bluuebunny/crossref_metadata_2025_split huggingface dataset:
A very long-acting IL-15: implications for the immunotherapy of cancer
Authors: Hangasky John A , Chen Wei , Dubois Sigrid P , Daenthanasanmak Anusara , Müller Jürgen R , Reid Ralph , Waldmann Thomas A , Santi Daniel V 
Published: January 2022

BackgroundInterleukin-15 (IL-15) is an important cytokine necessary for proliferation and maintenance of natural killer (NK) and CD8+T cells, and with great promise as an immuno-oncology therapeutic. However, IL-15 has a very short half-life and a single administration does not provide the sustained exposure required for optimal stimulation of target immune cells. The purpose of this work was to develop a very long-acting prodrug that would maintain IL-15 within a narrow therapeutic window for long periods—similar to a continuous infusion.MethodsWe prepared and characterized hydrogel microspheres (MS) covalently attached to IL-15 (MS~IL-15) by a releasable linker. The pharmacokinetics and pharmacodynamics of MS~IL-15 were determined in C57BL/6J mice. The antitumor activity of MS~IL-15 as a single agent, and in combination with a suitable therapeutic antibody, was tested in a CD8+T cell-driven bilateral transgenic adenocarcinoma mouse prostate (TRAMP)-C2 model of prostatic cancer and a NK cell-driven mouse xenograft model of human ATL (MET-1) murine model of adult T-cell leukemia.ResultsOn subcutaneous administration to mice, the cytokine released from the depot maintained a long half-life of about 168 hours over the first 5 days, followed by an abrupt decrease to about ~30 hours in accordance with the development of a cytokine sink. A single injection of MS~IL-15 caused remarkably prolonged expansions of NK and ɣδ T cells for 2 weeks, and CD44hiCD8+T cells for 4 weeks. In the NK cell-driven MET-1 murine model of adult T-cell leukemia, single-agent MS~IL-1550 μgor anti-CCR4 provided modest increases in survival, but a combination—through antibody-depedent cellular cytotoxicity (ADCC)—significantly extended survival. In a CD8+T cell-driven bilateral TRAMP-C2 model of prostatic cancer, single agent subcutaneous MS~IL-15 or unilateral intratumoral agonistic anti-CD40 showed modest growth inhibition, but the combination exhibited potent, prolonged bilateral antitumor activity.ConclusionsOur results show MS~IL-15 provides a very long-acting IL-15 with low Cmaxthat elicits prolonged expansion of target immune cells and high anticancer activity, especially when administered in combination with a suitable immuno-oncology agent.
Dl-3-n-butylphthalide attenuates brain injury caused by cortical infarction accompanied by cranial venous drainage disturbance
Authors: Song Kangping , Zeng Xiuli , Xie Xiaomei , Zhu Rongxuan , Liang Jianye , Chen Guobing , Huang Li’an 
Published: January 2022

BackgroundCerebral venous disorder may have a harmful effect on ischaemic stroke; however, the underlying mechanism remains to be elucidated. Although Dl-3-n-butylphthalide is a multitarget agent for antiischaemic stroke, its neuroprotective role in brain ischaemia accompanied by brain venous disturbance remains unclear. In this study, we induced cerebral venous disturbance by the occlusion of bilateral external jugular veins (EJVs) to explore the potential mechanism of the adverse effects of cerebrovenous disorders in cerebral infarction and explore the protective effect of Dl-3-n-butylphthalide on cerebral infarction accompanied through cerebral venous disturbance.MethodsCerebral venous disturbance was induced in Sprague-Dawley rats through the permanent occlusion of bilateral EJVs, and cerebral ischaemic stroke was induced through the permanent occlusion of the right cortical branches of the middle cerebral artery. 2,3,5-triphenyltetrazolium chloride staining, MRI, Evans blue extravasation and behavioural test were performed to evaluate infarction volume, cerebral blood flow (CBF), blood–brain barrier (BBB) integrity and neurological function. Immunofluorescence staining and western blot analysis were performed to detect loss of neuron, endothelial cells, pericytes and tight junctions.ResultsBilateral EJVs occlusion did not cause cerebral infarction; however, it increased the infarction volume compared with the simple middle cerebral artery occlusion (MCAO) group, accompanied by severe neuron loss, worse neurological function, lower CBF, increased EJVs pressure, exacerbated Evans blue extravasation and brain oedema, as well as attenuated angiogenesis. Dl-3-n-butylphthalide displayed a neuroprotective effect in rats with MCAO accompanied by EJVs occlusion by reducing neuron loss, accelerating CBF restoration, promoting angiogenesis and relieving BBB damage.ConclusionBilateral EJVs occlusion did not significantly affect normal rats but aggravated brain damage in the case of ischaemic stroke. Dl-3-n-butylphthalide treatment plays a neuroprotective role in rats with MCAO accompanied by EJVs occlusion, mainly due to the promotion of CBF restoration and BBB protection.
Laboratory-scale seismic CPT calibration chamber tests on Fraser River sand
Authors: Sadrekarimi Abouzar , Jones Stephen 
Published: January 2022

Physical modeling of cone penetration testing (CPT) can be carried out under known stress, deformation, and density conditions using laboratory calibration chambers. This study presents the results of reduced-scale model CPTs (MCPT) on Fraser River sand using a calibration chamber that allows anisotropic consolidation of soil specimens, as well as the measurement of shear wave velocity (VS), using bender elements. In addition to VS, MCPT can also measure cone tip resistance (qc), sleeve friction (fs), and pore water pressure developed behind the cone tip (Δu2). The CPT model tests are performed on Fraser River sand at different effective stresses and relative densities. The CPT calibration chamber test results are comparable with those of in situ seismic cone penetration tests (SCPT) in the Fraser River delta, existing correlations between VSand qc, and calibration chamber tests on other sands. This confirms the overall feasibility of the MCPT calibration chamber design for the measurements of qc, fs, and VSin sandy soils.
Application of Logistic Regression and Decision Tree Models in the Prediction of Activities of Daily Living in Patients with Stroke
Authors: Zhang Qile , Zhang Zheyu , Huang Xiuqing , Zhou Chun , Xu Jian 
Published: January 2022

An improvement in the activities of daily living (ADLs) is significantly related to the quality of life and prognoses of patients with stroke. However, the factors predicting significant improvement in ADL (SI-ADL) have not yet been clarified. Therefore, we sought to identify the key factors affecting SI-ADL in patients with stroke after rehabilitation therapy using both logistic regression modeling and decision tree modeling. We retrospectively collected and analyzed the clinical data of 190 patients with stroke who underwent rehabilitation therapy at our hospital between January 2020 and July 2020. General and rehabilitation therapy data were extracted, and the Barthel index (BI) score was used for outcome assessment. We defined SI-ADL as an improvement in the BI score by 15 points or more during hospitalization. Logistic regression and decision tree models were established to explore the SI-ADL predictors. We then used receiver operating characteristic (ROC) curves to compare the logistic regression and decision tree models. Univariate analysis revealed that compared with the non-SI-ADL group, the SI-ADL group showed a significantly shorter course of stroke, longer hospital stay, and higher rate of receiving occupational and speech therapies (all

P
<
0.05

). Binary logistic regression analysis revealed the course of stroke at admission (

odds

ratio

OR

=
0.986

,

95
%
confidence

interval

CI

=
0.979

–0.993;

P
<
0.001

) and the length of hospital stay (

OR
=
1.030

,

95
%
CI
=
1.013

–1.047; P =0.001) as the independent predictors of SI-ADL. ROC comparisons revealed no significant differences in the areas under the curves for the logistic regression and decision tree models (0.808 vs. 0.831;

z
=
0.977

,

P
=
0.329

). Both models identified the course of disease at admission and the length of hospital stay as key factors affecting SI-ADL. Early initiation of rehabilitation therapy is of immense importance for improving the ADLs in patients with stroke.
In Vitro Matured Human Pluripotent Stem Cell–Derived Cardiomyocytes Form Grafts With Enhanced Structure and Function in Injured Hearts
Authors: Dhahri Wahiba , Sadikov Valdman Tamilla , Wilkinson Dan , Pereira Elizabeth , Ceylan Eylül , Andharia Naaz , Qiang Beiping , Masoudpour Hassan , Wulkan Fanny , Quesnel Elya , Jiang Wenlei , Funakoshi Shunsuke , Mazine Amine , Gomez-Garcia M. Juliana , Latifi Neda , Jiang Yidi , Huszti Ella , Simmons Craig A. , Keller Gordon , Laflamme Michael A. 
Published: January 2022

Background:
Human pluripotent stem cell (hPSC)–derived cardiomyocytes (hPSC-CMs) have tremendous promise for application in cardiac regeneration, but their translational potential is limited by an immature phenotype. We hypothesized that large-scale manufacturing of mature hPSC-CMs could be achieved through culture on polydimethylsiloxane (PDMS)-lined roller bottles and that the transplantation of these cells would mediate better structural and functional outcomes than with conventional immature hPSC-CM populations.

Methods:
We comprehensively phenotyped hPSC-CMs after in vitro maturation for 20 and 40 days on either PDMS or standard tissue culture plastic substrates. All hPSC-CMs were generated from a transgenic hPSC line that stably expressed a voltage-sensitive fluorescent reporter to facilitate in vitro and in vivo electrophysiological studies, and cardiomyocyte populations were also analyzed in vitro by immunocytochemistry, ultrastructure and fluorescent calcium imaging, and bulk and single-cell transcriptomics. We next compared outcomes after the transplantation of these populations into a guinea pig model of myocardial infarction using end points including histology, optical mapping of graft- and host-derived action potentials, echocardiography, and telemetric electrocardiographic monitoring.

Results:

We demonstrated the economic generation of >1×10
8
mature hPSC-CMs per PDMS-lined roller bottle. Compared with their counterparts generated on tissue culture plastic substrates, PDMS-matured hPSC-CMs exhibited increased cardiac gene expression and more mature structural and functional properties in vitro. More important, intracardiac grafts formed with PDMS-matured myocytes showed greatly enhanced structure and alignment, better host-graft electromechanical integration, less proarrhythmic behavior, and greater beneficial effects on contractile function.

Conclusions:
We describe practical methods for the scaled generation of mature hPSC-CMs and provide the first evidence that the transplantation of more mature cardiomyocytes yields better outcomes in vivo.
When Mediators Need Machines (and Vice Versa): Towards a Research Agenda on Hybrid Peacemaking Intelligence
Authors: Hirblinger Andreas T. 
Published: January 2022

Abstract
The growing use of artificial intelligence (AI) in peace processes challenges the ways in which mediators conventionally generate and use knowledge to facilitate a convergence of conflict party positions. Mediators are increasingly unable to maintain their role as information brokers without the support of automated information gathering and analysis systems. However, the effectiveness of such AI-tools is likewise hampered by their limited autonomy across peacemaking contexts, by the paradigmatic nature of knowledge that is used to design AI-systems, and the influence of subjective factors that are difficult to measure. These challenges may be overcome by hybrid human-machine systems in support of peacemaking. This article formulates a research agenda for hybrid peacemaking intelligence that is concerned with the increasing interdependence of humans and machines. It suggests studying how agency is distributed in mediator-machine networks, the hermeneutics of machine-supported participatory approaches, and how hybrid arrangements change power relations in peacemaking.
The Role of Imams in Family Counselling with Muslim Families in Norway
Authors: Brekke Torkel , Hadi Fazal , Kozaric Edin 
Published: January 2022

Abstract
This article offers an analysis of the role of Muslim imams in family counselling in Norway based on a survey (N = 35) and in-depth interviews (N = 10) with imams. There has till now been little knowledge about these issues. We find that family counselling is an important part of the work that imams do and they have a high degree of awareness about their potential role as counsellors, but they are also wary of their clients’ high expectations and they stress the limitations of their own authority. One of the important issues the imams face in counselling has to do with the challenging role of Muslim husbands and the expectations husbands sometimes face.
Combination 5-Fluorouracil and Microneedling Therapy for Wound Modification: A Histological Murine Study
Authors: Watson Alison H. , O’Mary Hannah L. , Cui Zhengrong , Baer Susan C. , Somogyi Marie B. , Homer Natalie , Blaydon Sean M. , Huggins Jonathan , Shore John W. , Durairaj Vikram D. , Nakra Tanuj 
Published: January 2022

Purpose: Microneedling has been shown to enhance the efficacy of topical 5-fluorouracil (5-FU) for the treatment of dermatologic malignancies that along with our anecdotal clinical success of combination treatments for scar modification led the authors to investigate the effect of 5-FU and microneedling on wound healing. The current study evaluates the clinical and histological impact of topical 5-FU and microneedling therapy, separately, and in combination in a murine model. Methods: This is a randomized controlled trial in which 20 mice were randomized to 4 treatment groups: group 1 (n = 5) controls, group 2 (n = 5) microneedling alone, group 3 (n = 5) 5-FU alone, and group 4 (n = 5) combination 5-FU and microneedling. The interventions of interest were carried out on postoperative day 5, 10, 15, and 20 after wound induction. The clinical and histological wound appearance was graded by blinded oculoplastic surgeons and a blinded dermatopathologist, respectively. Statistical analysis was performed using a Kruskal-Wallis test with Dunn test for individual comparisons of treatment groups. Results: Blinded grading of the wound healing appearance at early, intermediate, and late healing time points demonstrated a statistically significant difference at the intermediate time point only. Histological analysis demonstrated a relative increase in epidermal thickness, dermal inflammation, and fibrosis in the combination treatment group. Statistically significant differences among the groups were identified in the degree of lymphocytic inflammation and for the amount of granulomatous inflammation. Discussion: This study was the first of its kind to investigate combination treatment with 5-FU and microneedling on a histopathologic level. In a murine model, this combination treatment resulted in increased degrees of wound inflammation and fibrosis relative to controls, and each treatment alone suggesting a histological basis that may relate to clinical impact, although future study in this area, to better understand the impact of these changes, is needed. Conclusion: Combination treatment with 5-FU and microneedling results in a histological increase in the degree of wound inflammation and fibrosis relative to controls and each treatment alone.
Airway and Feeding Outcomes in Pierre Robin Sequence: A Comparison of Three Management Strategies
Authors: Khansa Ibrahim , Aldabbeh Summer , Pearson Gregory D. , Baylis Adriane , Madhoun Lauren L. , Schoenbrunner Anna , Splaingard Mark , Kirschner Richard E. 
Published: January 2022

Background Controversy remains regarding optimal management of Pierre Robin sequence (PRS). The goal of this study was to compare airway and feeding outcomes in infants with PRS who underwent surgical intervention, specifically mandibular distraction osteogenesis (MDO) or tongue-lip adhesion (TLA), or who had conservative management (CM) without surgery. Methods All consecutive patients treated for PRS at a pediatric academic medical center, with at least one year follow-up, were included. Patients who underwent tracheostomy as an index procedure were excluded. Patients were divided into those who underwent MDO, TLA or CM. Feeding status and data from initial and follow-up polysomnograms were collected. Comparisons between groups were made using the Kruskal-Wallis test, followed by Mann-Whitney pairwise comparison with a Bonferroni correction, when appropriate. Results 67 neonates were included. 19 underwent TLA, 29 underwent MDO and 19 underwent CM. The proportions of syndromic patients were similar between groups. Patients undergoing CM had the lowest baseline AHI (9.1), but there were no significant differences between TLA (20.1) and MDO (25.4). At follow-up, the three groups had similar mean AHI (MDO 1.3, TLA 4.2, CM 4.5). A similar proportion of patients achieved AHI 5 or less (TLA 89.5%, MDO 96.6%, CM 84.2%). At one year, there were no significant differences in weight percentiles or in risk of failure-to-thrive between groups. One patient from the TLA group required a tracheostomy. Conclusion The three treatment modalities achieved high airway and feeding success rates. All three modalities should have a place in the armamentarium of the craniofacial surgeon.
Successful administration of mitotane (O, p′-DDD) in pediatric oncology
Authors: Strobbe Geoffrey , Fraipont Félicie , Raimbault Sandra , Mercier Sylvie , Stala Thibault , Naveau Marie , Villain Alexandre , Sakji Ilyes , Defachelles Anne-Sophie , Feutry Frédéric , Marliot Guillaume 
Published: January 2022

Introduction Mitotane (o, p′-DDD) is a molecule that was developed many years ago for adrenal cortical carcinoma, but no suitable pediatric dosage form is available for administration to young children. Mitotane requires therapeutic drug monitoring because of its long half-life and difficulty in stabilizing plasma concentrations. Furthermore, Mitotane is a highly lipophilic drug that requires concurrent lipid administration. Case report We present the case of a 3-year-old girl who was diagnosed with metastatic adrenal cortical carcinoma. Due to the difficulty in administering the tablets and the non-stabilized mitotane dosages, a nasogastric tube was inserted. An administration protocol based on dispersing the tablets in whole milk was established by the pharmacy team. This led to the stabilization of the disease for at least 1.5 years. Management and outcome Mitotanemia is difficult to stabilize even when treatment is administered orally. To maintain biological efficacy, we propose an easily reproducible protocol. The efficacy was stabilized at a dosage of 1500 mg per day. Mitotanemia fluctuated between 14 mg/mL, and 20 mg/mL. The implementation of this protocol prevented treatment discontinuation. Discussion The administration of narrow therapeutic range drugs via a nasogastric tube is a challenge for healthcare teams, particularly in pediatric patients. Based on the findings of this clinical case, clinicians should consider future use of this protocol. The use of whole milk as a vehicle for mitotane is a simple, effective, and reproducible method to administer the drug to pediatric patients and can be used for other similar cases.
Non-pharmacological interventions to reduce anxiety among children undergoing surgery: A systematic review
Authors: Mathias Edlin Glane , Pai Mamatha Shivananda , Guddattu Vasudeva , Bramhagen Ann-Cathrine 
Published: January 2022

A hospitalized child experiences anxiety more frequently as compared to non-hospitalized children. Surgery can be emotionally distressing for children, and subsequently their parents and caregivers, this distress can cause profound adverse impacts on children. We aimed to identify the effect of non-pharmacological interventions on children’s (1–18 years) anxiety undergoing surgery. The following databases: Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index of Nursing and Allied Health Literature (CINAHL), Proquest, Web" of Science, and Cochrane Central Register of Controlled Trials were systematically searched for full-text articles. The review included 15 randomized controlled trials. The risk of bias was assessed using Cochrane Risk of Bias tool. The interventions included in the study were preoperative education, puppet play, therapeutic play, distraction activities, parental presence, and clown therapy. The review presents a narrative reporting of the findings. This review identifies that non-pharmacological interventions are effective in reducing anxiety among children undergoing surgery. There are a limited number of studies from developing countries. Further research is required to underpin the use of these interventions with children before surgery.
Long-term Results of Interwoven Nitinol Stents to Treat the Radiocephalic Anastomotic Arteriovenous Fistula Stenosis
Authors: Thomas Shannon D. , Peden Samantha , Katib Nedal , Crowe Phillip , Barber Tracie , Varcoe Ramon L. 
Published: January 2022

Introduction: Juxta-anastomotic stenosis (JXAS) is a common problem afflicting the arteriovenous fistula (AVF). This study aimed to evaluate the safety and long-term efficacy of an interwoven nitinol stent (Supera, Abbott Vascular, Santa Clara, CA, USA) in the treatment of radiocephalic AVF JXAS. Methods: A single-center, retrospective, observational study was conducted of patients with failing AVF due to JXAS treated with an interwoven nitinol stent. End points included JXAS target lesion primary patency, access circuit primary patency, assisted access circuit primary patency, and endovascular intervention rate (EIR). Results: Sixty patients were treated with a Supera stent in the JXAS between February 2014 and March 2020. One patient was excluded (AVF used for illicit drug use), leaving 59 patients (67.8% male, mean age 66.9 ± 11.4 years [range: 40–84]) with typical medical comorbidities. Overall, 45.8% of patients had previous AVF intervention. The stent was inserted with a 100% technical success rate with a mean follow-up of 729.6 ± 456.0 days (range: 5–2182 days). Juxta-anastomotic stenosis target lesion primary patency was 68.2 ± 6.6%, 53.3 ± 7.5%, and 46.2 ± 8.1% at 12, 24, and 36 months, respectively. The EIR was .64 (0–3.29) procedures/patient/year, after which the assisted access circuit primary patency rate was 94.3 ± 3.2% at 12, 24, and 36 month time points. Three thrombosed circuits occurred which were all successfully salvaged with no difference in patency by indication for procedure and no AVFs lost/abandoned out to 3 years. Avoidance of stent post-dilatation and the presence of stent mal-apposition were associated with improved primary patency, and reduced EIR, which may suggest an importance in vessel preparation prior to stent implantation. Conclusion: Interwoven nitinol stent treatment of the failing AVF with JXAS results in promising 3 year JXAS patency, with a low rate of endovascular re-intervention for those circuits developing restenosis. All AVFs were maintained over 3 years, demonstrating this treatment allows for long-term radiocephalic AVF vascular access.