bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiorespiratory fitness and moderate-to-vigorous physical activity in older adults with multiple sclerosis
Authors: Motl Robert W , Baird Jessica F 
Published: November 2021

Background Cardiorespiratory fitness (VO2peak) may be a modifiable indicator of health status and well-being in older adults with multiple sclerosis. Purpose We examined differences in VO2peak and moderate-to-vigorous physical activity between older adults with multiple sclerosis and healthy controls, and whether moderate-to-vigorous physical activity accounted for group differences in VO2peak. Methods Older adults with multiple sclerosis ( n = 31) and healthy controls ( n = 29) completed a cardiopulmonary exercise test and wore an accelerometer for measuring moderate-to-vigorous physical activity. The data were analyzed using the Baron and Kenny approach for examining moderate-to-vigorous physical activity as a mediator of group differences in VO2peak. Results The multiple sclerosis group had significantly lower VO2peak and moderate-to-vigorous physical activity than healthy controls. VO2peak had a large correlation with moderate-to-vigorous physical activity ( r = .59). Group initially explained 8% of the variance in VO2peak ( β  =  −0.29). The inclusion of moderate-to-vigorous physical activity accounted for an additional 27% of the variance in VO2peak, but only moderate-to-vigorous physical activity ( β  =  0.57) was a statistically significant correlate of VO2peak. The effect of Group was attenuated and non-significant with the addition of moderate-to-vigorous physical activity in Step 2 (Group β Step 1  =  −0.29, Group β Step 2  =  −0.05). Conclusions Our results provide initial support for targeting moderate-to-vigorous physical activity as an approach for improving VO2peak in older adults with multiple sclerosis.
Economic Stress and Body Weight During the COVID-19 Pandemic
Authors: Mathieu-Bolh Nathalie 
Published: November 2021

The COVID-19 pandemic has caused income loss for many households, disrupting food consumption patterns and contributing to weight loss for some, and weight gain for others. In this article, I build a dynamic theoretical model that explains those empirical facts. The novelty of this paper is to incorporate stress caused by a lower than ideal income (economic stress) in a model of optimal intertemporal food consumption decisions made by a rational eater. In this framework, economic stress causes disutility and individuals can cope by increasing high-calorie food consumption (stress eating). The limitation to this coping mechanism is that being overweight from excessive calorie intake also decreases utility. Thus, a decrease in income causes updates of the constraints faced by rational consumers of food, which are a budget constraint, a stress constraint and a weight gain constraint. As a consequence, the effect of a decrease in income on body weight reflects a competing income effect as well as two effects specific to economic stress, which are an intertemporal substitution effect and a stress eating effect. Those effects explain opposite weight patterns observed during the pandemic. JEL Classification: D11, D91, I12, I14
Assessing quality and agreement of structured data in automatic versus manual abstraction of the electronic health record for a clinical epidemiology study
Authors: Brazeal Joseph Grant , Alekseyenko Alexander V , Li Hong , Fugal Mario , Kirchoff Katie , Marsh Courtney , Lewin David N , Wu Jennifer , Obeid Jihad , Wallace Kristin 
Published: November 2021

Objective We evaluate data agreement between an electronic health record (EHR) sample abstracted by automated characterization with a standard abstracted by manual review. Study Design and Setting We obtain data for an epidemiology cohort study using standard manual abstraction of the EHR and automated identification of the same patients using a structured algorithm to query the EHR. Summary measures of agreement (e.g., Cohen’s kappa) are reported for 12 variables commonly used in epidemiological studies. Results Best agreement between abstraction methods is observed among demographic characteristics such as age, sex, and race, and for positive history of disease. Poor agreement is found in missing data and negative history, suggesting potential impact for researchers using automated EHR characterization. EHR data quality depends upon providers, who may be influenced by both institutional and federal government documentation guidelines. Conclusion Automated EHR abstraction discrepancies may decrease power and increase bias; therefore, caution is warranted when selecting variables from EHRs for epidemiological study using an automated characterization approach. Validation of automated methods must also continue to advance in sophistication with other technologies, such as machine learning and natural language processing, to extract non-structured data from the EHR, for application to EHR characterization for clinical epidemiology.
Comparison of D-Dimer Level on Mild, Moderate and Severe COVID-19 at Immanuel Hospital Bandung City October 1 st - December 31 st, 2020
Authors: Gustian Hary , Pratiwi Regina Anjani Budi , Riantie Rini 
Published: November 2021

Abstract
Background: Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In COVID-19 there is a process of thrombosis and coagulopathy, which are systemic inflammation and endothelial disorders resulting in hypercoagulability. D-dimer is a laboratory test that can determine coagulation activation (hypercoagulability) and fibrinolysis. D-dimer can be used as a guide of anticoagulant and thrombolytic therapy and prognostic parameter in COVID-19 patients, where its value runs parallel to the severity of the disease and is associated with increased mortality.
Materials and methods: The whole sampling was taken from 59 medical records of inpatients confirmed with COVID-19 through the RT-PCR examination at Immanuel Hospital, Bandung City for the period of October 1 st - December 31 st, 2020. The value of d-dimer was taken from whole blood, tested with sandwich ELISA method with cut-off value (normal value) &lt; 0.5μg/ml. COVID-19 patient classification was based on the COVID-19 guideline from Indonesian Ministry of Health. The research method was observational analytical with cross-sectional design. Statistical test used was Kruskal-Wallis test with Mann-Whitney advanced test (α = 0.05).
Results: The mean d-dimer value in patients with mild, moderate, and severe COVID-19 was 0.3034 µg/mL; 0.5138 µg/mL; and 1.1751 µg/mL. The results of Kruskal-Wallis test showed a very significant difference in mean d-dimer values in mild, moderate, and severe COVID-19 patients. Mann-Whitney test showed that there was a very significant difference in the mean d-dimer value between mild and severe COVID-19 patients, also between moderate and severe COVID-19 patients with a value of p = 0.000 (p &lt;0.01). But there was no difference in the mean d-dimer value between mild and moderate COVID-19 patients, p = 0.454 (p&gt; 0.05).
Conclusion: There is a very significant difference in d-dimer values between mild, moderate and severe COVID-19 patients. The d-dimer value increases with the severity of COVID-19.
Keywords: COVID-19, mild COVID-19, moderate COVID-19, severe COVID-19, d-dimer

Disclosures
No relevant conflicts of interest to declare.
Hematopoietic Stem Cell Regeneration through Paracrine Regulation of the Wnt5a-Prox1 Signaling Axis
Authors: Lin Qiqi , Chatla Srinivas , Wu Limei , Chowdhury Fabliha , Du Wei 
Published: November 2021

Abstract
The crosstalk between bone marrow (BM) microenvironment (niche) and hematopoietic stem cells (HSCs) is critical for HSC regeneration after injury. Here we show that deletion of the genes encoding the DNA repair-deficient syndrome Fanconi anemia (FA), Fanca and Fancc, in mice dampens HSC regeneration through both direct effects on HSCs and indirect effects on BM niche cells. Specifically, Fanca- or Fancc-deficiency compromises hematologic recovery and dampens HSC regeneration following irradiation. FA HSCs show persistent upregulation of the Wnt target Prox1, a homeobox transcription factor, in response to total body irradiation (TBI). Accordingly, lineage-specific deletion of Prox1 improves long-term repopulation of the irradiated FA HSCs. Forced expression of Prox1 in wild-type (WT) HSC mimics the defective repopulation phenotype of FA HSCs. By analyzing paracrine factors in Wnt signaling, we found that WT mice, but not FA mice, show significant induction by TBI of BM stromal Wnt5a protein, which is produced in LepR +CXCL12 + BM stromal cells. Wnt5a treatment of irradiated FA mice enhances hematopoietic recovery and HSC regeneration. Conversely, Wnt5a neutralization in co-cultured LepR + BM stromal cells inhibits HSC regeneration and hematopoietic recovery following TBI. Mechanistically, Wnt5a secreted by LepR +CXCL12 + BM stromal cells inhibits b-catenin accumulation, thereby repressing Prox1 transcription in irradiated HSPCs. The detrimental effect of deregulated Wnt5a-Prox1 signaling on HSC regeneration and hematopoietic recovery is also observed in aged mice. Irradiation induces upregulation of Prox1 in the HSCs of aged mice, and deletion of Prox1 in aged HSCs improves HSC regeneration and hematopoietic recovery after irradiation. Finally, treatment of aged mice with Wnt5a enhances hematopoietic repopulation. Collectively, these findings identify the novel paracrine Wnt5a-Prox1 signaling axis in regulating HSC regeneration under conditions of injury and aging.

Disclosures
No relevant conflicts of interest to declare.
Effective Central Nervous System (CNS) Prophylaxis Chemotherapy Approach in High Risk Diffuse Large B-Cell Lymphoma (DLBCL): A Network Meta-Analysis
Authors: Haddad Philip A , Hammoud Dalia , Gallagher Kevin M. 
Published: November 2021

Abstract
Introduction: CNS relapses with DLBCL tend to be uncommon. The risk increases with certain DLBCL types and certain risk features. There is no consensus regarding the optimal approach to CNS prophylaxis for high-risk DLBCL patients. While some favor prophylaxis with high-dose systemic therapy or intrathecal chemotherapy (IT), some experts advocate combining both approaches. In the absence of randomized trials, the role of CNS chemotherapy prophylaxis remains controversial in DLBCL with contradictory comparative studies. The purpose of this meta-analysis is to evaluate the impact of CNS prophylaxis approaches on the clinical outcomes of high-risk DLBCL.
Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of DLBCL diagnosis, English language, IT or high-dose systemic prophylactic chemotherapy, and comparative studies reporting CNS recurrence rates. A frequentists and Bayesian network meta-analyses were conducted using the netmeta package and random-effects model.
Results: Twenty-one comparative studies with a total of 11,507 patients were included and analyzed. The relative risk (RR) of CNS recurrence was not statistically different between IT prophylaxis, high-dose chemotherapy, and no prophylaxis. However, the combination of IT prophylaxis and high-dose chemotherapy was found to be significantly associated with a reduced RR of CNS recurrence when compared to IT prophylaxis (RR=0.28, 95%CI 0.13-0.58), high-dose chemotherapy (RR=0.34, 95%CI 0.14-0.80), and no prophylaxis (RR=0.41, 95%CI 0.19-0.87).
Conclusions: This network meta-analysis is the first to compare the different CNS prophylactic approaches. It indicates that IT prophylaxis and high-dose chemotherapy each were not better than no prophylaxis. However, the combination of IT prophylaxis with high-dose chemotherapy was significantly superior to each approach alone as well as no prophylaxis. In the absence of randomized clinical trials, this network meta-analysis represents the most compelling data supporting the use of CNS prophylaxis in patients with high-risk DLBCL.

Disclosures
No relevant conflicts of interest to declare.
Comparison of Treatment Modalities in Frontline Therapy of Stages I/IE Extranodal NK/T-Cell Lymphoma-Nasal Type (ENKTL-N): An up-to-Date Network Meta-Analysis
Authors: Haddad Philip A , Hammoud Dalia , Gallagher Kevin M. 
Published: November 2021

Abstract
Introduction: Despite many studies reporting on the optimal therapies for early stage ENKTL-N in the front-line setting, this area continues to be subject to a significant controversy regarding single modalities versus combination or sequential approaches. All these comparative studies were small non-randomized studies that combined stages I & II. The results were often inconclusive and occasionally conflicting. In the absence of direct head-to-head randomized controlled trials in this clinical setting, a network meta-analysis was conducted to compare these therapeutic approaches and their respective impact on 5-year survival in stage I/IE ENKTL-N.
Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of stage I/IE ENKTL-N, treatment with chemotherapy (CT), radiation (RT), sequential CT and RT (SEQ), and chemoradiotherapy (CRT), comparative studies that reported predominantly (&gt;70%) I/IE 5-year overall survival (OS) and disease-free survival (DFS) rates. Studies that reported on mixed samples of early and advanced ENKTL were excluded. A frequentist network meta-analysis was conducted using the netmeta package and random-effects model.
Results: Seven studies comprising a total of 397 participants were included. Our network meta-analysis revealed that upfront RT tended to have better 5-year OS and DFS than CRT, SEQ, though it did not reach statistical significance. However, RT had a significantly superior 5-year OS when compared to CT (RR=0.43, 0.19-0.97). Based on the pair-wise and network meta-analyses, RT was ranked as the most effective first-line treatment approach followed by CRT, SEQ, and CT in decreasing order. Analysis of the 5-year DFS yielded similar findings. Inconsistency analysis did not reveal any significant differences between direct and indirect estimates.
Conclusion: This is the first network meta-analysis to compare all commonly utilized upfront treatment modalities in stages I/IE ENKTL-N. It indicates that upfront RT alone may be sufficient as there was no signal that chemotherapy added any OS or DFS advantages. Adequately powered randomized trials are warranted.

Disclosures
No relevant conflicts of interest to declare.
The Prognostic Significance of the Stage of Reaching MRD-Negative for Patients with Multiple Myeloma Received ASCT
Authors: Sun Qian , Li Juan 
Published: November 2021

Abstract
Objective: To explore the prognostic significance of the stage of reaching MRD-negative for patients with newly diagnosed multiple myeloma (NDMM) patients who received autologous hematopoietic stem cell transplantation (ASCT).
Methods: A retrospective analysis of 186 NDMM patients who received "induction therapy-ASCT-maintenance therapy" in our center and reached MRD-negative, according to the stage when the patient's MRD status turned negative (induction therapy, 3 months after ASCT, maintenance therapy) is divided into three stages, A, B, and C (Figure 1). We compared the clinical characteristics and prognosis of patients in the three stages.
Results: The median time to progress (TTP) of 186 patients was not reached, the median overall survival (OS) was 113.8 months, and the median follow-up time was 67.6 months; the number of cases in the three stages of A, B, and C was 73 (39.2%), 42 (22.6%), and 71 (38.2%), respectively (Figure 2). The median TTP of the patients in the three stages was not reached (P=0.013), and the median OS was not reached, not reached, and 71.2 months, respectively (P=0.026). Among the 124 standard-risk cytogenetics patients, the median TTP of the three stages of patients was not reached (P=0.121), and the median OS was not reached, not reached, and 99.6 months, respectively (P=0.091) (Figure 3). Among the 38 high-risk cytogenetics patients, the median TTP of patients in the three stages were unreached, 53.9 months, and 35.8 months (P=0.060), and the median OS was not reached, 71.2 months, and 60.2 months (P=0.625) (Figure 4). Among the 157 R-ISS Ⅰ-Ⅱ patients, the median TTP of the three stages was not reached (P=0.174), and the median OS was not reached, not reached, and 99.6 months (P=0.186) (Figure 5). Among 29 cases of R-ISS Ⅲ, the median TTP of the 3 stage patients was unreached, unreached, and 35.1 months (P&lt;0.001), and the median OS was unreached, unreached, and 48.5 months, respectively (P=0.020) (Figure 6).
Conclusion: For the same patients with MRD negative, the prognosis of patients reaching MRD-negative at different stages is different. The stage of reaching MRD-negative can predict the prognosis of patients with R-ISS stage Ⅲ, but cannot predict the prognosis of patients with R-ISS Ⅰ-Ⅱ.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
A Prospective Clinical Study of the Efficacy and Adverse Reactions of Azacitidine Combined with IA Regimen As the Induction Treatment of Newly Diagnosed AML
Authors: Kuang Lifen , Li Juan 
Published: November 2021

Abstract
Objective:
This single-arm prospective research (ChiCTR2100044731) aimed to evaluate the efficacy and safety of azacitidine combined with IA regimen in the induction treatment of newly diagnosed acute myeloid leukemia (AML), with a view to further improving the efficacy of acute myeloid leukemia with poor prognosis.
Methods:
Newly diagnosed AML (non-M3) patients who received azacitidine combined with IA regimen induction chemotherapy in the Department of Hematology of the First Affiliated Hospital of Sun Yat-sen University from November 2019 to February 2021 were enrolled, and the efficacy and side effect were analyzed.
Results: A total of 33 patients were enrolled. The median age of the enrolled patients was 43.36 years (17-63), including 16 males (48.5%) and 17 females (51.5%). According to NCCN risk stratification, there were 3 patients (9.1%) in the favor group (9.1%) ,13 cases (39.4%) in the intermediate group and 17 cases (51.5%) in the poor group.The CR rate of one cycle of azacitidine combined with IA regimen was 66.7%, with a PR rate of 12.1% and a NR rate of 21.2%. After propensity score matching with the newly diagnosed AML patients who received IA regimen as induction chemotherapy in our center, a paired study was carried out. The results showed that there was no significant difference between the 2 groups in the treatment CR rate (66.7% for azacitidine combined with IA vs 54.5% for IA, P=0.592, Fig1). Subgroup analysis (table 1) showed combination of azacitidine with IA significantly improved the CR rate of patients with a ratio of blasts in the bone marrow greater than 67% (83.3% vs 30.8%, P=0.014) and patients in the intermediate NCCN risk group (100.0% vs 37.5%, P=0.001).The duration of agranulocytosis in the azacitidine combined with IA chemotherapy group was longer than that in the IA group (21 days vs 19 days, P=0.045). There was no significant difference in the number of platelet transfusions and the number of red blood cell transfusions between the two groups, and there was no significant difference in the incidence of infection between the two groups (table 2).
Conclusions:
The remission rate of induction chemotherapy for azacitidine combined with IA regimen and IA regimen in newly diagnosed non-M3 AML patients is comparable. Patients with a ratio of immature cells in bone marrow greater than 67% and patients in the intermediate NCCN risk group may benefit from azacitidine combined with the IA regimen. The combination of azacitidine with IA regimen aggravated granular bone marrow suppression.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
The Immediate Effect of COVID-19 Vaccination on Anticoagulation Control in Patients Using Vitamin K Antagonists
Authors: Visser Chantal , Biedermann Joseph S. , Nierman Melchior C. , Van der Meer Felix J. M. , Gulpen Anouk J. W. , Moors Yvonne C. F. , Cannegieter Suzanne C. , Lijfering Willem M , Kruip Marieke J.H.A. , Dutch COVID & Thrombosis Coalition The 
Published: November 2021

Abstract
Background: In January 2021, the Dutch vaccination programme against SARS-CoV-2 was started. Clinical studies have shown that systemic reactions occur in up to 50% of vaccine recipients. Therefore, COVID-19 vaccination could affect anticoagulation control, potentially leading to an increased risk of thrombotic events and bleeding complications.
Aims: To investigate whether the BNT162b2 vaccine affects anticoagulation control in outpatients using Vitamin K antagonists (VKAs).
Methods: A case-crossover study was performed in a cohort of outpatient VKA users from four Dutch anticoagulation clinics who received a BNT162b2 vaccine. INR results and VKA dosages before the first vaccination, the reference period, were compared with those after the first and second vaccination.
Results: A total of 3148 outpatient VKA users were included, with a mean age (standard deviation (SD)) of 86.7 (8.7) years, of whom 43.8% were male, 67.0% used acenocoumarol and 33.0% phenprocoumon. We observed a decrease of 8.9% of INRs within range in the standard intensity group (target INR 2.0-3.0). There was both an increased risk of supratherapeutic [OR=1.34 (95% CI 1.08-1.67)] and subtherapeutic levels [OR=1.40 (95% CI 1.08-1.83)] after first vaccination. In the high-intensity group (target INR 2.5-3.5), the risk of a supratherapeutic INR was 2.3 times higher after first vaccination [OR=2.29 (95% CI 1.22-4.28)] and 3.3 times higher after second vaccination [OR 3.25 (95% CI 1.06-9.97).
Conclusion: BNT162b2 was associated with an immediate negative effect on anticoagulation control in patients treated with vitamin K antagonists, so it is advisable to monitor the INR short after vaccination, even in stable patients.
Figure 1 Figure 1.

Disclosures
Kruip: Daiichi Sankyo: Research Funding; Bayer: Honoraria, Research Funding.