bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel, point‐of‐care, whole‐blood assay utilizing dielectric spectroscopy is sensitive to coagulation factor replacement therapy in haemophilia A patients
Authors: Maji Debnath , Nayak Lalitha , Martin Janet , Sekhon Ujjal D. S. , Sen Gupta Anirban , Mohseni Pedram , Suster Michael A. , Ahuja Sanjay P. 
Published: July 2019

AbstractBackgroundReliable monitoring of coagulation factor replacement therapy in patients with severe haemophilia, especially those with inhibitors, is an unmet clinical need. While useful, global assays, eg thromboelastography (TEG), rotational thromboelastometry (ROTEM) and thrombin generation assay (TGA), are cumbersome to use and not widely available.ObjectiveTo assess the utility of a novel, point‐of‐care, dielectric microsensor – ClotChip – to monitor coagulation factor replacement therapy in patients with haemophilia A, with and without inhibitors.MethodsThe ClotChip Tpeak parameter was assessed using whole‐blood samples from children with severe haemophilia A, with (n = 6) and without (n = 12) inhibitors, collected pre‐ and postcoagulation factor replacement therapy. ROTEM, TGA and chromogenic FVIII assays were also performed. Healthy children (n = 50) served as controls.ResultsClotChip Tpeak values exhibited a significant decrease for samples collected postcoagulation factor replacement therapy as compared to baseline (pretherapy) samples in patients with and without inhibitors. A difference in Tpeak values was also noted at baseline among severe haemophilia A patients with inhibitors as compared to those without inhibitors. ClotChip Tpeak parameter exhibited a very strong correlation with clotting time (CT) of ROTEM, endogenous thrombin potential (ETP) and peak thrombin of TGA, and FVIII clotting activity.ConclusionsClotChip is sensitive to coagulation factor replacement therapy in patients with severe haemophilia A, with and without inhibitors. ClotChip Tpeak values correlate very well with ROTEM, TGA and FVIII assays, opening up possibilities for its use in personalized coagulation factor replacement therapy in haemophilia.
Risk of osteoporotic fractures as a consequence of haemophilia: A nationwide population‐based cohort study
Authors: Tuan Sheng‐Hui , Hu Li‐Yu , Sun Shu‐Fen , Huang Wan‐Yun , Chen Guan‐Bo , Li Min‐Hui , Liou I‐Hsiu 
Published: July 2019

AbstractAimLow bone mineral density occurs more commonly in patients with haemophilia (PWH) than the general population. However, the risk of haemophilia‐related osteoporotic fractures has not been well established. We aim to explore the relationship between haemophilia and the development of osteoporotic fractures following haemophilia.MethodsThis was a nationwide population‐based cohort study based on the data in the Taiwan National Health Insurance Research Database (TNHIRD). Patients who were diagnosed with haemophilia were selected. A comparison cohort was formed of patients without haemophilia who were matched according to age and sex. The incidence rate and the hazard ratios (HRs) of new‐onset osteoporotic fractures were calculated for both cohorts.ResultsThe haemophilia cohort consisted of 75 patients, and the comparison cohort comprised 300 matched control patients without haemophilia. The risk of osteoporotic fractures was higher in the haemophilia cohort than in the comparison cohort (HR = 5.41, 95% confidence interval [CI] = 2.42‐12.1, P < 0.001). After adjustments for age, sex, comorbidities, urbanizations and socio‐economic status, PWH were 4.37 times more likely to develop osteoporotic fractures (95% CI = 1.88‐10.17, P = 0.001) as compared to matched cohort. In addition, the incidence of newly diagnosed osteoporotic fractures was significantly increased after 5‐year follow‐up durations.ConclusionThough our study by TNHIRD presented methodologic flaws by its design nature, we observed that haemophilia may increase the risk of osteoporotic fractures and the cumulative incidence was significantly higher for PWH diagnosed more than 5 years. Clinicians should pay particular attention to osteoporotic fractures following haemophilia in PWH as they age.
Intermittent pneumatic compression in patients with ESRD. A systematic review
Authors: Torres Christian , Fuentes Harry E. , Saadaldin Hassan , Salazar Juan P. , Paz Luis H. , Diaz Luis , Doukky Rami , Hart Peter D. , Tafur Alfonso J. 
Published: July 2019

AbstractIntroduction:Patients with end‐stage renal disease (ESRD) experience frequent hemodialysis (HD) complications. Intradialytic hypotension (IDH) is a common complication presenting in approximately between 20 and 50% of HD sessions. Available interventions such as volume replacement or vasoactive medications are associated with significant side effects.Intermittent pneumatic compression (IPC) has been proposed as a feasible intervention for the prevention of IDH, treatment of peripheral arterial disease and venous ulcers. These devices apply intermittent pressure to the legs improving arterial blood flow, mobilization of pooled blood with an increase in venous return increasing the effective circulatory volume.Our goal was to identify the published clinical evidence on whether IPC has a circulatory benefit and is it well‐tolerated among patients receiving HD.Methods:We conducted a systematic review to identify studies assessing the efficacy and safety of IPC in patients with ESRD. Our primary outcome was IDH. Secondary outcomes such as HD comfort, ultrafiltration volume, and physical activity were collected. No restrictions where used and we included all observational and interventional studies. Two reviewers performed screening and study quality assessment.Findings:We included seven studies. Out of the seven studies, five addressed IDH, and the rest were included for secondary outcomes such as physical capacity and HD comfort. In one randomized crossover trial comparing exercise against IPC, 21 patients were randomized to 3 different arms (no intervention, cycling, IPC) a decrease in the rates of IDH with IPC was described (43%, 38%, and 24% respectively P = 0.014). The smaller studies corroborated these results. All studies where at high risk of bias.Discussion:IPC might offer significant benefits for patients undergoing HD not limited to prevention of IDH but also improvement of hemodialysis comfort and physical capacity. However, our results should be interpreted in the context of its limitations.
Evolution of Helicobacter pylori associated with gastroduodenal ulcers or erosions in children over the past 23 years: Decline or steady state?
Authors: Burgard Marie , Kotilea Kallirroi , Mekhael Joyce , Miendje‐Deyi Veronique Yvette , De Prez Carine , Vanderpas Jean , Cadranel Samy , Bontems Patrick 
Published: July 2019

AbstractBackgroundRecent data suggest that in children, the proportion of gastroduodenal ulcers/erosions associated with Helicobacter pylori infection is currently lower than expected. In this study, we trace this proportion over two decades.MethodsWe reviewed the reports of all upper gastrointestinal endoscopies with biopsies for histology and culture over the past 23 years. H pylori status was assessed using several invasive methods. The infection rate during different time periods was compared between children with lesions and controls.ResultsA total of 7849 endoscopies were performed in 5983 children (2874 F/3109 M, median age 7.6 years, range 0.1‐17.9 years). The endoscopy report was missing in 316 patients. At the first upper gastrointestinal endoscopy, 12.1% of the children presented with gastric and/or duodenal ulcers or erosions with an H pylori infection rate of 35.4%, whereas no such lesions were observed in 87.9% of children in whom the H pylori infection rate was 21.3%. The risk factors associated with such lesions were older age (P < 0.001), male sex (P = 0.002), and H pylori infection (P < 0.0001). Gastric ulcers were not significantly associated with H pylori (24% infected), whereas 52% of duodenal ulcers, 33% of gastric erosions, and 38% of duodenal erosions were associated with H pylori. The proportion of gastroduodenal lesions associated with H pylori remained stable over time. Children with H pylori infection and ulcers were older than those with H pylori infection without ulcers (P < 0.001).ConclusionsOur study indicates that in our pediatric population, the proportion of ulcers without H pylori infection is higher than previously suggested, and this prevalence has not changed over the past two decades.
Latin American Clinical Practice Guidelines on the Systemic Treatment of Psoriasis SOLAPSO – Sociedad Latinoamericana de Psoriasis (Latin American Psoriasis Society)
Authors: Kogan Nora , Raimondo Nélida , Gusis Simon E. , Izcovich Ariel , Abarca Duran Jorge A. , Barahona‐Torres Lilia , Blanco Orestes , Quintana Gerardo B. , Briones María C. , Castro Carla , Castro Vargas Evelyn G. , Criniti Juan , Diez de Medina Juan C. , Franco Manuel , Gómez Minerva , Levrero Patricia , Martínez López Jaime E. , Valenzuela Fernando 
Published: July 2019

AbstractThis Clinical Practice Guideline on the systemic treatment of Psoriasis includes the recommendations elaborated by a panel of experts from the Latin American Psoriasis Society SOLAPSO, who assessed the quality of the available evidence using the GRADE system and the PICO process to guide the literature search. To answer each question, the experts discussed the results of randomized controlled trials, observational studies and metanalysis evaluating the interventions identified (non‐biologics, biologics and phototherapy) in different populations of patients with moderate to severe plaque‐psoriasis, which was summarized in Tables ad‐hoc. The main end‐points considered to assess efficacy were PASI 50, 75, 90 and 100, PGA 0‐1 and significant improvement of health‐related quality of life. Specific adverse events, either severe or leading to treatment interruption, were also evaluated. The 31 recommendations included in this CPG follow the structure proposed by GRADE: direction (for or against) and strength (strong or weak). The goal of this CPG is to improve the management of patients with psoriasis by recommending interventions of proved benefit and providing a reference standard for the treating physician. Adhering to the contents of this CPG does not guarantee therapeutic success. The final decision on the specific treatment is the responsibility of the physician based on the individual circumstances and considering the values, the preferences and the opinions of the patient or caregivers.
METS‐IR, a novel simple insulin resistance indexes, is associated with hypertension in normal‐weight Chinese adults
Authors: Liu Xing Zhen , Fan Jie , Pan Shu Jun 
Published: July 2019

AbstractInsulin resistance (IR) plays a crucial role in the development of hypertension, so early recognition of IR is of substantial clinical importance for the management of hypertension. But traditional IR indexes are invasive, complex, and impractical. We aimed to evaluate the associations between three simple IR indexes and hypertension in different body mass index (BMI) categories. A total of 142 005 adults who did not take antihypertensive medication were included in this analysis. The ratio of triglycerides to high‐density lipoprotein cholesterol (TG/HDLc), the product of fasting triglycerides and glucose (TyG), and metabolic score for IR (METS‐IR) were calculated according to the corresponding formulas. The associations between them and hypertension were analyzed by logistic regression. Among the three indicators, only METS‐IR had positive correlations with blood pressure levels (all P < 0.001). After full adjustment, METS‐IR was significantly associated with hypertension in the normal BMI group but not in the elevated BMI group. The OR for hypertension in the normal BMI group in the highest quartile of METS‐IR was 2.884 (95% CI: 2.468‐3.369) in the total sample, 1.915 (95% CI: 1.614‐2.271) in females and 2.083 (95% CI: 1.717‐2.527) in males. Our findings indicate that METS‐IR, a simple and cost‐effective IR index, was strongly associated with hypertension in normal‐weight Chinese subjects. It could help monitor and manage hypertension in normal‐weight individuals.
NF‐κB/NKILA signaling modulates the anti‐cancerous effects of EZH2 inhibition
Authors: Duan Suzann , Chan Westin K. , Oman Andrew , Basile Dominic P. , Alvira Cristina M. , Buxton Iain L.O. , Iosef Cristiana 
Published: July 2019

AbstractA wealth of evidence supports the broad therapeutic potential of NF‐κB and EZH2 inhibitors as adjuvants for breast cancer treatment. We contribute to this knowledge by elucidating, for the first time, unique regulatory crosstalk between EZH2, NF‐κB and the NF‐κB interacting long non‐coding RNA (NKILA). We define a novel signaling loop encompassing canonical and non‐canonical actions of EZH2 on the regulation of NF‐κB/NKILA homeostasis, with relevance to breast cancer treatment. We applied a respective silencing approach in non‐transformed breast epithelial cells, triple negative MDA‐MB‐231 cells and hormone responsive MCF‐7 cells, and measured changes in EZH2/NF‐κB/NKILA levels to confirm their interdependence. We demonstrate cell line‐specific fluctuations in these factors that functionally contribute to epithelial‐to‐mesenchymal transition (EMT) remodelling and cell fate response. EZH2 inhibition attenuates MDA‐MB‐231 cell motility and CDK4‐mediated MCF‐7 cell cycle regulation, while inducing global H3K27 methylation and an EMT phenotype in non‐transformed cells. Notably, these events are mediated by a cell‐context dependent gain or loss of NKILA and NF‐κB. Depletion of NF‐κB in non‐transformed cells enhances their sensitivity to growth factor signaling and suggests a role for the host microenvironment milieu in regulating EZH2/NF‐κB/NKILA homeostasis. Taken together, this knowledge critically informs the delivery and assessment of EZH2 inhibitors in breast cancer.
Integrated analysis identified core signal pathways and hypoxic characteristics of human glioblastoma
Authors: Gao Yixing , Zhang Erlong , Liu Bao , Zhou Kai , He Shu , Feng Lan , Wu Gang , Cao Mianfu , Wu Haibo , Cui Youhong , Zhang Xia , Liu Xindong , Wang Yan , Gao Yuqi , Bian Xiuwu 
Published: July 2019

AbstractAs a hallmark for glioblastoma (GBM), high heterogeneity causes a variety of phenotypes and therapeutic responses among GBM patients, and it contributes to treatment failure. Moreover, hypoxia is a predominant feature of GBM and contributes greatly to its phenotype. To analyse the landscape of gene expression and hypoxic characteristics of GBM cells and their clinical significance in GBM patients, we performed transcriptome analysis of the GBM cell line U87‐MG and the normal glial cell line HEB under normoxia and hypoxia conditions, with the results of which were analysed using established gene ontology databases as well as The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia. We revealed core signal pathways, including inflammation, angiogenesis and migration, and for the first time mapped the components of the toll‐like receptor 6 pathway in GBM cells. Moreover, by investigating the signal pathways involved in homoeostasis, proliferation and adenosine triphosphate metabolism, the critical response of GBM to hypoxia was clarified. Experiments with cell lines, patient serum and tissue identified IL1B, CSF3 and TIMP1 as potential plasma markers and VIM, STC1, TGFB1 and HMOX1 as potential biopsy markers for GBM. In conclusion, our study provided a comprehensive understanding for signal pathways and hypoxic characteristics of GBM and identified new biomarkers for GBM patients.
A comparative dermoscopic and reflectance confocal microscopy study of naevi and melanoma with negative pigment network
Authors: Farnetani F. , Scope A. , Mazzoni L. , Mandel V.D. , Manfredini M. , Magi S. , Vaschieri C. , Kaleci S. , Longo C. , Ciardo S. , Stanganelli I. , Pellacani G. 
Published: July 2019

AbstractBackgroundNegative pigment network (NPN) is a dermoscopic structure observed more frequently among melanomas than naevi. Precise tissue correlates of NPN are still elusive.ObjectiveTo describe the reflectance confocal microscopy (RCM) findings underlying NPN in melanocytic neoplasms.MethodsWe retrospectively identified all melanocytic neoplasms displaying dermoscopic NPN that were imaged with RCM and subsequently biopsied between 2011 and 2015. Images from study lesions (n = 50) were evaluated for dermoscopic and RCM Criteria. Histopathological correlational study was performed in a subset of cases (n = 15).ResultsThe study data set consisted of 21 melanomas (42%) and 29 naevi (58%). Melanomas showed more frequently irregularly shaped globules than naevi (62% vs. 28%, P = 0.03); NPN also tended to be more asymmetrically located among melanomas (86%) than naevi (62%), albeit not significant (P = 0.06). Under RCM, we observed three patterns of dermal papillae (DP): (i) ‘Dark DP’ – whereby DP were devoid of nests and often surrounded by a junctional proliferation as thick‐Rings – this pattern was less common among melanomas (n = 10, 48%) than naevi (n = 23, 79%, P = 0.02); (ii) ‘Bulging DP’ – whereby junctional nests of melanocytes protrude into the DP, often in association with junctional proliferation as Meshwork – with comparable frequency among melanomas (n = 12, 57%) and naevi (n = 23, 79%, P = 0.09) and (iii) ‘Expanded DP’ – whereby junctional and/or dermal nests filled and expanded the DP, often in association with dermal–epidermal junction (DEJ) Clod pattern – seen more commonly among melanomas (n = 15, 71%) than naevi (n = 6, 21%, P < 0.001). Dermoscopy–RCM correlation and comparison to histopathological findings show that the hypo‐pigmented lines of NPN correlate with broadened epidermal retes, which often show overlying surface dells and wedge‐shaped hypergranulosis, while the pigmented globules of NPN correlate with a predominantly‐junctiona of melanocytes along and between the elongated retes.ConclusionsDermoscopic NPN correlates with three DEJ RCM patterns with differing frequency between naevi and melanomas.
No association between smoking and sentinel lymph node metastasis and survival in cutaneous melanoma
Authors: Tejera‐Vaquerizo A. , Descalzo‐Gallego M.A. , Traves V. , Requena C. , Bolumar I. , Pla A. , Nagore E. 
Published: July 2019

AbstractBackgroundThere is little evidence that smoking is associated with metastasis in patients with cutaneous melanoma.ObjectiveUsing a propensity score matching analysis, we assessed whether smoking was associated with a higher rate of sentinel lymph node (SLN) metastasis and worse survival in these patients.MethodsRetrospective cohort study at a referral hospital for melanoma. We studied 762 patients with known smoking status from the melanoma database of the Instituto Valenciano de Oncología who underwent SLN biopsy between 1 January 2000 and 31 December 2016. The patients were matched by smoking status. The matching procedure was implemented using three logistic regression models featuring never vs. former smokers, never vs. current smokers and former vs. current smokers. The study outcomes were disease‐free survival (DFS), melanoma‐specific survival (MSS), overall survival (OS) and SLN status.ResultsThe following groups were formed based on the propensity matching scores: 114 pairs of smokers vs. never smokers, 113 pairs of smokers vs. former smokers and 174 pairs of never smokers vs. former smokers. Smoking status was not associated with SLN metastasis or with DFS, MSS or OS in any of the three groups.ConclusionSmoking does not influence SLN metastasis or survival in patients with cutaneous melanoma.
Reassessment of venous thromboembolism and bleeding risk in medical patients receiving VTE prophylaxis
Authors: Tung Elaine C. , Yu Shi‐Yuan , Shah Kieran , Kinkade Angus , Tejani Aaron M. 
Published: July 2019

AbstractRationale, Aims, and ObjectivesThe majority of hospitalized nonsurgical medical patients receive pharmacological prophylaxis for venous thromboembolism (VTE), and reassessment of changes in thrombosis and bleeding risk factors during hospital admission may represent an opportunity to discontinue unnecessary or unsafe therapy. The use of validated, clinically derived risk assessment models (RAMs) represents a shift towards an individualized, patient‐centred approach to VTE prophylaxis. We are interested in using these tools to assess whether risk categories for VTE and bleeding change during admission and to assess whether such changes result in discontinuation of prophylaxis. Our primary objective was to determine whether VTE and bleed risk categories changed during the course of admission to warrant discontinuation of VTE prophylaxis, using the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) VTE and Bleed RAMs, respectively. Secondary objectives were to determine the number of patients whose risk categorizations for VTE and bleeding warranted discontinuation of VTE prophylaxis and to survey whether prophylaxis was continued or discontinued.MethodsA retrospective review was undertaken for a cross‐sectional, randomly selected sample of patients who received VTE prophylaxis while admitted to medical wards in a collection of regional hospitals.ResultsOf the 351 medical records reviewed, only eight patients (2.3%) changed their VTE risk category and six (1.7%) changed their bleed risk category to warrant discontinuation of VTE prophylaxis. Ninety patients (26%) were at high risk of VTE and low risk of bleed throughout admission, warranting continued VTE prophylaxis. The majority of patients remained at low risk of VTE throughout admission but remained on VTE prophylaxis until discharge.ConclusionsRisk categories for VTE and bleeding for medical patients did not appreciably change throughout hospital admission. Use of VTE RAMs at admission and prior to initiation of therapy should reduce unnecessary prophylaxis in the majority of medical patients who are at low risk of VTE.
Altered glucose catabolism in the presynaptic and perisynaptic compartments of SOD1G93A mouse spinal cord and motor cortex indicates that mitochondria are the site of bioenergetic imbalance in ALS
Authors: Ravera Silvia , Torazza Carola , Bonifacino Tiziana , Provenzano Francesca , Rebosio Claudia , Milanese Marco , Usai Cesare , Panfoli Isabella , Bonanno Giambattista 
Published: July 2019

AbstractAmyotrophic lateral sclerosis is an adult‐onset neurodegenerative disease that develops because of motor neuron death. Several mechanisms occur supporting neurodegeneration, including mitochondrial dysfunction. Recently, we demonstrated that the synaptosomes from the spinal cord of SOD1G93A mice, an in vitro model of presynapses, displayed impaired mitochondrial metabolism at early pre‐symptomatic stages of the disease, whereas perisynaptic astrocyte particles, or gliosomes, were characterized by mild energy impairment only at symptomatic stages. This work aimed to understand whether mitochondrial impairment is a consequence of upstream metabolic damage. We analyzed the critical pathways involved in glucose catabolism at presynaptic and perisynaptic compartments. Spinal cord and motor cortex synaptosomes from SOD1G93A mice displayed high activity of hexokinase and phosphofructokinase, key glycolysis enzymes, and of citrate synthase and malate dehydrogenase, key Krebs cycle enzymes, but did not display high lactate dehydrogenase activity, the key enzyme in lactate fermentation. This enhancement was evident in the spinal cord from the early stages of the disease and in the motor cortex at only symptomatic stages. Conversely, an increase in glycolysis and lactate fermentation activity, but not Krebs cycle activity, was observed in gliosomes from the spinal cord and motor cortex of SOD1G93A mice although only at the symptomatic stages of the disease. The cited enzymatic activities were enhanced in spinal cord and motor cortex homogenates, paralleling the time‐course of the effect observed in synaptosomes and gliosomes. The observed metabolic modifications might be considered an attempt to restore altered energetic balance and indicate that mitochondria represent the ultimate site of bioenergetic impairment.
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