bluuebunny/crossref_metadata_2025_split huggingface dataset:
Denosumab for Effective Tumor Size Reduction in Patients With Giant Cell Tumors of the Bone: A Systematic Review and Meta-Analysis
Authors: Yayan Josef 
Published: September 2020

Background: Denosumab is a human monoclonal antibody that has been used successfully in the treatment of giant cell tumors of bone. These tumors are rare and, in principle, benign, but they are highly aggressive, locally advanced, osteolytic bone tumors that can metastasize to the lungs. Denosumab is an effective treatment when these tumors cannot be surgically removed or when surgical resection is likely to lead to severe morbidity (eg, loss of limbs or joints). The aim of this systematic review and meta-analysis was to investigate patients with giant cell tumors of bone who experienced tumor progression during treatment with denosumab and to compare them with patients who experienced reduction of their giant cell tumors of bone during treatment with denosumab. Methods: Embase, Cochrane Library, and MEDLINE/PubMed databases were searched for trials submitted by January 7, 2020, that reported the efficacy and safety of denosumab in patients with giant cell tumors of bone. Results: Sixty studies were reviewed, involving a total of 1074 patients who had giant cell tumors of bone and were treated with denosumab. Of the 60 studies, 58% of the patients were from case series studies, 39% from open-label phase II studies, and 3% from case reports. The response rate for denosumab as a treatment for giant cell tumors of bone was 97.5%, with statistical significance ( P < .0001). Pain in the limbs was statistically the most common adverse event for denosumab treatment in case series studies ( P < .0001). No treatment-related deaths occurred in the reviewed studies. Conclusion: Cumulative evidence supports the addition of surgery to optimal medical therapy with denosumab to reduce tumor size, clinical symptoms, and mortality among patients with giant cell tumors of bone.
Novel use of existing technology: A preliminary study of patient portal use for telerehabilitation
Authors: Conroy Susan S , Harcum Stacey , Keldsen Linda , Bever Christopher T 
Published: September 2020

Patient portals (PPs) foster engagement and self-management of chronic disease and are emerging as extensions of the care continuum. Utilisation from a health service delivery perspective is growing; however, it is a relatively new model of care in the field of rehabilitation. This pilot, within a larger randomised controlled stroke rehabilitation trial, explored the feasibility and acceptance of secure messaging using an established nationwide PP system for e-visits. Fifteen participants with stroke-related arm disability were randomised to 6 weeks of home arm telerehabilitation. All were over the age of 60 and 73% lived with a spouse or significant other. Mean intervention time was 6.8 weeks, and participants sent 2.3 ± 1.4 messages per week to complete 15.1 h of reported therapy (prescribed therapy = 18 h). Portal use improved therapist efficiency and resulted in a 1:6 therapist to patient exercise time ratio compared with the conventional 1:1 ratio for in-person therapy. Low initial electronic health literacy, self-efficacy or cognitive scores did not prohibit utilisation, and satisfaction with secure messaging for patient–therapist communication was 3.5 ± 1.2 out of 5. Overall, PP-supported e-visits were a feasible and acceptable telerehabilitation care delivery method for this chronic stroke population. ClinicalTrials.gov Identifier NCT02665052. Registered 27 January 2016. https://clinicaltrials.gov/ct2/show/NCT02665052
Anaemia in chronic kidney disease pregnancy
Authors: Morton Adam , Burke Michael , Morton Anthony , Kumar Sailesh 
Published: September 2020

Aim To review the incidence and management of anaemia and outcomes in pregnancies in a cohort of Australian women with chronic kidney disease. Methods A retrospective audit of 63 pregnancies in 52 women with chronic kidney disease. Results Sixty-eight percent of chronic kidney disease pregnancies were complicated by haemoglobin less than 100 g/L. Iron stores were measured in only 62% of all pregnancies. Serum ferritin was less than 100 ng/ml in 95% of those tested. Erythropoietin-stimulating agents were used in 24 pregnancies (38%). Intravenous iron was used in only nine non-dialysis pregnancies. Conclusion Greater awareness of the importance of regular measurement of iron stores and appropriate levels for repletion in chronic kidney disease pregnancies amongst health professionals involved in obstetric care may result in earlier detection and treatment of iron deficiency, and potentially improve maternal and fetal outcomes.
Comparison of Insulin Pump Bolus Calculators Reveals Wide Variation in Dose Recommendations
Authors: Buchanan Jeanne , Zabinsky Jennifer A. , Ferrara-Cook Christine , Adi Saleh , Wong Jenise C. 
Published: September 2020

Background: The introduction of insulin pumps with bolus calculators (BCs) has improved glycemic outcomes and quality of life for those with type 1 diabetes. Despite the increased reliance on BCs, the formulas used to derive recommended boluses are not standardized. Our objective was to examine whether recommendations from different pump BCs vary significantly for identical clinical scenarios. Methods: Three commercially available insulin pump BCs were programmed with identical settings and then presented with combinations of blood glucose (BG) and carbohydrates (CHOs) to generate a 4-unit bolus. At one- and two-hour time points, while there was insulin-on-board (IOB) present, we simulated various BG and CHO scenarios in order to compare BC-recommended doses. Results: Differences in suggested doses were noted between BCs, as well as within the same brand. The greatest variation was apparent when BG was below target. Doses suggested by one BC varied depending on whether the IOB resulted from a previous dose given for BG or CHO, while the other two BCs adjusted for total IOB regardless of the source. Conclusions: In this simulation study, there were large differences in recommended doses between BCs due to the unique way each manufacturer incorporates IOB into their formulas as well as the pharmacokinetics used to derive the IOB amount. Providers should be aware that identical pump settings will result in a different dose recommendation for each pump brand and advise patients accordingly.
A Bibliometric Analysis and Visualization of Current Research Trends in the Treatment of Cervical Spondylotic Myelopathy
Authors: Yin Mengchen , Xu Chongqing , Ma Junming , Ye Jie , Mo Wen 
Published: September 2020

Study Design: Bibliometric analysis. Objective: Cervical spondylotic myelopathy (CSM) has become the most common cause of spinal cord dysfunction. Many topics of CSM still remain controversial. This study aimed to illustrate the overall knowledge structure and development trends of CSM. Methods: Research data sets were acquired from the Web of Science database and the time span was defined as “2000 to 2019.” VOS viewer and Citespace software was used to analyze the data and generate visualization knowledge maps. Annual trends of publications, distribution, H-index status, co-authorship status, and research hotspots were analyzed. Results: A total of 2367 publications met the requirement. The largest number of articles was from the United States, followed by Japan, China, Canada, and India. The highest H-index was found for articles from the United States. The highest number of articles was published in Spine. The cooperation between the countries, institutes, and authors were relatively weak. Cervical sagittal alignment, predictive factor, diffusion tensor imaging, and the natural history of CSM may become a frontier in this research field. Conclusion: The number of publications showed an upward trend with a stable rise. Most of the publications are limited to a few countries and institutions with relatively weak interaction. The United States, Canada, Japan, China, and India have made significant contributions to the field of CSM. The United States is the country with the highest productivity, not only in quality but also in quantity. Cervical sagittal alignment, predictive factor, diffusion tensor imaging, and the natural history of CSM are the research hotspots in the recent years.
Complications of Spine Surgery in “Super Obese” Patients
Authors: Katsevman Gennadiy A. , Daffner Scott D. , Brandmeir Nicholas J. , Emery Sanford E. , France John C. , Sedney Cara L. 
Published: September 2020

Study Design: Retrospective chart review with matched control. Objective: To evaluate the indications and complications of spine surgery on super obese patients. Methods: A retrospective review assessed super obese patients undergoing spine surgery at a level-1 trauma and spine referral center from 2012 to 2016. Outcomes were compared to age-matched controls with body mass index (BMI) <50 kg/m2. The control group was further subdivided into patients with BMI <30 kg/m2 (normal) and BMI between 30 and 50 kg/m2 (obese). Results: Sixty-three super obese patients undergoing 86 surgeries were identified. Sixty patients (78 surgeries) were in the control group. Age and number of elective versus nonelective cases were not significantly different. Mean BMI of the super obese group was 55 kg/m2 (range 50-77 kg/m2) versus 29 kg/m2 in the controls (range 20-49 kg/m2). Fifty-two percent of surgeries were elective, and the most common indication was degenerative disease (39%). Compared with controls, super obese patients had a higher complication rate (30% [n = 19] vs 10% [N = 6], P = .0055) but similar 30-day mortality rate (5% vs 5%), a finding that was upheld when comparing super obese with each of the control group stratifications (BMI 30-50 and BMI <30 kg/m2). The most common complication among super obese patients was wound dehiscence/infection (n = 8, 13%); 2 patients’ surgeries were aborted. Complication rates for elective surgery were 21% (n = 7) for super obese patients and 4% (n = 1) for controls ( P = .121); complication rates for nonelective procedures were 40% (n = 12) and 14% (n = 5), respectively ( P = .023). Conclusion: The complication rate of spine surgery in super obese patients (BMI ≥ 50 kg/m2) is significantly higher than other patients, particularly for nonelective cases.
Initiation and response of joint attention bids in autism spectrum disorder children depend on the visibility of the target
Authors: Cilia Federica , Touchet Claire , Vandromme Luc , Driant Barbara Le 
Published: September 2020

Background and aims Response to joint attention (RJA) and initiation of joint attention (IJA) are impaired in pre-schoolers with autism spectrum disorder (ASD). Children’s response to joint attention may depend on the presence of the target in the child's field of vision or on the type of deictic index (head and eye orientation, pointing and verbalisations) used by the adult to initiate joint attention. Methods This study deals with 50 ASD children aged from 2 years 8 months to 11 years 7 months, with a communicative level comparable to children under 31 months of age, according to the French version of the Early Social Communication Scales (ECSP, by its French acronym). We compared the aforementioned ASD children with 50 typically developing (TD) children, aged 9 to 30 months who had no communication disorders according to the ECSP. During the ECSP test, we analysed joint attention behaviours on three posters present or absent from the children's visual field. Results We did not observe any difference in the number of IJAs between groups, but ASD children were less responsive than TD children were. Our results showed a developmental progression in the responses of children with ASD if several deictic cues were used by an adult simultaneously (looking and pointing, or looking and verbalising to indicate a target), whether the referent was present or absent from the child’s visual field. In addition, we observed developmental progression when the referent was behind the child and the adult only used their gaze to refer to it. Conclusion Thus, we argue that the type of cues used affects ASD children’s response behaviours during joint attention towards a referent that may be present or absent from their visual field. Implications: Regarding the social and the sensory difficulties of children with ASD, many therapeutic approaches focus their intervention methods on non-verbal communication skills and joint attention. This fundamental research makes it possible to identify the most appropriate type of deictic index for children with ASD with developmental delay, depending on the presence or absence of the referent in the child's visual field.
Efficacy and safety results from CheckMate 140, a phase 2 study of nivolumab for relapsed/refractory follicular lymphoma
Authors: Armand Philippe , Janssens Ann , Gritti Giuseppe , Radford John , Timmerman John , Pinto Antonio , Mercadal Vilchez Santiago , Johnson Peter , Cunningham David , Leonard John P. , Rodig Scott J. , Martín-Regueira Patricia , Sumbul Anne , Samakoglu Selda , Tang Hao , Ansell Stephen M. 
Published: September 2020

Abstract
Nivolumab, an anti–programmed death-1 (PD-1) monoclonal antibody, showed promising activity in relapsed or refractory (R/R) follicular lymphoma (FL) in a phase 1 study. We conducted a phase 2 trial to further evaluate its efficacy and safety in patients with R/R FL and to explore biomarkers of response. Patients with R/R FL and at least 2 prior lines of therapy, each containing a CD20 antibody or an alkylating agent, were treated with nivolumab 3 mg/kg every 2 weeks. The primary end point was objective response rate (ORR) assessed by an independent radiologic review committee. Biomarker analyses included gene expression profiling and multiplex immunofluorescence studies of pretreatment tumor samples. A total of 92 patients were treated. After a minimum follow-up of 12 months, ORR was 4% (4 of 92 patients). Median progression-free survival (PFS) was 2.2 months (95% confidence interval [CI], 1.9-3.6 months). Median duration of response was 11 months (95% CI, 8-14 months). Exploratory analyses suggested that responders had significantly higher proportion of CD3+ T cells in the tumor microenvironment than nonresponders, but no significant differences in PD-1 or programmed death-ligand 1 expression were observed. High expression of a set of tumor-associated macrophage genes was associated with reduced PFS (hazard ratio, 3.28; 95% CI, 1.76-6.11; P = .001). The safety profile was consistent with previous reports of nivolumab. In conclusion, nivolumab monotherapy was associated with very limited activity in patients with R/R FL. Better understanding of the immune biology of this disease may facilitate the development of effective checkpoint-based strategies. This trial was registered at www.clinicaltrials.gov as #NCT02038946.
Plasmacytoid dendritic cell expansion defines a distinct subset of RUNX1-mutated acute myeloid leukemia
Authors: Xiao Wenbin , Chan Alexander , Waarts Michael R. , Mishra Tanmay , Liu Ying , Cai Sheng F. , Yao Jinjuan , Gao Qi , Bowman Robert L. , Koche Richard P. , Csete Isabelle S. , DelGaudio Nicole L. , Derkach Andriy , Baik Jeeyeon , Yanis Sophia , Famulare Christopher A. , Patel Minal , Arcila Maria E. , Stahl Maximilian , Rampal Raajit K. , Tallman Martin S. , Zhang Yanming , Dogan Ahmet , Goldberg Aaron D. , Roshal Mikhail , Levine Ross L. 
Published: September 2020

Abstract
Plasmacytoid dendritic cells (pDCs) are the principal natural type I interferon–producing dendritic cells. Neoplastic expansion of pDCs and pDC precursors leads to blastic plasmacytoid dendritic cell neoplasm (BPDCN), and clonal expansion of mature pDCs has been described in chronic myelomonocytic leukemia. The role of pDC expansion in acute myeloid leukemia (AML) is poorly studied. Here, we characterize patients with AML with pDC expansion (pDC-AML), which we observe in ∼5% of AML cases. pDC-AMLs often possess cross-lineage antigen expression and have adverse risk stratification with poor outcome. RUNX1 mutations are the most common somatic alterations in pDC-AML (&gt;70%) and are much more common than in AML without pDC expansion and BPDCN. We demonstrate that pDCs are clonally related to, as well as originate from, leukemic blasts in pDC-AML. We further demonstrate that leukemic blasts from RUNX1-mutated AML upregulate a pDC transcriptional program, poising the cells toward pDC differentiation and expansion. Finally, tagraxofusp, a targeted therapy directed to CD123, reduces leukemic burden and eliminates pDCs in a patient-derived xenograft model. In conclusion, pDC-AML is characterized by a high frequency of RUNX1 mutations and increased expression of a pDC transcriptional program. CD123 targeting represents a potential treatment approach for pDC-AML.
The critical role of CD4+ T cells in PD-1 blockade against MHC-II–expressing tumors such as classic Hodgkin lymphoma
Authors: Nagasaki Joji , Togashi Yosuke , Sugawara Takeaki , Itami Makiko , Yamauchi Nobuhiko , Yuda Junichiro , Sugano Masato , Ohara Yuuki , Minami Yosuke , Nakamae Hirohisa , Hino Masayuki , Takeuchi Masahiro , Nishikawa Hiroyoshi 
Published: September 2020

Abstract
Classic Hodgkin lymphoma (cHL) responds markedly to PD-1 blockade therapy, and the clinical responses are reportedly dependent on expression of major histocompatibility complex class II (MHC-II). This dependence is different from other solid tumors, in which the MHC class I (MHC-I)/CD8+ T-cell axis plays a critical role. In this study, we investigated the role of the MHC-II/CD4+ T-cell axis in the antitumor effect of PD-1 blockade on cHL. In cHL, MHC-I expression was frequently lost, but MHC-II expression was maintained. CD4+ T cells highly infiltrated the tumor microenvironment of MHC-II–expressing cHL, regardless of MHC-I expression status. Consequently, CD4+ T-cell, but not CD8+ T-cell, infiltration was a good prognostic factor in cHL, and PD-1 blockade showed antitumor efficacy against MHC-II–expressing cHL associated with CD4+ T-cell infiltration. Murine lymphoma and solid tumor models revealed the critical role of antitumor effects mediated by CD4+ T cells: an anti-PD-1 monoclonal antibody exerted antitumor effects on MHC-I−MHC-II+ tumors but not on MHC-I−MHC-II− tumors, in a cytotoxic CD4+ T-cell–dependent manner. Furthermore, LAG-3, which reportedly binds to MHC-II, was highly expressed by tumor-infiltrating CD4+ T cells in MHC-II–expressing tumors. Therefore, the combination of LAG-3 blockade with PD-1 blockade showed a far stronger antitumor immunity compared with either treatment alone. We propose that PD-1 blockade therapies have antitumor effects on MHC-II–expressing tumors such as cHL that are mediated by cytotoxic CD4+ T cells and that LAG-3 could be a candidate for combination therapy with PD-1 blockade.
Association between physical function and long-term care in community-dwelling older and oldest people: the SONIC study
Authors: Srithumsuk Werayuth , Kabayama Mai , Godai Kayo , Klinpudtan Nonglak , Sugimoto Ken , Akasaka Hiroshi , Takami Yoichi , Takeya Yasushi , Yamamoto Koichi , Yasumoto Saori , Gondo Yasuyuki , Arai Yasumichi , Masui Yukie , Ishizaki Tatsuro , Shimokata Hiroshi , Rakugi Hiromi , Kamide Kei 
Published: September 2020

Abstract
Background
Preventing the need for long-term care (LTC) by identifying physical function risk factors are important to decrease the LTC burden. The objective of this study was to investigate whether grip strength and/or walking speed, which are components of the frailty definition, are associated with LTC in community-dwelling older and oldest people.

Methods
The participants were 1098 community-dwelling older and oldest people who had not received LTC at the baseline. The endpoint was receiving LTC after the baseline survey. The independent variables were grip strength and walking speed, and participants were divided into two groups based on these variables. The confounding factors were age, sex, the Japanese version of the Montreal Cognitive Assessment (MoCA-J), hypertension, diabetes mellitus, stroke, joint diseases, living alone, body mass index, and serum albumin. We calculated the hazard ratio of receiving LTC using the Cox proportional hazard model.

Results
Among the 1098 participants, 107 (9.7%) newly received LTC during the follow-up. Regarding the physical function, only slow walking speed was significantly correlated with LTC after adjusting for all confounding factors except the MoCA-J score (HR = 1.74, 95% CI = 1.10–2.75, P = .018). However, slow walking speed was still a risk factor for LTC after adjusting for the MoCA-J score and other confounding factors (HR = 1.64, 95% CI = 1.03–2.60, P = .037).

Conclusions
The findings from this study may contribute to a better understanding of slow walking speed as a factor related to LTC, which might be a criterion for disability prevention and could serve as an outcome measure for physical function in older people.
Identification of quantitative trait nucleotides and candidate genes for soybean seed weight by multiple models of genome-wide association study
Authors: Karikari Benjamin , Wang Zili , Zhou Yilan , Yan Wenliang , Feng Jianying , Zhao Tuanjie 
Published: September 2020

AbstractBackgroundSeed weight is a complex yield-related trait with a lot of quantitative trait loci (QTL) reported through linkage mapping studies. Integration of QTL from linkage mapping into breeding program is challenging due to numerous limitations, therefore, Genome-wide association study (GWAS) provides more precise location of QTL due to higher resolution and diverse genetic diversity in un-related individuals.ResultsThe present study utilized 573 breeding lines population with 61,166 single nucleotide polymorphisms (SNPs) to identify quantitative trait nucleotides (QTNs) and candidate genes for seed weight in Chinese summer-sowing soybean. GWAS was conducted with two single-locus models (SLMs) and six multi-locus models (MLMs). Thirty-nine SNPs were detected by the two SLMs while 209 SNPs were detected by the six MLMs. In all, two hundred and thirty-one QTNs were found to be associated with seed weight in YHSBLP with various effects. Out of these, seventy SNPs were concurrently detected by both SLMs and MLMs on 8 chromosomes. Ninety-four QTNs co-localized with previously reported QTL/QTN by linkage/association mapping studies. A total of 36 candidate genes were predicted. Out of these candidate genes, four hub genes (Glyma06g44510, Glyma08g06420, Glyma12g33280andGlyma19g28070) were identified by the integration of co-expression network. Among them, three were relatively expressed higher in the high HSW genotypes at R5 stage compared with low HSW genotypes exceptGlyma12g33280. Our results show that using more models especially MLMs are effective to find important QTNs, and the identified HSW QTNs/genes could be utilized in molecular breeding work for soybean seed weight and yield.ConclusionApplication of two single-locus plus six multi-locus models of GWAS identified 231 QTNs. Four hub genes (Glyma06g44510,Glyma08g06420,Glyma12g33280&Glyma19g28070) detected via integration of co-expression network among the predicted candidate genes.