bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extending the time window for intravenous thrombolysis in acute ischemic stroke using magnetic resonance imaging-based patient selection
Authors: Ringleb Peter , Bendszus Martin , Bluhmki Erich , Donnan Geoffrey , Eschenfelder Christoph , Fatar Marc , Kessler Christof , Molina Carlos , Leys Didier , Muddegowda Girish , Poli Sven , Schellinger Peter , Schwab Stefan , Serena Joaquin , Toni Danilo , Wahlgren Nils , Hacke Werner ,   for the ECASS-4 study group
Published: April 2019

Background Intravenous thrombolysis with alteplase within a time window up to 4.5 h is the only approved pharmacological treatment for acute ischemic stroke. We studied whether acute ischemic stroke patients with penumbral tissue identified on magnetic resonance imaging 4.5–9 h after symptom onset benefit from intravenous thrombolysis compared to placebo. Methods Acute ischemic stroke patients with salvageable brain tissue identified on a magnetic resonance imaging were randomly assigned to receive standard dose alteplase or placebo. The primary end point was disability at 90 days assessed by the modified Rankin scale, which has a range of 0–6 (with 0 indicating no symptoms at all and 6 indicating death). Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. Results The trial was stopped early for slow recruitment after the enrollment of 119 (61 alteplase, 58 placebo) of 264 patients planned. Median time to intravenous thrombolysis was 7 h 42 min. The primary endpoint showed no significant difference in the modified Rankin scale distribution at day 90 (odds ratio alteplase versus placebo, 1.20; 95% CI, 0.63–2.27, P = 0.58). One symptomatic intracranial hemorrhage occurred in the alteplase group. Mortality at 90 days did not differ significantly between the two groups (11.5 and 6.8%, respectively; P = 0.53). Conclusions Intravenous alteplase administered between 4.5 and 9 h after the onset of symptoms in patients with salvageable tissue did not result in a significant benefit over placebo. (Supported by Boehringer Ingelheim, Germany; ISRCTN 71616222).
Impact of previous stroke on outcome after thrombectomy in patients with large vessel occlusion
Authors: Leker Ronen R , Cohen Jose E , Horev Anat , Tanne David , Orion David , Raphaeli Guy , Amsalem Jacob , Streifler Jonathan Y , Hallevi Hen , Bornstein Natan M , Yaghmour Nour E , Telman Gregory ,   On Behalf of the NASIS-REVASC Study Group
Published: April 2019

Background Many patients with large vessel occlusion (LVO) who are otherwise candidates for endovascular treatment (EVT) have had previous strokes. We aimed to examine the effect of previous stroke on outcome after EVT. Methods Consecutive patients with LVO were prospectively entered into a National Acute Stroke registry of patients undergoing EVT. Patients treated with EVT were divided into those with and without previous strokes. The rates of favorable reperfusion status, mortality, and excellent outcome at 90 days post-stroke as well as symptomatic intracranial hemorrhage (sICH) were evaluated. Results A total of 390 underwent EVT and 35 had previous strokes. Patients with previous strokes were significantly older; more frequently had a history of prior myocardial infarction and more often had pre-existing functional disability. Favorable target vessel recanalization was less frequently achieved in patients with previous strokes (60% vs. 82%; p = 0.005) and ordinal regression analysis for functional outcome revealed higher frequency of deterioration at three months in patients with previous strokes. Nevertheless, 9% of these patients maintained their previous disability state and sICH rates did not differ between the groups. Mortality rates at one year post stroke were significantly higher in patients with previous strokes (37% vs. 16%; p = 0.005). Conclusions Previous strokes are associated with higher likelihoods of mortality and unfavorable outcome in patients with LVO undergoing EVT. However, because some of these patients maintain their previous disability state, the presence of previous stroke should not be used as an exclusion criterion from EVT.
Project eARTh: participatory arts and mental health recovery, a qualitative study
Authors: Hui Ada , Stickley Theodore , Stubley Michelle , Baker Francesca 
Published: April 2019

Aims: To identify the potential mental health benefits of a rural-based participatory arts programme in the United Kingdom. Methods: Fourteen narrative interviews were conducted among participants of the Project eARTh programme. The data were subjected to a thematic analysis process. Results: Three overarching themes were identified: identity and self-expression; connectedness through occupation; wellbeing and personal growth. The importance of meaningful relationships was highlighted as preventing social isolation, particularly in rural locations. Engagement in artistic group activities enable participants to connect with their communities. Conclusions: Artistic activities help people to develop friendships and to engage with local communities in rural locations. Connectedness to people and places were valued by participants as part of their personal growth. The groups empower people to experience increased confidence and identities beyond illness narratives. Artistic group activities can benefit the mental health of participants in rural locations.
Participants’ perceptions of Kinesio tape for carpal tunnel syndrome: A qualitative study
Authors: Krause Donnamarie , Ryan Sheryl , Krpalek Dragana , Roll Shawn C , Javaherian-Dysinger Heather , Daher Noha 
Published: April 2019

Introduction Kinesio tape is an alternative non-surgical treatment approach for addressing symptoms of carpal tunnel syndrome. The purpose of the study was to investigate individuals’ experiences with the dorsal application of Kinesio tape for carpal tunnel syndrome management and its impact on pain and function. Method The study design was a limited phenomenological design study embedded in a randomized controlled trial. Daily symptom journals and semi-structured interviews were completed with 15 participants who were purposefully recruited and randomly allocated to the intervention group of a single blind randomized controlled trial. Kinesio tape was applied dorsally on the affected forearm, wrist, and digits for a duration of two weeks. Transcribed data were analyzed using descriptive coding, coding schemes, and frequency charts to identify emerging themes. Results Three themes emerged: Kinesio tape was positively perceived to be effective on decreasing pain, increasing self-efficacy, and improving daily functional performance on tasks previously avoided or abandoned. The most common problem identified was maintaining Kinesio tape on the hands and fingers, to which the majority of participants expressed a desire to learn application. Discussion Results of this study suggest that Kinesio tape is a positively perceived intervention for decreasing pain and increasing function for individuals with carpal tunnel syndrome and warrants further consideration as an alternative conservative intervention for carpal tunnel syndrome.
The Hospital (Not So) Quiet Zone: Creating an Environment for Patient Satisfaction Through Noise Reduction Strategies
Authors: Walker Linda , Karl Cherry A. 
Published: April 2019

Purpose: To determine whether using existing noise reduction strategies improves patients’ overall satisfaction level during hospitalization on an adult outpatient cardiology unit and to assess whether noise reduction strategies were effective to decrease the ambient noise for both staff and patient environments. Background: Excessive noise is a worldwide problem facing hospitals today. Noise has been proven to be detrimental to staff and patient well-being and hospital environment satisfaction levels. Intervention: Staff noise perception online surveys, a poster presentation, and education of noise reduction strategies were completed. Two 6-week phases of pre- and postimplementation noise reduction strategies were initiated including closing of the doors, verbal and visual alarm reminders for staff, posting quiet signs, and limiting equipment through the unit. Patient telephone interviews regarding the noise environment during hospitalization in both phases and a follow-up staff noise perception online survey were completed. Results: Staff surveys identified noise as an issue on the unit with staff communication (90%) being the main source. This correlated with patient surveys of five rooms closest to the desk considering the unit “noisy.” Post-implementation patient surveys noted that strategies created in helping the unit become “quiet/mostly quiet.” Closing patient doors was most effective in noise reduction, increasing patient unit satisfaction. Conclusion: The use of visual cues and staff education are effective in reducing noise levels. Decreased noise levels improved overall patient satisfaction with their hospital experience and created a less stressful work environment.
Surgical Approach to Frontal Sinus Osteoma: A Systematic Review
Authors: Watley Duncan C. , Mong Eric R. , Rana Nikunj A. , Illing Elisa A. , Chaaban Mohamad R. 
Published: April 2019

Background Osteoma of the paranasal sinuses are benign bony masses most commonly found in the frontal sinus. In the past, due to the anatomical complexity of the frontal sinus, these often required an open approach, but with the invention of angled tools and endoscopes, many rhinologists are now attempting endoscopic or combined resections. No large systematic reviews currently exist that describe the surgical management of frontal sinus osteoma. Objective To perform a systematic review detailing the surgical resection of frontal sinus osteoma. Review Methods: A systematic literature review was performed using PubMed, Embase, and Ovid databases. Data extracted included demographics, clinical presentation, radiologic, histologic findings, surgical approach, and recurrence. Results A total of 32 studies, with 477 surgically resected tumors, were included in the analysis. Sex data were available for 179 patients (M:F, 93:86), with a mean age of 43.2 years. All resected tumors presented symptomatically: facial pain/headache (80.2%), recurrent sinusitis (30.5%), mucocele (4.3%), cosmetic deformity other than proptosis (12.8%), and proptosis (5.5%). Transnasal endoscopic surgery alone was the most common surgical approach utilized (44.9%), followed by open osteoplastic flaps (36.9%) and endoscopic assisted (18.2%). Osteoma with anterior (79%) and posterior (73%) attachments were treated statistically more often with endoscopic approach compared with floor (42%) and extrasinus (50%) attachment ( P < .0005). There was no statistical difference in approach to masses that crossed the sagittal plane extending from the lamina papyracea (63% endoscopic, 29% endoscopic assisted, 8% open, P = .21). Mean follow-up was 29.7 months, with recurrence or persistent residual disease occurring in 12 patients. Conclusion Despite the increasing use of endoscopic alone procedures for expanding indications, patients may still require an open or endoscopic assisted approach for complete removal.
Somatization, Depression, and Anxiety Disorders in a Rhinology Practice
Authors: Alam Elie S. , Musselman Dominique L. , Chyou Darius , Shukri Ghaith , Levine Corinna G. , Sanghvi Saurin , Zhang Hang , Casiano Roy R. 
Published: April 2019

Background Patients present to rhinology clinics with various complaints. Symptoms may be attributable to objective findings, some remain unexplained. The objective is to investigate the incidence of psychological disorders in a rhinologic practice and evaluate a correlation of these psychiatric diseases with rhinologic symptoms. Methods Patients presenting to a rhinology clinic were administered the Generalized Anxiety Disorder 7 (GAD 7), Patient Health Questionnaire 9 (PHQ 9), and PHQ 15, psychometric instruments that can screen for generalized anxiety, major depression, and somatization disorder, respectively. Patients’ symptoms, endoscopic findings, medication, and psychiatric history were recorded. Multivariable analysis was performed for patients showed moderate-to-severe anxiety, depression, and somatic symptoms via 3 logistic regressions where the outcome was a GAD 7, PHQ 9, or PHQ 15 above 10. Results One hundred ninety-six patients were included for this study. There were 109 females and 87 males with a mean age of 49 years. Overall, 9%, 14%, and 21% exhibited moderate-to-severe anxiety, depressive, and somatization symptoms, respectively. Nasal obstruction was the only statistically significant variable that increased the odds of having moderate-to-severe anxiety symptoms. Similarly, headache, nasal obstruction, and anosmia/hyposmia were associated with increased odds of having depressive symptoms, and female gender, headache, and nasal discharge increased the odds of somatic symptom disorder. Edema was the only objective endoscopic finding, which was associated with depression only. Conclusions Patients should be counseled about the pathophysiology and psychiatric comorbidities affecting their primary rhinologic complaints. The provider needs to set realistic treatment expectations in order to achieve the desired clinical outcomes.
Plasma and Joint Fluid Glypican-3 Are Inversely Correlated with the Severity of Knee Osteoarthritis
Authors: Udomsinprasert Wanvisa , McConachie Ellie , Ngarmukos Srihatach , Theerawattanapong Nipaporn , Tanavalee Aree , Honsawek Sittisak 
Published: April 2019

Objective Glypican-3 possesses a possible action in regulation of bone growth and development implicated in osteoarthritis (OA) pathology. Therefore, this study aimed to investigate glypican-3 in plasma and synovial fluid of knee OA patients and to determine the possible association between glypican-3 levels and radiographic severity. Design A total of 80 knee OA patients and 80 healthy controls were recruited. Glypican-3 levels in plasma and synovial fluid were measured using enzyme-linked immunosorbent assay. The severity of knee OA was assessed by radiographic grading according to the Kellgren-Lawrence classification. Relative mRNA expression of glypican-3 in 10 inflamed synovial tissues from OA patients and 10 noninflamed synovial controls was quantified using real-time polymerase chain reaction. Results Plasma glypican-3 levels were significantly lower in OA patients than in healthy controls ( P = 0.03), whereas synovial fluid glypican-3 levels were remarkably greater than in paired plasma samples of OA patients ( P < 0.001). Subsequent analysis demonstrated that plasma and synovial fluid glypican-3 levels were inversely associated with the radiographic severity of knee OA ( r = −0.691, P < 0.001; r = −0.646, P < 0.001, respectively). Furthermore, there was a positive relationship between plasma and synovial fluid glypican-3 levels in knee OA patients ( r = 0.515, P < 0.001). Additionally, overexpression of glypican-3 mRNA was observed in inflamed synovium of OA patients ( P = 0.021). Conclusions The present study revealed that plasma and synovial glypican-3 levels were negatively associated with radiographic severity of knee OA. Glypican-3 could emerge as a potential biomarker for reflecting the severity of knee OA and might play a plausible role in the pathophysiology of degenerative joint disease.
A comparison study on hindfoot correction, Achilles tendon length and thickness between clubfoot patients treated with percutaneous Achilles tendon tenotomy versus casting alone using Ponseti method
Authors: Chandirasegaran Saturveithan , Gunalan Roshan , Aik Saw , Kaur Shaleen 
Published: April 2019

Purpose: To compare the hindfoot correction using clinical and ultrasonography assessment in clubfoot patients undergoing Achilles tendon tenotomy with patients corrected with casting alone. Method: A prospective observational study on idiopathic clubfoot patients less than 3 months old. Clinical assessment was done using hindfoot Pirani score and measurement of ankle dorsiflexion. Serial ultrasonography was done to measure the length and thickness of the Achilles tendon pre-hindfoot correction, 3 and 6 weeks post-hindfoot correction. Independent t-test was used to analyse the increase in ankle dorsiflexion, improvement in length and thickness of Achilles tendon between the two groups. Mann–Whitney U test was used to analyse the improvement in hindfoot Pirani score. Pearson correlation test was used for correlation in between clinical severity and ultrasonography assessment. Results: Twenty-three patients with bilateral clubfoot and four with unilateral clubfoot were recruited with a total of 50 clubfeet. Each group consists of 25 feet with a mean age of 2 months. Marked improvement in hindfoot correction was noted in tenotomy group compared to non-tenotomy group as evidenced by significant increase in Achilles tendon length, ankle dorsiflexion and improvement of hindfoot Pirani score. No significant difference in Achilles tendon thickness was noted between the two groups. Positive correlation was demonstrated between increase in Achilles tendon length and increase in ankle dorsiflexion as well as improvement in hindfoot Pirani score. Conclusion: We would like to propose Achilles tendon tenotomy in all clubfoot patients as it is concretely evident that superior hindfoot correction was achieved in tenotomy group.
Inhibition of platelet GPVI induces intratumor hemorrhage and increases efficacy of chemotherapy in mice
Authors: Volz Julia , Mammadova-Bach Elmina , Gil-Pulido Jesus , Nandigama Rajender , Remer Katharina , Sorokin Lydia , Zernecke Alma , Abrams Scott I. , Ergün Süleyman , Henke Erik , Nieswandt Bernhard 
Published: April 2019

Abstract
Maintenance of tumor vasculature integrity is indispensable for tumor growth and thus affects tumor progression. Previous studies have identified platelets as major regulators of tumor vascular integrity, as their depletion selectively rendered tumor vessels highly permeable and caused massive intratumoral hemorrhage. While these results established platelets as potential targets for antitumor therapy, their depletion is not a treatment option due to their essential role in hemostasis. Thus, a detailed understanding of how platelets safeguard vascular integrity in tumors is urgently demanded. Here, we show for the first time that functional inhibition of glycoprotein VI (GPVI) on the platelet surface with an antibody (JAQ1) F(ab)2 fragment rapidly induces tumor hemorrhage and diminishes tumor growth similar to complete platelet depletion while not inducing systemic bleeding complications. The intratumor bleeding and tumor growth arrest could be reverted by depletion of Ly6G+ cells, confirming them to be responsible for the induction of bleeding and necrosis within the tumor. In addition, JAQ1 F(ab)2–mediated GPVI inhibition increased intratumoral accumulation of coadministered chemotherapeutic agents, such as Doxil and paclitaxel, thereby resulting in a profound antitumor effect. In summary, our findings identify platelet GPVI as a key regulator of vascular integrity specifically in growing tumors and could serve as a basis for the development of antitumor strategies based on the interference with platelet function.
Identification of a novel enhancer of CEBPE essential for granulocytic differentiation
Authors: Shyamsunder Pavithra , Shanmugasundaram Mahalakshmi , Mayakonda Anand , Dakle Pushkar , Teoh Weoi Woon , Han Lin , Kanojia Deepika , Lim Mei Chee , Fullwood Melissa , An Omer , Yang Henry , Shi Jizhong , Hossain Mohammad Zakir , Madan Vikas , Koeffler H. Phillip 
Published: April 2019

Abstract
CCAAT/enhancer binding protein ε (CEBPE) is an essential transcription factor for granulocytic differentiation. Mutations of CEBPE occur in individuals with neutrophil-specific granule deficiency (SGD), which is characterized by defects in neutrophil maturation. Cebpe-knockout mice also exhibit defects in terminal differentiation of granulocytes, a phenotype reminiscent of SGD. Analysis of DNase I hypersensitive sites sequencing data revealed an open chromatin region 6 kb downstream of the transcriptional start site of Cebpe in murine myeloid cells. We identified an interaction between this +6-kb region and the core promoter of Cebpe using circular chromosome conformation capture sequencing (4C-seq). To understand the role of this putative enhancer in transcriptional regulation of Cebpe, we targeted it using catalytically inactive Cas9 fused to Krüppel-associated box (KRAB) domain and observed a significant downregulation of transcript and protein levels of CEBPE in cells expressing guide RNA targeting the +6-kb region. To further investigate the role of this novel enhancer further in myelopoiesis, we generated mice with deletion of this region using CRISPR/Cas9 technology. Germline deletion of the +6-kb enhancer resulted in reduced levels of CEBPE and its target genes and caused a severe block in granulocytic differentiation. We also identified binding of CEBPA and CEBPE to the +6-kb enhancer, which suggests their role in regulating the expression of Cebpe. In summary, we have identified a novel enhancer crucial for regulating expression of Cebpe and required for normal granulocytic differentiation.
PD-1 blockade with pembrolizumab for classical Hodgkin lymphoma after autologous stem cell transplantation
Authors: Armand Philippe , Chen Yi-Bin , Redd Robert A. , Joyce Robin M. , Bsat Jad , Jeter Erin , Merryman Reid W. , Coleman Kimberly C. , Dahi Parastoo B. , Nieto Yago , LaCasce Ann S. , Fisher David C. , Ng Samuel Y. , Odejide Oreofe O. , Freedman Arnold S. , Kim Austin I. , Crombie Jennifer L. , Jacobson Caron A. , Jacobsen Eric D. , Wong Jeffrey L. , Patel Sanjay S. , Ritz Jerome , Rodig Scott J. , Shipp Margaret A. , Herrera Alex F. 
Published: April 2019

Abstract
Autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL) who respond to salvage chemotherapy. However, relapse after ASCT remains a frequent cause of treatment failure, with poor subsequent prognosis. Because cHL is uniquely vulnerable to programmed cell death-1 (PD-1) blockade, PD-1 blockade given as consolidation after ASCT could improve ASCT outcomes. We therefore conducted a multicohort phase 2 study of pembrolizumab in patients with RR cHL after ASCT, hypothesizing that it would improve the progression-free survival (PFS) at 18 months after ASCT (primary end point) from 60% to 80%. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles, starting within 21 days of post-ASCT discharge. Thirty patients were treated on this study. The median age was 33 years, and 90% were high-risk by clinical criteria. Seventy-seven percent completed all 8 cycles. Toxicity was manageable, with 30% of patients experiencing at least 1 grade 3 or higher adverse event (AE), and 40% at least 1 grade 2 or higher immune-related AE. Two patients were lost to follow-up in complete remission at 12 months. The PFS at 18 months for the 28 evaluable patients was 82%, meeting the primary end point. The 18-month overall survival was 100%. In conclusion, pembrolizumab was successfully administered as post-ASCT consolidation in patients with RR cHL, and resulted in a promising PFS in a high-risk patient cohort, supporting the testing of this strategy in a randomized trial. This trial was registered at www.clinicaltrials.gov as #NCT02362997.