OM with effusion or without OM. These data will be utilized to identify research gaps, providing evidence-based prioritization for ongoing research.

Ethics and Dissemination

Data asset creation and priority analyses were approved by the Human Research Ethics Committee of Northern Territory Department of Health and Menzies School of Health Research (EC00153, 18-3281), the Child and Adolescent Health Service Human Research Ethics Committee and Western Australian Aboriginal Health Ethics Committee. Dissemination will be through peer review publication and conference presentations.
Major Grass Pollen Allergen Components and Cross-Reactive Carbohydrate Determinants in Mugwort-Sensitized Child Patients With Allergic Respiratory Disease in Western China
Authors: Liao Chenxi , Hou Xiangqing , Wu Liting , Luo Wenting , Zhang Hong , Sun Xin , Yu Yongmei , Zhang Xiaohua Douglas , Sun Baoqing
Published: April 2022

Mugwort is a common pollen allergen in western China, and this study aimed to investigate the patterns of molecular sensitization to major grass pollen allergens (mugwort, ragweed, bermuda grass, and timothy grass) and cross-reactive carbohydrate determinants (CCD) in children who were sensitized to mugwort in western China. Serum-specific IgE (sIgE) of major allergen components and CCD were detected among 121 mugwort SPT-positive children via the EUROBlotMaster system if the mugwort-sIgE was positive (MSP). A CCD inhibition test was further performed on the serum of patients with positive CCD-sIgE. Latent class analysis was used to identify the patterns of potential sensitization to major grass pollen allergens. Of a total of 100 patients with mugwort-sIgE positive (MSP), 52.0, 41.0, and 31.0% of them were positive to Art v 1, Art v 3, and Art v 4, respectively. An optimal model with three latent classes was determined using grass pollen allergens, components, and CCD. The sensitization patterns can be summarized as (1) MSP and cosensitized to ragweed, bermuda grass, and timothy grass (23.74%); (2) MSP and cosensitized to Art v 1 (54.08%); (3) MSP and cosensitized to Art v 4, Cyn d 12, Phl p 12 (22.18%). Additionally, CCD sIgE levels had a significant positive correlation with ragweed, bermuda grass, and timothy grass (P < 0.05), and CCD-Inhibitor can highly inhibit the above allergens sIgE. Our findings suggest that Art v 4 was the typical cross-reaction component of mugwort, which is cosensitized to Phl p 12 and Cyn d 12. A wide cross-reaction among ragweed, bermuda grass, and timothy grass caused by CCD was observed.
Exploiting Focused Ultrasound to Aid Intranasal Drug Delivery for Brain Therapy
Authors: Barbato Gaetano , Nisticò Robert , Triaca Viviana
Published: April 2022

Novel effective therapeutic strategies are needed to treat brain neurodegenerative diseases and to improve the quality of life of patients affected by Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Amyotrophic Lateral sclerosis (ALS) as well as other brain conditions. At present no effective treatment options are available; current therapeutics for neurodegenerative diseases (NDs) improve cognitive symptoms only transiently and in a minor number of patients. Further, most of the amyloid-based phase III clinical trials recently failed in AD, in spite of promising preclinical and phase I-II clinical trials, further pinpointing the need for a better knowledge of the early mechanisms of disease as well as of more effective routes of drug administration. In fact, beyond common pathological events and molecular substrates, each of these diseases preferentially affect defined subpopulations of neurons in specific neuronal circuits (selective neuronal vulnerability), leading to the typical age-related clinical profile. In this perspective, key to successful drug discovery is a robust and reproducible biological validation of potential new molecular targets together with a concomitant set up of protocols/tools for efficient and targeted brain delivery to a specific area of interest. Here we propose and discuss Focused UltraSound aided drug administration as a specific and novel technical approach to achieve optimal concentration of the drug at the target area of interest. We will focus on drug delivery to the brain through the nasal route coupled to FUS as a promising approach to achieve neuroprotection and rescue of cognitive decline in several NDs.
Single Nucleotide Variants as Proxies for HLA-A*31:01 in Native American Populations
Authors: Fernandes Vanessa Câmara , Pretti Marco Antônio M. , Tsuneto Luiza Tamie , Petzl-Erler Maria Luiza , Suarez-Kurtz Guilherme
Published: April 2022

Carbamazepine triggers dermatologic hypersensitivity reactions, associated with specific human leukocyte antigens (HLAs), especially HLA-B*15:02 and HLA-A*31:01. Previous efforts to identify single nucleotide variants (SNVs) with high predictive value as HLA proxies, revealed that rs1061235 and rs17179220 fulfill these requirements for HLA-A*31:01 in some but not all populations. Herein we explored the predictive performance of rs1061235 and rs17179220 as HLA-A*31:01 tags in populations of Native American ancestry, which are largely underrepresented in pharmacogenomic studies. The study cohorts comprised the overall Admixed American superpopulation of the 1000 Genomes Project (1 KG_AMR), a subcohort of individuals with predominant Native American ancestry (1 KG_NAT), the Native American population of the Human Genome Diversity Project (HGDP), plus Kaingang (KRC) and Guarani (GRC and GKW) adults from indigenous reservation areas in Brazil. The diversity of cohorts is reflected in the range of frequencies of HLA-A*31:01 (0.02–0.65), rs1061235 (0.03–0.13) and rs17179220 (0.12–0.66), as well as in the predictive performance of these SNVs as HLA-A*31:01 proxies. NPV (negative predictive value), the metric of primary interest for pharmacogenetic-informed carbamazepine prescription was maximal (NPV = 1.0) for both SNVs in 1 KG_AMR and 1 KG_NAT, for rs17179220, but not rs1061235 (NPV = 0.91) in HGDP, and for rs17179220 in GWK, but not GRC (NPV = 0.88) or KRC (NPV = 0.80). Collectively, the data support the notion that rs1061235 and rs17179220 are not optimal proxies for HLA-A*31:01 across populations of Native American ancestry.
Appropriateness of Antibiotic Prescriptions in Chinese Primary Health Care and the Impact of the COVID-19 Pandemic: A Typically Descriptive and Longitudinal Database Study in Yinchuan City
Authors: Zhao Houyu , Wang Shengfeng , Meng Ruogu , Liu Guozhen , Hu Jing , Zhang Huina , Yan Shaohua , Zhan Siyan
Published: April 2022

Background: The appropriateness of antibiotic prescriptions in primary care has not been well evaluated in China in recent years. Furthermore, the impact of coronavirus disease 2019 (COVID-19) on antibiotic prescriptions has not yet been investigated in China. We aimed to assess the appropriateness of antibiotic prescriptions and to evaluate the potential association between the COVID-19 pandemic and antibiotic prescriptions in primary care settings of Yinchuan, a city in China.

Methods: This study included 155 primary care institutions and 10,192,713 outpatient visits. Outpatient prescriptions were classified as appropriate, potentially appropriate, inappropriate, or not linked to any diagnosis for antibiotic use following a validated evaluation scheme. Interrupted time-series analyses were performed to assess the effects of the COVID-19 pandemic on antibiotic prescriptions in Chinese primary care facilities.

Results: During the study period, 1,287,678 (12.6%, 95% confidence interval [12.6–12.7]) of 10,192,713 outpatient visits in primary care resulted in antibiotic prescriptions. Among 1,287,678 antibiotic prescriptions, 653,335 (50.7% [50.6–50.9]) were inappropriate, 463,081 (36.0% [35.8–36.1]) were potentially appropriate, 171,056 (13.3% [13.1–13.5]) were appropriate, and 206 could not be linked to any diagnosis. Furthermore, patient, physician, and institutional factors were associated with inappropriate antibiotic prescriptions; there was an overall decreasing trend in the proportions of inappropriate antibiotic prescriptions, with the highest level in 2017 (67.1% [66.8–67.5]) and the lowest in 2021 (40.8% [40.3–41.3]). A total of 1,416,120 individual antibiotics were prescribed, of which 1,087,630 (76.8%) were broad-spectrum and 777,672 (54.9%) were classified in the World Health Organization’s “Watch” category. In addition, the COVID-19 pandemic was associated with changes of −2.8% (−4.4 to −1.3) in the level and 0.3% (0.2–0.3) in the monthly trend of antibiotic prescription rates, as well as changes of −5.9% (−10.2 to −1.5) in the level and 1.3% (1.0–1.6) in the monthly trend of the proportions of inappropriate antibiotic prescriptions.

Conclusion: More than half of the antibiotic prescriptions were inappropriate during the study period in primary care in Yinchuan. The COVID-19 pandemic may be associated with a decrease in the overall and inappropriate use of antibiotics in primary care settings in China.
Pharmaceutical Prospects of Curcuminoids for the Remedy of COVID-19: Truth or Myth
Authors: Fu Yaw-Syan , Ho Wan-Yi , Kang Ning , Tsai May-Jywan , Wu Jingyi , Huang Liyue , Weng Ching-Feng
Published: April 2022

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a positive-strand RNA virus, and has rapidly spread worldwide as a pandemic. The vaccines, repurposed drugs, and specific treatments have led to a surge of novel therapies and guidelines nowadays; however, the epidemic of COVID-19 is not yet fully combated and is still in a vital crisis. In repositioning drugs, natural products are gaining attention because of the large therapeutic window and potent antiviral, immunomodulatory, anti-inflammatory, and antioxidant properties. Of note, the predominant curcumoid extracted from turmeric (Curcuma longa L.) including phenolic curcumin influences multiple signaling pathways and has demonstrated to possess anti-inflammatory, antioxidant, antimicrobial, hypoglycemic, wound healing, chemopreventive, chemosensitizing, and radiosensitizing spectrums. In this review, all pieces of current information related to curcumin-used for the treatment and prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through in vitro, in vivo, and in silico studies, clinical trials, and new formulation designs are retrieved to re-evaluate the applications based on the pharmaceutical efficacy of clinical therapy and to provide deep insights into knowledge and strategy about the curcumin’s role as an immune booster, inflammatory modulator, and therapeutic agent against COVID-19. Moreover, this study will also afford a favorable application or approach with evidence based on the drug discovery and development, pharmacology, functional foods, and nutraceuticals for effectively fighting the COVID-19 pandemic.
MicroRNAs in Methamphetamine-Induced Neurotoxicity and Addiction
Authors: Deng Bi , Zhang Zhirui , Zhou Huixuan , Zhang Xinran , Niu Shuliang , Yan Xisheng , Yan Jie
Published: April 2022

Methamphetamine (METH) abuse remains a significant public health concern globally owing to its strong addictive properties. Prolonged abuse of the drug causes irreversible damage to the central nervous system. To date, no efficient pharmacological interventions are available, primarily due to the unclear mechanisms underlying METH action in the brain. Recently, microRNAs (miRNAs) have been identified to play critical roles in various cellular processes. The expression levels of some miRNAs are altered after METH administration, which may influence the transcription of target genes to regulate METH toxicity or addiction. This review summarizes the miRNAs in the context of METH use, discussing their role in the reward effect and neurotoxic sequelae. Better understanding of the molecular mechanisms involved in METH would be helpful for the development of new therapeutic strategies in reducing the harm of the drug.
Stochastic Resetting: A (Very) Brief Review
Authors: Gupta Shamik , Jayannavar Arun M.
Published: April 2022

Stochastic processes offer a fundamentally different paradigm of dynamics than deterministic processes that one is most familiar with, the most prominent example of the latter being Newton’s laws of motion. Here, we discuss in a pedagogical manner a simple and illustrative example of stochastic processes in the form of a particle undergoing standard Brownian diffusion, with the additional feature of the particle resetting repeatedly and at random times to its initial condition. Over the years, many different variants of this simple setting have been studied, including extensions to many-body interacting systems, all of which serve as illustrations of peculiar non-trivial and interesting static and dynamic features that characterize stochastic dynamics at long times. We will provide in this work a brief overview of this active and rapidly evolving field by considering the arguably simplest example of Brownian diffusion in one dimension. Along the way, we will learn about some of the general techniques that a physicist employs to study stochastic processes. Relevant to the special issue, we will discuss in detail how introducing resetting in an otherwise diffusive dynamics provides an explicit optimization of the time to locate a misplaced target through a special choice of the resetting protocol. We also discuss thermodynamics of resetting, and provide a bird’s eye view of some of the recent work in the field of resetting.
Role of Inflammation in the Pathogenesis of Atrial Fibrillation
Authors: Ihara Kensuke , Sasano Tetsuo
Published: April 2022

Atrial fibrillation (AF) is one of the most common arrhythmias encountered in clinical practice. AF is a major risk factor for stroke, which is associated with high mortality and great disability and causes a significant burden on society. With the development of catheter ablation, AF has become a treatable disease, but its therapeutic outcome has been limited so far. In persistent and long-standing AF, the expanded AF substrate is difficult to treat only by ablation, and a better understanding of the mechanism of AF substrate formation will lead to the development of a new therapeutic strategy for AF. Inflammation is known to play an important role in the substrate formation of AF. Inflammation causes and accelerates the electrical and structural remodeling of the atria via pro-inflammatory cytokines and other inflammatory molecules, and enhances the AF substrate, leading to the maintenance of AF and further inflammation, which forms a vicious spiral, so-called “AF begets AF”. Breaking this vicious cycle is expected to be a key therapeutic intervention in AF. In this review, we will discuss the relationship between AF and inflammation, the inflammatory molecules included in the AF-related inflammatory process, and finally the potential of those molecules as a therapeutic target.
Effect of Piriformospora indica-Induced Systemic Resistance and Basal Immunity Against Rhizoctonia cerealis and Fusarium graminearum in Wheat
Authors: Li Liang , Guo Nannan , Feng Yu , Duan Mengmeng , Li Chunhui
Published: April 2022

Wheat is among the top 10 and most widely grown crops in the world. However, wheat is often infected with many soil-borne diseases, including sharp eyespot, mainly caused by the necrotrophic fungus Rhizoctonia cerealis, and Fusarium head blight (FHB), caused by Fusarium graminearum, resulting in reduced production. Piriformospora indica is a root endophytic fungus with a wide range of host plants, which increases their growth and tolerance to biotic and abiotic stresses. In this study, the capability of P. indica to protect wheat seedlings against R. cerealis and F. graminearum was investigated at the physiological, biochemical, and molecular levels. Our results showed that P. indica significantly reduced the disease progress on wheat caused by F. graminearum and R. cerealis in vivo, but not showed any antagonistic effect on F. graminearum and R. cerealis in vitro. Additionally, P. indica can induce systemic resistance by elevating H2O2 content, antioxidase activity, relative water content (RWC), and membrane stability index (MSI) compared to the plants only inoculated with F. graminearum or R. cerealis and control. RNA-seq suggested that transcriptome changes caused by F. graminearum were more severe than those caused by R. cerealis. The number of differentially expressed genes (DEGs) in the transcriptome can be reduced by the addition of P. indica: for F. graminearum reduced by 18% and for R. cerealis reduced 58%. The DEGs related to disease resistance, such as WRKY and MAPK, were upregulated by P. indica colonization. The data further revealed that the transcriptional resistance to F. graminearum and R. cerealis mediated by P. indica is quite different.
Effects of Litter and Root Manipulations on Soil Bacterial and Fungal Community Structure and Function in a Schrenk’s Spruce (Picea schrenkiana) Forest
Authors: Zhu Haiqiang , Gong Lu , Luo Yan , Tang Junhu , Ding Zhaolong , Li Xiaochen
Published: April 2022

Soil microorganisms are the key driver of the geochemical cycle in forest ecosystem. Changes in litter and roots can affect soil microbial activities and nutrient cycling; however, the impact of this change on soil microbial community composition and function remain unclear. Here, we explored the effects of litter and root manipulations [control (CK), doubled litter input (DL), litter removal (NL), root exclusion (NR), and a combination of litter removal and root exclusion (NI)] on soil bacterial and fungal communities and functional groups during a 2-year field experiment, using illumina HiSeq sequencing coupled with the function prediction platform of PICRUSt and FUNGuild. Our results showed that litter and root removal decreased the diversity of soil bacteria and fungi (AEC, Shannon, and Chao1). The bacterial communities under different treatments were dominated by the phyla Proteobacteria, Acidobacteria, and Actinomycetes, and NL and NR reduced the relative abundance of the first two phyla. For the fungal communities, Basidiomycetes, Ascomycota, and Mortierellomycota were the dominant phyla. DL increased the relative abundance of Basidiomycetes, while NL and NR decreased the relative abundance of Ascomycota. We also found that litter and root manipulations altered the functional groups related to the metabolism of cofactors and vitamins, lipid metabolism, biosynthesis of other secondary metabolites, environmental adaptation, cell growth, and death. The functional groups including ectomycorrhizal, ectomycorrhizal-orchid mycorrhizal root-associated biotrophs and soil saprotrophs in the fungal community were also different among the different treatments. Soil organic carbon (SOC), pH, and soil water content are important factors driving changes in bacterial and fungal communities, respectively. Our results demonstrate that the changes in plant detritus altered the soil microbial community structure and function by affecting soil physicochemical factors, which provides important data for understanding the material cycle of forest ecosystems under global change.
Untargeted Metabolomics Sheds Light on the Diversity of Major Classes of Secondary Metabolites in the Malpighiaceae Botanical Family
Authors: Mannochio-Russo Helena , de Almeida Rafael F. , Nunes Wilhan D. G. , Bueno Paula C. P. , Caraballo-Rodríguez Andrés M. , Bauermeister Anelize , Dorrestein Pieter C. , Bolzani Vanderlan S.
Published: April 2022

Natural products produced by plants are one of the most investigated natural sources, which substantially contributed to the development of the natural products field. Even though these compounds are widely explored, the literature still lacks comprehensive investigations aiming to explore the evolution of secondary metabolites produced by plants, especially if classical methodologies are employed. The development of sensitive hyphenated techniques and computational tools for data processing has enabled the study of large datasets, being valuable assets for chemosystematic studies. Here, we describe a strategy for chemotaxonomic investigations using the Malpighiaceae botanical family as a model. Our workflow was based on MS/MS untargeted metabolomics, spectral searches, and recently described in silico classification tools, which were mapped into the latest molecular phylogeny accepted for this family. The metabolomic analysis revealed that different ionization modes and extraction protocols significantly impacted the chemical profiles, influencing the chemotaxonomic results. Spectral searches within public databases revealed several clades or genera-specific molecular families, being potential chemical markers for these taxa, while the in silico classification tools were able to expand the Malpighiaceae chemical space. The classes putatively annotated were used for ancestral character reconstructions, which recovered several classes of metabolites as homoplasies (i.e., non-exclusive) or synapomorphies (i.e., exclusive) for all sampled clades and genera. Our workflow combines several approaches to perform a comprehensive evolutionary chemical study. We expect it to be used on further chemotaxonomic investigations to expand chemical knowledge and reveal biological insights for compounds classes in different biological groups.