bluuebunny/crossref_metadata_2025 huggingface dataset:
Flash Glucose Monitoring to Assess Glycemic Control and Variability in Hemodialysis Patients: The GIOTTO Study
Authors: Mambelli Emanuele , Cristino Stefania , Mosconi Giovanni , Göbl Christian , Tura Andrea
Published: July 2021

Background: Flash glucose monitoring (FGM) is a technology with considerable differences compared to continuous glucose monitoring (CGM), but it has been scarcely studied in hemodialysis patients. Thus, we aimed assessing the performance of FGM in such patients by comparison to self-monitoring of blood glucose (SMBG). We will also focus on estimation of glycemic control and variability, and their relationships with parameters of glucose homeostasis.

Methods: Thirty-one patients (20 with type 2 diabetes, T2DM, 11 diabetes-free, NODM) collected readings by FGM and SMBG for about 12 days on average. Readings by FGM and SMBG were compared by linear regression, Clarke error grid, and Bland-Altman analyses. Several indices of glycemic control and variability were computed. Ten patients also underwent oral glucose tolerance test (OGTT) for assessment of insulin sensitivity/resistance and insulin secretion/beta-cell function.

Results: Flash glucose monitoring and SMBG readings showed very good agreement in both T2DM and NODM (on average, 97 and 99% of readings during hemodialysis in A+B Clarke regions, respectively). Some glycemic control and variability indices were similar by FGM and SMBG (p = 0.06–0.9), whereas others were different (p = 0.0001–0.03). The majority of control and variability indices were higher in T2DM than in NODM, according to both FGM and SMBG (p = 0.0005–0.03). OGTT-based insulin secretion was inversely related to some variability indices according to FGM (R < −0.72, p < 0.02).

Conclusions: Based on our dataset, FGM appeared acceptable for glucose monitoring in hemodialysis patients, though partial disagreement with SMBG in glycemic control/variability assessment needs further investigations.
Impact of COVID-19 Pandemic on the Clinical Activities in Obstetrics and Gynecology: A National Survey in China
Authors: Li Lei , Cao Yang , Fan Junning , Li Ting , Lang Jinghe , Zhang Heping , Lv Jun , Zhu Lan ,   Chinese Medical Doctor Association
Published: July 2021

Objective: Few studies have quantified the influence of coronavirus disease 2019 (COVID-19) pandemic on medical providers. This is the first national study to investigate the impact of the pandemic on physicians practicing obstetrics and gynecology in China.

Methods: A two-stage, stratified, cluster sampling method was performed based on the city categories (category 1, fewer than 10,000 beds; category 2, 10,000–30,000; and category 3, more than 30,000) and public hospital levels (primary, secondary, and tertiary). Physicians practicing obstetrics and gynecology reported the relevant changes in their general clinical activities and changes in the management of specific diseases or conditions occurring during the periods that they were most strongly affected. These changes were compared by municipal and hospital characteristics.

Results: Questionnaires were collected from a representative sample of 11,806 physicians actively practicing obstetrics and gynecology in 779 hospitals from 157 cities of 31 provinces. Except emergency visits and online consultations, category 3 cities, tertiary hospitals and general hospitals had greater reductions in overall clinical activities than category 1 cities, primary hospitals and specialized hospitals (all adjusted p < 0.05), respectively. The differences also existed in the management of specific diseases and conditions, especially for less urgent conditions, including cervical cancer screening, instructions regarding contraception and miscarriage, and assisted reproduction (all p < 0.05).

Conclusions: During the COVID-19 pandemic, the clinical obstetrics and gynecology activities in China markedly decreased, with significant differences across municipal and hospital characteristics.

Trial Registration: This study was registered with ClinicalTrials.gov on July 27, 2020 (NCT04491201).
Long-Term Follow-Up Results of Fecal Microbiota Transplantation for Irritable Bowel Syndrome: A Single-Center, Retrospective Study
Authors: Cui Jiaqu , Lin Zhiliang , Tian Hongliang , Yang Bo , Zhao Di , Ye Chen , Li Ning , Qin Huanlong , Chen Qiyi
Published: July 2021

Objective: This study aimed to investigate the long-term efficacy of fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS).

Study Methods: In this single-center long-term follow-up study, FMT treatment was administered to patients with moderate to severe IBS (IBS severity scoring system (IBS-SSS) > 175). After 1 year of treatment, it was decided whether to repeat FMT based on IBS-SSS score (IBS-SSS > 175). Baseline characteristics before and after FMT and questionnaires were completed at 1, 3, 6, 12, 24, 36, 48, and 60 months after FMT. The study outcomes included treatment efficacy rates, change of IBS-SSS, IBS-specific quality of life and fatigue, effect on stool frequency, Bristol Stool Scale for IBS-C and IBS-D, and side effects.

Results: A total of 227 patients (47.58% IBS-C, 39.21% IBS-D, and 13.22% IBS-M) were recruited (142 females and 85 males with a mean age of 41.89 ± 13.57 years). The efficacy rates were 108 (51.92%), 147 (74.62%), 125 (74.41 %), 88 (71.54%), 78 (75.00%), 65 (73.03%), 45 (61.64%), and 37 (62.71%) at different follow-up time points. The total IBS-SSS score was 321.37 ± 73.89 before FMT, which significantly decreased after 1 month. The IBS-specific quality of life (IBS-QoL) score was 40.24 ± 11.34 before FMT, increased gradually, and was significantly higher at 3 months compared to before FMT. The total Fatigue Assessment Scale (FAS) score was 47 ± 8.64 before FMT and was significantly lower at 3 months. During follow-up, 89 (39.21%) side effects occurred that were alleviated by symptomatic treatment, and no serious adverse events were detected.

Conclusion: Based on 60 months of long-term follow-up, the safety and efficacy of FMT for IBS was established. However, as the treatment effect declines over time, periodic and repetitive FMT is required for a sustained effect.
Lactobacillus plantarum in Dual-Species Biofilms With Listeria monocytogenes Enhanced the Anti-Listeria Activity of a Commercial Disinfectant Based on Hydrogen Peroxide and Peracetic Acid
Authors: Bonneville Lourenço , Maia Vera , Barroso Inês , Martínez-Suárez Joaquín V. , Brito Luisa
Published: July 2021

The aim of this work was to investigate the effect of dual-species biofilms of Listeria monocytogenes with Lactobacillus plantarum on the anti-Listeria activity of a hydrogen peroxide/peracetic acid based commercial disinfectant (P3, Oxonia) when using conditions approaching the food industry environment. Nine strains of L. monocytogenes, including eight persistent strains collected from the meat industry and one laboratory control strain, were used in mono and in dual-species biofilms with a strain of L. plantarum. Biofilms were produced on stainless steel coupons (SSCs), at 11°C (low temperature) or at 25°C (control temperature), in TSB-YE (control rich medium) or in 1/10 diluted TSB-YE (mimicking the situation of biofilm formation after a deficient industrial cleaning procedure). The biofilm forming ability of the strains was evaluated by enumeration of viable cells, and the antibiofilm activity of P3 was assessed by the log reduction of viable cells on SSC. In both nutrient conditions and at low temperature, there was no significant difference (p > 0.05) between L. monocytogenes biofilm forming ability in mono- and in dual-species biofilms. In dual-species biofilms, L. monocytogenes was the dominant species. However, it was generally more susceptible to the lower concentration of P3 0.5% (v/v) than in pure culture biofilms. The presence of L. plantarum, although without significant interference in the number of viable cells of L. monocytogenes, enhanced the efficacy of the anti-Listeria activity of P3, since dual-species biofilms were easier to control. The results presented here reinforce the importance of the investigation into co-culture biofilms produced in food industry conditions, namely at low temperatures, when susceptibility to sanitizers is being assessed.
Lack of the Bacterial Phytochrome Protein Decreases Deinococcus radiodurans Resistance to Mitomycin C
Authors: Jung Jong-Hyun , Jeong Soyoung , Im Seonghun , Kim Min-Kyu , Seo Ho Seong , Lim Sangyong
Published: July 2021

Deinococcus radiodurans known for its extraordinary resistance to ionizing radiation contains bacterial phytochrome (BphP), a member of the family of red/far-red light-sensing proteins. In this study, we constructed a bphP mutant strain (ΔbphP) to investigate the role of D. radiodurans BphP (DrBphP) in the DNA damage response. When cells were incubated under light and dark conditions following exposure to DNA damaging agents, such as γ- and UV-radiation and mitomycin C (MMC), no significant difference in cell survival was observed between the wild-type D. radiodurans strain (WT) and ΔbphP. However, when continuously exposed to MMC under light conditions, the WT strain notably exhibited increased survival compared to cells grown in the dark. The increased survival was not observed in the ΔbphP strain. These results are indicative of the protective role of light-activated DrBphP in the presence of MMC. Site-directed mutagenesis revealed that the conserved amino acids Cys-24 and His-532 involved in chromophore binding and signal transduction, respectively, were essential for the protective function of DrBphP. Inactivation of the cognate response regulator (RR; DrBphR) of DrBphP increased MMC resistance in the dark. In trans complementation of the bphP bphR double mutant strain (ΔbphPR) with DrBphR decreased MMC resistance. Considering that DrBphP acts as a light-activated phosphatase that dephosphorylates DrBphR, it appears that phosphorylated DrBphR exerts a negative effect on cell survival in the presence of MMC. DrBphP overexpression resulted in an increase in MMC resistance of ΔbphPR, implying that other RRs might be involved in the DrBphP-mediated signaling pathway. A mutant lacking the dr_0781 gene (Δdr_0781) demonstrated the same MMC phenotype as ΔbphR. Survival was further increased in the bphR dr_0781 double mutant strain compared to each single mutant ΔbphR or Δdr_0781, suggesting that DR_0781 is also involved in the DrBphP-dependent MMC sensitivity. This study uncovered a previously unknown phenomenon of red/far-red light-dependent DNA damage survival mediated by BphP by identifying the conditions under which DrBphP exhibits a fitness advantage.
Prenatal Depression, Breastfeeding, and Infant Gut Microbiota
Authors: Rodriguez Nicole , Tun Hein M. , Field Catherine J. , Mandhane Piushkumar J. , Scott James A. , Kozyrskyj Anita L.
Published: July 2021

Depressive symptoms are common during pregnancy and are estimated to affect 7–20% of pregnant women, with higher prevalence found in those with a prior history of depression, in ethnic minorities, and those with increased exposure to stressful life events. Maternal depression often remains undiagnosed, and its symptoms can increase adverse health risks to the infant, including impaired cognitive development, behavioral problems, and higher susceptibility to physical illnesses. Accumulating research evidence supports the association between maternal physical health elements to infant gut health, including factors such as mode of delivery, medication, feeding status, and antibiotic use. However, specific maternal prenatal psychosocial factors and their effect on infant gut microbiota and immunity remains an area that is not well understood. This article reviews the literature and supplements it with new findings to show that prenatal depression alters: (i) gut microbial composition in partially and fully formula-fed infants at 3–4 months of age, and (ii) gut immunity (i.e., secretory Immunoglobulin A) in all infants independent of breastfeeding status. Understanding the implications of maternal depression on the infant gut microbiome is important to enhance both maternal and child health and to better inform disease outcomes and management.
Characterization of Shallow Whole-Metagenome Shotgun Sequencing as a High-Accuracy and Low-Cost Method by Complicated Mock Microbiomes
Authors: Xu Wenyi , Chen Tianda , Pei Yuwei , Guo Hao , Li Zhuanyu , Yang Yanan , Zhang Fang , Yu Jiaqi , Li Xuesong , Yang Yu , Zhao Bowen , Wu Chongming
Published: July 2021

Characterization of the bacterial composition and functional repertoires of microbiome samples is the most common application of metagenomics. Although deep whole-metagenome shotgun sequencing (WMS) provides high taxonomic resolution, it is generally cost-prohibitive for large longitudinal investigations. Until now, 16S rRNA gene amplicon sequencing (16S) has been the most widely used approach and usually cooperates with WMS to achieve cost-efficiency. However, the accuracy of 16S results and its consistency with WMS data have not been fully elaborated, especially by complicated microbiomes with defined compositional information. Here, we constructed two complex artificial microbiomes, which comprised more than 60 human gut bacterial species with even or varied abundance. Utilizing real fecal samples and mock communities, we provided solid evidence demonstrating that 16S results were of poor consistency with WMS data, and its accuracy was not satisfactory. In contrast, shallow whole-metagenome shotgun sequencing (shallow WMS, S-WMS) with a sequencing depth of 1 Gb provided outputs that highly resembled WMS data at both genus and species levels and presented much higher accuracy taxonomic assignments and functional predictions than 16S, thereby representing a better and cost-efficient alternative to 16S for large-scale microbiome studies.
Integrative Studies on a New Ciliate Campanella sinica n. sp. (Protista, Ciliophora, Peritrichia) Based on the Morphological and Molecular Data, With Notes on the Phylogeny and Systematics of the Family Epistylididae
Authors: Wang Zhe , Wu Tong , Lu Borong , Chi Yong , Zhang Xue , Al-Farraj Saleh A. , Song Weibo , Warren Alan , Li Lifang , Wang Chundi
Published: July 2021

During an investigation on freshwater peritrichs, a new colonial sessilid ciliate, Campanella sinica n. sp., was isolated from aquatic plants in an artificial freshwater pond in Qingdao, China. Specimen observations of this species were performed both in vivo and using silver staining. C. sinica n. sp. is characterized by the appearance of the mature colony, which is up to 2 cm high and contains more than 1,000 zooids, the asymmetric horn-shaped zooids, strongly everted and multi-layered peristomial lip, the slightly convex peristomial disc, and the well-developed haplokinety and polykinety, which make more than four circuits of the peristome before descending into the infundibulum. The small subunit ribosomal DNA (SSU rDNA), 5.8s rDNA and its flank internal transcribed spacers (ITS1-5.8s rDNA-ITS2), and large subunit ribosomal DNA (LSU rDNA) are sequenced and used for phylogenetic analyses which reveal that the family Epistylididae Kahl, 1933 is non-monophyletic whereas the genus Campanella is monophyletic and nests within the basal clade of the sessilids. The integrative results support the assertion that the genus Campanella represents a separate lineage from other epistylidids, suggesting a further revision of the family Epistylididae is needed. We revise Campanella including the transfer into this genus of a taxon formerly assigned to Epistylis, which we raise to species rank, i.e., Campanella ovata (Nenninger, 1948) n. grad. & n. comb. (original combination Epistylis purneri f. ovataNenninger, 1948). In addition, we provide a key to the identification of the species of Campanella.
Deciphering the Oncogenic Role of VPS28 Modulated by miR-491-5p in Breast Cancer Cells Using In Silico and Functional Analysis
Authors: Shi Wenjie , Hu Daojun , Xing Yu , Zhuo Rui , Lao Qiufeng , Liu Hui , Pang Weiyi
Published: July 2021

Vacuolar protein sorting–associated protein 28 (VPS28), one of the four cytosolic proteins comprising the endosomal sorting complex required for the transport I (ESCRT-I) component, has been reported to be linked to various cancers. However, less evidence is available regarding the involvement of VPS28 in breast cancer. To this end, this study focused on exploring the function of VPS28 in breast cancer cells using the in silico analysis. VPS28 expression pattern data in breast cancer tissues were collected using the Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases and analyzed to assess the association of VPS28 with breast cancer prognosis. The elevated VPS28 expression was found in breast cancer tissues and was associated with a poor prognosis (p < 0.001). A higher VPS28 expression indicated a short survival duration (HR = 2.43; 95% CI: 1.44–4.1; p < 0.001). The CCLE database showed that VPS28 was expressed in breast cancer cell lines. The upstream targets of VPS28 were identified using the mirDIP, starBase, and TargetScan online tools. The correlation and binding relationship between miR-491-5p and VPS28 was analyzed. VPS28 or miR-491-5p gain and loss of function experiments were performed to verify their potential effect on the biological functions of breast cancer cells. Knockdown of VPS28 was shown to suppress the biological functions and enhance the apoptosis of breast cancer cell lines. Micro RNA-491-5p, identified as a posttranscriptional regulator of VPS28, was downregulated in breast cancer tissues. In contrast to the miR-491-5p inhibitor, the miR-491-5p mimic could suppress the migration, wound healing ability, and proliferation, while accelerating apoptosis. However, co-transfection of VPS28 and miR-491-5p counteracted the effect of the miR-491-5p mimic on breast cancer cell functions. Thus, our in silico analysis demonstrates that miR-491-5p can suppress breast cancer progression by attenuating the expression of VPS28.
Overview on the Role of E-Cadherin in Gastric Cancer: Dysregulation and Clinical Implications
Authors: Zhao Huichen , Hu Huihui , Chen Beibei , Xu Weifeng , Zhao Jing , Huang Chen , Xing Yishu , Lv Huifang , Nie Caiyun , Wang Jianzheng , He Yunduan , Wang Sai-Qi , Chen Xiao-Bing
Published: July 2021

Gastric cancer is the fifth most common cancer and the third most common cause of cancer death all over the world. E-cadherin encoded by human CDH1 gene plays important roles in tumorigenesis as well as in tumor progression, invasion and metastasis. Full-length E-cadhrin tethered on the cell membrane mainly mediates adherens junctions between cells and is involved in maintaining the normal structure of epithelial tissues. After proteolysis, the extracellular fragment of the full-length E-cadhein is released into the extracellular environment and the blood, which is called soluble E-cadherin (sE-cadherin). sE-cadherin promots invasion and metastasis as a paracrine/autocrine signaling molecule in the progression of various types of cancer including gastric cancer. This review mainly summarizes the dysregulation of E-cadherin and the regulatory roles in the progression, invasion, metastasis, and drug-resistance, as well as its clinical applications in diagnosis, prognosis, and therapeutics of gastric cancer.
A Shift in Tissue Stiffness During Hippocampal Maturation Correlates to the Pattern of Neurogenesis and Composition of the Extracellular Matrix
Authors: Ryu Youngjae , Iwashita Misato , Lee Wonyoung , Uchimura Kenji , Kosodo Yoichi
Published: July 2021

Aging changes the mechanical properties of brain tissue, such as stiffness. It has been proposed that the maintenance and differentiation of neural stem cells (NSCs) are regulated in accordance with extracellular stiffness. Neurogenesis is observed in restricted niches, including the dentate gyrus (DG) of the hippocampus, throughout mammalian lifetimes. However, profiles of tissue stiffness in the DG in comparison with the activity of NSCs from the neonatal to the matured brain have rarely been addressed so far. Here, we first applied ultrasound-based shear-wave elasticity imaging (SWEI) in living animals to assess shear modulus as in vivo brain stiffness. To complement the assay, atomic force microscopy (AFM) was utilized to determine the Young’s modulus in the hippocampus as region-specific stiffness in the brain slice. The results revealed that stiffness in the granule cell layer (GCL) and the hilus, including the subgranular zone (SGZ), increased during hippocampal maturation. We then quantified NSCs and immature neural cells in the DG with differentiation markers, and verified an overall decrease of NSCs and proliferative/immature neural cells along stages, showing that a specific profile is dependent on the subregion. Subsequently, we evaluated the amount of chondroitin sulfate proteoglycans (CSPGs), the major extracellular matrix (ECM) components in the premature brain by CS-56 immunoreactivity. We observed differential signal levels of CSPGs by hippocampal subregions, which became weaker during maturation. To address the contribution of the ECM in determining tissue stiffness, we manipulated the function of CSPGs by enzymatic digestion or supplementation with chondroitin sulfate, which resulted in an increase or decrease of stiffness in the DG, respectively. Our results illustrate that stiffness in the hippocampus shifts due to the composition of ECM, which may affect postnatal neurogenesis by altering the mechanical environment of the NSC niche.
Cardiovascular MRI Compared to Echocardiography to Identify Cardioaortic Sources of Ischemic Stroke: A Systematic Review and Meta-Analysis
Authors: Meinel Thomas R. , Eggimann Angela , Brignoli Kristina , Wustmann Kerstin , Buffle Eric , Meinel Felix G. , Scheitz Jan F. , Nolte Christian H. , Gräni Christoph , Fischer Urs , Kaesmacher Johannes , Seiffge David J. , Seiler Christian , Jung Simon
Published: July 2021

Background: To compare the diagnostic yield of echocardiography and cardiovascular MRI (CMR) to detect structural sources of embolism, in patients with ischemic stroke with a secondary analysis of non-stroke populations.

Methods and Results: We searched MEDLINE/Embase (from 01.01.2000 to 24.04.2021) for studies including CMR to assess prespecified sources of embolism. Comparison included transthoracic and/or transesophageal echocardiography. Two authors independently screened studies, extracted data and assessed bias using the QUADAS-2 tool. Estimates of diagnostic yield were reported and pooled. Twenty-seven studies with 2,525 patients were included in a study-level analysis. Most studies had moderate to high risk of bias. Persistent foramen ovale, complex aortic plaques, left ventricular and left atrial thrombus were the most common pathologies. There was no difference in the yield of left ventricular thrombus detection between both modalities for stroke populations (4 studies), but an increased yield of CMR in non-stroke populations (28.1 vs. 16.0%, P < 0.001, 10 studies). The diagnostic yield in stroke patients for detection of persistent foramen ovale was lower in CMR compared to transoesophageal echocardiography (29.3 vs. 53.7%, P < 0.001, 5 studies). For both echocardiography and CMR the clinical impact of the management consequences derived from many of the diagnostic findings remained undetermined in the identified studies.

Conclusions: Echocardiography and CMR seem to have similar diagnostic yield for most cardioaortic sources of embolism except persistent foramen ovale and left ventricular thrombus. Randomized controlled diagnostic trials are necessary to understand the impact on the management and potential clinical benefits of the assessment of structural cardioaortic stroke sources.

Registration: PROSPERO: CRD42020158787.
Multidimensional Factors Can Explain the Clinical Worsening in People With Parkinson's Disease During the COVID-19 Pandemic: A Multicenter Cross-Sectional Trial
Authors: Silva-Batista Carla , Coelho Daniel Boari , Júnior Renato Campos Freire , Almeida Lorena Rosa , Guimarães Adriana , Nóbrega Katia Cirilo Costa , Machado Sanchez Hugo , Lindquist Ana Raquel Rodrigues , Israel Vera Lúcia , Kanegusuku Hélcio , Guimarães Rachel , Beckmann Bosaipo Nayanne , Barbosa Richelma , Correa Clynton Lourenço , Finatto Maria José , Mendes Felipe Augusto dos Santos , Piemonte Maria Elisa Pimentel
Published: July 2021

Background: Self-reported clinical worsening by people with Parkinson's disease (PD) during social distancing may be aggravated in Brazil, where the e/tele-health system is precarious.

Objectives: This study aims to investigate self-reported changes in motor and non-motor aspects during social distancing in people with PD living in Brazil and to investigate the factors that might explain these changes.

Methods: In this multicenter cross-sectional trial, 478 people with a diagnosis of idiopathic PD (mean age = 67, SD = 9.5; 167 female) were recruited from 14 centers distributed throughout the five geographical regions of Brazil. The evaluators from each center applied a questionnaire by telephone, which included questions (previous and current period of social distancing) about the motor and non-motor experiences of daily living, quality of life, daily routine, and physical activity volume.

Results: Self-reported clinical worsening in non-motor and motor aspects of daily life experiences (Movement Disorder Society-Unified PD Rating Scale—parts IB and II—emotional and mental health, and fear of falling) and in the quality of life was observed. Only 31% of the participants reported a guided home-based physical activity with distance supervision. Perceived changes in the quality of life, freezing of gait, decreased physical activity volume, daily routine, and fear of falling explained the self-reported clinical worsening (P < 0.05).

Conclusions: Self-reported clinical worsening in people with PD living in Brazil during social distancing can also be aggravated by the precarious e/tele-health system, as perception of decreased physical activity volume and impoverishment in daily routine were some of the explanatory factors. Considering the multifaceted worsening, the implementation of a remote multi-professional support for these people is urgent.
High-Frequency Oscillations on Interictal Epileptiform Discharges in Routinely Acquired Scalp EEG: Can It Be Used as a Prognostic Marker?
Authors: El Shakankiry Hanan , Arnold Susan T.
Published: July 2021

Introduction

Despite all the efforts for optimizing epilepsy management in children over the past decades, there is no clear consensus regarding whether to treat or not to treat epileptiform discharges (EDs) after a first unprovoked seizure or the optimal duration of therapy with anti-seizure medication (ASM). It is therefore highly needed to find markers on scalp electroencephalogram (EEG) that can help identify pathological EEG discharges that require treatment.

Aim of the study

This retrospective study aimed to identify whether the coexistence of ripples/high-frequency oscillations (HFOs) with interictal EDs (IEDs) in routinely acquired scalp EEG is associated with a higher risk of seizure recurrence and could be used as a prognostic marker.

Methods

100 children presenting with new onset seizure to Children’s Medical Center- Dallas during 2015–2016, who were not on ASM and had focal EDs on an awake and sleep EEG recorded with sample frequency of 500 HZ, were randomly identified by database review. EEGs were analyzed blinded to the data of the patients. HFOs were visually identified using review parameters including expanded time base and adjusted filter settings.

Results

The average age of patients was 6.3 years (±4.35 SD). HFOs were visually identified in 19% of the studied patients with an inter-rater reliability of 99% for HFO negative discharges and 78% agreement for identification of HFOs. HFOs were identified more often in the younger age group; however, they were identified in 11% of patients >5 years old. They were more frequently associated with spikes than with sharp waves and more often with higher amplitude EDs. Patients with HFOs were more likely to have a recurrence of seizures in the year after the first seizure (P< 0.05) and to continue to have seizures after 2 years (P< 0.0001). There was no statistically significant difference between the two groups with regards to continuing ASM after 2 years.

Conclusion

Including analysis for HFOs in routine EEG interpretation may increase the yield of the study and help guide the decision to either start or discontinue ASM. In the future, this may also help to identify pathological discharges with deleterious effects on the growing brain and set a new target for the management of epilepsy.
Plant Extracts Rich in Polyphenols as Potent Modulators in the Growth of Probiotic and Pathogenic Intestinal Microorganisms
Authors: Milutinović Milica , Dimitrijević-Branković Suzana , Rajilić-Stojanović Mirjana
Published: July 2021

Medicinal plants and their extracts contain substantial quantities of polyphenols. As metabolically active plant metabolites, polyphenols are food components with a wide range of biological activities. Given their poor absorbability in the digestive tract their activity toward the human host is typically mediated through interaction with intestinal microbes. As a result, polyphenols comprise a novel group of prebiotics. In this study, we tested the effect of five polyphenol-rich extracts from four medicinal herbs on the growth of probiotic and pathogenic microbes. The studied medicinal herbs were Gentiana asclepiadea L. (willow gentian), Hypericum perforatum L. (St. John's wort), Satureja montana L. (winter savory), and Achillea millefolium L. (yarrow). All these plants are traditionally used for the treatment of digestive problems. Extracts were prepared using safe solvent combinations. We tested the impact of addition of plant extracts on the growth of three probiotic lactobacilli and probiotic yeast Saccharomyces boulardii. The effect of addition of plant extracts to liquid media (concentration range 0.25–10 mg/mL) on the growth of probiotics, was tested in vitro. The antimicrobial activity of the extracts was tested against several opportunistic bacteria and yeast. St. John's wort, winter savory, and willow gentian extracts showed a stimulative effect on probiotic yeast growth, while the highest growth-stimulating effect was achieved when microwave-assisted yarrow extract was used in the concentration of 0.5 mg/mL. Under these conditions growth of S. boulardii was increased 130-fold. In addition, the yarrow extract stimulated the growth of Lactiplantibacillus plantarum 299v. The growth of two Lacticasibacillus rhamnosus strains was not stimulated by the addition of any extracts. Our results show that plant polyphenol-rich extracts can influence the growth of microorganisms that are typical members of the intestinal microbiota. For the first time we demonstrate that probiotic yeast growth can be stimulated by extracts of medicinal herbs, which when accompanied by suppression of Candida yeasts suggests a potential benefit of the treatment in diseases that are associated with fungal dysbiosis.
Racial and Ethnic Differences in the Financial Consequences of Cancer-Related Employment Disruption
Authors: Biddell Caitlin B. , Wheeler Stephanie B. , Angove Rebekah S.M. , Gallagher Kathleen D. , Anderson Eric , Kent Erin E. , Spees Lisa P.
Published: July 2021

Introduction

Cancer-related employment disruption contributes to financial toxicity and associated clinical outcomes through income loss and changes in health insurance and may not be uniformly experienced. We examined racial/ethnic differences in the financial consequences of employment disruption.

Methods

We surveyed a national sample of cancer patients employed at diagnosis who had received assistance from a national nonprofit about the impact of cancer diagnosis and treatment on employment. We used logistic regression models to examine racial/ethnic differences in income loss and changes in health insurance coverage.

Results

Of 619 cancer patients included, 63% identified as Non-Hispanic/Latinx (NH) White, 18% as NH Black, 9% as Hispanic/Latinx, 5% as other racial/ethnic identities, and 5% unreported. Over 83% reported taking a significant amount of time off from work during cancer diagnosis and treatment, leading to substantial income loss for 64% and changes in insurance coverage for 31%. NH Black respondents had a 10.2 percentage point (95% CI: 4.8 – 19.9) higher probability of experiencing substantial income loss compared to NH White respondents, and Hispanic or Latinx respondents had a 12.4 percentage point (95% CI: 0.3 – 24.5) higher probability compared to NH White respondents, controlling for clinical characteristics (i.e., cancer type, stage and age at diagnosis, and time since diagnosis). Similarly, NH Black respondents had a 9.3 percentage point (95% CI: -0.7 – 19.3) higher probability of experiencing changes in health insurance compared to NH White respondents, and Hispanic or Latinx respondents had a 10.0 percentage point (95% CI: -3.0 – 23.0) higher probability compared to NH White respondents.

Discussion

Compared with NH White respondents, NH Black and Hispanic/Latinx respondents more commonly reported employment-related income loss and health insurance changes. Given documented racial/ethnic differences in job types, benefit generosity, and employment protections as a result of historic marginalization, policies to reduce employment disruption and its associated financial impact must be developed with a racial equity lens.
5-ALA in Suspected Low-Grade Gliomas: Current Role, Limitations, and New Approaches
Authors: Kiesel Barbara , Freund Julia , Reichert David , Wadiura Lisa , Erkkilae Mikael T. , Woehrer Adelheid , Hervey-Jumper Shawn , Berger Mitchel S. , Widhalm Georg
Published: July 2021

Radiologically suspected low-grade gliomas (LGG) represent a special challenge for the neurosurgeon during surgery due to their histopathological heterogeneity and indefinite tumor margin. Therefore, new techniques are required to overcome these current surgical drawbacks. Intraoperative visualization of brain tumors with assistance of 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence is one of the major advancements in the neurosurgical field in the last decades. Initially, this technique was exclusively applied for fluorescence-guided surgery of high-grade glioma (HGG). In the last years, the use of 5-ALA was also extended to other indications such as radiologically suspected LGG. Here, we discuss the current role of 5-ALA for intraoperative visualization of focal malignant transformation within suspected LGG. Furthermore, we discuss the current limitations of the 5-ALA technology in pure LGG which usually cannot be visualized by visible fluorescence. Finally, we introduce new approaches based on fluorescence technology for improved detection of pure LGG tissue such as spectroscopic PpIX quantification fluorescence lifetime imaging of PpIX and confocal microscopy to optimize surgery.
Development and Validation of a Radiosensitivity Prediction Model for Lower Grade Glioma Based on Spike-and-Slab Lasso
Authors: Du Zixuan , Cai Shang , Yan Derui , Li Huijun , Zhang Xinyan , Yang Wei , Cao Jianping , Yi Nengjun , Tang Zaixiang
Published: July 2021

Background and Purpose

Lower grade glioma (LGG) is one of the leading causes of death world worldwide. We attempted to develop and validate a radiosensitivity model for predicting the survival of lower grade glioma by using spike-and-slab lasso Cox model.

Methods

In this research, differentially expressed genes based on tumor microenvironment was obtained to further analysis. Log-rank test was used to identify genes in patients who received radiotherapy and patients who did not receive radiotherapy, respectively. Then, spike-and-slab lasso was performed to select genes in patients who received radiotherapy. Finally, three genes (INA, LEPREL1 and PTCRA) were included in the model. A radiosensitivity-related risk score model was established based on overall rate of TCGA dataset in patients who received radiotherapy. The model was validated in TCGA dataset that PFS as endpoint and two CGGA datasets that OS as endpoint. A novel nomogram integrated risk score with age and tumor grade was developed to predict the OS of LGG patients.

Results

We developed and verified a radiosensitivity-related risk score model. The radiosensitivity-related risk score is served as an independent prognostic indicator. This radiosensitivity-related risk score model has prognostic prediction ability. Moreover, the nomogram integrated risk score with age and tumor grade was established to perform better for predicting 1, 3, 5-year survival rate.

Conclusions

This model can be used by clinicians and researchers to predict patient’s survival rates and achieve personalized treatment of LGG.
Feasibility and Outcome of PSMA-PET-Based Dose-Escalated Salvage Radiotherapy Versus Conventional Salvage Radiotherapy for Patients With Recurrent Prostate Cancer
Authors: Vogel Marco M. E. , Dewes Sabrina , Sage Eva K. , Devecka Michal , Eitz Kerstin A. , Gschwend Jürgen E. , Eiber Matthias , Combs Stephanie E. , Schiller Kilian
Published: July 2021

Introduction

Prostate-specific membrane antigen-positron emission tomography-(PSMA-PET) imaging facilitates dose-escalated salvage radiotherapy (DE-SRT) with simultaneous-integrated boost (SIB) for PET-positive lesions in patients with prostate cancer (PC). Therefore, we aimed to compare toxicity rates of DE-SRT with SIB to conventional SRT (C-SRT) without SIB and to report outcome.

Materials and Methods

We evaluated 199 patients who were treated with SRT between June 2014 and June 2020. 101 patients received DE-SRT with SIB for PET-positive local recurrence and/or PET-positive lymph nodes. 98 patients were treated with C-SRT to the prostate bed +/− elective pelvic lymphatic pathways without SIB. All patients received PSMA-PET imaging prior to DE-SRT ([68Ga]PSMA-11: 45.5%; [18F]-labeled PSMA: 54.5%). Toxicity rates for early (<6 months) and late (>6 months) gastrointestinal (GI) toxicities rectal bleeding, proctitis, stool incontinence, and genitourinary (GU) toxicities hematuria, cystitis, urine incontinence, urinary obstruction, and erectile dysfunction were assessed. Further, we analyzed the outcome with disease-free survival (DFS) and prostate-specific antigen (PSA) response.

Results

The overall toxicity rates for early GI (C-SRT: 2.1%, DE-SRT: 1.0%) and late GI (C-SRT: 1.4%, DE-SRT: 5.3%) toxicities ≥ grade 2 were similar. Early GU (C-SRT: 2.1%, DE-SRT: 3.0%) and late GU (C-SRT: 11.0%, DE-SRT: 14.7%) toxicities ≥ grade 2 were comparable, as well. Early and late toxicity rates did not differ significantly between DE-SRT versus C-SRT in all subcategories (p>0.05). PSA response (PSA ≤0.2 ng/ml) in the overall group of patients with DE-SRT was 75.0% and 86.4% at first and last follow-up, respectively.

Conclusion

DE-SRT showed no significantly increased toxicity rates compared with C-SRT and thus is feasible. The outcome of DE-SRT showed good results. Therefore, DE-SRT with a PSMA-PET-based SIB can be considered for the personalized treatment in patients with recurrent PC.
Extracts of Vine Tea Improve Diet-Induced Non-Alcoholic Steatohepatitis Through AMPK-LXRα Signaling
Authors: Chen Yu-jun , Song Hai-yan , Zhang Zi-wei , Chen Qian , Tang Zhi-peng , Gu Ming
Published: July 2021

Chinese vine tea can improve glucose and lipid metabolic disorders. However, its protective effects in non-alcoholic steatohepatitis (NASH) and its underlying molecular mechanisms remain unclear. Liver X receptor α (LXRα) inhibition and adenosine monophosphate-(AMP)-activated protein kinase (AMPK) activation can enhance control of NASH. AMPK activators have also been shown to inactivate LXRα. Here, the anti-NASH effects of vine tea extract (VTE) dosed at 1 g.100 g−1 diet were investigated using NASH mice challenged with a methionine and choline-deficient l-amino acid diet (MCDD) and a high-fat diet (HFD). Pharmacological mechanisms of VTE were explored using TUNEL staining, AMPK inhibition, Western blot, reporter assays, qRT-PCR analyses, and immunofluorescence. VTE treatment improved fatty liver in HFD-induced mice, while it alleviated the progression of NASH including protecting against liver lipid accumulation, steatosis, endoplasmic reticulum stress, apoptosis, inflammation, and functional injury in MCDD-fed mice. VTE reduced the action of hepatic lipogenic genes, F4/80, pro-inflammatory cytokines, CHOP, and cleaved Caspase-3 expression, while promoting expression of fatty acid oxidation genes CPT1α, ß. VTE also enhanced AMPK and blocked LXRα signaling in mouse livers. In vitro results indicated that VTE increased AMPK phosphorylation and reduced LXRα activity in HepG2 cells. Conversely, the antagonistic effect of VTE on LXRα was decreased through AMPK inhibition. Our data suggests that VTE may improve diet-induced NASH, which involves the pharmacological modulation of the AMPK-LXRα signaling pathway.
Machine Learning in Model-free Mechanical Property Imaging: Novel Integration of Physics With the Constrained Optimization Process
Authors: Hoerig Cameron , Ghaboussi Jamshid , Wang Yiliang , Insana Michael F.
Published: July 2021

The Autoprogressive Method (AutoP) is a fundamentally different approach to solving the inverse problem in quasi-static ultrasonic elastography (QUSE). By exploiting the nonlinear adaptability of artificial neural networks and physical constraints imposed through finite element analysis, AutoP is able to build patient specific soft-computational material models from a relatively sparse set of force-displacement measurement data. Physics-guided, data-driven models offer a new path to the discovery of mechanical properties most effective for diagnostic imaging. AutoP was originally applied to modeling mechanical properties of materials in geotechnical and civil engineering applications. The method was later adapted to reconstructing maps of linear-elastic material properties for cancer imaging applications. Previous articles describing AutoP focused on high-level concepts to explain the mechanisms driving the training process. In this review, we focus on AutoP as applied to QUSE to present a more thorough explanation of the ways in which the method fundamentally differs from classic model-based and other machine learning approaches. We build intuition for the method through analogy to conventional optimization methods and explore how maps of stresses and strains are extracted from force-displacement measurements in a model-free way. In addition, we discuss a physics-based regularization term unique to AutoP that illuminates the comparison to typical optimization procedures. The insights gained from our hybrid inverse method will hopefully inspire others to explore combinations of rigorous mathematical techniques and conservation principles with the power of machine learning to solve difficult inverse problems.
Secrecy Performance Analysis of Hybrid RF/VLC Dual-Hop Relaying Systems
Authors: Liu Jiaoli , Wang Jinyuan , Zhang Bingyuan , Wang Qinglin
Published: July 2021

In this article, the secrecy performance of a hybrid radio frequency (RF)/visible light communication (VLC) system is studied. In this hybrid system, the source node (i.e., Alice) transmits information to the relay node via the outdoor RF link. Nakagami-m fading and path loss are considered for the RF link. The relay node includes an outdoor component and an indoor component, which are connected by using a wired medium. The outdoor component receives and recovers information by using the decode-and-forward (DF) relaying scheme and then transmits it to the indoor component. The indoor component then converts the received electrical signal into an optical signal by using a light-emitting diode. A legitimate receiver (i.e., Bob) deployed on the floor receives the optical signal. An eavesdropper (i.e., Eve) deployed in the RF or VLC link wiretaps the confidential information. In this study, we use the secrecy outage probability (SOP) and the probability of strictly positive secrecy capacity (SPSC) to evaluate the system performance. We then obtain the closed-form expression for a lower bound on the SOP and an exact closed-form expression for the probability of SPSC when the RF and VLC links are wiretapped, respectively. Numerical results are presented to validate the accuracy of our derivations. We further discuss the effects of the noise standard deviation, the equivalent threshold of the signal-to-noise ratio, and the floor radius on the system secrecy performance when the VLC link is eavesdropped upon. For the case when the RF link is eavesdropped upon, the impacts of the distance between Alice and the relay, the path loss exponent, the fading factor, and the distance between Alice and Eve on secrecy performance are also provided.
Medicinal Plants, Phytochemicals, and Their Impacts on the Maturation of the Gastrointestinal Tract
Authors: Mukonowenzou Nyasha Charity , Adeshina Kehinde Ahmad , Donaldson Janine , Ibrahim Kasimu Ghandi , Usman Dawoud , Erlwanger Kennedy Honey
Published: July 2021

The gastrointestinal tract (GIT) is the first point of contact for ingested substances and thus represents a direct interface with the external environment. Apart from food processing, this interface plays a significant role in immunity and contributes to the wellbeing of individuals through the brain-gut-microbiota axis. The transition of life from the in utero environment, to suckling and subsequent weaning has to be matched by phased development and maturation of the GIT; from an amniotic fluid occupancy during gestation, to the milk in the suckling state and ultimately solid food ingestion at weaning. This phased maturation of the GIT can be affected by intrinsic and extrinsic factors, including diet. Despite the increasing dietary inclusion of medicinal plants and phytochemicals for health benefits, a dearth of studies addresses their impact on gut maturation. In this review we focus on some recent findings mainly on the positive impact of medicinal plants and phytochemicals in inducing precocious maturation of the GIT, not only in humans but in pertinent animals. We also discuss Paneth cells as mediators and potential markers of GIT maturation.
Need for Speed: The Importance of Physiological Strain Rates in Determining Myocardial Stiffness
Authors: Caporizzo Matthew A. , Prosser Benjamin L.
Published: July 2021

The heart is viscoelastic, meaning its compliance is inversely proportional to the speed at which it stretches. During diastolic filling, the left ventricle rapidly expands at rates where viscoelastic forces impact ventricular compliance. In heart disease, myocardial viscoelasticity is often increased and can directly impede diastolic filling to reduce cardiac output. Thus, treatments that reduce myocardial viscoelasticity may provide benefit in heart failure, particularly for patients with diastolic heart failure. Yet, many experimental techniques either cannot or do not characterize myocardial viscoelasticity, and our understanding of the molecular regulators of viscoelasticity and its impact on cardiac performance is lacking. Much of this may stem from a reliance on techniques that either do not interrogate viscoelasticity (i.e., use non-physiological rates of strain) or techniques that compromise elements that contribute to viscoelasticity (i.e., skinned or permeabilized muscle preparations that compromise cytoskeletal integrity). Clinically, cardiac viscoelastic characterization is challenging, requiring the addition of strain-rate modulation during invasive hemodynamics. Despite these challenges, data continues to emerge demonstrating a meaningful contribution of viscoelasticity to cardiac physiology and pathology, and thus innovative approaches to characterize viscoelasticity stand to illuminate fundamental properties of myocardial mechanics and facilitate the development of novel therapeutic strategies.