bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermo- and pH-Responsive CeF3 Nanocrystals/HPC–PAA Complex Nanogel and Its Drug Release Behavior
Authors: Liu Ben , Song Qiusheng , Zhang Qiancheng , Ma Haihong , Zhang Ziwen , Wang Dapeng
Published: July 2019

In this study, a kind of novel rare-earth nanocrystals/hydroxypropylcellulose–poly (acrylic acid) (HPC–PAA) complex fluorescent nanogel, its responsive behavior to environmental temperature and pH value were reported. For preparation, with HPC being used as template, HPC–PAA nanogel was first synthesized by polymerization and crosslinking reaction of acrylic acid (AA) in water solution. In the process, a redox initiator, which composed of ammonium persulfate (APS) and N,N,N′,N′-tetramethylethylenediamine (TEMED), was used to initiate the reaction. Then, the as-prepared nanogel reacted with Ce(NO[Formula: see text] and NH4F solution successively, and a novel CeF3 nanocrystals/HPC–PAA complex nanogel was fabricated. The microstructure of the nanogel was characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD), Thermogravimetric (TG) and Transmission electron microscopy (TEM). The environmental sensitivity of the nanogel was investigated by photoluminescence (PL) and UV–Visible spectrophotometer (UV–Vis). The thermo- and pH-sensitive fluorescence were studied by PL at various temperatures and pH values; besides, the behavior of drug loading and release was researched by PL with a famous antibiotic of Ibuprofen as model drug. The results show that the PL intensity of the nanogel was largely affected by environmental temperature, or content of Ibuprofen loaded in the nanogel. The as-prepared nanogel can be used as useful sensitive material to detect temperature and pH value change, and drug loading or release property of Ibuprofen can be detected by PL emission of the nanogels conveniently.
The vitamin D-folate hypothesis in human vascular health
Authors: Wolf S. Tony , Kenney W. Larry
Published: July 2019

The vitamin D-folate hypothesis has been proposed as an explanation for the evolution of human skin pigmentation. According to this hypothesis, a darkened skin pigment was adapted by early human populations living in equatorial Africa to protect against photodegradation of bioavailable folate by ultraviolet radiation (UVR). As humans moved away from the equator to more northern latitudes and occupied regions of lower UVR exposure and greater seasonal variation, however, depigmentation occurred to allow for adequate biosynthesis of vitamin D. Vitamin D and folate are both recognized for their evolutionary importance in healthy pregnancy and early childhood development. More recently, evidence has emerged demonstrating the importance of both vitamin D and folate in vascular health via their effects in reducing oxidative stress and improving nitric oxide (NO) bioavailability. Thus, populations with darkened skin pigmentation may be at elevated risk of vascular dysfunction and cardiovascular disease in low UVR environments due to hypovitaminosis D; particularly important as darkly-pigmented African-Americans represent an at-risk population for cardiovascular disease. Conversely, lightly pigmented populations in high UVR environments may be at risk of deleterious vascular effects of UVR-induced folate degradation. The focus of this review is to explore the currently available literature regarding the potential role of UVR in vascular health via its differential effects on vitamin D and folate metabolism, as well as the interaction between skin pigmentation, genetics, and environment in modulating the vascular influence of UVR exposure.
Interindividual differences in the ischemic stimulus and other technical considerations when assessing reactive hyperemia
Authors: Rosenberry Ryan , Trojacek Darian , Chung Susie , Cipher Daisha J. , Nelson Michael D.
Published: July 2019

Reactive hyperemia is an established, noninvasive technique to assess microvascular function and a powerful predictor of all-cause and cardiovascular morbidity and mortality. Emerging evidence from our laboratory suggests a close link between reactive hyperemia and the metabolic rate of the ischemic limb and the existence of large interindividual differences contributing to markedly different stimuli to vasodilate. Here we relate forearm tissue desaturation (i.e., the ischemic stimulus to vasodilate, measured by near-infrared spectroscopy) to brachial artery hyperemic velocity and flow (measured using duplex ultrasound) across a wide range of ischemic stimuli. Twelve young and 11 elderly individuals were prospectively studied. To recapitulate conventional vascular occlusion testing, reactive hyperemia was first assessed using a standard 5-min occlusion period. Then, to evaluate the dose dependence of tissue ischemia on reactive hyperemia, we randomly performed 4-, 6-, and 8-min cuff occlusions in both groups. In all cases, peak velocity, as well as the 5-s average velocity, immediately after the cuff occlusion was significantly higher in the young than the elderly group; however, tissue desaturation was also much more pronounced in the young group ( P < 0.05), representing a greater ischemic stimulus. Remarkably, when reactive hyperemia was adjusted for the ischemic vasodilatory stimulus, group differences in reactive hyperemia were abrogated. Together, these data challenge conventional interpretations of reactive hyperemia and show that the ischemic stimulus to vasodilate varies across individuals and that the level of reactive hyperemia is often coupled to the magnitude of tissue desaturation.
Novel Recommendation System for Tourist Spots Based on Hierarchical Sampling Statistics and SVD++
Authors: Li Guangli , Hua Jin , Yuan Tian , Wu Jinpeng , Jiang Ziliang , Zhang Hongbin , Li Tao
Published: July 2019

Recommendation system for tourist spots has very high potential value including social and economic benefits. The traditional clustering algorithms were usually used to build a recommendation system. However, clustering algorithms have the risk on falling into local minimums, which may decrease the final recommendation performance heavily. Few works focused their research on tourist spots recommendation and few recommendation systems consider the population attributes information for fitting the user implicit preference. To address the problem, we focused our research work on designing a novel recommendation system for tourist spots. First a new dataset named “Smart Travel” is created for the following experiments. Then hierarchical sampling statistics (HSS) model is used to acquire the user preference for different population attributes. A new recommendation list named LA is generated in turn by fitting the excavated the user preference. More importantly, SVD++ algorithm rather than those traditional clustering algorithms is used to predict the user ratings. And a new recommendation list named LB is generated in turn on the basis of rating predictions. Finally, the two lists LA and LB are fused together to boost the final recommendation performance. Experimental results demonstrate that the mean precision, mean recall, and mean F1 values of the proposed recommendation system improve about 7.5%, 6.2%, and 6.5%, respectively, compared to the best competitor. The novel recommendation system is especially better at recommending a group of tourist spots, which means it has higher practical value.
Links between High-Sensitivity C-Reactive Protein and Pulse Wave Analysis in Middle-Aged Patients with Hypertension and High Normal Blood Pressure
Authors: Mozos Ioana , Jianu Daniela , Gug Cristina , Stoian Dana
Published: July 2019

Arterial stiffness and arterial age provide valuable prognostic cardiovascular information. The present study aimed at assessing the levels of vitamin D, high-sensitivity C-reactive protein (hsCRP), low-density lipoprotein cholesterol (LDL), and oxidized LDL (oxLDL) in a group of middle-aged hypertensive patients and their relationship with pulse wave velocity (PWV), central blood pressure, and early arterial aging (EAA), respectively. A total of 56 patients, aged 48±6 years, 57% males, with hypertension and high normal blood pressure (HNBP), were investigated using a Mobile-O-Graph, to assess central and peripheral blood pressure, PWV, and arterial age. Additionally, hsCRP, LDL, oxLDL, and 25-hydroxy vitamin D3 were assessed. PWV, 25-hydroxy vitamin D3, hsCRP, oxLDL, and LDL levels were 7.26±0.69 m/s, 25.99±11.17 microg/l, 0.48±0.44 mg/dl, 261.37±421 ng/ml, and 145.73±39.53 mg/dl, respectively. Significant correlations were obtained between oxLDL and pulse pressure amplification (rS=−0.347, p=0.028) and between hsCRP and LDL levels with PWV and EAA, respectively. ROC curve analysis revealed that hsCRP is a sensitive and specific predictor of EAA and increased PWV values. Concluding, vitamin D deficiency and increased hsCRP and LDL values are very common, and high oxidized LDL is related to pulse pressure amplification in patients with elevated blood pressure. Vitamin D level and high-sensitivity C-reactive protein and LDL provide valuable information in middle-aged hypertensive and HNBP patients related to arterial stiffness and early arterial aging, but only hsCRP is a sensitive predictor of EAA and PWV.
Efficacy of Terpenoid in Attenuating Aortic Atherosclerosis in Apolipoprotein-E Deficient Mice: A Meta-Analysis of Animal Studies
Authors: Liu Han , Zhang Yang , Sun Siqiao , Wang Shuai
Published: July 2019

Background. The apolipoprotein E knockout (ApoE -/-) mouse model is well established for the study of terpenoids in the prevention of atherosclerosis. Studies investigating the clinical benefit of terpenoids in humans are scarce. This systematic review and meta-analysis evaluated the effects of terpenoid administration on atherosclerotic lesion area in ApoE -/- mice.Methods. A comprehensive literature search using PubMed, Embase, and the Cochrane Library databases was performed to identify studies that assessed the effects of terpenoids on atherosclerosis in ApoE -/- mice. The primary outcome was atherosclerotic lesion area, and study quality was estimated using SYRCLE’s risk of bias tool.Results. The meta-analysis included 25 studies. Overall, terpenoids significantly reduced atherosclerotic lesion area when compared to vehicle control (P<0.00001; SMD: -0.55; 95% CI: -0.72, -0.39). In terpenoid type and dose subgroup analyses, sesquiterpenoid (P=0.002; SMD -0.93; 95% CI: -1.52, -0.34), diterpenoid (P=0.01; SMD: -0.30; 95% CI: -0.54, -0.06), triterpenoid (P<0.00001; SMD: -0.66; 95% CI: -0.94, -0.39), tetraterpenoid (P<0.0001; SMD: -1.81; 95% CI: -2.70, -0.91), low dose (P=0.0001; SMD: -0.51; 95% CI: -0.76, -0.25), medium dose (P<0.0001; SMD: -0.48; 95% CI: -0.72, -0.24), and high dose (P=0.002; SMD: -1.07; 95% CI: -1.74, -0.40) significantly decreased atherosclerotic lesion area when compared to vehicle control. PROSPERO register number is CRD42019121176.Conclusion. Sesquiterpenoid, diterpenoid, triterpenoid, and tetraterpenoid have potential as antiatherosclerotic agents with a wide range of doses. This systematic review provides a reference for research programs aimed at the development of terpenoid-based clinical drugs.
Circulating Angptl3 and Angptl8 Are Increased in Patients with Hypothyroidism
Authors: Yang Longyan , Yin Ruili , Wang Zongwei , Wang Xiaobo , Zhang Yuanyuan , Zhao Dong
Published: July 2019

Purpose. Angiopoietin-like proteins (Angptls) play critical roles in biological processes, primarily in lipid metabolism. The functional state of the thyroid has a profound influence on metabolism in the human body. Therefore, the aim of this study was to investigate possible changes in serum Angptl3, 4, and 8 levels in hypothyroid patients. Methods. The study included 29 patients with clinical hypothyroidism, 30 patients with subclinical hypothyroidism, and 29 healthy subjects. Baseline clinical indices, including serum thyroid function tests, were recorded and serum Angptl3, 4, and 8 levels were measured across the three groups. Results. Serum Angptl3 and 8 levels were significantly higher in the hypothyroid groups compared to the control group (p < 0.05). There were no differences in Angptl4 levels among the three groups (p > 0.05). Positive correlations were identified between Angptl3 and high-density lipoprotein cholesterol (r = 0.431, p < 0.001), and there was a negative correlation between Angptl3 and total tri-iodothyronine (TT3) (r = -0.220, p = 0.047) and free tri-iodothyronine (r = - 0.279, p = 0.013) levels. Angptl8 was positively correlated with triglyceride (r = 0.267, p = 0.012) and cholesterol levels (r= 0.235, p = 0.028) but was negatively correlated with tri-iodothyronine (r = -0.24, p = 0.031). Furthermore, we used receiver operating characteristic curve analysis to evaluate the diagnostic performance of Angptl3 and 8 in discriminating thyroid dysfunction. The area under curve for detecting thyroid dysfunction based on Angptl3 and Angptl8 was 0.763. Conclusions. Our data show that serum Angptl3 and 8 levels are increased in clinical and subclinical hypothyroid patients and that Angptl3 and 8 may serve as possible biomarkers of hypothyroid disease.
Coalitional Game Theoretical Approach for VANET Clustering to Improve SNR
Authors: Sulistyo Selo , Alam Sahirul , Adrian Ronald
Published: July 2019

Clustering is considered as the potential approach for network management in vehicular ad hoc network (VANET). The performance of clustering is often assessed based on the stability of the clusters. Hence, most of the clustering methods aim to establish stable clusters. However, besides the stability of cluster, good link quality must be provided, especially when reliable and high-capacity transmission is demanded. Therefore, this paper proposes a clustering method based on coalitional game theory with the purpose to improve the average of vehicle-to-vehicle (V2V) signal-to-noise ratio (SNR) and channel capacity while maintaining the stability of the cluster. In the proposed method, each vehicle attempts to form a cluster with other vehicles according to coalition value. To attain the purpose of clustering, the value of coalition is formulated based on the V2V SNR, connection lifetime, and speed difference between vehicles. In fast-changing network topology, the higher average of SNR can be achieved but the stability of cluster becomes hard to be maintained. Based on the simulation results, SNR improvement can be adjusted in order to balance with the cluster stability by setting the parameters in the proposed method accordingly. Further simulation results show that the proposed method can obtain a higher average of V2V SNR and channel capacity than other relevant methods.
Nature and Origin of Mineralizing Fluids in Hyperextensional Systems: The Case of Cretaceous Mg Metasomatism in the Pyrenees
Authors: Quesnel Benoît , Boiron Marie-Christine , Cathelineau Michel , Truche Laurent , Rigaudier Thomas , Bardoux Gérard , Agrinier Pierre , de Saint Blanquat Michel , Masini Emmanuel , Gaucher Eric C.
Published: July 2019

During the Albian, the hyperextension of the Pyrenean passive margin led to a hyperthinning of the continental crust and the subsequent subcontinental mantle exhumation. The giant Trimouns talc-chlorite deposit represents the most prominent occurrence of Albian metasomatism in the Pyrenees, with the occurrence of the largest talc deposit worldwide. Consequently, this deposit, which is located on a fault zone and a lithological contact, represents one of the major drains at the scale of the Pyrenees and one of the best geological targets in order to determine the origin(s) of the fluid(s) that circulated during this period. Talc-chlorite ore is characterized by the presence of brines trapped in dolomite, quartz, and calcite fluid inclusions in the vicinity of the talc-rich zone. Considered as being responsible for the formation of talc, these fluids may be interpreted in several ways: (i) primary brines expelled from Triassic evaporites, (ii) secondary brines produced through halite leaching by diagenetic/metamorphic fluids, and (iii) brines derived from seawater serpentinization of mantle rocks. Stable isotope analyses (δ13C, δ18O, δD, and δ37Cl) and Cl/Br ratio measurements in fluid inclusions and their host minerals were carried out in order to determine the origin of the fluid(s) involved in the formation of the ore deposit. The data are consistent with a primary brine origin for the mineralizing fluid, which could have been expelled from the Triassic levels. Other hypotheses have been tested, for example, the production of brines via the seawater concentration during serpentinization. The geochemical proxies used in this study provide equivocal results. The first hypothesis is by far the most realistic one considering the numerous occurrences of Trias formations nearby, their deformation during the extension, and the drainage of the expulsed brines as evidenced by the high-salinity fluid inclusions found all around the deposit. Alternatively, the exhumation of the mantle is considered as a major source of heat and stress that favored brine migration along the major shear zones. Our results fit well with brine circulation in a hyperextensional geodynamic context, which is related to the formation of the talc-chlorite ore, the thinning of the continental crust, and the exhumation of the subcontinental mantle, in accordance with recent works.
A Discrete Dipole Approximation Solver Based on the COCG-FFT Algorithm and Its Application to Microwave Breast Imaging
Authors: Hosseinzadegan Samar , Fhager Andreas , Persson Mikael , Meaney Paul
Published: July 2019

We introduce the discrete dipole approximation (DDA) for efficiently calculating the two-dimensional electric field distribution for our microwave tomographic breast imaging system. For iterative inverse problems such as microwave tomography, the forward field computation is the time limiting step. In this paper, the two-dimensional algorithm is derived and formulated such that the iterative conjugate orthogonal conjugate gradient (COCG) method can be used for efficiently solving the forward problem. We have also optimized the matrix-vector multiplication step by formulating the problem such that the nondiagonal portion of the matrix used to compute the dipole moments is block-Toeplitz. The computation costs for multiplying the block matrices times a vector can be dramatically accelerated by expanding each Toeplitz matrix to a circulant matrix for which the convolution theorem is applied for fast computation utilizing the fast Fourier transform (FFT). The results demonstrate that this formulation is accurate and efficient. In this work, the computation times for the direct solvers, the iterative solver (COCG), and the iterative solver using the fast Fourier transform (COCG-FFT) are compared with the best performance achieved using the iterative solver (COCG-FFT) in C++. Utilizing this formulation provides a computationally efficient building block for developing a low cost and fast breast imaging system to serve under-resourced populations.
A Three-Dimensional Musculoskeletal Model of the Western Lowland Gorilla Foot: Examining Muscle Torques and Function
Authors: Goh Colleen , Blanchard Mary L. , Crompton Robin H. , Gunther Michael M. , Macaulay Sophie , Bates Karl T.
Published: July 2019

Due to difficulty of obtaining accurate quantitative data on foot muscles, relatively little has been done to study foot muscle function in non-human apes. Gorilla feet are known to be similar in bony proportions and mechanics to those of humans, hence are key to understanding human foot evolution and its ecological context. We present the first 3D musculoskeletal computer model of a western lowland gorilla foot, giving muscle torques about the tarsometatarsal, metatarsophalangeal and interphalangeal joints of digits 2–5. Peak flexor torque around the fifth metatarsophalangeal joint occurs at a highly flexed position, suggesting an ability to maintain flexed postures around lateral metatarsophalangeal joints, useful for grasping vertical supports. For distal interphalangeal joints, flexor torques peaked the more medial the digit at relatively flexed postures. We report, for the first time, interossei acting upon proximal and distal interphalangeal joints. All these facilitate maintenance of flexed positions around distal interphalangeal joints, likely used for grasping of small supports/objects. Humans lack these features, suggesting that semi-arboreal early hominins made less use of the peripheral canopy than gorillines. Information here could be used in gorilla enclosure design to encourage wild-type locomotor repertoires in captivity.
Correlation between Early Tumor Marker Response and Imaging Response in Patients with Advanced Hepatocellular Carcinoma Treated with Lenvatinib
Authors: Kodama Kenichiro , Kawaoka Tomokazu , Namba Maiko , Uchikawa Shinsuke , Ohya Kazuki , Morio Kei , Nakahara Takashi , Murakami Eisuke , Yamauchi Masami , Hiramatsu Akira , Imamura Michio , Chayama Kazuaki , Aikata Hiroshi
Published: July 2019

Aim: This study investigated early tumor marker response and treatment response in patients with advanced hepatocellular carcinoma (HCC) treated with lenvatinib. Methods: Twenty patients with advanced HCC who received lenvatinib were enrolled in this retrospective study. α-Fetoprotein (AFP) and des-γ-carboxyprothrombin (DCP) levels were measured before treatment as well as 2 and 4 weeks after treatment. The objective response rate was evaluated by mRECIST at 6 weeks. Results: The response rate was 30% (complete response/partial response/stable disease/progressive disease: n = 0/6/6/8 cases) by mRECIST. At 4 weeks, the AFP levels of 12 patients (80%) were lower than at baseline. The AFP levels of 9 patients (60%) continued decreasing from 2 weeks to 4 weeks (sustained-reduction group). In this group, the response rate was 67%. The median AFP change rate was –39% at 4 weeks. In imaging responders, the AFP change rate significantly decreased (p = 0.02). The DCP change rate had no significant correlation with imaging response. The AFP-sustained-reduction group had significantly higher adherence to lenvatinib than the non-sustained-reduction group (p = 0.02). Conclusion: With lenvatinib therapy for HCC, the AFP levels of most patients had declined at 2 weeks, and at 4 weeks the AFP-sustained-reduction group demonstrated a higher objective response.
In the Beginning ... It was Already the End
Authors: Janeiro Claudia , Santos Rita , Teixeira João , Mesquita Pedro , Eça Rosário , Vale Luis
Published: July 2019

Sometimes, the presentation of some diseases can be fulminating. The authors present the case of a 51-year- old male brought to the emergency department visibly drunk and complaining of abdominal pain. Immediately, the diagnosis of hemorrhagic shock due to an accentuated drop of the hemoglobin level was made. After stabilization, he underwent a computed tomography of the abdomen, revealing a hepatocellular carcinoma with rupture of the Glisson capsule and massive intraperitoneal hemorrhage. With this case, the authors want to bring attention to a rare first presentation of hepatocellular carcinoma with a catastrophic result.
Overweight and Lonely? A Representative Study on Loneliness in Obese People and Its Determinants
Authors: Jung Franziska U. , Luck-Sikorski Claudia
Published: July 2019

Obesity is associated with physical and medical restrictions and comorbidities, but it also entails psychosocial effects such as social isolation and feelings of rejection. The aim of this study was to investigate the link between loneliness and weight stigma in a large sample of obese individuals. Results were derived from a large representative sample (n = 1,000). The survey included the 3-item version of the UCLA loneliness scale, the Patient Health Questionnaire (PHQ-9) as well as the Weight Bias Internalization scale (WBIS). The mean UCLA score was 1.943 (SD = 0.771). Respondents with higher levels of depression (B = 0.176), higher internalized weight bias (B = 0.435), and the experience of discrimination (B = 0.286) reported higher levels of loneliness. Future studies should investigate the mediation pathways between obesity, loneliness, and its determinants to provide a framework for successful interventions as part of obesity management programs.
Complications after Anterior Temporal Lobectomy for Medically Intractable Epilepsy: A Systematic Review and Meta-Analysis
Authors: Brotis Alexandros G. , Giannis Theofanis , Kapsalaki Eftychia , Dardiotis Efthymios , Fountas Kostas N.
Published: July 2019

Background: The efficacy of surgery in the management of patients with longstanding temporal lobe epilepsy has been established. Anterior temporal lobectomy (ATL) is the most frequently implemented procedure. However, there is an obvious need to assess its perioperative safety. Objective: We conducted a meta-analysis to estimate the postoperative mortality (Q1) and morbidity (Q2) associated with ATL for medically intractable epilepsy. In addition, we tried to identify the most frequent complications after ATL and assess their relative frequency (Q3) in children and adults. Methods: Fixed- and random-effects model meta-analysis was conducted to assess the proportion estimate for each outcome individually. Results: The postoperative mortality and cumulative morbidity were estimated to be as high as 0.01 (95% CI: 0.01, 0.02) and 0.17 (95% CI: 0.12, 0.24), respectively. Psychiatric disorders were the most common postoperative complications after ATL, with an estimated frequency as high as 0.07 (95% CI: 0.04, 0.10), followed by visual field defects (0.06; 0.03, 0.11), and cognitive disorders (0.05; 0.02, 0.10). Less frequent complications included hemiparesis and language disorders (0.03; 0.01, 0.06), infections (0.03; 0.02, 0.04), hemorrhage (0.02; 0.01, 0.05), cranial nerve deficits (0.03; 0.02, 0.05), extra-axial fluid collections (0.02; 0.01, 0.03), and medical complications (0.02; 0.01, 0.03). Conclusions: Even though the mortality after ATL is minimal, the overall morbidity cannot be ignored. Psychiatric disturbances, visual field defects, and cognitive disorders are the most common postoperative complications, and should be considered during the preoperative planning and consultation.
Detecting Foreign Accents in Song
Authors: Mageau Marly , Mekik Can , Sokalski Ashley , Toivonen Ida
Published: July 2019

This paper presents three experiments exploring the perception and production of accents in song. In a perception experiment, participants listened to passages sung and spoken by native and non-native speakers of English. The participants did better at identifying native speakers when listening to the spoken passages. Accents were also judged as more native-like in song than in speech. In addition, two production experiments compared the acoustic characteristics (pitch, duration, F1 and F2) of sung and spoken vowels, produced by native and non-native speakers of English. Both native and non-native speakers changed the pitch and duration of their vowels when singing; the vowel quality was not consistently shifted. Together, the results indicate that the melody imposed by the song impacts the suprasegmental properties of pronunciation whereas the segmental properties remain largely intact. Based on these results, we conclude that a main reason why accents are more difficult to detect in song than in speech is that the rhythm and melody imposed by the song mask intonational cues to accent.
The Specific Organism: Not Bacterial Gram Type: Drives the Inflammatory Response in Septic Shock
Authors: Linder Adam , Fjell Chris D. , Inghammar Malin , Hsu Joseph , Walley Keith R. , Boyd John H. , Russell James A.
Published: July 2019

Background and Hypothesis: The inflammatory response was targeted by unsuccessful therapies but ignored pathogen. We hypothesized that the inflammatory response differs according to organism in human septic shock. Materials and Methods: We measured 39 cytokines at baseline and 24 h in patients (n = 363) in the Vasopressin and Septic Shock Trial (VASST). We compared cytokine profiles (cytokine functional class) at baseline and at 24 h by organism and used hierarchical clustering to classify cytokines according to 28-day outcomes. Results: In 363 patients, 88 and 176 patients had at least 1 species isolated from blood and other sites, respectively. Cytokine levels differed significantly according to organism: Neisseria meningitidis and Streptococcus pneumoniae had the highest (baseline and at 24 h), while Enterococcus faecalis (blood) had the lowest mean cytokine levels. N. meningitidis and Klebsiella pneumoniae had significantly higher cytokine levels at baseline versus 24 h (p = 0.01 and 0.02, respectively); E. faecalis had significantly higher cytokine levels at 24 h versus baseline. Hierarchical clustering heat maps showed that pathogens elicited similar cytokine responses not related to the functional cytokine class. Conclusion: The organism type induces different cytokine profiles in septic shock. Specific gram-positive and gram-negative pathogens stimulated similar plasma cytokine-level patterns.
Long Noncoding RNA Linc00632 Inhibits Interleukin-13-Induced Inflammatory Cytokine and Mucus Production in Nasal Epithelial Cells
Authors: Yue Liyan , Yin Xiaoyan , Hao Fang , Dong Jinhui , Ren Xiumin , Xu Ou , Shan Chunguang
Published: July 2019

Allergic rhinitis (AR) is an allergic disease characterized as (immunoglobulin E)-mediated type I hypersensitivity disorder. The interleukin-13 (IL-13) signaling pathway has been implicated in the pathogenesis of AR. In the present study, we investigated the regulatory role and mechanism of long noncoding RNA Linc00632 in IL-13-induced inflammatory cytokine and mucus production in nasal epithelial cells (NECs) from AR patients. We evaluated the expression of Linc00632 in nasal tissues from AR patients and in IL-13-treated NECs. We explored the role of Linc00632 in granulocyte-macrophage colony-stimulating factor (GM-CSF), eotaxin, and MUAC5AC production in IL-13-treated NECs. We searched for the potential target of Linc00632. Downregulation of Linc00632 was identified in nasal tissues of AR patients and in IL-13-treated NECs. Linc00632 inhibited IL-13-induced GM-CSF, eotaxin, and MUAC5AC production. Linc00632 targeted miR-498 and negatively regulated its expression. MiR-498 targeted IL1RN and inhibition of miR-498 suppressed IL-13-induced GM-CSF, eotaxin, and MUC5AC expression. The regulation of IL-13-induced dysfunction of NECs by Linc00632 depended on miR-498. Linc00632 inhibited IL-13-induced GM-CSF, eotaxin, and MUAC5AC production in IL-13-treated NECs by targeting miR-498.
Outcomes for Relapsed and Refractory Peripheral T-Cell Lymphoma Patients after Front-Line Therapy from the COMPLETE Registry
Authors: Lansigan Frederick , Horwitz Steven M. , Pinter-Brown Lauren C. , Rosen Steven T. , Pro Barbara , Hsi Eric D. , Federico Massimo , Gisselbrecht Christian , Schwartz Marc , Bellm Lisa A. , Acosta Mark , Shustov Andrei R. , Advani Ranjana H. , Feldman Tatyana , Lechowicz Mary Jo , Smith Sonali M. , Tulpule Anil , Craig Michael D. , Greer John P. , Kahl Brad S. , Leach Joseph W. , Morganstein Neil , Casulo Carla , Park Steven I. , Foss Francine M.
Published: July 2019

Background: Outcomes for patients with peripheral T-cell lymphoma (PTCL) who fail to achieve complete response (CR) or relapse after front-line therapy are poor with lack of prospective outcomes data. Objectives: COMPLETE is a prospective registry of 499 patients enrolled at academic and community sites in the United States detailing patient demographics, treatment and outcomes for patients with aggressive T cell lymphomas. We report results for patients with primary refractory and relapsed disease. Methods: Primary refractory disease was defined as an evaluable best response to initial treatment (induction ± maintenance or consolidation/transplant) other than CR, and included a partial response, progressive disease, or no response/stable disease. Relapsed disease was defined as an evaluable best response to initial treatment of CR, followed by disease progression at a later date, irrespective of time to progression. Patients were included in the analysis if initial treatment began within 30 days of enrollment and treatment duration was ≥4 days. Results: Of 420 evaluable patients, 97 met the definition for primary refractory and 58 with relapsed disease. In the second-line setting, relapsed patients received single-agent therapies more often than refractory patients (52 vs. 28%; p = 0.01) and were more likely to receive single-agent regimens (74 vs. 53%; p = 0.03). The objective response rate to second-line therapy was higher in relapsed patients (61 vs. 40%; p = 0.04) as was the proportion achieving a CR (41 vs. 14%; p = 0.002). Further, relapsed patients had longer overall survival (OS) compared to refractory patients, with a median OS of 29.1 versus 12.3 months. Conclusions: Despite the availability of newer active single agents, refractory patients were less likely to receive these therapies and continue to have inferior outcomes compared to those with relapsed disease. PTCL in the real world remains an unmet medical need, and improvements in front-line therapies are needed.
Mechanism-Based Treatment Strategies for IBD: Cytokines, Cell Adhesion Molecules, JAK Inhibitors, Gut Flora, and More
Authors: Schreiner Philipp , Neurath Markus F. , Ng Siew C. , El-Omar Emad M. , Sharara Ala I. , Kobayashi Taku , Hisamatsu Tadakazu , Hibi Toshifumi , Rogler Gerhard
Published: July 2019

Background: Although TNF inhibitors revolutionized the therapy of inflammatory bowel disease (IBD), we have been reaching a point where other therapies with different mechanisms of action are necessary. A rising number of elderly IBD patients with contraindications to established therapies and a growing group of patients losing response to anti-TNF therapy compel us to find safer, better-tolerated, and, ideally, personalized treatment options. However, in order to choose the right drug to fit a patient, it is indispensable to understand the pathomechanism involved in IBD. Summary: The aim of this review is to explain the inflammatory signaling pathways in IBD and how to inhibit them with current and future therapeutic approaches. Next to biologic agents targeting inflammatory cytokines (anti-TNF agents, anti-IL-12/-23 agents, and specific inhibitors of IL-23), biologics blocking leukocyte trafficking to the gut (anti-integrin antibodies) are available nowadays. More recently, small molecules inhibiting the JAK-STAT pathway (JAK inhibitors) or preventing lymphocyte trafficking (sphingosine-1-phosphate modulators) have been approved or are under investigation. Furthermore, modifying the microbiota has potential therapeutic effects on IBD, and autologous hematopoietic or mesenchymal stem cell transplantation may be considered for a highly selected group of IBD patients. Key Message: Physicians should understand the different mechanisms of action of the potential therapies for IBD to select the right drug for the right patient.
Preoperative Thrombocytosis in Patients Undergoing Radical Cystectomy for Urothelial Cancer of the Bladder: An Independent Prognostic Parameter for an Impaired Oncological Outcome
Authors: Jokisch Jan-Friedrich , Grimm Tobias , Buchner Alexander , Kretschmer Alexander , Weinhold Philipp , Stief Christian G. , Karl Alexander , Schulz Gerald Bastian
Published: July 2019

Background: Preoperative thrombocytosis (PTC) is frequently observed in various solid malignancies and often associated with an unfavourable oncological outcome. Objectives: The aim of this study was to investigate the influence of PTC in patients undergoing radical cystectomy (RC) for urothelial carcinoma (UC) of the bladder on the oncological prognosis and additionally on perioperative blood transfusions (PBT). Method: A retrospective analysis of 866 patients undergoing RC in a tertiary care centre was performed. PTC was defined as a platelet count >400 G/L. A chi-square test and Mann-Whitney test were used to investigate the association of PTC with categorical clinicopathological variables. A logrank test and multivariable Cox regression analyses were used to assess the association of PTC with cancer-specific survival. Results: PTC was detected in 8% (n = 67) of the patients and was significantly associated with muscle invasion (p = 0.004), advanced tumour stages (p = 0.003) and nodal metastases (p < 0.001) and with a higher rate of PBT (p< 0.001). In the multivariate analysis, PTC was significantly related to poor oncological survival (hazard ratio 2.23, 95% CI 1.51–3.30, p < 0.001). Conclusion: PTC is significantly associated with an impaired oncological outcome in patients undergoing RC for UC. PTC therefore represents an independent and easy to determine prognostic parameter for patients’ oncological outcome. Intriguingly, PTC is significantly associated with an increased rate of PBT.
Evaluation of Electrocardiographic Parameters Predicting Cardiovascular Events in Patients with End-Stage Renal Disease before and after Transplantation
Authors: Buerschaper Laura , Floege Jürgen , Mühlfeld Anja , Schlieper Georg
Published: July 2019

Background and Objectives: Cardiovascular (CV) mortality represents the leading cause of death in patients with end-stage renal disease (ESRD). Efficient screening is required to detect CV disease at an early stage, but the best diagnostic work-up is uncertain. The aim of this study was to identify electrocardiographic parameters in dialysis patients associated with an increased frequency of CV events. Methods: A 12-lead electrocardiogram was performed in 139 patients who were on the renal transplant waiting list and who subsequently received a kidney transplant. CV events were analyzed from the day of listing for kidney transplantation until 1 year after renal transplantation. Results: Multivariate Cox regression analysis showed that an elevated T:R ratio in anterior and inferior leads was independently associated with CV events (T:R ratio of anterior leads hazard ratio [HR] 1.32 [95% CI 1.09–1.59; p = 0.004] and inferior leads HR 2.15 [95% CI 1.23–3.77; p = 0.008]). In particular, a T:R ratio in inferior leads exceeding 0.6 was associated with CV events in a Kaplan-Meier analysis. Conclusions: Taken together, we found an increased T:R ratio in ESRD patients to be a predictive marker for CV events.
Novel CYP24A1 Mutation in a Young Male Patient with Nephrolithiasis: Case Report
Authors: Jiráčková Jana , Hyšpler Radomir , Alkanderi Sumaya , Pavlíková Ladislava , Palicka Vladimir , Sayer John A.
Published: July 2019

Background/Aims: The CYP24A1 gene encodes the vitamin D 24-hydroxylase enzyme, which hydroxylates active forms of vitamin D into inactive forms. Biallelic mutations in the CYP24A1 gene can lead to elevated levels of active vitamin D metabolites and, consequently, to hypercalcemia, hypercalciuria, nephrocalcinosis, and nephrolithiasis; however, monoallelic mutations have been associated only with milder phenotypes. In the present manuscript, we report the case of a young male patient who presented hypercalcemia and nephrolithiasis, suppressed parathormone, and elevated 1,25 dihydroxy vitamin D levels. Methods: Biochemical analyses were performed on Cobas 8000, F. Hoffmann-La Roche AG, Basel, Switzerland. The proband was initially evaluated for occult malignancies by body imaging, serum electrophoresis, and tumor markers, which did not reveal any pathology. DNA samples of the proband and his sibling were then examined using Sanger sequencing. Results: Genetic analysis revealed 2 compound heterozygous CYP24A1 mutations (p.L148P and p.R223*). The novel nonsense CYP24A1 mutation, p.R223*, was also found heterozygously in other family members with a medical history of nephrolithiasis. Conclusions: The identification of this gene mutation causing hypercalcemia, hypercalciuria, and renal stones allows the specific management of endogenous vitamin D production.
Outpatient Parenteral Antimicrobial Treatment for Non-Cystic Fibrosis Bronchiectasis Exacerbations: A Prospective Multicentre Observational Cohort Study
Authors: López-Cortés Luis Eduardo , Ayerbe-García Rut , Carrasco-Hernández Laura , Fraile-Ramos Elena , Carmona-Caballero Juan Manuel , Quintana-Gallego Esther , Valido-Morales Agustín , Praena Julia , Pachón-Diaz Jerónimo ,   DOMUS OPAT Group
Published: July 2019

Background: The recently published guidelines of the Spanish Society of Pulmonology and Thoracic Surgery encourage physicians to use outpatient antimicrobial therapy to treat exacerbations in patients with non-cystic fibrosis bronchiectasis (NCFB). The published literature on this topic, however, is scarce. Methods: We report a prospective observational cohort study of patients with NCFB who received treatment at home for at least one exacerbation episode between September 2012 and September 2017 as part of an outpatient parenteral antimicrobial therapy (OPAT) program. Patients were included in the analysis if they fulfilled all of the following criteria: established diagnosis of bronchiectasis according to current guidelines criteria, clinical exacerbation, requiring intravenous antibiotics because of failure to respond to oral antibiotics, or isolation of a microorganism resistant to oral options. Objectives: To evaluate the effectiveness and safety of the treatment of patients with NCFB exacerbations in an OPAT program under “real-world” conditions. Results: Sixty-seven patients were treated in the OPAT program due to bacterial exacerbations of NCFB. Forty-five (67.2%) patients were admitted to hospital for a median of 7 days before starting OPAT. Sixty-three (94%) patients achieved resolution of the exacerbation at the end of therapy. Four patients needed hospital readmission, and one died. The OPAT program saved 11,586 days of hospital admission, equivalent to EUR 7,866,904. Conclusions: OPAT appears to be a safe, effective, and efficient strategy for treating patients with exacerbations of NCFB.
Transplant-Amenable Hepatocellular Carcinoma in a Fontan Patient
Authors: Rutledge Brian Patrick , Devara Anupama , Benjaram Sindhuri , Judd Stephanie , Ehrinpreis Murray
Published: July 2019

The Fontan circulation alters a patient’s physiology and imparts long-term risks related to chronically elevated systemic venous pressure. An increasing number of patients with Fontan physiology are surviving into adulthood and are at risk of hepatic sequalae. The ideal timeline and method of hepatic surveillance in the Fontan population remains to be defined. In this case, the patient was diagnosed with hepatocellular carcinoma more than 20 years after undergoing the Fontan procedure and was a candidate for combined heart-liver transplant. That her disease progressed prior to organ availability supports the argument for hepatic surveillance in this population.
Laparoscopic Partial versus Total Adrenalectomy in Nonhereditary Unilateral Adrenal Masses
Authors: Balci Melih , Tuncel Altug , Aslan Yilmaz , Aykanat Can , Berker Dilek , Guzel Ozer
Published: July 2019

Objective: To compare the surgical outcomes and clinical improvement 1 year after laparoscopic partial and total adrenalectomy for the treatment of patients with nonhereditary unilateral functional adrenal adenomas. Material and Methods: From March 2016 to January 2018, we performed 15 laparoscopic partial adrenalectomy (LPA; Group 1) and 25 laparoscopic total adrenalectomy (LTA; Group 2) procedures. The key points reside in adenoma identification, preservation of the remaining glandular parenchyma, and its blood supply with dissection in the space between the adenoma and the normal parenchyma. The operative and clinical outcomes were compered. Results: The mean age of the patients was 45.1 (17–69) years and the median follow-up was 15 (12–26) months. Operative time, blood loss, and hospital stay were similar between the groups. No major perioperative and postoperative complications occurred. After surgery, all patients had resolution of their symptoms, with no patient in Group 1 requiring steroid replacement. However, a patient in Group 2 required steroid replacement therapy. On postoperative imaging, no residual and recurrent mass was detected. Conclusions: Our results showed that LPA is safe and feasible, and has similar therapeutic results compared with LTA in patients with a nonhereditary hormonally active unilateral adrenal mass. Furthermore, LPA can obviate the need for steroid replacement in these patients.
Altruistic Behavior Depending on Opponents’ Body Weight: An Experimental Approach
Authors: Bernard Marie , Riedel-Heller Steffi G. , Luck-Sikorski Claudia
Published: July 2019

Background: Obesity is a worldwide public health issue, not only because it is associated with numerous comorbid diseases but also because of its impact on the social level. This study aims to investigate (a) whether altruistic behavior differs between people with obesity and people who are not obese, (b) altruistic behavior toward people who are obese, in particular, women who are obese, and (c) implicit and explicit attitudes toward people with obesity as predictors for divergent altruistic behavior. Methods: An experimental approach called the dictator game was applied. In total, 168 participants of normal weight were asked to divide a monetary reward between themselves and two opponents, one person who was obese and one with normal weight. In addition, participants’ implicit and explicit attitudes toward people with obesity as well as other sociodemographic data were assessed. Results: We found that altruistic behavior did not differ between obese and nonobese opponents (t(166) = –0.57, p = 0.71), nor did we find less altruistic attitudes toward women with obesity (t(85) = –0.03, p = 0.39). Linear regression models show less altruistic behavior among people with stronger explicit antifat attitudes (p = 0.015). However, although we found that participants held implicit attitudes toward people with obesity, these attitudes did not predict altruistic behavior toward people with obesity. Conclusion: Although numerous studies reported discrimination toward people with obesity in several areas of life, we did not find discrimination in form of less altruistic behavior toward people with obesity. Moreover, although we found implicit antifat attitudes among the participants, these attitudes did not predict altruistic behavior toward people of divergent weight groups. Therefore, future research should investigate more intensively the diverse facets of discrimination toward people with obesity, if and to what extent implicit antifat attitudes have a quantifiable impact on the stigmatization and or discrimination process, and the hypotheses in a more hidden way, since manipulation check revealed that the majority of participants anticipated the underlying idea of the dictator game.