bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Vaccination Coverage Disparity and the Dynamics of the COVID-19 Delta and Omicron Waves in the US
Authors: Cuadros Diego F. , Moreno Claudia M. , Musuka Godfrey , Miller F. DeWolfe , Coule Phillip , MacKinnon Neil J.
Published: June 2022

Objective

The US recently suffered the fourth and most severe wave of the COVID-19 pandemic. This wave was driven by the SARS-CoV-2 Omicron, a highly transmissible variant that infected even vaccinated people. Vaccination coverage disparities have played an important role in shaping the epidemic dynamics. Analyzing the epidemiological impact of this uneven vaccination coverage is essential to understand local differences in the spread and outcomes of the Omicron wave. Therefore, the objective of this study was to quantify the impact of vaccination coverage disparity in the US in the dynamics of the COVID-19 pandemic during the third and fourth waves of the pandemic driven by the Delta and Omicron variants.

Methods

This cross-sectional study used COVID-19 cases, deaths, and vaccination coverage from 2,417 counties. The main outcomes of the study were new COVID-19 cases (incidence rate per 100,000 people) and new COVID-19 related deaths (mortality rate per 100,000 people) at county level and the main exposure variable was COVID-19 vaccination rate at county level. Geospatial and data visualization analyses were used to estimate the association between vaccination rate and COVID-19 incidence and mortality rates for the Delta and Omicron waves.

Results

During the Omicron wave, areas with high vaccination rates (>60%) experienced 1.4 (95% confidence interval [CI] 1.3–1.7) times higher COVID-19 incidence rate compared to areas with low vaccination rates (<40%). However, mortality rate was 1.6 (95% CI 1.5–1.7) higher in these low-vaccinated areas compared to areas with vaccination rates higher than 60%. As a result, areas with low vaccination rate had a 2.2 (95% CI 2.1–2.2) times higher case-fatality ratio. Geospatial clustering analysis showed a more defined spatial structure during the Delta wave with clusters with low vaccination rates and high incidence and mortality located in southern states.

Conclusions

Despite the emergence of new virus variants with differential transmission potential, the protective effect of vaccines keeps generating marked differences in the distribution of critical health outcomes, with low vaccinated areas having the largest COVID-19 related mortality during the Delta and Omicron waves in the US. Vulnerable communities residing in low vaccinated areas, which are mostly rural, are suffering the highest burden of the COVID-19 pandemic during the vaccination era.
Neutrophils Dominate the Cervical Immune Cell Population in Pregnancy and Their Transcriptome Correlates With the Microbial Vaginal Environment
Authors: Mohd Zaki Amirah , Hadingham Alicia , Flaviani Flavia , Haque Yasmin , Mi Jia Dai , Finucane Debbie , Dalla Valle Giorgia , Mason A. James , Saqi Mansoor , Gibbons Deena L. , Tribe Rachel M.
Published: June 2022

The cervicovaginal environment in pregnancy is proposed to influence risk of spontaneous preterm birth. The environment is shaped both by the resident microbiota and local inflammation driven by the host response (epithelia, immune cells and mucous). The contributions of the microbiota, metabolome and host defence peptides have been investigated, but less is known about the immune cell populations and how they may respond to the vaginal environment. Here we investigated the maternal immune cell populations at the cervicovaginal interface in early to mid-pregnancy (10–24 weeks of gestation, samples fromN = 46 women), we confirmed neutrophils as the predominant cell type and characterised associations between the cervical neutrophil transcriptome and the cervicovaginal metagenome (N = 9 women). In this exploratory study, the neutrophil cell proportion was affected by gestation at sampling but not by birth outcome or ethnicity. Following RNA sequencing (RNA-seq) of a subset of neutrophil enriched cells, principal component analysis of the transcriptome profiles indicated that cells from seven women clustered closely together these women had a less diverse cervicovaginal microbiota than the remaining three women. Expression of genes involved in neutrophil mediated immunity, activation, degranulation, and other immune functions correlated negatively withGardnerella vaginalisabundance and positively withLactobacillus inersabundance; microbes previously associated with birth outcome. The finding that neutrophils are the dominant immune cell type in the cervix during pregnancy and that the cervical neutrophil transcriptome of pregnant women may be modified in response to the microbial cervicovaginal environment, or vice versa, establishes the rationale for investigating associations between the innate immune response, cervical shortening and spontaneous preterm birth and the underlying mechanisms.
Dysbiosis of the Gut Microbiome Is Associated With Histopathology of Lung Cancer
Authors: Qin Xiong , Bi Ling , Yang Wenxiao , He Yiyun , Gu Yifeng , Yang Yong , Gong Yabin , Wang Yichao , Yan Xiaoxia , Xu Ling , Xiao Haibo , Jiao Lijing
Published: June 2022

Lung cancer is a malignancy with high incidence and mortality worldwide. Previous studies have shown that the gut microbiome plays an important role in the development and progression of metabolic cancers. However, data on the characteristics of the gut microbiome with different histopathology types of lung cancer remain scant. We collected stool samples from 28 healthy people (HP) and 61 lung cancer patients. The lung cancer patients were classified into three types according to their histopathology: Atypical Adenomatous Hyperplasia/Adenocarcinoma in situ (AAH/AIS), Minimally Invasive Adenocarcinoma (MIA), and Invasive Adenocarcinoma (IA). In addition, we employed 16S rRNA gene amplicon sequencing to analyze the characteristics of the gut microbiome in these patients. Our analysis revealed that the categorized cancer patients had unique intestinal flora characteristics, and had lower density and flora diversity compared to healthy people. Besides, the structure of the flora families and genera was more complex, and each group presented specific pathogenic microbiota. The patients in the AAH/AIS group and HP group had relatively similar flora structure compared with the IA and MIA groups. In addition, we identified several flora markers that showed significant changes with the development of lung cancer. Lung cancer gut microbiota showed a decrease in short-chain fatty acids (SCFAs) producing and anti-inflammatory bacteria compared to healthy people, while some pathogenic bacteria such as proinflammatory or tumor-promoting bacteria were more abundant in lung cancer patients. On the other hand, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Group (COG) annotation demonstrated suppression of some dominant metabolism-related pathways in lung cancer. These findings provide new biomarkers for the diagnosis and prognostic assessment of lung cancer and lay the basis for novel targeted therapeutic strategies for the prevention and treatment of lung cancer.

Clinical Trial Registration

[www.ClinicalTrials.gov], identifier [NCT03244605].
Identification of a New Antifungal Peptide W1 From a Marine Bacillus amyloliquefaciens Reveals Its Potential in Controlling Fungal Plant Diseases
Authors: Wen Qiao , Liu Ruizhe , Ouyang Zhenxiao , He Tianliang , Zhang Weini , Chen Xinhua
Published: June 2022

A bacterium, Bacillus amyloliquefaciens W0101, isolated from the Arctic Ocean, showed potent antifungal activity against several plant pathogenic fungi. An antifungal peptide W1, with a molecular weight of approximately 2.4 kDa, was purified from the culture supernatant of the strain W0101 using ion-exchange chromatography and high-performance liquid chromatography. By analysis of Liquid Chromatograph-Mass Spectrometer, the peptide W1 was identified as a new antifungal peptide derived from the fragment of preprotein translocase subunit YajC. Further analysis revealed that W1 could disrupt the hyphae and spores of Sclerotinia sclerotiorum and inhibit its growth. W1 suppressed S. sclerotiorum and Fusarium oxysporum at a minimum inhibitory concentration of 140 and 58 μg/ml, respectively. The antifungal activity of W1 remained stable at 20–80°C or pH 6–11, with reduced activity at 100–110°C and pH 4–5, and under three protease treatments. Additionally, W1 also had a certain extent of metal ion resistance. These results therefore suggest that the peptide W1 from marine B. amyloliquefaciens W0101 may represent a new antifungal peptide with potential application in the biocontrol of plant diseases.
Mini Review Therapeutic Strategies Targeting for Biofilm and Bone Infections
Authors: Wu Shizhou , Wu Binjie , Liu Yunjie , Deng Shu , Lei Lei , Zhang Hui
Published: June 2022

Bone infection results in a complex inflammatory response and bone destruction. A broad spectrum of bacterial species has been involved for jaw osteomyelitis, hematogenous osteomyelitis, vertebral osteomyelitis or diabetes mellitus, such as Staphylococcus aureus (S. aureus), coagulase-negative Staphylococcus species, and aerobic gram-negative bacilli. S. aureus is the major pathogenic bacterium for osteomyelitis, which results in a complex inflammatory response and bone destruction. Although various antibiotics have been applied for bone infection, the emergence of drug resistance and biofilm formation significantly decrease the effectiveness of those agents. In combination with gram-positive aerobes, gram-negative aerobes and anaerobes functionally equivalent pathogroups interact synergistically, developing as pathogenic biofilms and causing recurrent infections. The adhesion of biofilms to bone promotes bone destruction and protects bacteria from antimicrobial agent stress and host immune system infiltration. Moreover, bone is characterized by low permeability and reduced blood flow, further hindering the therapeutic effect for bone infections. To minimize systemic toxicity and enhance antibacterial effectiveness, therapeutic strategies targeting on biofilm and bone infection can serve as a promising modality. Herein, we focus on biofilm and bone infection eradication with targeting therapeutic strategies. We summarize recent targeting moieties on biofilm and bone infection with peptide-, nucleic acid-, bacteriophage-, CaP- and turnover homeostasis-based strategies. The antibacterial and antibiofilm mechanisms of those therapeutic strategies include increasing antibacterial agents’ accumulation by bone specific affinity, specific recognition of phage-bacteria, inhibition biofilm formation in transcription level. As chronic inflammation induced by infection can trigger osteoclast activation and inhibit osteoblast functioning, we additionally expand the potential applications of turnover homeostasis-based therapeutic strategies on biofilm or infection related immunity homeostasis for host-bacteria. Based on this review, we expect to provide useful insights of targeting therapeutic efficacy for biofilm and bone infection eradication.
Alterations of RNA Modification in Mouse Germ Cell-2 Spermatids Under Hypoxic Stress
Authors: He Tong , Guo Huanping , Xia Lin , Shen Xipeng , Huang Yun , Wu Xiao , Jiang Xuelin , Xu Yinying , Tan Yi , Zhang Yunfang , Tan Dongmei
Published: June 2022

Hypoxia is a known stress factor in mammals and has been shown to potentially impair male fertility, which manifests as spermatogenic dysfunction and decreased semen quality. Studies have shown that RNA modifications, the novel post-transcriptional regulators, are involved in spermatogenesis, and hypoxia-induced alterations in RNA modification in testes and sperm cells may be associated with impaired spermatogenesis in mice. However, the molecular mechanisms via which RNA modifications influence spermatogenesis under hypoxic stress conditions are unclear. In this study, we generated a mouse Germ Cell-2 spermatid (GC-2spd) hypoxia model by culturing cells in a 1% O2 incubator for 48 h or treating them with CoCl2 for 24 h. The hypoxia treatment significantly inhibited proliferation and induced apoptosis in GC-2spd cells. The RNA modification signatures of total RNAs (2 types) and differentially sized RNA fragments (7 types of approximately 80 nt-sized tRNAs; 9 types of 17–50 nt-sized sncRNAs) were altered, and tRNA stability was partially affected. Moreover, the expression profiles of sncRNAs, such as microRNAs, tsRNAs, rsRNAs, and ysRNAs, were significantly regulated, and this might be related to the alterations in RNA modification and subsequent transcriptomic changes. We comprehensively analyzed alterations in RNA modification signatures in total RNAs, tRNAs (approximately 80 nt), and small RNAs (17–50 nt) as well as the expression profiles of sncRNAs and transcriptomes in hypoxia-treated GC-2spd cells; our data suggested that RNA modifications may be involved in cellular responses under hypoxic stress conditions and could provide a basis for a better understanding of the molecular mechanisms underlying male infertility.
A Combination of Curcuma longa and Diazepam Attenuates Seizures and Subsequent Hippocampal Neurodegeneration
Authors: Nascimento Chirlene Pinheiro , Ferreira Luan Oliveira , Silva Alex Luiz Menezes da , Silva Ana Beatriz Nardelli da , Rodrigues Joao Cleiton Martins , Teixeira Leonan Lima , Azevedo Julianne Elba Cunha , Araujo Daniella Bastos de , Hamoy Akira Otake , Gonçalves Beatriz Holanda , Coelho Brenda Hosana De Oliveira , Lopes Dielly Catrina Favacho , Hamoy Moisés
Published: June 2022

Epilepsy is one of the most common neurological disorders, which occurs due to the instability in the inhibitory and excitatory synaptic transmissions in the brain. However, many patients develop resistance to the available drugs, which results in cell degeneration caused due to inadequate control of the seizures. Curcumin,Curcuma longa, is known to be effective for the treatment of organic disorders and may prevent seizures, reduce oxidative stress, and decrease brain damage. Given this, the present study evaluated the antiepileptic effects ofC. longain comparison with both the diazepam and the combined application of these two substances, in terms of their effects on the brain activity and the potential histopathological changes in the hippocampus. This study used male Wistar rats (age: 10–12 weeks; weight: 260 ± 20 g), which were pretreated for 4 days with either saline,C. longa, diazepam, orC. longa+ diazepam; and on the fifth day, pentylenetetrazol (PTZ) was administered to induce the seizure. In theC. longagroup, a significant increase was observed in the latency of the onset of seizure-related behavior. Surprisingly, however, the combined treatment resulted in the best control of the seizure-related behavior, with the greatest latency of the onset of spasms and isolated clonic seizures. This group also obtained the best results in the electroencephalographic trace and seizure control, with a reduction in the frequency and amplitude of the spike-waves. In the saline group, PTZ significantly reduced the number of cells present in the CA1 and CA3 regions of the hippocampus, while the combined treatment obtained the best results in terms of the preservation of the neuron-like cells. These findings indicate thatC. longamay contribute to the control of both seizures and the cell damage induced by PTZ, and that its association with diazepam may be a potentially effective option for the treatment of epilepsy in the future.
A Method to Combine Neurofilament Light Measurements From Blood Serum and Plasma in Clinical and Population-Based Studies
Authors: Rübsamen Nicole , Willemse Eline A. J. , Leppert David , Wiendl Heinz , Nauck Matthias , Karch André , Kuhle Jens , Berger Klaus
Published: June 2022

Introduction

Neurofilament light (NfL) can be detected in blood of healthy individuals and at elevated levels in those with different neurological diseases. We investigated if the choice of biological matrix can affect results when using NfL as biomarker in epidemiological studies.

Method

We obtained paired serum and EDTA-plasma samples of 299 individuals aged 37–67 years (BiDirect study) and serum samples of 373 individuals aged 65–83 years (MEMO study). In BiDirect, Passing–Bablok analyses were performed to assess proportional and systematic differences between biological matrices. Associations between serum or EDTA-plasma NfL and renal function (serum creatinine, serum cystatin C, glomerular filtration rate, and kidney disease) were investigated using linear or logistic regression, respectively. All regression coefficients were estimated (1) per one ng/L increase and (2) per one standard deviation increase (standardization using z-scores). In MEMO, regression coefficients were estimated (1) per one ng/L increase of serum or calculated EDTA-plasma NfL and (2) per one standard deviation increase providing a comparison to the results from BiDirect.

Results

We found proportional and systematic differences between paired NfL measurements in BiDirect, i.e., serum NfL [ng/L] = −0.33 [ng/L] + 1.11 × EDTA-plasma NfL [ng/L]. Linear regression coefficients for the associations between NfL and renal function did not vary between the different NfL measurements. In MEMO, one standard deviation increase in serum NfL was associated with greater changes in the outcomes than in BiDirect.

Conclusion

Although there are differences between serum and EDTA-plasma NfL, results can be used interchangeably if standardized values are used.
Left Hemisphere Bias of NIH Stroke Scale Is Most Severe for Middle Cerebral Artery Strokes
Authors: Vitti Emilia , Kim Ganghyun , Stockbridge Melissa D. , Hillis Argye E. , Faria Andreia V.
Published: June 2022

NIHSS score is higher for left vs. right hemisphere strokes of equal volumes. However, differences in each vascular territory have not been evaluated yet. We hypothesized that left vs. right differences are driven by the middle cerebral artery (MCA) territory, and there is no difference between hemispheres for other vascular territories. This study is based on data from 802 patients with evidence of acute ischemic stroke in one major arterial territory (MCA, n = 437; PCA, n = 209; ACA, n = 21; vertebrobasilar, n = 46). We examined differences in patients with left or right strokes regarding to lesion volume, NIHSS, and other covariates (age, sex, race). We used linear models to test the effects of these covariates on NIHSS. We looked at the whole sample as well as in the sample stratified by NIHSS (≤5 or >5) and by lesion location (MCA or PCA). Patients with left MCA strokes had significantly higher NIHSS than those with right strokes. Only patients with MCA strokes showed NIHSS score affected by the hemisphere when controlling for stroke volume and patient's age. This difference was driven by the more severe strokes (NIHSS>5). It is important to consider this systematic bias in the NIHSS when using the score for inclusion criteria for treatment or trials. Patients with right MCA stroke may be under-treated and left with disabling deficits that are not captured by the NIHSS.
Effects of an Oral Contraceptive on Dynamic Brain States and Network Modularity in a Serial Single-Subject Study
Authors: Jensen Kristian Høj Reveles , McCulloch Drummond E-Wen , Olsen Anders Stevnhoved , Bruzzone Silvia Elisabetta Portis , Larsen Søren Vinther , Fisher Patrick MacDonald , Frokjaer Vibe Gedsoe
Published: June 2022

Hormonal contraceptive drugs are used by adolescent and adult women worldwide. Increasing evidence from human neuroimaging research indicates that oral contraceptives can alter regional functional brain connectivity and brain chemistry. However, questions remain regarding static whole-brain and dynamic network-wise functional connectivity changes. A healthy woman (23 years old) was scanned every day over 30 consecutive days during a naturally occurring menstrual cycle and again a year later while using a combined hormonal contraceptive. Here we calculated graph theory-derived, whole-brain, network-level measures (modularity and system segregation) and global brain connectivity (characteristic path length) as well as dynamic functional brain connectivity using Leading Eigenvector Dynamic Analysis and diametrical clustering. These metrics were calculated for each scan session during the serial sampling periods to compare metrics between the subject’s natural and contraceptive cycles. Modularity, system segregation, and characteristic path length were statistically significantly higher across the natural compared to contraceptive cycle scans. We also observed a shift in the prevalence of two discrete brain states when using the contraceptive. Our results suggest a more network-structured brain connectivity architecture during the natural cycle, whereas oral contraceptive use is associated with a generally increased connectivity structure evidenced by lower characteristic path length. The results of this repeated, single-subject analysis allude to the possible effects of oral contraceptives on brain-wide connectivity, which should be evaluated in a cohort to resolve the extent to which these effects generalize across the population and the possible impact of a year-long period between conditions.
BrainPhys Neuronal Media Support Physiological Function of Mitochondria in Mouse Primary Neuronal Cultures
Authors: Faria-Pereira Andreia , Temido-Ferreira Mariana , Morais Vanessa A.
Published: June 2022

In vitro neuronal cultures are extensively used in the field of neurosciences as they represent an accessible experimental tool for neuronal genetic manipulation, time-lapse imaging, and drug screening. Optimizing the cultivation of rodent primary neuronal cultures led to the development of defined media that support the growth and maintenance of different neuronal types. Recently, a new neuronal medium, BrainPhys (BP), was formulated envisioning the mimicry of brain physiological conditions and suitability for cultured human iPSC-derived neurons and rat primary neurons. However, its advantages in mouse primary neuronal cultures and its effects in neuronal bioenergetics are yet to be demonstrated. In this study, we validated the beneficial use of BP in mouse primary neuronal cultures based on the observation that neuronal cultures in BP media showed enhanced ATP levels, which increased throughout neuronal maturation, a finding that correlates with higher mitochondrial activity and ATP production at later maturation stages, as well as an increased glycolysis response on mitochondrial inhibition and increased mitochondrial fuel flexibility. Taken together, our data demonstrate that BP medium promotes mitochondrial activity along with neuronal maturation of in vitro cultures.
Intestinal Microbiota Regulate Certain Meat Quality Parameters in Chicken
Authors: Lei Jiaqi , Dong Yuanyang , Hou Qihang , He Yang , Lai Yujiao , Liao Chaoyong , Kawamura Yoichiro , Li Junyou , Zhang Bingkun
Published: June 2022

Growing evidence of intestinal microbiota-muscle axis provides a possibility to improve meat quality of broilers through regulating intestinal microbiota. Water-holding capacity is a crucial factor to evaluate the meat quality. High quality of water-holding capacity is usually described as a low drip-losing rate. This study aimed to explore the relationship between intestinal microbiota and water-holding capacity of muscle in broilers. According to our results, two native breeds of broilers (the Arbor Acres broilers and the Beijing-You broilers) exhibited remarkable differences in microbiota composition. However, the regular of gut bacteria compositions gradually became similar when the two breeds of broiler were raised in a same feeding environment. Therefore, this similar regular of intestinal microbiota induced similar water-holding capacity of the muscle from the two breeds. In subsequent fecal microbiota transplantation (FMT) experiments, the intestinal microbiota community of the Arbor Acres broilers was remodeling by oral gavage of bacterial suspension that was derived from the Beijing-You broilers. Then, not only body weight and abdominal fat rate were increased, but also drip loss of muscle was decreased in the Arbor Acres broilers. Additionally, muscle fiber diameter of biceps femoris muscle and expression of MyoD1 were notably enlarged. Muscle fiber diameter and related genes were deemed as important elements for water-holding capacity of muscle. Simultaneously, we screened typical intestinal bacteria in both the two native breeds of broilers by 16S rDNA sequencing. Lachnoclostridium was the only bacteria genus associated with drip-losing rate, meat fiber diameter, body weight, and abdominal fat rate.

Importance

Higher body weight and superior meat quality in livestock imply an adequate source of protein and substantial commercial value. Regulating the intestinal microbiota of broilers is a promising approach to optimize commercial phenotypes. Our results indicate that the intestinal microbiota profile could be reconstructed by external factors, leading to advantageous changes in muscle characteristics. The cecum microbiota of native broilers have the ability to improve certain meat quality and production performance. The population of Lachnoclostridium spp. could be used to regulate body weight and drip-losing rate in broilers, but more study is needed.
Anticancer Effect of Spices Used in Mediterranean Diet: Preventive and Therapeutic Potentials
Authors: Talib Wamidh H. , AlHur Mallak J. , Al.Naimat Sumaiah , Ahmad Rawand E. , Al-Yasari Arkan Hadi , Al-Dalaeen Anfal , Thiab Samar , Mahmod Asma Ismail
Published: June 2022

Cancer is one of the leading causes of death worldwide, with almost 10 million cancer-related deaths worldwide in 2020, so any investigation to prevent or cure this disease is very important. Spices have been studied widely in several countries to treat different diseases. However, studies that summarize the potential anticancer effect of spices used in Mediterranean diet are very limited. This review highlighted chemo-therapeutic and chemo-preventive effect of ginger, pepper, rosemary, turmeric, black cumin and clove. Moreover, the mechanisms of action for each one of them were figured out such as anti-angiogenesis, antioxidant, altering signaling pathways, induction of cell apoptosis, and cell cycle arrest, for several types of cancer. The most widely used spice in Mediterranean diet is black pepper (Piper nigrum L). Ginger and black cumin have the highest anticancer activity by targeting multiple cancer hallmarks. Apoptosis induction is the most common pathway activated by different spices in Mediterranean diet to inhibit cancer. Studies discussed in this review may help researchers to design and test new anticancer diets enriched with selected spices that have high activities.
Sex-Based Differences in Factors Associated With Sugar-Sweetened Beverage Consumption Among Korean High School Students
Authors: Ra Jin Suk , Park Moonkyoung
Published: June 2022

This study aimed to identify sex-based differences in the individual and environmental factors associated with sugar-sweetened beverage (SSB) consumption among Korean high school students. Secondary data were obtained from the 15th (2019) Korea Youth Risk Behavior Web-based Survey. In this study, we analyzed data from 13,066 high school students (5,874 boys and 7,192 girls) who answered questions regarding SSB consumption and individual and environmental factors. Complex sampling analysis (descriptive statistics and logistic regression analysis) was conducted using the SPSS Statistics 26.0 software. Most adolescents (97% boys and 95.2% girls) reported having consumed SSBs in the last seven days. Individual factors, such as increased stress, sleep dissatisfaction, and fast-food intake (more than thrice a week) were positively associated with SSB consumption among adolescent boys and girls. Environmental factors like high education levels (above college) of mothers were negatively associated with SSB consumption among both boys and girls. Furthermore, current alcohol consumption, smoking, low vegetable intake (less than thrice a week) in boys, and more than 2 h a day of screen-based sedentary behavior in girls were positively associated with SSB consumption. According to the results, individual factors associated with SSB consumption varied according to the sex of adolescents. Thus, sex differences in factors associated with SSB consumption in adolescents should be considered as basic knowledge for developing strategies for reducing SSB consumption.
National Effort to Re-Establish Heavy Ion Cancer Therapy in the United States
Authors: Pompos Arnold , Foote Robert L. , Koong Albert C. , Le Quynh Thu , Mohan Radhe , Paganetti Harald , Choy Hak
Published: June 2022

In this review, we attempt to make a case for the establishment of a limited number of heavy ion cancer research and treatment facilities in the United States. Based on the basic physics and biology research, conducted largely in Japan and Germany, and early phase clinical trials involving a relatively small number of patients, we believe that heavy ions have a considerably greater potential to enhance the therapeutic ratio for many cancer types compared to conventional X-ray and proton radiotherapy. Moreover, with ongoing technological developments and with research in physical, biological, immunological, and clinical aspects, it is quite plausible that cost effectiveness of radiotherapy with heavier ions can be substantially improved.
Synergistic Therapeutic Effects of Low Dose Decitabine and NY-ESO-1 Specific TCR-T Cells for the Colorectal Cancer With Microsatellite Stability
Authors: Yu Ganjun , Wang Wenying , He Xiaobo , Xu Jia , Xu Rongrong , Wan Tao , Wu Yanfeng
Published: June 2022

Patients of colorectal cancer (CRC) with microsatellite stability (MSS) show poor clinical response and little beneficial result from the immune-checkpoint inhibitors, due to the ‘cold’ tumor microenvironment. Meanwhile, decitabine can drive the ‘cold’ microenvironment towards ‘hot’ in multiple ways, such as upregulating the tumor associated antigen (TAA) and human leukocyte antigen (HLA) molecular. NY-ESO-1, one of the most important TAAs, can be observably induced in tumors by low dose decitabine, and present itself as ideal targets for antigen specific T cell receptor engineered T (TCR-T) cells. We innovatively used a synergistic tactic, combining decitabine and NY-ESO-1 specific TCR-T cells, for fighting the MSS CRC. Firstly, we confirmed the lysing effect of the NY-ESO-1 TCR-T cells on the NY-ESO-1+ and HLA-A2+ cells in vitro and in vivo. In A375 tumor-bearing mice, the results showed that NY-ESO-1 TCR-T cell therapy could inhibit A375 tumor growth and prolonged the survival time. Furthermore, the synergistic effect of decitabine and NY-ESO-1 TCR-T cells was shown to induce an even higher percentage of tumor cells being lysed in vitro than other control groups, and more potent tumor inhibition and longer survival time were observed in vivo. The innovative synergistic therapeutic strategy of decitabine and TCR-T cells for the CRC with MSS may be also effective in the treatment of other epithelial malignancies. Decitabine may likewise be adopted in combination with other cellular immunotherapies.
Long Non-Coding RNA-TMPO-AS1 as ceRNA Binding to let-7c-5p Upregulates STRIP2 Expression and Predicts Poor Prognosis in Lung Adenocarcinoma
Authors: Wang Juan , Yuan Yixiao , Tang Lin , Zhai Haoqing , Zhang Dahang , Duan Lincan , Jiang Xiulin , Li Chen
Published: June 2022

Background

Striatin-interacting protein 2 (STRIP2), also called Fam40b, has been reported to regulate tumor cell growth. But the role of STRIP2 in lung adenocarcinoma (LUAD) has not been discovered clearly. Thus, the aim of our study is to explore the function and underlying mechanism of STRIP2 in LUAD.

Methods

Expression of STRIP2 was determined using the Cancer Genome Atlas (TCGA), GTEx, Ualcan, and the Human Protein Altas databases. The Correlation of STRIP2 and survival was detected by PrognoScan and Kaplan–Meier plotter databases. Besides, the correlation between STRIP2 expression and tumor immune infiltration as well as immune checkpoints were analyzed by the ssGSEA method. The biological function of STRIP2 and its co-expression genes was determined by gene ontology (GO) and Genes and Genomes (KEGG), respectively. Finally, the expression level and biological function of STRIP2 in LUAD were determined by qPCR, CCK8, transwell, and wound healing assays.

Results

This manuscript revealed a significantly increased expression of mRNA and protein of STRIP2 in lung adenocarcinoma compared with the adjacent normal tissues. GEO and Kaplan–Meier plotter databases showed higher STRIP2 expression levels were correlated with poor prognosis survival of LUAD. Moreover, Cox regression analysis suggested that a higher STRIP2 level served as an independent risk factor in predicting deteriorative overall survival (OS) for LUAD patients. SsGSEA results showed STRIP2 expression level was positively correlated with infiltrating levels of Th2 cells in LUAD. Lastly, GO analysis indicated the biological processes were enriched in nuclear division and positive regulation of the cell cycle. KEGG signaling pathway analysis showed STRIP2 was correlated with the MAPK signaling pathway and the TNF signaling pathway. The GSEA database showed that STRIP2 was positively associated with the epithelial–mesenchymal transition, cell cycle, and TNF signaling pathway. The QRT-PCR assay showed that STRIP2 was upregulated in LUAD cell lines. Cell proliferation and migration were inhibited in LUAD by knockdown of STRIP2. Moreover, we confirmed that the TMPO-AS1/let-7c-5p/STRIP2 network regulates STRIP2 overexpression in LUAD and is associated with poor prognosis.

Conclusion

Our findings indicated that STRIP2 acted as a crucial oncogene in LUAD and was correlated with unfavorable survival and tumor infiltration inflation.
Reliability of Cell-Free DNA and Targeted NGS in Predicting Chromosomal Abnormalities of Patients With Myeloid Neoplasms
Authors: Ip Andrew , Della Pia Alexandra , Kim Gee Youn (Geeny) , Lofters Jason , Behrmann James , Patel Dylon , Kats Simone , Estella Jeffrey Justin , De Dios Ivan , Ma Wanlong , Pecora Andrew L. , Goy Andre H. , Koprivnikar Jamie , McCloskey James K. , Albitar Maher
Published: June 2022

Introduction

Cytogenetic analysis is important for stratifying patients with various neoplasms. We explored the use of targeted next generation sequencing (NGS) in detecting chromosomal structural abnormalities or copy number variations (CNVs) in patients with myeloid neoplasms.

Methods

Plasma cell-free DNA (cfDNA) from 2821 myeloid or lymphoid neoplasm patients were collected. cfDNA was sequenced using a 275 gene panel. CNVkit software was used for analyzing and visualizing CNVs. Cytogenetic data from corresponding bone marrow (BM) samples was available on 89 myeloid samples.

Results

Of the 2821 samples, 1539 (54.5%) showed evidence of mutations consistent with the presence of neoplastic clones in circulation. Of these 1539 samples, 906 (59%) showed abnormalities associated with myeloid neoplasms and 633 (41%) with lymphoid neoplasms. Chromosomal structural abnormalities in cfDNA were detected in 146 (16%) myeloid samples and 76 (12%) lymphoid samples. Upon comparison of the myeloid samples with 89 BM patients, NGS testing was able to reliably detect chromosomal gain or loss, except for fusion abnormalities. When cytogenetic abnormalities were classified according to prognostic classes, there was a complete (100%) concordance between cfDNA NGS data and cytogenetic data.

Conclusions

This data shows that liquid biopsy using targeted NGS is reliable in detecting chromosomal structural abnormalities in myeloid neoplasms. In specific circumstances, targeted NGS may be reliable and efficient to provide adequate information without the need for BM biopsy considering broad mutation profiling can be obtained through adequate sequencing within the same test. Overall, this study supports the use of liquid biopsy for early diagnosis and monitoring of patients with myeloid neoplasms.
Epigenetic Mechanisms Influencing Therapeutic Response in Breast Cancer
Authors: Arruabarrena-Aristorena Amaia , Toska Eneda
Published: June 2022

The majority of breast cancers are estrogen receptor (ER)+ and agents targeting the ER signaling pathway have markedly increased survival for women with breast cancer for decades. However, therapeutic resistance eventually emerges, especially in the metastatic setting. In the past decade disrupted epigenetic regulatory processes have emerged as major contributors to carcinogenesis in many cancer types. Aberrations in chromatin modifiers and transcription factors have also been recognized as mediators of breast cancer development and therapeutic outcome, and new epigenetic-based therapies in combination with targeted therapies have been proposed. Here we will discuss recent progress in our understanding of the chromatin-based mechanisms of breast tumorigenesis, how these mechanisms affect therapeutic response to standard of care treatment, and discuss new strategies towards therapeutic intervention to overcome resistance.
Characteristics of People Seeking Prescribed Cannabinoids for the Treatment of Chronic Pain: Evidence From Project Twenty 21
Authors: Schlag Anne Katrin , Lynskey Michael , Fayaz Alan , Athanasiou-Fragkouli Alkyoni , Brandner Brigitta , Haja Barbara , Iveson Elizabeth , Nutt David J.
Published: June 2022

Background

Prescribed cannabinoids are now legal in the UK and increasingly being used for a variety of conditions, with one of the most frequent conditions being chronic pain. This paper describes the characteristics of individuals seeking prescribed cannabinoids for the treatment of chronic pain in Project Twenty 21, a UK based real world data registry of prescribed cannabis patients.

Method

By 1st November 2021 data were available for 1,782 people who had sought treatment with medical cannabis as part of Project Twenty 21. The most common diagnosis among this cohort was chronic pain with 949 (53.5%) of the cohort reporting a primary condition related to chronic pain. Medical and self-report data on the characteristics of these patients, their health status and type/s of cannabinoid/s prescribed are summarized in this report.

Results

Of the 949 people reporting chronic pain as a primary condition 54.7% were male and their average age was 42.0 years (range = 18–84). Patients reported a low quality of life and high levels of comorbidity: people reported an average of 4.6 comorbid conditions with the most common comorbid conditions including anxiety, depression, insomnia and stress. A range of cannabinoid products were prescribed with the most common products being classified as high THC flower (48.5%). The majority of patients also reported using at least one other prescribed medication (68.7%).

Conclusions

Consistent with findings in other national and international databases, chronic pain was the most common primary condition in this real world study of prescribed cannabinoids. There was considerable variation in the types of chronic pain, comorbid pathology and in the characteristics of products being prescribed to treat these conditions. Together, this evidence supports the utility of real world evidence, as opposed to clinical trial approaches to studying the potential benefits of prescribed cannabinoids in treating chronic pain.
Investigational Drugs for the Treatment of Depression (Part 1): Monoaminergic, Orexinergic, GABA-Ergic, and Anti-Inflammatory Agents
Authors: Vasiliu Octavian
Published: June 2022

Therapeutic management of depression has currently important limitations, and its low efficacy is reflected in high rates of non-response even after multiple trials of antidepressants. Almost two-thirds of the patients diagnosed with major depression who received a 4–6 weeks trial of antidepressant could not reach remission, and more than 30% of these patients are considered treatment-resistant. In bipolar depression, the situation is also discouraging if we analyze the high suicide rate, the risk for the treatment-emergent affective switch when antidepressants are added, the high rate of treatment resistance (up to 25%), and the severe functional impairments associated with these episodes. Therefore, new therapeutic agents are needed, as well as new pathogenetic models for depression. The vast majority of the currently approved antidepressants are based on the monoamine hypothesis, although new drugs exploiting different neurotransmitter pathways have been recently approved by FDA. Brexanolone, an allopregnanolone analog, is an example of such new antidepressants, and its approval for post-partum depression inspired the search for a new generation of neurosteroids and GABA-ergic modulators, with an easier way of administration and superior tolerability profile. Orexin receptors antagonists are also extensively studied for different psychiatric disorders, depression included, in phase II trials. Antiinflammatory drugs, both cyclo-oxygenase 2 inhibitors and biological therapy, are investigated in patients with depressive disorders based on the proven correlation between inflammation and mood disorders in preclinical and clinical studies. Also, a new generation of monoamine-based investigational drugs is explored, ranging from triple reuptake inhibitors to atypical antipsychotics, in patients with major depression. In conclusion, there is hope for new treatments in uni- and bipolar depression, as it became clear, after almost seven decades, that new pathogenetic pathways should be targeted to increase these patients’ response rate.
Brevilin A Ameliorates Acute Lung Injury and Inflammation Through Inhibition of NF-κB Signaling via Targeting IKKα/β
Authors: Liu Lu , Chen Xian , Jiang Yifang , Yuan Yun , Yang Luyao , Hu Qiongying , Tang Jianyuan , Meng Xianli , Xie Chunguang , Shen Xiaofei
Published: June 2022

Acute lung injury (ALI) is life-threatening disease characterized by uncontrolled inflammatory response. IKKα/β, the key kinases in the activation of NF-κB pathway, are implicated in inflammatory pulmonary injury, and represent attractive targets for ALI therapy. Brevilin A (BVA) is a sesquiterpene lactone from Centipeda minima, a Chinese herb used to treat inflammatory diseases. This study aims to investigate the inhibition of BVA on ALI, with focus on clarifying the molecular mechanisms involved in BVA-mediated anti-inflammatory activity in macrophages. Briefly, BVA significantly inhibited the production of NO and PGE2 by suppressing iNOS and COX2 expression, and suppressed the mRNA expression of IL-1β, IL-6, and TNFα in LPS/IFNγ-stimulated RAW264.7 macrophages. The anti-inflammatory activity of BVA was further confirmed in LPS/IFNγ-stimulated BMDMs and TNFα/IFNγ-exposed RAW264.7 cells. In vivo, BVA effectively attenuated LPS-induced lung damage, inflammatory infiltration, and production of pro-inflammatory cytokines, including MPO, IL-1β, IL-6, TNFα, and PGE2. Mechanistically, BVA could covalently bind to the cysteine 114 of IKKα/β, and effectively inhibiting the activity and function of IKKα/β, thereby resulting in the suppression of phosphorylation and degradation of IκBα and the subsequent activation of NF-κB signaling. Furthermore, pretreatment of DTT, a thiol ligand donor, significantly abolished BVA-mediated effects in LPS/IFNγ-stimulated RAW264.7 cells, suggesting the crucial role of the electrophilic α, β-unsaturated ketone of BVA on its anti-inflammatory activity. These results suggest that BVA ameliorates ALI through inhibition of NF-κB signaling via covalently targeting IKKα/β, raising the possibility that BVA could be effective in the treatment of ALI and other diseases harboring aberrant NF-κB signaling.
The Anti-Glioma Effect of Juglone Derivatives through ROS Generation
Authors: Zhang Jinsen , Fu Minjie , Wu Jinfeng , Fan Fengfeng , Zhang Xin , Li Chunjie , Yang Hui , Wu Yonghe , Yin Yiming , Hua Wei
Published: June 2022

Juglone has been extensively reported as a natural antitumor pigment. However, it is easy to be oxidized due to active hydroxy in the quinone. Here, we designed some new juglone derivatives, as the hydroxy was replaced by methyl (D1), allyl (D2), butyl (D3), and benzyl (D4) groups. Nuclear magnetic resonance spectra and mass spectrometry were applied to confirm the derivatives and oxidative products of juglone. U87 and U251 cell lines were used for tests in vitro, and primary human glioblastoma cells were applied for in vivo experiments. The CCK8 and EdU assay demonstrated the anti-tumor effect of the four derivatives, and IC50 for U87 was 3.99, 3.28, 7.60, and 11.84 μM, respectively. In U251, IC50 was 7.00, 5.43, 8.64, and 18.05 μM, respectively. D2 and D3 were further selected, and flow cytometry showed that apoptosis rates were increased after D2 or D3 treatment via ROS generation. Potential targets were predicted by network pharmacology analysis, most of which were associated with apoptosis, cell cycle, and metabolism pathway. CDC25B and DUSP1 were two of the most likely candidates for targets. The orthotopic glioblastoma model was established to evaluate the anti-glioma effect and side-effect of juglone derivatives, and the in vivo experiments confirmed the anti-glioma effects of juglone derivatives. In conclusion, new derivatives of juglone were created via chemical group substitution and could inhibit glioma cell viability and proliferation and induce apoptosis rate via ROS generation.
Fluid-Structure Interaction Simulations of Repaired Type A Aortic Dissection: a Comprehensive Comparison With Rigid Wall Models
Authors: Zhu Yu , Mirsadraee Saeed , Rosendahl Ulrich , Pepper John , Xu Xiao Yun
Published: June 2022

This study aimed to evaluate the effect of aortic wall compliance on intraluminal hemodynamics within surgically repaired type A aortic dissection (TAAD). Fully coupled two-way fluid-structure interaction (FSI) simulations were performed on two patient-specific post-surgery TAAD models reconstructed from computed tomography angiography images. Our FSI model incorporated prestress and different material properties for the aorta and graft. Computational results, including velocity, wall shear stress (WSS) and pressure difference between the true and false lumen, were compared between the FSI and rigid wall simulations. It was found that the FSI model predicted lower blood velocities and WSS along the dissected aorta. In particular, the area exposed to low time-averaged WSS (≤0.2 Pa) was increased from 21 cm2 (rigid) to 38 cm2 (FSI) in patient 1 and from 35 cm2 (rigid) to 144 cm2 (FSI) in patient 2. FSI models also produced more disturbed flow where much larger regions presented with higher turbulence intensity as compared to the rigid wall models. The effect of wall compliance on pressure difference between the true and false lumen was insignificant, with the maximum difference between FSI and rigid models being less than 0.25 mmHg for the two patient-specific models. Comparisons of simulation results for models with different Young’s moduli revealed that a more compliant wall resulted in further reduction in velocity and WSS magnitudes because of increased displacements. This study demonstrated the importance of FSI simulation for accurate prediction of low WSS regions in surgically repaired TAAD, but a rigid wall computational fluid dynamics simulation would be sufficient for prediction of luminal pressure difference.