bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of Auxiliary VerifyNow Point-of-Care Assays to Assess the Pharmacodynamics of RUC-4, a Novel αIIbβ3 Receptor Antagonist
Authors: Bentur Ohad S. , Li Jihong , Jiang Caroline S. , Martin Linda H. , Kereiakes Dean J. , Coller Barry S. 
Published: September 2021

AbstractIntroduction Prehospital therapy of ST-elevation myocardial infarction (STEMI) with αIIbβ3 antagonists improves clinical outcomes, but they are difficult to use in prehospital settings. RUC-4 is a novel αIIbβ3 antagonist being developed for prehospital therapy of STEMI that rapidly achieves high-grade platelet inhibition after subcutaneous administration. Standard light transmission aggregometry (LTA) is difficult to perform during STEMI, so we applied VerifyNow (VN) assays to assess the pharmacodynamics of RUC-4 relative to aspirin and ticagrelor.Methods Blood from healthy volunteers was anticoagulated with phenylalanyl-prolyl-arginyl chloromethyl ketone (PPACK) or sodium citrate, treated in vitro with RUC-4, aspirin, and/or ticagrelor, and tested with the VN ADP + PGE1, iso-TRAP, and base channel (high concentration iso-TRAP + PAR-4 agonist) assays. The results were correlated with both ADP (20 µM)-induced LTA and flow cytometry measurement of receptor occupancy and data from individuals treated in vivo with RUC-4.Results RUC-4 inhibited all three VN assays, aspirin did not affect the assays, and ticagrelor markedly inhibited the ADP + PGE1 assay, slightly inhibited the iso-TRAP assay, and did not inhibit the base channel assay. RUC-4's antiplatelet effects were potentiated in citrate compared with PPACK. Cut-off values were determined to correlate the results of the VN iso-TRAP and base channel assays with 80% inhibition of LTA.Conclusion The VN assays can differentiate the early potent anti-αIIbβ3 effects of RUC-4 from delayed effects of P2Y12 antagonists in the presence of aspirin. These pharmacodynamic assays can help guide the clinical development of RUC-4 and potentially be used to monitor RUC-4's effects in clinical practice.
Rectal Acetaminophen Improves Shunt Volume and Reduces Patent Ductus Arteriosus Ligation in Extremely Preterm Infants
Authors: Castaldo Michael P. , Neary Elaine , Bischoff Adrianne R. , Resende Maura H.F. , Weisz Dany E. , Jain Amish , Giesinger Regan E. , McNamara Patrick J. 
Published: September 2021

Objective An alternative therapy for preterm infants with a hemodynamically significant patent ductus arteriosus (hsPDA) is needed when cyclooxygenase inhibitors fail or where treatment is contraindicated due to coexisting renal failure, necrotizing enterocolitis, and/or intestinal perforation. No studies have evaluated the efficacy of per rectum (PR) acetaminophen. The study aimed to evaluate the efficacy of PR acetaminophen in modulating the risk of PDA ligation.
Study Design A retrospective matched case–control study was conducted to compare neonates born <29 weeks' gestation with evidence of hsDA, in an era when rescue rectal acetaminophen was used (January 2014–March 2018) as a treatment strategy, versus historical controls (July 2006–August 2012). All patients underwent comprehensive echocardiography assessment of ductal shunt volume according to a standardized protocol. Acetaminophen treated neonates were matched according to demographics, gestation, preintervention echocardiography features, and comorbidities. Control patients were selected when an echocardiography was performed at an equivalent postnatal age. Infants with a genetic syndrome, severe congenital malformation, or major forms of congenital heart disease excluding small atrial septal defect or ventricular septal defect, PDA, or patent formale ovale were excluded. The primary outcome was surgical ligation of the PDA. Secondary outcomes included echocardiography indices of hemodynamic significance, the composite of death, or severe BPD (defined by ventilator dependence at 36 weeks postmenstrual age). Descriptive statistics and univariate (t-tests, Fisher's exact test, and Mann–Whitney U test) analyses were used to evaluate clinical and echocardiography characteristics of the groups and compare outcomes.
Results Forty infants (20 cases and 20 controls), with similar demographic and echocardiography features, were compared. Cases received 6.8 ± 0.7 days (60 mg/kg/day) of PR acetaminophen. Responders (n = 12, 60%) had echocardiography evidence of reduced ductal diameter (2.2 mm [1.9–2.6] to 1.1 mm [0–1.7], p = 0.002), left ventricular output (363 ± 108–249 ± 61 mL/min/kg; p = 0.002) and left atrium to aortic root ratio (1.7 ± 0.3–1.3 ± 0.2; p = 0.002) following treatment. The rate of PDA ligation was 50% lower (p = 0.02) and composite outcome of death or severe bronchopulmonary dysplasia was reduced (p = 0.04) in the acetaminophen group.
Conclusion Rectal acetaminophen was associated with improvement in echocardiography indices of PDA shunt volume, a 50% reduction in PDA ligation rates and a reduction in the composite outcome of death or severe BPD. Pharmacologic and further prospective clinical studies are needed.
Key Points
Predicting Outcome in Skull Base Osteomyelitis: An Assessment of Demographic, Clinical, and Pathological Attributes
Authors: Saxena Alisha , Paul Birinder Singh , Singh Gagandeep , Ahluwalia Archana , Paul Gunchan 
Published: September 2021

Abstract

Objective Skull base osteomyelitis (SBO) is an enigmatic clinical diagnosis which is difficult to decipher and is associated with poor outcomes. The study aims to examine the demographic and clinical characteristics of patients with SBO and its outcomes.

Materials and Methods Medical records of 30 patients with diagnosis of SBO over past 5 years were assessed for demographic and clinical characteristics, type of SBO, radiological parameters, treatment received, procedure performed, microbiological profile, comorbidities, and complications including cranial nerve (CN) palsies. These factors were analyzed for prediction of outcome (death or survival).

Statistical Analysis Microsoft Office Excel 2010 SAS 10.0 for Windows was used. Student's t-test for continuous variables (age, duration of symptoms, number of days of hospitalization, and treatment duration) and chi-square test for categorical variables (imaging findings, symptomatology, presence of comorbidities, surgical procedure, complications, and type of antibiotics) were utilized.

Results We found SBO was the disease of elderly population (64.07 ± 6.13 years) with male predominance (83.3%) highly associated with uncontrolled diabetes status (93.3%). Headache (100%) and CN palsy (80%) were the most common neurological presenting complaints followed by stroke (17%) and encephalopathy (10%). Pathological and radiological correlation showed that fungal infection (Aspergillus) was associated with anterior SBO (10%), while bacteria (Pseudomonas) was cultured from posterior SBO (30%). Fifty per cent of patients were alive after 1 year out of which 33% had good functional outcome. The mortality rate was 33.3% in our cohort and multiple lower CN palsies (p = 0.04), suboptimal duration of medical treatment (p = 0.03), surgical intervention during clinical course (p = 0.02), and development of intracranial or extracranial complications (p = 0.03) were the predictors of mortality.

Conclusion Early diagnosis including identification of pathogenic organisms and optimal duration of treatment are crucial factors for improved outcomes in SBO.
Association of Mean Platelet Volume with Risk Factors and Functional Outcome in Acute Ischemic Stroke
Authors: OT Sreejith , Zafar Lubna , Beg Mujahid , Siddiqui Obaid Ahmed 
Published: September 2021

Abstract

Background Stroke is the second leading cause of death in the world and a major cause of disability, with ischemic stroke contributing to 87% of all strokes. Platelets are central in the formation of thrombus, and in the process, they enlarge in size, become active, and secrete prothrombotic factors. This is supported by the presence of large platelets in ischemic stroke, where they may be implicated in the pathogenesis of vessel occlusion, leading to stroke. The mean platelet volume (MPV) is an important laboratory marker of platelet function and activation.

Materials and Methods The present study was conducted to assess the role of MPV in the pathogenesis, severity, and outcome of ischemic stroke. It was an observational study in 100 acute ischemic stroke (AIS) patients (excluding cardioembolic stroke) admitted to the Medicine wards, Department of Medicine, Jawaharlal Nehru Medical College, a tertiary care hospital at Aligarh. The MPV was correlated with the conventional risk factors of ischemic stroke and outcome (using modified Rankin scale [mRS]). The study revealed statistically significant correlation between MPV and hypertension, type 2 diabetes mellitus, and carotid intima media thickness (CIMT). Also, the MPV at presentation positively correlated with mRS (correlation coefficient 0.818); thus, high MPV was associated with more severe disability.

Conclusion The MPV at the time of presentation of ischemic stroke may be useful in predicting the severity of stroke and neurological recovery. However, a larger study including diverse population is required to endorse its predictive value in AIS.
Etiological and Radiological Spectrum of Longitudinal Myelitis: A Hospital-Based Study in North East India
Authors: Synmon Baiakmenlang , Phukan Pranjal , Sharma Shri Ram , Hussain Mussaraf 
Published: September 2021

Abstract

Introduction An inflammatory lesion of the spinal cord where three or more than three vertebral segments of the cord is involved is called longitudinal extensive myelitis (LETM). It has several varied causes out of which neuromyelitis optica (NMO) and its spectrum disorder have received a distinct entity. Various radiological and clinical features help us to suspect an etiology which then further guides us into the treatment protocol and prognosis of the patients.

Materials and Methods A retrospective study performed in a referral center in North East India in 15 months. Thirty-two patients of LETM were enrolled based on clinical and radiological available data. An attempt was made to classify the various etiologies and correlate with their radiological findings.

Results The most common etiology noted was NMO seen in 7 patients (21.8%) followed by tuberculosis (TB) (18.7%) and post-infection myelitis (18.7%). Other etiology seen was acute disseminated encephalomyelitis (6.24%), spinal cord infarct (3.12%), radiation myelitis (6.24%), Japanese encephalitis sequalae (3.12%), systemic lupus erythematosus (3.12%), and remained undiagnosed in six patients (18.7%). Radiologically, cervico-dorsal spine was most common location in NMO (71%) whereas dorsolumbar in TB (50%). The lesion was predominantly central in both NMO (100%) and TB (80%) as compared with the other causes of LETM. It was noted that more than 50% of the transverse area of the cord was involved in both NMO (71%) and TB (50%), but < 50% involvement were more common in the post-infectious and others causes of LETM.

Conclusion LETM has a various differential diagnosis, infection need to be kept in mind while ruling out NMO. Radiological features can suggest or help differentiate the various etiologies of LETM but NMO and infection like TB almost has the same features except for a different cord site predilection.
Head and Neck Free Flap Reconstruction in an Academic versus a Community Setting
Authors: Lewcun Joseph , Massand Sameer , Trangucci John , Shen Chan , Johnson Timothy S. 
Published: September 2021

Abstract
Background Head and neck free flap reconstructions are complex procedures requiring extensive resources, and have the potential to be highly morbid. As such, it is imperative that they should be performed in an appropriate setting, optimizing outcomes while limiting morbidity. The aim of this study is to identify any disparities in the treatment outcomes of patients undergoing head and neck free flap reconstruction by a single surgeon in an academic versus a community hospital setting.
Methods A retrospective review of all patients who underwent head and neck free flap reconstruction for any indication by a single surgeon from 2009 to 2019 was conducted. All surgeries were performed at one of two hospitals: one academic medical center and one community hospital. Demographics and rates of partial or complete flap failure, medical complications, surgical complications, mortality, and other secondary outcomes were compared between the two settings.
Results Ninety-two patients who underwent head and neck free flap reconstruction were included. Fifty-seven (62%) of free flap reconstructions were performed in the academic medical center, while 35 (38%) were performed in the community hospital. There were no significant differences in complete flap loss, either intraoperative or postoperative (p = 0.5060), partial flap loss (p = 0.5827), postoperative surgical complications (p = 0.2930), or medical complications (p = 0.7960) between groups. The in-hospital mortality rate was 0% (n = 0) at the university hospital as compared with 5.7% at the community hospital (p = 0.0681). The mean operative time was 702.3 minutes at the university hospital and 606.3 minutes at the community hospital (p = 0.0080).
Conclusion Head and neck free flap surgery can be performed safely in either an academic or a community setting, with no difference in primary outcomes of surgery. Preferential selection of either treatment setting should be based on consideration of patient needs and availability of auxiliary specialty services.
Extended Cranial Ultrasound Views in Infants with Acute Brain Stem/Infratentorial Lesions: Diagnosis of a Progressive Midline Glioma in a 6-Week-Old Infant
Authors: Lange Matthias , Mitzlaff Bernd , Beske Florian , Koester Holger , Aumann Wiebke , Woitzik Johannes , Mueller Hermann L. , Heep Axel 
Published: September 2021

AbstractCentral nervous system (CNS) tumors are the most common solid tumors in children and adolescents. However, in neonates and children aged younger than a year, they are very rare. Clinical presentation in neonates is often subtle and nonspecific. When neurological symptoms are apparent at this age, cranial ultrasound (CUS) is often done as the initial evaluation, with a standard approach through the anterior fontanel (AF), followed by further imaging, such as magnetic resonance imaging (MRI), if necessary. We report the first neonatal case of a rapidly progressive diffuse midline glioma positive for histone H3 K27M mutation (World Health Organization [WHO] grade IV) in which using extended (transmastoid) CUS studies through the mastoid fontanelle (MF) in the second month of life defined the lesion in the brainstem.
Reclaiming agency: skills, academics and students in the Social Sciences
Authors: David Maxine , Maurer Heidi 
Published: September 2021

AbstractThe adoption of active learning pedagogy and, later, the institution of the employability agenda in Higher Education have resulted in a severe loss of agency for academics and students in the Social Sciences. In this article, we reflect on our experiences of applying active learning methods. We argue that we have been part of a change that has occasioned a loss of key skills development, especially those associated with traditional learning and academic thinking. An overly headlong rush to implement the “new” over the “old” saw the discarding of certain skills central to the active learning agenda. Further, the emphasis on student satisfaction, professionalisation and quality assurance pushed the academic to the sidelines, to the detriment of Higher Education. We, therefore, first critique the skills debate and identify shortcomings in the active learning application that emerged from that debate. We focus on the skills emphasised in practice, how they are portrayed in opposition (instead of complementarity) to academic skills, and how they undermine the agency academics and students really require. Next, we propose a reconsideration of necessary but undervalued skills like reading, listening and note-taking.
Gold and silver nanocomposite-based biostable and biocompatible electronic textile for wearable electromyographic biosensors
Authors: Lim Taehwan , Zhang Huanan , Lee Sohee 
Published: September 2021

Wearable biosensors have received significant attention due to the possibility of measuring physiological signals on demand. Particularly, the monitoring of electromyographic (EMG) signals on demand by wearable platforms has significant potential to revolutionize the diagnostics and treatment of neuromuscular diseases and for advancing human–computer interfaces. Electronic textile-based biosensors have several advantages, including the simple scale-up process and the ease of fabricating multiple large area electrodes over the whole body to obtain precise measurements. Hence, the electronic textile production requires an affordable approach to fabricate biocompatible and biostable electronic circuits on textile materials. This work explores the possibility of combining screen printing and electrodeposition techniques to produce a biostable nanocomposite-based EMG biosensor on textile. Screen printing was selected to fabricate conductive fabrics that would ultimately be a highly durable textile-based sensor. Silver paste, including microscale silver flakes, was printed on PET/cotton blended fabrics. However, the microscale silver surface was limited for EMG sensors due to low surface area and toxicity, causing low signal detection performance and skin irritation. Gold nanoparticles (Au NPs) were deposited on silver flakes to address the requirements of high-performance and biocompatible biosensors. We confirmed that the gold functionalization improved electrical and electrochemical performance. In addition, various tests were performed to determine electrochemical and biological stability under physiological conditions. The test results proved that Au NPs have successfully encapsulated the surface of silver flakes, preventing the exposure of the silver to the physiological environment. EMG signal recording was performed to confirm the functionalization effect that improved the signal to noise ratio (SNR) of 12.5 with 120 nm Au NPs. Moreover, EMG sensing from bicep workouts and finger movements showed the high sensitivity of the electronic fabrics. Although the SNR of EMG signals dropped to 7.2 after a 15-time washing test, the stabilized SNR after 5 washing cycles indicated that the Au/Ag biosensors showed washing durability. The study demonstrates that this affordable approach can be considered for large-scale production of wearable EMG biosensors.
Structural basis for isoform-specific inhibition of human CTPS1
Authors: Lynch Eric M. , DiMattia Michael A. , Albanese Steven , van Zundert Gydo C. P. , Hansen Jesse M. , Quispe Joel D. , Kennedy Madison A. , Verras Andreas , Borrelli Kenneth , Toms Angela V. , Kaila Neelu , Kreutter Kevin D. , McElwee Joshua J. , Kollman Justin M. 
Published: September 2021

Significance
An effective immune response depends on the proliferation of T cells, a process that requires the enzyme CTP synthase 1 (CTPS1). Individuals lacking CTPS1 due to a rare genetic disorder exhibit severe immunodeficiencies but lack other major clinical consequences; the requirement for CTP synthase outside of the immune response is met by a second isoform, CTPS2. Inhibiting CTPS1 without affecting CTPS2 is therefore a promising strategy for treating autoimmune disorders and T cell cancers while avoiding off-target effects. We characterize both CTPS1-selective and nonselective inhibitors. Structures of CTPS bound to inhibitors reveal the mechanisms of inhibition and CTPS1 selectivity. Differences in product feedback inhibition between CTPS1 and CTPS2 explain how CTPS1 may sustain enzymatic activity required for T cell proliferation.
Presentation followed by negotiation
Authors: Izutsu Katsunobu , Narita Izutsu Mitsuko 
Published: September 2021

Abstract
This study explores the sequential pattern of
sentence- or utterance-final pragmatic particles in Ainu, an
indigenous language of Japan, and demonstrates that the particle
sequences largely exhibit an ordering summarized as presentation
followed by negotiation: a particle concerning the “presentation” of
a speech act is followed by another particle representing the
“negotiation” with the addressee for a speech act. These
“presenting” and “negotiating” functions are further analyzed with
respect to the speech event conception that underlies those
functions.
Verb-based discourse markers in Italian
Authors: Badan Linda 
Published: September 2021

Abstract
This research deals with verb-based discourse
markers in the regional Italian of Veneto: guarda
(te) ‘look you’, vedi (te) ‘see you’.
We show that these markers differ in terms of functions and
syntactic features. We argue that the functions differ depending on
the discourse markers’ syntactic position: some functions can be
realized only in the left periphery, while others can be realized in
both peripheries. When in the left periphery, the discourse markers
express the speaker’s attitude, have their own illocutionary force
and are much more independent from the preceding linguistic context.
Conversely, the discourse markers that can be realized in both
peripheries seem to have a reinforcement and interactional role,
being strictly dependent on the dialogical context.
Emoji as graphic discourse markers
Authors: Wiese Heike , Labrenz Annika 
Published: September 2021

Abstract
We investigate emoji as graphic discourse
markers in German WhatsApp® messages. As comparably novel devices in
the rapidly evolving domain of digital messenging, emoji provide an
interesting example to observe change in progress. We present a
corpus study and an experimental study. Main results are (i) an
overall salience of subjective and intersubjective discourse
meanings for emoji, with (ii) a general advantage for the former,
especially for emoji that iconically include more active elements,
while (iii) dominance relations can be modulated by left- vs.
right-peripheral positions in favor of subjective vs.
intersubjective meanings, respectively. By approaching emoji as
discourse markers, the studies contribute to our understanding of
their pragmatic contribution and provide novel evidence on
positional-functional associations for pragmatic markers.
Functional asymmetry and left-to-right movement
Authors: Bai Yinchun 
Published: September 2021

Abstract
This corpus-based study of the discourse marker
speaking of X addresses the issues of
functional asymmetry and left-to-right movement. It shows that
speaking of X has different pragmatic
functions, which may express different degrees of
(inter)subjectivity in different peripheral positions. But these
functions are not strictly confined to certain peripheries and,
diachronically, there is no statistically significant evidence of
further (inter)subjectification or change in peripheral preferences.
This study thus confirms that the functional asymmetry hypothesis is
better understood as a strong tendency that holds better for certain
functional domains than for others and it serves as a counterexample
to the related left-to-right movement hypothesis therewith.
Literacy histories and talk around texts
Authors: Ávila Reyes Natalia 
Published: September 2021

Abstract
This chapter discusses the value of emic research methods and techniques for studying the academic writing of underrepresented students. In a global context of growing university enrolment, academic writing is seen as one of the main challenges that historically underrepresented students face when admitted to higher education. Studying academic writing in this context calls for a critical stance on language and an emic perspective on research to counteract deficit models that prevail in this kind of research. An ethnographic approach responds to the ontologies and epistemologies needed for this endeavour. Drawing on two research projects, this chapter exemplifies the power of tools such as literacy histories and talk around texts to unveil multiple forms of agency enacted by student writers.