bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative medicine rehabilitation for children with cerebral palsy: a study protocol for a multicenter pragmatic randomized controlled trial
Authors: Lee Mi-Joo , Yun Young-Ju , Yu Sun-ae , Shin Yong-Beom , Kim Soo-Yeon , Han Jun-hee 
Published: August 2020

Abstract
Background
Traditional Korean medicine (TKM) has been employed for the treatment of children with cerebral palsy in Korea; however, the addition of TKM to usual rehabilitation (UR) treatment is hindered by insufficient evidence of clinical improvement with TKM in patients with cerebral palsy. In this study, we will evaluate the effectiveness and safety of integrative medicine rehabilitation (IMR) for cerebral palsy through a randomized controlled clinical study.

Methods
Eighty children (2–6 years old) diagnosed with cerebral palsy will be recruited and randomly divided into groups A and B. Patients in group A will receive IMR with UR, while those in group B will receive only UR during weeks 1–12 of the study. IMR includes acupuncture treatment (head and limb acupuncture) three times a week and the administration of herbal medicine (Yukgunza-tang and Yukmijihwang-tang extracts) twice a day in parallel with UR. Evaluations will be conducted at the beginning of the study and at 12 and 24 weeks (follow-up). The primary outcome is the Gross Motor Function Measure-88 score, and the secondary outcomes are the scores for the Goal Attainment Scale, Korean Bayley Scales of Infant Development III, and the Pediatric Quality of Life Inventory, and adverse events.

Discussion
This will be the first pragmatic randomized controlled trial to evaluate the efficacy and safety of IMR in children with cerebral palsy in Korea. The results will help to demonstrate if IMR is an effective therapeutic approach for cerebral palsy.

Trial registration
Ministry of Food and Drug Safety 31361 (http://www.mfds.go.kr). Registered on 29 June 2017. Clinical Research Information Service KCT0002620 (https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=9819). Registered on 29 December 2017.
Cardiovascular disease in diffuse idiopathic skeletal hyperostosis (DISH): from theory to reality—a 10-year follow-up study
Authors: Glick Karina , Novofastovski Irina , Schwartz Naama , Mader Reuven 
Published: August 2020

Abstract
Objective
To describe actual cardiovascular events over a decade in patients with diffuse idiopathic skeletal hyperostosis (DISH), without previously known CV diseases.

Methods
The medical records of patients with DISH and controls, beginning in 2006 (without known CV disease), were reviewed. Demographic, constitutional, and laboratory data were collected. Comparison of CV events following 2006 was performed according to the outcome definitions set by the Framingham score 2: coronary event demonstrated by a coronary imaging modality, acute myocardial infarction (MI), coronary death, congestive heart failure with a reduced ejection fraction, and angina pectoris.

Results
Data were available for 45 patients with DISH and 47 controls without DISH from the original cohort (91.8% and 97.9% respectively). By the Framingham score, 28.6% (± 20.33) of the DISH patients were expected to be affected with CVD at 10 years of follow-up. We observed that nearly 39% of them developed CVD during that period (95% CI 23.8–53.5%). The incidence of MI over the 10-year period was significantly higher in the DISH group (P = 0.005). The DISH group had higher morbidity with a higher composite outcome of 38.8% vs 25.5% in the control cohort, and the number of non-elective hospital admissions per patient, despite neither reaching statistical significance.

Conclusion
Our study showed that the Framingham score underestimates the real risk for developing CVD in patients with DISH, specifically the risk for MI. We propose more scrutiny is warranted in evaluating CV risk in these patients, more demanding treatment target goals should be established, and earlier and more aggressive medical interventions should be undertaken, particularly primary prevention. Larger prospective studies are needed to corroborate these findings.
Discontinuation of hydroxychloroquine in older patients with systemic lupus erythematosus: a multicenter retrospective study
Authors: Fernandez-Ruiz Ruth , Bornkamp Nicole , Kim Mimi Y. , Askanase Anca , Zezon Anna , Tseng Chung-E , Belmont H. Michael , Saxena Amit , Salmon Jane E. , Lockshin Michael , Buyon Jill P. , Izmirly Peter M. 
Published: August 2020

AbstractBackgroundAlthough hydroxychloroquine (HCQ) is a mainstay of treatment for patients with systemic lupus erythematosus (SLE), ocular toxicity can result from accumulated exposure. As the longevity of patients with SLE improves, data are needed to balance the risk of ocular toxicity and the risk of disease flare, especially in older patients with quiescent disease. Accordingly, this study was initiated to examine the safety of HCQ withdrawal in older SLE patients.MethodsData were obtained by retrospective chart review at three major lupus centers in New York City. Twenty-six patients who discontinued HCQ and thirty-two patients on HCQ matched for gender, race/ethnicity, and age were included in this study. The primary outcome was the occurrence of a lupus flare classified by the revised version of the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Flare composite index, within 1 year of HCQ withdrawal or matched time of continuation.ResultsFive patients (19.2%) in the HCQ withdrawal group compared to five (15.6%) in the HCQ continuation group experienced a flare of any severity (odds ratio [OR] = 1.28; 95% CI 0.31, 5.30;p = 0.73). There were no severe flares in either group. The results were similar after adjusting for length of SLE, number of American College of Rheumatology criteria, low complement levels, and SELENA-SLEDAI score, and in a propensity score analysis (OR = 1.18; 95% CI 0.23, 6.16;p = 0.84). The analysis of time to any flare revealed a non-significant earlier time to flare in the HCQ withdrawal group (log-rankp = 0.67). Most flares were in the cutaneous and musculoskeletal systems, but one patient in the continuation group developed pericarditis. The most common reason for HCQ withdrawal was retinal toxicity (42.3%), followed by patient’s preference (34.6%), other confirmed or suspected adverse effects (15.4%), ophthalmologist recommendation for macular degeneration (3.8%), and rheumatologist recommendation for quiescent SLE (3.8%).ConclusionsIn this retrospective study of older stable patients with SLE on long-term HCQ, withdrawal did not significantly increase the risk of flares.
Undercarboxylated osteocalcin correlates with insulin secretion in Japanese individuals with diabetes
Authors: Funakoshi Shogo , Yoshimura Kumiko , Hirano Seiki , Ohmi Satoko , Amano Eri , Fukuda Yoshiharu , Terada Yoshio , Fujimoto Shimpei 
Published: August 2020

Abstract
Background
Undercarboxylated osteocalcin (ucOC) is a secreted protein produced by osteoblasts that regulates insulin secretion and insulin sensitivity in rodents. However, the significance of these effects on glucose metabolism in human remains unknown. Moreover, the pathophysiological roles of ucOC on varying degrees of glucose intolerance, including diabetes need to be elucidated. In the present study, correlations between ucOC and indices of insulin secretion and sensitivity were analyzed in normal glucose tolerance (NGT), impaired glucose metabolism (IGM), and diabetes mellitus (DM) groups.

Methods
Based on 75 g OGTT data in Japanese individuals without diabetic medication, or medications which may affect ucOC levels, individuals were classified as having normal glucose tolerance (NGT), impaired glucose metabolism (IGM), or diabetes (DM). In each group, 25 individuals were consecutively recruited [total 75 individuals, age: 65 ± 11 (mean ± SD); BMI: 24.9 ± 3.8 kg/m2]. QUICKI and Matsuda index (MI) were calculated as insulin sensitivity indices. Homeostasis model assessment (HOMA)-β and insulinogenic index (IGI) were calculated as insulin secretion indices. UcOC was measured using ECLIA. Normally-distributed loge-transformed (ln-) values were used for ucOC, HOMA-β, IGI, and MI.

Results
The ucOC was not significantly different among the three groups. The results of multiple regression analysis showed that ln-ucOC did not significantly correlate with age, sex, BMI, waist circumference, fasting plasma glucose, plasma glucose 120 min after glucose loading, fasting plasma immunoreactive insulin, ln-HOMA-β, QUICKI, or ln-MI in any of the three groups. Interestingly, ln-ucOC correlated with ln-IGI (r = 0.422, P = 0.0354) and HbA1c (r = − 0.574, P = 0.0027) only in the DM group. There was no significant correlation between ln-IGI and age, sex, BMI, or HbA1c in the DM group. Further, the results of multiple regression analysis showed that ln-IGI could be independently predicted by BMI (β = 0.598, P = 0.0014) and ln-ucOC (β = 0.641, P = 0.0007) in the DM group (R2 = 0.488, P = 0.0006).

Conclusion
In our study, ucOC positively correlated with insulin secretion independently of BMI in Japanese individuals with diabetes. These results suggest that ucOC plays more important roles in insulin secretion than in insulin sensitivity in individuals with diabetes.
A new nucleosomic-based model to identify and diagnose SSc-ILD
Authors: Guiot Julien , Henket Monique , Andre Béatrice , Herzog Marielle , Hardat Nathalie , Njock Makon-Sebastien , Moermans Catherine , Malaise Michel , Louis Renaud 
Published: August 2020

AbstractBackgroundSystemic sclerosis (SSc) is a rare connective tissue disease associated with rapid evolving interstitial lung disease (SSc-ILD), driving its mortality. Specific biomarkers associated with the evolution of the lung disease are highly needed. We aimed to identify specific biomarkers of SSc-ILD to predict the evolution of the disease. Nucleosomes are stable DNA/protein complexes that are shed into the blood stream making them ideal candidates for biomarkers.MethodsWe studied circulating cell-free nucleosomes (cf-nucleosomes) in SSc patients, 31 with ILD (SSc-ILD) and 67 without ILD. We analyzed plasma levels for cf-nucleosomes and investigated whether global circulating nucleosome levels in association with or without other biomarkers of interest for systemic sclerosis or lung fibrosis (e.g., serum growth factors: IGFBP-1 and the MMP enzyme: MMP-9), could be suitable potential biomarkers for the correct identification of SSc-ILD disease.ResultsWe found that H3.1 nucleosome levels were significantly higher in patients with SSc-ILD compared SSc patients without ILD (p< 0.05) and levels of MMP-9 were significantly increased in patients with SSc-ILD compared to SSc patients without ILD (p< 0.05). Conversely, IGFBP-1 was significantly reduced in patients with SSc-ILD compared to SSc without ILD (p< 0.001). The combination of cf-nucleosomes H3.1 coupled to MMP-9 and IGFBP-1 increased the sensitivity for the differential detection of SSc-ILD. High levels of accuracy were reached with this combined model: its performances are strong with 68.4% of positive predictive value and 77.2% of negative predictive value for 90% of specificity. With our model, we identified a significant negative correlation with FVC % pred (r= −0.22) and TLC % pred (r= −0.31). The value of our model at T1 (baseline) has a predictive power over the Rodnan score at T2 (after 6-18 months), showed by a significant linear regression withR2= 19% (p= 0.013). We identified in the sole group of SSc-ILD patients a significant linear regression with aR2= 54.4% with the variation of DLCO between T1 and T2 (p< 0.05).ConclusionIn our study, we identified a new blood-based model with nucleosomic biomarker in order to diagnose SSc-ILD in a SSc cohort. This model is correlated with TLC and FVC at baseline and predictive of the skin evolution and the DLCO. Further longitudinal exploration studies should be performed in order to evaluate the potential of such diagnostic and predictive model.
Repurposed agents in the Alzheimer’s disease drug development pipeline
Authors: Bauzon Justin , Lee Garam , Cummings Jeffrey 
Published: August 2020

Abstract
Background
Treatments are needed to address the growing prevalence of Alzheimer’s disease (AD). Clinical trials have failed to produce any AD drugs for Food and Drug Administration (FDA) approval since 2003, and the pharmaceutical development process is both time-consuming and costly. Drug repurposing provides an opportunity to accelerate this process by investigating the AD-related effects of agents approved for other indications. These drugs have known safety profiles, pharmacokinetic characterization, formulations, doses, and manufacturing processes.

Methods
We assessed repurposed AD therapies represented in Phase I, Phase II, and Phase III of the current AD pipeline as registered on ClinicalTrials.gov as of February 27, 2020.

Results
We identified 53 clinical trials involving 58 FDA-approved agents. Seventy-eight percent of the agents in trials had putative disease-modifying mechanisms of action. Of the repurposed drugs in the pipeline 20% are hematologic-oncologic agents, 18% are drugs derived from cardiovascular indications, 14% are agents with psychiatric uses, 12% are drug used to treat diabetes, 10% are neurologic agents, and the remaining 26% of drugs fall under other conditions. Intellectual property strategies utilized in these programs included using the same drug but altering doses, routes of administration, or formulations. Most repurposing trials were supported by Academic Medical Centers and were not funded through the biopharmaceutical industry. We compared our results to a European trial registry and found results similar to those derived from ClinicalTrials.gov.

Conclusions
Drug repurposing is a common approach to AD drug development and represents 39% of trials in the current AD pipeline. Therapies from many disease areas provide agents potentially useful in AD. Most of the repurposed agents are generic and a variety of intellectual property strategies have been adopted to enhance their economic value.
Production of dengue virus-like particles serotype-3 in silkworm larvae and their ability to elicit a humoral immune response in mice
Authors: Utomo Doddy Irawan Setyo , Pambudi Sabar , Sjatha Fithriyah , Kato Tatsuya , Park Enoch Y. 
Published: August 2020

AbstractTo develop monovalent dengue virus-like particle for serotype 3 (DENV-LP/3), we prepared and expressed two structural polyprotein constructs using silkworm and Bm5 cells: DENV-3 Capsid-premembrane-envelope (DENV-3CprME) and premembrane-envelope (DENV-3prME). The expressed PA-tagged 3CprME and 3prME polypeptides were partially purified by PA-tag affinity chromatography and had molecular weights of 85 and 75 kDa, respectively. Expressed proteins were separately verified using the following primary antibodies: the anti-PA tag antibody, DENV premembrane polyclonal antibody, and DENV envelope polyclonal antibody. Transmission electron microscopy revealed that these DENV-3CprME and 3prME formed rough, spherical DENV-LPs (DENV-LP/3CprME and DENV-LP/3prME), respectively, with a diameter of 30–55 nm. The heparin-binding assay demonstrated that these DENV-LPs contained the envelope protein domain III on their surfaces. Both DENV-LPs showed an affinity to sera from human dengue patients and immunized mice. Immunization of mice with DENV-LP/3prME significantly induced the level of antibodies compared with DENV-LP/3CprME. These results indicate that DENV-LP/3prME is suitable as a vaccine candidate compared with DENV-LP/3CprME.
Heat shock drives genomic instability and phenotypic variations in yeast
Authors: Shen Li , Wang Yu-Ting , Tang Xing-Xing , Zhang Ke , Wang Pin-Mei , Sui Yang , Zheng Dao-Qiong 
Published: August 2020

AbstractHigh temperature causes ubiquitous environmental stress to microorganisms, but studies have not fully explained whether and to what extent heat shock would affect genome stability. Hence, this study explored heat-shock-induced genomic alterations in the yeast Saccharomyces cerevisiae. Using genetic screening systems and customized single nucleotide polymorphism (SNP) microarrays, we found that heat shock (52 °C) for several minutes could heighten mitotic recombination by at least one order of magnitude. More than half of heat-shock-induced mitotic recombinations were likely to be initiated by DNA breaks in the S/G2 phase of the cell cycle. Chromosomal aberration, mainly trisomy, was elevated hundreds of times in heat-shock-treated cells than in untreated cells. Distinct chromosomal instability patterns were also observed between heat-treated and carbendazim-treated yeast cells. Finally, we demonstrated that heat shock stimulates fast phenotypic evolutions (such as tolerance to ethanol, vanillin, fluconazole, and tunicamycin) in the yeast population. This study not only provided novel insights into the effect of temperature fluctuations on genomic integrity but also developed a simple protocol to generate an aneuploidy mutant of yeast.
A technique of tripled coincidence points for solving a system of nonlinear integral equations in POCML spaces
Authors: Hammad Hasanen A. , La Sen Manuel De 
Published: August 2020

AbstractThis manuscript aims to initiate some recent theoretical consequences related to tripled coincidence points for non-self mappings via the notion ofC-type functions in partially ordered complete metric-like space (for short, POCML space). Our contributions unify and expand some previous studies in this line. Moreover, some corollaries and suitable examples are presented to demonstrate the novelty of the results established. Ultimately, two applications are given here to boost our theoretical consequences, the first one about the contributions of the integral type to obtain a triple coincidence points and the other application is about solving a system of nonlinear integral equations.
Some Hermite–Hadamard type inequalities for generalized h-preinvex function via local fractional integrals and their applications
Authors: Sun Wenbing 
Published: August 2020

AbstractThe concept of generalized h-preinvex function on real linear fractal sets $R^{\beta }$

R
β

($0 < \beta \le 1$
0
<
β
≤
1
) is introduced, which extends generalized preinvex, generalized s-preinvex, generalized Godunova–Levin preinvex, and generalized P-preinvex functions. In addition, some Hermite–Hadamard type inequalities for these classes of functions involving local fractional integrals are established. Lastly, the upper bounds for generalized expectation, generalized rth moment, and generalized variance of a continuous random variable are given to illustrate the applications of the obtained results.
Characterization and modeling of an edge computing mixed reality workload
Authors: Toczé Klervie , Lindqvist Johan , Nadjm-Tehrani Simin 
Published: August 2020

AbstractThe edge computing paradigm comes with a promise of lower application latency compared to the cloud. Moreover, offloading user device computations to the edge enables running demanding applications on resource-constrained mobile end devices. However, there is a lack of workload models specific to edge offloading using applications as their basis.In this work, we build upon the reconfigurable open-source mixed reality (MR) framework MR-Leo as a vehicle to study resource utilisation and quality of service for a time-critical mobile application that would have to rely on the edge to be widely deployed. We perform experiments to aid estimating the resource footprint and the generated load by MR-Leo, and propose an application model and a statistical workload model for it. The idea is that such empirically-driven models can be the basis of evaluations of edge algorithms within simulation or analytical studies.A comparison with a workload model used in a recent work shows that the computational demand of MR-Leo exhibits very different characteristics from those assumed for MR applications earlier.
Profiling of miRNAs in porcine Sertoli cells
Authors: Chen Xiaoxu , Zheng Yi , Li Xueliang , Gao Qiang , Feng Tongying , Zhang Pengfei , Liao Mingzhi , Tian Xiu’e , Lu Hongzhao , Zeng Wenxian 
Published: August 2020

Abstract
Background
Sertoli cells (SCs) create a specialized environment to support and dictate spermatogenesis. MicroRNAs (miRNAs), a kind of ~ 22 nt small noncoding RNAs, have been reported to be highly abundant in mouse SCs and play critical roles in spermatogenesis. However, the miRNAs of porcine SCs remain largely unknown.

Methods
We isolated porcine SCs and conducted small RNA sequencing. By comparing miRNAs in germ cells, we systematically analyzed the miRNA expression pattern of porcine SCs. We screened the highly enriched SC miRNAs and predicted their functions by Gene Ontology analysis. The dual luciferase assay was used to elucidate the regulation of tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3) by ssc-miR-149.

Results
The analysis showed that 18 miRNAs were highly expressed in SCs and 15 miRNAs were highly expressed in germ cells. These miRNAs were predicted to mediate SC and germ cell functions. In addition, ssc-miR-149 played critical roles in SCs by targeting TRAF3.

Conclusion
Our findings provide novel insights into the miRNA expression pattern and their regulatory roles of porcine SCs.
Autonomous underwater videography and tracking of basking sharks
Authors: Hawkes L. A. , Exeter O. , Henderson S. M. , Kerry C. , Kukulya A. , Rudd J. , Whelan S. , Yoder N. , Witt M. J. 
Published: August 2020

Abstract
Background
Biologging studies have revealed a wealth of information about the spatio-temporal movements of a wide range of vertebrates large enough to carry electronic tracking tags. Advances in autonomous underwater vehicles (AUVs or UAVs) and unmanned aerial vehicles (commonly known as drones), which can carry far larger payloads of sensor technologies, have revealed insights into the environment through which animals travel. Some AUVs have been used to film target animals, but are generally limited to periods as long as a drone operator can actively follow an animal. In the present study, we use an AUV, the REMUS-100 SharkCam, paired with a custom transponder tag attached to the shark, to autonomously follow three basking sharks for a cumulative total of 10.9 h to collect video and environmental data on their sub-surface behaviour. The basking shark is the second largest fish in the world and is endangered globally, but despite being subject to various biologging studies, little is known of this species breeding ecology and their mating grounds remain unknown.

Results
We detail the first successful autonomous tracking of basking sharks, comprising three missions that filmed basking sharks in mid-water and close to benthic habitats. Sharks spent very little time feeding, and travelled relatively close to sandy, rocky and algae-covered benthos. One basking shark was observed defecating. Conspecifics were not observed in the three missions, nor were courtship or breeding behaviours. AUV offset distances for videography were determined iteratively through tracking. These offsets varied depending on the trade-off of between water clarity and proximity of the AUV for obtaining useful video data and directly influencing shark behaviour.

Conclusions
The present study is the first successful use of an AUV to gain insight into the sub-surface behaviour of basking sharks.