bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early non-invasive brain stimulation with modified constraint-induced movement therapy for motor and functional upper limb recovery in stroke patients: Study protocol
Authors: A Garrido Maricel , A Άlvarez Evelyn , L Acevedo Fabrizio , I Moyano Álvaro , P Castillo Natalia , A Cavada Gabriel 
Published: April 2020

Introduction Upper limb motor impairment after a stroke is an important sequela. Constraint-induced movement therapy is a rehabilitation approach that has strong evidence. The incorporation of transcranial direct-current stimulation has been proposed; however, there is a lack of studies that confirm its benefits. The principal aim is to compare the effectiveness of 7 days of active versus sham bi-hemispheric transcranial direct-current stimulation, combined with modified constraint-induced movement therapy, for motor and functional recovery of the hemiparetic upper limb in subacute stroke patients. Method/design Randomized, double blind, sham-controlled, parallel group clinical trial in two stroke units. Participants: adults over 18 years, at least 2 days post unihemispheric stroke event, with hemiparesis, and without severe pain, aphasia or cognitive impairment. Intervention: Patients will receive 7 days of continuous therapy and be assigned to one of the treatment groups: active bi-hemispheric transcranial direct-current stimulation or sham bi-hemispheric transcranial direct-current stimulation. Measurement: Evaluations will take place at days 0, 5, 7 and 10, and at 3rd months. The Fugl-Meyer Assessment – Upper Extremity, Wolf Motor Function Test, Functional Independence Measure and Stroke Impact Scale are considered. Discussion Modified constraint-induced movement therapy plus transcranial direct-current stimulation in subacute stroke patients with hemiparesis could maximize motor and functional recovery. Trial registration: ClinicalTrials.gov identifier NCT03452254.
Co-activation of rhythms during alpha band oscillations as an interictal biomarker of exploding head syndrome
Authors: Fotis Sakellariou Dimitris , Nesbitt Alexander David , Higgins Sean , Beniczky Sandor , Rosenzweig Jan , Drakatos Panagis , Gildeh Nadia , Murphy Patrick Brian , Kent Brian , Williams Adrian John , Kryger Meir , Goadsby Peter J , Leschziner Guy Doron , Rosenzweig Ivana 
Published: April 2020

Background Exploding head syndrome is a rarely reported benign sensory parasomnia that may nonetheless have significant impact on patients’ quality of life and their perceived well-being. To date, the mechanisms underlying attacks, characterised by a painless perception of abrupt, loud noises at transitional sleep-wake or wake-sleep states, are by and large unclear. Methods and results In order to address the current gap in the knowledge of potential underlying pathophysiology, a retrospective case-control study of polysomnographic recordings of patients presenting to a tertiary sleep disorders clinic with exploding head syndrome was conducted. Interictal (non-attack associated) electroencephalographic biomarkers were investigated by performing macrostructural and event-related dynamic spectral analyses of the whole-night EEG. In patients with exploding head syndrome, additional oscillatory activity was recorded during wakefulness and at sleep/wake periods. This activity differed in its frequency, topography and source from the alpha rhythm that it accompanied. Conclusion Based on these preliminary findings, we hypothesise that at times of sleep-wake transition in patients with exploding head syndrome, aberrant attentional processing may lead to amplification and modulation of external sensory stimuli.
CD4+CD28null T cells are expanded in moderately active systemic lupus erythematosus and secrete pro-inflammatory interferon gamma, depending on the Disease Activity Index
Authors: Kosmaczewska Agata , Ciszak Lidia , Stosio Malgorzata , Szteblich Aleksandra , Madej Marta , Frydecka Irena , Wiland Piotr , Szmyrka Magdalena 
Published: April 2020

Background Pathogenic CD4+CD28null cells are characterized by inflammatory cytokine synthesis and tropism to the inflamed tissues. Recent studies showed the involvement of CD28null T cells in a severe clinical outcome of lupus. However, their role in moderately active disease is still unresolved. Methods We examined the levels of circulating CD4+CD28null cells and CD8+CD28null suppressor T cells. We also compared the CD4+CD28null and CD4+CD28+ T-cell functional properties, including the expression of interferon gamma (IFN-γ) and Ki67 among systemic lupus erythematosus (SLE) patients ( n = 20) and healthy controls ( n = 20). All the patients were under immunosuppressive treatment and exhibited moderate SLE activity (median SLE Disease Activity Index (SLEDAI) = 6). Results In patients, we found elevated CD4+CD28null and unchanged levels of suppressor CD8+CD28null T cells. There was no difference between patients and controls in IFN-γ and Ki67-expressing CD4+, CD4+CD28+, and CD4+CD28null T cells, except for higher IFN-γ levels in CD4+CD28+ T cells in SLE. In each studied group, we observed a higher preponderance of IFN-γ- and Ki67-expressing cells among CD4+CD28null T cells and lower levels of IFN-γ in CD4+CD28null T cells compared to the CD28+ subset. Similarly, Ki67 intensity was decreased in healthy CD4+CD28null cells, whereas in patients, comparably high expression was observed in both subsets. IFN-γ intensity in CD4+CD28null T cells correlated with SLEDAI. Conclusion SLE with a moderately active clinical course is characterized by peripheral blood expansion of CD4+CD28null T cells and a normal abundance of suppressor CD8+CD28null T cells. The demonstration that these pathogenic CD4+ T cells, despite the lack of CD28, maintain the ability to produce pro-inflammatory IFN-γ positively correlated with disease activity as well as relatively high proliferative capacity may suggest their potentially predictive role in SLE flares.
Two successful deliveries of healthy children by a young woman diagnosed and treated during induction and relapsed therapy for acute promyelocytic leukemia
Authors: Dang Chee Chean , Guan Yong Khee , Lau Ngee Siang , Chan Siok Yee 
Published: April 2020

Introduction Acute promyelocytic leukemia is an oncologic emergency. The limited cases reported in the literature have led to poor understanding of the safety of management of acute promyelocytic leukemia during pregnancy. Case report Herein is an acute promyelocytic leukemia case of a 22-year-old young pregnant woman who had various social problems. The patient was diagnosed with acute promyelocytic leukemia in her the second trimester of her first pregnancy. Management and outcome: She was treated with all-trans-retinoic acid with idarubicin and successfully delivered a healthy baby. She completed induction with idarubicin but defaulted her all-trans-retinoic acid, 6-mercaptopurine and methotrexate maintenance. She relapsed after one year and was salvaged with all-trans-retinoic acid high dose cytarabine and arsenic trioxide. She went into remission and had autologous stem cells collected and was planned for an autologous stem cell transplant but she defaulted. She relapsed when she was pregnant with her second baby during her third trimester (29+weeks) 10 months later. Salvage chemotherapy with arsenic trioxide, all-trans-retinoic acid and idarubicin was given. Patient underwent an emergency lower segment caesarian section at 31 weeks of pregnancy due to abnormal fetal cardiotocography. A healthy baby was delivered. Discussion This drug regimen is controversial during pregnancy owing to the teratogenic effects and fatal retinoic acid syndrome especially in early gestation. In this case, patient was started the induction therapy of all-trans-retinoic acid treatment at her second trimester during her first pregnancy. Conclusion Our lady demonstrated the possibility of using all-trans-retinoic acid and arsenic trioxide and chemotherapy during second and third trimester with successful pregnancy outcomes.
Adherence and adverse events of intraperitoneal chemotherapy in optimally debulked ovarian cancer patients: Real-life study
Authors: Ballesta-López Octavio , Albert-Marí Asunción , Borrell-García Carmela , Melián-Sosa Marcos , Salvador-Coloma Carmen , Santaballa-Bertrán Ana , Poveda-Andrés José Luis 
Published: April 2020

Purpose Intraperitoneal with intravenous chemotherapy (IP/IV) is the recommended option for patients with stage III cancer with optimally debulked (<1 cm residual) disease based on randomized controlled trials and showing important improvements in overall survival and progression free survival. However, its application has not been largely adopted due to its difficult administration that requires a trained nurse staff. The aim of this work was to study the completion and the toxicity of an IP outpatient chemotherapy regimen in optimally debulked stage III ovarian cancer patients. Methods A single-center, retrospective observational study in women with stage III ovarian cancer following optimal cytoreductive surgery (<1 cm) followed by IP/IV chemotherapy from 2009 to 2017. The IP/IV regimen was as it follows: IV paclitaxel 175 mg/m2 in 3 h, day 1; IP cisplatin (100 mg/m2—until December 2013—or 75 mg/m2), day 2; IP paclitaxel 60 mg/m2, day 8, each 21 days for six cycles. Results A total of 60 patients received IP/IV regimen. Of these, 41 patients (68.3%) completed the six IP chemotherapy cycles and 51 (84.9%) completed four or more cycles. Most of the adverse events reported were non-hematological and G1-2. There was no difference neither in adherence nor in the frequency of adverse events between both cisplatin groups. Despite a high rate of adverse events, IP chemotherapy can be delivered with a high completion rate and manageable toxicity to patients with optimally debulked ovarian cancer.
Success of Students Screened as Twice-Exceptional as a Function of Major Selection and Academic Strength
Authors: Snyder Kelly H. , McClurg Virginia M. , Wu Jiaju , McCallum R. Steve 
Published: April 2020

In this study, the success of 6,054 college students screened as twice-exceptional (2e; i.e., those with significantly discrepant math vs. reading scores on the ACT [formerly, American College Test] or SAT [formerly, Scholastic Aptitude Test]) was examined based on major selection and type of potential learning disability using a screening technique proposed by McCallum et al. There were no differences in high school grade point average, college grade point average, or first-year retention rates between students screened as 2e who had a major in line with their academic strength versus those who did not ( p >  .05). However, students screened as 2e based on an exceptionally high math score but a lower reading score yielded statistically significantly higher rates of retention ( p <  .05) than students screened as 2e with the reverse pattern of scores (i.e., gifted in reading with a potential learning disability in math). Implications for screening 2e students are discussed.
Three-dimensional models of breast cancer–fibroblasts interactions
Authors: Singh Sunil , Tran Sydnie , Putman Justin , Tavana Hossein 
Published: April 2020

Tumor microenvironment is a complex niche consisting of cancer cells and stromal cells in a network of extracellular matrix proteins and various soluble factors. Dynamic interactions among cellular and non-cellular components of the tumor microenvironment regulate tumor initiation and progression. Fibroblasts are the most abundant stromal cell type and dynamically interact with cancer cells both in primary tumors and in metastases. Cancer cells activate resident fibroblasts to produce and secrete soluble signaling molecules that support proliferation, migration, matrix invasion, and drug resistance of cancer cell and tumor angiogenesis. In recent years, various forms of three-dimensional tumor models have been developed to study tumor–stromal interactions and to identify anti-cancer drugs that block these interactions. There is currently a technological gap in development of tumor models that are physiologically relevant, scalable, and allow convenient, on-demand addition of desired components of the tumor microenvironment. In this review, we discuss three studies from our group that focus on developing bioengineered models to study tumor-stromal signaling. We will present these studies chronologically and based on their increasing complexity. We will discuss the validation of the models using a CXCL12-CXCR4 chemokine-receptor signaling present among activated fibroblasts and breast cancer cells in solid tumors, highlight the advantages and shortcomings of the models, and conclude with our perspectives on their applications.Impact statementTumor stroma plays an important role in progression of cancers to a fatal metastatic disease. Modern treatment strategies are considering targeting tumor stroma to improve outcomes for cancer patients. A current challenge to develop stroma-targeting therapeutics is the lack of preclinical physiologic tumor models. Animal models widely used in cancer research lack human stroma and are not amenable to screening of chemical compounds for cancer drug discovery. In this review, we outline in vitro three-dimensional tumor models that we have developed to study the interactions among cancer cells and stromal cells. We describe development of the tumor models in a modular fashion, from a spheroid model to a sophisticated organotypic model, and discuss the importance of using correct physiologic models to recapitulate tumor-stromal signaling. These biomimetic tumor models will facilitate understanding of tumor-stromal signaling biology and provide a scalable approach for testing and discovery of cancer drugs.
Current perspectives on the cellular and molecular features of epigenetic ageing
Authors: Raj Kenneth , Horvath Steve 
Published: April 2020

It has been noted for quite some time that DNA methylation levels decline with age. The significance of this change remained unknown until it became possible to measure methylation status of specific sites on the DNA. It was observed that while the methylation of some sites does indeed decrease with age, that of others increase or remain unchanged. The application of machine learning methods to these quantitative changes in multiple sites, allowed the generation of a highly accurate estimator of age, called the epigenetic clock. The application of this clock on large human epidemiological data sets revealed that discordance between the predicted (epigenetic age) and chronological age is associated with many age-related pathologies, particularly when the former is greater than the latter. The epigenetic clock clearly captures to some degree, biological features that accompany the ageing process. Despite the ever-increasing scope of pathologies that are found to be associated with accelerated epigenetic ageing, the basic principles that underlie the ticking of the clock remain elusive. Here, we describe the known molecular and cellular attributes of the clock and consider their properties, and proffer opinions as to how they may be connected and what might be the underlying mechanism. Emerging from these considerations is the inescapable view that epigenetic ageing begins from very early moments after the embryonic stem cell stage and continues un-interrupted through the entire life-course. This appears to be a consequence of processes that are necessary for the development of the organism from conception and to maintain it thereafter through homeostasis. Hence, while the speed of ageing can, and is affected by external factors, the essence of the ageing process itself is an integral part of, and the consequence of the development of life.Impact statementThe field of epigenetic ageing is relatively new, and the speed of its expansion presents a challenge in keeping abreast with new discoveries and their implications. Several reviews have already addressed the great number of pathologies, health conditions, life-style, and external stressors that are associated with changes to the rate of epigenetic ageing. While these associations highlight and affirm the ability of epigenetic clock to capture biologically meaningful changes associated with age, they do not inform us about the underlying mechanisms. In this very early period since the development of the clock, there have been rather limited experimental research that are aimed at uncovering the mechanism. Hence, the perspective that we proffer is derived from available but nevertheless limited lines of evidence that together provide a seemingly coherent narrative that can be tested. This, we believe would be helpful towards uncovering the workings of the epigenetic clock.
Ultrasound-guided catheter-directed foam sclerotherapy can be safely applied for the treatment of great saphenous varicose veins in elderly patients
Authors: Kahraman Nail , Özsin Kadir K 
Published: April 2020

Objectives Although many published series have shown the results of ultrasound-guided catheter-directed foam sclerotherapy, little is known about the outcomes and complications in older patients. Methods A total of 152 patients older than 65 years (group 1: 61.8% male, mean age 69.0 ± 4.5 years) and 244 patients younger than 65 years (group 2: 48.8% male, mean age 45.7 ± 11.2 years) were included in the study. Ultrasound-guided catheter-directed foam sclerotherapy was performed in patients with great saphenous vein valvular incompetence and saphenofemoral junction incompetence. Occlusion status was recorded by ultrasonography. Venous clinical severity score and visual analog score were calculated pre- and post-intervention. Results Complete occlusion rate of the great saphenous vein at 12 months post-procedure for the groups 1 and 2 was 86.4% and 86.3%, respectively. Venous clinical severity score and visual analog score were signiﬁcantly different before ultrasound-guided catheter-directed foam sclerotherapy and four weeks after ultrasound-guided catheter-directed foam sclerotherapy ( p < 0.001) in both the groups. There were no observed major complications in both the groups. Conclusions With low complication rate and acceptable total occlusion rate, ultrasound-guided catheter-directed foam sclerotherapy can be considered a reliable treatment for older patients.
Pediatric acute appendicitis: Searching the diagnosis in portal vein
Authors: Aydin Sonay , Ucan Berna 
Published: April 2020

Introduction Acute appendicitis is the most common reason for emergency abdominal surgery in the pediatric population. Ultrasound (US) is a widely used modality to diagnose acute appendicitis. The aim of this study was to evaluate the effectiveness of portal vein diameter and flow velocity in acute appendicitis diagnosis. Methods Portal vein diameter and flow velocity were measured in children who were referred to radiology with a clinical diagnosis of acute appendicitis. The largest appendix diameter and leukocyte count of the patients were recorded. A control group was created which consisted of healthy children, and their portal vein diameter and flow velocities were also measured. Results The median age of the population was 10 years (range, 3–17 years). Mean portal vein diameter was 7.53 ± 1.55 mm in the control group, 7.92 ± 1.88 mm in the other diagnosis group, and 8.76 ± 1.91 mm in the acute appendicitis group. Mean portal vein diameter was significantly higher in the acute appendicitis group (p = 0.001). Median portal vein flow velocity was 17 cm/s (10–29 cm/s) in the control group, 18.3 cm/s (8–27 cm/s) in the other diagnosis group, and 20.5 cm/s in the acute appendicitis group. Median portal vein flow velocity was significantly higher in the acute appendicitis group (p = 0.00). Conclusion Detecting an increase in portal vein diameter and/or flow velocity in equivocal cases may support other clinical signs associated with acute appendicitis. Portal vein diameter and flow velocity can serve as additional diagnostic markers in acute appendicitis cases.
Physical activity attenuates cardiovascular risk and mortality in men and women with and without the metabolic syndrome – a 20-year follow-up of a population-based cohort of 60-year-olds
Authors: Ekblom-Bak Elin , Halldin Mats , Vikström Max , Stenling Andreas , Gigante Bruna , de Faire Ulf , Leander Karin , Hellénius Mai-Lis 
Published: April 2020

Abstract

Aims
The purpose of this study was to analyse the association of leisure-time physical activity of different intensities at baseline, and cardiovascular disease incidence, cardiovascular disease mortality and all-cause mortality in a population-based sample of 60-year-old men and women with and without established metabolic syndrome, for more than 20 years of follow-up. A secondary aim was to study which cardiometabolic factors may mediate the association between physical activity and long-term outcomes.

Methods
A total of 3693 participants (53% women) underwent physical examination and laboratory tests, completed an extensive questionnaire at baseline 1997–1999 and were followed until their death or until 31 December 2017. First-time cardiovascular disease events and death from any cause were ascertained through regular examinations of national registers.

Results
Metabolic syndrome prevalence was 23.0%. In metabolic syndrome participants, light physical activity attenuated cardiovascular disease incidence (hazard ratio = 0.71; 95% confidence interval 0.50–1.00) compared to sedentary (reference) after multi-adjustment. Moderate/high physical activity was inversely associated with both cardiovascular disease and all-cause mortality, but became non-significant after multi-adjustment. Sedentary non-metabolic syndrome participants had lower cardiovascular disease incidence (0.47; 0.31–0.72) but not significantly different cardiovascular disease (0.61; 0.31–1.19) and all-cause mortality (0.92; 0.64–1.34) compared to sedentary metabolic syndrome participants. Both light and moderate/high physical activity were inversely associated with cardiovascular disease and all-cause mortality in non-metabolic syndrome participants (p&lt;0.05). There were significant variations in several central cardiometabolic risk factors with physical activity level in non-metabolic syndrome participants. Fibrinogen mediated the protective effects of physical activity in non-metabolic syndrome participants.

Conclusion
Physical activity of different intensities attenuated cardiovascular risk and mortality in 60-year old men and women with metabolic syndrome during a 20-year follow-up.