bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination immunotherapy with interleukin‐2 surface‐modified tumor cell vaccine and programmed death receptor‐1 blockade against renal cell carcinoma
Authors: Zhang Xinji , Shi Xiaojun , Li Jinlong , Hu Zhiming , Gao Jimin , Wu Shihao , Long Zhaolin
Published: October 2018

Immunotherapy may be an effective way to prevent postoperative recurrence of renal cell carcinoma. Streptavidin‐interleukin‐2 (SA‐IL‐2) surface‐modified tumor cell vaccine developed through our protein‐anchor technology could induce specific antitumor T‐cell responses, but this immunotherapy cannot completely eradicate the tumor. These effector T cells highly expressed programmed death receptor‐1 (PD‐1), and the expression of programmed death ligand‐1 (PD‐L1) in the tumor environment also was upregulated after SA‐IL‐2‐modified vaccine therapy. PD‐1/PD‐L1 interaction promotes tumor immune evasion. Adding PD‐1 blockade to SA‐IL‐2‐modified vaccine therapy increased the number of CD4+, CD8+ and CD8+interferon‐γ+ but not CD4+Foxp3+ T cells. PD‐1 blockade could rescue the activity of tumor‐specific T lymphocytes induced by the SA‐IL‐2‐modified vaccine. Combination therapy delayed tumor growth and protected mice against a second Renca cells but not melanoma cells challenge. Taken together, PD‐1 blockade could reverse immune evasion in the treatment with SA‐IL‐2‐modified vaccine, and eventually induce a stronger specific antitumor immune response against renal cell carcinoma.
High‐throughput screening in colorectal cancer tissue‐originated spheroids
Authors: Kondo Jumpei , Ekawa Tomoya , Endo Hiroko , Yamazaki Kanami , Tanaka Norio , Kukita Yoji , Okuyama Hiroaki , Okami Jiro , Imamura Fumio , Ohue Masayuki , Kato Kikuya , Nomura Taisei , Kohara Arihiro , Mori Seiichi , Dan Shingo , Inoue Masahiro
Published: October 2018

Patient‐derived cancer organoid culture is an important live material that reflects clinical heterogeneity. However, the limited amount of organoids available for each case as well as the considerable amount of time and cost to expand in vitro makes it impractical to perform high‐throughput drug screening using organoid cultures from multiple patients. Here, we report an advanced system for the high‐throughput screening of 2427 drugs using the cancer tissue‐originated spheroid (CTOS) method. In this system, we apply the CTOS method in an ex vivo platform from xenograft tumors, using machines to handle CTOS and reagents, and testing a CTOS reference panel of multiple CTOS lines for the hit drugs. CTOS passages in xenograft tumors resulted in minimal changes of morphological and genomic status, and xenograft tumor generation efficiently expanded the number of CTOS to evaluate multiple drugs. Our panel of colorectal cancer CTOS lines exhibited diverse sensitivities to the hit compounds, demonstrating the usefulness of this system for investigating highly heterogeneous disease.
Automated symptom and treatment side effect monitoring for improved quality of life among adults with diabetic peripheral neuropathy in primary care: a pragmatic, cluster, randomized, controlled trial
Authors: Adams A. S. , Schmittdiel J. A. , Altschuler A. , Bayliss E. A. , Neugebauer R. , Ma L. , Dyer W. , Clark J. , Cook B. , Willyoung D. , Jaffe M. , Young J. D. , Kim E. , Boggs J. M. , Prosser L. A. , Wittenberg E. , Callaghan B. , Shainline M. , Hippler R. M. , Grant R. W.
Published: October 2018

Aims

To evaluate the effectiveness of automated symptom and side effect monitoring on quality of life among individuals with symptomatic diabetic peripheral neuropathy.

Methods

We conducted a pragmatic, cluster randomized controlled trial (July 2014 to July 2016) within a large healthcare system. We randomized 1834 primary care physicians and prospectively recruited from their lists 1270 individuals with neuropathy who were newly prescribed medications for their symptoms. Intervention participants received automated telephone‐based symptom and side effect monitoring with physician feedback over 6 months. The control group received usual care plus three non‐interactive diabetes educational calls. Our primary outcomes were quality of life (EQ‐5D) and select symptoms (e.g. pain) measured 4–8 weeks after starting medication and again 8 months after baseline. Process outcomes included receiving a clinically effective dose and communication between individuals with neuropathy and their primary care provider over 12 months. Interviewers collecting outcome data were blinded to intervention assignment.

Results

Some 1252 participants completed the baseline measures [mean age (sd): 67 (11.7), 53% female, 57% white, 8% Asian, 13% black, 20% Hispanic]. In total, 1179 participants (93%) completed follow‐up (619 control, 560 intervention). Quality of life scores (intervention: 0.658 ± 0.094; control: 0.653 ± 0.092) and symptom severity were similar at baseline. The intervention had no effect on primary [EQ‐5D: −0.002 (95% CI −0.01, 0.01), P = 0.623; pain: 0.295 (−0.75, 1.34), P = 0.579; sleep disruption: 0.342 (−0.18, 0.86), P = 0.196; lower extremity functioning: −0.079 (−1.27, 1.11), P = 0.896; depression: −0.462 (−1.24, 0.32); P = 0.247] or process outcomes.

Conclusions

Automated telephone monitoring and feedback alone were not effective at improving quality of life or symptoms for people with symptomatic diabetic peripheral neuropathy.

Trial Registration: ClinicalTrials.gov (NCT02056431).
Population, general practitioner and practice characteristics are associated with screening procedures for microvascular complications in Type 2 diabetes care in Norway
Authors: Bakke Å. , Tran A. T. , Dalen I. , Cooper J. G. , Løvaas K. F. , Jenum A. K. , Berg T. J. , Madsen T. V. , Nøkleby K. , Gjelsvik B. , Claudi T. , Skeie S. , Carlsen S. , Sandberg S. , Thue G.
Published: October 2018

Aims

To assess population, general practitioner (GP) and practice characteristics associated with the performance of microvascular screening procedures and to propose strategies to improve Type 2 diabetes care.

Methods

A cross‐sectional survey in Norway (281 GPs from 77 practices) identified 8246 people with a Type 2 diabetes duration of 1 year or more. We used multilevel regression models with either the recording of at least two of three recommended screening procedures (albuminuria, monofilament, eye examination) or each procedure separately as dependent variable (yes/no), and characteristics related to the person with diabetes, GP or practice as independent variables.

Results

The performance of recommended screening procedures was recorded in the following percentages: albuminuria 31.5%, monofilament 27.5% and eye examination 60.0%. There was substantial heterogeneity between practices, and between GPs within practices for all procedures. Compared with people aged 60–69 years, those aged < 50 years were less likely to have an albuminuria test performed [odds ratio (OR) 0.75, 95% CI 0.61 to 0.93] and eye examination (OR 0.79, 95% CI 0.66 to 0.95). People with macrovascular disease had fewer screening procedures recorded (OR 0.68, 95% CI 0.59 to 0.78). Use of an electronic diabetes form was associated with improved screening  (OR 2.65, 95% CI 1.86 to 3.78). GPs with high workload recorded fewer procedures (OR 0.59, 95% CI 0.39 to 0.90).

Conclusions

Performance of screening procedures was suboptimal overall, and in people who should be prioritized. Performance varied substantially between GPs and practices. The use of a structured diabetes form should be mandatory.
Body size explains interspecific variation in size–latitude relationships in geographically widespread beetle species
Authors: Tseng Michelle , Soleimani Pari Sina
Published: October 2018

1. In most birds and mammals, larger individuals of the same species tend to be found at higher latitudes, but in insects, body size–latitude relationships are highly variable.

2. Recent studies have shown that larger‐bodied insect species are more likely to decrease in size when reared at increased temperature, compared with smaller‐sized species. These findings have led to the prediction that a positive relationship between body size and latitude should be more prevalent in larger‐bodied insect species.

3. This study measured the body size of > 4000 beetle specimens (12 species) collected throughout North America. Some beetle species increased in size with latitude, while others decreased. Importantly, mean species body size explained c. 30% of the interspecific variation in the size–latitude response.

4. As predicted, larger‐bodied beetle species were more likely to show a positive relationship between body size and latitude (Bergmann's rule), and smaller‐bodied species were more likely to show a negative body size–latitude relationship (inverse Bergmann's rule).

5. These body size–latitude patterns suggest that size‐specific responses to temperature may underlie global latitudinal distributions of body size in Coleoptera, as well as other insects.
Validation of a non-invasive method for the early detection of metabolic syndrome: a diagnostic accuracy test in a working population
Authors: Romero-Saldaña Manuel , Tauler Pedro , Vaquero-Abellán Manuel , López-González Angel-Arturo , Fuentes-Jiménez Francisco-José , Aguiló Antoni , Álvarez-Fernández Carlos , Molina-Recio Guillermo , Bennasar-Veny Miquel
Published: October 2018

Objectives

A non-invasive method for the early detection of metabolic syndrome (NIM-MetS) using only waist-to-height ratio (WHtR) and blood pressure (BP) has recently been published, with fixed cut-off values for gender and age. The aim of this study was to validate this method in a large sample of Spanish workers.

Design

A diagnostic test accuracy to assess the validity of the method was performed.

Setting

Occupational health services.

Participants

The studies were conducted in 2012–2016 on a sample of 60 799 workers from the Balearic Islands (Spain).

Interventions

The NCEP-ATP III criteria were used as the gold standard. NIM-MetS has been devised using classification trees (the χ2automatic interaction detection method).

Main outcome measures

Anthropometric and biochemical variables to diagnose MetS. Sensitivity, specificity, validity index and Youden Index were determined to analyse the accuracy of the diagnostic test (NIM-MetS).

Results

With regard to the validation of the method, sensitivity was 54.7%, specificity 94.9% and the Validity Index 91.2%. The cut-off value for WHtR was 0.54, ranging from 0.51 (lower age group) to 0.56 (higher age group). Variables more closely associated with MetS were WHtR (area under the curve (AUC)=0.85; 95% CI 0.84 to 0.86) and systolic BP (AUC=0.79; 95% CI 0.78 to 0.80)). The final cut-off values for the non-invasive method were WHtR ≥0.56 and BP ≥128/80 mm Hg, which includes four levels of MetS risk (very low, low, moderate and high).

Conclusions

The analysed method has shown a high validity index (higher than 91%) for the early detection of MetS. It is a non-invasive method that is easy to apply and interpret in any healthcare setting. This method provides a scale of MetS risk which allows more accurate detection and more effective intervention.
Mixed-methods evaluation of the Perioperative Medicine Service for High-Risk Patients Implementation Pilot (POMSHIP): a study protocol
Authors: Walker David , Wagstaff Duncan , McGuckin Dermot , Vindrola-Padros Cecilia , Swart Nicholas , Morris Stephen , Crowe Sonya , Fulop Naomi J , Moonesinghe S Ramani
Published: October 2018

Introduction

Perioperative complications have a lasting effect on health-related quality of life and long-term survival. The Royal College of Anaesthetists has proposed the development of perioperative medicine (POM) services as an intervention aimed at improving postoperative outcome, by providing better coordinated care for high-risk patients. The Perioperative Medicine Service for High-risk Patients Implementation Pilot was developed to determine if a specialist POM service is able to reduce postoperative morbidity, failure to rescue, mortality and cost associated with hospital admission. The service involves individualised objective risk assessment, admission to a postoperative critical care unit and follow-up on the surgical ward by the POM team. This paper introduces the service and how it will be evaluated.

Methods and analysis of the evaluation

A mixed-methods evaluation is exploring the impact of the service. Clinical effectiveness of the service is being analysed using a ‘before and after’ comparison of the primary outcome (the PostOperative Morbidity Score). Secondary outcomes will include length of stay, validated surveys to explore quality of life (EQ-5D) and quality of recovery (Quality of Recovery-15 Score). The impact on costs is being analysed using ‘before and after’ data from the Patient-Level Information and Costing System and the National Schedule of Reference Costs. The perceptions and experiences of staff and patients with the service, and how it is being implemented, are being explored by a qualitative process evaluation.

Ethics and dissemination

The study was classified as a service evaluation. Participant information sheets and consent forms have been developed for the interviews and approvals required for the use of the validated surveys were obtained. The findings of the evaluation are being used formatively, to make changes in the service throughout implementation. The findings will also be used to inform the potential roll-out of the service to other sites.
Moderation of alcohol consumption as a recommendation in European hypertension management guidelines: a survey on awareness, screening and implementation among European physicians
Authors: Zaidi Touis Laila , Bolbrinker Juliane , Riemer Thomas Günther , Kreutz Reinhold
Published: October 2018

Objectives

Moderation of alcohol consumption is included as a class I, level of evidence A recommendation in the current European guidelines for the management of hypertension. We investigated its awareness and self-reported implementation among European physicians across different specialties and workplaces.

Design and setting

A cross-sectional survey study conducted in two annual German meetings (German Society of Cardiology and the German Society of Internal Medicine) and two annual European meetings (European Society of Hypertension and European Society Cardiology) in 2015.

Participants

1064 physicians attending the European meetings were interviewed including 52.1% cardiologists, 29.2% internists and 8.8% general practitioners.

Main outcome measures

Physician screening of alcohol consumption, awareness and self-implementation of the recommendation of the current European guidelines about moderation of alcohol consumption for the management of hypertension.

Results

Overall, 81.9% of physicians reported to generally quantify alcohol consumption in patients with hypertension. However, only 28.6% and 14.5% of participants reported screening alcohol consumption in their patients with newly detected or treatment-resistant hypertension. Physicians recommended a maximum alcohol intake of 13.1±11.7 g/day for women (95% CI 12.3 to 13.8) and 19.9±15.6 g/day for men (95% CI 18.8 to 20.9). In case of moderate to high alcohol consumption, 10.3% would manage only hypertension without addressing alcohol consumption, while 3.7% of the physicians would do so in case of alcohol dependence (p<0.001).

Conclusions

The average amount of alcohol intake per day recommended by European physicians in this survey was in agreement with the guidelines. The low number of physicians that screen for alcohol consumption in patients with newly detected and with treatment-resistant hypertension indicates an important deficit in the management of hypertension.
A Fulminant Case of Acute Respiratory Distress Syndrome Associated with Mycoplasma Pneumonia Treated with Nasal High-Flow Oxygen Therapy
Authors: Kawakami Naoki , Namkoong Ho , Ohata Takanori , Sakaguchi Shinji , Saito Fumitake , Yuki Hideki
Published: October 2018

Introduction. The prognosis of mycoplasma pneumonia in adults is generally favorable, but a few patients show progression to acute respiratory distress syndrome (ARDS). We have described the management of a patient who showed progression of mycoplasma pneumonia to ARDS. Presentation of Case. A 26-year-old male patient with no significant past medical or social history presented with a 5-day history of fever. Following this, he was diagnosed with bacterial pneumonia and treated with tazobactam/piperacillin; however, he showed little clinical improvement with this treatment approach. We diagnosed the patient with mycoplasma pneumonia with an antigen test and treated him with azithromycin and prednisolone. Despite the appropriate antimicrobial therapy, his symptoms worsened and therefore we changed his oxygen therapy from a reservoir mask to nasal high-flow oxygen in addition to minocycline. Consequently, with this treatment, he recovered from severe mycoplasma pneumonia. Discussion. In patients with severe pneumonia who experience respiratory failure, it has been reported that nasal high-flow oxygen therapy is not inferior to noninvasive positive pressure ventilation therapy regarding intubation rate. In this case, induction of nasal high-flow oxygen therapy led to avoidance of ventilator management. This is a valuable case report highlighting the optimal outcome of nasal high-flow oxygen therapy in a fulminant case of acute respiratory distress syndrome. Conclusion. In patients who present with severe mycoplasma pneumonia with respiratory failure, nasal high-flow oxygen therapy can help reduce the needs for ventilator management including intubation.
Study of Mechanical Property of Rock under Uniaxial Cyclic Loading and Unloading
Authors: Guo Hongjun , Ji Ming , Zhang Yidong , Zhang Meng
Published: October 2018

Through studying the mechanics, energy, and deformation features of rock under uniaxial cyclic loading and unloading, the findings are as follows: (1) under cyclic loading and unloading, the curve of stress and strain for loading and unloading in every cycle was not superposition reciprocally but formed an acutifoliate hysteresis loop. The distribution of the hysteresis loop became denser with the cycles and moved toward the direction of strain increasing. (2) The area of the hysteresis loop indicated the inner damage degree of rock. And the hysteresis energy accumulated was stronger; the damage of rock was more serious. Furthermore, the hysteresis energy grew linearly along with load, and the hysteresis energy accumulated had a trend exponential growth with cycle continuing. (3) The elasticity modulus grew in the form of logarithm as a whole. In each cycle, elasticity modulus for unloading was greater than that for loading. When it exceeded a certain value, elasticity modulus for reloading was less than elasticity modulus for unloading. (4) The cyclic loading and unloading had a strength impact that was gradually stronger and stronger as the cycle went on the sample of rock.
Directional Correlation Filter Bank for Robust Head Pose Estimation and Face Recognition
Authors: Chen Si , Yan Dong , Yan Yan
Published: October 2018

During the past few decades, face recognition has been an active research area in pattern recognition and computer vision due to its wide range of applications. However, one of the most challenging problems encountered by face recognition is the difficulty of handling large head pose variations. Therefore, the efficient and effective head pose estimation is a critical step of face recognition. In this paper, a novel feature extraction framework, called Directional Correlation Filter Bank (DCFB), is presented for head pose estimation. Specifically, in the proposed framework, the 1-Dimensional Optimal Tradeoff Filters (1D-OTF) corresponding to different head poses are simultaneously and jointly designed in the low-dimensional linear subspace. Different from the traditional methods that heavily rely on the precise localization of the key facial feature points, our proposed framework exploits the frequency domain of the face images, which effectively captures the high-order statistics of faces. As a result, the obtained features are compact and discriminative. Experimental results on public face databases with large head pose variations show the superior performance obtained by the proposed framework on the tasks of both head pose estimation and face recognition.
Congenital Glaucoma: a Novel Ocular Manifestation of Hajdu-Cheney Syndrome
Authors: Swan L. , Gole G. , Sabesan V. , Cardinal J. , Coman D.
Published: October 2018

Hajdu-Cheney Syndrome (HSC) is a rare multisystem disease in which the phenotype involves acro-osteolysis, severe osteoporosis, short stature, wormian bones, facial dysmorphism, central neurological abnormalities, cardiovascular defects, and polycystic kidneys. We describe an infant with severe manifestations of HCS in whom congenital glaucoma was a significant early feature, which has not been reported to date. HCS cases reported to date have involved truncating mutations in exon 34 ofNOTCH2upstream the PEST domain that lead to the development of a truncated and stable NOTCH2 protein which upregluates notch signaling. We describe a hitherto undescribed missense mutation that is predicted to be pathogenic, with functional characterization remaining to be performed. Serpentine fibula-polycystic kidney syndrome (SFPKS) is allelic to HCS and commonly associated with missenseNOTCH2mutations. Our patient provides new ophthalmological manifestations of HCS and provides insight into the potential role of notch signaling in the anterior chamber development.
The Evaluation of the Relationship between sTREM-1, VEGF-B, and VEGF Gene Expression Levels with Disease Activity of Behçet’s Patients
Authors: Harmanci Kadir , Akan Ozden Yildirim , Pirildar Timur , Ortan Pinar , Ulman Cevval
Published: October 2018

Background. There is no specific marker that shows the disease activity in Behçet’s disease. Aim. In this study, we aimed to investigate VEGF-B and VEGF gene expressions and sTREM-1 levels in association with the activation of Behçet’s disease. Study Design. Case-control study. Methods. Clinical features of patients who applied in the rheumatology clinic and were diagnosed with BD according to the international working group’s criteria were investigated. 30 healthy volunteers and 30 patients in the active period according to the EBDCAF scoring were studied. VEGF-B and VEGF gene expressions and sTREM-1 levels were studied in the serum samples of the patients and the control subjects. Results. The VEGF-B expressions and sTREM-1 levels were higher in the BD than those in the healthy group, but this difference did not reach statistical significance. VEGF gene expression was statistically significant (p=0.008). Behçet’s disease patients with oral aphthae, genital ulcer, eye, joint, vascular, skin, and neurological involvement were analyzed separately as subgroups. We find that VEGF gene expression level of Behçet’s disease patients with joint involvement (arthritis/arthralgia) and also VEGF-B and VEGF gene expression of Behçet’s disease with vascular involvement (DVT/thrombophlebitis) were significantly higher (p=0.035, p=0.021). Each subgroup was analyzed with the control group. We determined that VEGF gene expression in all subgroups was significantly higher than that in the control group. At the same time, VEGF-B levels of patients with genital ulcer and vascular involvement (DVT/thrombophlebitis) were significantly higher than those in the control group. Conclusion. VEGF-B and VEGF gene expressions can be activity indicators for BD. In addition, this study shows that new treatment options should be explored for Behçet’s disease patients with joint and vascular involvement. In the following years, new treatment methods are needed to investigate for revealing the role of the etiopathogenesis of BD and the activation and prognosis of VEGF by examining this study and providing much more participation. In our study group, the sTREM-1 levels were high but the results did not reach statistical significance. More studies are needed with larger groups in order the highlight the exact role of STREM-1 in Behçet’s disease.
Application of Chitosan Composite Flocculant in Tap Water Treatment
Authors: Kangama Awa , Zeng Defang , Tian Xu , Fang Jinfu
Published: October 2018

The chitosan is a good flocculant for tap water treatment because of its properties such as faster deposition rate and higher removal efficiency for COD (organic matter), SS (suspended solids), and metal ions. However, its high price limits the use in tap water treatment. In this paper, in order to reduce costs, chitosan (CTS), polyaluminum chloride (CF-PAC), and modified rectorite (Al(OH)3 + HCl) were combined to prepare the flocculant for tap water treatment. In order to get the optimal composite flocculant formula, first, we combined these flocculants in two-by-two schema and then we combined all the three flocculants together with various dosing amounts. Through comparison between different combination schemas, the best formula of the composite chitosan flocculant was found to be CTS (ml) : CF-PAC (ml) : modified rectorite (Al(OH)3 + HCl) (ml) = 1 : 30 : 5, with a turbidity removal rate of 96.38% and a removal rate of aluminum up to 80.1%, while the treatment cost is the lowest. In addition, we have designed a cost-effective method for the treatment cost evaluation. As raw water, we used water from the Han River, which is used as raw water at Zonguan Waterworks. In order to show the effectiveness of our optimal composite chitosan formula, we have compared our treatment results to those of the aluminum polyaluminum chloride flocculant currently used in Zonguan’s water treatment plants.
A Randomized Trial of Insulin Glargine plus Oral Hypoglycemic Agents versus Continuous Subcutaneous Insulin Infusion to Treat Newly Diagnosed Type 2 Diabetes
Authors: Lin Shuo , Chen Mu , Chen Wanling , Lin Keyi , Mu Panwei , Zhu Bilian , Xu Wen , Wang Manman , Weng Jianping , Zeng Longyi
Published: October 2018

Aims. Basal insulin plus oral hypoglycemic agents (OHAs) has not been investigated for early intensive antihyperglycemic treatment in people with newly diagnosed type 2 diabetes. This study is aimed at comparing the short-term (over a period of 12 days) effects of basal insulin glargine plus OHAs and continuous subcutaneous insulin infusion (CSII) on glycemic control and beta-cell function in this setting. Methods. An open-label parallel-group study. Newly diagnosed hospitalized patients with type 2 diabetes and fasting plasma glucose (FPG) ≥11.1 mmol/L or glycated hemoglobin (HbA1c) ≥9% (75 mmol/mol) were randomized to CSII or insulin glargine in combination with metformin and gliclazide. The primary outcome measure was the mean amplitude of glycemic excursions (MAGE), and secondary endpoints included time to reach glycemic control target (FPG < 7 mmol/L and 2-hour postprandial plasma glucose < 10 mmol/L), markers of β-cell function, and hypoglycemia. Results. Subjects in the CSII (n=35) and basal insulin plus OHA (n=33) groups had a similar significant reduction from baseline to end of treatment in glycated albumin (−6.44 ± 3.23% and− 6.42 ± 3.56%, P=0.970). Groups A and B have comparable time to glycemic control (3.6 ± 1.2 days and 4.0 ± 1.4 days), MAGE (3.40 ± 1.40 mmol/L vs. 3.16 ± 1.38 mmol/L; p=0.484), and 24-hour mean blood glucose (7.49 ± 0.96 mmol/L vs. 7.02 ± 1.03 mmol/L). Changes in the C-peptide reactivity index, the secretory unit of islet in transplantation index, and insulin secretion-sensitivity index-2 indicated a greater β-cell function improvement with basal insulin plus OHAs versus CSII. Conclusions. Short-term insulin glargine plus OHAs may be an alternative to CSII for initial intensive therapy in people with newly diagnosed type 2 diabetes.
The Myc/Max/Mxd Network Is a Target of Mutated Flt3 Signaling in Hematopoietic Stem Cells in Flt3-ITD-Induced Myeloproliferative Disease
Authors: Basit Farhan , Andersson Maria , Hultquist Anne
Published: October 2018

Acute myeloid leukemia (AML) has poor prognosis due to various mutations, e.g., in the FLT3 gene. Therefore, it is important to identify pathways regulated by the activated Flt3 receptor for the discovery of new therapeutic targets. The Myc network of oncogenes and tumor suppressor genes is involved in mechanisms regulating proliferation and survival of cells, including that of the hematopoietic system. In this study, we evaluated the expression of the Myc oncogenes and Mxd antagonists in hematopoietic stem cell and myeloid progenitor populations in the Flt3-ITD-knockin myeloproliferative mouse model. Our data shows that the expression of Myc network genes is changed in Flt3-ITD mice compared with the wild type. Mycn is increased in multipotent progenitors and in the pre-GM compartment of myeloid progenitors in the ITD mice while the expression of several genes in the tumor suppressor Mxd family, including Mxd1, Mxd2, and Mxd4, is concomitantly downregulated, as well as the expression of the Mxd-related gene Mnt and the transcriptional activator Miz-1. LSKCD150+CD48− hematopoietic long-term stem cells are decreased in the Flt3-ITD cells while multipotent progenitors are increased. Of note, PKC412-mediated inhibition of Flt3-ITD signaling results in downregulation of cMyc and upregulation of the Myc antagonists Mxd1, Mxd2, and Mxd4. Our data provides new mechanistic insights into downstream alterations upon aberrant Flt3 signaling and rationale for combination therapies for tyrosine kinase inhibitors with Myc antagonists in treating AML.
Efficacy of Second-Look Ultrasound with MR Coregistration for Evaluating Additional Enhancing Lesions of the Breast: Review of the Literature
Authors: Mazzei Maria Antonietta , Di Giacomo Letizia , Fausto Alfonso , Gentili Francesco , Mazzei Francesco Giuseppe , Volterrani Luca
Published: October 2018

Contrast enhanced magnetic resonance imaging (CE-MRI) has acquired a central role in the field of diagnosis and evaluation of breast cancer due to its high sensitivity; on the other hand, MRI has shown a variable specificity because of the wide overlap between the imaging features of benign and malignant lesions. Therefore, when an additional breast lesion is identified at CE-MRI, a second look with targeted US is generally performed because it provides additional information to further characterise the target lesion and makes it possible to perform US-guided biopsies which are costless and more comfortable for patients compared with MRI-guided ones. Nevertheless, there is not always a correspondence between CE-MR findings and targeted US due to several factors including different operator’s experience and position of patients. A new technique has recently been developed in order to overcome these limitations: US with MR coregistration, which can synchronise a sonography image and the MR image with multiplanar reconstruction (MPR) of the same section in real time. The aim of our study is to review the literature concerning the second look performed with this emerging and promising technique, showing both advantages and limitations in comparison with conventional targeted US.
A Study on Adiabatic Temperature Rise Test and Temperature Stress Simulation of Rock-Fill Concrete
Authors: Zhang Xiaofei , Liu Qian , Zhang Xin , Li Yanlong , Wang Xiaoping
Published: October 2018

In the present study, we investigate the effect of the adiabatic temperature rise property of rock-fill concrete (RFC) on the temperature stress and crack resistance of RFC gravity dams. We conducted tests on the adiabatic temperature rise of RFC with a rock-fill ratio of 42%, 49%, and 55%, respectively. Based on the regression analysis of the test data, a calculation model of the adiabatic temperature rise, considering the rock-fill ratio, is developed, and the finite element analysis software ANSYS is employed to simulate the whole process of the temperature and temperature stress fields of a RFC gravity dam. The main findings of the study are as follows: (1) Both the adiabatic temperature rise rate and the final adiabatic temperature rise of RFC are negatively correlated with the rock-fill ratio. (2) The calculation model of the adiabatic temperature rise of RFC is characterized by its high accuracy, which can help predict the adiabatic temperature rise of RFC with different rock-fill ratios. (3) Without any temperature control measures, the maximum temperature stress of RFC generated by the temperature rise of hydration heat in the RFC gravity dam is 0.93 MPa, which meets the standard of temperature stress control. The results of the present study indicate that dam construction with RFC can simplify the measures of temperature control and crack prevention, improve the construction efficiency, and reduce the cost of dam construction.
UBE2D1 RNA Expression Was an Independent Unfavorable Prognostic Indicator in Lung Adenocarcinoma, but Not in Lung Squamous Cell Carcinoma
Authors: Hou Liyan , Li Yingbo , Wang Ying , Xu Dongqiang , Cui Hailing , Xu Xiaoyan , Cong Ying , Yu Chengyong
Published: October 2018

In this study, we investigated the potential prognostic value of ubiquitin-conjugating enzyme E2D1 (UBE2D1) RNA expression in different histological subtypes of non-small-cell lung cancer (NSCLC). A retrospective study was performed by using molecular, clinicopathological, and survival data in the Cancer Genome Atlas (TCGA)—Lung Cancer. Results showed that both lung adenocarcinoma (LUAD) (N=514) and lung squamous cell carcinoma (LUSC) (N=502) tissues had significantly elevated UBE2D1 RNA expression compared to the normal tissues (p<0.001 and p=0.036, respectively). UBE2D1 RNA expression was significantly higher in LUAD than in LUSC tissues. Increased UBE2D1 RNA expression was independently associated with shorter OS (HR: 1.359, 95% CI: 1.031–1.791, p=0.029) and RFS (HR: 1.842, 95% CI: 1.353–2.508, p<0.001) in LUAD patients, but not in LUSC patients. DNA amplification was common in LUAD patients (88/551, 16.0%) and was associated with significantly upregulated UBE2D1 RNA expression. Based on these findings, we infer that UBE2D1 RNA expression might only serve as an independent prognostic indicator of unfavorable OS and RFS in LUAD, but not in LUSC.
Some Properties for Solutions of Riemann-Liouville Fractional Differential Systems with a Delay
Authors: Zhao Jing , Meng Fanwei
Published: October 2018

In this paper, we study properties for solutions of Riemann-Liouville (R-L) fractional differential systems with a delay. Some results on integral inequalities are first presented by Ho¨lder inequality. Then we investigate properties on solutions for R-L fractional systems with a delay by using the obtained inequalities and obtain upper bound of solutions. Finally, an illustrative example is considered to support our new results.
Trajectory Modelling to Assess Trends in Long-Term Readmission Rate among Abdominal Aortic Aneurysm Patients
Authors: Rao Ahsan , Bottle Alex , Bicknell Collin , Darzi Ara , Aylin Paul
Published: October 2018

Introduction. The aim of the study was to use trajectory analysis to categorise high-impact users based on their long-term readmission rate and identify their predictors following AAA (abdominal aortic aneurysm) repair. Methods. In this retrospective cohort study, group-based trajectory modelling (GBTM) was performed on the patient cohort (2006-2009) identified through national administrative data from all NHS English hospitals. Proc Traj software was used in SAS program to conduct GBTM, which classified patient population into groups based on their annual readmission rates during a 5-year period following primary AAA repair. Based on the trends of readmission rates, patients were classified into low- and high-impact users. The high-impact group had a higher annual readmission rate throughout 5-year follow-up. Short-term high-impact users had initial high readmission rate followed by rapid decline, whereas chronic high-impact users continued to have high readmission rate. Results. Based on the trends in readmission rates, GBTM classified elective AAA repair (n=16,973) patients into 2 groups: low impact (82.0%) and high impact (18.0%). High-impact users were significantly associated with female sex (P=0.001) undergoing other vascular procedures (P=0.003), poor socioeconomic status index (P<0.001), older age (P<0.001), and higher comorbidity score (P<0.001). The AUC for c-statistics was 0.84. Patients with ruptured AAA repair (n=4144) had 3 groups: low impact (82.7%), short-term high impact (7.2%), and chronic high impact (10.1%). Chronic high impact users were significantly associated with renal failure (P<0.001), heart failure (P = 0.01), peripheral vascular disease (P<0.001), female sex (P = 0.02), open repair (P<0.001), and undergoing other related procedures (P=0.05). The AUC for c-statistics was 0.71. Conclusion. Patients with persistent high readmission rates exist among AAA population; however, their readmissions and mortality are not related to AAA repair. They may benefit from optimization of their medical management of comorbidities perioperatively and during their follow-up.
Influence Factors Analysis of RC Beams under Falling Weight Impact Based on HJC Model
Authors: Long Xiaohong , Turgun Ahmed , Yue Rong , Ma Yongtao , Luo Hui
Published: October 2018

Impact loads may cause serious or even fatal damage to the structure (component), in most existing specifications in China, and there are no special terms that take impact load into consideration. So, the response analysis of the structure (component) under impact loads is very important. In this paper, the sensitivity analysis was conducted for the 22 parameters of the Holmquist–Johnson concrete (HJC) constitutive model of concrete, and the sensitive parameters of the HJC model are identified with A, B, G, Pl, μl, and fc respectively. LS‐DYNA nonlinear transient finite element analysis code was used for this paper. Based on the validation of finite element modeling and choosing midspan deflection of RC beams and impact loads as response indices, some influencing factors on RC beams under falling weight impact were investigated, such as the mass and speed of falling weight, impact position, the strength of concrete and rebar, longitudinal reinforcement ratio, and the span of the beam.
Time Course Changes of the Mechanical Properties of the Iris Pigment Epithelium in a Rat Chronic Ocular Hypertension Model
Authors: Li Tan , Li Lin , Liu Zhicheng
Published: October 2018

Background. The flow field of aqueous humor correlates to the stiffness of iris pigment epithelium (IPE) which acts as a wall of posterior chamber. We focus on the variations of IPE stiffness in a rat ocular hypertension (OHT) model, so as to prepare for exploring the mechanism of duration of OHT. Methods. Episcleral venous cauterization (EVC) was applied on one eye of male adult Sprague-Dawley rats to induce chronic high intraocular pressure. According to the duration of OHT (0, 1, 2, 4, and 8 weeks), rats were randomly divided into Gw0, Gw1, Gw2, Gw4, and Gw8. Atomic force microscope (AFM) analysis was applied to test IPE stiffness in three regions: iris root, mid-periphery, and pupillary-margin in each group. Histological changes of IPE were also examined in Gw4 and Gw8. Results. There was an overall growing tendency of IPE stiffness in EVC eye. IPE in EVC eye was significantly stiffer than fellow eye in Gw2, Gw4, and Gw8 (in iris root, mid-periphery, and pupillary-margin, p<0.05). IPE in EVC eye in pupillary-margin was significantly stiffer than iris root in Gw4 and Gw8 (p<0.05). In EVC eye, IPE becomes thinner and IPE cell density decreases. Conclusion. IPE stiffness increases gradually with the duration of chronic high intraocular pressure.
Hydroethanolic Extracts of Erigeron floribundus and Azadirachta indica Reduced Plasmodium berghei Parasitemia in Balb/c Mice
Authors: Tepongning Roselyne Nzangue , Mbah Javeres Ntepe , Avoulou Francky Love , Jerme Marie Madeleine , Ndanga Evrard-Kevin Kene , Fekam Fabrice Boyom
Published: October 2018

Malaria is one of the most important infectious diseases in Africa especially in Cameroon. The nonaccessibility to current treatments for poor people and the appearance of drug‐resistant Plasmodium falciparum parasites stimulate the search for alternative treatments. The aim of this study was to evaluate the antimalarial activity and the safety of hydroethanolic extracts from Erigeron floribundus and Azadirachta indica. The crude hydroethanolic extracts of E. floribundus (HEEF) and A. indica (HEAI) were prepared via maceration of the whole plant powder of E. floribundus and the leaves of A. indica in 70% ethanol. The antimalarial activity was determined according to Peter’s 4‐day suppressive test using the murine model Plasmodium berghei/Balb C mice, while the acute and subacute toxicity tests were assessed according to the OECD 425 and 407 guidelines, respectively. The results indicate a reduction of parasitemia ranging from 49.75 ± 3.64 to 69.28 ± 1.36% for HEAI and from 30.46 ± 4.30 to 62.36 ± 2.32% for HEEI. Overall, HEEF and HEAI at doses of 60, 120, and 240 mg/kg b.w. and 75, 150, and 300 mg/kg b.w., respectively, showed a significant (p≤0.001) parasitemia reduction on P. berghei infecting BALB/c mice. HEEF and HEAI caused a significant (p<0.001) attenuation of body temperature drop in mice compared to negative control, except for the 150 mg/kg b.w. dose in the female group. Moreover, there was no mice mortality observed with these extracts even at 5000 mg/kg, while the aspartate amino transferase (ASAT) level of mice treated with 300 mg/kg b.w. of HEAI extract increased when compared with the control. The results of this study support the traditional use of these plants species extracts against malaria infection in rural zones of Northern Cameroon, therefore confirming their potential as sources for the development of efficient phytomedicines for malaria‐poverty disease alleviation.
Role of the Specialized Proresolving Mediator Resolvin D1 in Systemic Lupus Erythematosus: Preliminary Results
Authors: Navarini Luca , Bisogno Tiziana , Margiotta Domenico Paolo Emanuele , Piccoli Alessandra , Angeletti Silvia , Laudisio Alice , Ciccozzi Massimo , Afeltra Antonella , Maccarrone Mauro
Published: October 2018

Objective. Systemic lupus erythematosus (SLE) is an autoimmune systemic disease and its pathogenesis has not yet been completely clarified. Patients with SLE show a deranged lipid metabolism, which can contribute to the immunopathogenesis of the disease and to the accelerated atherosclerosis. Resolvin D1 (RvD1), a product of the metabolism of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA), acts as a specialized proresolving mediator which can contribute in restoring the homeostasis in inflamed tissues. The aim of the present pilot study is to evaluate plasma levels of RvD1 in patients with SLE and healthy subjects, investigating its potential role as a biomarker of SLE and assessing its relationship with disease activity and laboratory parameters. Methods. Thirty patients with SLE and thirty age- and sex-matched healthy subjects (HSs) have been consecutively recruited at Campus Bio-Medico University Hospital. RvD1 plasma levels were measured by ELISA according to the manufacturer’s protocol (Cayman Chemical Co.). RvD1 levels were compared using Mann–Whitney test. Discriminatory ability for SLE has been evaluated by the area under the ROC curve. Results. Lower levels of RvD1, 45.6 (35.5–57.4) pg/ml, in patients with SLE have been found compared to HSs, 65.1 (39.43–87.95) pg/ml (p=0.0043). The area under the ROC curve (AUC) for RvD1 was 0.71 (95% CI: 0.578–0.82) and the threshold value of RvD1 for the classification of SLE was <58.4 pg/ml, sensitivity 80% (95% CI: 61.4–92.3), and specificity 63.3% (95% CI: 43.9–80.1), likelihood ratio 2.2 (95% CI: 1.3–3.6). Conclusions. The present preliminary study allows hypothesizing a dysregulation of RvD1 in patients with SLE, confirming the emerging role of bioactive lipids in this disease.
Metastatic Cecal Adenocarcinoma to the Gallbladder Presenting with Acute Cholecystitis
Authors: Bukhari Nedal , Abdulkader Marwah
Published: October 2018

Colorectal cancer (CRC) is one of the most common cancers and the second highest cause of cancer-related deaths (Jemal et al., 2011). Common presentations of CRC include alterations in bowel habit, weight loss, and lower gastrointestinal bleeding. We report a case of a 74-year-old male who presented with fever and right upper quadrant pain, with positive Murphy’s sign on examination. The case was initially managed with a routine cholecystectomy. Histological examination revealed a moderately differentiated adenocarcinoma with a superimposed histologically proven acute acalculous cholecystitis. CT scan done postsurgery showed a cecal mass with retroperitoneal lymphadenopathy. Biopsy result of cecal mass was remarkable for colon adenocarcinoma. We are not aware of any similar prior cases reported in English literature.
Shock Wave Therapy Enhances Mitochondrial Delivery into Target Cells and Protects against Acute Respiratory Distress Syndrome
Authors: Lin Kun-Chen , Wallace Christopher Glenn , Yin Tsung-Cheng , Sung Pei-Hsun , Chen Kuan-Hung , Lu Hung-I , Chai Han-Tan , Chen Chih-Hung , Chen Yi-Ling , Li Yi-Chen , Shao Pei-Lin , Lee Mel S. , Sheu Jiunn-Jye , Yip Hon-Kan
Published: October 2018

This study tested the hypothesis that shock wave therapy (SW) enhances mitochondrial uptake into the lung epithelial and parenchymal cells to attenuate lung injury from acute respiratory distress syndrome (ARDS). ARDS was induced in rats through continuous inhalation of 100% oxygen for 48 h, while SW entailed application 0.15 mJ/mm2for 200 impulses at 6 Hz per left/right lung field. In vitro and ex vivo studies showed that SW enhances mitochondrial uptake into lung epithelial and parenchyma cells (allp<0.001). Flow cytometry demonstrated that albumin levels and numbers of inflammatory cells (Ly6G+/CD14+/CD68+/CD11b/c+) in bronchoalveolar lavage fluid were the highest in untreated ARDS, were progressively reduced across SW, Mito, and SW + Mito (allp<0.0001), and were the lowest in sham controls. The same profile was also seen for fibrosis/collagen deposition, levels of biomarkers of oxidative stress (NOX-1/NOX-2/oxidized protein), inflammation (MMP-9/TNF-α/NF-κB/IL-1β/ICAM-1), apoptosis (cleaved caspase 3/PARP), fibrosis (Smad3/TGF-β), mitochondrial damage (cytosolic cytochrome c) (allp<0.0001), and DNA damage (γ-H2AX+), and numbers of parenchymal inflammatory cells (CD11+/CD14+/CD40L+/F4/80+) (p<0.0001). These results suggest that SW-assisted Mito therapy effectively protects the lung parenchyma from ARDS-induced injury.
Cyclin G2 Suppresses Glomerulosclerosis by Regulating Canonical Wnt Signalling
Authors: Zhao Chenyang , Gao Jinlan , Li Sen , Liu Qi , Hou Xiaoyu , Liu Shenghuan , Xing Xuesha , Sun Manni , Wang Shusen , Luo Yang
Published: October 2018

Recent data has shown that cyclin G2 (CCNG2) is an atypical cyclin that inhibits cell cycle progression and is often dysregulated in human cancers. The involvement of cyclin G2 in the occurrence and development of diabetic nephropathy (DN) has not been determined. In the present study, we conducted cyclin G2 knockout studies to determine whether this protein regulates glomerulosclerosis in DN mice. We found that cyclin G2 regulated the expression of renal glomerulosclerosis-related proteins via the canonical Wnt signalling pathway in glomerular mesangial cells. A cyclin G2 deficiency resulted in more severe renal injury in DN mice. These findings provided new insight into the pathogenesis of DN, revealing that cyclin G2 has a protective role in glomerulosclerosis and is a potential new target for the prevention and treatment of DN.