bluuebunny/crossref_metadata_2025_split huggingface dataset:
P285 Using FITBITR for fitness monitoring in patients attending the AS residential course at RNHRD: it does make a difference!
Authors: Jamal Muhammad Safwan , Saeed Sadaf , Clarke Emily , Sengupta Raj 
Published: April 2020

Abstract

Background
Wearable technology has become a very popular tool in fitness training. It empowers people to be in charge of their own health and encourages them to exercise more. At the Royal National Hospital for Rheumatic Diseases we have been offering dedicated inpatient courses for management of spondyloarthropathy patients. Historically this course has helped patients with chronic arthritis to improve their physical well being while also focusing on different extra articular aspects of their condition like fatigue, sleep and pain issues. As part of this programme, we provided patients with Fitbit devices to evaluate whether regular recording of their activity and sleep tracking had an impact on their overall physical activity.

Methods
Patients attending the 2 weeks’ residential course from July 2018 to June 2019 were provided with Fitbit devices and were given a paper chart to log their data in. The patients gave verbal permission for their data to be included for audit purposes. The demographic data regarding the patients was collected through electronic patient record system. Bath indices were collected from electronic patient record system and results were compiled through Microsoft Excel.

Results
Data from 42 patients was collected. Data from 38 patients was analysed. Data for sleep indices was incomplete in 16 patients. 67% participants on the course were male and 33% were female. 90% patients had a diagnosis of ankylosing spondylitis, 5% had nonradiographic SpA and the rest had PsA or undifferentiated SpA. Majority of patients (97%) had improvement in their BASMI scores with a mean improvement of 37%. 51% patients improved their physical activity with an average increase in their step count by 13.3% compared to baseline. The participants on average spent 55.67 minutes being active on the course. While resting, majority of patients spent more time being awake or in light sleep (mean 14.3% and 54% respectively) although it might have been confounded by their stay in hospital. The verbal feedback from patients regarding the use of these devices has been mostly positive and it encouraged them to be more active.

Conclusion
Majority of patients attending the residential course noticed an improvement in their arthritis. The verbal feedback on using Fitbit devices to track daily activity and sleep was positive as it encouraged patients to increase their activity and improve sleep hygiene in future. Further refinement in data collection process and including other variables like pain, stiffness and fatigue scores can be valuable in a more focused discussion regarding management strategies of spondyloarthritis.

Disclosures
M. Jamal None. S. Saeed None. E. Clarke None. R. Sengupta None.
Asylum-Seekers Prosecuted for Human Smuggling: A Case Study of Scafisti in Italy
Authors: Patanè Flavia , Bolhuis Maarten P , van Wijk Joris , Kreiensiek Helena 
Published: April 2020

Abstract
States increasingly prosecute irregular migrants – asylum-seekers included – for their (alleged) involvement in human smuggling during their own migration journey. Based on a literature review and interviews with lawyers, prosecutors, judges, and migrants on Sicily, this article provides insight into the nature and scale of this phenomenon in Italy and discusses the effects of criminal prosecution on these migrants’ asylum procedures. From 2015–2018, as a standard operating procedure, roughly 1,300 “captains” and navigators – scafisti (literally: smugglers by boat) – of small dinghies with migrants arriving in Italy have been arrested for suspicion of “aiding clandestine (or irregular) immigration”. Most scafisti are migrants themselves and there are strong indications that they were forced to steer or navigate the boat. These prosecuted migrants face many difficulties in proving duress and are often inadequately advised about the consequences of a criminal conviction on their subsequent immigration procedures. After a conviction, as well as after an acquittal, they are often excluded from official reception centres and have difficulties accessing asylum procedures. When they manage to apply for asylum, they will be denied international protection if they have been convicted. When they cannot be expelled, they may end up in a legal limbo, having to rely on a temporary humanitarian status with strict limitations.
Transient brain networks underlying interpersonal strategies during synchronized action
Authors: Heggli Ole Adrian , Konvalinka Ivana , Cabral Joana , Brattico Elvira , Kringelbach Morten L , Vuust Peter 
Published: April 2020

Abstract
Interpersonal coordination is a core part of human interaction, and its underlying mechanisms have been extensively studied using social paradigms such as joint finger-tapping. Here, individual and dyadic differences have been found to yield a range of dyadic synchronization strategies, such as mutual adaptation, leading–leading, and leading–following behaviour, but the brain mechanisms that underlie these strategies remain poorly understood. To identify individual brain mechanisms underlying emergence of these minimal social interaction strategies, we contrasted EEG-recorded brain activity in two groups of musicians exhibiting the mutual adaptation and leading–leading strategies. We found that the individuals coordinating via mutual adaptation exhibited a more frequent occurrence of phase-locked activity within a transient action–perception-related brain network in the alpha range, as compared to the leading–leading group. Furthermore, we identified parietal and temporal brain regions that changed significantly in the directionality of their within-network information flow. Our results suggest that the stronger weight on extrinsic coupling observed in computational models of mutual adaptation as compared to leading–leading might be facilitated by a higher degree of action–perception network coupling in the brain.
Channelopathy and Carbohydrates: Bad Mix for Migraines
Authors: Stanton Angela A. 
Published: April 2020

Migraine is among the top 20 most disabling diseases
1. Despite the significant progress in pain management, migraine‐cause is still not understood. Most research is focused on pain, making it difficult to see the cause of migraine. How nutrition affects ionic channels and electrolyte homeostasis have not yet been connected to migraines.Migraine is caused by channelopathy
2 the following way: hyper‐sensory brain
3; increased sensory‐neuron connections
4; extra voltage used by extra connections
5,
6; extra voltage uses more sodium
7; glucose entering cells causes sodium efflux
8; kidneys waste potassium
9,
10 and water to spare sodium; reduced sodium in circulation triggers increased aldosterone, cortisol, and adrenaline
11; cortisol and adrenaline increase glucose in the blood
12; glucose entering cells causes sodium and water efflux (as noted earlier), initiating the previous steps with adrenaline and cortisol
8. This cycle leads to migraine.In this presentation, I derive the migraine‐process, forming a coherent picture and show how the proper nutrition may prevent migraines. There is a considerable interplay between nutrition high in carbohydrates, low in salt, and migraines. Carbohydrates have a detrimental effect on electrolytes, which may be the most important factor in migraine cause.Support or Funding InformationStanton Migraine Protocol Inc.,
Unique Substrate Specificity of Human Phospholipase A2s
Authors: Hayashi Daiki , Mouchlis Varnavas D. , Dennis Edward A. 
Published: April 2020

Phospholipase A2 (PLA2) constitutes a superfamily of enzymes that hydrolyze the sn‐2 acyl‐chain of phospholipids which are the major components of cell membranes. PLA2 produces free fatty acids and lysophospholipids as products which serve as lipid mediators and precursors of bioactive lipids. Among them, the release of ω‐6 and ω‐3 fatty acids including arachidonic acid (AA, ω‐6), eicosapentaenoic acid (EPA, ω‐3), and docosahexaenoic acid (DHA, ω‐3) is a pivotal role of PLA2s because the fatty acids are precursors of various eicosanoids and related bioactive oxylipins responsible for inflammation and resolution. Additionally, in contrast to conventional ester‐linked phospholipids, we also investigated PLA2 specificity toward sn‐1 vinyl ether‐linked phospholipids and phosphatidylinositol phosphates (PIPs) which are involved in various signaling processes.Cytosolic PLA2 (cPLA2), calcium‐independent PLA2 (iPLA2), and secreted PLA2 (sPLA2) are the three major PLA2s that are well studied, and a significant number of PLA2‐related disorders have been reported. Therefore, investigating the substrate specificity of PLA2 toward different phospholipids, can be a key to understanding the etiology of PLA2‐related disorders and developing novel therapeutic targets. Recently, we developed a high‐throughput lipidomics‐based assay to measure PLA2 activity and successfully employed it to investigate the general specificity of PLA2s
(1). In the present study, we investigated the specificity of the three major PLA2s toward phospholipids containing ω‐6 and ω‐3 fatty acids in the sn‐2 position, sn‐1 vinyl ethers, and PIPs using this lipidomics‐based assay. Also, we determined the optimal binding of the substrate in the active site of each PLA2 by molecular dynamics (MD) simulations to explain the observed specificity.cPLA2 showed high activity toward AA and EPA, and prefers sn‐1 vinyl ether phospholipids over ester phospholipids. iPLA2 showed the highest activity toward EPA, and no preference was observed between a vinyl ether and an ester. sPLA2 showed a preference for DHA and ester phospholipids. In addition, we determined that although additional phosphates on the inositol headgroup attenuated the activity of all three PLA2s, at least cPLA2 and iPLA2 could hydrolyze PI(4,5)P2. MD simulations revealed that the active site of cPLA2 could precisely bind AA and EPA in the sn‐2 position but not DHA. In summary, the present study revealed a unique and distinct substrate specificity for each of the PLA2s and explained the observed preference of cPLA2 for AA and EPA.Support or Funding InformationSupported by NIH grant GM20501‐43
HUMAN ALLOGRAFTS IMPROVE HEALING OUTCOMES IN CHRONIC WOUNDS
Authors: Tabor Aaron J. , Kellar Robert 
Published: April 2020

BackgroundChronic wounds affect an estimated 8 million people worldwide and are often a result of underlying health conditions, such as obesity, diabetes, malnutrition, etc. The related morbidity and mortality places an increased burden on the healthcare system. Regenerative approaches, which engages and stimulates the body’s innate healing capabilities is addressing the limited successes in current standard of care treatments. Axolotl Biologix is a regenerative medicine company that produces allograft products from the human amnion. Axolotl Ambient™ and Shot™, conditioned media rich in cytokines and growth factors, are derived from human amniotic mesenchymal stromal cells. Axolotl DualGraft™ is a dehydrated, acellular, double layer, human amniotic membrane that encourages soft tissue repair by serving as a barrier, extracellular matrix scaffold, and provides a source of matrix‐bound growth factors.MethodsBoth allografts were used to facilitate repair and regeneration in a patient with difficult to close or intractable full‐thickness wounds. Axolotl Ambient™ was injected into the wound margin and Axolotl DualGraft™ was placed within the exposed wound bed. Wounds were bandaged per standard of care and imaged regularly to monitor wound healing progression. A range of bioassays were performed to ascertain the biological activity of the allografts.ResultsMultiple applications and injections of Ambient and DualGraft resulted in the formation of granulation tissue, restoration of blood flow, pain sensation, epithelialization, and wound closure. Bioassays confirmed the allografts contain measurable amounts of growth factors that promote angiogenesis, proliferation, tissue remodeling and reduction in inflammation.ConclusionsClinical application of the allografts in intractable wounds yielded dramatic improvement in wound repair by stimulating the normal physiological wound healing processes by the addition of exogenous growth factors, providing a scaffold in the wound bed, promoting normal blood flow, re‐epithelialization, and tissue remodeling. Longitudinal case studies are ongoing, concurrent with benchtop research to further elucidate the mechanisms of action responsible for reported clinical benefits in difficult to heal wounds.Support or Funding InformationN/A
Hyperstable Cell‐Penetrating Peptides from Medicinal Plants
Authors: Tam James P. , Kam Antony , Loo Shining 
Published: April 2020

A longstanding interest of our laboratory is to study cysteine‐rich peptides (CRPs) from medicinal plants as an inspiration to design orally‐active compounds. Plants produce CRPs as part of their host‐defense mechanism against microbes and insects. Most CRPs contain 15 to 25% of cysteine per molecule and are characterized by their cystine scaffold
[1–
4]. CRPs can display both hydrophilic and hydrophobic surface patches due to the cystine dense core which causes hydrophobic side chains to flip outwards, resulting in a unique “inside‐out” feature. As hydrophobicity is a major driving force for cell penetration
[5], we hypothesized that CRPs penetrate cells and bind to intracellular targets to exert their biological effects. Here, we report the discovery of hyperstable and cell‐penetrating CRPs, roseltide rT1 and rT7, from Hibiscus sabdariffa of the Malvaceae family. We show that both roseltide rT1 and rT7 are highly resistant against proteolytic degradation. Using live‐cell confocal microscopy, we show that cationic roseltide rT1 and anionic roseltide rT7 are cell‐penetrating. Functionally, we demonstrate that roseltide rT1 targets the mitochondria via TOM20 and increases cellular ATP production
[4]. Roseltide rT7, on the other hand, inhibits the 20S proteasome, which in turn, reduces tumor necrosis factor‐induced IκB□ degradation, and decreases intercellular adhesion molecule‐1 expressions. Taken together, our results demonstrate that hyperstable CRPs are cell‐penetrating and targets intracellularly to elucidate their biological effects.Support or Funding InformationThis research was supported in part by Nanyang Technological University Internal Funding ‐ Synzymes and Natural Products (SYNC) and the AcRF Tier 3 funding (MOE2016‐T3‐1‐003).
NMI and IFP35 are key DAMP molecules in inflammatory bowel diseases
Authors: Cheng Sijing , Jiao Na , Lin Xutao , Li Yichen , Huang Yibo , Vermeire Severine , Zou Yifeng , Zhu Ruixin , Liang Huanhuan , Liu Yingfang , Zhu Lixin , Lan Ping 
Published: April 2020

Background & AimN‐myc and STAT interactor (NMI) and interferon‐induced protein 35 (IFP35) are damage‐associated molecular patterns (DAMPs), that mediate pro‐inflammatory reactions upon cell or tissue damage. Excessive signaling mediated by DAMP molecules can lead to several chronic inflammatory diseases. Here we investigated potential roles for NMI and IFP35 in the pathogenesis of inflammatory bowel diseases (IBD) including Crohn’s disease and ulcerative colitis.MethodDifferentially expressed genes (DEG) were identified in the colonic mucosa of CD and UC in comparison with controls by the gene expression microarray dataset that was validated by quantitative real‐time polymerase chain reaction and immunohistochemistry.ResultNMI and IFP35 were highly elevated in the colonic mucosa of both CD and UC patients, compared to healthy controls. The fold changes of NMI in the colonic epithelium of CD and UC were 1.78 (P < 0.05) and 1.79 (P <0.05), respectively; while the fold changes of IFP35 were 1.73(P<0.05 ) and 1.74 (P<0.05), respectively in CD and UC. More importantly, the expression of NMI and IFP35 decreased to normal levels in the responders after infliximab treatment, but remained elevated in the non‐responders of the infliximab treatment. Compared to the controls, the fold changes of NMI in CD and UC non‐responder was 1.92 (P<0.05) and 1.65(P<0.05), respectively; the fold changes of IFP35 in CD and UC non‐responders were 1.64(P<0.05) and 1.4(P<0.05), respectively. Consistently, the expression levels of the downstream molecules including TLR4, TNF and IL‐6 paralleled and positively associated with those of the NMI/IFP35 (P < 0.05).ConclusionsOur observations suggest that DAMP molecules NMI/IFP35 may mediate the early events of the IBD pathogenesis. We are confirming these observations at RNA and protein levels. Future plans include intervention studies using therapeutic antibodies to block NMI/IFP35 activities in IBD animal models. Considering that many DAMP molecules are effective targets in the treatment of chronic inflammatory diseases, we are optimistic about the future clinical application of NMI/IFP35 for the treatment of IBD.Support or Funding Information1.National Natural Science Foundation of China 81774152, 31200986, 41530105, 81770571,81970452. 2.Guangzhou laboratory clinical innovation project 2018GZR0201005. 3.National Postdoctoral Program for Innovative Talents of China BX20190393. 4.Natural Science Foundation of Shanghai 16ZR1449800. 5.the University at Buffalo Community of Excellence in Genome, Environment and Microbiome (GEM).
Hyaluronic Acid Receptor‐RHAMM Mediates Renal Carcinoma Metastasis
Authors: Moran Heriberto , Cancel Limary M , Huang Jing , Rodriguez Nora , Munn Lance L , Tarbell John M 
Published: April 2020

The surface proteoglycan/glycoprotein layer (glycocalyx) on tumor cells has been associated with cellular functions that can potentially enable invasion and metastasis. In addition, aggressive renal carcinoma cells (SN12L1) with high metastatic potential have enhanced invasion rates compared to low metastatic (SN12C) cells in response to interstitial flow stimuli in vitro. Our previous studies suggest that heparan sulfate (HS) and hyaluronic acid (HA) in the glycocalyx play important roles in this flow mediated mechanotransduction and upregulation of invasive and metastatic potential. We examined HA receptor‐RHAMM protein levels in both SN12L1 and SN12C cell lines. We observed significantly higher RHAMM levels, but not CD44 levels, in flow dependent SN12L1 cells compared to SN12C cells suggesting that RHAMM may be transmitting the mechanical signal from hyaluronic acid to the cell. To examine this, we knocked down the expression of RHAMM by siRNA in SN12L1 cells. RHAMM knock‐down cells displayed suppression of flow induced migration suggesting that RHAMM receptor transmits the flow signal to the cell. SAHA (Suberoylanilide Hydroxamic Acid) is a small molecule drug (Vorinostat) that, in addition to functioning as an HDAC inhibitor, has been reported to inhibit the HS synthetic enzyme NDST1. We have previously demonstrated that NDST1 knockdown in highly metastatic SN12L1 cells blocked flow‐induced migration in vitro and reduced metastasis from the kidney by 95% in a mouse model
[1]. We conducted flow induced migration assays in highly metastatic SN12L1 cells in the presence of 1.0 uM SAHA. SN12L1 cells treated with 1.0 uM SAHA displayed suppression of flow induced migration consistent with previous results showing NDST1 knockdown in highly metastatic SN12L1 cells blocked flow induced migration in vitro. We also examined the effect of flow on the glycocalyx and found that SN12L1 cells exposed to 24 hours of flow increased their HS expression by 3‐fold compared to static control. We have previously shown that flow sensed by HS is transmitted to the cell by glypican‐1
[2]. All of our data are consistent with the hypothesis that RHAMM is transmitting the mechanical signal from hyaluronic acid to the cell and HS is a flow sensor linked to glypican‐1.Support or Funding InformationFunding informationGrant: RO1CA204949 Targeting glycocalyx mediated mechanisms of tumor metastasis
SPARC Distribution of Intrinsic Cardiac Neurons Projecting to the Sinoatrial Node in Male and Female Rats: A Comparison
Authors: Chen Jin , Tappan Susan , Vadigepalli Rajanikanth , Schwaber James S. , Cheng Zixi J. 
Published: April 2020

Multiple intrinsic cardiac ganglionated plexuses (ICGPs) in the intrinsic cardiac nervous system (ICN) are located on the posterior surface of the left and right atria. However, it is not clear which ICGPs project to the sinoatrial node (SAN) in male and female rats. Our goal is to compare the distribution of ICN neurons projecting to SAN in male and female rats. In this study, the SAN cells were first identified by immunostaining with Hyperpolarization Activated Cyclic Nucleotide Gated Potassium Channel 4 (HCN4), a pacemaker channel marker. The SAN were focally injected with fluorescent tracer Fast DiI to retrogradely label ICN neurons which projected to the SAN region (2 %; 4–5 μl/SAN injection; n=5/sex). After DiI injection, the animals were returned to their cages for 14 days for tracer transportation. Four to five days before sacrifice, Fluorogold (FG) was injected intraperitoneally to counterstain all ICN neurons, and at the end of the time point, animals were perfused and fixed through the heart. The left and right atria were cut open and prepared as whole mounts for analysis. The distribution of tracer‐labeled ICN neurons in the whole mounts of the left and right atria were imaged, overlaid, and analyzed using the Neurolucida Tracing and Digitization System (n=5/sex). We found that: 1) Consistent with our previous finding, there are multiple ICGPs. In each animal, there is a large ICGP near SAN. 2) DiI injection into the SAN region can retrogradely label ICN neurons in both male and female rats. These labeled‐ICN neurons are mainly located in this ICGP in both male and female, with some DiI‐labeled neurons in other ICGPs. Thus, the male and female may have a similar distribution pattern of ICN neurons projecting to the SAN. Our work may contribute to the understanding of the topographical organization of ICN innervation of the heart in the male and female rats.Support or Funding InformationSupported by NIH SPARC OT2OD023848 (PD/PI: K. Shivkumar; Subaward PI: Z.J. Cheng, J. S. Schwaber, R. Vadigepalli).