bluuebunny/crossref_metadata_2025_split huggingface dataset:
GBT1118, a potent allosteric modifier of hemoglobin O2affinity, increases tolerance to severe hypoxia in mice
Authors: Dufu Kobina , Yalcin Ozlem , Ao-ieong Eilleen S. Y. , Hutchaleelala Athiwat , Xu Qing , Li Zhe , Vlahakis Nicholas , Oksenberg Donna , Lehrer-Graiwer Josh , Cabrales Pedro 
Published: May 2017

Adaptation to hypoxia requires compensatory mechanisms that affect O2transport and utilization. Decreased hemoglobin (Hb) O2affinity is considered part of the physiological adaptive process to chronic hypoxia. However, this study explores the hypothesis that increased Hb O2affinity can complement acute physiological responses to hypoxia by increasing O2uptake and delivery compared with normal Hb O2affinity during acute severe hypoxia. To test this hypothesis, Hb O2affinity in mice was increased by oral administration of 2-hydroxy-6-{[(2 S)-1-(pyridine-3-carbonyl)piperidin-2yl] methoxy}benzaldehyde (GBT1118; 70 or 140 mg/kg). Systemic and microcirculatory hemodynamics and oxygenation parameters were studied during hypoxia in awake-instrumented mice. GBT1118 increased Hb O2affinity and decreased the Po2at which 50% of Hb is saturated with O2(P50) from 43 ± 1.1 to 18.3 ± 0.9 mmHg (70 mg/kg) and 7.7 ± 0.2 mmHg (140 mg/kg). In a dose-dependent fashion, GBT1118 increased arterial O2saturation by 16% (70 mg/kg) and 40% (140 mg/kg) relative to the control group during 5% O2hypoxia. In addition, a GBT1118-induced increase in Hb O2affinity reduced hypoxia-induced hypotension compared with the control group. Moreover, microvascular blood flow was higher during hypoxia in GBT1118-treated groups than the control group. The increased O2saturation and improved blood flow in GBT1118-treated groups preserved higher interstitial tissue Po2than in the control group during 5% O2hypoxia. In conclusion, increased Hb O2affinity enhanced physiological tolerance to hypoxia, as evidenced by improved hemodynamics and tissue oxygenation. Therefore, pharmacologically induced increases in Hb O2affinity become a potential therapeutic approach to improve tissue oxygenation in pulmonary diseases characterized by severe hypoxemia.NEW & NOTEWORTHY This study establishes that pharmacological modification of hemoglobin O2affinity can be a promising and novel therapeutic strategy for the treatment of hypoxic hypoxia and paves the way for the clinical development of molecules that prevent hypoxemia.
ВИКОРИСТАННЯ ІНФОРМАЦІЙНИХ ТЕХНОЛОГІЙ ДЛЯ ВІДНОВЛЕННЯ ПАЦІЄНТІВ ПІСЛЯ ЕНДОПРОТЕЗУВАННЯ КУЛЬШОВОГО СУГЛОБА
Authors: Hlyniana О. О. , Popadiuha Yu. A. 
Published: May 2017

The usage of information technologies for recovery after total hip replacement was considered. The algorithm of making a decision by a rehabilitologist during the procedure with mechanical facilities was developed. High effectiveness of mechanical facilities usage for patients’ recovery was observed.
Migraine and Cerebrovascular Atherosclerosis in Patients With Ischemic Stroke
Authors: van Os Hendrikus J.A. , Mulder Inge A. , Broersen Alexander , Algra Ale , van der Schaaf Irene C. , Kappelle L. Jaap , Velthuis Birgitta K. , Terwindt Gisela M. , Schonewille Wouter J. , Visser Marieke C. , Ferrari Michel D. , van Walderveen Marianne A.A. , Wermer Marieke J.H. 
Published: May 2017

Background and Purpose—
Migraine is a well-established risk factor for ischemic stroke, but migraine is also related to other vascular diseases. This study aims to investigate the association between migraine and cerebrovascular atherosclerosis in patients with acute ischemic stroke.

Methods—
We retrieved data on patients with ischemic stroke from the DUST (Dutch Acute Stroke Study). Migraine history was assessed with a migraine screener and confirmed by telephone interview based on the ICHD criteria (International Classification of Headache Disorders). We assessed intra- and extracranial atherosclerotic changes and quantified intracranial internal carotid artery calcifications as measure of atherosclerotic burden on noncontrast computed tomography and computed tomographic angiography. We calculated risk ratios with adjustments for possible confounders with multivariable Poisson regression analyses.

Results—
We included 656 patients, aged 18 to 99 years, of whom 53 had a history of migraine (29 with aura). Patients with migraine did not have more frequent atherosclerotic changes in intracranial (51% versus 74%; adjusted risk ratio, 0.82; 95% confidence interval, 0.64–1.05) or extracranial vessels (62% versus 79%; adjusted risk ratio, 0.93; 95% confidence interval, 0.77–1.12) than patients without migraine and had comparable internal carotid artery calcification volumes (largest versus medium and smallest volume tertile, 23% versus 35%; adjusted risk ratio, 0.93; 95% confidence interval, 0.57–1.52).

Conclusions—
Migraine is not associated with excess atherosclerosis in large vessels in patients with acute ischemic stroke. Our findings suggest that the biological mechanisms by which migraine results in ischemic stroke are not related to macrovascular cerebral atherosclerosis.
Self-Reported Stroke Risk Stratification
Authors: Howard George , McClure Leslie A. , Moy Claudia S. , Howard Virginia J. , Judd Suzanne E. , Yuan Ya , Long D. Leann , Muntner Paul , Safford Monika M. , Kleindorfer Dawn O. 
Published: May 2017

Background and Purpose—
The standard for stroke risk stratification is the Framingham Stroke Risk Function (FSRF), an equation requiring an examination for blood pressure assessment, venipuncture for glucose assessment, and ECG to determine atrial fibrillation and heart disease. We assess a self-reported stroke risk function (SRSRF) to stratify stroke risk in comparison to the FSRF.

Methods—
Participants from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) were evaluated at baseline and followed for incident stroke. The FSRF was calculated using directly assessed stroke risk factors. The SRSRF was calculated from 13 self-reported questions to exclude those with prevalent stroke and assess stroke risk. Proportional hazards analysis was used to assess incident stroke risk using the FSRF and SRSRF.

Results—

Over an average 8.2-year follow-up, 939 of 23 983 participants had a stroke. The FSRF and SRSRF produced highly correlated risk scores (
r
Spearman
=0.852; 95% confidence interval, 0.849–0.856); however, the SRSRF had higher discrimination of stroke risk than the FSRF (c
SRSRF
=0.7266; 95% confidence interval, 0.7076–0.7457; c
FSRF
=0.7075; 95% confidence interval, 0.6877–0.7273;
P
=0.0038). The 10-year stroke risk in the highest decile of predicted risk was 11.1% for the FSRF and 13.4% for the SRSRF.

Conclusions—
A simple self-reported questionnaire can be used to identify those at high risk for stroke better than the gold standard FSRF. This instrument can be used clinically to easily identify individuals at high risk for stroke and also scientifically to identify a subpopulation enriched for stroke risk.
Pro-inflammatory activation of primary microglia and macrophages increases 18 kDa translocator protein expression in rodents but not humans
Authors: Owen David R , Narayan Nehal , Wells Lisa , Healy Luke , Smyth Erica , Rabiner Eugenii A , Galloway Dylan , Williams John B , Lehr Joshua , Mandhair Harpreet , Peferoen Laura AN , Taylor Peter C , Amor Sandra , Antel Jack P , Matthews Paul M , Moore Craig S 
Published: May 2017

The 18kDa Translocator Protein (TSPO) is the most commonly used tissue-specific marker of inflammation in positron emission tomography (PET) studies. It is expressed in myeloid cells such as microglia and macrophages, and in rodent myeloid cells expression increases with cellular activation. We assessed the effect of myeloid cell activation on TSPO gene expression in both primary human and rodent microglia and macrophages in vitro, and also measured TSPO radioligand binding with 3H-PBR28 in primary human macrophages. As observed previously, we found that TSPO expression increases (∼9-fold) in rodent-derived macrophages and microglia upon pro-inflammatory stimulation. However, TSPO expression does not increase with classical pro-inflammatory activation in primary human microglia (fold change 0.85 [95% CI 0.58–1.12], p = 0.47). In contrast, pro-inflammatory activation of human monocyte-derived macrophages is associated with a reduction of both TSPO gene expression (fold change 0.60 [95% CI 0.45–0.74], p = 0.02) and TSPO binding site abundance (fold change 0.61 [95% CI 0.49–0.73], p < 0.0001). These findings have important implications for understanding the biology of TSPO in activated macrophages and microglia in humans. They are also clinically relevant for the interpretation of PET studies using TSPO targeting radioligands, as they suggest changes in TSPO expression may reflect microglial and macrophage density rather than activation phenotype.
An Observational Study of Suicide Death in Homeless and Precariously Housed People in Toronto
Authors: Sinyor Mark , Kozloff Nicole , Reis Catherine , Schaffer Ayal 
Published: May 2017

Objective: Homelessness has been identified as an important risk factor for suicide death, but there is limited research characterising homeless people who die by suicide. The goal of this study is to identify personal, clinical, and suicide method-related factors that distinguish homeless and precariously housed people who die from suicide from those who are not homeless at the time of suicide. Methods: Coroner records were reviewed for all suicide deaths in Toronto from 1998 to 2012. Data abstracted included housing status as well as other demographics, clinical variables such as the presence of mental illness, and suicide method. Results: Of 3319 suicide deaths, 60 (1.8%) were homeless and 230 (6.9%) were precariously housed. Homeless and precariously housed people were each younger than nonhomeless people ( P < 0.0001). Compared with nonhomeless, homeless people were more likely to be male and less likely to be married, to have interpersonal conflict, or to leave a suicide note. Homeless people and precariously housed were more likely to have died by fall/jump than nonhomeless people (62%, 57%, and 29%, respectively). Conclusions: Homeless and precariously housed people are overrepresented among suicide deaths in a large urban center and differ demographically, clinically, and in their suicide method from nonhomeless people who die by suicide. Targeted suicide prevention strategies should aim to address factors specific to homeless people.
Analyzing Circle of Willis blood flow in ischemic stroke patients through 3D Stroke Arterial Flow Estimation
Authors: Chien Aichi , Viñuela Fernando 
Published: May 2017

Background The objective of ischemic stroke (IS) treatment is to achieve revascularization in cerebral arteries to restore blood flow. However, there is no available method to extract arterial flow data from clinical CTA images. We developed 3D Stroke Arterial Flow Estimation (SAFE), which provides blood flow data throughout the Circle of Willis based on 3D CTA and allows comparison of arterial flow distribution in the brain. Methods We implemented a newly developed 3D vascular reconstruction algorithm for clinical stroke CTA images. Based on the patient-specific vascular structure, SAFE calculates time-resolved blood flow information for the entire Circle of Willis and allows quantitative flow study of IS cases. Clinical IS cases are presented to demonstrate the feasibility. Four patients with CTA images and CT perfusion data were studied. To validate the SAFE analysis, correlation analysis comparing blood flow at the MCA, ICA, and BA was performed. Results Different blood flow patterns were found in individual IS patients. Altered flow patterns and high collateral flow rates were found near occlusions in all cases. Quantitative comparison of blood flow data showed that SAFE obtained flow data and CTP were significantly correlated and provide complementary information about cerebral blood flow for individual patients. Conclusions We present SAFE analysis for collecting detailed time-resolved cerebral arterial flow data in the entire Circle of Willis for IS. Further study with more cases may be important to test the clinical utilization of SAFE and helpful to the study of the underlying hemodynamics of stroke.
When support is needed: Social support solicitation and provision in an online alcohol use disorder forum
Authors: Liu Yan , Kornfield Rachel , Shaw Bret R , Shah Dhavan V , McTavish Fiona , Gustafson David H 
Published: May 2017

Background Obtaining adequate social support presents a challenge for many in addiction recovery. Increasingly, individuals in recovery use online forums to exchange support with peers, yet it is unclear which help-seeking strategies most effectively recruit peer support, and which forms of support are most valued by recipients. Methods This study applied quantitative content analysis to examine social support solicitation and delivery in an online forum for alcohol use disorder (AUD). We compared the frequency with which peers provided informational, emotional, and companionship support after solicitations that: (1) were direct or indirect, (2) disclosed positive or negative emotions, and (3) mentioned or did not mention recovery problems. We assessed likelihood that recipients would express gratitude after receiving each type of support, and assessed whether the “match” between solicitation and disclosure styles influenced rates of gratitude expression. Results Emotional disclosures, whether positive or negative, received the highest volume of supportive replies. Emotional support was the most common response to solicitations overall, and was disproportionately offered after recipients disclosed positive emotions. Informational support was disproportionately offered after recipients disclosed negative emotions or recovery problems, or explicitly requested help. Regardless of their solicitation style, recipients expressed more gratitude after receiving emotional support than other support types. Conclusions Providing emotional support was common in an online AUD forum, and precipitated expressing gratitude from recipients to support providers. The results may be helpful in guiding participants to more effectively obtain and provide recovery support in online forums.
Return to Preoperative Function After Autologous Cartilage Implantation of the Knee in Active Military Servicemembers
Authors: Zarkadis Nicholas J. , Kusnezov Nicholas A. , Garcia EStephan J. , Pallis Mark P. , Waterman Brian R. 
Published: May 2017

Background: Autologous chondrocyte implantation (ACI) has been shown to provide adequate durability, pain relief, and improved long-term functional outcomes in the average patient, but proof of its efficacy in individuals with greater than average physical demands is scarce. Further knowledge is required to understand which patients may benefit from ACI and to identify which risk factors are associated with failure to return to the preinjury activity level. Purpose: To determine the occupational outcomes, rates of reoperation, and variables predictive of suboptimal outcomes after ACI. Study Design: Case series; Level of evidence, 4. Methods: All active-duty military servicemembers in the United States who underwent ACI of the knee between 2004 and 2014 were identified. Demographic information, injury characteristics, surgical variables, and clinical and surgical outcomes were extracted from the medical record. Univariate and multivariate analyses were used to determine significant independent predictors of clinical and surgical failures. Results: A total of 90 patients (91 knees) met the inclusion criteria. The cohort was predominantly male (86%), with a mean age of 34.5 ± 6.3 years (range, 20-50 years). The most common location of the articular cartilage lesion was the patellofemoral compartment (54 lesions, 59%), and the mean Outerbridge grade and size were 3.8 ± 0.4 and 4.00 ± 2.77 cm2 (range, 1.2-15.0 cm2), respectively. A total of 72 patients (79%) had at least 1 previous knee procedure. Nearly three-quarters of patients (71%) underwent concomitant procedures. At a mean follow-up of 59.9 ± 27.1 months (range, 24.0-140.1 months), 60% of our patients reported significant improvement in knee pain and did not require further surgical intervention. Multivariate analysis identified age <30 years as the only significant independent predictor of both clinical ( P = .011) and overall failure ( P = .014). Moderate-demand military occupational specialties ( P = .036), exclusive involvement of the patellofemoral compartment ( P = .045), and use of a periosteal patch ( P = .0173) were additionally found to be independent predictors of surgical failure. Conclusion: Treatment of articular cartilage defects of the knee with ACI in physically active young individuals can return nearly two-thirds of individuals to daily activity with decreased pain and improved function. Risk factors for failure after ACI surgery were age younger than 30 years, lower demand occupation, exclusive involvement of the patellofemoral compartment, prior microfracture, and use of a periosteal patch.
A novel lightweight URL phishing detection system using SVM and similarity index
Authors: Zouina Mouad , Outtaj Benaceur 
Published: May 2017

AbstractThe phishing is a technique used by cyber-criminals to impersonate legitimate websites in order to obtain personal information. This paper presents a novel lightweight phishing detection approach completely based on the URL (uniform resource locator). The mentioned system produces a very satisfying recognition rate which is 95.80%. This system, is an SVM (support vector machine) tested on a 2000 records data-set consisting of 1000 legitimate and 1000 phishing URLs records. In the literature, several works tackled the phishing attack. However those systems are not optimal to smartphones and other embed devices because of their complex computing and their high battery usage. The proposed system uses only six URL features to perform the recognition. The mentioned features are the URL size, the number of hyphens, the number of dots, the number of numeric characters plus a discrete variable that correspond to the presence of an IP address in the URL and finally the similarity index. Proven by the results of this study the similarity index, the feature we introduce for the first time as input to the phishing detection systems improves the overall recognition rate by 21.8%.
Analysis of Hypo- and Hyperphosphatemia in an Intensive Care Unit Cohort
Authors: Broman Marcus , Wilsson Amanda M. J. , Hansson Fredrik , Klarin Bengt 
Published: May 2017

BACKGROUND:
Blood phosphate levels are vulnerable to fluctuations and changes in phosphate levels are often neglected. The aim of this study was to evaluate whether deviations in phosphate levels correlate to higher 180-day overall mortality or morbidity.

METHODS:
Four thousand six hundred fifty-six patients with 19,467 phosphate values treated at the adult intensive care unit at Skåne University Hospital, Lund, Sweden during 2006–2014 were retrospectively divided into a control group and 3 study groups: hypophosphatemia, hyperphosphatemia, and a mixed group showing both hypo/hyperphosphatemia. Sex, age, disease severity represented by maximal organ system Sequential Organ Failure Assessment score, renal Sequential Organ Failure Assessment score, lowest ionized calcium value, and diagnoses classes were included in a Cox hazard model to adjust for confounding factors, with time to death in the first 180 days from the intensive care unit (ICU) admission as outcome.

RESULTS:
When compared to normophosphatemic controls, the hyperphosphatemic study group was associated with higher risk of death with a hazard ratio of 1.2 (98.3% confidence interval 1.0–1.5, P = .0089). Mortality in the hypophosphatemic or mixed study group did not differ from controls. The mixed group showed markedly longer ventilator times and ICU stays compared to all other groups.

CONCLUSIONS:
Phosphate alterations in ICU patients are common and associated with worse morbidity and mortality. Many underlying pathophysiologic mechanisms may play a role. A rapidly changing phosphate level or isolated hypo or hyperphosphatemia should be urgently corrected.
Haptoglobin Administration in Cardiovascular Surgery Patients: Its Association With the Risk of Postoperative Acute Kidney Injury
Authors: Kubota Kenta , Egi Moritoki , Mizobuchi Satoshi 
Published: May 2017

BACKGROUND:
Acute kidney injury (AKI) often occurs after cardiac surgery. During cardiac surgery, plasma free hemoglobin (fHb) would increase due to hemolysis. Since plasma fHb is thought to be nephrotoxic, haptoglobin, which is an fHb scavenger, may have the potential to prevent postoperative AKI (pAKI). However, there have been few studies in which the association of intraoperative administration of haptoglobin with the incidence of AKI after cardiac surgery was assessed.

METHODS:
This study was a retrospective observational study to assess the independent association of intraoperative administration of haptoglobin with the incidence pAKI in cardiac surgery patients. We screened cardiac surgery patients who required cardiopulmonary bypass from 2008 to 2015. We excluded patients who required renal replacement therapy preoperatively. We also excluded patients in whom descending aortic replacement was performed. pAKI was defined according to AKI Network criteria. A propensity score–matched model was used to adjust confounders. For sensitive analysis, we further developed a logistic regression model.

RESULTS:
We included 1326 patients in this study. The incidence of AKI in the total cohort was 25.5% (338 patients). Haptoglobin was administered in 260 patients (19.6%). In the crude cohort, the incidence of AKI in patients with haptoglobin administration was 24.6%, which was not significantly different from the incidence of 25.7% in those without haptoglobin administration (P = .72; odds ratio, 0.94 [95% confidence interval, 0.69–1.29]). After propensity score matching, we had 249 patients in each group (for a total of 498 patients). In this propensity score–matched cohort, the incidence of AKI in patients with haptoglobin administration was 22.5%, which was significantly lower than the incidence of 30.9% in those without haptoglobin administration (P = .033; odds ratio, 0.65 [0.43–0.97]). In our logistic regression model for the risk of pAKI, haptoglobin administration was independently associated with decreased risk of AKI (P = .029; adjusted odds ratio, 0.54 [0.31, 0.93]).

CONCLUSIONS:
In this hypothesis-generating, single-center retrospective observational study, intraoperative administration of haptoglobin was independently associated with lower risk of AKI after cardiovascular surgery.