bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I study of the combination of anti-GD2 antibody 3F8 and barley-derived (1→3,1→4)-β-D-glucan for patients with resistant neuroblastoma
Authors: Modak S. , Kushner B. H. , Kramer K. , Vickers A. , Cheung N. 
Published: March 2020

9566 Background: Beta glucans are complex, naturally occurring polysaccharides that prime leucocyte dectin and CR3 receptors. Based on our preclinical observations that oral barley-derived (1→3,1→4)-β-D-Glucan (BG) synergizes with the murine anti-GD2 antibody 3F8 against neuroblastoma (NB) (Clin Cancer Res 8:1217), we conducted a phase I study to determine the safety of the combination of BG and 3F8 in patients with resistant NB. Methods: Heavily pre-treated patients with recurrent or refractory advanced stage NB were treated with 3F8/BG. Each cycle consisted of intravenous (IV) 3F8 at a fixed dose of 10 mg/m2/day ×10 days, plus oral BG dose escalated from 10 to 80 mg/kg/day ×10 days in 4 cohorts of 6 patients each. Patients without human anti-mouse antibody (HAMA) could be re-treated up to a total of 4 cycles. Results: Twenty-three patients with stage 4 and one with stage 3 NB (M:F = 11:13; median age 8 (range 2–19) years completed 47 cycles of therapy with 3F8/BG. 8 patients had progressive disease (PD) while 16 had stable refractory NB (SD) at enrollment. All patients completed at least one cycle of therapy and were evaluated for toxicity and response. Maximum tolerated dose for BG was not reached. Two patients developed dose-limiting toxicities (DLT). Both had grade 4 thrombocytopenia after completing one cycle of treatment: one at BG dose of 20mg/kg/day and the other at 40 mg/kg/day. Both cases responded to therapy with a short course of ITP (idiopathic thrombocytopenic purpura) therapy; one subsequently developed chronic ITP. There were no other >grade 2 toxicities related to 3F8/BG therapy. 14, 4, 2 and 6 patients completed 1, 2, 3 and 4 cycles respectively. Reasons for withdrawal in patients who did not complete 4 cycles were PD in 10, persistently elevated HAMA in 6 and DLT in 2. Overall 11 patients had SD and 13 PD. 14/23 patients with positive MIBG scans prior to therapy demonstrated improvement after one cycle. Responses did not correlate with BG dose received. 7 patients, all with residual disease survive at a median of 40 (range 24–45) months post-treatment. Conclusions: 3F8/BG is well tolerated and shows activity against resistant NB. Further clinical investigation of this novel combination is warranted. No significant financial relationships to disclose.
Effect of gilteritinib on survival in patients with FLT3-mutated (FLT3mut+) relapsed/refractory (R/R) AML who have common AML co-mutations or a high FLT3-ITD allelic ratio.
Authors: Levis Mark J. , Perl Alexander E. , Martinelli Giovanni , Cortes Jorge E. , Neubauer Andreas , Berman Ellin , Montesinos Pau , Baer Maria R. , Larson Richard A. , Chou Wen-Chien , Yokoyama Hisayuki , Recher Christian , Yoon Sung-Soo , Hill Jason E , Rosales Matt , Liu Charles , Bahceci Erkut 
Published: March 2020

7000 Background: The FLT3 inhibitor, gilteritinib, showed superior response and overall survival (OS) compared with salvage chemotherapy (SC) in patients (pts) with FLT3mut+ R/R AML in the phase 3 ADMIRAL study. We analyzed the impact of baseline co-mutations and FLT3-ITD allelic ratio (AR) on response and OS. Methods: A total of 37 recurrently mutated genes in AML (Archer Core Myeloid Panel) were analyzed by next-generation sequencing; the cutoff for co-mutation positivity (co-mut+) was ≥0.027. Baseline FLT3-ITD AR ( FLT3-ITD to FLT3 wild-type DNA) was measured by the LeukoStrat CDx FLT3 Mutation Assay. The median FLT3-ITD AR value of 0.77 was used to define high (≥0.77) vs low (<0.77) FLT3-ITD AR. Results: Analysis of 361 FLT3mut+ pts identified four major co-mutation cohorts, each with ≥10% of pts: NPM1 (n=173; 47.9%), DNMT3A (n=115; 31.9%), DNMT3A/NPM1 (n=86; 23.8%) , and WT1 (n=65; 18.0%). In addition, seven pts (1.9%) had all three co-mutations (ie, NPM1, DNMT3A, and WT1). The gilteritinib arm had superior response rates and OS across all four major co-mutation cohorts, with the greatest survival benefit in pts with DNMT3A/NPM1 co-mut+ (Table). In FLT3-ITD AR analyses (n=335), gilteritinib conferred longer OS than SC in pts with a high or low FLT3-ITD AR (gilteritinib: high FLT3-ITD AR, 7.1 mos vs low FLT3-ITD AR, 10.6 mos; SC: high FLT3-ITD AR, 4.3 mos vs low FLT3-ITD AR, 6.9 mos). In both arms, OS was longer in the low FLT3-ITD AR cohort than the high FLT3-ITD AR cohort but the difference in the gilteritinib arm was not statistically significant (gilteritinib: HR=1.341, P=0.0712; SC: HR=2.01, P=0.0021). Conclusions: The ADMIRAL trial shows that the clinical benefit of gilteritinib in FLT3mut+ R/R AML is maintained regardless of NPM1, DNMT3A, DNMT3A/ NPM1, or WT1 co-mut+ or high FLT3-ITD AR. Clinical trial information: NCT02421939. [Table: see text]
Reducing Infusion Clinic Wait Times Using Quality Improvement
Authors: Plourde Collin L. , Varnado William T. , Gleaton Barbara J. , Das Devika G. 
Published: March 2020

PURPOSE: Long wait times are a common occurrence for chemotherapy infusion patients and are a source of decreased patient satisfaction. Our facility sought to decrease outpatient infusion clinic wait times by 20% using the Model for Improvement, quality improvement tools, and Plan-Do-Study-Act cycles. METHODS: A multidisciplinary team was formed to address clinic wait times. Patient interviews, time studies, process mapping, brainstorming sessions, affinity diagrams, fishbone diagrams, and surveys were used to define the problem and to develop an intervention. Wait times from check-in until medication administration were analyzed using statistical process control charts. Our Plan-Do-Study-Act cycle led to the addition of a “fast-track” clinic title for patients not waiting for laboratory results on the day of treatment and changes in clinic communication. The fast-track clinic signaled for those patients to have priority for vital sign collection and earlier notification to pharmacy to begin preparing medications. RESULTS: Baseline wait times for patients not requiring laboratories on the day of treatment averaged 1 hour and 33 minutes. After intervention, using statistical process control charts, a shift was observed with a new average wait time of 1 hour and 12 minutes (a 23% decrease). Wait times for patients requiring laboratories on the day of treatment did not change significantly. CONCLUSION: Implementation of a fast-track clinic title and improving communication resulted in a significant reduction in wait times for patients not requiring laboratories on the day of treatment. Future efforts will focus on sustainment and improving wait times for all patients.
Bone marrow adipose cells – cellular interactions and changes with obesity
Authors: Boroumand Parastoo , Klip Amira 
Published: March 2020

ABSTRACT
The bone marrow is a spatially restricted niche, housing cells of the hematopoietic and mesenchymal lineages in various hierarchical commitment states. Although highly localized, cells within this niche are also subject to regulation by environmental and/or circulatory changes through extensive vascularization. Bone marrow adipocytes, derived from mesenchymal stem cells and once known as marrow space fillers, are a heterogeneous population. These cells reside in distinct niches within the bone marrow and interact with proximal cells, such as hematopoietic precursors and lineage-committed cells. In this diverse cellular milieu, bone marrow adipocytes influence commitment decisions and cellular lineage selection by interacting with stem and progenitor cells. In addition, bone marrow adipocytes respond to environmental changes, such as obesity, by undergoing hypertrophy, hyperplasia or adoption of characteristics resembling those of peripheral brown, beige or white adipocytes. Here, we review recent findings and concepts on the influence of bone marrow adipocytes on hematopoietic and other cellular lineages within this niche. We discuss how changes in local, systemic, cellular and secreted signals impact on mesenchymal stem cell expansion, differentiation and lineage commitment. Furthermore, we highlight that bone marrow adipocytes may be intermediaries conveying environmental cues to influence hematopoietic cellular survival, proliferation and preferential differentiation.
Leadership for the Team Physician
Authors: Tayne Samantha , Hutchinson Mark R. , O'Connor Francis G. , Taylor Dean C. , Musahl Volker , Indelicato Peter 
Published: March 2020

Abstract
Physician leadership of the interdisciplinary sports medicine team depends on fundamental leadership skills that often are overlooked in medical school. These leadership skills include effective communication, emotional intelligence, teamwork, selfless service, integrity, and critical thinking while utilizing an athlete-centered approach. Development of these skills will help to navigate team management and important decisions, such as return to play. The leadership session at the Advanced Team Physician Course sought to acknowledge the gap in medical training regarding leadership education and began to address it in a forum specifically for team physicians. Here we provide a summary of the lectures and presentations from the 2018 Advanced Team Physician Course in an effort to benefit a broader physician audience. This material should act as a framework for current and future team physicians to solidify their role as the leader of the medical team in caring for the athlete.
Cigarette smoke inhalation impairs angiogenesis in early bone healing processes and delays fracture union
Authors: Chang Chao-Jui , Jou I-Ming , Wu Tung-Tai , Su Fong-Chin , Tai Ta-Wei 
Published: March 2020

Aims Cigarette smoking has a negative impact on the skeletal system, causes a decrease in bone mass in both young and old patients, and is considered a risk factor for the development of osteoporosis. In addition, it disturbs the bone healing process and prolongs the healing time after fractures. The mechanisms by which cigarette smoking impairs fracture healing are not fully understood. There are few studies reporting the effects of cigarette smoking on new blood vessel formation during the early stage of fracture healing. We tested the hypothesis that cigarette smoke inhalation may suppress angiogenesis and delay fracture healing. Methods We established a custom-made chamber with airflow for rats to inhale cigarette smoke continuously, and tested our hypothesis using a femoral osteotomy model, radiograph and microCT imaging, and various biomechanical and biological tests. Results In the smoking group, Western blot analysis and immunohistochemical staining revealed less expression of vascular endothelial growth factor (VEGF) and von Willebrand factor (vWF). The smoking group also had a lower microvessel density than the control group. Image and biochemical analysis also demonstrated delayed bone healing. Conclusion Cigarette smoke inhalation was associated with decreased expression of angiogenic markers in the early bone healing phase and with impaired bone healing. Cite this article: Bone Joint Res. 2020;9(3):99–107.
Can joint fluid metabolic profiling (or “metabonomics”) reveal biomarkers for osteoarthritis and inflammatory joint disease?
Authors: Akhbari Pouya , Karamchandani Urvi , Jaggard Matthew K. J. , Graça Goncalo , Bhattacharya Rajarshi , Lindon John C. , Williams Horace R. T. , Gupte Chinmay M. 
Published: March 2020

Aims Metabolic profiling is a top-down method of analysis looking at metabolites, which are the intermediate or end products of various cellular pathways. Our primary objective was to perform a systematic review of the published literature to identify metabolites in human synovial fluid (HSF), which have been categorized by metabolic profiling techniques. A secondary objective was to identify any metabolites that may represent potential biomarkers of orthopaedic disease processes. Methods A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines using the MEDLINE, Embase, PubMed, and Cochrane databases. Studies included were case series, case control series, and cohort studies looking specifically at HSF. Results The primary analysis, which pooled the results from 17 published studies and four meeting abstracts, identified over 200 metabolites. Seven of these studies (six published studies, one meeting abstract) had asymptomatic control groups and collectively suggested 26 putative biomarkers in osteoarthritis, inflammatory arthropathies, and trauma. These can broadly be categorized into amino acids plus related metabolites, fatty acids, ketones, and sugars. Conclusion The role of metabolic profiling in orthopaedics is fast evolving with many metabolites already identified in a variety of pathologies. However, these results need to be interpreted with caution due to the presence of multiple confounding factors in many of the studies. Future research should include largescale epidemiological metabolic profiling studies incorporating various confounding factors with appropriate statistical analysis to account for multiple testing of the data. Cite this article: Bone Joint Res. 2020;9(3):108–119.
Transmissive resonant fiber-optic gyroscope employing Kagome hollow-core photonic crystal fiber resonator
Authors: Suo Xinxin , Yu Haicheng , Li Jing , Wu Xudong 
Published: March 2020

A novel scheme for a double closed-loop resonant fiber-optic gyroscope (R-FOG) employing a high-performance transmissive Kagome hollow-core photonic crystal fiber (HCPCF) resonator is proposed. We use specially designed Kagome HCPCFs and a meniscus lens module to form a resonator, whose finesse is 58.2 with a length of 5.6 m and a diameter of 13 cm; the theoretical sensitivity of the R-FOG is better than 0.05°/h. Based on the novel Kagome HCPCF resonator, a double closed-loop R-FOG is set up and the performance of the R-FOG system is experimentally studied. It demonstrates that white noise dominates in the output at the integration time of 200 s and a bias stability of 0.15°/h and angle random walk coefficient of

0.04

∘

h

1

/

2

are achieved. Over a dynamic range of

−

100

∘

/

s

to 100°/s, the scale factor nonlinearity of the FOG is 310 ppm, which shows significant improvement compared with the single closed-loop R-FOG system. The novel double closed-loop R-FOG proposed is quite feasible for tactical grade applications.
Ultra-large local field enhancement effect of isolated thick triangular silver nanoplates on a silicon substrate in the green waveband
Authors: Feng Huimin , Dong Jianjie , Wu Xianxin , Yang Fengyou , Ma Lijun , Liu Xinfeng , Liu Qian 
Published: March 2020

The local field enhancement in plasmonic nanostructures is vital for surface enhanced Raman scattering (SERS). However, it remains a challenge to achieve a large local field enhancement at an illumination wavelength in the green waveband. Here we report on an ultra-large local field enhancement effect of isolated thick triangular silver nanoplates (ITTSNPs) on a silicon substrate at an illumination wavelength in the green waveband. We show that when the thickness of the ITTSNP is larger than a critical thickness depending on the illumination wavelength, a large local field enhancement with an enhancement factor (EF) greater than 350 can be achieved at an illumination wavelength in the green waveband, which is due to the excitation of strong localized surface plasmon polaritons only at three top apexes of the ITTSNP. Furthermore, we experimentally demonstrate that at an excitation wavelength of 514.5 nm, the average SERS EF of the ITTSNPs can exceed

10

11

, and the sensitivity for the detection of Rhodamine 6 G molecules can reach

10

−
12

M

.
Nonalcoholic Fatty Liver Disease and Sarcopenia Are Independently Associated With Cardiovascular Risk
Authors: Han Eugene , Lee Yong-ho , Kim Young Dae , Kim Beom Kyung , Park Jun Yong , Kim Do Young , Ahn Sang Hoon , Lee Byung-Wan , Kang Eun Seok , Cha Bong-Soo , Han Kwang-Hyub , Nam Hyo Suk , Heo Ji Hoe , Kim Seung Up 
Published: March 2020

OBJECTIVES:
Nonalcoholic fatty liver disease (NAFLD) and sarcopenia have a close association with an increased risk of atherosclerotic cardiovascular disease (ASCVD). This study investigated the influence of NAFLD and sarcopenia on ASCVD risk.

METHODS:
Data from the 2008–2011 Korean National Health and Nutrition Examination Surveys database were analyzed (n = 7,191). The sarcopenia index was calculated using dual-energy x-ray absorptiometry. Sarcopenia was defined as the lowest quintile sarcopenia index value (cutoffs = 0.882 for men and 0.582 for women). NAFLD was defined as a comprehensive NAFLD score ≥40. Liver fibrosis was assessed using the fibrosis-4 (FIB-4) index. ASCVD risk was evaluated using American College of Cardiology/American Heart Association guidelines. High probability of ASCVD was defined as ASCVD risk >10%.

RESULTS:
The prevalence rates of NAFLD and sarcopenia were 31.2% (n = 2,241) and 19.5% (n = 1,400), respectively. The quartile-stratified ASCVD risk scores were positively associated with NAFLD and sarcopenia (all P for trend < 0.001). Subjects with both NAFLD and sarcopenia had a higher risk for high probability of ASCVD (odds ratio = 1.83, P = 0.014) compared with controls without NAFLD and sarcopenia. Among subjects with NAFLD, FIB-4–defined significant liver fibrosis and sarcopenia additively raised the risk for high probability of ASCVD (odds ratio = 3.56, P < 0.001) compared with controls without FIB-4–defined significant liver fibrosis or sarcopenia.

DISCUSSION:
NAFLD and sarcopenia were significantly associated with an increased risk of ASCVD in the general population. In addition, NAFLD with significant liver fibrosis and sarcopenia were significantly associated with an increased risk of ASCVD in subjects with NAFLD.
Altered Microbiota Diversity and Bile Acid Signaling in Cirrhotic and Noncirrhotic NASH-HCC
Authors: Sydor Svenja , Best Jan , Messerschmidt Insa , Manka Paul , Vilchez-Vargas Ramiro , Brodesser Susanne , Lucas Christina , Wegehaupt Annemarie , Wenning Chiara , Aßmuth Sophia , Hohenester Simon , Link Alexander , Faber Klaas Nico , Moshage Han , Cubero Francisco Javier , Friedman Scott L. , Gerken Guido , Trauner Michael , Canbay Ali , Bechmann Lars P. 
Published: March 2020

OBJECTIVES:
The precipitous increase in nonalcoholic steatohepatitis (NASH) is accompanied by a dramatic increase in the incidence of NASH-related hepatocellular carcinoma (HCC). HCC in NASH has a higher propensity to arise without pre-existing cirrhosis compared with other chronic liver diseases.

METHODS:
To identify the potential links between liver and gut in NASH-related hepatocarcinogenesis, we compared the gut microbiota and mediators of bile acid (BA) signaling in the absence or presence of cirrhosis through the analysis of stool and serum samples from patients with NASH non-HCC and NASH-HCC and healthy volunteers.

RESULTS:
Serum levels of total and individual BA were higher in NASH compared with healthy controls. Furthermore, serum levels of the primary conjugated BAs glycine-conjugated cholic acid, taurine-conjugated cholic acid, glycine-conjugated chenodeoxycholic acid, and taurine-conjugated chenodeoxycholic acid were significantly increased in cirrhotic vs noncirrhotic patients, independent of the occurrence of HCC. By contrast, serum FGF19 levels were higher in patients with NASH-HCC and associated with tumor markers as well as an attenuation of BA synthesis. Specific alterations in the gut microbiome were found for several bacteria involved in the BA metabolism including Bacteroides and Lactobacilli. Specifically, the abundance of Lactobacilli was associated with progressive disease, serum BA levels, and liver injury in NASH and NASH-HCC.

DISCUSSION:
Here, we demonstrate a clear association of the altered gut microbiota and primary conjugated BA composition in cirrhotic and noncirrhotic patients with NASH-HCC. Microbiota-associated alterations in BA homeostasis and farnesoid X receptor signaling, via FGF19, might thus contribute to fibrogenesis, liver injury, and tumorigenesis in NASH-HCC.
Combined Use of Common Fecal and Blood Markers for Detection of Endoscopically Active Inflammatory Bowel Disease
Authors: Mak Lung-Yi , Tong Teresa S. M. , Cheung Ka-Shing , Chen Li-Jia , Lui Ka-Luen , Lau Kam-Shing , Leung Wai K. 
Published: March 2020

INTRODUCTION:
Monitoring of disease activity is essential in patients with inflammatory bowel disease. Although endoscopic remission is the ideal therapeutic goal, noninvasive biomarkers (blood and fecal) are more acceptable to patients and are less costly. We evaluated the performance of combinations of fecal and blood markers on the detection of endoscopically active disease.

METHODS:
Patients with ulcerative colitis (UC) or Crohn's disease (CD) on stable medications were recruited. Blood markers included C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, platelet count (PLT), and hemoglobin. Fecal biomarkers included fecal calprotectin (FCT) and fecal immunochemical test (FIT). These markers were compared with the endoscopic Mayo score for UC and the Simple Endoscopic Score for CD.

RESULTS:
One hundred thirteen patients (mean age 44.7 years, 63.7% men, 54.9% patients with UC and 45.1% patients with CD) were recruited. FCT correlated well with FIT (r = 0.58), CRP (r = 0.56), ESR (r = 0.40), albumin (r = −0.54), PLT (r = 0.61), and hemoglobin (r = −0.35; all Ps < 0.001). Among 66 patients with endoscopic evaluation, 39.4% with endoscopically active disease had higher FCT, FIT, CRP, ESR, PLT, lower albumin, and hemoglobin compared with those in endoscopic remission (all Ps < 0.01). All 7 markers demonstrated good area under receiver operating characteristics (>0.7), with FCT being the best (0.91) for endoscopically active disease. Combining FCT and FIT improved the specificity to 95%, but the sensitivity decreased to 65.4%. In the subgroup analysis of UC, adding PLT to FIT improved the sensitivity and specificity to 100% and 90.9%, respectively.

DISCUSSION:
The combined use of fecal biomarkers and blood indexes is superior to the use of fecal biomarkers alone in identifying endoscopically active disease.
Surface-induced phase transitions in thin films of dendrimer block copolymers
Authors: Lin Bo , Zheng Chen , Zhu Qingying , Xie Fang 
Published: March 2020

Abstract
The phase morphologies and phase transitions of dendrimer block copolymer thin films confined between two homogeneous, planar hard substrates had been investigated by a three-dimensional real space self-consistent field theory (SCFT). From the perspectives of property and strength of the preferential substrate, when the film system confined within neutral substrates, the thinner film was easier to take the undulated and perpendicular cylinder phases. For the attractive preference of the substrate on block segment A, the polymer films tended to take the surface-wetting structures that was composed by block segment A. On the contrary, for the repulsive preference of the substrate on block segment A, a phase transition of cylinder-lamellae could be observed increasing with the relative surface strength of the preferential substrate.