bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Pain in the African Prehospital Setting: A Scoping Review
Authors: Lourens Andrit , McCaul Michael , Parker Romy , Hodkinson Peter
Published: April 2019

Background. Acute pain is a common reason for seeking prehospital emergency care. Regrettably, acute pain is often underestimated and poorly managed in this setting. The scoping review was conducted to gain insight into existing research on the topic and to make recommendations for future work. Objectives. To identify all available evidence related to acute pain assessment and management in the African prehospital setting, describe the extent of the evidence, encapsulate findings, and identify research gaps. Methods. The scoping review considered primary and secondary research related to acute pain assessment and management of both medical and traumatic origins in all age groups in the African prehospital setting. The search strategy aimed to identify published, unpublished, and ongoing research which met the inclusion criteria. Potentially eligible studies were identified by a comprehensive search of electronic databases, trial registers, dissertation/thesis databases, grey literature databases, and conference proceedings. Screening and data extraction were conducted independently and in duplicate. Results. The comprehensive search identified 3823 potential studies, duplicate titles were removed, and 3358 titles/abstracts were screened. Full text of 66 potentially eligible titles was screened, 60 were excluded, and six publications met the inclusion criteria. Despite recommendations for pain assessment during general patient care, most studies reported no/limited pain assessment. In general, pain management was concluded to be insufficient and not conforming to best practice. Conclusions. Only six publications addressing prehospital acute pain care in Africa could be identified, possibly indicative of a knowledge gap. Future research is indicated to enable a better understanding of the epidemiology of acute pain and barriers and enablers of acute pain care and to develop evidence-based clinical practice guidelines (CPGs) catering for all EMS systems in Africa. Additionally, educational initiatives should be implemented to improve the quality of acute pain care and to monitor quality through continuous quality improvement (CQI) programs.
Study on Flow Characteristics in Volute of Centrifugal Pump Based on Dynamic Mode Decomposition
Authors: Li Yi-bin , He Chang-hong , Li Jian-zhong
Published: April 2019

To investigate the unsteady flow characteristics and their influence mechanism in the volute of centrifugal pump, the Reynolds time‐averaged N‐S equation, RNG k‐ε turbulence model, and structured grid technique are used to numerically analyze the transient flow‐field characteristics inside the centrifugal pump volute. Based on the quantified parameters of flow field in the volute of centrifugal pump, the velocity mode contours and oscillation characteristics of the mid‐span section of the volute of centrifugal pump are obtained by dynamic mode decomposition (DMD) for the nominal and low flow‐rate condition. The research shows that the first‐order average flow mode extracted by DMD is the dominant flow structure in the flow field of the volute. The second‐order and third‐order modes are the most important oscillation modes causing unsteady flow in the volute, and the characteristic frequency of the two modes is consistent with the blade passing frequency and the 2x blade passing frequency obtained by the fast Fourier transform (FFT). By reconstructing the internal flow field of the volute with the blade passing frequency for the nominal flow‐rate condition, the periodic variation of the unsteady flow structure in the volute under this frequency is visually reproduced, which provides some ideas for the study of the unsteady structure in the internal flow field of centrifugal pumps.
A Systematic Review and Meta-Analysis of Clinical Outcomes of Intravitreal Anti-VEGF Agent Treatment Immediately after Cataract Surgery for Patients with Diabetic Retinopathy
Authors: Zhao Li-Quan , Cheng Jin-Wei
Published: April 2019

Aims. To examine possible benefits of intravitreal anti-vascular endothelial growth factor (VEGF) agent treatment immediately after cataract surgery for patients with diabetic retinopathy (DR). Methods. A comprehensive literature search was performed using the Cochrane collaboration methodology to identify randomized controlled trials (RCTs) and comparative studies of cataract surgery with or without anti-VEGF agent treatment for any diabetic retinopathy. Meta-analyses were performed for clinical outcome parameters including changes in macular thickness (MT), best-corrected visual acuity (BCVA), incidence of diabetic retinopathy and maculopathy progression, laser treatment rate, and other complications. Results. Nine RCTs and 3 nonrandomized comparative studies were identified and used for comparing cataract surgery with intravitreal bevacizumab (IVB) or intravitreal ranibizumab (IVR) treatment (338 eyes, intervention group) to cataract surgery alone (329 eyes, control group). Analysis of all data showed that the mean BCVA at 1 week postoperatively had no statistically significant difference in the two groups, but at 1, 3, and 6 months postoperatively, the mean BCVA was statistically significantly better in the anti-VEGF treatment group than that in cataract surgery alone group. Analysis of all data showed that the mean MT was statistically significantly less in the anti-VEGF treatment group at 1 week and 1, 3, and 6 months postoperatively (P=0.05, P=0.006, P=0.0001, and P=0.0001, respectively); but postoperative clinical outcomes were differentiated from the type of anti-VEGF agents, IVB or IVR, and the existing macular edema preoperatively. Intravitreal anti-VEGF agent treatment statistically significantly reduced the incidence of diabetic retinopathy progression and maculopathy progression compared to the control group (P=0.0003, P<0.00001, respectively). Conclusion. IVB or IVR treatment immediately after cataract surgery may represent a safe and effective strategy to prevent postoperative macular thickening or reduce macular edema and result in greater mean improvements in visual acuity for diabetic patients.
Combination of an E-Nose and an E-Tongue for Adulteration Detection of Minced Mutton Mixed with Pork
Authors: Tian Xiaojing , Wang Jun , Ma Zhongren , Li Mingsheng , Wei Zhenbo
Published: April 2019

An E-panel, comprising an electronic nose (E-nose) and an electronic tongue (E-tongue), was used to distinguish the organoleptic characteristics of minced mutton adulterated with different proportions of pork. Meanwhile, the normalization, stepwise linear discriminant analysis (step-LDA), and principle component analysis were employed to merge the data matrix of E-nose and E-tongue. The discrimination results were evaluated and compared by canonical discriminant analysis (CDA) and Bayesian discriminant analysis (BAD). It was shown that the capability of discrimination of the combined system (classification error 0%∼1.67%) was superior or equable to that obtained with the two instruments separately, and E-tongue system (classification error for E-tongue 0∼2.5%) obtained higher accuracy than E-nose (classification error 0.83%∼10.83% for E-nose). For the combined system, the combination of extracted data of 6 PCs of E-nose and 5 PCs of E-tongue was proved to be the most effective method. In order to predict the pork proportion in adulterated mutton, multiple linear regression (MLR), partial least square analysis (PLS), and backpropagation neural network (BPNN) regression models were used, and the results were compared, aiming at building effective predictive models. Good correlations were found between the signals obtained from E-tongue, E-nose, and fusion data of E-nose and E-tongue and proportions of pork in minced mutton with correlation coefficients higher than 0.90 in the calibration and validation data sets. And BPNN was proved to be the most effective method for the prediction of pork proportions with R2 higher than 0.97 both for the calibration and validation data set. These results indicated that integration of E-nose and E-tongue could be a useful tool for the detection of mutton adulteration.
Delayed Presentation of Iliac Vein Injury: A Severe Complication at Retropubic Midurethral Sling Arm Removal
Authors: Uberoi Pansy , Jellison Forrest
Published: April 2019

Midurethral slings are the most common treatment for female stress urinary incontinence. Perioperative vascular injuries during placement of a retropubic midurethral sling (RMUS) are uncommon but have been described. The objective of this case report is to describe a complication of delayed presentation from a vascular injury at the time of retropubic sling arm removal not previously documented in the literature. This life-threating complication should be considered and precautions should be taken at retropubic sling arm removal. Prevention is accomplished by proper visualization of pelvic vasculature and/or eliminating tension on sling before excision.
Analysis of Parameter Correlations of the ECOM Solar Radiation Pressure Model for GPS Orbit
Authors: Bae Tae-Suk , Hong Chang-Ki
Published: April 2019

The modeling of solar radiation pressure is the most important issue in precision GNSS orbit determination and is usually represented by constant and periodic terms in three orthogonal axes. Unfortunately, these parameters are generally correlated with each other due to overparameterization, and furthermore, the correlation does not remain constant throughout a long-term period. A total of 500 weeks of GPS daily solutions were estimated with the empirical CODE orbit model (ECOM) to cover various block types of satellites. The statistics of the postfit residuals were analyzed in this study, which shows the dominant annual variation of the correlations over time. There is no significant difference between eclipsing and noneclipsing satellites, and the frequency of the correlation exactly corresponds to the GPS draconitic year. Based on the residual analysis, the ECOM is the most appropriate for the Block IIR/IIR-M satellites but does not properly account for the behavior of either older Block IIA or newer IIF satellites. In addition, the daily mean residuals show a different pattern for satellite orbital planes. Therefore, the orbit model should be customized for the block types and orbital plane for better representation of multi-GNSS orbits.
Ischemia Injury: A New Method Accelerates Bone Healing in a Rat Tibia Fracture Model
Authors: Liu Yang , Wang Dong , Wu Xueqiang , Zhou Junlin
Published: April 2019

To find a simple and noninvasive method to promote fracture healing, we are trying to explore whether repetitive brief ischemia would promote bone healing. 88 rats divided into 6 groups were used to make right tibia closed fracture caused by the heavy weight collision method. Healthy side groups received homemade tourniquet placed on left and affected side group placed on right thigh 10 min inflated/10 min deflated 3 times every 24 hours or 48 hours after tibia fractured. Rats in control groups received homemade tourniquet uninflated placed on right thigh 1 hour every 24 hours or 48 hours. X-rays were checked at 1, 2, and 4 weeks. Micro-CT inspected the bone healing at 2 and 4 weeks. Serum cytokines, such as bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), diethanolamine enzyme activity unit of alkaline phosphatase (ALP) and transforming growth factor-β1 (TGF-β1), interleukin 10 (IL-10) and interleukin 6 (IL-6), were checked at 1, 2, and 4 weeks. Local histology was evaluated at 2 weeks. HE dye and BMP-2, VEGF, TGF-β, and ALP immunohistochemical stains were made. Callus areas of posterior-anterior and lateral views were calculated and repetitive brief ischemia increased the callus areas ratio at 1 and 2 weeks. Besides, from micro-CT results, repetitive brief ischemia increased the bone volume (BV) at 2 and 4 weeks and also increased the total bone tissue volume (TV) at 2 weeks and BV/TV at 4 weeks. The serum cytokines, such as BMP-2, VEGF, diethanolamine enzyme activity unit of ALP and TGF-β1, have increased by repetitive brief ischemia at 1, 2 weeks. It is opposite of affected side group that the level of serum IL-10 increased and IL-6 decreased in healthy side group at 1, 2 weeks. Repetitive brief ischemia increased the callus area at 2 weeks and boosted the synthesis of BMP-2, VEGF, TGF-β, and ALP in the fracture region at 2 weeks from tissue stains. Repetitive brief ischemia promotes bone healing no matter on the affected side or the healthy side limb.
Wide Variation of Squeezing Force and Dispensing Time Interval among Eyedropper Bottles
Authors: Kashiwagi Kenji
Published: April 2019

Purpose. We aimed to investigate squeezing force and dispensing time interval of the first and second eye drops among a variety of eyedropper bottles and to clarify associated factors within these parameters. Methods. A total of 87 eyedropper bottles were involved in this study. We developed a squeezing force measuring system consisting of a syringe pump, digital force gauge, and custom-made test stand to measure the squeezing force and dispensing interval. The eyedropper bottle was housed in the system vertically, and measurements were repeated five times. We investigated the differences in squeezing force and dispensing interval by categories, including those that targeted ocular disease, brand or generic eyedroppers, shapes of eyedropper bottles, and the presence of a membrane filter inside the tip of the eyedropper bottle. Results. The mean squeezing forces of the first drop and the second drops were 8.3 ± 3.0 N and 10.4 ± 3.2 N, respectively. Both squeezing forces had a wide variation of more than threefold. A mean interval between the first and second drops was 3.1 ± 1.2 sec with a maximum difference of more than sevenfold. Round shapes of eyedropper bottles and the presence of filter membranes significantly increased the squeezing force. Conclusions. The squeezing force of eyedropper bottles was very wide, which may affect proper eye drop instillation. Unification of eyedropper bottles or developing mechanical aids may be useful for proper eye drop treatment.
Role of Maize Weevil, Sitophilus zeamais Motsch. on Spread of Aspergillus section flavi in Different Nepalese Maize Varieties
Authors: Bhusal K. , Khanal D.
Published: April 2019

Experiments were conducted to find out the role of maize weevil, Sitophilus zeamais Motsch. on spread of green fungus, Aspergillus section flavi, in different varieties of stored maize in laboratory in 2016. Lab experiment was conducted to find the role of weevil on spread of A. flavus on five main varieties of maize grown at Nepal in split plot design, namely, Arun-2, Arun-4, Manakamana-1, Manakamana-3, and Rampur composite with three replications at NAST, Khumaltar, from August to September 2016. One hundred grams of each maize variety was exposed to weevil along with fungus and with fungus only to see the spread of the fungus under presence and absence of weevil. Among the tested five maize varieties, the lowest infestation was observed on Rampur Composite (14.99%) while it was the highest on Manakamana-3 (87.70%). The highest mean infestation (75.58%) was found under weevil released condition while it was lower (62.16%) under nonreleased condition. In presence of weevil, the infestation of the fungus increased and in their absence the infestation was low which signifies the role of weevil in fungal spread. All indices indicate that Rampur composite is the best variety among the five tested varieties in terms of storage under the presence of fungus and weevils. This study also indicates ample scope for further study on different varieties of maize under several storage conditions.
Effect of Wuzi Yanzong on Reproductive Hormones and TGF-β1/Smads Signal Pathway in Rats with Oligoasthenozoospermia
Authors: Yang Zhuo , Zhang Xi , Chen Zhimin , Hu Changjiang
Published: April 2019

Introduction. Wuzi Yanzong (WZYZ) formula, a famous traditional Chinese medicinal prescription, has been widely used to treat kidney essence insufficiency-induced oligoasthenozoospermia in ancient and modern clinical practice. Previous studies have demonstrated that WZYZ formula exhibits significantly therapeutic activity. The aim of this study was to evaluate the effect of WZYZ formula on the reproductive hormone levels and the TGF-β1/Smads signal pathway in the testis, to explore the underlying mechanisms of WZYZ formula to improve spermatogenic function of testis in rats with oligoasthenozoospermia. Materials and Methods. In order to control the quality of the drug, the main components of the WZYZ formula were analyzed by HPLC. A rat model of oligoasthenozoospermia was established, by daily administration of tripterygium glucosides for 4 weeks, and treated with 1.62g/kg of WZYZ formula. The testes were histopathologically examined and serum levels of gonadotropin release hormone (GnRH), estradiol (E2), follicle-stimulating hormone (FSH), testosterone (T), and luteinizing hormone (LH) were measured by ELISA. TGf-β1, Smad2, and Smad4 mRNA and protein levels in the testis were evaluated by immunohistochemistry (IHC), quantitative real-time RT-PCR (qRT-PCR), and Western blotting (WB). Result. Oral administration of WZYZ formula restored testicular structure and significantly increased the histology score in the oligoasthenozoospermic rats. In addition, WZYZ also significantly increased the serum levels of GnRH, LH, E2, and T and decreased that of FSH. Meanwhile, TGf-β1, Smad2, and Sma4 expression levels were significantly decreased. Conclusions. WZYZ alleviates oligoasthenozoospermia by restoring the reproductive hormones and targeting the TGf-β1/Smads pathway.
Hypoglycemic Activity ofTilia americana,Borago officinalis,Chenopodium nuttalliae, andPiper sanctumon Wistar Rats
Authors: Rodríguez-Magaña Martha P. , Cordero-Pérez Paula , Rivas-Morales Catalina , Oranday-Cárdenas María A. , Moreno-Peña Diana P. , García-Hernández David G. , Leos-Rivas Catalina
Published: April 2019

Diabetes mellitus (DM) is considered the epidemic of the 21st century. Traditional medicine uses plants to treat DM; many of these have hypoglycemic effects in both animal models and diabetic patients. Our objective was to evaluate the hypoglycemic activity ofTilia americana,Borago officinalis,Chenopodium nuttalliae, andPiper sanctumon diabetic rats. The methanolic extracts of the plants under study were obtained by Soxhlet extraction. Toxicity was evaluated onArtemia salina; the antioxidant potential was evaluated using the DPPH technique. Hypoglycemic capacity at doses of 250 and 500 mg/kg was tested on Wistar rats with diabetes induced by alloxan (120 mg/kg). The toxicity onA. salinawas null for the extracts ofB. officinalisandP. sanctum, moderate forT. americana, and highly toxic forC. nuttalliae. The relevant extract ofT. americanavar. mexicana showed antioxidant activity. Three plants of the studied plants showed hypoglycemic activity:Tilia Americana(p=0.0142),Borago officinalis(p=0.0112), andPiper sanctum(p=0.0078);P. sanctumwas the one that showed the greatest reduction in glucose levels at a lower dose.
Occurrence and Characterization of Salmonella Isolated from Large-Scale Breeder Farms in Shandong Province, China
Authors: Yang Jie , Gao Siwei , Chang Yajie , Su Mingliu , Xie Yutong , Sun Shuhong
Published: April 2019

This study aimed to investigate the prevalence and antimicrobial resistance of Salmonella spp. isolated from large-scale breeder farms in Shandong Province, China. A total of 63 Salmonella isolates (63/409, 15.4%) were identified from 409 samples collected from five large-scale breeder farms in Shandong Province. These Salmonella isolates were assayed for serotype, antimicrobial susceptibility, prevalence of class 1 integrons, quinolone resistance genes, and β-lactamase genes and subtyped by multilocus sequence typing (MLST). Among these isolates, S. Enteritidis (100%) was the predominant serovar, and high antimicrobial resistance rates to nalidixic acid (100.0%), streptomycin (100.0%), ampicillin (98.4%), and erythromycin (93.7%) were observed. All of the isolates carried blaTEM. MLST results showed that only one sequence type (ST11) was identified. Our findings indicated that Salmonella was generally prevalent not only on broiler farms but also on breeder farms.
Network Analyses of Differentially Expressed Genes in Osteoarthritis to Identify Hub Genes
Authors: Li Zhaoyan , Zhong Lei , Du Zhenwu , Chen Gaoyang , Shang Jing , Yang Qiwei , Wang Qingyu , Song Yang , Zhang Guizhen
Published: April 2019

Background. Osteoarthritis (OA) is the most common degenerative disease in orthopedics. However, the cause and underlying molecular mechanisms are not clear. This study aims to identify the hub genes and pathways involved in the occurrence of osteoarthritis. Methods. The raw data of GSE89408 were downloaded from the Gene Expression Omnibus (GEO) database, and the differentially expressed genes (DEGs) were identified by R software. The DAVID database was used for pathway and gene ontology analysis, and p<0.05 and gene count >2 were set as the cut-off point. Moreover, protein-protein interaction (PPI) network construction was applied for exploring the hub genes in osteoarthritis. The expression levels of the top ten hub genes in knee osteoarthritis synovial membranes and controls were detected by quantitative real-time PCR system. Results. A total of 229 DEGs were identified in osteoarthritis synovial membranes compared with normal synovial membranes, including 145 upregulated and 84 downregulated differentially expressed genes. The KEGG pathway analysis results showed that up-DEGs were enriched in proteoglycans in cytokine-cytokine receptor interaction, chemokine signaling pathway, rheumatoid arthritis, and TNF signaling pathway, whereas down-DEGs were enriched in the PPAR signaling pathway and AMPK signaling pathway. The qRT-PCR results showed that the expression levels of ADIPOQ, IL6, and CXCR1 in the synovium of osteoarthritis were significantly increased (p <0.05).
Effect of the Intensive Plasticizing Zone Design on the Effectiveness of Corotating Twin-Screw Extrusion
Authors: Sasimowski Emil , Majewski Łukasz
Published: April 2019

The aim of this study was to investigate the effect of a new intensive plasticizing and mixing screw zone design on the effectiveness of the corotating twin-screw extrusion process for talc-filled polypropylene. The study determined the effect of the angle between the trilobe kneading elements forming the intensive plasticizing and mixing zone of the screws, the screw rotational speed, and the polypropylene/talc filling ratio on the characteristics of the extrusion process in a corotating twin-screw extruder EHP-2x20. The paper describes the experimental design and obtained results as well as the developed empirical models for selected variables of the extrusion process.
A Phase I/II Trial of MEC (Mitoxantrone, Etoposide, Cytarabine) in Combination with Ixazomib for Relapsed Refractory Acute Myeloid Leukemia
Authors: Advani Anjali S. , Cooper Brenda , Visconte Valeria , Elson Paul , Chan Ricky , Carew Jennifer , Wei Wei , Mukherjee Sudipto , Gerds Aaron , Carraway Hetty , Nazha Aziz , Hamilton Betty , Sobecks Ronald , Caimi Paolo , Tomlinson Benjamin , Malek Ehsan , Little Jane , Miron Alexander , Pink John , Maciejewski Jaroslaw , Unger Allison , Kalaycio Matt , de Lima Marcos , Sekeres Mikkael A.
Published: April 2019

Purpose:

The prognosis of patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) remains poor, and novel therapies are needed. The proteasome pathway represents a potential therapeutic target. A phase I trial of the second-generation proteasome inhibitor ixazomib in combination with MEC (mitoxantrone, etoposide, and cytarabine) was conducted in patients with R/R AML.

Patients and Methods:

Dose escalation of ixazomib was performed using a standard 3 × 3 design. Gene-expression profiling was performed on pretreatment and posttreatment bone marrow or blood samples.

Results:

The maximum tolerated dose of ixazomib in combination with MEC was 1.0 mg. The dose limiting toxicity was thrombocytopenia. Despite a poor risk population, the response rate [complete remission (CR)/CR with incomplete count recovery (CRi)] was encouraging at 53%. Gene-expression analysis identified two genes, IFI30 (γ-interferon inducible lysosomal thiol reductase) and RORα (retinoic orphan receptor A), which were significantly differentially expressed between responding and resistant patients and could classify CR.

Conclusions:

These results are encouraging, but a randomized trial is needed to address whether the addition of ixazomib to MEC improves outcome. Gene-expression profiling also helped us identify predictors of response and potentially novel therapeutic targets.
Clinical Utility of Comprehensive Cell-free DNA Analysis to Identify Genomic Biomarkers in Patients with Newly Diagnosed Metastatic Non–small Cell Lung Cancer
Authors: Leighl Natasha B. , Page Ray D. , Raymond Victoria M. , Daniel Davey B. , Divers Stephen G. , Reckamp Karen L. , Villalona-Calero Miguel A. , Dix Daniel , Odegaard Justin I. , Lanman Richard B. , Papadimitrakopoulou Vassiliki A.
Published: April 2019

Purpose:

Complete and timely tissue genotyping is challenging, leading to significant numbers of patients with newly diagnosed metastatic non–small cell lung cancer (mNSCLC) being undergenotyped for all eight genomic biomarkers recommended by professional guidelines. We aimed to demonstrate noninferiority of comprehensive cell-free DNA (cfDNA) relative to physician discretion standard-of-care (SOC) tissue genotyping to identify guideline-recommended biomarkers in patients with mNSCLC.

Patients and Methods:

Prospectively enrolled patients with previously untreated mNSCLC undergoing physician discretion SOC tissue genotyping submitted a pretreatment blood sample for comprehensive cfDNA analysis (Guardant360).

Results:

Among 282 patients, physician discretion SOC tissue genotyping identified a guideline-recommended biomarker in 60 patients versus 77 cfDNA identified patients (21.3% vs. 27.3%; P < 0.0001 for noninferiority). In tissue-positive patients, the biomarker was identified alone (12/60) or concordant with cfDNA (48/60), an 80% cfDNA clinical sensitivity for any guideline-recommended biomarker. For FDA-approved targets (EGFR, ALK, ROS1, BRAF) concordance was >98.2% with 100% positive predictive value for cfDNA versus tissue (34/34 EGFR-, ALK-, or BRAF-positive patients). Utilizing cfDNA, in addition to tissue, increased detection by 48%, from 60 to 89 patients, including those with negative, not assessed, or insufficient tissue results. cfDNA median turnaround time was significantly faster than tissue (9 vs. 15 days; P < 0.0001). Guideline-complete genotyping was significantly more likely (268 vs. 51; P < 0.0001).

Conclusions:

In the largest cfDNA study in previously untreated mNSCLC, a validated comprehensive cfDNA test identifies guideline-recommended biomarkers at a rate at least as high as SOC tissue genotyping, with high tissue concordance, more rapidly and completely than tissue-based genotyping.

See related commentary by Meador and Oxnard, p. 4583
Engineering Multidimensional Evolutionary Forces to Combat Cancer
Authors: McCoach Caroline E. , Bivona Trever G.
Published: April 2019

With advances in technology and bioinformatics, we are now positioned to view and manage cancer through an evolutionary lens. This perspective is critical as our appreciation for the role of tumor heterogeneity, tumor immune compartment, and tumor microenvironment on cancer pathogenesis and evolution grows. Here, we explore recent knowledge on the evolutionary basis of cancer pathogenesis and progression, viewing tumors as multilineage, multicomponent organisms whose growth is regulated by subcomponent fitness relationships. We propose reconsidering some current tenets of the cancer management paradigm in order to take better advantage of crucial fitness relationships to improve outcomes of patients with cancer.

Significance:

Tumor and tumor immune compartment and microenvironment heterogeneity, and their evolution, are critical disease features that affect treatment response. The impact and interplay of these components during treatment are viable targets to improve clinical response. In this article, we consider how tumor cells, the tumor immune compartment and microenvironment, and epigenetic factors interact and also evolve during treatment. We evaluate the convergence of these factors and suggest innovative treatment concepts that leverage evolutionary relationships to limit tumor growth and drug resistance.
The Association between Inflammatory Markers in the Acute Phase of Stroke and Long-Term Stroke Outcomes: Evidence from a Population-Based Study of Stroke
Authors: Mobarra Naser , Morovatdar Negar , Di Napoli Mario , Stranges Saverio , Behrouz Reza , Amiri Amin , Farzadfard Mohammad Taghi , Hashemy Seyed Isaac , Oskoii Reza , Khorram Bita , Azarpazhooh Mahmoud Reza
Published: April 2019

Background: Little is known about the association between inflammatory markers in the acute stroke phase and long-term stroke outcomes. Methods: In a population-based study of stroke with 5 years follow-up, we measured the level of serum heat shock protein 27 immunoglobulin G antibody (anti-HSP27), C-reactive protein (CRP), and pro-oxidant antioxidant balance (PAB) in the acute stroke phase. We analyzed the association between these inflammatory biomarkers and stroke outcomes (recurrence, death and disability/functional dependency) with using multivariable Cox proportional hazard models. Results: Two hundred sixty-five patients with first-ever stroke were included in this study. The severity of stroke at admission, measured by National Institute of Health Score Scale was associated with serum concentration of CRP (Spearman’s rank correlation coefficient rs = 0.2; p = 0.004). CRP also was associated with 1-year combined death and recurrence rate ([adjusted hazard ratio 1.06, 95% CI 1.01–1.12; p = 0.02]). However, we did not find any association between the concentrations of CRP, anti-HSP27, PAB, and 5-year death and stroke recurrence rates. None of 3 biomarkers was associated with the long-term disability rate (defined as modified Rankin Scale >2) and functional dependency (defined as Barthel Index <60). Conclusion: CRP has a significant direct, yet weak, correlation to the severity of stroke. In addition, the level of CRP at admission may have a clinical implication to identify those at a higher risk of death or recurrence.
Depressive Psoriasis-Patienten können ein schlechteres Ansprechen auf Etanercept zeigen
Authors: Sondermann Wiebke
Published: April 2019

Background/Aims: This study aimed to investigate the predicting values of depression and anxiety symptoms for clinical response to etanercept treatment in psoriasis patients. Methods: A total of 85 psoriasis patients who received 6 months of etanercept treatment were consecutively enrolled in this prospective cohort study. The Psoriasis Area and Severity Index (PASI) score was evaluated at month 0 (M0), M1, M3, and M6, and the corresponding PASI 75/90 response at each visit was assessed. Also, anxiety and depression symptoms were assessed by the Hospital Anxiety and Depression Scale (HADS) at M0, M1, M3, and M6. Results: Depression symptoms were observed to correlate with female gender (p = 0.004), longer disease duration (p = 0.018), and higher PASI score (p < 0.001), and anxiety symptoms were seen to be associated with female gender (p = 0.017), larger psoriasis-affected body surface area (p = 0.049), and higher PASI score (p = 0.017) in psoriasis patients. After etanercept treatment, HADS-Depression (HADS-D) and HADS-Anxiety (HADS-A) scores were both decreased at M1, M3, and M6 (all p < 0.001) compared with M0. Most importantly, baseline depressed patients presented with a lower PASI 75 response rate at M3 (p = 0.014) and M6 (p = 0.005), and a reduced PASI 90 response rate at M6 (p = 0.045) compared with baseline non-depressed patients. Furthermore, multivariate logistic regression analyses revealed that depression symptoms at baseline were an independent predictive factor for the lower possibility of both PASI 75 response (p = 0.048) and PASI 90 response (p = 0.048) achievements at M6 in psoriasis patients. However, no correlation of baseline anxiety symptoms with PASI 75/90 responses was observed. Conclusion: Depression symptoms at baseline independently predict a worse clinical response to etanercept treatment in psoriasis patients.
Changes of Dyspeptic Symptom after Successful Eradication in Helicobacter pylori-Associated Dyspepsia
Authors: Tsuda Momoko , Kato Mototsugu , Ono Shoko , Matsuda Kana , Miyamoto Shuichi , Abiko Satoshi , Ono Masayoshi , Mizushima Takeshi , Yamamoto Keiko , Nakagawa Manabu , Mabe Katsuhiro , Nakagawa Soichi , Kudo Takahiko , Nishikawa Keiko , Shimizu Yuichi , Asaka Masahiro , Sakamoto Naoya
Published: April 2019

Background: Helicobacter pylori (H. pylori) gastritis could cause dyspepsia, and eradication is recommended as the first-line treatment. Patients who continuously have their symptoms under control > 6 months after eradication are defined as having H. pylori-associated dyspepsia (HPD), whereas patients who do not benefit from successful eradication are defined as having functional dyspepsia. Objectives: We assessed changes in dyspeptic symptoms after successful eradication of H. pylori by using a questionnaire. Methods: We studied H. pylori-infected dyspeptic participants with abdominal symptom scores > 4 points on the Global Overall Symptom (GOS) scoring items and received eradication therapy. We evaluated their symptoms using the GOS questionnaire before their eradications, at 1-month and at 1-year check-ups after eradication therapy. Results: Thirty dyspeptic participants (mean age 59.6 ± 15.3 years) answered every questionnaire. Fourteen participants (46.7%) had HPD, whereas 16 participants (53.3%) were non-HPD patients. The questionnaire at 1 month showed sensitivity of 64.3% (9/14) and specificity of 56.3% (9/16) for HPD. Approximately 60% of H. pylori-infected dyspepsia participants were identified as having HPD or non-HPD within 1 month after their eradications. Conclusions: Approximately 60% of HPD participants improved at 1 month after eradication. The questionnaire at 1 month helped diagnose HPD in advance and guided next treatment choice.
Caspase-14 als mögliches therapeutisches Ziel beim chronischen Handekzem
Authors: Traidl-Hoffmann Claudia
Published: April 2019

Aim: To investigate whether the skin barrier function is impaired with regard to the pH value, water content, transepidermal water loss (TEWL), and the integrity of the stratum corneum, and whether the expression of caspase-14 is altered in moderate to severe chronic hand eczema (CHE). Methods: Thirty patients with moderate to severe CHE treated at our institute and 30 healthy volunteers were included in this study. The pH value, water content, TEWL, and the integrity of the stratum corneum were measured in all subjects. Results: Significantly increased pH value, decreased water content, elevated TEWL, and impaired integrity of the stratum corneum were observed in the lesional skin of CHE patients compared with the nonlesional skin of CHE patients and the normal skin of healthy volunteers. The expression of caspase-14 decreased in the lesional and nonlesional skin of CHE patients compared with the normal skin of healthy volunteers, especially prominent in the nonlesional skin. The mean optical density (OD) value of immunohistochemical staining for caspase-14 was significantly lower in the nonlesional skin than in the lesional skin and normal skin (p < 0.01 for both). Although the mean OD value was lower in the lesional skin than in the normal skin, the difference was not statistically significant (p > 0.05). Conclusion: Skin barrier dysfunction indeed occurs in CHE patients, which may be related to mechanisms associated with a downregulated expression of caspase-14.
Rapidly Progressive Glomerulonephritis with Delayed Appearance of Anti-Glomerular Basement Membrane Antibody Successfully Treated with Multiple Courses of Steroid Pulse Therapy
Authors: Toyota Satoshi , Eriguchi Masahiro , Hasegawa Shoko , Ueki Kenji , Matsukuma Yuta , Tsuchimoto Akihiro , Fujisaki Kiichiro , Torisu Kumiko , Tsuruya Kazuhiko , Nakano Toshiaki , Kitazono Takanari
Published: April 2019

Patients with anti-glomerular basement membrane (GBM) antibody glomerulonephritis typically exhibit rapidly progressive glomerulonephritis (RPGN). The renal outcome as well as the prognosis of this disease is worse than other forms of RPGN such as those from microscopic polyangiitis. Therefore, early therapeutic intervention is essential to improve its prognosis. One month before referral to our hospital, a 54-year-old female attended another hospital because of macrohematuria. At that time, she had proteinuria and macrohematuria with normal renal function, was negative for anti-GBM antibodies, and was diagnosed with chronic glomerulonephritis. A month later when she was admitted to our hospital, she showed renal insufficiency and was positive for anti-GBM antibodies. Immediately after recognizing the anti-GBM antibody status, plasma exchange and the first course of steroid pulse therapy was started. After 5 days of therapy, renal biopsy confirmed severe crescentic glomerulonephritis in which all the observed glomeruli were involved with cellular crescents. Despite this, she survived without end-stage renal disease after three courses of steroid pulse therapy and seven sessions of plasma exchange. This favorable outcome reflects the repeated analysis of anti-GBM antibodies within a very short period and the rapid therapeutic intervention in addition to the intensive immunosuppressive therapies.
Vibrio parahaemolyticus Induced Cellulitis and Septic Shock after a Sea Beach Holiday in a Patient with Leg Ulcers
Authors: Guillod Caroline , Ghitti Francesca , Mainetti Carlo
Published: April 2019

Infections with Vibrio parahaemolyticus, a gram-negative bacterium found in salt water, are mainly gastrointestinal or cutaneous. The development of sepsis is not uncommon. We report the case of an 85-year-old patient who developed lower limb cellulitis caused by V. parahaemolyticus, originating from leg ulcers and complicated by septicaemia and septic shock, after a sea beach holiday. We discuss the epidemiology, pathogenesis, clinical manifestations and treatment of V. parahaemolyticus infections.
Incidence and Mortality of Parkinson’s Disease in Estonia
Authors: Kadastik-Eerme Liis , Taba Nele , Asser Toomas , Taba Pille
Published: April 2019

Background: There is lack of data on the incidence of Parkinson’s disease (PD) based on repeat studies. Mortality rates of PD in Estonia have never been studied before. Objectives: To estimate the incidence and mortality rates of PD in ­Estonia, to compare current incidence rates with those of the prior epidemiological study in Estonia, and to examine the reported causes of death of the study population. Methods: Eligible subjects were identified from multiple case-finding sources. Subjects were subsequently tracked on the Electronic-Health Record until either the end of the study, or their death. Incidence rates and standardized mortality ratios (SMR) were calculated. Causes of death were identified, based on the data from death certificates. Results: In the current study, the overall age-adjusted incidence rate was 28.0/100,000 person-years (95% CI 25.2–30.8). Compared with the previous study, the age-adjusted incidence rate inEstonia has not significantly changed (rate ratio 1.11; p = 0.19). Overall SMR for the inception cohort of PD cases with a median follow-up time of 5 years was 1.12 (95% CI 0.88–1.36; p = 0.3). For those deceased subjects known to have had clinically diagnosed PD, this was mentioned on 46.8% of death certificates. Conclusions: Over the last 20 years, the overall incidence of PD in Estonia has remained comparatively stable. The data did not show an excess mortality in PD patients (vs. general population) in the first 5 years of the disease.
Definition and Validity of the Construct “Problematic Khat Use”: A Systematic Review
Authors: Mihretu Awoke , Nhunzvi Clement , Fekadu Abebaw , Norton Sam , Teferra Solomon
Published: April 2019

Background: Problematic khat use, not khat use per se, is a public health and social concern for the public, researchers, and policy makers. However, the construct problematic khat use is not well-established and not fully recognized in the modern definition of substance use disorders including Diagnostic Statistic Manual (DSM-5) and international classification of diseases (ICD-10), although DSM-5 included it in the “stimulant use disorder” category. Existing scoping reviews have focused on khat use, which could not allow the differentiation of khat use from problematic khat use. Thus, the aim of this systematic review was to define and validate the construct problematic khat use. Methods: This systematic review was reported following the PRISMA guidelines. We searched all English language studies without publication date restriction from 5 databases; PubMed, EMBASE, psychINFO, SocINDEX, and Google scholar. All studies that defined, explored, evaluated, or measured the construct problematic khat use were included. Adapted data extraction tool and criteria for quality evaluation were employed. We presented the results in tables and thematic synthesis of the major findings. Result: Overall, 30 qualitative and cross-sectional design studies were included. Associated harms with khat use, an increased amount used, increased frequency of use, and withdrawal experiences were indicators of problematic khat use. Using khat on an average of 3 or more times per week and using other psychoactive substances during and after khat use were frequently used to define problematic khat use. The most frequently reported withdrawal symptoms were depressed mood, irritability, fatigue, lack of motivation, increased sleep, and appetite. The existing measures (severity of dependence scale and DSM-5) of problematic khat use had psychometrically acceptable properties in terms of construct, criterion, and convergent validity, but they are poor in terms of other domains of validity including content, conceptual, and semantic validity. Conclusion: Problematic khat use constitutes, but is not limited to, harms, increased use over time, and frequent engagement in other psychoactive substances misuse. Khat use is different from problematic khat use since it is occasional and used for prayer, social, and functional reasons. Strong empirical studies that could establish thresholds for patterns of problematic khat use and a culturally suitable problematic khat use measures that follows a bottom-up approach of scale development are warranted.
Um olhar europeu sobre a América Latina: entrevista com Thomas Fischer
Authors: Maluly Luciano Victor Barros , De Oliveira Dennis , Moraes Junior Enio
Published: April 2019

Historiador e professor, Thomas Fischer estuda o continente latino-americano desde a década de 1970. Para o presidente da Associação Alemã de Pesquisa sobre a América Latina, a heterogeneidade é uma característica da região.
Circulating Markers of Inflammation Persist in Children and Adults With Giant Aneurysms After Kawasaki Disease
Authors: Lech Miroslaw , Guess Jamey , Duffner Jay , Oyamada Jun , Shimizu Chisato , Hoshino Shinsuke , Farutin Victor , Bulik Dorota A. , Gutierrez Bryan , Sarvaiya Hetal , Kapoor Bulbul , Koppes Laura , Saldova Radka , Stockmann Henning , Albrecht Simone , McManus Ciara , Rudd Pauline M. , Kaundinya Ganesh V. , Manning Anthony M. , Bosques Carlos J. , Kahn Andrew M. , Daniels Lori B. , Gordon John B. , Tremoulet Adriana H. , Capila Ishan , Gunay Nur Sibel , Ling Leona E. , Burns Jane C.
Published: April 2019

Background:

The sequelae of Kawasaki disease (KD) vary widely with the greatest risk for future cardiovascular events among those who develop giant coronary artery aneurysms (CAA). We sought to define the molecular signature associated with different outcomes in pediatric and adult KD patients.

Methods:

Molecular profiling was conducted using mass spectrometry–based shotgun proteomics, transcriptomics, and glycomics methods on 8 pediatric KD patients at the acute, subacute, and convalescent time points. Shotgun proteomics was performed on 9 KD adults with giant CAA and matched healthy controls. Plasma calprotectin was measured by ELISA in 28 pediatric KD patients 1 year post-KD, 70 adult KD patients, and 86 healthy adult volunteers.

Results:

A characteristic molecular profile was seen in pediatric patients during the acute disease, which resolved at the subacute and convalescent periods in patients with no coronary artery sequelae but persisted in 2 patients who developed giant CAA. We, therefore, investigated persistence of inflammation in KD adults with giant CAA by shotgun proteomics that revealed a signature of active inflammation, immune regulation, and cell trafficking. Correlating results obtained using shotgun proteomics in the pediatric and adult KD cohorts identified elevated calprotectin levels in the plasma of patients with CAA. Investigation of expanded pediatric and adult KD cohorts revealed elevated levels of calprotectin in pediatric patients with giant CAA 1 year post-KD and in adult KD patients who developed giant CAA in childhood.

Conclusions:

Complex patterns of biomarkers of inflammation and cell trafficking can persist long after the acute phase of KD in patients with giant CAA. Elevated levels of plasma calprotectin months to decades after acute KD and infiltration of cells expressing S100A8 and A9 in vascular tissues suggest ongoing, subclinical inflammation. Calprotectin may serve as a biomarker to inform the management of KD patients following the acute illness.
Synchronous Bidirectional Neural Machine Translation
Authors: Zhou Long , Zhang Jiajun , Zong Chengqing
Published: April 2019

Existing approaches to neural machine translation (NMT) generate the target language sequence token-by-token from left to right. However, this kind of unidirectional decoding framework cannot make full use of the target-side future contexts which can be produced in a right-to-left decoding direction, and thus suffers from the issue of unbalanced outputs. In this paper, we introduce a synchronous bidirectional–neural machine translation (SB-NMT) that predicts its outputs using left-to-right and right-to-left decoding simultaneously and interactively, in order to leverage both of the history and future information at the same time. Specifically, we first propose a new algorithm that enables synchronous bidirectional decoding in a single model. Then, we present an interactive decoding model in which left-to-right (right-to-left) generation does not only depend on its previously generated outputs, but also relies on future contexts predicted by right-to-left (left-to-right) decoding. We extensively evaluate the proposed SB-NMT model on large-scale NIST Chinese-English, WMT14 English-German, and WMT18 Russian-English translation tasks. Experimental results demonstrate that our model achieves significant improvements over the strong Transformer model by 3.92, 1.49, and 1.04 BLEU points, respectively, and obtains the state-of-the-art per- formance on Chinese-English and English- German translation tasks.1