bluuebunny/crossref_metadata_2025_split huggingface dataset:
Receptive Arts Engagement for Health: A Holistic and Trans-Disciplinary Approach to Creating a Multisensory Environment
Authors: Cavanagh Bliss , Haracz Kirsti , Lawry Miranda , James Carole 
Published: December 2020

Multisensory environments are increasingly being used in health care settings with reported benefits including relaxation, supporting self-regulation, enhancing mood, and reducing chronic pain. However, limited research exists that explores the impact of multisensory environment design on engagement. In response, this article presents a qualitative study exploring the creative design attributes that cultivated participant engagement and shaped their overall experience of spending time in an artistically created multisensory environment: the Sensory-Art Space (SAS). A maximum variation approach to sampling was used to select 18 participants. Data were gathered via semi-structured interviews and were audio-recorded and transcribed verbatim before being analyzed thematically. Our findings produced three key themes. The first two themes were: the ambience of everything and variation: it’s always my choice, which identified aspects of the artistic design that fostered engagement and the sense of connection and ownership of the SAS captured in the third theme, a space that’s yours. Based on analysis of participant responses, creative design considerations were identified that could assist the development of future multisensory spaces and highlighted the importance of a holistic and curatorial approach to enhance engagement value.
The evolution of factor XI and the kallikrein-kinin system
Authors: Ponczek Michał B. , Shamanaev Aleksandr , LaPlace Alec , Dickeson S. Kent , Srivastava Priyanka , Sun Mao-fu , Gruber Andras , Kastrup Christian , Emsley Jonas , Gailani David 
Published: December 2020

AbstractFactor XI (FXI) is the zymogen of a plasma protease (FXIa) that contributes to hemostasis by activating factor IX (FIX). In the original cascade model of coagulation, FXI is converted to FXIa by factor XIIa (FXIIa), a component, along with prekallikrein and high-molecular-weight kininogen (HK), of the plasma kallikrein-kinin system (KKS). More recent coagulation models emphasize thrombin as a FXI activator, bypassing the need for FXIIa and the KKS. We took an evolutionary approach to better understand the relationship of FXI to the KKS and thrombin generation. BLAST searches were conducted for FXI, FXII, prekallikrein, and HK using genomes for multiple vertebrate species. The analysis shows the KKS appeared in lobe-finned fish, the ancestors of all land vertebrates. FXI arose later from a duplication of the prekallikrein gene early in mammalian evolution. Features of FXI that facilitate efficient FIX activation are present in all living mammals, including primitive egg-laying monotremes, and may represent enhancement of FIX-activating activity inherent in prekallikrein. FXI activation by thrombin is a more recent acquisition, appearing in placental mammals. These findings suggest FXI activation by FXIIa may be more important to hemostasis in primitive mammals than in placental mammals. FXI activation by thrombin places FXI partially under control of the vitamin K-dependent coagulation mechanism, reducing the importance of the KKS in blood coagulation. This would explain why humans with FXI deficiency have a bleeding abnormality, whereas those lacking components of the KKS do not.
CAR T cells or allogeneic transplantation as standard of care for advanced large B-cell lymphoma: an intent-to-treat comparison
Authors: Dreger Peter , Dietrich Sascha , Schubert Maria-Luisa , Selberg Lorenz , Bondong Andrea , Wegner Mandy , Stadtherr Peter , Kimmich Christoph , Kosely Florentina , Schmitt Anita , Pavel Petra , Liebers Nora , Luft Thomas , Hegenbart Ute , Radujkovic Aleksandar , Ho Anthony Dick , Müller-Tidow Carsten , Schmitt Michael 
Published: December 2020

Abstract
CD19-directed chimeric antigen receptor (CAR) T-cell treatment has evolved as standard of care (SOC) for multiply relapsed/refractory (R/R) large B-cell lymphoma (LBCL). However, its potential benefit over allogeneic hematopoietic cell transplantation (alloHCT) remains unclear. We compared outcomes with both types of cellular immunotherapy (CI) by intention to treat (ITT). Eligble were all patients with R/R LBCL and institutional tumor board decision recommending SOC CAR T-cell treatment between July 2018 and February 2020, or alloHCT between January 2004 and February 2020. Primary end point was overall survival (OS) from indication. Altogether, 41 and 60 patients for whom CAR T cells and alloHCT were intended, respectively, were included. In both cohorts, virtually all patients had active disease at indication. CI was recommended as part of second-line therapy for 21 alloHCT patients but no CAR T-cell patients. Median OS from indication was 475 days with CAR T cells vs 285 days with alloHCT (P = .88) and 222 days for 39 patients for whom alloHCT beyond second line was recommended (P = .08). Of CAR T-cell and alloHCT patients, 73% and 65%, respectively, proceeded to CI. After CI, 12-month estimates for nonrelapse mortality, relapse incidence, progression-free survival, and OS for CAR T cells vs alloHCT were 3% vs 21% (P = .04), 59% vs 44% (P = .12), 39% vs 33% (P = .97), and 68% vs 54% (P = .32), respectively. In conclusion, CAR T-cell outcomes were not inferior to alloHCT outcomes, whether measured by ITT or from CI administration, supporting strategies preferring CAR T cells over alloHCT as first CI for multiply R/R LBCL.
Intrabone transplantation of CD34+ cells with optimized delivery does not enhance engraftment in a rhesus macaque model
Authors: Stringaris Kate , Hoyt Robert F. , Davidson-Moncada Jan K. , Pantin Jeremy M. , Tisdale John F. , Uchida Naoya , Raines Lydia N. , Reger Robert , Sato Noriko , Dunbar Cynthia E. , Hunt Timothy J. , Clevenger Randall R. , Krouse Allen , Metzger Mark E. , Bonifacino Aylin C. , Telford William , Choyke Peter L. , Engels Theresa , Donahue Robert E. , Childs Richard W. 
Published: December 2020

Abstract
Intrabone (IB) injection of umbilical cord blood has been proposed as a potential mechanism to improve transplant engraftment and prevent graft failure. However, conventional IB techniques produce low retention of transplanted cells in the marrow. To overcome this barrier, we developed an optimized IB (OIB) injection method using low-volume, computer-controlled slow infusion that promotes cellular retention in the marrow. Here, we compare engraftment of CD34+ cells transplanted in a myeloablative rhesus macaque (RM) model using the OIB method compared with IV delivery. RM CD34+ cells obtained by apheresis were split equally for transduction with lentiviral vectors encoding either green fluorescent protein or yellow fluorescent protein reporters. Following conditioning, one marked autologous population of CD34+ cells was injected directly IB using the OIB method and the other was injected via slow IV push into the same animal (n = 3). Daily flow cytometry of blood quantified the proportion of engrafting cells deriving from each source. Marrow retention was examined using positron emission tomography/computed tomography imaging of 89Zirconium (89Zr)-oxine–labeled CD34+ cells. CD34+ cells injected via the OIB method were retained in the marrow and engrafted in all 3 animals. However, OIB-transplanted progenitor cells did not engraft any faster than those delivered IV and contributed significantly less to hematopoiesis than IV-delivered cells at all time points. Rigorous testing of our OIB delivery system in a competitive RM myeloablative transplant model showed no engraftment advantage over conventional IV infusion. Given the increased complexity and potential risks of IB vs IV approaches, our data do not support IB transplantation as a strategy to improve hematopoietic engraftment.
Climate change causes changes in biochemical markers of kidney disease
Authors: Ephraim Richard Kobina Dadzie , Asamoah Christopher Amey , Abaka-Yawson Albert , Kwadzokpui Precious Kwablah , Adusei Samuel 
Published: December 2020

Abstract
Background
Climate change is a significant threat to the health of the Ghanaian people. Evidence abounds in Ghana that temperatures in all the ecological zones are rising, whereas rainfall levels have been generally reducing and patterns are increasingly becoming erratic. The study estimated the impact of climate variation between seasons on biochemical markers of kidney disease.

Methods
This study conveniently recruited 50 apparently healthy peasant farmers and hawkers at Wa in the Upper West Region of Ghana. A pre-study screening for hepatitis A and C, Diabetes mellitus, hypertension was done. Serum creatinine and urea levels were analyzed to rule out kidney preexisting kidney disease. Baseline data was collected by estimating urea, creatinine, sodium, potassium, eGFR (estimated glomerular filtration rate) as well as for hemoglobin (Hb) and hematocrit (Hct) concentrations. Anthropometric data such as height, weight and blood pressure were measured by trained personnel. The study participants were closely followed and alerted deep in the dry season for the second sampling (urea, creatinine, hemoglobin, hematocrit, blood pressure, anthropometry).

Results
This study recruited more males (58.82%) than females (41.15%), majority (52.92%) of which were aged 25–29 years with the youngest being 22 years and the eldest being 35 years. The study found body mass index (p < 0.001), systolic blood pressure (p = 0.019), creatinine (p < 0.001), urea (p = 0.013) and eGFR (p < 0.001) to be significantly influenced by climate change. Stage 1 hypertension was predominant among the study participants during the dry season, 8 (15.69%) than was observed during the rainy season, 4 (7.84%) nonetheless the number of participants with normal BMI rose from 49.02% in the rainy season to 62.75% during the dry reason. Additionally, the study observed that the impact of climate change on systolic blood pressure and urea varied based on age and sex.

Conclusion
This study revealed that climatic changes cause variations in various biochemical parameters used to assess kidney function. Public health education on climatic changes and its implication including precautionary measures should be done among inhabitants of Wa and its environs to reduce its effect. Additionally, appropriate dietary patterns should also be advised to avoid the development of non-communicable diseases such as hypertension and obesity that are known principal causes of Chronic Kidney Disease (CKD).
Wheeze and cough measurements at night in children with respiratory symptoms
Authors: Lindenhofer Markus , Roth Lena , Mädel Clemens , Götzinger Florian , Kainz Katharina , Lex Christiane , Frischer Thomas , Reinweber Matthias , Zacharasiewicz Angela 
Published: December 2020

Abstract
Background
Nocturnal cough and wheeze are important symptoms when diagnosing any respiratory disease in a child, but objective measurements of these symptoms are not performed.

Methods
The aim of our study was to analyze the use of an automated detection system to assess breath sounds objectively in comparison to cough and wheeze questionnaires and to evaluate its feasibility in clinical practice.

Results
Forty-nine recordings of thirty-nine children were processed (asthma n = 13; cystic fibrosis n = 2; pneumonia n = 5; suspicion of habit cough n = 7; prolonged, recurrent or chronic cough n = 13), and cough and asthma scores were compared to the objective nocturnal recordings. Time for audio-validation of recordings took between 2 and 40 min (mean: 14.22 min, (SD): 10.72). Accuracy of the automated measurement was higher for cough than for wheezing sounds. Nocturnal cough readings but not wheeze readings correlated with some of the corresponding scores.

Conclusion
To our knowledge this is the first study using a new device to assess nocturnal cough and obstructive breath sounds objectively in children with a wide variety of respiratory diseases. The assessment proved user friendly. We obtained additional information on nighttime symptoms, which would otherwise have remained obscure. Further studies to assess possible diagnostic and therapeutic benefits of this device are needed.
Identification of KRAS mutation in a patient with linear nevus sebaceous syndrome: a case report
Authors: Pan Chun , Zhou Xiaowei , Hong Anlan , Fang Fang , Wang Yan 
Published: December 2020

Abstract
Background
Linear nevus sebaceous syndrome (LNSS) is a rare genetic disease characterized by large linear sebaceous nevus typically on the face, scalp, or neck. LNSS could be accompanied by multisystem disorders including the central nervous system. Herein, we report gene mutational profile via whole exome sequencing of both lesional and non-lesional skin samples in a LNSS patient.

Case presentation
A 17-year-old girl presented with multisystem abnormalities, including large skin lesions, ocular disorders, abnormal bone development and neurological symptoms. A diagnosis of LNSS was established based on clinical manifestations, histopathological and imaging findings. The skin lesions were resected and no recurrence was noted at the time of drafting this report. Whole exome sequencing of genomic DNA revealed the following 3 mutations in the lesions of the index patient: KRAS (c.35G > A, p.G12D), PRKRIR (c.A1674T, p.R558S), and RRP7A (c. C670T, p.R224W), but no mutation was found in the healthy skin and peripheral blood sample of the index patient, or in the blood samples of her parents and sibling. PCR-mediated Sanger sequencing of DNA derived from lesional skin sample of the index patient verified KRAS mutation, but not PRKRIR (c.A1674T, p.R558S) and RRP7A (c. C670T, p.R224W). None of the 3 mutations was found in Sanger sequencing in skin lesions of 60 other cases of nevus sebaceous patients.

Conclusions
Our findings show the relevance of KRAS mutation to LNSS, providing new clues in understanding related genetic heterogeneity which could aid genetic counselling for LNSS patients.
Age dependency of EQ-5D-Youth health states valuations on a visual analogue scale
Authors: Retra Jim G. A. , Essers Brigitte A. B. , Joore Manuela A. , Evers Silvia M. A. A. , Dirksen Carmen D. 
Published: December 2020

AbstractBackgroundExamine whether the use of different ages has an impact on the valuation of EQ-5D-Y health states for a hypothetical child or adolescent.MethodsA survey was administered during regular classes among a convenience sample of university students in the Netherlands. Respondents first valued 6 EQ-5D-Y health states (2 mild, 2 moderate, 2 severe) describing a hypothetical child/adolescent of a certain age on a visual analogue scale (VAS). After 1 h respondents valued the same six health states again but this time the age of the child was different. Age differed between 4, 10 and 16 year old.ResultsNumber of respondents was 311. No significant differences in valuation of the six health states were found between the age of 10 and 16. One moderate health state was valued significantly better for a 4-year old compared to a 10 and a 16 year old. The same applied for one severe health state that was valued higher for a 4-year old compared to a 16-year old.ConclusionOur study shows that, except for one moderate and one severe health state, other EQ-5D-Y health states were not valued significantly different when description of age differed. It is possible that problems in specific health domains are considered more severe for older children/adolescents compared to younger children who might still be dependent on their caregivers. Future research should examine whether our findings are also present in a broader set of EQ-5D-Y health states, with a choice-based method like TTO or DCE, and a more heterogeneous sample.
Sulforaphane induces colorectal cancer cell proliferation through Nrf2 activation in a p53-dependent manner
Authors: Gwon Yunjeong , Oh Jisun , Kim Jong-Sang 
Published: December 2020

AbstractSulforaphane is a well-known phytochemical that stimulates nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant cellular response. In this study, we found that sulforaphane promoted cell proliferation in HCT116 human colon cancer cells expressing a normal p53 gene in a dose-dependent but biphasic manner. Since p53 has been reported to contribute to cell survival by regulating various metabolic pathways to adapt to mild stress, we further examined cellular responses in both p53-wild-type (WT) and p53-knockout (KO) HCT116 cells exposed to sulforaphane in vitro and in vivo. Results demonstrated that sulforaphane treatment activated Nrf2-mediated antioxidant enzymes in both p53-WT and p53-KO cells, decreased apoptotic protein expression in WT cells but increased in KO cells in a dose-dependent manner, and increased the expression of a mitochondrial biogenesis marker PGC1α in WT cells but decreased in KO cells. Moreover, a low dose of sulforaphane promoted tumor growth, upregulated the Nrf2 signaling pathway, and decreased apoptotic cell death in p53-WT HCT116 xenografts compared to that in p53-KO HCT116 xenografts in BALB/c nude mice. These findings suggest that sulforaphane can influence colon cancer cell proliferation and mitochondrial function through a crosstalk between the Nrf2 signaling pathway and p53 axis.
Optimal Monitoring of Weekly IGF-I Levels During Growth Hormone Therapy With Once-Weekly Somapacitan
Authors: Juul Kildemoes Rasmus , Højby Rasmussen Michael , Agersø Henrik , Overgaard Rune Viig 
Published: December 2020

Abstract

Context
Somapacitan is a long-acting growth hormone (GH) in development for once-weekly treatment of GH deficiency (GHD). Optimal monitoring of insulin-like growth factor-I (IGF-I) levels must account for weekly IGF-I fluctuations following somapacitan administration.

Objective
To develop and assess the reliability of linear models for predicting mean and peak IGF-I levels from samples taken on different days after dosing.

Design
A pharmacokinetic/pharmacodynamic model was used to simulate IGF-I data in adults and children following weekly somapacitan treatment of GHD.

Setting and Patients
39 200 IGF-I profiles were simulated with reference to data from 26 adults and 23 children with GHD.

Intervention(s)
The simulated dose range was 0.02 to 0.12 mg/kg for adults and 0.02 to 0.16 mg/kg for children. Simulated data with &gt;4 average standard deviation score were excluded.

Main Outcome Measure(s)
Linear models for predicting mean and peak IGF-I levels based on IGF-I samples from different days after somapacitan dose.

Results
Robust linear relationships were found between IGF-I sampled on any day after somapacitan dose and the weekly mean (R2 &gt; 0.94) and peak (R2 &gt; 0.84). Prediction uncertainties were generally low when predicting mean from samples taken on any day (residual standard deviation [RSD] ≤ 0.36) and peak from samples taken on day 1 to 4 (RSD ≤ 0.34). IGF-I monitoring on day 4 and day 2 after dose provided the most accurate estimate of IGF-I mean (RSD &lt; 0.2) and peak (RSD &lt; 0.1), respectively.

Conclusions
Linear models provided a simple and reliable tool to aid optimal monitoring of IGF-I by predicting mean and peak IGF-I levels based on an IGF-I sample following dosing of somapacitan. A short visual summary of our work is available (1).
11-Oxygenated Androgens Useful in the Setting of Discrepant Conventional Biomarkers in 21-Hydroxylase Deficiency
Authors: Jha Smita , Turcu Adina F , Sinaii Ninet , Brookner Brittany , Auchus Richard J , Merke Deborah P 
Published: December 2020

Abstract

Context
Serum 17-hydroxyprogesterone (17OHP) and androstenedione (A4) are the conventional biomarkers used to assess disease control in patients with 21-hydroxylase deficiency (21OHD). However, discrepancy between the two is not uncommon, limiting interpretation.

Objective
To evaluate 11-oxyandrogens in discriminating good versus poor disease control in 21OHD in the setting of discrepant 17OHP and A4.

Methods
Retrospective analysis of 2738 laboratory assessments obtained as part of Natural History Study of congenital adrenal hyperplasia (CAH) at the National Institutes Health Clinical Center. Patients with discrepant 17OHP and A4 and available sera were selected. A 15-steroid mass-spectrometry panel was performed in sera from patients with 21OHD and age- and sex-matched controls. Patients were categorized in “good” or “poor” control based on clinical assessment (bone age advancement, signs and symptoms of precocious puberty, menstrual irregularity, hirsutism, or hypogonadotrophic hypogonadism).

Results
Discrepant 17OHP and A4 was found in 469 (17%) laboratory assessments. Of these, 403 (86%) had elevated 17OHP with A4 in reference range. Of 46 patients with available sera, 30 (65%) were in good control. Median fold elevation relative to controls was higher in patients with poor versus good control for 11-hydroxytestosterone (median [interquartile range], 2.82 [1.25-5.43] vs 0.91 [0.49- 2.07], P = .003), and 11-ketotestosterone (3.57 [2.11-7.41] vs 1.76 [1.24-4.00], P = .047). Fold elevation of 11-hydroxytestosterone between 3.48 (sensitivity 97%, specificity 47%) and 3.88 (sensitivity 100%, specificity 40%) provided the best discrimination between poor vs good control.

Conclusion
11-Oxyandrogens, especially 11-hydroxytestosterone, may be useful in the management of CAH when conventional biomarkers are inconclusive.
Development of the Student’s Educational Independence in the Course of Designing His Individual Educational Route
Authors: Kazanceva Elena , Zhdanova E. 
Published: December 2020

The authors of the article substantiate the relevance of expanding the term “educational independence” to the concept of “educational
independence”, which is proposed for use in primary school didactics. Educational independence, in contrast to educational independence, is not limited to educational situations, but also manifests itself in arbitrary cognitive activity, which meets modern requirements for learning outcomes, regardless of its period. However, when characterizing educational independence, it is necessary to take into account the individual capabilities of children of primary school age. As an effective means of developing educational independence, the article considers the construction of an individual educational route for a younger student, analyzes the process of its development using the Moodle distance learning system, which includes four stages: diagnostic, design, technological and evaluation. The sequence of joint actions of a teacher and a student to draw up a map of his individual educational route within the framework of a separate academic subject is given.
Multimedia Educational Presentations for Independent (Autonomous) Work of Younger Students
Authors: Bulycheva N. , Savochkina E. , Shtil'man N. 
Published: December 2020

The article reveals the possibilities of using multimedia educational presentations as a means of methodological support of the distance
educational process in primary school. It is emphasized that multimedia educational presentations are considered by the authors only as an
emergency alternative to traditional education, in conditions when there is a need for a general temporary transition to its distance form. The
problems of organizing distance learning, which are especially relevant for primary school, and the ways of their solution with the help of
multimedia educational presentations, which are able to stimulate independent (autonomous) work of primary schoolchildren with minimal
involvement of adult family members, are identified. The requirements for a multimedia educational presentation are given, which correspond
to the recommendations of the Ministry of Education of the Russian Federation for mastering the Basic educational program of an elementary
school, as well as its characteristics and an algorithm for creating. The description of the multimedia educational presentation on the subject
“Literary reading” for the lesson in the distance mode is given.