bluuebunny/crossref_metadata_2025 huggingface dataset:
Firmicutes Dysbiosis After Chlorhexidine Prophylaxis in Healthy Patients Submitted to Impacted Lower Third Molar Extraction
Authors: Neves Carlos Augusto das , Alves Carlos Henrique , Rocha Natália Conceição , Rizzardi Karina Ferreira , Russi Karolyne Larissa , Palazzi Alexandre Augusto Albigiante , Parisotto Thaís Manzano , Girardello Raquel
Published: August 2021

Prophylaxis with antiseptic and antibiotic therapy is common in impacted lower third molar surgeries, despite the lack of consensus among professionals and researchers in the indication for healthy patients. The aim of the present preliminary study was to verify the impact of prophylaxis therapy with antiseptic and antibiotic in healthy patients submitted to impacted lower third molar extraction, according to oral microorganism quantification. Eleven patients submitted to impacted lower third molar extraction, under prophylactic therapy with 0.12% chlorhexidine and amoxicillin in four experimental phases, were evaluated. Our results showed no significant reduction in total bacteria load, as well as in Bacteroidetes and C. albicans loads in the oral cavity, after prophylactic therapy with antiseptic and antibiotic. On the other hand, there was a significant difference between the Firmicutes levels across the follow-up, and this effect seems to be large (ηp²=0.94). Post-hoc test demonstrated that the levels of Firmicutes in T1 were higher than T0, T2, and T3, suggesting a microbiota dysbiosis, when 0.12% chlorhexidine use, which may be responsible for selection of antibiotic-resistant microorganisms. Our results alert for an overuse of antiseptic and antibiotics by dentists and for a better evaluation of the available protocols.
DEAD-Box Helicase DDX6 Facilitated RIG-I-Mediated Type-I Interferon Response to EV71 Infection
Authors: Zhang Rui , Cheng Min , Liu Bingxin , Yuan Meng , Chen Deyan , Wang Yujiong , Wu Zhiwei
Published: August 2021

Previous studies have shown that DEAD (Asp-Glu-Ala-Asp)-box RNA helicases play important roles in viral infection, either as cytosolic sensors of pathogenic molecules or as essential host factors against viral infection. In the current study, we found that DDX6, an RNA helicase belonging to the DEAD-box family of helicase, exhibited anti-Enterovirus 71 activity through augmenting RIG-I-mediated type-I IFN response. Moreover, DDX6 binds viral RNA to form an RNA-protein complex to positively regulate the RIG-I-mediated interferon response; however, EV71 has evolved a strategy to antagonize the antiviral effect of DDX6 by proteolytic degradation of the molecule through its non-structural protein 2A, a virus-encoded protease.
eCPR Combined With Therapeutic Hypothermia Could Improve Survival and Neurologic Outcomes for Patients With Cardiac Arrest: A Meta-Analysis
Authors: Duan Jingwei , Ma Qingbian , Zhu Changju , Shi Yuanchao , Duan Baomin
Published: August 2021

Background: Extracorporeal membrane oxygenation with CPR (eCPR) or therapeutic hypothermia (TH) seems to be a very effective CPR strategy to save patients with cardiac arrest (CA). Furthermore, the subsequent post-CA neurologic outcomes have become the focus. Therefore, there is an urgent need to find a way to improve survival and neurologic outcomes for CA.

Objective: We conducted this meta-analysis to find a more suitable CPR strategy for patients with CA.

Method: We searched four online databases (PubMed, Embase, CENTRAL, and Web of Science). From an initial 1,436 articles, 23 studies were eligible into this meta-analysis, including a total of 2,035 patients.

Results: eCPR combined with TH significantly improved the short-term (at discharge or 28 days) survival [OR = 2.27, 95% CIs (1.60–3.23), p < 0.00001] and neurologic outcomes [OR = 2.60, 95% CIs (1.92–3.52), p < 0.00001). At 3 months of follow-up, the results of survival [OR = 3.36, 95% CIs (1.65–6.85), p < 0.0008] and favorable neurologic outcomes [OR = 3.02, 95% CIs (1.38–6.63), p < 0.006] were the same as above. Furthermore, there was no difference in any bleeding needed intervention [OR = 1.33, 95% CIs (0.09–1.96), p = 0.16] between two groups.

Conclusions: From this meta-analysis, we found that eCPR combined with TH might be a more suitable CPR strategy for patients with CA in improving survival and neurologic outcomes, and eCPR with TH did not increase the risk of bleeding. Furthermore, single-arm meta-analyses showed a plausible way of temperature and occasion of TH.
Outflow Through Aortic Side Branches Drives False Lumen Patency in Type B Aortic Dissection
Authors: Logghe Gerlinde , Trachet Bram , Segers Patrick , De Backer Julie , Mulorz Joscha , Dueppers Philip , Vermassen Frank , Schelzig Hubert , Van Herzeele Isabelle , Wagenhäuser Markus U.
Published: August 2021

Objective: Thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD) aims to induce false lumen (FL) thrombosis by sealing intimal tears between the true (TL) and the FL, and blocking the inflow into the FL. Incomplete thrombosis of the FL is correlated with poor clinical outcome. We hypothesize that the number of major and minor branches arising from the FL affects FL patency and may negatively influence TEVAR induced FL thrombosis.

Methods: Computed tomography (CT)-scans from 89 patients diagnosed with TBAD [best medical treatment (BMT) n = 52, TEVAR n = 37] from two high-volume vascular surgery centers were analyzed retrospectively. Analysis included evaluation of the FL patency status, the number, location and size of intimal tears, and the presence of minor and major side branches originating from the FL. Multiple regression analysis was conducted to evaluate obtained parameters as predictors for FL thrombosis status.

Results: In univariate analysis, the strongest correlation for FL patency was found for the number of major (R = 0.79) and minor (R = 0.86) side branches originating from the FL. When applying a multiple linear regression model, the number of major (normalized beta 0.37; P < 0.001) and minor (normalized beta 0.41; P < 0.01) side branches arising from the FL were valid predictors for the axial length of the patent and non-patent FL, and additionally determined the length of the patent FL at 12-month follow-up in patients that underwent TEVAR.

Conclusions: Our data suggest that the number of minor side branches that originate from the FL in TBAD is an important determinant of FL patency, to a greater degree than previously assumed.
Countering the Deleterious Effects of Electromagnetic Pulse
Authors: Sands Timothy
Published: August 2021

Robot systems like automated shipping swinging robots, wire transducer sensors and even computer indigenous time sensors (amongst others) often use oscillating circuits such as the famous van der Pol system, while this manuscript investigates protection of such sensor circuitry to spurious voltage spikes accompanying an electromagnetic pulse. These spurious voltages can lead to uncontrolled robot motion and even debilitation. A very brief discussion of electromagnetic pulses yields design parameters to evaluate circuit responses to realistic disturbing pulses. Recent research in nonlinear-adaptive methods to protect circuits are described to highlight the proposed novelty: utilization of feedback rules as adaptive mechanisms to modify the otherwise nonlinear feedforwards systems improving the results in recent literature. Feedback is iterated to select adaption parameters that simultaneously produce favorable circuit performance in addition to effective parameter identification inherent in the adaption (to provide meaningful parameter estimates to unspecified future applications). Spurious voltages were rapidly rejected with a mere 0.3% trajectory deviation, stabilizing quickly with a final (steady state) deviation of 0.01%. The demonstrated abilities to reject the deleterious spurious effects are compared to nominal figures of merit for timing accuracy of various computer systems to conclude the proposed methods are effective for some applications, but insufficient for others.
Selected Physical and Flowability Properties of Evolving Distillers Dried Grains With Solubles (DDGS)
Authors: Rosentrater Kurt A , Zhang Weitao
Published: August 2021

With the rapid development of the ethanol industry over the past few decades, research on distillers dried grains with solubles (DDGS), its main coproduct, has increased in recent years. However, research about the basic properties of DDGS lacks comprehensiveness. This study examined 16 DDGS samples from 10 ethanol plants in the Midwest U.S., and used standard laboratory methods to measure a series of physical and flowability properties. Results showed an average moisture content of 8.69% (w. b.), water activity of 0.55, angle of repose of 48.04°, shear strength of 0.0324 kg/cm2, geometric mean diameter (dgw) of 0.74 mm, geometric standard deviation (Sgw) of 1.72 mm, loose bulk density of 483.9 kg/m3, packed bulk density of 568.5 kg/m3, Hunter L of 56.71, Hunter a of 13.85, and Hunter b of 46.51. This study represents a step toward a more complete understanding of DDGS, and how various properties change as production practices evolve in the ethanol industry.
Diversity and Variation of Asymbiotic Nitrogen-Fixing Microorganisms in Alpine Grasslands on the Tibetan Plateau
Authors: Li Wenyan , Li Fei , Zeng Haijun , Ma Lin , Qi Lingyan , Wang Xiaochun , Wang Wenyin , Peng Zhen , Degen A. Allan , Bai Yanfu , Zhang Tao , Huang Mei , Han Jin , Shang Zhanhuan
Published: August 2021

Asymbiotic nitrogen-fixing (ANF) bacteria contribute a substantial amount of nitrogen in ecosystems, especially in those with low symbiotic nitrogen fixation (SNF) capability. Degradation of alpine grassland is widespread on the Tibetan Plateau and sown grassland has become one of the main strategies for grassland restoration. However, the diversity and community structure of ANF bacteria in different grassland types remain unknown. The aim of this study was to fill this gap. Soil samples were obtained from 39 grassland plots selected from three counties in the eastern Tibetan Plateau. The plots were classified as natural grassland (NG), sown grassland (SG), lightly degraded grassland (LDG), and severely degraded grassland (SDG). ANF microbial communities of the four grassland types were compared at the level of community and species diversity by 16S rRNA high-throughput sequencing technology. The phylum Proteobacteria accounted for >72% of the ANF bacteria. The community structures of soil ANF bacteria differed significantly (p < 0.01) among grassland types. We concluded that: (1) planting gramineous forage could possibly mitigate the decrease in diversity of soil ANF bacteria caused by grassland degradation; and (2) the diversity of soil ANF bacteria in alpine grassland of the Tibetan Plateau is closely related to grassland degradation and restoration.
Identification and Validation of a PPP1R12A-Related Five-Gene Signature Associated With Metabolism to Predict the Prognosis of Patients With Prostate Cancer
Authors: Zou Zhihao , Liu Ren , Liang Yingke , Zhou Rui , Dai Qishan , Han Zhaodong , Jiang Minyao , Zhuo Yangjia , Zhang Yixun , Feng Yuanfa , Zhu Xuejin , Cai Shanghua , Lin Jundong , Tang Zhenfeng , Zhong Weide , Liang Yuxiang
Published: August 2021

Background

Prostate cancer (PCa) is the most common malignant male neoplasm in the American male population. Our prior studies have demonstrated that protein phosphatase 1 regulatory subunit 12A (PPP1R12A) could be an efficient prognostic factor in patients with PCa, promoting further investigation. The present study attempted to construct a gene signature based on PPP1R12A and metabolism-related genes to predict the prognosis of PCa patients.

Methods

The mRNA expression profiles of 499 tumor and 52 normal tissues were extracted from The Cancer Genome Atlas (TCGA) database. We selected differentially expressed PPP1R12A-related genes among these mRNAs. Tandem affinity purification-mass spectrometry was used to identify the proteins that directly interact with PPP1R12A. Gene set enrichment analysis (GSEA) was used to extract metabolism-related genes. Univariate Cox regression analysis and a random survival forest algorithm were used to confirm optimal genes to build a prognostic risk model.

Results

We identified a five-gene signature (PPP1R12A, PTGS2, GGCT, AOX1, and NT5E) that was associated with PPP1R12A and metabolism in PCa, which effectively predicted disease-free survival (DFS) and biochemical relapse-free survival (BRFS). Moreover, the signature was validated by two internal datasets from TCGA and one external dataset from the Gene Expression Omnibus (GEO).

Conclusion

The five-gene signature is an effective potential factor to predict the prognosis of PCa, classifying PCa patients into high- and low-risk groups, which might provide potential novel treatment strategies for these patients.
Analysis of the Expression and Prognostic Value of Annexin Family Proteins in Bladder Cancer
Authors: Wu WenBo , Jia GaoZhen , Chen Lei , Liu HaiTao , Xia ShuJie
Published: August 2021

Background

Bladder cancer (BC) is the most common tumor of the urinary system. Non-muscle-invasive bladder cancer (NMIBC) has a high recurrence rate after surgery, and patients with muscle-invasive bladder cancer (MIBC) have poor quality of life after radical surgery. Understanding the molecular mechanism of bladder cancer is helpful for providing a more appropriate treatment approach. Annexins are calcium-binding proteins and play an important role in different tumor cells. However, the role of the annexin family in bladder cancer has not been studied in detail.

Methods

ONCOMINE, UALCAN, TIMER2.0, Kaplan-Meier Plotter, cBioPortal, and WebGestalt were utilized in this study.

Results

ANXA2, ANXA3, ANXA4, ANXA8, and ANXA9 were significantly increased in bladder tumor tissues, while ANXA6, ANXA7, and ANXA11 were significantly decreased. ANXA1, ANXA2, ANXA3, ANXA5, ANXA6, ANXA7, and ANXA9 had prognostic value in bladder cancer. In addition, specific annexins were specifically expressed in different subtypes of MIBC and were related to the histological morphology of bladder tumors. ANXA1, ANXA2, ANXA3, ANXA5, ANXA6, ANXA7, and ANXA8 were highly expressed in basal-subtype MIBC, while ANXA4, ANXA9, ANXA10, and ANXA11 were mainly expressed in luminal-subtype MIBC. Finally, we analyzed the possible mechanisms of ANXAs in different subtypes of bladder cancer through GO and KEGG analyses and the correlation between ANXAs and immune infiltration in the tumor microenvironment.

Conclusion

Taken together, our results indicate that annexins might play important roles in BC and have the potential to be used as markers for subtype classification.
The Potential of Self-Managed Abortion to Expand Abortion Access in Humanitarian Contexts
Authors: Jayaweera Ruvani , Powell Bill , Gerdts Caitlin , Kakesa Jessica , Ouedraogo Ramatou , Ramazani Uwezo , Wado Yohannes Dibaba , Wheeler Erin , Fetters Tamara
Published: August 2021

Refugees and displaced people face uniquely challenging barriers to abortion access, including the collapse of health systems, statelessness, and a lack of prioritization of sexual and reproductive health services by humanitarian agencies. This article summarizes the evidence around abortion access in humanitarian contexts, and highlights the opportunities for interventions that could increase knowledge and support around self-managed abortion. We explore how lessons learned from other contexts can be applied to the development of effective interventions to reduce abortion-related morbidity and mortality, and may improve access to information about safe methods of abortion, including self-management, in humanitarian settings. We conclude by laying out a forward-thinking research agenda that addresses gaps in our knowledge around abortion access and experiences in humanitarian contexts.
The Inflammatory Feed-Forward Loop Triggered by the Complement Component C3 as a Potential Target in Endometriosis
Authors: Agostinis Chiara , Zorzet Sonia , Balduit Andrea , Zito Gabriella , Mangogna Alessandro , Macor Paolo , Romano Federico , Toffoli Miriam , Belmonte Beatrice , Morello Gaia , Martorana Anna , Borelli Violetta , Ricci Giuseppe , Kishore Uday , Bulla Roberta
Published: August 2021

The complement system is a major component of humoral innate immunity, acting as a first line of defense against microbes via opsonization and lysis of pathogens. However, novel roles of the complement system in inflammatory and immunological processes, including in cancer, are emerging. Endometriosis (EM), a benign disease characterized by ectopic endometrial implants, shows certain unique features of cancer, such as the capacity to invade surrounding tissues, and in severe cases, metastatic properties. A defective immune surveillance against autologous tissue deposited in the peritoneal cavity allows immune escape for endometriotic lesions. There is evidence that the glandular epithelial cells found in endometriotic implants produce and secrete the complement component C3. Here, we show, using immunofluorescence and RT-qPCR, the presence of locally synthesized C3 in the ectopic endometriotic tissue, but not in the eutopic tissue. We generated a murine model of EM via injection of minced uterine tissue from a donor mouse into the peritoneum of recipient mice. The wild type mice showed greater amount of cyst formation in the peritoneum compared to C3 knock-out mice. Peritoneal washings from the wild type mice with EM showed more degranulated mast cells compared to C3 knock-out mice, consistent with higher C3a levels in the peritoneal fluid of EM patients. We provide evidence that C3a participates in an auto-amplifying loop leading to mast cell infiltration and activation, which is pathogenic in EM. Thus, C3 can be considered a marker of EM and its local synthesis can promote the engraftment of the endometriotic cysts.
Unravelling the Shared Genetic Mechanisms Underlying 18 Autoimmune Diseases Using a Systems Approach
Authors: Gokuladhas Sreemol , Schierding William , Golovina Evgeniia , Fadason Tayaza , O’Sullivan Justin
Published: August 2021

Autoimmune diseases (AiDs) are complex heterogeneous diseases characterized by hyperactive immune responses against self. Genome-wide association studies have identified thousands of single nucleotide polymorphisms (SNPs) associated with several AiDs. While these studies have identified a handful of pleiotropic loci that confer risk to multiple AiDs, they lack the power to detect shared genetic factors residing outside of these loci. Here, we integrated chromatin contact, expression quantitative trait loci and protein-protein interaction (PPI) data to identify genes that are regulated by both pleiotropic and non-pleiotropic SNPs. The PPI analysis revealed complex interactions between the shared and disease-specific genes. Furthermore, pathway enrichment analysis demonstrated that the shared genes co-occur with disease-specific genes within the same biological pathways. In conclusion, our results are consistent with the hypothesis that genetic risk loci associated with multiple AiDs converge on a core set of biological processes that potentially contribute to the emergence of polyautoimmunity.
Prednisone Reprograms the Transcriptional Immune Cell Landscape in CNS Autoimmune Disease
Authors: Li He , Gao Yuehan , Xie Lihui , Wang Rong , Duan Runping , Li Zhaohuai , Chen Binyao , Zhu Lei , Wang Xianggui , Su Wenru
Published: August 2021

Glucocorticoids (GCs) are widely used immunosuppressive drugs for autoimmune diseases, although considerable gaps exist between current knowledge of the mechanisms of GCs and their conclusive immune-regulatory effects. Here we generated a single-cell transcriptional immune cell atlas based on prednisone-treated or untreated experimental autoimmune uveitis (EAU) mice. Immune cells were globally activated in EAU, and prednisone partially reversed this effect in terms of cell composition, gene expression, transcription factor regulation, and cell-cell communication. Prednisone exerted considerable rescue effects on T and B cells and increased the proportion of neutrophils. Besides commonly regulated transcriptional factors (Fosb, Jun, Jund), several genes were only regulated in certain cell types (e.g. Cxcr4 and Bhlhe40 in T cells), suggesting cell-type-dependent immunosuppressive properties of GC. These findings provide new insights into the mechanisms behind the properties and cell-specific effects of GCs and can potentially benefit immunoregulatory therapy development.
Should Hybrids Be Used in Coral Nurseries? A Case Study Comparing Caribbean Acropora spp. and Their Hybrid in the Bahamas
Authors: VanWynen Cassie M. , Hightshoe Morgan V. , Fogarty Nicole D. , Dahlgren Craig P. , Gilliam David S.
Published: August 2021

For decades, coral reef ecosystems have been in decline due to environmental stressors such as rising sea temperatures, increased disease prevalence, and other local anthropogenic sources. Considering this decline, coral restoration efforts in the Caribbean have been implemented to promote reef recovery with a focus on the coral genus Acropora. Current methods target the threatened species Acropora cervicornis and A. palmata, but little is known about the restoration potential of their hybrid taxon, A. prolifera. Using interspecific hybrids with higher fitness than one or both parental species has gained traction as a novel restoration technique. For this study, three in situ coral tree nurseries were established around Great Stirrup Cay, The Bahamas, to compare the growth and survival among acroporid taxa. Three 150 mm fragments from six putative genotypes of each acroporid taxa were collected from reefs around New Providence, The Bahamas, and transported to Great Stirrup Cay in June 2018. One fragment from each genotype was transported to each nursery site, cut into three sections (apical, middle, and basal), and suspended from PVC coral trees. Fragment survival was collected monthly for 13 months, and Total Linear Extension (TLE) values were calculated for each fragment monthly for 12 months. Nursery site significantly affected fragment survival, while taxon and fragment section did not. Total fragment mortality was 29.3% in the first month but ranged from 0 to 5% for the rest of the study period until July 2019 (32.7% of remaining fragments died primarily at N1). Overall, A. prolifera growth was significantly greater than the parental species. Taxon, nursery site, and fragment section were identified as important factors affecting TLE. Apical A. prolifera fragment sections at site N3 had the greatest average linear growth at 12 months and had the greatest average growth rate per month. This study highlights the rapid growth rate of hybrid corals and suggests that fragment sections have equivalent survival and growth. Consequently, these results suggest that restoration managers may capitalize on fast growing hybrids for outplanting to degraded reefs and to increase the scale of nursery projects.
Salinity Driven Selection and Local Adaptation in Baltic Sea Mytilid Mussels
Authors: Knöbel Loreen , Nascimento-Schulze Jennifer C. , Sanders Trystan , Zeus Dominique , Hiebenthal Claas , Barboza Francisco R. , Stuckas Heiko , Melzner Frank
Published: August 2021

Baltic blue mussels can colonise and dominate habitats with far lower salinity (<10 psu) than other Mytilus congeners. Pervasive gene flow was observed between Western Baltic Mytilus edulis living at high salinity conditions and Eastern Baltic M. trossulus living at lower salinites, with highest admixture proportions within a genetic transition zone located at intermediate salinities (Darss Sill area). Yet, we do not understand the impacts of low salinity on larval performance, and how salinity may act as an early selective pressure during passive larval drift across salinity gradients. This study tested whether larvae originating from two different populations along the natural salinity cline in the Baltic Sea have highest fitness at their native salinities. Our results suggest that Eastern Baltic M. trossulus (Usedom, 7 psu) and Western Baltic M. edulis (Kiel, 16 psu) larvae display better performance (fitness components: growth, mortality, settlement success) when reared at their respective native salinities. This suggests that these populations are adapted to their local environment. Additionally, species diagnostic markers were used for genetic analyses of transition zone (Ahrenshoop, 11 psu) mussel larvae exposed to low salinity. This revealed that low salinity selection resulted in a shift towards allele frequencies more typical for Eastern Baltic M. trossulus. Thus, salinity acts as a selective pressure during the pre-settlement phase and can shape the genetic composition of Baltic mussel populations driving local adaptation to low salinity. Future climate change driven desalination, therefore, has the potential to shift the Baltic Sea hybrid gradient westward with consequences for benthic ecosystem structure.
Evaluation of the Anti-fouling Efficacy of Bacillus licheniformis Extracts Under Environmental and Natural Conditions
Authors: Muras Andrea , Larroze Severine , Mayer Celia , Teixeira Tânia , Wengier Reut , Benayahu Yehuda , Otero Ana
Published: August 2021

There is an increasing interest in developing innovative coatings and testing natural products with anti-fouling activity to substitute current highly toxic biocides that have a harmful impact on marine organisms. Bacillus licheniformis species have shown different anti-biofilm and anti-fouling activities in vitro, but so far, its efficacy in field trials has not been tested. For this purpose, the capacity of different extracts of B. licheniformis NCTC 10341T to prevent micro and macro-fouling was first tested in vitro. The methanol cell extract (MCE) inhibited bacterial biofilm formation without significantly affecting planktonic growth and displayed a significant efficacy to prevent larval settlement of the macro-fouler Bugula neritina in vitro without inducing lethality. Additionally, the MCE presented low toxicity against the non-target species Artemia salina. The B. licheniformis MCE was then incorporated in a self-polishing paint at 2 and 5% w/w and tested in a static immersion experiment in the Gulf of Aqaba (northern Red Sea) for 180 days. Fouling coverage decreased by 30% in the 5% MCE-treated panels in comparison with the control panels. Differences in the anti-biofilm activity of the extracts depending on the culture medium highlight the importance of the strict control of culture conditions for the production of biomass with stable bioactive activity. The results indicate the potential of B. licheniformis NCTC 10341T crude extracts for environmentally friendly anti-fouling applications, although a deeper characterization of the bioactive compounds present in the B. licheniformis MCE and its mode of action is required to allow strict control of the activity of the extracts to achieve large-scale industrial production.
Terahertz Transmission Characteristics of Double-Layer Plasmonic Metamaterial and LC-Based Structure
Authors: Yang Jun , Xu Junjie , Mao Rongxin , Li Ying , Yin Zhiping , Deng Guangsheng , Cai Fei
Published: August 2021

In this paper, we present a novel design of an electrically tunable metamaterial device in the terahertz frequency range of 325–500 GHz. The device is analyzed and optimized using an equivalent circuit and numerical simulation. The experimental and simulation results are almost identical in the entire design frequency range. A maximum modulation depth of 90.87% is achieved in the transmission window. The bandpass width decreases from 102.55 to 28.7 GHz as the bias voltage increases from 0 to 30 V. This structure provides new insights into the potential of electrically tunable terahertz devices for a wide range of applications.
The Risk of Tuberculosis Infection in Non-dialysis Chronic Kidney Disease Patients
Authors: Li Chia-Hsiang , Chen Hung-Jen , Chen Wei-Chun , Tu Chih-Yen , Hsia Te-Chun , Hsu Wu-Huei , Chang Chiz-Tzung , Huang Chiu-Ching , Bau Da-Tian , Chou Che-Yi
Published: August 2021

Background: Patients with chronic kidney disease (CKD) receiving maintenance renal replacement therapy are at higher risk of tuberculosis (TB) infection. The risk of TB infection in CKD patients not receiving dialysis is unknown.

Aim: We conduct this study to test the hypothesis that TB infection is negatively correlated to renal function.

Design: Non-dialysis CKD stage 1–5 patients, admitted in China Medical University Hospital from January of 2003 to May of 2014, were enrolled in this study and were prospectively followed up to the diagnosis of TB, death, loss to follow-up, or December 2014. The risk factors of TB infection were analyzed using competing-risks regression analysis with time-varying covariates. The initiation of dialysis and patients' death were considered as competing events. Patients' estimated glomerular filtration rate (eGFR) and body mass index (BMI) were recorded at enrollment.

Results: They were followed-up for a median duration of 1.4 years. Of the 7221 patients, TB infection was identified in 114 patients. Higher eGFR was associated with lower risk of TB infection (P < 0.01). The adjusted subdistribution hazard ratio (aSHR) was 0.82 [95% confidence interval (CI), 0.72 to 0.94] for every 5 ml/min/1.73 m2 increase in eGFR. In addition, higher BMI (p = 0.01) was associated with a lower risk of TB infection and the aSHR was 0.91 (95% CI, 0.85 to 0.98) for every 1 kg/m2 increase in BMI.

Conclusion: Renal function and body mass index are independently associated with the risk of tuberculosis infection in patients with chronic kidney disease not receiving dialysis.
Frailty Status Among the Elderly of Different Genders and the Death Risk: A Follow-Up Study
Authors: Shi Jing , Tao Yongkang , Meng Li , Zhou Baiyu , Duan Chunbo , Xi Huan , Yu Pulin
Published: August 2021

Background: Frailty in the elderly population is currently a frontier and focus in the field of health and aging. The goal of this study was to explore the frailty status among the elderly of different genders and its influence on the risk of death during 11 years.

Methods: Frailty index (FI) was used to evaluate the frailty status in the elderly based on the baseline data conducted in 2009; and death as outcome variables collected in 2020 were analyzed. The difference of the frailty level and mortality of different genders was compared. Cox regression and Kaplan–Meier curves were applied to evaluate the influence on the risk of death and the 11-year survival of the elderly at different level of frailty, respectively.

Results: Totally, 1,246 elderly people were recruited. The mortality in men (43.7%, 227/519) was statistically higher than that in women (34.3%, 249/727) (x2 = 11.546, P = 0.001). Deficits accumulated exponentially with age, and at all ages, women accumulated more deficits than do men on average (B = 0.030 vs. 0.028, t = 4.137, P = 0.023). For any given level of frailty, the mortality rate is higher in men than in women, and the difference in mortality between genders reached the peak when FI value was 0.26. Cox regression analysis showed that FI value had a greater impact on the risk of death in older men (HR = 1.171, 95%CI: 1.139~1.249)than that in older women (HR = 1.119, 95%CI: 1.039~1.137). Survival analysis showed that the median 11-year survival time in women was longer than that in men (95.26 vs. 89.52 months, Log rank = 9.249, P = 0.002). Kaplan–Meier curves showed that the survival rate decreased with the increase of frailty, and at the same level of frailty, survival time in older women was longer than that in older men, except for severe frailty (FI ≥ 0.5).

Conclusion: The frailty status and its influence on mortality are different among the older people of different genders; therefore, specific interventions for frailty should be conducted in the elderly population of different genders, as well as of different degrees of frailty.
Impact of First-Line Antimicrobials on Chlamydia trachomatis-Induced Changes in Host Metabolism and Cytokine Production
Authors: Käding Nadja , Schmidt Nis , Scholz Celeste , Graspeuntner Simon , Rupp Jan , Shima Kensuke
Published: August 2021

Urogenital infections with Chlamydia trachomatis (C. trachomatis) are the most common bacterial sexually transmitted diseases worldwide. As an obligate intracellular bacterium, chlamydial replication and pathogenesis depends on the host metabolic activity. First-line antimicrobials such as doxycycline (DOX) and azithromycin (AZM) have been recommended for the treatment of C. trachomatis infection. However, accumulating evidence suggests that treatment with AZM causes higher rates of treatment failure than DOX. Here, we show that an inferior efficacy of AZM compared to DOX is associated with the metabolic status of host cells. Chlamydial metabolism and infectious progeny of C. trachomatis were suppressed by therapeutic relevant serum concentrations of DOX or AZM. However, treatment with AZM could not suppress host cell metabolic pathways, such as glycolysis and mitochondrial oxidative phosphorylation, which are manipulated by C. trachomatis. The host cell metabolic activity was associated with a significant reactivation of C. trachomatis after removal of AZM treatment, but not after DOX treatment. Furthermore, AZM insufficiently attenuated interleukin (IL)-8 expression upon C. trachomatis infection and higher concentrations of AZM above therapeutic serum concentration were required for effective suppression of IL-8. Our data highlight that AZM is not as efficient as DOX to revert host metabolism in C. trachomatis infection. Furthermore, insufficient treatment with AZM failed to inhibit chlamydial reactivation as well as C. trachomatis induced cytokine responses. Its functional relevance and the impact on disease progression have to be further elucidated in vivo.
The Association Between Mycobacteria-Specific Antigen-Induced Cytokines and Host Response to Latent Tuberculosis Infection Treatment in a Chinese Population
Authors: Cao Xuefang , Xin Henan , Zhang Haoran , Liu Jianmin , Pan Shouguo , Du Ying , Feng Boxuan , Quan Zhusheng , Guan Ling , Shen Fei , Liu Zisen , Wang Dakuan , Zhang Bin , Guan Xueling , Yan Jiaoxia , Jin Qi , Gao Lei
Published: August 2021

Objectives

Exploring biomarkers monitoring latent tuberculosis infection (LTBI) treatment effectiveness would benefit optimizing the therapeutic regimen. This study aims to identify potential mycobacteria-specific antigen-induced cytokines associated with host responses to preventive treatment.

Methods

Based on a randomized controlled trial on LTBI treatment among individuals with chest radiography abnormalities suggestive of prior tuberculosis (TB), the dynamically changed cytokine levels in QuantiFERON-TB Gold In-Tube (QFT) supernatants were estimated during the treatment by bead-based multiplex assays and enzyme-linked immunosorbent assay.

Results

In total, 63 treated participants and 32 untreated controls were included in the study. The levels of 13 background-corrected mycobacteria-specific antigen-stimulated cytokines [basic fibroblast growth factor (FGF), growth-regulated oncogene (GRO)-α, interleukin (IL)-1α, IL-1ra, IL-12 (p70), stem cell factor (SCF), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), IL-8, interferon (IFN)-α2, IL-5, IL-12 (p40), leukemia inhibitory factor (LIF), and IL-17A] were found to be statistically different between before and after treatment in treated participants, while no statistically differences were observed in untreated controls. Among these 13 cytokines, the level of IL-8 was significantly lower in the QFT reversed group than that in the non-reversed group (p= 0.028) among treated participants, while such a difference was not found for untreated controls (p= 0.292).

Conclusion

Our results suggested that the lower level of mycobacteria-specific antigen-induced IL-8 might be associated with the host’s positive response to LTBI treatment.
Case Report: Chronic Adaptive Deep Brain Stimulation Personalizing Therapy Based on Parkinsonian State
Authors: Nakajima Asuka , Shimo Yasushi , Fuse Atsuhito , Tokugawa Joji , Hishii Makoto , Iwamuro Hirokazu , Umemura Atsushi , Hattori Nobutaka
Published: August 2021

We describe the case of a 51-year-old man with Parkinson's disease (PD) presenting with motor fluctuations, who received bilateral subthalamic deep brain stimulation (DBS) with an adaptive DBS (aDBS) device, Percept™ PC (Medtronic, Inc. , Minneapolis, MN). This device can deliver electrical stimulations based on fluctuations of neural oscillations of the local field potential (LFP) at the target structure. We observed that the LFP fluctuations were less evident inside the hospital than outside, while the stimulation successfully adapted to beta oscillation fluctuations during the aDBS phase without any stimulation-induced side effects. Thus, this new device facilitates condition-dependent stimulation; this new stimulation method is feasible and provides new insights into the pathophysiological mechanisms of PD.
Small RNA Sequencing Identifies PIWI-Interacting RNAs Deregulated in Glioblastoma—piR-9491 and piR-12488 Reduce Tumor Cell Colonies In Vitro
Authors: Bartos Michael , Siegl Frantisek , Kopkova Alena , Radova Lenka , Oppelt Jan , Vecera Marek , Kazda Tomas , Jancalek Radim , Hendrych Michal , Hermanova Marketa , Kasparova Petra , Pleskacova Zuzana , Vybihal Vaclav , Fadrus Pavel , Smrcka Martin , Lakomy Radek , Lipina Radim , Cesak Tomas , Slaby Ondrej , Sana Jiri
Published: August 2021

Glioblastoma (GBM) is the most frequently occurring primary malignant brain tumor of astrocytic origin. To change poor prognosis, it is necessary to deeply understand the molecular mechanisms of gliomagenesis and identify new potential biomarkers and therapeutic targets. PIWI-interacting RNAs (piRNAs) help in maintaining genome stability, and their deregulation has already been observed in many tumors. Recent studies suggest that these molecules could also play an important role in the glioma biology. To determine GBM-associated piRNAs, we performed small RNA sequencing analysis in the discovery set of 19 GBM and 11 non-tumor brain samples followed by TaqMan qRT-PCR analyses in the independent set of 77 GBM and 23 non-tumor patients. Obtained data were subsequently bioinformatically analyzed. Small RNA sequencing revealed 58 significantly deregulated piRNA molecules in GBM samples in comparison with non-tumor brain tissues. Deregulation of piR-1849, piR-9491, piR-12487, and piR-12488 was successfully confirmed in the independent groups of patients and controls (all p < 0.0001), and piR-9491 and piR-12488 reduced GBM cells’ ability to form colonies in vitro. In addition, piR-23231 was significantly associated with the overall survival of the GBM patients treated with Stupp regimen (p = 0.007). Our results suggest that piRNAs could be a novel promising diagnostic and prognostic biomarker in GBM potentially playing important roles in gliomagenesis.
The Use of Micro Retractor in Endoscopic Endonasal Posterior Pseudocapsule Resection of Pituitary Macroadenoma. Technical Note
Authors: Xie Tao , Zhang Xiaobiao , Qu Chenghui , Li Chen
Published: August 2021

Background

The endoscopic endonasal approach and extra-pseudocapsule resection may be the main progress in modern pituitary surgery. However, for pituitary macroadenomas, discerning the pseudocapsule in the posterior plane of the tumor may be difficult. When the anterior-inferior debulking is performed, the early subsidence of the thinning normal pituitary gland and enlarged diaphragm may obstruct the surgical dissection view.

Method

We describe the technique of using a micro retractor for the endoscopic endonasal posterior pseudocapsule resection of pituitary macroadenomas. This micro retractor that was 2 mm in width was placed at the 12 o’clock position on the nostrils, and the end was fixed in the flexible arms of the self-retaining retractor system. The head of the micro retractor elevated the herniated diaphragm sellae in order to continue the posterior pseudocapsule resection of the pituitary macroadenoma.

Result

The technique was performed very easily and no complication was observed.

Conclusion

The use of this micro retractor can increase the view of the posterior margin of the adenomas to facilitate the pseudocapsule dissection.
Ivermectin has New Application in Inhibiting Colorectal Cancer Cell Growth
Authors: Zhou Shican , Wu Hang , Ning Wenjuan , Wu Xiao , Xu Xiaoxiao , Ma Yuanqiao , Li Xingwang , Hu Junhong , Wang Chenyu , Wang Junpeng
Published: August 2021

Colorectal cancer (CRC) is the third most common cancer worldwide and still lacks effective therapy. Ivermectin, an antiparasitic drug, has been shown to possess anti-inflammation, anti-virus, and antitumor properties. However, whether ivermectin affects CRC is still unclear. The objective of this study was to evaluate the influence of ivermectin on CRC using CRC cell lines SW480 and SW1116. We used CCK-8 assay to determine the cell viability, used an optical microscope to measure cell morphology, used Annexin V-FITC/7-AAD kit to determine cell apoptosis, used Caspase 3/7 Activity Apoptosis Assay Kit to evaluate Caspase 3/7 activity, used Western blot to determine apoptosis-associated protein expression, and used flow cytometry and fluorescence microscope to determine the reactive oxygen species (ROS) levels and cell cycle. The results demonstrated that ivermectin dose-dependently inhibited colorectal cancer SW480 and SW1116 cell growth, followed by promoting cell apoptosis and increasing Caspase-3/7 activity. Besides, ivermectin upregulated the expression of proapoptotic proteins Bax and cleaved PARP and downregulated antiapoptotic protein Bcl-2. Mechanism analysis showed that ivermectin promoted both total and mitochondrial ROS production in a dose-dependent manner, which could be eliminated by administering N-acetyl-l-cysteine (NAC) in CRC cells. Following NAC treatment, the inhibition of cell growth induced by ivermectin was reversed. Finally, ivermectin at low doses (2.5 and 5 µM) induced CRC cell arrest. Overall, ivermectin suppressed cell proliferation by promoting ROS-mediated mitochondrial apoptosis pathway and inducing S phase arrest in CRC cells, suggesting that ivermectin might be a new potential anticancer drug therapy for human colorectal cancer and other cancers.
Toxicity of Immune-Checkpoint Inhibitors in Hematological Malignancies
Authors: Hradska Katarina , Hajek Roman , Jelinek Tomas
Published: August 2021

Immune checkpoint inhibitors (ICIs), especially those targeting the programmed-death 1 (PD-1) receptor and its ligands, have become indispensable agents in solid tumor anti-cancer therapy. Concerning hematological malignancies, only nivolumab and pembrolizumab have been approved for the treatment of relapsed and refractory classical Hodgkin lymphoma and primary mediastinal large B cell lymphoma to date. Nevertheless, clinical research in this field is very active. The mechanism of action of ICIs is based on unblocking the hindered immune system to recognize and eliminate cancer cells, but that also has its costs in the form of ICI-specific immune related adverse events (irAEs), which can affect any organ system and can even be lethal. In this article, we have reviewed all prospective blood cancer clinical trials investigating ICIs (both monotherapy and combination therapy) with available toxicity data with the purpose of determining the incidence of irAEs in this specific setting and to offer a brief insight into their management, as the use of immune checkpoint blockade is not so frequent in hemato-oncology.
Distribution Evaluation of Tenofovir in the Breast Milk of Mothers With HBeAg-Positive Chronic HBV Infection After Treatment With Tenofovir Alafenamide and Tenofovir Disoproxil Fumarate by a Sensitive UPLC-MS/MS Method
Authors: Yang Na , Zhou Guanlun , Cheng Xiaoliang , He Jun , Chen Yan , Chen Chao , Li Meijuan , Ge Jiajia , Wang Min , Zhang Tianqi , Ge Weihong , Zhu Huaijun , Han Guorong
Published: August 2021

Tenofovir alafenamide (TAF) is a novel prodrug of tenofovir (TFV) that has been approved for the treatment of chronic hepatitis B virus (HBV) infection. It has greater plasma stability and more favorable renal safety than tenofovir disoproxil fumarate (TDF), the first approved oral prodrug of TFV. However, the distribution of TFV in the breast milk of mothers treated with TAF is still unclear. In this study, sixteen participants with chronic HBV infection were enrolled and received antiretroviral therapy with 25 mg of TAF or 300 mg of TDF daily from 24 to 28 weeks of gestation until the 4th week postpartum. For the first time, the distribution of TFV in the breast milk of mothers with chronic HBV infection treated with TAF and its difference from TDF were evaluated by using a sensitive UPLC–MS/MS method. Chromatographic separation was achieved on a Waters ACQUITY UPLC BEH C18 column (1.7 µm 2.1 × 100 mm). Mass spectrometry analysis was performed in positive electrospray ionization mode and multiple reaction monitoring (MRM) conditions of transitions m/z 288.1→176.2 for TFV. This method was linear from 0.5 to 500 ng/ml. Surprisingly, on the third postpartum day, the median Cmax of TFV in the breast milk was much higher in the mothers treated with TAF (101.2 ng/ml) than TDF (21.6 ng/ml) at a similar Tmax of 4 h. Accordingly, the median AUC0-8 value was 755.6 ng h/mL in the mothers taking TAF, which was at a 5-fold higher level than TDF. The concentration of TFV in the breast milk of mothers in both groups decreased with increasing lactation time. These data indicated that there was a relatively higher exposure of TFV in the breast milk of mothers taking TAF, despite the lower dosage compared to TDF. This study provides support for further evaluating the safety of breastfeeding after the administration of TAF and TDF.
Correlation Between Soluble Klotho and Vascular Calcification in Chronic Kidney Disease: A Meta-Analysis and Systematic Review
Authors: Liu QiFeng , Yu LiXia , Yin XiaoYa , Ye JianMing , Li ShaSha
Published: August 2021

Background: The correlation between soluble Klotho (sKlotho) level and vascular calcification (VC) in patients with chronic kidney disease (CKD) remains controversial. Using meta-analysis, we aimed to address this controversy and assess the feasibility of applying sKlotho as a biomarker for VC.

Methods: Medical electronic databases were thoroughly searched for eligible publications on the association between sKlotho level and VC in CKD patients. Effectors, including correlation coefficients (r), odds ratios (ORs), hazard ratio (HR) or β-values, and 95% confidence intervals (CIs) were extracted and combined according to study design or effector calculation method. Pooled effectors were generated using both random-effects models and fixed-effects models according to I2-value. Origin of heterogeneity was explored by sensitivity analysis and subgroup analysis.

Results: Ten studies with 1,204 participants from a total of 1,199 publications were eligible and included in this meta-analysis. The combined correlation coefficient (r) was [−0.33 (−0.62, −0.04)] with significant heterogeneity (I2 = 89%, p < 0.001) based on Spearman correlation analysis, and this significant association was also demonstrated in subgroups. There was no evidence of publication bias. The combined OR was [3.27 (1.70, 6.30)] with no evidence of heterogeneity (I2 = 0%, p = 0.48) when sKlotho was treated as a categorical variable or [1.05 (1.01, 1.09)] with moderate heterogeneity (I2 = 63%, p = 0.10) when sKlotho was treated as a continuous variable based on multivariate logistic regression. No significant association was observed and the pooled OR was [0.29 (0.01, 11.15)] with high heterogeneity (I2 = 96%, p < 0.001) according to multivariate linear regression analysis. There was an inverse association between sKlotho and parathyroid hormone levels. The combined coefficient (r) was [−0.20 (−0.40, −0.01)] with significant heterogeneity (I2 = 86%, p < 0.001), and without obvious publication bias. No significant association was found between sKlotho and calcium or phosphate levels.

Conclusion: There exists a significant association between decreased sKlotho level and increased risk of VC in CKD patients. This raises the possibility of applying sKlotho as a biomarker for VC in CKD populations. Large, prospective, well-designed studies or interventional clinical trials are required to validate our findings.