bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrahepatic cholangiocarcinoma induced M2-polarized tumor-associated macrophages facilitate tumor growth and invasiveness
Authors: Yuan Hui , Lin Zelong , Liu Yingjun , Jiang Yuchuan , Liu Ke , Tu Mengxian , Yao Nan , Qu Chen , Hong Jian
Published: December 2020

Background

M2-polarized tumor-associated macrophages (M2-TAMs) have been shown to correlate with the progression of various cancers, including intrahepatic cholangiocarcinoma (ICC). However, the interactions and mechanism between M2 macrophages and ICC are not completely clear. We aimed to clarify whether M2 macrophages promote the malignancy of ICC and its mechanism.

Methods

Two progressive murine models of ICC were used to evaluate the alterations in different macrophage populations and phenotypes. Furthermore, we assessed M2 macrophage infiltration in 48 human ICC and 15 normal liver samples. The protumor functions and the underlying molecular mechanisms of M2 macrophages in ICC were investigated in an in vitro coculture system.

Results

We found that the number of M2 macrophages was significantly higher in ICC tissues than in normal bile ducts in the two murine models. M2 macrophage infiltration was highly increased in peritumoral compared with intratumoral regions and normal liver (p < 0.01). ICC cells induced macrophages to differentiate into the M2-TAM phenotype, and coculture with these M2 macrophages promoted ICC cell proliferation, invasion and epithelial–mesenchymal transition (EMT) in vitro. Mechanistically, M2-TAM-derived IL-10 promoted the malignant properties of ICC cells through STAT3 signaling. Furthermore, blockade of IL-10/STAT3 signaling partly rescued the effects of M2 macrophages on ICC.

Conclusion

Our results indicated that M2-polarized macrophages induced by ICC promote tumor growth and invasiveness through IL-10/STAT3-induced EMT and might be a potential therapeutic target for ICC.
RRM2 protects against ferroptosis and is a tumor biomarker for liver cancer
Authors: Yang Yueyue , Lin Jiafei , Guo Susu , Xue Xiangfei , Wang Yikun , Qiu Shiyu , Cui Jiangtao , Ma Lifang , Zhang Xiao , Wang Jiayi
Published: December 2020

Background

Ferroptosis is the process of cell death triggered by lipid peroxides, and inhibition of glutathione (GSH) synthesis leads to ferroptosis. Liver cancer progression is closely linked to ferroptosis suppression. However, the mechanism by which inhibition of GSH synthesis suppresses potential ferroptosis of liver cancer cells and whether ferroptosis-related liver cancer biomarkers have a promising diagnostic value remain unknown.

Methods

Ribonucleotide reductase regulatory subunit M2 (RRM2) levels were measured using an enzyme linked immunosorbent assay (ELISA), quantitative RT-PCR (qPCR), immunoblotting (IB) and immunochemistry (IHC). Cell viability and cell death were measured by a CellTiter-Glo luminescent cell viability assay and staining with SYTOX Green followed by flow cytometry, respectively. Metabolites were measured using the indicated kits. The Interaction between glutathione synthetase (GSS) and RRM2 was measured using immunofluorescence (IF), co-immunoprecipitation (co-IP) and the proximal ligation assay (PLA). The diagnostic value was analyzed using the area under the receiver operating characteristic curve (AUC-ROC). Bioinformatics analysis was performed using the indicated database.

Results

RRM2 showed specifically elevated levels in liver cancer and inhibited ferroptosis by stimulating GSH synthesis via GSS. Mechanistically, phosphorylation of RRM2 at the Threonine 33 residue (T33) was maintained at normal levels to block the RRM2–GSS interaction and therefore protected RRM2 and GSS from further proteasome degradation. However, under ferroptotic stress, RRM2 was dephosphorylated at T33, thus the RRM2–GSS interaction was promoted. This resulted in the translocation of RRM2 and GSS to the proteasome for simultaneous degradation. Clinically, serum RRM2 was significantly associated with serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (γ-GT), albumin (ALB) and total bilirubin. The AUC-ROC for the combination of RRM2 with AFP was 0.947, with a sensitivity of 88.7% and a specificity of 97.0%, which indicates better diagnostic performance compared to either RRM2 or AFP alone.

Conclusion

RRM2 exerts an anti-ferroptotic role in liver cancer cells by sustaining GSH synthesis. Serum RRM2 will be useful as a biomarker to evaluate the degree to which ferroptosis is suppressed and improve diagnostic efficiency for liver cancer.
Prevention of re-establishment of malaria: historical perspective and future prospects
Authors: Nasir S. M. Ibraheem , Amarasekara Sachini , Wickremasinghe Renu , Fernando Deepika , Udagama Preethi
Published: December 2020

Prevention of re-establishment (POR) refers to the prevention of malaria outbreak/epidemic occurrence or preventing re-establishment of indigenous malaria in a malaria-free country. Understanding the effectiveness of the various strategies used for POR is, therefore, of vital importance to countries certified as “malaria-free” or to the countries to be thus certified in the near future. This review is based on extensive review of literature on both the POR strategies and elimination schemes of countries, (i) that have reached malaria-free status (e.g. Armenia, Mauritius, Sri Lanka), (ii) those that are reaching pre-elimination stage (e.g. South Korea), and (iii) countries at the control phase (e.g. India). History has clearly shown that poorly implemented POR programmes can result in deadly consequences (e.g. Sri Lanka); conversely, there are examples of robust POR programmes that have sustained malaria free status that can serve as examples to countries working toward elimination. Countries awaiting malaria elimination status should pre-plan their POR strategies. Malaria-free countries face the risk of resurgence mostly due to imported malaria cases; thus, a robust passenger screening programme and cross border collaborations are crucial in a POR setting. In addition, sustained vigilance, and continued funding for the national anti-malarial campaign programme and for related research is of vital importance for POR. With distinct intrinsic potential for malaria in each country, tailor-made POR programmes are built through continuous and robust epidemiological and entomological surveillance, particularly in countries such as Sri Lanka with increased receptivity and vulnerability for malaria transmission. In summary, across all five countries under scrutiny, common strengths of the POR programmes are (i) a multipronged approach, (ii) strong passive, active, and activated passive case detection, (iii) Indoor residual spraying (IRS), and (iv) health education/awareness programmes.
DNA methylation of insulin-like growth factor 2 and H19 cluster in cord blood and prenatal air pollution exposure to fine particulate matter
Authors: Wang Congrong , Plusquin Michelle , Ghantous Akram , Herceg Zdenko , Alfano Rossella , Cox Bianca , Nawrot Tim S.
Published: December 2020

Background

The IGF2 (insulin-like growth factor 2) and H19 gene cluster plays an important role during pregnancy as it promotes both foetal and placental growth. We investigated the association between cord blood DNA methylation status of the IGF2/H19 gene cluster and maternal fine particulate matter exposure during fetal life. To the best of our knowledge, this is the first study investigating the association between prenatal PM2.5 exposure and newborn DNA methylation of the IGF2/H19.

Methods

Cord blood DNA methylation status of IGF2/H19 cluster was measured in 189 mother-newborn pairs from the ENVIRONAGE birth cohort (Flanders, Belgium). We assessed the sex-specific association between residential PM2.5 exposure during pregnancy and the methylation level of CpG loci mapping to the IGF2/H19 cluster, and identified prenatal vulnerability by investigating susceptible time windows of exposure. We also addressed the biological functionality of DNA methylation level in the gene cluster.

Results

Prenatal PM2.5 exposure was found to have genetic region-specific significant association with IGF2 and H19 during specific gestational weeks. The association was found to be sex-specific in both gene regions. Functionality of the DNA methylation was annotated by the association to fetal growth and cellular pathways.

Conclusions

The results of our study provided evidence that prenatal PM2.5 exposure is associated with DNA methylation in newborns’ IGF2/H19. The consequences within the context of fetal development of future phenotyping should be addressed.
DeepFlower: a deep learning-based approach to characterize flowering patterns of cotton plants in the field
Authors: Jiang Yu , Li Changying , Xu Rui , Sun Shangpeng , Robertson Jon S. , Paterson Andrew H.
Published: December 2020

Background

Flowering is one of the most important processes for flowering plants such as cotton, reflecting the transition from vegetative to reproductive growth and is of central importance to crop yield and adaptability. Conventionally, categorical scoring systems have been widely used to study flowering patterns, which are laborious and subjective to apply. The goal of this study was to develop a deep learning-based approach to characterize flowering patterns for cotton plants that flower progressively over several weeks, with flowers distributed across much of the plant.

Results

A ground mobile system (GPhenoVision) was modified with a multi-view color imaging module, to acquire images of a plant from four viewing angles at a time. A total of 116 plants from 23 genotypes were imaged during an approximately 2-month period with an average scanning interval of 2–3 days, yielding a dataset containing 8666 images. A subset (475) of the images were randomly selected and manually annotated to form datasets for training and selecting the best object detection model. With the best model, a deep learning-based approach (DeepFlower) was developed to detect and count individual emerging blooms for a plant on a given date. The DeepFlower was used to process all images to obtain bloom counts for individual plants over the flowering period, using the resulting counts to derive flowering curves (and thus flowering characteristics). Regression analyses showed that the DeepFlower method could accurately (R2 = 0.88 and RMSE = 0.79) detect and count emerging blooms on cotton plants, and statistical analyses showed that imaging-derived flowering characteristics had similar effectiveness as manual assessment for identifying differences among genetic categories or genotypes.

Conclusions

The developed approach could thus be an effective and efficient tool to characterize flowering patterns for flowering plants (such as cotton) with complex canopy architecture.
Simplified sigmoidal curve fitting for a 6 MV FFF photon beam of the Halcyon to determine the field size for beam commissioning and quality assurance
Authors: Choi Min-Geon , Law Martin , Yoon Do-Kun , Tamura Mikoto , Matsumoto Kenji , Otsuka Masakazu , Kim Moo-Sub , Djeng Shih-Kien , Monzen Hajime , Suh Tae Suk
Published: December 2020

Background

An O-ring gantry-type linear accelerator (LINAC) with a 6-MV flattening filter-free (FFF) photon beam, Halcyon, includes a reference beam that contains representative information such as the percent depth dose, profile and output factor for commissioning and quality assurance. However, because it does not provide information about the field size, we proposed a method to determine all field sizes according to all depths for radiation therapy using simplified sigmoidal curve fitting (SCF).

Methods

After mathematical definition of the SCF using four coefficients, the defined curves were fitted to both the reference data (RD) and the measured data (MD). For good agreement between the fitting curve and the profiles in each data set, the field sizes were determined by identifying the maximum point along the third derivative of the fitting curve. The curve fitting included the field sizes for beam profiles of 2 × 2, 4 × 4, 6 × 6, 8 × 8, 10 × 10, 20 × 20 and 28 × 28 cm2as a function of depth (at 1.3, 5, 10 and 20 cm). The field size results from the RD were compared with the results from the MD using the same condition.

Results

All fitting curves show goodness of fit, R2, values that are greater than 0.99. The differences in field size between the RD and the MD were within the range of 0 to 0.2 cm. The smallest difference in the field sizes at a depth of 10 cm, which is a surface-to-axis distance, was reported.

Conclusion

Application of the SCF method has been proven to accurately capture the field size of the preconfigured RD and the measured FFF photon beam data for the Halcyon system. The current work can be useful for beam commissioning as a countercheck methodology to determine the field size from RD in the treatment planning system of a newly installed Halcyon system and for routine quality assurance to ascertain the correctness of field sizes for clinical use of the Halcyon system.
Incidence and root causes of surgical site infections after gastrointestinal surgery at a public teaching hospital in Sudan
Authors: Hassan Rawan Sharaf Eldein Elamein , Osman Sarah Osman Sayed , Aabdeen Mohamed Abdulmonem Salih , Mohamed Walid Elhaj Abdelrahim , Hassan Razan Sharaf Eldein Elamein , Mohamed Sagad Omer Obeid
Published: December 2020

Background

Surgical site infections (SSIs) are common healthcare-associated infections and associated with prolonged hospital stays, additional financial burden, and significantly hamper the potential benefits of surgical interventions. Causes of SSIs are multi-factorials and patients undergoing gastrointestinal tract procedures carry a high risk of bacterial contamination. This study aimed to determine the prevalence, associated factors, and causing microorganisms of SSIs among patients undergoing gastrointestinal tract surgeries.

Methods

A hospital based, cross-sectional study conducted at Soba University Hospital in Khartoum, Sudan. We included all patients from all age groups attending the gastrointestinal tract surgical unit between 1st September and 31st December 2017. We collected data about the socio-demographic characteristics, risk factors of SSI, and isolated microorganisms from patients with SSIs. A Chi-square test was conducted to determine the relationship between the independent categorical variables and the occurrence of SSI. The significance level for all analyses was set at p < .05.

Results

A total of 80 participants were included in the study. The mean age was 51 +/- 16 years and most of the patients (67.5%) did not have any chronic illness prior to the surgical operation. Most of them (46.3%) of them underwent large bowel surgery. Twenty-two patients (27.5%) developed SSI post operatively and superficial SSI was the most common type of SSIs (81.8%). Occurrence of SSI was found to be associated with long operation time (p > .001), malignant nature of the disease (p > .001), intra-operative blood loss (p > .001), and intra-operative hypotension (p = .013). The most prevalent microorganism isolated from SSI patients was E coli (47.8%), followed by Enterococcus fecalis (13.0%) and combined Pseudomonas aeruginosa + E coli infection (13.0%).

Conclusions

The results showed a high prevalence of SSIs among patients attending the gastrointestinal tract surgical unit and the most prevalent microorganism isolated from them was E coli. Measures should be taken to reduce the magnitude of SSI by mitigating the identified associated factors.
Thromboembolic complications in critically ill COVID-19 patients are associated with impaired fibrinolysis
Authors: Kruse Jan Matthias , Magomedov Abakar , Kurreck Annika , Münch Frédéric H. , Koerner Roland , Kamhieh-Milz Julian , Kahl Andreas , Gotthardt Inka , Piper Sophie K. , Eckardt Kai-Uwe , Dörner Thomas , Zickler Daniel
Published: December 2020

Background

There is emerging evidence for enhanced blood coagulation in coronavirus 2019 (COVID-19) patients, with thromboembolic complications contributing to morbidity and mortality. The mechanisms underlying this prothrombotic state remain enigmatic. Further data to guide anticoagulation strategies are urgently required.

Methods

We used viscoelastic rotational thromboelastometry (ROTEM) in a single-center cohort of 40 critically ill COVID-19 patients.

Results

Clear signs of a hypercoagulable state due to severe hypofibrinolysis were found. Maximum lysis, especially following stimulation of the extrinsic coagulation system, was inversely associated with an enhanced risk of thromboembolic complications. Combining values for maximum lysis with D-dimer concentrations revealed high sensitivity and specificity of thromboembolic risk prediction.

Conclusions

The study identifies a reduction in fibrinolysis as an important mechanism in COVID-19-associated coagulopathy. The combination of ROTEM and D-dimer concentrations may prove valuable in identifying patients requiring higher intensity anticoagulation.
Electrical impedance tomography to titrate positive end-expiratory pressure in COVID-19 acute respiratory distress syndrome
Authors: Perier François , Tuffet Samuel , Maraffi Tommaso , Alcala Glasiele , Victor Marcus , Haudebourg Anne-Fleur , Razazi Keyvan , De Prost Nicolas , Amato Marcelo , Carteaux Guillaume , Mekontso Dessap Armand
Published: December 2020

Rationale

Patients with coronavirus disease-19-related acute respiratory distress syndrome (C-ARDS) could have a specific physiological phenotype as compared with those affected by ARDS from other causes (NC-ARDS).

Objectives

To describe the effect of positive end-expiratory pressure (PEEP) on respiratory mechanics in C-ARDS patients in supine and prone position, and as compared to NC-ARDS. The primary endpoint was the best PEEP defined as the smallest sum of hyperdistension and collapse.

Methods

Seventeen patients with moderate-to-severe C-ARDS were monitored by electrical impedance tomography (EIT) and evaluated during PEEP titration in supine (n = 17) and prone (n = 14) position and compared with 13 NC-ARDS patients investigated by EIT in our department before the COVID-19 pandemic.

Results

As compared with NC-ARDS, C-ARDS exhibited a higher median best PEEP (defined using EIT as the smallest sum of hyperdistension and collapse, 12 [9, 12] vs. 9 [6, 9] cmH2O, p < 0.01), more collapse at low PEEP, and less hyperdistension at high PEEP. The median value of the best PEEP was similar in C-ARDS in supine and prone position: 12 [9, 12] vs. 12 [10, 15] cmH2O, p = 0.59. The response to PEEP was also similar in C-ARDS patients with higher vs. lower respiratory system compliance.

Conclusion

An intermediate PEEP level seems appropriate in half of our C-ARDS patients. There is no solid evidence that compliance at low PEEP could predict the response to PEEP.
Association of breast cancer with MRI background parenchymal enhancement: the IMAGINE case-control study
Authors: Watt Gordon P. , Sung Janice , Morris Elizabeth A. , Buys Saundra S. , Bradbury Angela R. , Brooks Jennifer D. , Conant Emily F. , Weinstein Susan P. , Kontos Despina , Woods Meghan , Colonna Sarah V. , Liang Xiaolin , Stein Matthew A. , Pike Malcolm C. , Bernstein Jonine L.
Published: December 2020

Background

Background parenchymal enhancement (BPE) on breast magnetic resonance imaging (MRI) may be associated with breast cancer risk, but previous studies of the association are equivocal and limited by incomplete blinding of BPE assessment. In this study, we evaluated the association between BPE and breast cancer based on fully blinded assessments of BPE in the unaffected breast.

Methods

The Imaging and Epidemiology (IMAGINE) study is a multicenter breast cancer case-control study of women receiving diagnostic, screening, or follow-up breast MRI, recruited from three comprehensive cancer centers in the USA. Cases had a first diagnosis of unilateral breast cancer and controls had no history of or current breast cancer. A single board-certified breast radiologist with 12 years’ experience, blinded to case-control status and clinical information, assessed the unaffected breast for BPE without view of the affected breast of cases (or the corresponding breast laterality of controls). The association between BPE and breast cancer was estimated by multivariable logistic regression separately for premenopausal and postmenopausal women.

Results

The analytic dataset included 835 cases and 963 controls. Adjusting for fibroglandular tissue (breast density), age, race/ethnicity, BMI, parity, family history of breast cancer, BRCA1/BRCA2 mutations, and other confounders, moderate/marked BPE (vs minimal/mild BPE) was associated with breast cancer among premenopausal women [odds ratio (OR) 1.49, 95% CI 1.05–2.11; p = 0.02]. Among postmenopausal women, mild/moderate/marked vs minimal BPE had a similar, but statistically non-significant, association with breast cancer (OR 1.45, 95% CI 0.92–2.27; p = 0.1).

Conclusions

BPE is associated with breast cancer in premenopausal women, and possibly postmenopausal women, after adjustment for breast density and confounders. Our results suggest that BPE should be evaluated alongside breast density for inclusion in models predicting breast cancer risk.
Physico-chemical assessment of torrefied Eurasian pinecones
Authors: Dhaundiyal Alok , Atsu Divine , Toth Laszlo
Published: December 2020

Background

Biomass pre-treatment is gaining attention as a standalone process to improve the qualitative aspect of the lignocellulosic material. It has been gaining ground in the power station by replacing the coal with the pre-treated biomass. In this context, this paper enlightens the operating condition of carrying out the torrefaction so that the process can be made relatively more effective. The influence of physico-chemical characteristics on the heat of reaction of pyrolysis reactions, mass loss and temperature regimes are evaluated by thermogravimetry of the pre-treated samples of the pinecone; whereas, the structural transformation in the basic constituents is determined via knowing the fractional change in cellulose, hemicellulose and acid-insoluble lignin contents of the pine cone. The thermogravimetric (TGA) and differential thermal analysis (DTA) were performed to determine the physical as well as the thermal behaviour of the thermally processed biomass. The samples had undergone thermal decomposition at heating rates of 5 °C min−1, 10 °C min−1 and 15 °C min−1. Nitrogen gas was used as a purge gas for the pyrolysis of the pre-treated samples. The volumetric rate of 200 ml min−1 was pre-set for the thermal decomposition of the samples at 600 °C; whereas, the selected torrefaction temperature range varied from 210 to 250 °C.

Results

The heat of reaction for the pre-treated samples was found to vary from 1.04 to 1.52 MJ kg−1; whereas, it was 0.91–1.54 MJ kg−1 for the raw samples. The total annual production cost of processing 3.6 Mg of fuel in a year at a pilot scale was $ 36.72; whereas, the fiscal burden per kilogram of fuel during thermal degradation of the processed fuel was reduced by 0.08–1.5ȼ. The entropy of the system decreased with an increasing ramp rate. The exergetic gain in the system increased by 1–2%. The loss of energy during the energy-intensive processing of the pre-treated fuel was relatively low at a heating rate of 5 °C min−1.

Conclusion

By the physico-chemical assessment, it was determined that pinecones required the highest torrefaction temperature and time to provide the upgraded pinecones. It was concluded that the duration of the torrefaction should be at least 15 min for a temperature of 250 °C so that the chemical exergy of the system, energy yield and the energy density of the processed material are qualitatively improved. The volatile and ash contents were noticed to decrease during the torrefaction process. The least fractional change in the volatile content was estimated at 210 °C for a torrefaction time of 15 min; whereas, the ash content was minimum at 210 °C for a torrefaction time of 5 min.
Heparan sulfate functions are altered in the osteoarthritic cartilage
Authors: Shamdani Sara , Chantepie Sandrine , Flageollet Camille , Henni-Chebra Nadia , Jouan Yohann , Eymard Florent , Hay Eric , Cohen-Solal Martine , Papy-Garcia Dulce , Chevalier Xavier , Albanese Patricia
Published: December 2020

Background

Heparan sulfate (HS) proteoglycans (PG) may be found at the chondrocyte surface and in the pericellular cartilage matrix, and are involved in cell-cell and cell-matrix interactions. An important function of HS chains is to regulate cell fate through specific interactions with heparin-binding proteins (HBP) modulated by their complex sulfation pattern. Osteoarthritis (OA) is a joint disorder characterized by the degradation of articular cartilaginous extracellular matrix. The aim of this study was to investigate HS structure and functions in osteoarthritic cartilages compared to normal cartilages (controls).

Methods

Glycosaminoglycans (GAG) were extracted from human macroscopically normal cartilages (controls,n = 7) and (OA cartilagesn = 11). HS were isolated and quantified using the DMMB quantification method. Their structure and functions were then compared using respectively a HPLC analysis and HBP binding tests and their phenotypic effects on murine chondrocytes were studied by RQ-PCR. Statistical analyzes were performed using a one-way ANOVA followed by a Dunnett’s test or attest for pairwise comparisons.

Results

In OA, HS were characterized by increased sulfation levels compared to controls. Moreover, the capacity of these HS to bind HBP involved in the OA pathophysiological process such as FGF2 and VEGF was reduced. Chondroitin sulfates and keratan sulfates regulated these binding properties. Finally, HS from OA cartilages induced the mRNA levels of catabolic markers such as MMP3, MMP13, and TS4 and inhibited the mRNA levels of anabolic markers such as COL2, ACAN, SOX9, and VEGF in murine articular chondrocytes.

Conclusion

The sulfation of HS chains was increased in OA cartilages with changes in HBP binding properties and biological effects on chondrocyte phenotypes. Thus, modified HS present in altered cartilages could be a novel therapeutic target in OA.
Preclinical comparison of four [18F, natGa]rhPSMA-7 isomers: influence of the stereoconfiguration on pharmacokinetics
Authors: Wurzer Alexander , Parzinger Mara , Konrad Matthias , Beck Roswitha , Günther Thomas , Felber Veronika , Färber Stefanie , Di Carlo Daniel , Wester Hans-Jürgen
Published: December 2020

Introduction

Radiohybrid (rh) ligands, a novel class of prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals, can be labeled either with [18F]fluorine via isotopic exchange or with radiometals (such as [68Ga]Gallium, [177Lu]Lutetium, [225Ac]Actinium). Among these, [18F, natGa]rhPSMA-7 has recently entered clinical assessment.

Aim

Since [18F, natGa]rhPSMA-7 is composed of four stereoisomers ([18F, natGa]rhPSMA-7.1, -7.2, -7.3 and -7.4), we initiated a preclinical selection process to identify the isomer with the most favorable pharmacokinetics for further clinical investigation.

Methods

A synthetic protocol for enantiopure [19F, natGa]rhPSMA-7 isomers has been developed. The comparative evaluation of the four isomers comprised human serum albumin binding, lipophilicity, IC50, internalization and classical biodistribution studies and competition experiments in LNCaP tumor-bearing CB-17 SCID mice. In addition, a radio high-performance liquid chromatography-based method was developed allowing quantitative, intraindividual comparison of [18F, natGa]rhPSMA-7.1 to -7.4 in LNCaP tumor-bearing mice.

Results

Cell studies revealed high PSMA affinity and internalization for [18/19F, natGa]rhPSMA-7.2, -7.3 and -7.4, whereas [18/19F, natGa]rhPSMA-7.1 showed approximately twofold lower values. Although the biodistribution profile obtained was typical of PSMA inhibitors, it did not allow for selection of a lead candidate for clinical studies. Thus, an intraindividual comparison of all four isomers in LNCaP tumor-bearing mice was carried out by injection of a diastereomeric mixture, followed by analysis of the differential uptake and excretion pattern of each isomer. Based on its high tumor accumulation and low uptake in blood, liver and kidneys, [18F, natGa]rhPSMA-7.3 was identified as the preferred isomer and transferred into clinical studies.

Conclusion

[18F, natGa]rhPSMA-7.3 has been selected as a lead compound for clinical development of a [18F]rhPSMA-based candidate. The intraindividual differential uptake and excretion analysis in vivo allowed for an accurate comparison and assessment of radiopharmaceuticals.
Construction of a mApple-D6A3-mediated biosensor for detection of heavy metal ions
Authors: Ji Yangyang , Guan Feifei , Zhou Xin , Liu Xiaoqing , Wu Ningfeng , Liu Daling , Tian Jian
Published: December 2020

Pollution of heavy metals in agricultural environments is a growing problem to the health of the world’s human population. Green, low-cost, and efficient detection methods can help control such pollution. In this study, a protein biosensor, mApple-D6A3, was built from rice-derived Cd2+-binding protein D6A3 fused with the red fluorescent protein mApple at the N-terminus to detect the contents of heavy metals. Fluorescence intensity of mApple fused with D6A3 indicated the biosensor’s sensitivity to metal ions and its intensity was more stable under alkaline conditions. mApple-D6A3 was most sensitive to Cu2+, then Ni2+, then Cd2+. Isothermal titration calorimetry experiments demonstrated that mApple-D6A3 successfully bound to each of these three metal ions, and its ability to bind the ions was, from strongest to weakest, Cu2+  > Cd2+  > Ni2+. There were strong linear relationships between the fluorescence intensity of mApple-D6A3 and concentrations of Cd2+ (0–100 μM), Cu2+ (0–60 μM) and Ni2+ (0–120 μM), and their respective R2 values were 0.994, 0.973 and 0.973. When mApple-D6A3 was applied to detect concentrations of heavy metal ions in water (0–0.1 mM) or culture medium (0–1 mM), its accuracy for detection attained more than 80%. This study demonstrates the potential of this biosensor as a tool for detection of heavy metal ions.
Multiple organs involved in the pathogenesis of non-alcoholic fatty liver disease
Authors: Li Xiaoyan , Wang Hua
Published: December 2020

Non-alcoholic fatty liver disease (NAFLD) represents the leading cause of chronic liver disease worldwide and the anticipated health burden is huge. There are limited therapeutic approaches for NAFLD now. It’s imperative to get a better understanding of the disease pathogenesis if new treatments are to be discovered. As the hepatic manifestation of metabolic syndrome, this disease involves complex interactions between different organs and regulatory pathways. It’s increasingly clear that brain, gut and adipose tissue all contribute to NAFLD pathogenesis and development, in view of their roles in energy homeostasis. In the present review, we try to summarize currently available data regarding NAFLD pathogenesis and to lay a particular emphasis on the inter-organ crosstalk evidence.
On global dynamics of 2D convective Cahn–Hilliard equation
Authors: Zhao Xiaopeng
Published: December 2020

In this paper, we study the long time behavior of solution for the initial-boundary value problem of convective Cahn–Hilliard equation in a 2D case. We show that the equation has a global attractor in$H^{4}(\Omega )$H4(Ω)when the initial value belongs to$H^{1}(\Omega )$H1(Ω).
SARS-Coronavirus-2 cases in healthcare workers may not regularly originate from patient care: lessons from a university hospital on the underestimated risk of healthcare worker to healthcare worker transmission
Authors: Schneider Sandra , Piening Brar , Nouri-Pasovsky Pauline Assina , Krüger Anne Caroline , Gastmeier Petra , Aghdassi Seven Johannes Sam
Published: December 2020

Background

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents an unprecedented healthcare challenge. Various SARS-CoV-2 outbreaks in healthcare facilities have been reported. Healthcare workers (HCWs) may play a critical role in the spread of the virus, particularly when asymptomatic. We examined four healthcare-associated outbreaks of SARS-CoV-2 infections that occurred at a university hospital in Berlin, Germany. We aimed to describe and analyze the spread of the virus in order to draw conclusions for effective containment of SARS-CoV-2 in healthcare facilities.

Methods

Healthcare-associated outbreaks of SARS-CoV-2 infections were defined as two or more laboratory confirmed infections with SARS-CoV-2 where an epidemiological link within the healthcare setting appeared likely. We focused our analysis on one of three sites of the Charité-University Medicine hospital within a 2 month period (March and April 2020).

Results

We observed four healthcare-associated outbreaks of SARS-CoV-2 infections, with a total of 24 infected persons (23 HCWs and one patient). The outbreaks were detected in the departments of nephrology and dialysis (n = 9), anesthesiology (n = 8), surgical pediatrics (n = 4), and neurology (n = 3). Each outbreak showed multiple unprotected contacts between infected HCWs. A combination of contact tracing, testing, physical distancing and mandatory continuous wearing of face masks by all HCWs was able to contain all four outbreaks.

Conclusions

HCW to HCW transmission represented the likely source of the four outbreaks. Ensuring proper physical distancing measures and wearing of protective equipment, also when interacting with colleagues, must be a key aspect of fighting COVID-19 in healthcare facilities.
Impact of a multifaceted intervention to improve antibiotic prescribing: a pragmatic cluster-randomised controlled trial
Authors:   on behalf of the GREPHEPI Group, Figueiras Adolfo , López-Vázquez Paula , Gonzalez-Gonzalez Cristian , Vázquez-Lago Juan Manuel , Piñeiro-Lamas María , López-Durán Ana , Sánchez Coro , Herdeiro María Teresa , Zapata-Cachafeiro Maruxa
Published: December 2020

Objectives

This study sought to assess the effectiveness and return on investment (ROI) of a multifaceted intervention aimed at improving antibiotic prescribing for acute respiratory infections in primary care.

Design

Large-sized, two-arm, open-label, pragmatic, cluster-randomised controlled trial.

Setting

All primary care physicians working for the Spanish National Health Service (NHS) in Galicia (region in north-west Spain).

Participants

The seven spatial clusters were distributed by unequal randomisation (3:4) of the intervention and control groups. A total of 1217 physicians (1.30 million patients) were recruited from intervention clusters and 1393 physicians (1.46 million patients) from control clusters.

Interventions

One-hour educational outreach visits tailored to training needs identified in a previous study; an online course integrated in practice accreditation; and a clinical decision support system.

Main outcome measures

Changes in the ESAC (European Surveillance of Antimicrobial Consumption) quality indicators for outpatient antibiotic use. We used generalised linear mixed and conducted a ROI analysis to ascertain the overall cost savings.

Results

Median follow-up was 19 months. The adjusted effect on overall antibiotic prescribing attributable to the intervention was − 4.2% (95% CI: − 5.3% to − 3.2%), with this being more pronounced for penicillins − 6.5 (95% CI: − 7.9% to − 5.2%) and for the ratio of consumption of broad- to narrow-spectrum penicillins, cephalosporins, and macrolides − 9.0% (95% CI: − 14.0 to − 4.1%). The cost of the intervention was €87 per physician. Direct savings per physician attributable to the reduction in antibiotic prescriptions was €311 for the NHS and €573 for patient contributions, with an ROI of €2.57 and €5.59 respectively.

Conclusions

Interventions designed on the basis of gaps in physicians’ knowledge of and attitudes to misprescription can improve antibiotic prescribing and yield important direct cost savings.

Trial registration: Current Controlled Trials ISRCTN24158380. Registered 5 February 2009.
A preliminary study on designing a cluster randomized control trial of two new mosquito nets to prevent malaria parasite infection
Authors: Minakawa Noboru , Kongere James O. , Sonye George O. , Lutiali Peter A. , Awuor Beatrice , Kawada Hitoshi , Isozumi Rie , Futami Kyoko
Published: December 2020

Background

Although long-lasting insecticidal nets (LLINs) are the most effective tool for preventing malaria parasite transmission, the nets have some limitations. For example, the increase of LLIN use has induced the rapid expansion of mosquito insecticide resistance. More than two persons often share one net, which increases the infection risk. To overcome these problems, two new mosquito nets were developed, one incorporating piperonyl butoxide and another covering ceilings and open eaves. We designed a cluster randomized controlled trial (cRCT) to evaluate these nets based on the information provided in the present preliminary study.

Results

Nearly 75% of the anopheline population in the study area in western Kenya was Anopheles gambiae s. l., and the remaining was Anopheles funestus s. l. More female anophelines were recorded in the western part of the study area. The number of anophelines increased with rainfall. We planned to have 80% power to detect a 50% reduction in female anophelines between the control group and each intervention group. The between-cluster coefficient of variance was 0.192. As the number of clusters was limited to 4 due to the size of the study area, the estimated cluster size was 7 spray catches with an alpha of 0.05. Of 1619 children tested, 626 (48%) were Plasmodium falciparum positive using a rapid diagnostic test (RDT). The prevalence was higher in the northwestern part of the study area. The number of children who slept under bed nets was 929 (71%). The P. falciparum RDT-positive prevalence (RDTpfPR) of net users was 45%, and that of non-users was 55% (OR 0.73; 95% CI 0.56, 0.95). Using 45% RDTpfPR of net users, we expected each intervention to reduce prevalence by 50%. The intracluster correlation coefficient was 0.053. With 80% power and an alpha of 0.05, the estimated cluster size was 116 children. Based on the distribution of children, we modified the boundaries of the clusters and established 300-m buffer zones along the boundaries to minimize a spillover effect.

Conclusions

The cRCT study design is feasible. As the number of clusters is limited, we will apply a two-stage procedure with the baseline data to evaluate each intervention.
Community’s misconception about COVID-19 and its associated factors among Gondar town residents, Northwest Ethiopia
Authors: Mekonnen Habtamu Sewunet , Azagew Abere Woretaw , Wubneh Chalachew Adugna , Belay Getaneh Mulualem , Assimamaw Nega Tezera , Agegnehu Chilot Desta , Azale Telake , Azene Zelalem Nigussie , Merid Mehari Woldemariam , Muluneh Atalay Goshu , Geberu Demiss Mulatu , Kassa Getahun Molla , Yenit Melaku Kindie , Tilahun Sewbesew Yitayih , Gelaye Kassahun Alemu , Tamiru Animut Tagele , Rade Bayew Kelkay , Taye Eden Bishaw , Taddese Asefa Adimasu , Andualem Zewudu , Dagne Henok , Gashaye Kiros Terefe , Kabito Gebisa Guyasa , Mekonnen Tesfaye Hambisa , Wami Sintayehu Daba , Azanaw Jember , Adane Tsegaye , Alemayehu Mekuriaw
Published: December 2020

Background

Despite the implementation of various strategies such as the declaration of COVID-19 emergency state, staying at home, lockdown, and massive protective equipment distribution, still COVID-19 is increasing alarmingly. Therefore, the study aimed to assess the community’s perception of COVID-19 and its associated factors in Gondar town, Northwest Ethiopia.

Methods

A community-based cross-sectional study was employed among 635 Gondar administrative town residents, from April 20 to April 27, 2020. Study participants were selected using a cluster sampling technique. Data were collected using an interviewer-administered structured questionnaire. Epi-Data version 4.6 and STATA 14 were used for data entry and analysis, respectively. Logistic regressions (bivariable and multivariable) were performed to identify statistically significant variables at p < 0.05.

Results

Of the 635 study participants, 623 have completed the study with a 98.1% response rate. The mean age of participants was 36.32 years (SD ± 13.24). The overall magnitude of the community’s misconception about COVID-19 stood at 56.9% (349). Age and religion showed a negative association with misconceptions. To be specific, being in the age group of 27–33 (AOR = 0.52, 95% CI 0.32, 0.86) and being a Muslim (AOR 0.51, 95% CI 0.34, 0.78) were negatively associated with the misconception of COVID-19, whereas occupation and awareness showed positive associations with the misconception. To be specific, having an unemployed occupational status (AOR = 1.79, 95% CI 1.14, 2.82) and being unaware of the number of cases of COVID-19 (AOR 1.66, 95% CI 1.05, 2.62) were positively associated with the community’s misconception on COVID-19.

Conclusion

The magnitude of the community’s misconception about COVID-19 among Gondar town residents was high. Age, religion, unemployment, and unawareness about the number of COVID-19 cases were significant factors of misconception about COVID-19. Thus, stakeholders ought to build community perceptions about COVID 19. To resolve misinformation about COVID-19, accurate and relevant information should be provided to the community using appropriate communication media.
Which seismic attributes are best for subtle fault detection?
Authors: Hussein Marwa , Stewart Robert R. , Wu Jonny
Published: December 2020

Subtle fault detection plays a vital role in reservoir development studies because faults may form baffles or conduits that significantly control how a petroleum reservoir is swept. Small-throw faults are often overlooked in interpreting seismic amplitude data. However, seismic attributes can aid in mapping small faults. Over the years, dozens of seismic attributes have been developed that offer additional features for interpreters with associated caveats. Using the Maui 3D seismic data acquired in the Offshore Taranaki Basin, New Zealand, we have generated seismic attributes that are typically useful for fault detection. We find that multiattribute analysis provides greater geologic information than would be obtained by the analysis of individual attribute volumes. We extract the geologic content of multiple attributes in two ways: interactive corendering of different seismic attributes and the unsupervised machine learning algorithm self-organizing maps (SOM). Corendering seismic attributes that are mathematically independent but geologically interrelated provides a well-integrated structural image. We suggest eight combinations of 16 various attributes useful for a human interpreter with interest in fault and fracture detection. Current interpretation display capabilities constrain corendering to only four attribute volumes. Therefore, we use principal component analysis and SOM techniques to efficiently integrate the geologic information contained within many attributes. This approach gathers the data into one classification volume based on the interrelationships between seismic attributes. We show that our resulting SOM classification volume better highlights small faults that are difficult to image using conventional seismic interpretation techniques. We find that SOM works best when a fault exhibits anomalous features for multiple attributes within the same voxel. However, human interpreters are more adept at recognizing spatial patterns within various attributes and can place them in an appropriate geologic context.
Innovations in Diabetes Care for a Better “New Normal” Beyond COVID-19
Authors: Agarwal Shivani , Griffith Michelle L , Murphy Elizabeth J , Greenlee Carol , Boord Jeffrey , Gabbay Robert A
Published: December 2020

The coronavirus disease pandemic has created opportunities for innovation in diabetes care that were not possible before. From the lens of this “new normal” state, we have an opportunity to rapidly implement, test, and iterate models of diabetes care to achieve the quadruple aim of improving medical outcomes, patient experience, provider satisfaction, and reducing costs. In this perspective, we discuss several innovative diabetes models of care which promote collaborative care models and improve access to high-quality specialty diabetes care. We discuss ongoing threats to diabetes care innovation, and offer practical solutions to foster evolution and sustain current strides made during the pandemic.
Oxygen limitation fails to explain upper chronic thermal limits and the temperature size rule in mayflies
Authors: Funk David H. , Sweeney Bernard W. , Jackson John K.
Published: December 2020

An inability to adequately meet tissue oxygen demands has been proposed as an important factor setting upper thermal limits in ectothermic invertebrates (especially aquatic species) as well as explaining the observed decline in adult size with increased rearing temperature during the immature stages (a phenomenon known as the Temperature Size Rule, or TSR). We tested this by rearing three aquatic insects (the mayflies Neocloeon triangulifer and two species of the Cloeon dipterum complex) through their entire larval life under a range of temperature and oxygen concentrations. Hyperoxia did not extend upper thermal limits, nor did it prevent the loss of size or fertility experienced near upper chronic thermal limits. At moderate temperatures, the TSR pattern was observed under conditions of hyperoxia, normoxia, and hypoxia, suggesting little or no influence of oxygen on this trend. However, for a given rearing temperature, adults were smaller and less fecund under hypoxia due to a lowering of growth rates. These mayflies greatly increased the size of their gills in response to lower dissolved oxygen concentrations but not under oxygen-saturated conditions over a temperature range yielding the classic TSR response. Using ommatidium diameter as a proxy for cell size we found the classic TSR pattern observed under moderate temperature conditions was due primarily to a change in the number of cells rather than cell size. We conclude overall that a failure to meet tissue oxygen demands is not a viable hypothesis for explaining either the chronic thermal limit or TSR pattern in these species.