bluuebunny/crossref_metadata_2025 huggingface dataset:
LINC00221 silencing prevents the progression of hepatocellular carcinoma through let-7a-5p-targeted inhibition of MMP11
Authors: Yang Lin , Si Hailong , Ma Meng , Fang Yu , Jiang Yina , Wang Jintao , Zhang Cheng , Xiao Haijuan
Published: April 2021

Background

Microarray profiles of hepatocellular carcinoma (HCC) identified that long intergenic noncoding RNA 00221 (LINC00221) was upregulated. Herein, we aimed to identify the functional significance and underlying mechanisms of LINC00221 in HCC.

Methods and results

Human HCC samples had increased expression of LINC00221. Effects of LINC00221 on HCC cellular functions were analyzed using gain- and loss-function approaches. LINC00221 knockdown repressed HCC cell growth, migration, and invasion and enhanced their apoptosis. This anti-tumor effect was validated in vivo. Online prediction showed the potential binding relationship between LINC00221 and let-7a-5p, as well as that between let-7a-5p and matrix metalloproteinase 11 (MMP11). The results of luciferase, RNA immunoprecipitation, and RNA pull-down assays identified that LINC00221 interacted with let-7a-5p to increase expression of MMP11. Furthermore, we demonstrated that LINC00221 silencing increased let-7a-5p and inhibited MMP11 expression, thereby delaying the progression of HCC in vitro.

Conclusions

Silencing of LINC00221 could prevent HCC progression via upregulating let-7a-5p and downregulating MMP11. As such, LINC00221 inhibition presents a promising antitumor strategy for the treatment of HCC.
Quantification of the misidentification of Plasmodium knowlesi as Plasmodium malariae by microscopy: an analysis of 1569 P. knowlesi cases
Authors: Mahittikorn Aongart , Masangkay Frederick Ramirez , Kotepui Kwuntida Uthaisar , Milanez Giovanni De Jesus , Kotepui Manas
Published: April 2021

Background

Plasmodium knowlesi is recognized as the fifth Plasmodium species causing malaria in humans. It is morphologically similar to the human malaria parasite Plasmodium malariae, so molecular detection should be used to clearly discriminate between these Plasmodium species. This study aimed to quantify the rate at which P. knowlesi is misidentified as P. malariae by microscopy in endemic and non-endemic areas.

Methods

The protocol of this systematic review was registered in the PROSPERO International Prospective Register of Systematic Reviews (ID = CRD42020204770). Studies reporting the misidentification of P. knowlesi as P. malariae by microscopy and confirmation of this by molecular methods in MEDLINE, Web of Science and Scopus were reviewed. The risk of bias in the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). The pooled prevalence and 95% confidence interval (CI) of the misidentification of P. knowlesi as P. malariae by microscopy were estimated using a random effects model. Subgroup analysis of the study sites was performed to demonstrate any differences in the misidentification rates in different areas. Heterogeneity across the included studies was assessed and quantified using Cochran’s Q and I2 statistics, respectively. Publication bias in the included studies was assessed using the funnel plot, Egger’s test and contour-enhanced funnel plot.

Results

Among 375 reviewed studies, 11 studies with a total of 1569 confirmed P. knowlesi cases in humans were included. Overall, the pooled prevalence of the misidentification of P. knowlesi as P. malariae by microscopy was estimated at 57% (95% CI 37–77%, I2: 99.3%). Subgroup analysis demonstrated the highest rate of misidentification in Sawarak, Malaysia (87%, 95% CI 83–90%, I2: 95%), followed by Sabah, Malaysia (85%, 95% CI 79–92%, I2: 85.1%), Indonesia (16%, 95% CI 6–38%), and then Thailand (4%, 95% CI 2–9%, I2: 95%).

Conclusion

Although the World Health Organization (WHO) recommends that all P. malariae-positive diagnoses made by microscopy in P. knowlesi endemic areas be reported as P. malariae/P. knowlesi malaria, the possibility of microscopists misidentifying P. knowlesi as P. malariae is a diagnostic challenge. The use of molecular techniques in cases with malariae-like Plasmodium with high parasite density as determined by microscopy could help identify human P. knowlesi cases in non-endemic countries.
Efficacy of interceptor® G2, a long-lasting insecticide mixture net treated with chlorfenapyr and alpha-cypermethrin against Anopheles funestus: experimental hut trials in north-eastern Tanzania
Authors: Tungu Patrick K. , Michael Elisante , Sudi Wema , Kisinza William W. , Rowland Mark
Published: April 2021

Background

The effectiveness of long-lasting insecticidal nets (LLIN), the primary method for preventing malaria in Africa, is compromised by evolution and spread of pyrethroid resistance. Further gains require new insecticides with novel modes of action. Chlorfenapyr is a pyrrole insecticide that disrupts mitochrondrial function and confers no cross-resistance to neurotoxic insecticides. Interceptor® G2 LN (IG2) is an insecticide-mixture LLIN, which combines wash-resistant formulations of chlorfenapyr and the pyrethroid alpha-cypermethrin. The objective was to determine IG2 efficacy under controlled household-like conditions for personal protection and control of wild, pyrethroid-resistant Anopheles funestus mosquitoes.

Methods

Experimental hut trials tested IG2 efficacy against two positive controls—a chlorfenapyr-treated net and a standard alpha-cypermethrin LLIN, Interceptor LN (IG1)—consistent with World Health Organization (WHO) evaluation guidelines. Mosquito mortality, blood-feeding inhibition, personal protection, repellency and insecticide-induced exiting were recorded after zero and 20 washing cycles. The trial was repeated and analysed using multivariate and meta-analysis.

Results

In the two trials held in NE Tanzania, An. funestus mortality was 2.27 (risk ratio 95% CI 1.13–4.56) times greater with unwashed Interceptor G2 than with unwashed Interceptor LN (p = 0.012). There was no significant loss in mortality with IG2 between 0 and 20 washes (1.04, 95% CI 0.83–1.30, p = 0.73). Comparison with chlorfenapyr treated net indicated that most mortality was induced by the chlorfenapyr component of IG2 (0.96, CI 0.74–1.23), while comparison with Interceptor LN indicated blood-feeding was inhibited by the pyrethroid component of IG2 (IG2: 0.70, CI 0.44–1.11 vs IG1: 0.61, CI 0.39–0.97). Both insecticide components contributed to exiting from the huts but the contributions were heterogeneous between trials (heterogeneity Q = 36, P = 0.02). WHO susceptibility tests with pyrethroid papers recorded 44% survival in An. funestus.

Conclusions

The high mortality recorded by IG2 against pyrethroid-resistant An. funestus provides first field evidence of high efficacy against this primary, anthropophilic, malaria vector.
Airborne Benzo[a]Pyrene may contribute to divergent Pheno-Endotypes in children
Authors: Choi Hyunok , Dostal Miroslav , Pastorkova Anna , Rossner Pavel , Sram Radim J.
Published: April 2021

Background

Asthma represents a syndrome for which our understanding of the molecular processes underlying discrete sub-diseases (i.e., endotypes), beyond atopic asthma, is limited. The public health needs to characterize etiology-associated endotype risks is becoming urgent. In particular, the roles of polyaromatic hydrocarbon (PAH), globally distributed combustion by-products, toward the two known endotypes – T helper 2 cell high (Th2) or T helper 2 cell low (non-Th2) – warrants clarification.

Objectives

To explain ambient B[a]P association with non-atopic asthma (i.e., a proxy of non-Th2 endotype) is markedly different from that with atopic asthma (i.e., a proxy for Th2-high endotype).

Methods

In a case-control study, we compare the non-atopic as well as atopic asthmatic boys and girls against their respective controls in terms of the ambient Benzo[a]pyrene concentration nearest to their home, plasma 15-Ft2-isoprostane (15-Ft2-isoP), urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), and lung function deficit. We repeated the analysis for i) dichotomous asthma outcome and ii) multinomial asthma—overweight/obese (OV/OB) combined outcomes.

Results

The non-atopic asthma cases are associated with a significantly higher median B[a]P (11.16 ng/m3) compared to that in the non-atopic controls (3.83 ng/m3; P-value < 0.001). In asthma-OV/OB stratified analysis, the non-atopic girls with lean and OV/OB asthma are associated with a step-wisely elevated B[a]P (median,11.16 and 18.00 ng/m3, respectively), compared to the non-atopic lean control girls (median, 4.28 ng/m3, P-value < 0.001). In contrast, atopic asthmatic children (2.73 ng/m3) are not associated with a significantly elevated median B[a]P, compared to the atopic control children (2.60 ng/m3; P-value > 0.05). Based on the logistic regression model, on ln-unit increate in B[a]P is associated with 4.7-times greater odds (95% CI, 1.9–11.5, P = 0.001) of asthma among the non-atopic boys. The same unit increase in B[a]P is associated with 44.8-times greater odds (95% CI, 4.7–428.2, P = 0.001) among the non-atopic girls after adjusting for urinary Cotinine, lung function deficit, 15-Ft2-isoP, and 8-oxodG.

Conclusions

Ambient B[a]P is robustly associated with non-atopic asthma, while it has no clear associations with atopic asthma among lean children. Furthermore, lung function deficit, 15-Ft2-isoP, and 8-oxodG are associated with profound alteration of B[a]P-asthma associations among the non-atopic children.
Correction to: LncRNA PTAR promotes EMT and invasionmetastasis in serous ovarian cancer by competitively binding miR-101-3p to regulate ZEB1 expression
Authors: Liang Haihai , Yu Tong , Han Yue , Jiang Hua , Wang Chengyu , You Tianyi , Zhao Xiaoguang , Shan Huitong , Yang Rui , Yang Lida , Shan Hongli , Gu Yunyan
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Correction to: LMTK3 inhibition affects microtubule Stability
Authors: Cilibrasi Chiara , Ditsiou Angeliki , Papakyriakou Athanasios , Mavridis George , Eravci Murat , Stebbing Justin , Gagliano Teresa , Giamas Georgios
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Central composite design for the development of carvedilol-loaded transdermal ethosomal hydrogel for extended and enhanced anti-hypertensive effect
Authors: Amarachinta Padmanabha Rao , Sharma Garima , Samed Noufel , Chettupalli Ananda Kumar , Alle Madhusudhan , Kim Jin-Chul
Published: April 2021

Background

Carvedilol, the anti-hypertensive drug, has poor bioavailability when administered orally. Ethosomes-mediated transdermal delivery is considered a potential route of administration to increase the bioavailability of carvedilol. The central composite design could be used as a tool to optimize ethosomal formulation. Thus, this study aims to optimize carvedilol-loaded ethosomes using central composite design, followed by incorporation of synthesized ethosomes into hydrogels for transdermal delivery of carvedilol.

Results

The optimized carvedilol-loaded ethosomes were spherical in shape. The optimized ethosomes had mean particle size of 130 ± 1.72 nm, entrapment efficiency of 99.12 ± 2.96%, cumulative drug release of 97.89 ± 3.7%, zeta potential of − 31 ± 1.8 mV, and polydispersity index of 0.230 ± 0.03. The in-vitro drug release showed sustained release of carvedilol from ethosomes and ethosomal hydrogel. Compared to free carvedilol-loaded hydrogel, the ethosomal gel showed increased penetration of carvedilol through the skin. Moreover, ethosomal hydrogels showed a gradual reduction in blood pressure for 24 h in rats.

Conclusions

Taken together, central composite design can be used for successful optimization of carvedilol-loaded ethosomes formulation, which can serve as the promising transdermal delivery system for carvedilol. Moreover the carvedilol-loaded ethosomal gel can extend the anti-hypertensive effect of carvedilol for a longer time, as compared to free carvedilol, suggesting its therapeutic potential in future clinics.
Proteomics and ultrastructural analysis of Hermetia illucens (Diptera: Stratiomyidae) larval peritrophic matrix
Authors: Lin Yu-Bo , Rong Jing-Jing , Wei Xun-Fan , Sui Zhuo-Xiao , Xiao Jinhua , Huang Da-Wei
Published: April 2021

Background

The black soldier fly (Hermetia illucens) has significant economic potential. The larvae can be used in financially viable waste management systems, as they are voracious feeders able to efficiently convert low-quality waste into valuable biomass. However, most studies on H. illucens in recent decades have focused on optimizing their breeding and bioconversion conditions, while information on their biology is limited.

Methods

About 200 fifth instar well-fed larvae were sacrificed in this work. The liquid chromatography-tandem mass spectrometry and scanning electron microscopy were employed in this study to perform a proteomic and ultrastructural analysis of the peritrophic matrix (PM) of H. illucens larvae.

Results

A total of 565 proteins were identified in the PM samples of H. illucen, of which 177 proteins were predicted to contain signal peptides, bioinformatics analysis and manual curation determined 88 proteins may be associated with the PM, with functions in digestion, immunity, PM modulation, and others. The ultrastructure of the H. illucens larval PM observed by scanning electron microscopy shows a unique diamond-shaped chitin grid texture.

Conclusions

It is the first and most comprehensive proteomics research about the PM of H. illucens larvae to date. All the proteins identified in this work has been discussed in details, except several unnamed or uncharacterized proteins, which should not be ignored and need further study. A comparison of the ultrastructure between H. illucens larval PM and those of other insects as observed by SEM indicates that the PM displays diverse textures on an ultra-micro scale and we suscept a unique diamond-shaped chitin grid texture may help H. illucens larval to hold more food. This work deepens our understanding of the molecular architecture and ultrastructure of the H. illucens larval PM.
SUVmax reduction predicts long-term survival in patients of non-pCR both in the tumor and lymph nodes after neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma
Authors: Nagaki Yushi , Motoyama Satoru , Sato Yusuke , Wakita Akiyuki , Fujita Hiromu , Sasaki Yoshihiro , Imai Kazuhiro , Minamiya Yoshihiro
Published: April 2021

Background

A pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NACRT) ensures long-term survival in esophageal squamous cell carcinoma (ESCC) patients following esophagectomy, but pCR patients are a minority. The aim here was to identify prognostic factors in patients with non-pCR ESCC after NACRT.

Methods

This is a retrospective study. Investigated were 5-year overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) among non-pCR ESCC patients divided into pT0N0, primary site pCR (pT0N+), lymph node pCR (pT+N0), and non-pCR in both the tumor and lymph node (pT+N+) subgroups after NACRT and esophagectomy. Focusing on the SUVmax reduction rate in the primary tumor in 88 patients who underwent FDG-PET before and after NACRT, we used univariate and multivariate Cox proportional hazard models to identify prognostic factors.

Results

Although there were no significant survival differences among non-pCR ESCC patients with pT0N+, pT+N0, or pT+N+, survival rate among pT+N+patients was the poorest. After setting a 60% cutoff for the SUVmax reduction rate in the tumor, RFS curves for non-pCR patients significantly differed between patients above the cutoff and those below it. For pT+N+ patients, the SUVmax reduction rate (<60% vs ≥ 60%) was an independent prognostic factor of OS, DSS, and RFS.

Conclusion

Because ESCC patients with SUVmax reduction rates of <60% in the tumor after NACRT and categorized as pT+N+ after NACRT had significantly poorer prognoses, even after esophagectomy, a change in treatment strategy may be an option to improve survival.
Thin endometrium is associated with the risk of hypertensive disorders of pregnancy in fresh IVF/ICSI embryo transfer cycles: a retrospective cohort study of 9,266 singleton births
Authors: Liu Xiaojie , Wang Jingwan , Fu Xiao , Li Jing , Zhang Meng , Yan Junhao , Gao Shanshan , Ma Jinlong
Published: April 2021

Background

Thin endometrial thickness (EMT) has been suggested to be associated with reduced incidence of pregnancy rate after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment, but the effect of thin endometrium on obstetric outcome is less investigated. This study aims to determine whether EMT affects the incidence of obstetric complications in fresh IVF/ICSI-embryo transfer (ET) cycles.

Methods

We conducted a retrospective cohort study collecting a total of 9266 women who had singleton livebirths after fresh IVF/ICSI-ET treatment cycles at the Center for Reproductive Medicine Affiliated to Shandong University between January 2014 and December 2018. The women were divided into three groups according to the EMT: 544 women with an EMT ≤8 mm, 6234 with an EMT > 8–12 mm, and 2488 with an EMT > 12 mm. The primary outcomes were the incidence of obstetric complications including hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), placental abruption, placenta previa, postpartum hemorrhage (PPH) and cesarean section. Multivariable logistic regression analysis was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for associations between the EMT measured on the day of human chorionic gonadotropin (HCG) trigger and the risk of the outcomes of interest.

Results

The HDP incidence rate of pregnant women was highest in EMT ≤ 8 mm group and significantly higher than those in EMT from > 8–12 mm and EMT > 12 mm group, respectively (6.8% versus 3.6 and 3.5%, respectively; P = 0.001). After adjustment for confounding variables by multivariate logistic regression analysis, a thin EMT was still statistically significant associated with an increased risk of HDP. Compared with women with an EMT > 8–12 mm, women with an EMT ≤8 mm had an increased risk of HDP (aOR = 1.853, 95% CI 1.281–2.679, P = 0.001).

Conclusion

A thin endometrium (≤8 mm) was found to be associated with an increased risk of HDP after adjustment for confounding variables, indicating that the thin endometrium itself is a risk factor for HDP. Obstetricians should remain aware of the possibility of HDP when women with a thin EMT achieve pregnancy through fresh IVF/ICSI–ET treatment cycles.
Projections of psychiatrists’ distribution for patients in Japan: a utilization-based approach
Authors: Sugawara Norio , Yasui-Furukori Norio , Shimoda Kazutaka
Published: April 2021

Background

Depopulation accompanied by population aging is a major public health concern in Japan. Although adequate allocation of mental healthcare resources is needed, there have been few studies on the impact of population change on the supply–demand balance for mental illness in Japan. The aim of this study is to predict psychiatrists' distribution for patients with mental illness via a utilization-based approach.

Methods

We set patients with schizophrenia, mood disorders, vascular dementia or Alzheimer’s disease as study subjects and conducted analyses for 2015, 2025, 2035, and 2045 across all prefectures. Moreover, we evaluated the regional maldistribution of demand and supply by calculating the number of psychiatrists per patient, Gini coefficients (GC), and Herfindahl–Hirschman Index (HHI).

Results

The mean number of psychiatrists per patient for patients with schizophrenia, mood disorders, vascular dementia, and Alzheimer’s disease in 2025, 2035, and 2045 was significantly lower than in 2015. For all of the abovementioned diseases, both the GC and HHI will increase until 2045.

Conclusion

If psychiatrists are allocated at the current population-to-psychiatrist ratio, the shortage of psychiatrists will continue to worsen in the future. To overcome this inequity, policy makers should make plans to shift responsibilities from psychiatrists to other mental health workers and to ensure the adequate geographical allocation of healthcare resources.
Radiotherapeutic treatment options for oligotopic malignant liver lesions
Authors: Wust Peter , Beck Marcus , Dabrowski Robert , Neumann Oliver , Zschaeck Sebastian , Kaul David , Modest Dominik P. , Stromberger Carmen , Gebauer Bernhard , Ghadjar Pirus
Published: April 2021

Background

Several radiotherapeutic approaches for patients with oligotopic malignant liver lesions unfit for surgical resection exist. The most advanced competitive techniques are high-dose-rate (HDR) brachytherapy, Cyberknife, volume-modulated-arc therapy (VMAT) and Tomotherapy. We evaluated the optimal technique by a planning study for a single ablative dose with different lesion sizes.

Methods

We compared dose distributions of HDR-brachytherapy with stereotactic ablative radiotherapy using the Cyberknife, VMAT or Tomotherapy. Tumor-control-probabilities (TCP), normal-tissue-complication-probabilities (NTCP) were determined in a theoretical framework applying a single dose of 20 Gy (demanding 95% coverage) for intrahepatic lesions of 1–5 cm in size. We evaluated therapeutic ratios by TCP (mean dose in the lesion) relative to high-dose (conformality) or low-dose liver exposition in dependency on the lesion size for each technique. In addition, we considered treatment times and accuracy (clinical target volume vs planning target volume).

Results

HDR-brachtherapy has the highest therapeutic ratios with respect to high-dose as well as low-dose liver exposition even for extended lesions, and the Cyberknife being suited second best. However, for lesions ≥ 3 cm diameter the therapeutic ratios of all ablative techniques are increasingly converging, and better tolerance and shorter treatment times of noninvasive external techniques become more important. On the other hand, mean tumor doses of HDR-brachytherapy of near 60 Gy are unattainable by the other techniques gaining only 22–34 Gy, and the conformality of HDR-brachytherapy is still rather good for lesions ≥ 3 cm diameter.

Conclusions

HDR-brachytherapy is by far the most effective technique to treat intrahepatic lesions by a single fraction, but sparing of the surroundings declines with increasing lesion size and approaches the benchmarks of external beam radiosurgery techniques. External beam radiotherapy has the advantage to use suitable fractionation schedules.
The safety and efficacy of Glubran 2 as biliostatic agent in liver resection
Authors: Patrone Renato , Granata Vincenza , Belli Andrea , Palaia Raffaele , Albino Vittorio , Piccirillo Mauro , Fusco Roberta , Tatangelo Fabiana , Nasti Guglielmo , Avallone Antonio , Izzo Francesco
Published: April 2021

Background

Biloma, an encapsulated collection of bile outside the biliary tree, supported by a predominantly iatrogenic biliary fistula, and bile likeage are two of the most important surgical complications after liver resection. We, hypothesized to conduct a project aimed to prevent, or reduce, the formation of biloma or biliary fistula applying on the hepatic resection area the cyanoacrylate glue (Glubran2).

Methods

We searched in our surgical database all patients underwent liver resection for mCRC from January 2013 to December 2018 and we found a total of 510 patients. 205 patients for Group A (study population: included patients in which we have used Glubran2 during surgical procedure) and 113 patients for Group B (control group), were enrolled.

Results

In both Groups no patients died during hospitalization and the 30-day mortality was 0 %. During follow-up in Group A, a biliary fistula was found in 2 patients (1 %) versus 3 patients in the Group B (2,6 %). In patients enrolled in Group A no adverse event were reported relate to the use of Glubran2.

Conclusions

It is possible to affirm that the use of Glubran2 as biliostatic agent after liver resection is useful to prevent bile leakage complication and biloma formation and its use demonstrated to be safe and feasible during liver surgery.
Synovial fluid neutrophils in oligoarticular juvenile idiopathic arthritis have an altered phenotype and impaired effector functions
Authors: Arve-Butler Sabine , Schmidt Tobias , Mossberg Anki , Berthold Elisabet , Gullstrand Birgitta , Bengtsson Anders A. , Kahn Fredrik , Kahn Robin
Published: April 2021

Background

Neutrophils are the most prevalent immune cells in the synovial fluid in inflamed joints of children with oligoarticular juvenile idiopathic arthritis (JIA). Despite this, little is known about neutrophil function at the site of inflammation in JIA and how local neutrophils contribute to disease pathogenesis. This study aimed to characterize the phenotype and function of synovial fluid neutrophils in oligoarticular JIA.

Methods

Neutrophils obtained from paired blood and synovial fluid from patients with active oligoarticular JIA were investigated phenotypically (n = 17) and functionally (phagocytosis and oxidative burst, n = 13) by flow cytometry. In a subset of patients (n = 6), blood samples were also obtained during inactive disease at a follow-up visit. The presence of CD206-expressing neutrophils was investigated in synovial biopsies from four patients by immunofluorescence.

Results

Neutrophils in synovial fluid had an activated phenotype, characterized by increased CD66b and CD11b levels, and most neutrophils had a CD16hi CD62Llowaged phenotype. A large proportion of the synovial fluid neutrophils expressed CD206, a mannose receptor not commonly expressed by neutrophils but by monocytes, macrophages, and dendritic cells. CD206-expressing neutrophils were also found in synovial tissue biopsies. The synovial fluid neutrophil phenotype was not dependent on transmigration alone. Functionally, synovial fluid neutrophils had reduced phagocytic capacity and a trend towards impaired oxidative burst compared to blood neutrophils. In addition, the effector functions of the synovial fluid neutrophils correlated negatively with the proportion of CD206+ neutrophils.

Conclusions

Neutrophils in the inflamed joint in oligoarticular JIA were altered, both regarding phenotype and function. Neutrophils in the synovial fluid were activated, had an aged phenotype, had gained monocyte-like features, and had impaired phagocytic capacity. The impairment in phagocytosis and oxidative burst was associated with the phenotype shift. We speculate that these neutrophil alterations might play a role in the sustained joint inflammation seen in JIA.
A review of flash glucose monitoring in type 2 diabetes
Authors: Krakauer Marcio , Botero Jose Fernando , Lavalle-González Fernando J. , Proietti Adrian , Barbieri Douglas Eugenio
Published: April 2021

Background

Continuous glucose monitoring systems are increasingly being adopted as an alternative to self-monitoring of blood glucose (SMBG) by persons with diabetes mellitus receiving insulin therapy.

Main body

The FreeStyle Libre flash glucose monitoring system (Abbott Diabetes Care, Witney, United Kingdom) consists of a factory-calibrated sensor worn on the back of the arm which measures glucose levels in the interstitial fluid every minute and stores the reading automatically every 15 min. Swiping the reader device over the sensor retrieves stored data and displays current interstitial glucose levels, a glucose trend arrow, and a graph of glucose readings over the preceding 8 h. In patients with type 2 diabetes (T2D) receiving insulin therapy, pivotal efficacy data were provided by the 6-month REPLACE randomized controlled trial (RCT) and 6-month extension study. Compared to SMBG, the flash system significantly reduced the time spent in hypoglycemia and frequency of hypoglycemic events, although no significant change was observed in glycosylated hemoglobin (HbA1c) levels. Subsequent RCTs and real-world chart review studies have since shown that flash glucose monitoring significantly reduces HbA1c from baseline. Real-world studies in both type 1 diabetes or T2D populations also showed that flash glucose monitoring improved glycemic control. Higher (versus lower) scanning frequency was associated with significantly greater reductions in HbA1c and significant improvements in other measures such as time spent in hypoglycemia, time spent in hyperglycemia, and time in range. Additional benefits associated with flash glucose monitoring versus SMBG include reductions in acute diabetes events, all-cause hospitalizations and hospitalized ketoacidosis episodes; improved well-being and decreased disease burden; and greater treatment satisfaction.

Conclusion

T2D patients who use flash glucose monitoring might expect to achieve significant improvement in HbA1c and glycemic parameters and several associated benefits.
Effects of intermittently scanned continuous glucose monitoring on blood glucose control and the production of urinary ketone bodies in pregestational diabetes mellitus
Authors: Li Shu-ying , Guo Hang , Zhang Yi , Li Pei , Zhou Pei , Sun Li-rong , Li Jing , Chen Li-ming
Published: April 2021

Objective

To investigate the effects of intermittently scanned continuous glucose monitoring (isCGM) on blood glucose control, clinical value of blood glucose monitoring and production of urinary ketone bodies in pregestational diabetes mellitus.

Method

A total of 124 patients with pregestational diabetes mellitus at 12–14 weeks of gestation admitted to the gestational diabetes clinic of our hospital from December 2016 to December 2018 were selected and randomly divided into two groups. Sixty patients adopted self-monitoring of blood glucose (SMBG) were taken as the control group, and the other 64 patients adopted isCGM system by wearing the device for 14 days. Blood sugar control, glycosylated albumin level, ketone production in urine, the maximum and minimum of blood sugar value measured by different monitoring methods and their occurrence time were observed in the two groups.

Result

(1) No statistically significant differences were found between the groups in terms of maternal age, gestational age at first visit, family history, duration of diabetes, education level, total insulin dose, chronic hypertension, abortion history, nulliparity, assisted reproductive technology, history of macrosomia childbirth, pre-pregnancy BMI, and overweight (%) at the first visit and hypoglycemia, (2) the value of Glycated Albumin was lower in the CGM group compared to the control group at 2ed weeks (14.6 ± 2.2 vs. 16.8 ± 2.7, p < 0.001). The women in the CGM group spent increased time in the recommended glucose control target range of 3.5–7.8 mmol/L (69 ± 10% vs. 62 ± 11%, p < 0.001) and reduced time above target compared with those in the control group at 2 weeks (25 ± 7% vs. 31 ± 8%, p < 0.001). In the second week of the study, the positive rate of urinary ketone body in isCGM group was lower than that in the control group (42 ± 5 vs. 54 ± 5, p < 0.001), and (3) the minimum blood glucose of 31.2% (20/64) cases in isCGM group appeared during 0:00–2:59 at night, and 26.6% (17/64) cases appeared during 3:00–5:59 at night. The minimum values of 40.0% (24/60) cases in the control group appeared within the 30 min before lunch, 23.3% (14/60) within the 30 min before breakfast, and 11.7% (7/60) within the 30 min before dinner. The cases of minimum of blood sugar before meals accounted for 75% of all the minimum values, and the cases of minimum at night only accounted for 8.3%.

Conclusion

Intermittently scanned continuous glucose monitoring can reduce hyperglycemia exposure and ketone body formation in pregestational diabetes mellitus. In addition, isCGM is better than SMBG in detecting nocturnal hypoglycemia.
A comparative study of the effects of Aducanumab and scanning ultrasound on amyloid plaques and behavior in the APP23 mouse model of Alzheimer disease
Authors: Leinenga Gerhard , Koh Wee Kiat , Götz Jürgen
Published: April 2021

Background

Aducanumab is an anti-amyloid-β (Aβ) antibody that achieved reduced amyloid pathology in Alzheimer’s disease (AD) trials; however, it is controversial whether it also improved cognition, which has been suggested would require a sufficiently high cumulative dose of the antibody in the brain. Therapeutic ultrasound, in contrast, has only begun to be investigated in human AD clinical trials. We have previously shown that scanning ultrasound in combination with intravenously injected microbubbles (SUS), which temporarily and safely opens the blood-brain barrier (BBB), removes amyloid and restores cognition in APP23 mice. However, there has been no direct testing of how the effects of SUS compare to immunotherapy or whether a combination therapy is more effective.

Methods

In a study comprising four treatment arms, we tested the efficacy of an Aducanumab analog, Adu, both in comparison to SUS, and as a combination therapy, in APP23 mice (aged 13–22 months), using sham as a control. The active place avoidance (APA) test was used to test spatial memory, and histology and ELISA were used to measure amyloid. Brain antibody levels were also determined.

Results

We found that both Adu and SUS reduced the total plaque area in the hippocampus with no additive effect observed with the combination treatment (SUS + Adu). Whereas in the cortex where there was a trend towards reducing the total plaque area from either Adu or SUS, only the combination treatment yielded a statistically significant decrease in total plaque area compared to sham. Only the SUS and SUS + Adu groups included animals that had their plaque load reduced to below 1% from above 10%. There was a robust improvement in spatial memory for the SUS + Adu group only, and in this group the level of Adu, when measured 3 days post-treatment, was 5-fold higher compared to those mice that received Adu on its own.

Together, these findings suggest that SUS should be considered as a treatment option for AD. Alternatively, a combination trial using Aducanumab together with ultrasound to increase brain levels of the antibody may be warranted.
Purification and characterization of thermoactive serratiopeptidase from Serratia marcescens AD-W2
Authors: Chander Devtulya , Khosla Jasmine Kour , Koul Diksha , Hossain Md. Mehedi , Dar Mohd Jamal , Chaubey Asha
Published: April 2021

Serratiopeptidase is a proteolytic enzyme extensively used as an anti-inflammatory and analgesic drug. Present work reports a thermoactive serratiopeptidase from Serratia marcescens AD-W2, a soil isolate from the North-Western Himalayan region of India. The extracellular metalloprotease has been purified by a simple two-step procedure resulting in a specific activity of 20,492 Units/mg protein with 5.28-fold purification. The molecular mass of the metalloprotease, as determined by SDS-PAGE was ~ 51 kDa. The purified serratiopeptidase presented optimum activity at pH 9.0, temperature 50 °C and stability in wide pH and temperature range. Critical temperature of 50 °C confirmed the thermoactivity of the purified serratiopeptidase. The kinetic studies of the purified serratiopeptidase revealed Vmax and Km of 57,256 Units/mL and 1.57 mg/mL, respectively, for casein. The purified serratiopeptidase from S. marcescens AD-W2 was found to be 100% identical to serralysin from Serratia marcescens ATCC 21074/E-15. The catalytic domain comprising of Zn coordinated with three histidine residues (His192, His196, His202), along with glutamate (Glu193) and tyrosine (Tyr232) residues, further confirmed that the purified protein is identical to serralysin.
Relation extraction for coal mine safety information using recurrent neural networks with bidirectional minimal gated unit
Authors: Liu Xiulei , Hou Shoulu , Qin Zhihui , Liu Sihan , Zhang Jian
Published: April 2021

The data of coal mine safety field are massive, multi-source and heterogeneous. It is of practical importance to extract information from big data to achieve disaster precaution and emergency response. Existing approaches need to build more features and rely heavily on the linguistic knowledge of researchers, leading to inefficiency, poor portability, and slow update speed. This paper proposes a new relation extraction approach using recurrent neural networks with bidirectional minimal gated unit (MGU) model. This is achieved by adding a back-to-front MGU layer based on original MGU model. It does not require to construct complex text features and can capture the global context information by combining the forward and backward features. Evident from extensive experiments, the proposed approach outperforms the existing initiatives in terms of training time, accuracy, recall and F value.
Correction to: Arabic text summarization using deep learning approach
Authors: Al-Maleh Molham , Desouki Said
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
The protective effect of Rubus fruticosus L. on blood composition in cyclophosphamide treated male rats
Authors: Mirazi Naser , Shahabi Baher Ida , Izadi Zahra , Hosseini Abdolkarim
Published: April 2021

Background

Some chemotherapy drugs such cyclophosphamide (CP) has destructive effects on hematopoietic cells in the bone marrow tissue. Due to antioxidant and anti-inflammatory features, medicinal herbs have protective effects on the bone marrow tissue. The aim of this experimental study is to examine the protective effects of Rubus fruticosus L. extract (RF) on blood parameters in male rats treated with CP.

Methods

In this experimental study, 35 male Wistar rats (220–250 g) were randomly divided into 5 groups (n = 7): Control (0.5 mL normal saline), CP (15 mg/kg), positive control (RF per se 200 mg/kg), treatment 1 (CP 15 mg/kg + RF 100 mg/kg), and treatment 2 (CP 15 mg/kg + RF 200 mg/kg). All drugs and extracts were given intraperitoneally for 15 consecutive days. At the end of the intervention, all animals were euthanized and their blood samples were collected by cardiac puncture in anti-coagulant tubes for blood parameters evaluation.

Results

The data analysis showed that CP has decreased significantly in RBC, WBC, Platelets number, hemoglobin and hematocrit in rats (p < 0.05). RF could protect hematopoiesis in CP-induced rats (p < 0.05).

Conclusion

The use of RF can protect the blood hematopoietic tissue in bone marrow and prevent CP toxic effects.
Characteristics of adrenal insufficiency in hemodialysis patients
Authors: Ohashi Naro , Sakao Yukitoshi , Sato Taichi , Ishigaki Sayaka , Isobe Shinsuke , Fujikura Tomoyuki , Kato Akihiko , Yasuda Hideo
Published: April 2021

Background

Adrenal insufficiency causes abnormal subjective symptoms such as general fatigue, signs such as hypotension, and abnormalities such as hypoglycemia and leads to poor prognosis. However, all these are also observed in hemodialysis (HD) patients without adrenal insufficiency. The morphology of the adrenal glands in HD patients with adrenal insufficiency is unclear. Therefore, this study was performed to clarify the characteristics of adrenal insufficiency in HD patients.

Methods

Seventeen HD patients who had abnormal subjective symptoms and test results indicating adrenal insufficiency and whose serum cortisol levels were less than 18 μg/dL were recruited.

Results

Seven HD patients were diagnosed with adrenal insufficiency. No significant differences were found about abnormal subjective symptoms and images between patients with and without adrenal insufficiency. The levels of serum cortisol and serum cholinesterase were significantly lower in patients with adrenal insufficiency than in those without adrenal insufficiency. A plasma cortisol level of 8.45 μg/dL showed the highest sensitivity and specificity in the receiver operating characteristic curve. The serum cortisol levels were significantly and negatively associated with the plasma ferritin levels in patients with adrenal insufficiency. Multiple linear regression analyses revealed that the serum cortisol levels showed a significant negative association with the plasma ferritin levels after adjustments.

Conclusions

It is difficult to infer adrenal insufficiency in HD patients by subjective symptoms and images of the adrenal glands. Adrenal insufficiency correlates with nutritional and inflammatory status, and the levels of serum cholinesterase and plasma ferritin might reflect their corresponding status.
Transcriptomic studies of systemic lupus erythematosus
Authors: Nakano Masahiro , Iwasaki Yukiko , Fujio Keishi
Published: April 2021

The management of systemic lupus erythematosus (SLE) remains challenging for clinicians because of the clinical heterogeneity of this disease. In attempts to identify useful biomarkers for the diagnosis of and treatment strategies for SLE, previous microarray and RNA sequencing studies have demonstrated several disease-relevant signatures in SLE. Of these, the interferon (IFN) signature is complex, involving IFNβ- and IFNγ-response genes in addition to IFNα-response genes. Some studies revealed that myeloid lineage/neutrophil and plasma cell signatures as well as the IFN signature were correlated with disease activity, lupus nephritis, and complications of pregnancy, although some of these findings remain controversial. Cell-type-specific gene expression analysis revealed the importance of an exhaustion signature in CD8+ T cells for SLE outcome. Recent single-cell RNA sequencing analyses of SLE blood and tissues demonstrated molecular heterogeneity and identified several distinct subpopulations as key players in SLE pathogenesis. Further studies are required to identify novel treatment targets and determine precise patient stratification in SLE. In this review, we discuss the findings and limitations of SLE transcriptomic studies.
Safety and efficacy of directly acting antivirals (sofosbuvir and daclatasvir) in treatment of chronic HCV in HIV-HCV co-infected Egyptian patients
Authors: Mohamed Inas E L-Khedr , EL-Saeed Kadry Mohamed , Al-Sadik Mahmoud Hassan , Anwar Christina Alphonse
Published: April 2021

Background

Cure of chronic hepatitis C (HCV) in HIV/HCV co-infected patients is a priority due to their increased risk of complications. Daclatasvir and sofosbuvir treatment regimens with or without ribavirin are considered an important chance for better HCV treatment in patients with HIV/HCV co-infection. This study aimed at the assessment of safety and efficacy of sofosbuvir-daclatasvir treatment regimens in HIV/HCV co-infected Egyptian patients.

Results

Thirty HIV/HCV co-infected adult patients were included. All patients completed the study duration without major problems or drug interactions, HCV PCR was negative for all patients at the end of treatment, yet 12 weeks after ending treatment, only one patient (3.33%) had HCV relapse.

Liver enzymes showed a significant decrease by the end of treatment and 12 weeks after end of treatment in comparison with their values before treatment (P-value = 0.0001). CD4 counts as well showed significant increase. There was non-significant change in serum albumin, total bilirubin, alfa fetoprotein, complete blood count (CBC), coagulation profile, random blood sugar, or serum creatinine. Ultrasonographic findings did not show significant difference.

Conclusion

Combination of daclatasvir and sofosbuvir have showed 96.67% sustained virologic response at 12 weeks after treatment (SVR 12) among HIV/HCV co-infected patients, with a good safety profile. Moreover, the treated patients showed a significant increase in CD4 lymphocytic count.
Robust AVO inversion for the fluid factor and shear modulus
Authors: Zhou Lin , Liu Xingye , Li Jingye , Liao Jianping
Published: April 2021

Seismic estimation of the fluid factor and shear modulus plays an important role in reservoir fluid identification and characterization. Various amplitude variation with offset inversion methods have been used to estimate these two parameters, which are generally based on approximate formulations of the Zoeppritz equations. However, the accuracy of these methods is limited because the forward modeling ability of approximate equations is incorrect under the conditions of strong impedance contrast and large incidence angles. Therefore, to improve the estimation accuracy, we have used the Zoeppritz equations to directly invert for the fluid factor and shear modulus. Based on the poroelasticity theory, we derive the Zoeppritz equations in a new form containing the fluid factor, shear modulus, density, and dry-rock velocity ratio squared. The objective function is then constructed using these equations in a Bayesian framework with the addition of a differentiable Laplace distribution blockiness constraint term to the prior model to enhance the fluid boundaries. Finally, the nonlinear objective function is solved by combining the Taylor expansion and the iterative reweighted least-squares algorithm. Numerical experiments indicate that the inversion accuracy of our method may heavily depend on the parameter of the dry-rock velocity ratio square that is assumed to be static. However, tests on synthetic and field data show that our method can estimate the fluid factor and shear modulus with satisfactory accuracy in the case of choosing a reasonable static value of this parameter. In addition, we determine that the accuracy of this method is higher than that of the linearized formulation.
Dealiased seismic data interpolation using a deep-learning-based prediction-error filter
Authors: Fang Wenqian , Fu Lihua , Liu Shaoyong , Li Hongwei
Published: April 2021

Deep-learning (DL) technology has emerged as a new approach for seismic data interpolation. DL-based methods can automatically learn the mapping between regularly subsampled and complete data from a large training data set. Subsequently, the trained network can be used to directly interpolate new data. Therefore, compared with traditional methods, DL-based methods reduce the manual workload and render the interpolation process efficient and automatic by avoiding the selection of hyperparameters. However, two limitations of DL-based approaches exist. First, the generalization performance of the neural network is inadequate when processing new data with a different structure compared to the training data. Second, the interpretation of the trained networks is very difficult. To overcome these limitations, we have combined the deep neural network and classic prediction-error filter (PEF) methods, proposing a novel seismic data dealiased interpolation framework called prediction-error filters network (PEFNet). The PEFNet designs convolutional neural networks to learn the relationship between the subsampled data and the PEFs. Thus, the filters estimated by the trained network are used for the recovery of missing traces. The learning of filters enables the network to better extract the local dip of seismic data and has a good generalization ability. In addition, PEFNet has the same interpretability as traditional PEF-based methods. The applicability and the effectiveness of our method are demonstrated here by synthetic and field data examples.
Digital rock physics applied to squirt flow
Authors: Lissa Simón , Ruf Matthias , Steeb Holger , Quintal Beatriz
Published: April 2021

We have developed a workflow for computing the seismic-wave moduli dispersion and attenuation due to squirt flow in a numerical model derived from a micro X-ray computed tomography image of cracked (through thermal treatment) Carrara marble sample. To generate the numerical model, the image is processed, segmented, and meshed. The finite-element method is adopted to solve the linearized, quasistatic Navier-Stokes equations describing laminar flow of a compressible viscous fluid inside the cracks coupled with the quasistatic Lamé-Navier equations for the solid phase. We compute the effective P- and S-wave moduli in the three Cartesian directions for a model in dry conditions (saturated with air) and for a smaller model fully saturated with glycerin and having either drained or undrained boundary conditions. For the model saturated with glycerin, the results indicate significant and frequency-dependent P- and S-wave attenuation and the corresponding dispersion caused by squirt flow. Squirt flow occurs in response to fluid pressure gradients induced in the cracks by the imposed deformations. Our digital rock-physics workflow can be used to interpret laboratory measurements of attenuation using images of the rock sample.