bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of age‐associated comorbidities on responses to combination antiretroviral therapy in older people living with HIV
Authors: Ahn Mi Young , Jiamsakul Awachana , Khusuwan Suwimon , Khol Vohith , Pham Thuy T , Chaiwarith Romanee , Avihingsanon Anchalee , Kumarasamy Nagalingeswaran , Wong Wing Wei , Kiertiburanakul Sasisopin , Pujari Sanjay , Nguyen Kinh V , Lee Man Po , Kamarulzaman Adeeba , Zhang Fujie , Ditangco Rossana , Merati Tuti P , Yunihastuti Evy , Ng Oon Tek , Sim Benedict L H , Tanuma Junko , Ratanasuwan Winai , Ross Jeremy , Choi Jun Yong ,   IeDEA Asia‐Pacific
Published: February 2019

AbstractIntroductionMultiple comorbidities among HIV‐positive individuals may increase the potential for polypharmacy causing drug‐to‐drug interactions and older individuals with comorbidities, particularly those with cognitive impairment, may have difficulty in adhering to complex medications. However, the effects of age‐associated comorbidities on the treatment outcomes of combination antiretroviral therapy (cART) are not well known. In this study, we investigated the effects of age‐associated comorbidities on therapeutic outcomes of cART in HIV‐positive adults in Asian countries.MethodsPatients enrolled in the TREAT Asia HIV Observational Database cohort and on cART for more than six months were analysed. Comorbidities included hypertension, diabetes, dyslipidaemia and impaired renal function. Treatment outcomes of patients ≥50 years of age with comorbidities were compared with those <50 years and those ≥50 years without comorbidities. We analysed 5411 patients with virological failure and 5621 with immunologic failure. Our failure outcomes were defined to be in‐line with the World Health Organization 2016 guidelines. Cox regression analysis was used to analyse time to first virological and immunological failure.ResultsThe incidence of virologic failure was 7.72/100 person‐years. Virological failure was less likely in patients with better adherence and higher CD4 count at cART initiation. Those acquiring HIV through intravenous drug use were more likely to have virological failure compared to those infected through heterosexual contact. On univariate analysis, patients aged <50 years without comorbidities were more likely to experience virological failure than those aged ≥50 years with comorbidities (hazard ratio 1.75, 95% confidence interval (CI) 1.31 to 2.33, p < 0.001). However, the multivariate model showed that age‐related comorbidities were not significant factors for virological failure (hazard ratio 1.31, 95% CI 0.98 to 1.74, p = 0.07). There were 391 immunological failures, with an incidence of 2.75/100 person‐years. On multivariate analysis, those aged <50 years without comorbidities (p = 0.025) and age <50 years with comorbidities (p = 0.001) were less likely to develop immunological failure compared to those aged ≥50 years with comorbidities.ConclusionsIn our Asia regional cohort, age‐associated comorbidities did not affect virologic outcomes of cART. Among those with comorbidities, patients <50 years old showed a better CD4 response.
Chemokine-triggered microtubule polymerization promotes neutrophil chemotaxis and invasion but not transendothelial migration
Authors: Yadav Sandeep Kumar , Stojkov Darko , Feigelson Sara W , Roncato Francesco , Simon Hans-Uwe , Yousefi Shida , Alon Ronen 
Published: February 2019

Abstract
Microtubules (MTs) are critically involved in the transport of material within cells, but their roles in chemotactic leukocyte motility and effector functions are still obscure. Resting neutrophils contain few MTs assembled in an MT organizing center (MTOC) behind their multilobular nuclei. Using a probe of real-time tubulin polymerization, SiR-tubulin, we found that neutrophils elongated their MTs within minutes in response to signals from the two prototypic chemotactic peptides, CXCL1 and fMLP. Taxol, a beta-tubulin binding and MT stabilizing drug, was found to abolish this CXCL1- and fMLP-stimulated MT polymerization. Nevertheless, taxol treatment as well as disruption of existing and de novo generated MTs did not impair neutrophil protrusion and squeezing through IL-1β-stimulated endothelial monolayers mediated by endothelial deposited CXCL1 and neutrophil CXCR2. Notably, CXCL1-dependent neutrophil TEM was not associated with neutrophil MT polymerization. Chemokinetic neutrophil motility on immobilized CXCL1 was also not associated with MT polymerization, and taxol treatment did not interfere with this motility. Nevertheless, and consistent with its ability to suppress MT polymerization induced by soluble CXCL1 and fMLP, taxol treatment inhibited neutrophil chemotaxis toward both chemotactic peptides. Taxol treatment also suppressed CXCL1- and fMLP-triggered elastase-dependent neutrophil invasion through collagen I barriers. Collectively, our results highlight de novo chemoattractant-triggered MT polymerization as key for neutrophil chemotaxis and elastase-dependent invasion but not for chemotactic neutrophil crossing of inflamed endothelial barriers.
Evolutionary implications of fetal and maternal microvillous surfaces in epitheliochorial placentae
Authors: Kazemian Ali , Hooshmandabbasi Reyhaneh , Schraner Elisabeth M. , Boos Alois , Klisch Karl 
Published: February 2019

AbstractAccording to the “parent‐offspring conflict hypothesis” the rapid evolution and diversification of the mammalian placenta is driven by divergent optima of resource allocation between fetus and mother. The fetus has an interest to maximize its resource intake, while the mother has an interest to restrict the transfer of resources, and thus retain resources for subsequent pregnancies. In the epitheliochorial placenta, the contacting fetal and maternal surfaces at the feto‐maternal interface are covered with microvilli, which leads to an increase of membrane surfaces available for transport processes. Because membranes are the site of active transport, the conflict hypothesis predicts that the fetal surfaces at the feto‐maternal interfaces are larger than the maternal ones. We use transmission electron microscopy and a stereological method to estimate the factors by which the apical fetal and maternal membranes are enlarged by the microvilli. Ten species with an epitheliochorial placenta were studied. Focused ion beam—scanning electron microscopy (FIB‐SEM) was used to create three‐dimensional models of the interdigitating microvilli of the bovine and porcine placenta. In all species, the fetal surface was larger than the maternal. This was due to a higher number of fetal microvilli and to the presence of membrane folds at the base of the fetal, but not of maternal microvilli. Our results suggest that the ultrastructural morphology of the feto‐maternal interface in the epitheliochorial placenta is shaped by conflicting interests between fetus and mother and thus represent a so far neglected arena of the parent‐offspring conflict.
Comparing invasive with MRI‐derived intracranial pressure measurements in healthy elderly and brain trauma cases: A pilot study
Authors: Burman Ritambhar , Shah Ashish H. , Benveniste Ronald , Jimsheleishvili George , Lee Sang H. , Loewenstein David , Alperin Noam 
Published: February 2019

BackgroundIntracranial pressure (ICP) is an important physiological parameter in several neurological disorders. Considerable effort has been made to measure ICP noninvasively. MR‐based ICP (MR‐ICP) is a nonempirical method based on principles of cerebrospinal fluid (CSF) physiology, where ICP is obtained from measurements of blood and CSF flows to and from the cranium during the cardiac cycle.PurposeTo compare MR‐ICP with invasive ICP measurements obtained using lumbar puncture (LP) or external ventricular drainage (EVD).Study TypeProspective, cross‐sectional, observational study.SubjectsTen cognitively healthy elderly subjects (age 69.6 ± 6.6 years; seven females) and six brain trauma patients (age 36.8 ± 19.7 years; two females).Field StrengthVelocity encoding cine phase‐contrast at 1.5 T and 3 T.AssessmentMR‐ICP and craniospinal compliance distribution were estimated from arterial inflow and venous outflow to and from cranium, and craniospinal CSF flow at the upper cervical region, measured using cine phase contrast MRI. LP (done 177 ± 163 days after scan) and EVD measurements (at the time of scan) were performed in lateral recumbent and supine positions, respectively.Statistical TestsLinear regression was used to assess the relationships of MR‐ICP with invasive ICP, and the dependency of these measurements on age, weight, height, and BMI. A Shapiro–Wilks test and Bland–Altman plot were respectively used to evaluate the normality and agreement between these two pressure distributions. Student's t‐test was used throughout the analysis to compare differences between the EVD and LP cohorts.ResultsIn the combined cohort, MR‐ICP and invasive ICP were positively correlated (r = 0.95, P < 0.001), with invasive ICP being higher than MR‐ICP by 2.2 mmHg on average. In the healthy cohort, the cranial contribution to total craniospinal compliance was negatively correlated with MR‐ICP (r = −0.90, P < 0.001).Data ConclusionMR‐ICP provides a reliable estimate of ICP, with 14 out of 16 datapoints within the clinically acceptable error. Craniospinal compliance distribution plays a role in modulating ICP in supine position.Level of Evidence: 3Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2019;50:975–981.
Nicotinamide mononucleotide alters mitochondrial dynamics by SIRT3‐dependent mechanism in male mice
Authors: Klimova Nina , Long Aaron , Kristian Tibor 
Published: February 2019

AbstractNicotinamide adenine dinucleotide (NAD+) is a central signaling molecule and enzyme cofactor that is involved in a variety of fundamental biological processes. NAD+ levels decline with age, neurodegenerative conditions, acute brain injury, and in obesity or diabetes. Loss of NAD+ results in impaired mitochondrial and cellular functions. Administration of NAD+ precursor, nicotinamide mononucleotide (NMN), has shown to improve mitochondrial bioenergetics, reverse age‐associated physiological decline, and inhibit postischemic NAD+ degradation and cellular death. In this study, we identified a novel link between NAD+ metabolism and mitochondrial dynamics. A single dose (62.5 mg/kg) of NMN, administered to male mice, increases hippocampal mitochondria NAD+ pools for up to 24 hr posttreatment and drives a sirtuin 3 (SIRT3)‐mediated global decrease in mitochondrial protein acetylation. This results in a reduction of hippocampal reactive oxygen species levels via SIRT3‐driven deacetylation of mitochondrial manganese superoxide dismutase. Consequently, mitochondria in neurons become less fragmented due to lower interaction of phosphorylated fission protein, dynamin‐related protein 1 (pDrp1 [S616]), with mitochondria. In conclusion, manipulation of mitochondrial NAD+ levels by NMN results in metabolic changes that protect mitochondria against reactive oxygen species and excessive fragmentation, offering therapeutic approaches for pathophysiologic stress conditions.
The Effects of a Verbal and a Figural Creativity Training on Different Facets of Creative Potential
Authors: Fink Andreas , Reim Thomas , Benedek Mathias , Grabner Roland H. 
Published: February 2019

AbstractThis study investigated the effects of different types of creativity interventions on different facets of creative potential, also including more school‐related creativity demands. In a sample of 77 fourth‐graders in the age between 9 and 12 years, we administered a verbal and a figural creativity training, realized in two school lessons over two consecutive days each. As outcome measures, creative potential in both the verbal and the figural domain by means of two well‐established divergent thinking tasks was assessed. As additional measures of creative potential, a story completion task and a picture painting task were administered to examine training effects on more school‐related types of creative behavior. The verbal training was found to increase both verbal and figural divergent thinking ability, but not creative potential in the story completion and the picture painting task. The figural training yielded significant training effects only regarding the picture painting task. Findings suggest a specific training effect of the figural creativity training, and moreover indicate that the verbal creativity training, rather than stimulating “verbal” creative abilities per se, was more strongly concerned with domain‐general creativity processes including ideational fluency, flexibility, and originality that are characteristics of divergent thinking tasks across different domains.
Cumulative smoking exposure and cessation associated with the recurrence of periodontitis in periodontal maintenance therapy: A 6‐year follow‐up
Authors: Costa Fernando Oliveira , Cota Luís Otávio Miranda 
Published: February 2019

AbstractBackgroundThis study followed individuals in periodontal maintenance therapy (PMT) over 6 years and longitudinally evaluated the effects of cumulative smoking exposure and duration of smoking cessation on the recurrence of periodontitis.MethodsFrom a 6‐year follow‐up cohort study with 212 individuals in PMT, 142 patients who attended at least one PMT visit within 12 months were determined to be elegible. According to smoking habits they were categorized into three groups: non‐smokers (NS; n = 95), former smokers (FS; n = 22), and current smokers (CS; n = 25). Complete periodontal examination and smoking habits were evaluated at two instances: T1 (first time, after active periodontal therapy) and T2 (second time, 6 years). Associations between the recurrence of periodontitis (RP; probing depth ≥4 mm and clinical attachment loss ≥3 mm, together with the presence of bleeding on probing and/or suppuration), smoking status, and potential risk variables were analyzed by univariate and multivariate analysis, when appropriate.ResultsThe RP in NS, FS, and CS groups was 44.2%, 68.2%, and 80.0%, respectively. After adjusting for confounders, odds ratios (95% confidence interval) for the RP in T2 was 2.80 (2.11 to 5.14) for FS and 5.97 (3.58 to 9.88) for CS. There was a significant dose‐response relationship between pack‐years of smoking and the RP, as well as a significant decrease in the risk for the RP as the years of smoking cessation increased.ConclusionDuring 6 years of PMT, cumulative smoking exposure and shorter time since smoking cessation were significantly associated with the RP.
Systemic treatment for metastatic colorectal cancer in the era of precision medicine
Authors: Sandhu Jaideep , Lavingia Viraj , Fakih Marwan 
Published: February 2019

AbstractThe treatment of metastatic colorectal cancer has evolved over the last two decades with the FDA approval of several cytotoxic, biological, and targeted agents. In this paper, we review the impact of sidedness, RAS, BRAF, HER‐2, and other immune biomarkers on metastatic colorectal cancer treatment selection and sequencing in both the palliative and curative intent settings.
Historical perspective: Two decades of progress in treating metastatic colorectal cancer
Authors: Lee Rachel M. , Cardona Kenneth , Russell Maria C. 
Published: February 2019

AbstractColorectal cancer is the third most commonly diagnosed cancer in the United States. While screening methods strive to improve rates of early stage detection, 25% of patients have metastatic disease at the time of diagnosis, with the most common sites being the liver, lung, and peritoneum. While once perceived as hopeless, the last two decades have seen substantial strides in the medical, surgical, and regional therapies to treat metastatic disease offering significant improvements in survival.
Complex Posttraumatic Stress Disorder in Patients Exposed to Emotional Neglect and Traumatic Events: Latent Class Analysis
Authors: Eidhof Marloes B. , Djelantik A. A. A. Manik J. , Klaassens Ellen R. , Kantor Viktoria , Rittmansberger Doris , Sleijpen Marieke , Steenbakkers Anne , Weindl Dina , ter Heide F. Jackie June 
Published: February 2019

AbstractThe inclusion of a complex posttraumatic stress disorder (CPTSD) diagnosis in the 11th revision of the International Classification of Diseases reflects growing evidence that a subgroup of individuals with PTSD also suffer from disturbances in emotion regulation, interpersonal skills, and self‐concept, which together are termed “disturbances in self‐organization” (DSO). Although CPTSD is assumed to result from exposure to complex traumatic events, emotional neglect may be an important contributor. This study investigated the presence of CPTSD, defined by endorsement of PTSD and DSO symptoms in a clinical postwar generation sample. The sample consisted of 218 patients who had been exposed to emotional neglect in childhood, a subgroup of whom had also been exposed to potentially traumatic events. Using items from the Harvard Trauma Questionnaire and the Brief Symptom Inventory, a latent class analysis revealed two classes: high endorsement of almost all CPTSD symptoms (n = 83; 38.1%) and low endorsement of all CPTSD symptoms (n = 135; 61.9%). Contrary to our hypothesis, no DSO‐only class was found. The R3step method showed gender and number of traumatic events to be significant predictors of class membership. Compared to the low endorsement class, individuals in the CPTSD class were more likely to be female, p = .013, and to report a higher number of traumatic experiences, p < .001. The potential intermediary role of emotional neglect in the development of DSO and CPTSD is discussed.
Intra‐ and Inter‐Rater Agreement Describing Myometrial Lesions Using Morphologic Uterus Sonographic Assessment: A Pilot Study
Authors: Rasmussen Christina Kjaergaard , Van den Bosch Thierry , Exacoustos Caterina , Manegold‐Brauer Gwendolin , Benacerraf Beryl R. , Froyman Wouter , Landolfo Chiara , Condorelli Margherita , Egekvist Anne G. , Josefsson Hampus , Leone Francesco Paolo Giuseppe , Jokubkiene Ligita , Zannoni Letizia , Epstein Elisabeth , Installé Arnaud , Dueholm Margit 
Published: February 2019

ObjectivesTo evaluate the intra‐ and inter‐rater agreement for myometrial lesions using Morphologic Uterus Sonographic Assessment terminology.MethodsThirteen raters with high (n = 6) or medium experience (n = 7) assessed 30 3‐dimensional ultrasound clips with (n = 20) and without (n = 10) benign myometrial lesions. Myometrial lesions were reported as poorly or well defined and then systematically evaluated for the presence of individual features. The clips were blindly assessed twice (at a 2‐month interval). Intra‐ and inter‐rater agreements were calculated with κ statistics.ResultsThe reporting of poorly defined lesions reached moderate intra‐rater agreement (κ = 0.49 [high experience] and 0.47 [medium experience]) and poor inter‐rater agreement (κ = 0.39 [high experience] and 0.25 [medium experience]). The reporting of well‐defined lesions reached good to very good intra‐rater agreement (κ = 0.73 [high experience] and 0.82 [medium experience]) and good inter‐rater agreement (κ = 0.75 [high experience] and 0.63 [medium experience]). Most individual features associated with ill‐defined lesions reached moderate intra‐ and inter‐rater agreement among highly experienced raters (κ = 0.41–0.60). The least reproducible features were myometrial cysts, hyperechoic islands, subendometrial lines and buds, and translesional flow (κ = 0.11–0.34). Most individual features associated with well‐defined lesions reached moderate to good intra‐ and inter‐rater agreement among all observers (κ = 0.41–0.80). The least reproducible features were a serosal contour, asymmetry, a hyperechoic rim, and fan‐shaped shadows (κ = 0.00–0.35).ConclusionsThe reporting of well‐defined lesions showed excellent agreement, whereas the agreement for poorly defined lesions was low, even among highly experienced raters. The agreement on identifying individual features varied, especially for features associated with ill‐defined lesions. Guidelines on minimum requirements for features associated with ill‐defined lesions to be interpreted as poorly defined lesions may improve agreement.
An Interesting Observation Regarding Retrograde Vertebral Artery Flow in Patients With Dialysis Access Fistulas
Authors: Naidich James B. , Weiss Amanda , Molmenti Ernesto P. , Naidich Jason J. , Pellerito John S. 
Published: February 2019

ObjectivesRetrograde vertebral artery flow, the steal phenomenon, is most frequently caused by a flow‐limiting stenosis of the proximal subclavian artery. The reversal of flow can be incomplete, resulting in bidirectional flow: retrograde in systole and antegrade in diastole. Less often, retrograde vertebral artery flow is the consequence of increased subclavian flow, as might occur with a well‐functioning dialysis access fistula. Our objective was to evaluate bidirectional vertebral artery flow associated with dialysis access fistulas.MethodsWe retrospectively reviewed the direction of flow through the vertebral artery in systole and diastole of 335 patients with dialysis fistulas who had undergone extracranial cerebral vascular Doppler examinations.ResultsFifteen patients had retrograde flow in their vertebral artery ipsilateral with the side of their fistula. There was completely reversed flow in 1 patient and bidirectional flow in the other 14. For each of these 14, the flow was antegrade in early systole and retrograde in diastole. Compression of the fistula restored the antegrade flow.ConclusionsUnder conditions of reduced subclavian artery flow, bidirectional vertebral artery flow will be retrograde in early systole and antegrade in diastole. Under conditions of increased subclavian artery flow, bidirectional flow through the vertebral artery will be antegrade in early systole and retrograde in diastole.
A composite method to identify desertification ‘hotspots’ and ‘brightspots’
Authors: Singh Rimjhim Bhatnagar , Ajai  
Published: February 2019

AbstractDesertification has become one of the greatest environmental concerns of our planet. Implementation of the action plans for arresting land degradation and for employing rehabilitation measures over a large spatial scale is not feasible due to the amount of time, effort, and cost involved. However, if the ‘hotspots’ the ‘brightspots’, and the ‘potential areas’ are identified, the task would be relatively easy. In this paper, a method is proposed to identify the pieces of degraded land with varying severity levels (in terms of ‘hotspots’, ‘brightspots’, and ‘potential areas’), using Bowen ratio, land surface temperature (LST), Ra, and Normalized Difference Vegetation Index (NDVI). Although the zone falls in the semiarid class, the microclimate analysis of the study area revealed high aridity. The combined analysis of LST, Ra, and NDVI helped in identifying the areas susceptible to land degradation (particularly, salinization and water erosion). Analysis of the vegetation type and condition showed their variable roles towards the protection of soil from erosion, drought, and fire. Using these analyses together with the ecosystemic approach of Bowen ratio, ‘hotspots’, ‘brightspots’, and ‘potential areas’ were identified at the pixel level. For validation, Desertification Status Map was employed. The investigations revealed that around 49% of the study area falls under the category of ‘hotspots’ (with an error estimate of 13%) and another 49% as ‘brightspots’. The findings revealed that instead of targeting the entire area for implementation of the mitigation measures with the same efforts, it would be better to focus on the specific pieces of land (‘hotspots’) to optimally utilize the available resources.