bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced Hypercoagulability in Sickle Cell Anaemia Patients with Chronic Leg Ulcers
Authors: Sackey David , Dei-Adomakoh Yvonne , Olayemi Edeghonghon
Published: November 2020

Sickle Cell Anaemia (SCA) is associated with a hypercoagulable state resulting in a predisposition to venous thromboembolism. With improvements in the quality of care, more patients with SCA survive into adulthood with an associated increase in the frequency of end-organ damage and chronic complications such as chronic leg ulcers (CLUs). These ulcers rarely occur in the first decade of life and are recurrent, painful, and slow-to-heal. This study tested the hypothesis that coagulation is enhanced in SCA patients with CLU. 145 participants (50 SCA with CLU, 50 SCA without CLU, and 45 with haemoglobin AA) were assessed to determine their coagulation profile using selected tests of coagulation. The SCA with the CLU group had the lowest mean haemoglobin (Hb) concentration. SCA patients with and without CLUs had elevated mean platelet counts, shorter mean aPTT, and marginally prolonged mean PT  compared to HbAA patients. SCA with CLUs patients had a significantly shortened aPTT than those without CLUs (

p

 = 0.035) and HbAA (

p

 = 0.009). There were significant differences in the mean PT between SCA with CLUs patients and HbAA (

p

 = 0.017); SCA without CLU and HbAA (

p

 = 0.014). SCA with and without CLUs patients had higher mean D-dimer levels compared to HbAA. There was a negative correlation between Hb concentration and duration of CLU (r = -0.331,

p

 = 0.021). In conclusion, our study demonstrates a heightened hypercoagulability in SCA patients with CLUs. We did not test for platelet activation, and it is not clear what role, if any, the enhanced hypercoagulability plays in the pathogenesis of CLUs in SCA. It will be useful to ascertain if antiplatelet agents or/and anticoagulants quicken the healing of CLUs in SCA patients.
Driver Attribute Filling for Genes in Interaction Network via Modularity Subspace-Based Concept Learning from Small Samples
Authors: Xie Fei , Xi Jianing , Duan Qun
Published: November 2020

The aberrations of a gene can influence it and the functions of its neighbour genes in gene interaction network, leading to the development of carcinogenesis of normal cells. In consideration of gene interaction network as a complex network, previous studies have made efforts on the driver attribute filling of genes via network properties of nodes and network propagation of mutations. However, there are still obstacles from problems of small size of cancer samples and the existence of drivers without property of network neighbours, limiting the discovery of cancer driver genes. To address these obstacles, we propose an efficient modularity subspace based concept learning model. Our model can overcome the curse of dimensionality due to small samples via dimension reduction in the task of attribute concept learning and explore the features of genes through modularity subspace beyond the network neighbours. The evaluation analysis also demonstrates the superiority of our model in the task of driver attribute filling on two gene interaction networks. Generally, our model shows a promising prospect in the application of interaction network analysis of tumorigenesis.
Lipoxin A4 Reduces Ventilator-Induced Lung Injury in Rats with Large-Volume Mechanical Ventilation
Authors: Wang Qi , Xu Guang-xiao , Tai Qi-hang , Wang Yan
Published: November 2020

Ventilator-induced lung injury (VILI) is a severe and inevitable complication in patients who require mechanical ventilation (MV) for respiratory support. Lipoxin A4 is an endogenous anti-inflammatory and antioxidant mediator. The present study determined the effects of lipoxin A4 on VILI. Twenty-four rats were randomized to the sham, VILI, and lipoxin A4 (LX4) groups. The rats in the VILI and LX4 groups received large-volume MV for 4 hours to simulate VILI. Capillary permeability was evaluated using the PaO2/FiO2 ratio, lung wet/dry weight ratio, and protein level in the lung. VILI-induced inflammation was assessed by measuring cytokines in serum and lung tissue, the expression and activity of NF-κB, and phosphorylated myosin light chain. The oxidative stress response, lung tissue injury, and apoptosis in lung tissue were also estimated, and the expression of apoptotic proteins was examined. MV worsened all of the indices compared to the sham group. Compared to the VILI group, the LX4 group showed significantly improved alveolar-capillary permeability (increased PaO2/FiO2 and decreased wet/dry weight ratios and protein levels), ameliorated histological injury, and reduced local and systemic inflammation (downregulated proinflammatory factors and NF-κB expression and activity). Lipoxin A4 notably inhibited the oxidative stress response and apoptosis and balanced apoptotic protein levels in lung tissue. Lipoxin A4 protects against VILI via anti-inflammatory, antioxidant, and antiapoptotic effects.
Paricalcitol Attenuates Contrast-Induced Acute Kidney Injury by Regulating Mitophagy and Senescence
Authors: Bae Eunjin , Kim Jin Hyun , Jung Myeong Hee , Jang Si Jung , Lee Tae Won , Jung Sehyun , Lee Seunghye , Jang Ha Nee , Chang Se-Ho , Park Dong Jun
Published: November 2020

Contrast-induced acute kidney injury (CI-AKI) is the third most common cause of hospital-acquired renal failure, with an incidence of 11%. However, the disease mechanism remains unclear, and no effective treatment is available. Paricalcitol has been reported to be effective in animal models of kidney injury. We hypothesized that paricalcitol could play a renoprotective role against CI-AKI. Rats were divided into control, paricalcitol, contrast, and paricalcitol-plus-contrast groups. We used a previously published protocol to produce CI-AKI. Paricalcitol (0.3 μg/kg) was administered intraperitoneally before 24 h and 30 min before indomethacin. We used HK-2 cells to evaluate the effects of paricalcitol on mitophagy and senescence. Ioversol triggered renal dysfunction, increasing blood urea nitrogen and serum creatinine. Significant tubular damage, increased 8-OHdG expression, and apoptosis were apparent. Ioversol injection induced high expression levels of the mitophagy markers Pink1, Parkin, and LC3 and the senescence markers β-galactosidase and p16INK4A. Paricalcitol pretreatment prevented renal dysfunction and reduced tissue damage by reducing both mitophagy and senescence. Cellular morphological changes were found, and expression of LC3B and HMGB1 was increased by ioversol in HK-2 cells. Paricalcitol countered these effects. This study showed that mitochondria might drive injury phenotypes in CI-AKI, and that paricalcitol protects against CI-AKI by decreasing mitochondrial damage.
Efficacy and Safety of Mesenchymal Stem Cells in Treatment of Complex Perianal Fistulas: A Meta-Analysis
Authors: Cheng Fang , Huang Zhong , Li Zhi
Published: November 2020

Complex perianal fistula is a highly debilitating and difficult to treat condition. Local mesenchymal stem cell (MSC) therapy for perianal fistula has shown considerable promise but still remains controversial. Therefore, we performed the meta-analysis to evaluate the efficacy and safety of local MSC therapy for complex perianal fistula. PubMed and Embase databases were searched for published randomized clinical trials (RCTs) that reported local MSC therapy for complex perianal fistulas. The effectiveness and safety data analysis was conducted using RevMan5.3. Subgroup analyses were performed based on the characteristics of the studies. Seven RCTs with 730 participants were included. Local MSC treatment showed significantly higher healing rate (HR) of perianal fistulas compared to control (odds ratio (OR) = 2.03; 95% confidence interval (CI) 1.50, 2.74;

P
<
0.00001

). MSCs combined with fibrin glue therapy can improve the HR compared with fibrin glue alone (

OR
=
3.27

; 95% CI 1.15, 9.28;

P
=
0.03

). Subgroup analyses showed that local therapy can improve the HR in patients with perianal fistulas associated with Crohn’s disease (CD) (

OR
=
2.05

; 95% CI 1.41, 3.00;

P
=
0.0002

) and cryptoglandular origin (no-Crohn) (

OR
=
2.98

; 95% CI 0.86, 10.29;

P
=
0.08

). The pooled OR for studies that combined reepithelialization of the external opening with pelvic magnetic resonance imaging (MRI) to evaluate the healing of fistulas was 1.77 (95% CI 1.28, 2.45;

P
=
0.0006

). The pooled OR for studies where fistula healing was defined as complete reepithelialization of external openings was 5.92 (95% CI 1.34, 26.15;

P
=
0.02

). Both autologous MSCs (

OR
=
3.19

; 95% CI 1.05, 9.65;

P
=
0.04

) and allogeneic MSCs (

OR
=
1.97

; 95% CI 1.34, 2.91;

P
=
0.0006

) can obtain higher HR for perianal fistula compared with control. The adipose-derived MSC group can obtain higher HR than the control group (

OR
=
2.29

; 95% CI 1.38, 3.79;

P
=
0.001

). There were no significant differences in adverse events (AEs) (

OR
=
1.06

; 95% CI 0.71, 1.59;

P
=
0.77

). None of the adverse events was judged to be related to MSCs. Our study supported that local MSC therapy alone or combined with fibrin glue is safe and efficacious for complex perianal fistula. In the future, more RCTs are needed to confirm this conclusion.
Fractal Characteristics of Pores in the Longtan Shales of Guizhou, Southwest China
Authors: Huang Yuqi , Zhang Peng , Zhang Jinchuan , Tang Xuan , Liu Chengwei , Yang Junwei
Published: November 2020

The pore structure of marine-continental transitional shales from the Longtan Formation in Guizhou, China, was investigated using fractal dimensions calculated by the FHH (Frenkel-Halsey-Hill) model based on low-temperature N2 adsorption data. Results show that the overall

D
1

(fractal dimension under low relative pressure,

P
/

P

0

≤
0.5

) and

D
2

(fractal dimension under high relative pressure,

P
/

P

0

>
0.5

) values of Longtan shales were relatively large, with average values of 2.7426 and 2.7838, respectively, indicating a strong adsorption and storage capacity and complex pore structure. The correlation analysis of fractal dimensions with specific surface area, average pore size, and maximum gas absorption volume indicates that

D
1

can comprehensively characterize the adsorption and storage capacity of shales, while

D
2

can effectively characterize the pore structure complexity. Further correlation among pore fractal dimension, shale organic geochemical parameters, and mineral composition parameters shows that there is a significant positive correlation between fractal dimensions and organic matter abundance as well as a complex correlation between fractal dimension and organic matter maturity. Fractal dimensions increase with an increase in clay mineral content and pyrite content but decrease with an increase in quartz content. Considering the actual geological evaluation and shale gas exploitation characteristics, a lower limit for

D
1

and upper limit for

D
2

should be set as evaluation criteria for favorable reservoirs. Combined with the shale gas-bearing property test results of Longtan shales in Guizhou, the favorable reservoir evaluation criteria are set as

D
1
≥
2.60

and

D
2
≤
2.85

. When

D
1

is less than 2.60, the storage capacity of the shales is insufficient. When

D
2

is greater than 2.85, the shale pore structure is too complicated, resulting in poor permeability and difficult exploitation.
Mode of Action of Shan‐Zhu‐Yu (Cornus officinalis Sieb. et Zucc.) in the Treatment of Depression Based on Network Pharmacology
Authors: Liu Ping , Yang Ping , Zhang Lan
Published: November 2020

Background. Although the traditional Chinese medicine Shan‐Zhu‐Yu may be efficacious against depression, its mechanism of action is unknown. In this study, we aimed to explore the possible mechanisms of action of Shan‐Zhu‐Yu in the treatment of depression using network pharmacology. Methods. The active ingredients and targets of Shan‐Zhu‐Yu were obtained from the Traditional Chinese Medicine System Pharmacology Database (TCMSP) database and converted into gene names using UniProt. Then, the target genes of depression were collected using GeneCards and OMIM. Drug disease intersection genes were obtained using a Venn tool, and a protein‐protein interaction network was constructed using STRING. Cytoscape was used to construct an active ingredients‐targets‐drug‐disease network. GO and KEGG pathway enrichment analyses were performed using DAVID. Furthermore, Autodock was used to evaluate drug and target binding and explore possible molecular mechanisms. Results. We identified 9721 disease genes, 13 active ingredients, 50 target genes, and 48 drug disease intersecting genes. The results of the GO enrichment analysis suggested that Shan‐Zhu‐Yu affects the activity of G protein‐coupled amine, neurotransmitter, steroid hormone, nuclear, and G protein‐coupled neurotransmitter receptors in the treatment of depression by acting on hormone and nuclear receptor binding. The main signaling pathways were associated with neuroactive ligand‐receptor interaction, calcium, cGMP‐PKG, apoptosis, estrogen, p53, and AGE‐RAGE. Molecular docking confirmed that the active components of Shan‐Zhu‐Yu (e.g., telocinobufagin and β‐sitosterol) docked suitably with NR3C1, Bax, Bcl-2, and caspase-3. Shan‐Zhu‐Yu may exert its therapeutic effects on depression via multiple targets and pathways. Conclusions. The present study elucidates that Shan‐Zhu‐Yu suppresses the expression of Bax and caspase-3 and promotes that of NR3C1 and Bcl-2 through neuroactive ligand‐receptor interaction and apoptosis signaling pathways. Therefore, Shan‐Zhu‐Yu is a potential treatment option for depression, and the results of this study will provide new reference points for future experimental research and a scientific basis for its widespread clinical application.
Application of Distributed Parameter Model to Assessment of Glioma IDH Mutation Status by Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Authors: Li Zongfang , Zhao Wei , He Bo , Koh Tong San , Li Yanxi , Zeng Yizhen , Zhang Zhuo , Zhang Jingzhong , Hou Zujun
Published: November 2020

Previous studies using contrast-enhanced imaging for glioma isocitrate dehydrogenase (IDH) mutation assessment showed promising yet inconsistent results, and this study attempts to explore this problem by using an advanced tracer kinetic model, the distributed parameter model (DP). Fifty-five patients with glioma examined using dynamic contrast-enhanced imaging sequence at a 3.0 T scanner were retrospectively reviewed. The imaging data were processed using DP, yielding the following parameters: blood flow F, permeability-surface area product PS, fractional volume of interstitial space Ve, fractional volume of intravascular space Vp, and extraction ratio E. The results were compared with the Tofts model. The Wilcoxon test and boxplot were utilized for assessment of differences of model parameters between IDH-mutant and IDH-wildtype gliomas. Spearman correlation r was employed to investigate the relationship between DP and Tofts parameters. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis and quantified using the area under the ROC curve (AUC). Results showed that IDH-mutant gliomas were significantly lower in F (

P

 = 0.018), PS (

P
<
0.001

), Vp (

P
<
0.001

), E (

P
<
0.001

), and Ve (

P

 = 0.002) than IDH-wildtype gliomas. In differentiating IDH-mutant and IDH-wildtype gliomas, Vp had the best performance (AUC = 0.92), and the AUCs of PS and E were 0.82 and 0.80, respectively. In comparison, Tofts parameters were lower in Ktrans (

P

 = 0.013) and Ve (

P
<
0.001

) for IDH-mutant gliomas. No significant difference was observed in Kep (

P

 = 0.525). The AUCs of Ktrans, Ve, and Kep were 0.69, 0.79, and 0.55, respectively. Tofts-derived Ve showed a strong correlation with DP-derived Ve (r > 0.9,

P
<
0.001

). Ktrans showed a weak correlation with F (r < 0.3,

P

 > 0.16) and a very weak correlation with PS (r < 0.06,

P

 > 0.8), both of which were not statistically significant. The findings by DP revealed a tissue environment with lower vascularity, lower vessel permeability, and lower blood flow in IDH-mutant than in IDH-wildtype gliomas, being hostile to cellular differentiation of oncogenic effects in IDH-mutated gliomas, which might help to explain the better outcomes in IDH-mutated glioma patients than in glioma patients of IDH-wildtype. The advantage of DP over Tofts in glioma DCE data analysis was demonstrated in terms of clearer elucidation of tissue microenvironment and better performance in IDH mutation assessment.
Economic Policy Uncertainty and Stock Returns of Africa: A Wavelet Coherence Analysis
Authors: Asafo-Adjei Emmanuel , Agyapong Daniel , Agyei Samuel Kwaku , Frimpong Siaw , Djimatey Reginald , Adam Anokye M.
Published: November 2020

This study explores how global economic policy uncertainty (EPU) shocks comove with stock returns (SR) of eight African countries—Botswana, Ghana, Kenya, Morocco, Namibia, Nigeria, South Africa, and Zambia. The study employed daily data from December 2010 to December 2019 using wavelet coherence analysis. The results showed that global EPU comoves with most of the SR of African markets and was concentrated in the longer term, especially during the period between 2011 and 2019, although not substantially. The findings indicate that short-term investments in African stocks are less susceptible to global economic policy uncertainty. It is recommended that foreign investors could hedge agaist policy uncertainties by investing in stock listed in African Stock exchanges while appropriate country-level policies are deployed to manage long-term effect of EPU.
Experimental Study on the Effective Utilization of Reserves in Tight Sandstone Gas Reservoirs and Their Applications
Authors: Zhang Jie , Fang Feifei , Shen Weijun , Liu Huaxun , Gao Shusheng , Ye Liyou
Published: November 2020

The effective utilization of reserves in tight sandstone reservoirs is one of the major concerns in terms of the development of tight sandstone gas reservoirs. However, the characteristics of reserve utilization are not fully understood, and many uncertainties still exist in the process. For this purpose, long cores on the Su 6 block of Sulige tight sandstone gas field in China were selected, and a multipoint embedded measurement system was established to study the characteristics of effective reserve utilization. Then, the effects of the related reservoir properties and production parameters were investigated. Based on the similarity theory, the effective conversion relationship between the physical experiment and the actual field production was established. The results showed that the pressure distribution in the exploitation of tight gas reservoir is nonlinear, and water cut in the reservoir will hinder the effective utilization of reserves. The lower the reservoir permeability, the larger the negative effect of water on reservoir utilization. Lower gas production rate and higher original pressure are associated with a smoother drawdown curve, which results in larger reserve utilization. The moving boundary expands with time, and its initial propagation velocity increase and then decrease. Additionally, the water cut in the reservoir can delay the spread of moving boundary propagation. The experimental results are consistent with the actual results of the field production by the similarity criterion, which can reflect and predict the production performance in tight gas reservoirs effectively. These results can provide a better understanding of reservoir pressure distribution and effective utilization of reserves to optimize the gas recovery and development benefit in tight sandstone gas reservoirs.
An Automated Real-Time Localization System in Highway and Tunnel Using UWB DL-TDoA Technology
Authors: Wen Long , Han Jinkun , Song Liangliang , Zhang Qi , Li Kai , Li Zhi , Zhang Weimin , Zhang Beihai , You Xin , Sung Yunsick , Ji Sumi , Song Wei
Published: November 2020

There exists an electromagnetic shielding effect on radio signals in a tunnel, which results in no satellite positioning signal in the tunnel scenario. Moreover, because vehicles always drive at a high speed on the highway, the real-time localization system (RTLS) has a bottleneck in a highway scenario. Thus, the navigation and positioning service in tunnel and highway is an important technology difficulty in the construction of a smart transportation system. In this paper, a new technology combined downlink time difference of arrival (DL-TDoA) is proposed to realize precise and automated RTLS in tunnel and highway scenarios. The DL-TDoA inherits ultra-wideband (UWB) technology to measure the time difference of radio signal propagation between the location tag and four different location base stations, to obtain the distance differences between the location tag and four groups of location base stations. The proposed solution achieves a higher positioning efficiency and positioning capacity to achieve dynamic RTLS. The DL-TDoA technology based on UWB has several advantages in precise positioning and navigation, such as positioning accuracy, security, anti-interference, and power consumption. In the final experiments on both static and dynamic tests, DL-TDoA represents high accuracy and the mean errors of 11.96 cm, 37.11 cm, 50.06 cm, and 87.03 cm in the scenarios of static tests and 30 km/h, 60 km/h, and 80 km/h in dynamic tests, respectively, which satisfy the requirements of RTLS.
Existence and Large Time Behavior of Entropy Solutions to One-Dimensional Unipolar Hydrodynamic Model for Semiconductor Devices with Variable Coefficient Damping
Authors: Li Yan , Cheng Yanqiu , Yu Huimin
Published: November 2020

In this paper, we investigate the global existence and large time behavior of entropy solutions to one-dimensional unipolar hydrodynamic model for semiconductors in the form of Euler-Possion equations with time and spacedependent damping in a bounded interval. Firstly, we prove the existence of entropy solutions through vanishing viscosity method and compensated compactness framework. Based on the uniform estimates of density, we then prove the entropy solutions converge to the corresponding unique stationary solution exponentially with time. We generalize the existing results to the variable coefficient damping case.
High Hidden Burden of Diabetes Mellitus among Adults Aged 18 Years and Above in Urban Northwest Ethiopia
Authors: Wolde Haileab Fekadu , Derso Terefe , Biks Gashaw Andargie , Yitayal Mezgebu , Ayele Tadesse Awoke , Gelaye Kassahun Alemu , Demissie Getu Debalkie , Azale Telake , Misganaw Bisrat , Kebede Adane , Teshome Destaw Fetene , Dellie Endalkachew , Gebremedhin Tsegaye , Atnafu Asmamaw
Published: November 2020

Background. Ethiopia is one of the sub-Saharan African countries with a rapidly increasing burden of diabetes mellitus (DM). There is limited updated information about the community-based burden of the disease and its associated factors in Ethiopia which is very crucial to plan effective prevention and control measures against the disease. This study is aimed at determining the burden of DM and its associated factors in urban northwest Ethiopia. Methods. A community-based cross-sectional study was conducted from April to May 2019 among residentsaged≥18years in Gondar town and urban kebeles (lowest administrative units of the country) of Health and Demographic Surveillance System site (HDSS) in Dabat district. A multistage sampling technique was used to select 773 participants. World Health Organization (WHO) stepwise approach for noncommunicable disease surveillance was used to collect the data. Fasting blood glucoseFBS≥126 mg/dlwas used to diagnose DM. Descriptive statistics were done to describe the variables of the study. Prevalence with its 95% confidence interval (CI) was estimated. Binary logistic regression model was fitted, variables withpvalue < 0.05 were considered to have a significant association with the outcome, and odds ratio (OR) was used to measure the strength of association. Result. Of the total participants, 6.34% (95% CI; 4.82, 8.29) were found to be diabetic. Of these, 40 (81.6%) were newly diagnosed. Besides, the prevalence of prediabetes was 9.31% (95% CI: 7.45, 11.58). Increased age (AOR=1.06, 95% CI; 1.04, 1.09) and eating vegetables one to three days per week (AOR =0.29, 95% CI; 0.13, 0.65) were significantly associated with diabetes. Conclusion. The overall prevalence of DM is a bit higher than the national estimate, while the proportion of undiagnosed DM which can easily progress to disabling and life-threatening complications was alarmingly high. Age and frequency of eating vegetables per week were associated with diabetes. In light of this finding, future prevention and control measures against the diseases should consider the identified factors. There should also be improved access to screening services.
Relationship between Depression Symptoms and Different Types of Measures of Obesity (BMI, SAD) in US Women
Authors: Zhou Yang , Yang Guifang , Peng Wen , Zhang Hongliang , Peng Zhenyu , Ding Ning , Guo Tao , Cai Yuzhong , Deng Qijian , Chai Xiangping
Published: November 2020

Objective. To estimate the relationship between obesity (defined by both BMI and SAD) and various levels of depressive symptoms in women in the United States. Methods. This is a cross-sectional design. All data were collected from NHANES 2011-2012 and 2013-2014. The Patient Health Questionnaire (PHQ-9) was the primary variable used to index depressive symptoms. SAD was assessed using an abdominal caliper. We stratified participates into three groups according to SAD (trisection): T1: low (11.8-18.4 cm), T2: middle (18.5-22.8 cm), and T3: high (22.9-40.1 cm). Other data were collected following the NHANES protocols. We aimed to investigate the effects of obesity on the depression in the NHANES populations. Results. A total of 4477 women were enrolled in the final study population. Participants with a high SAD had the highest risk of clinical depression symptoms (

OR
=
1.2

, 95% CI: 1.1-1.4), which was, in particular, the case for moderate-severe depression (

OR
=
1.4

, 95% CI: 1.1-1.7) and severe depression (

OR
=
1.4

, 95% CI: 1.0-1.9). We also found a significant relationship between SAD and BMI (

r
=
0.836

). We did, however, not find a significant relationship between BMI and severe depression. Conclusions. SAD had a better correlation with clinical depression symptoms than BMI, especially regarding severe depression symptoms.
Dysregulated Glutamate Transporter SLC1A1 Propels Cystine Uptake via Xc− for Glutathione Synthesis in Lung Cancer
Authors: Guo Wenzheng , Li Kaimi , Sun Beibei , Xu Dongliang , Tong Lingfeng , Yin Huijing , Liao Yueling , Song Hongyong , Wang Tong , Jing Bo , Hu Min , Liu Shuli , Kuang Yanbin , Ling Jing , Li Qi , Wu Yadi , Wang Qi , Yao Feng , Zhou Binhua P. , Lin Shu-Hai , Deng Jiong
Published: November 2020

Cancer cells need to generate large amounts of glutathione (GSH) to buffer oxidative stress during tumor development. A rate-limiting step for GSH biosynthesis is cystine uptake via a cystine/glutamate antiporter Xc−. Xc− is a sodium-independent antiporter passively driven by concentration gradients from extracellular cystine and intracellular glutamate across the cell membrane. Increased uptake of cystine via Xc− in cancer cells increases the level of extracellular glutamate, which would subsequently restrain cystine uptake via Xc−. Cancer cells must therefore evolve a mechanism to overcome this negative feedback regulation. In this study, we report that glutamate transporters, in particular SLC1A1, are tightly intertwined with cystine uptake and GSH biosynthesis in lung cancer cells. Dysregulated SLC1A1, a sodium-dependent glutamate carrier, actively recycled extracellular glutamate into cells, which enhanced the efficiency of cystine uptake via Xc− and GSH biosynthesis as measured by stable isotope-assisted metabolomics. Conversely, depletion of glutamate transporter SLC1A1 increased extracellular glutamate, which inhibited cystine uptake, blocked GSH synthesis, and induced oxidative stress-mediated cell death or growth inhibition. Moreover, glutamate transporters were frequently upregulated in tissue samples of patients with non–small cell lung cancer. Taken together, active uptake of glutamate via SLC1A1 propels cystine uptake via Xc− for GSH biosynthesis in lung tumorigenesis.

Significance:

Cellular GSH in cancer cells is not only determined by upregulated Xc− but also by dysregulated glutamate transporters, which provide additional targets for therapeutic intervention.
Optimizing the Use of Telemedicine in Oncology Care: Postpandemic Opportunities
Authors: Knudsen Karen E. , Willman Cheryl , Winn Robert
Published: November 2020

Utilization of telehealth as part of the cancer care delivery continuum dramatically escalated in response to the COVID-19 pandemic at major cancer centers across the globe. The rapid shift toward telehealth visits for nontreatment cancer care provided immediate benefit through reducing unnecessary risk of exposure, overcoming transportation barriers faced by both patients and caregivers, and fast-tracking care transformation. As such, delineating the impact of telehealth on access, health equity, quality, and outcomes will be essential for refining the use of digital strategies and telehealth toward optimizing cancer care. Herein, experiences to date with telehealth usage for oncology care are reviewed, and priorities are outlined for postpandemic opportunities to improve the lives of patients with cancer through telemedicine.
Characterization of Clonal Evolution in Microsatellite Unstable Metastatic Cancers through Multiregional Tumor Sequencing
Authors: Bonneville Russell , Paruchuri Anoosha , Wing Michele R. , Krook Melanie A. , Reeser Julie W. , Chen Hui-Zi , Dao Thuy , Samorodnitsky Eric , Smith Amy M. , Yu Lianbo , Nowacki Nicholas , Chen Wei , Roychowdhury Sameek
Published: November 2020

Microsatellites are short, repetitive segments of DNA, which are dysregulated in mismatch repair-deficient (MMRd) tumors resulting in microsatellite instability (MSI). MSI has been identified in many human cancer types with varying incidence, and microsatellite instability-high (MSI-H) tumors often exhibit increased sensitivity to immune-enhancing therapies such as PD-1/PD-L1 inhibition. Next-generation sequencing (NGS) has permitted advancements in MSI detection, and recent computational advances have enabled characterization of tumor heterogeneity via NGS. However, the evolution and heterogeneity of microsatellite changes in MSI-positive tumors remains poorly described. We determined MSI status in 6 patients using our previously published algorithm, MANTIS, and inferred subclonal composition and phylogeny with Canopy and SuperFreq. We developed a simulated annealing-based method to characterize microsatellite length distributions in specific subclones and assessed the evolution of MSI in the context of tumor heterogeneity. We identified three to eight tumor subclones per patient, and each subclone exhibited MMRd-associated base substitution signatures. We noted that microsatellites tend to shorten over time, and that MMRd fosters heterogeneity by introducing novel mutations throughout the disease course. Some microsatellites are altered among all subclones in a patient, whereas other loci are only altered in particular subclones corresponding to subclonal phylogenetic relationships. Overall, our results indicate that MMRd is a substantial driver of heterogeneity, leading to both MSI and subclonal divergence.

Implications:

We leveraged subclonal inference to assess clonal evolution based on somatic mutations and microsatellites, which provides insight into MMRd as a dynamic mutagenic process in MSI-H malignancies.
A Rare Case Report of Posterior Ectopic Cilia in a 41-Year-Old Saudi Male
Authors: Al-Najmi Yahya , Abdalla Elsayed Maram
Published: November 2020

There is a wide spectrum of cilial anomalies; however, ectopic cilia are the rarest of the cilial anomalies. We report, to the best of our knowledge, the third worldwide case of this eyelid anomaly in the inferior palpebral conjunctiva and the first with a long-term follow-up of 18 months without recurrence following excision. The 41-year-old Saudi male presented with posterior ectopic cilia in the palpebral conjunctiva of the left lower eyelid. This rare anomaly was not associated with other findings. Eighteen months after complete excision of the cilia (along with the adjacent conjunctiva and tarsal plate), there was no recurrence of the ectopic cilia. This case highlights the importance of considering ectopic cilia when patients present with focal punctate keratopathy and the importance of excision of the cilia along with the adjacent conjunctiva and tarsal plate to prevent recurrence.
Spontaneous Erosion of Retained Bone Chip into Anal Canal Following Progressive Perineal Urethroplasty with Inferior Pubectomy: Lessons Learnt!
Authors: Singh Shrawan Kumar , Devana Sudheer Kumar , Tyagi Shantanu
Published: November 2020

We present a never before reported delayed complication of progressive perineal urethroplasty with inferior pubectomy in a young male, where retained bone chip spontaneously erodes through anal canal. Our case cautions urologists doing inferior pubectomy for pelvic fracture urethral distraction defect to make sure that no loose bony fragment is left in the operative field. We also emphasize to make sure to nibble the sharp bony margins of the cut pubic bone after inferior pubectomy so that it will not impinge onto the anterior wall of rectum eliminating the risk of delayed perforation of rectum or anal canal.
Chromosomal Evolution in Aspredinidae (Teleostei, Siluriformes): Insights on Intra- and Interspecific Relationships with Related Groups
Authors: Ferreira Milena , de Jesus Isac S. , Viana Patrik F. , Garcia Caroline , Matoso Daniele A. , Cioffi Marcelo B. , Bertollo Luiz A.C. , Feldberg Eliana
Published: November 2020

The family Aspredinidae comprises a clade of complex systematic relationships, both from molecular and morphological approaches. In this study, conventional and molecular cytogenetic studies coupled with nucleotide sequencing were performed in 6 Aspredininae species (Amaralia hypsiura, Bunocephalus cf. aloikae, Bunocephalus amaurus, Bunocephalus aff. coracoideus, Bunocephalus verrucosus, and Platystacus cotylephorus) from different locations of the Amazon hydrographic basin. Our results showed highly divergent diploid numbers (2n) among the species, ranging from 49 to 74, including the occurrence of an XX/X0 sex chromosome system. A neighbor-joining phylogram based on the cytochrome c oxidase I (COI) showed that Bunocephalus coracoideus is not a monophyletic clade, but closely related to B. verrucosus. The karyotypic data associated with COI suggest an ancestral karyotype for Aspredinidae with a reduced 2n, composed of bi-armed chromosomes and a trend toward chromosomal fissions resulting in higher diploid number karyotypes, mainly composed of acrocentric chromosomes. Evolutionary relationships were discussed under a phylogenetic context with related species from different Siluriformes families. The karyotype features and chromosomal diversity of Aspredinidae show an amazing differentiation, making this family a remarkable model for investigating the evolutionary dynamics in siluriforms as well as in fish as a whole.
The Effect of Patient’s Choice of Cognitive Behavioural or Psychodynamic Therapy on Outcomes for Panic Disorder: A Doubly Randomised Controlled Preference Trial
Authors: Svensson Martin , Nilsson Thomas , Perrin Sean , Johansson Håkan , Viborg Gardar , Falkenström Fredrik , Sandell Rolf
Published: November 2020

Introduction: It remains unclear whether offering psychiatric patients their preferred treatment influences outcomes at the symptom level. Objective: To assess whether offering patients with panic disorder with/without agoraphobia (PD/A) a choice between 2 psychotherapies yields superior outcomes to random assignment. Methods: In a doubly randomised, controlled preference trial (DRCPT), 221 adults with PD/A were randomly assigned to: choosing panic-focused psychodynamic therapy (PFPP) or panic control treatment (PCT; a form of cognitive behavioural therapy); random assignment to PFPP or PCT; or waiting list control. Primary outcomes were PD/A severity, work status and work absences at post-treatment assessment. Outcomes at post-treatment assessment, 6-, 12-, and 24-month follow-ups were assessed using segmented multilevel linear growth models. Results: At post-treatment assessment, the choice and random conditions were superior to the control for panic severity but not work status/absences. The choice and random conditions did not differ during treatment or follow-up for the primary outcomes. For panic severity, PCT was superior to PFPP during treatment (standardised mean difference, SMD, –0.64; 95% confidence interval, CI, –1.02 to –0.25); PFPP was superior to PCT during follow-up (SMD 0.62; 95% CI 0.27–0.98). There was no allocation by treatment type interaction (SMD –0.57; 95% CI –1.31 to 0.17). Conclusions: Previous studies have found that offering patients their preferred treatment yields small to moderate effects but have not employed designs that could rigorously test preference effects. In this first DRCPT of 2 evidence-based psychotherapies, allowing patients with PD/A to choose their preferred treatment was not associated with improved outcomes. Further DRCPTs are needed.
Microbiome and Cervical Cancer
Authors: Castanheira Cristina Paula , Sallas Mayara Luciana , Nunes Rafaella Almeida Lima , Lorenzi Noely Paula Cristina , Termini Lara
Published: November 2020

Persistent infection with some types of mucosal human papillomavirus (HPV) is the etiological factor for the development of cervical cancer and its precursor lesions. Besides, several cofactors are known to play a role in cervical disease onset and progression either by favoring or by preventing HPV infection and persistence. The microbiome of a healthy female genital tract is characterized by the presence of 1 or few varieties of lactobacilli. However, high-throughput studies addressing the bacterial diversity and abundance in the female genital tract have shown that several factors, including hormonal levels, hygiene habits, and sexually transmitted diseases may disrupt the natural balance, favoring the outgrowth of some groups of bacteria, which in turn may favor some pathological states. Recently, the vaginal microbiome has emerged as a new variable that could greatly influence the natural history of HPV infections and their clinical impact. In this context, changes in the vaginal microbiome have been detected in women infected with HPV and women with HPV-associated lesions and cancer. However, the role of specific bacteria groups in the development/progression or prevention/regression of HPV-associated pathologies is not well understood. In this review we summarize the current knowledge concerning changes in vaginal microbiome and cervical disease. We discuss the potential functional interplay between specific bacterial groups and HPV infection outcomes.
Hepatocellular Carcinoma with Atrial Extension: A Case Report
Authors: Dantas Eduardo , Matos Daniel , Coelho Mariana , Sequeira Cristiana , Cardoso Cláudia , Oliveira Ana Paula
Published: November 2020

Hepatocellular carcinoma is a common malignancy usually associated with cirrhosis. Despite being a highly aggressive tumor with several cases of vascular invasion, metastatic disease to the heart is a rare condition. A 65-year-old male cirrhotic patient was admitted with dyspnea, ascites, and lower extremity edema. A transthoracic echocardiogram showed a large mass in the right atrium. Further imaging studies revealed the presence of hepatocellular carcinoma extending from the liver to the right atrium through the inferior vena cava. The cardiac mass was surgically removed to treat the symptoms of right heart failure, but unfortunately the patient died on the 30th day after surgery due to septic shock.
Imaging Identification of Rapidly Progressing Autosomal Dominant Polycystic Kidney Disease: Simple Eligibility Criterion for Tolvaptan
Authors: Higashihara Eiji , Horie Shigeo , Muto Satoru , Kawano Haruna , Tambo Mitsuhiro , Yamaguchi Tsuyoshi , Taguchi Satoru , Kaname Shinya , Yokoyama Kenich , Yoshioka Tatsuya , Furukawa Toshihito , Fukuhara Hiroshi
Published: November 2020

Background: Tolvaptan was approved for the treatment of autosomal dominant polycystic kidney disease (ADPKD). However, the official indication of “rapidly progressive disease” is described differently in the clinical guidelines. We aim to define “rapidly progressive disease” by risk of ESRD, which is evaluated using estimated height-adjusted total kidney volume (HtTKV) growth rate. Methods: The risk of ESRD was retrospectively analyzed in 617 initially non-ESRD adults with ADPKD and observed with standard of care between 2007 and 2018. The estimated annual growth rate of the HtTKV, termed as eHTKV-α (%/year), is derived from the following equation: [HtTKV at age t] = K(1 + eHTKV-α/100)t, where K = 150 mL/m is used in Mayo Imaging Classification and K = 130 mL/m is proposed for individually stable eHTKV-α value from baseline. The accuracy of eHTKV-α to predict ESRD for censored ages was analyzed using time-dependent receiver-operating characteristic curves (ROC). The cutoff point of initially measured eHTKV-α to predict ESRD was assessed using Kaplan-Meier and Cox’s proportional hazards models. Performance characteristics of the cutoff point for censored ages were calculated using time-dependent ROC and validated by the bootstrap method. Results: The area under the time-dependent ROC of eHTKV-α to predict ESRD at age 65 was 0.89 ± 0.04 (K = 130). The mean renal survival was less than 70 years at eHTKV-α ≥4.0%/year (K = 130). Mean renal survival was approximately 12 years shorter, and hazard ratio of ESRD was more than 5-time higher at this cutoff point than at lower point. Time-dependent sensitivity for age 65 and cutoff point of 4.0%/year (K = 130) was 93.4 ± 0.3%. Between cutoff points ≥4.0%/year (K = 130) and ≥3.5%/year (K = 150), there was no significant difference in performance characteristics and accuracy to predict ESRD. Conclusion: eHTKV-α well predicts ESRD. Initially, measured eHTKV-α ≥4.0%/year (K = 130) defines high-risk ESRD. Without additional conditions, a single eHTKV-α cutoff point identifies subjects that are most likely to benefit from tolvaptan.
Modulating TSH Receptor Signaling for Therapeutic Benefit
Authors: Krause Gerd , Eckstein Anja , Schülein Ralf
Published: November 2020

Autoimmune thyroid-stimulating antibodies are activating the thyrotropin receptor (TSHR) in both the thyroid and the eye, but different molecular mechanisms are induced in both organs, leading to Graves’ disease (GD) and Graves’ orbitopathy (GO), respectively. Therapy with anti-thyroid drugs to reduce hyperthyroidism (GD) by suppressing the biosynthesis of thyroid hormones has only an indirect effect on GO, since it does not causally address pathogenic TSHR activation itself. GO is thus very difficult to treat. The activated TSHR but also the cross-interacting insulin-like growth factor 1 receptor (IGF-1R) contribute to this issue. The TSHR is a heptahelical G-protein-coupled receptor, whereas the IGF-1R is a receptor tyrosine kinase. Despite these fundamental structural differences, both receptors are phosphorylated by G-protein receptor kinases, which enables β-arrestin binding. Arrestins mediate receptor internalization and also activate the mitogen-activated protein kinase pathway. Moreover, emerging results suggest that arrestin plays a critical role in the cross-interaction of the TSHR and the IGF-1R either in their common signaling pathway and/or during an indirect or potential TSHR/IGF-1R interaction. In this review, novel pharmacological strategies with allosteric small-molecule modulators to treat GO and GD on the level of the TSHR and/or the TSHR/IGF-1R cross-interaction will be discussed. Moreover, monoclonal antibody approaches targeting the TSHR or the IGF-1R and thereby preventing activation of either receptor will be presented. Another chapter addresses the immunomodulation to treat GO using TSHR-derived peptides targeting the human leukocyte antigen DR isotope (HLA-DR), which is a feasible approach to tackle GO, since HLA-DR and TSHR are overexpressed in orbital tissues of GO patients.
Training of trainers: An action-based research for improving the pedagogical skills of academicians
Authors: Özer Bayram , Duran Volkan , Tekke Mustafa
Published: November 2020

Based on the philosophy of lifelong education, private/public institutions and organizations invest in continuous training of human resources. Universities also organize in-service trainings regarding the general principles of teaching and learning in the context lifelong learning activities for the development of the pedagogical skills of the academicians who have difficulty in using teaching skills and principles in the courses in their universities. Therefore, a Project entitled as Training of Trainers based on action research based on qualitative research design was carried out for aiming at providing pedagogical education for the academicians who work in different departments of Ondokuz Mayis University who are experts in different disciplines but who do not have pedagogical background in order to gain experience in basic skills and principles in education area so as to improve the quality of education in this way. During the project, which lasted for a total of 2 years, 246 academicians were trained in 24 different subjects, the opinions of the participants were taken and the distribution of these views was reflected in the tables in text. Finally, the asymptotic Significance (2-sided) for Pearson Chi-Square indicates of the yes/no answer indicates that there is a dramatic change regarding the effectiveness of the program. It is seen that it meets the needs of academicians. Therefore, the program based on action research design shows that such in-service pedagogical programs could be useful for higher education in this respect.
Bullying behavior among students
Authors: Ulfah Maria , Gustina Erni
Published: November 2020

This study aimed to investigate whether communication patterns, peers’ involvement and gender different can be the predictors of adolescent bullying behavior. This study involved 193 adolescents of grade 8 and 9 with the most adolescents of 14 years old who had filled in questionnaires. The results showed the prevalence of adolescent involvement in bullying which was 62.69%. Parental communication patterns have an OR = 1.64 (95% CI=0.87-3.09). Peers involvement in bullying behavior (OR=1.92; 95% CI=1.01-3.66). Adolescent girls were more involved in bullying behavior (59.59%) compared to adolescent boys (OR=3.32; 95% CI=1.69-6.54). Poor parental communication patterns, peers influence negatively predict to the bullying behavior in adolescent. Bullying is higher in boys than girls where as boys has a greater chance of bullying than girls. Therefore, bullying intervention programs are needed in schools.