bluuebunny/crossref_metadata_2025_split huggingface dataset:
Percutaneous Implantation of Adult Sized Stents for Coarctation of the Aorta in Children ≤20 kg
Authors: Boe Brian A. , Armstrong Aimee K. , Janse Sarah A. , Loccoh Eméfah C. , Stockmaster Katie , Holzer Ralf J. , Cheatham Sharon L. , Cheatham John P. , Berman Darren P. 
Published: February 2021

Background:
Stent implantation (SI) is more effective than balloon angioplasty for the treatment of coarctation of the aorta (CoA). Due to technical factors, balloon angioplasty is more commonly performed in small patients. We sought to evaluate outcomes of percutaneous adult sized SI for the treatment of CoA in small patients.

Methods:
A single-center retrospective review of all patients ≤20 kg who underwent percutaneous adult sized SI for native or recurrent CoA from 2004 to 2015 was performed.

Results:

Thirty-nine patients (20 patients ≤10 kg) were identified, with 28 (71.8%) having recurrent CoA and 22 (56.4%) previously failed balloon angioplasty. At the time of SI, the median (range) patient age and weight were 1.1 (0.3–7.9) years and 10 (5.5–20.4) kg, respectively. SI resulted in significant improvements in the median gradient (26 mm Hg [interquartile range (IQR), 18–42] to 0 mm Hg [IQR, 0–2];
P
< 0.05) and median minimum diameter (3.6 mm [IQR, 2.4–4.8] to 7.7 mm [IQR, 6.5–9.4];
P
<0.05). Seven patients (18%) had procedural adverse events. Twenty-seven (69%) patients underwent elective reintervention at a median time of 49.3 (IQR, 26.5–63.2) months from SI, with 8 (21%) stents requiring repeat SI for stent fracture. Over a median follow-up of 67.2 (IQR, 33.8–116.1) months, 25 patients (69%) were without hypertension or blood pressure gradient. Three (11%) patients developed femoral arterial occlusion.

Conclusions:
Adult sized SI is an alternative to surgical intervention for small patients with CoA. SI carries a risk of access-related complications, which may improve with the development of lower profile stents with adult sized maximum diameters.
Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease
Authors: Ye Nan , Jardine Meg J. , Oshima Megumi , Hockham Carinna , Heerspink Hiddo J.L. , Agarwal Rajiv , Bakris George , Schutte Aletta E. , Arnott Clare , Chang Tara I. , Górriz Jose L. , Cannon Christopher P. , Charytan David M. , de Zeeuw Dick , Levin Adeera , Mahaffey Kenneth W. , Neal Bruce , Pollock Carol , Wheeler David C. , Luca Di Tanna Gian , Cheng Hong , Perkovic Vlado , Neuen Brendon L. 
Published: February 2021

Background:
People with type 2 diabetes and chronic kidney disease experience a high burden of hypertension, but the magnitude and consistency of blood pressure (BP) lowering with canagliflozin in this population are uncertain. Whether the effects of canagliflozin on kidney and cardiovascular outcomes vary by baseline BP or BP-lowering therapy is also unknown.

Methods:
The CREDENCE trial (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) randomized people with type 2 diabetes and chronic kidney disease to canagliflozin or placebo. In a post hoc analysis, we investigated the effect of canagliflozin on systolic BP across subgroups defined by baseline systolic BP, number of BP-lowering drug classes, and history of apparent treatment-resistant hypertension (BP ≥130/80 mm Hg while receiving ≥3 classes of BP-lowering drugs, including a diuretic). We also assessed whether effects on clinical outcomes differed across these subgroups.

Results:

The trial included 4401 participants, of whom 3361 (76.4%) had baseline systolic BP ≥130 mm Hg, and 1371 (31.2%) had resistant hypertension. By week 3, canagliflozin reduced systolic BP by 3.50 mm Hg (95% CI, –4.27 to –2.72), an effect maintained over the duration of the trial, with similar reductions across BP and BP-lowering therapy subgroups (all
P
interaction ≥0.05). Canagliflozin also reduced the need for initiation of additional BP-lowering agents during the trial (hazard ratio, 0.68 [95% CI, 0.61–0.75]). The effect of canagliflozin on kidney failure, doubling of serum creatinine, or death caused by kidney or cardiovascular disease (hazard ratio, 0.70 [95% CI, 0.59–0.82]) was consistent across BP and BP-lowering therapy subgroups (all
P
interaction ≥0.35), as were effects on other key kidney, cardiovascular, and safety outcomes.

Conclusions:
In people with type 2 diabetes and chronic kidney disease, canagliflozin lowers systolic BP across all BP-defined subgroups and reduces the need for additional BP-lowering agents. These findings support use of canagliflozin for end-organ protection and as an adjunct BP-lowering therapy in people with chronic kidney disease.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02065791.
Freedom of Religion in the Workplace
Authors: Begović Nedim 
Published: February 2021

Abstract
The article analyses the case law of the European Court of Human Rights on accommodation of Islamic observances in the workplace. The author argues that the Court has not hitherto provided adequate incentives to the states party to the European Convention on Human Rights to accommodate the religious needs of Muslim employees in the workplace. Given this finding, the author proposes that the accommodation of Islam in the workplace should, as a matter of priority, be provided within a national legal framework. In Bosnia and Herzegovina, this could be achieved through an instrument of contracting agreement between the state and the Islamic Community in Bosnia and Herzegovina.
Hurricane Risk Perceptions and Evacuation Decision-Making in the Age of COVID-19
Authors: Collins Jennifer , Polen Amy , McSweeney Killian , Colón-Burgos Delián , Jernigan Isabelle 
Published: February 2021

AbstractThe COVID-19 pandemic increases the complexity of planning for hurricanes as social distancing is in direct conflict with human mobility and congregation. COVID-19 presents not only urgent challenges for this hurricane season due to the likeliness of continued or heightened COVID-19 threat, but also challenges with the next hurricane season with additional waves of the pandemic. There is severe urgency to understand the impact of COVID-19 risk perceptions and the extent people are willing to risk their lives by sheltering in place rather than evacuating during severe hurricanes. In June 2020, a survey (in both English and Spanish) of 40 questions was disseminated through regional planning councils, emergency management, and the media to Florida residents. A total of 7,072 people responded from over 50 counties. Most data obtained were ordinal or categorical in nature, encouraging usage of nonparametric analysis and chi-square tests. Almost half the respondents view themselves as vulnerable to COVID-19 due to preexisting health conditions, and 74.3% of individuals viewed the risk of being in a shelter during the COVID-19 pandemic as more dangerous than enduring hurricane hazards. Additionally, there was a significant number of individuals who would choose to not utilize a public shelter during COVID-19 when they would have previously. Officials can use the results of this study regarding how household evacuation plans change with social distancing to better inform strategies of shelter preparedness and COVID-19 risk mitigation to minimize risk to those in harm’s way of storm surge and other hurricane effects during a mandatory evacuation order.
Impact of Urbanization on the Nature of Precipitation at Toronto, Ontario, Canada
Authors: Gough William A. 
Published: February 2021

AbstractA newly developed precipitation phase metric is used to detect the impact of urbanization on the nature of precipitation at Toronto, Ontario, Canada, by contrasting the relative amounts of rain and snow. A total of 162 years of observed precipitation data were analyzed to classify the nature of winter-season precipitation for the city of Toronto. In addition, shorter records were examined for nearby climate stations in less-urbanized areas in and near Toronto. For Toronto, all winters from 1849 to 2010 as well as three climate normal periods (1961–90, 1971–2000, and 1981–2010) were thus categorized for the Toronto climate record. The results show that Toronto winters have become increasingly “rainy” across these time periods in a statistically significant fashion, consistent with a warming climate. Toronto was compared with the other less urban sites to tease out the impacts of the urban heat island from larger-scale warming. This yielded an estimate of 19%–27% of the Toronto shift in precipitation type (from snow to rain) that can be attributed to urbanization for coincident time periods. Other regions characterized by similar climates and urbanization with temperatures near the freezing point are likely to experience similar climatic changes expressed as a change in the phase of winter-season precipitation.
Diapycnal Mixing in the Subthermocline of the Mariana Ridge from High-Resolution Seismic Images
Authors: Tang Qunshu , Jing Zhiyou , Lin Jianmin , Sun Jie 
Published: February 2021

AbstractThe Mariana Ridge is one of the prominent mixing hotspots of the open ocean. The high-resolution underway marine seismic reflection technique provides an improved understanding of the spatiotemporal continuous map of ocean turbulent mixing. Using this novel technique, this study quantifies the diapycnal diffusivity of the subthermocline (300–1200-m depth) turbulence around the Mariana Ridge. The autotracked wave fields on seismic images allow us to derive the dissipation rate ε and diapycnal diffusivity Kρ based on the Batchelor model, which relates the horizontal slope spectra with +1/3 slope to the inertial convective turbulence regime. Diffusivity is locally intensified around the seamounts exceeding 10−3 m2 s−1 and gradually decreases to 10−5–10−4 m2 s−1 in ~60-km range, a distance that may be associated with the internal tide beam emanating paths. The overall pattern suggests a large portion of the energy dissipates locally and a significant portion dissipates in the far field. Empirical diffusivity models Kρ(x) and Kρ(z), varying with the distance from seamounts and the height above seafloor, respectively, are constructed for potential use in ocean model parameterization. Geographic distributions of both the vertically averaged dissipation rate and diffusivity show tight relationships with the topography. Additionally, a strong agreement of the dissipation results between seismic observation and numerical simulation is found for the first time. Such an agreement confirms the suitability of the seismic method in turbulence quantification and suggests the energy cascade from large-scale tides to small-scale turbulence via possible mechanisms of local direct tidal dissipation, near-local wave–wave interactions, and far-field radiating and breaking.
Metformin Upregulates Mir-26a to Improve Erythropoiesis in Preclinical Models of Diamond Blackfan Anemia through Suppression of Nlk Expression
Authors: Wilkes Mark C , Siva Kavitha , Mercado Jacqueline D , Wentworth Ethan Patrick , Saxena Mallika , Chen Jun , Narla Anupama , Glader Bertil , Lin Shuo , Serrano Manuel , Flygare Johan , Sakamoto Kathleen M. 
Published: February 2021

Nemo-like Kinase (NLK) is an atypical member of the Mitogen-activated protein (MAP) kinase family and shares a highly conserved kinase domain with other MAP kinases. For this reason it is challenging to design small molecules that specifically inhibit NLK. In hematopoiesis, NLK expression is suppressed in all lineages except erythroid progenitors. In non-erythroid progenitors, micro-ribonucleic acid (miR)-181 is upregulated and binds to the 3' untranslated region (UTR) of NLK transcripts, resulting in dramatic degradation of NLK transcripts.
NLK is not activated or required for healthy erythropoiesis, but in Diamond Blackfan Anemia (DBA), NLK is chronically hyper-activated, which contributes to failed erythroid expansion and disease pathogenesis. Given the sensitivity of NLK transcripts to 3'UTR binding-mediated degradation, we hypothesized that targeting NLK degradation by upregulating miRNAs that bind the NLK 3'-UTR could provide an alternative approach to directly inhibiting the kinase to suppress aberrant NLK activity in bone marrow progenitors from DBA patients.
One miRNA binding site that is present in the NLK-3'UTR is miR-26a. We determined that miR-26a is upregulated 2.4-fold (p=0.009) in CD235+ erythrocytes by the Type 2 diabetes drug metformin. Metformin suppressed NLK expression 62.4% (p=0.006) and improved erythroid expansion 4-fold (p=0.001) in human and 6-fold (p=0.042) in zebrafish models of DBA. This effect required an intact miR-26a binding site within the NLK 3'UTR. However, metformin failed to induce miR-26a in murine models of DBA, however the exogenous expression of miR-26a suppressed NLK 36.4% (p=0.028) and improved erythropoiesis 2-fold (p=0.017).
In summary, targeted suppression of NLK through metformin-mediated upregulation of NLK transcript-binding miRNAs effectively improved red blood cell production from 5.6% up to 33.3% of controls in a preclinical model of DBA. These results suggest that metformin is a potential drug for treatment of DBA.

Disclosures
Glader: Agios Pharmaceuticals, Inc.: Consultancy.

OffLabel Disclosure:
metformin. This drug is given to differentiating HSPCs in vitro to examine effect on specific kinases.
Level of Scientific Evidence Underlying Recommendations from the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Hematologic Malignancies: Are We Moving Forward?
Authors: Desai Aakash , Fuentes Harry E , Tella Sri Harsha , Scheckel Caleb J , Poonacha Thejaswi , Go Ronald S. 
Published: February 2021

Background: National Comprehensive Cancer Network (NCCN) guidelines are the most comprehensive and widely used standard for clinical care in malignant hematology by clinicians and payers in the US. The level of scientific evidence in NCCN guidelines for malignant hematological conditions has not been recently investigated. We describe the distribution of categories of evidence and consensus (EC) among the 10 most common hematologic malignancies with regard to recommendations for staging, initial and salvage therapy, and surveillance.
Methods: NCCN uses a system of guideline development distinct from other major professional organizations. The NCCN definitions for EC are: category I, high level of evidence such as randomized controlled trials with uniform consensus; category IIA, lower level of evidence with uniform consensus; category IIB, lower level of evidence without a uniform consensus but with no major disagreement; and category III, any level of evidence but with major disagreement. We compared our results with previously published results from 2011 guidelines.
Results: Total recommendations increased by 16.6% from 1160 (2011) to 1353 (2020). Of the 1353 recommendations, Category 1, 2A, 2B and 3 EC were 5%, 91%, 4%, 1% while in 2011 they were 3%, 93%, 4% and 0% respectively. Recommendations with category 1 EC were found in all guidelines, except for Burkitt's Lymphoma. 6.3% of therapeutic recommendations were category 1 EC with the majority (56.4%) pertaining to initial therapy. Guidelines with highest proportions of therapeutic recommendations with category 1 EC were Multiple Myeloma (12.4%), CLL/SLL (6.9%) and AML (5.6%). Between 2011 and 2020, the proportion of category I recommendations increased significantly only in Follicular lymphoma and CLL/SLL. No category 1 EC recommendations existed in staging or surveillance.
Conclusion: Recommendations issued in the 2020 NCCN guidelines are largely developed from lower levels of evidence but with uniform expert opinion. Despite the major advances in hematology in the past decade, this is largely unchanged. Our study underscores the urgent need and available opportunities to expand the current evidence base in malignant hematological disorders which forms the platform for clinical practice guidelines.
Figure

Disclosures
No relevant conflicts of interest to declare.
This Is a Title: Cytarabine Combined with PD-1 Inhibitor in the Treatment of R/R-AML: A Report of 3 Cases and Literature Review
Authors: Wang Yu , Jiang Chuanyan , Yang Xi , Dai Jingying , Zou Mengying , Wang Yijing , Wang Jun , Wu Jiafei , LI Hui 
Published: February 2021

Objectives: To explore the efficacy and safety of high-dose cytarabine combined with PD-1 inhibitors and demethylation drugs in relapsed and refractory acute myeloid leukemia (R/R-AML) in Chinaand to investigatethe dynamic changes of Treg cells, CD4+ T cells, CD8+ T cells, TNF-α, INF-γ, and IL-6 in the prognosis of the disease.
Methods:A total of three patients with R/R-AML treated in our department were included in the study. None of the three patients had received at least two courses of standard chemotherapy before and did not obtain remission.The cellular immunity and cytokines were evaluated on the 1st, 8th, 15th, and 22nd day of the treatment.In the study,eligible R/ R-AML patients (n=3) were treated with azacytidine 75mg/m2 d1-d7, cytarabine 2g/m2 d1-d5, PD-1 inhibitor 200mg d1、d14.The efficacy were evaluated by CR, PR, ORR, PFS, OS, and ED. The safety were evaluated by hematological and non-hematological toxicity.
Results: Among the three patients, one patient achieved CR, and one patient achieved PR. The patient who achieved CR successfully underwent allo-HSCT. One patient did not achieve remission and died of disease progression. Three patients were well tolerated to chemotherapy, and non-hematological toxicity was mainly respiratory tract infection, gastrointestinal reaction, and liver function damage.At present, no immune-related tissue injury was observed. Grade III-IV hematologic toxicity was the major adverse reaction, and the longest duration of agranulocytosis was 22 days.The proportion of Treg cells decreased, and the proportion of CD4+ T cells and CD8+ T lymphocytes increased in 2 patients after treatment. One patient received CR and underwent allo-HSCT. One patient showed an increase in the proportion of Treg cells, but there was no significant dynamic change in CD4+ T lymphocytes and CD8+ T lymphocytes. INF-γ increased in 1 patient. Dynamic changes in IL-10, IL-6, and TNF-α were not observed.
Conclusions: PD-1 inhibitor combined with high dose cytarabine based chemotherapy may be a salvage treatment for R/R-AML. The dynamic changes of CD4+ T lymphocyte, CD8+ T lymphocyte, Treg cell, and INF-α may reflect the therapeutic effect in advance.

Disclosures
No relevant conflicts of interest to declare.
Adipocyte Fatty Acid Binding Protein Promotes Multiple Myeloma through Regulating Bone Marrow Microenvironment
Authors: Shu Lingling , Li Jinyuan , Wang Weida , Wu Xiaoping , Huang Hanying , Hu Fang , Liang Yang 
Published: February 2021

Multiple myeloma (MM) is a plasma cell malignancy in bone marrow, which often occurs in middle-aged and elderly people and also obese patients. Aging and obesity can lead to the ectopic accumulation of adipocytes in bone marrow, which can cause the change of bone marrow microenvironment. Bone marrow adipocyte (BMA) displays distinct immune regulatory properties rather than provides energy substrates. Despite BMA accounts for 70% of the entire volume of bone marrow microenvironment, while the mechanisms still remain elusive. The present study aims to investigate the precise mechanism of BMA promoting myeloma pathogenesis and new potential therapeutic strategies targeting bone marrow microenvironment.
Newly diagnosed MM patients and their relative healthy control in our cancer center were recruited. We found that the quantity of BMA increased significantly in multiple myeloma patients, accompanied with the elevated level of adipocyte fatty acid binding protein (A-FABP) by flow cytometry and immunohistochemistry staining. A-FABP is a fatty acid chaperone, which abundantly expressed in adipocytes, playing a critical role in lipid metabolism and immune response. To further explore the role of A-FABP in the pathogenesis of MM, A-FABP knockout (KO) mice and their wide type (WT) littermates were employed and fed with stand chow or high fat diet (HFD). Tumor burden and MM-related osteolytic lesions were significantly lower in A-FABP KO mice comparing to their WT littermates fed with HFD. It was observed that A-FABP deficiency did not change the content of BMA in bone marrow, but cytokines levels in bone marrow such as TNFα, IL-6, RANKL, DPP4 were significantly reduced. The infiltration and pro-inflammatory polarization (M1/M2) of macrophages (MΦ) decreased significantly. Moreover, A-FABP promotes the expression of Th1 and Th17 cells, while the percentage of Th2 and Treg cells are significantly declined. Furthermore, pharmacological inhibition of A-FABP by administration BMS309403 also alleviates the invasion and metastasis of MM in mouse. In addition, co-culture of myeloma cells with pharmacological inhibition or genetic depletion of A-FABP in adipocytes significantly decreased the uptake of free fatty acid and oxygen consumption of myeloma cells.
In conclusion, A-FABP increased in BMA in response to aging or obesity, remodeled the energy and lipid metabolism of myeloma cells, and manipulated bone marrow microenvironment to a pro-tumor environment, promoting the proliferation and migration of myeloma cells. This study will shed light on the potential of A-FABP specific inhibitor BMS309403 as the therapeutic strategy of multiple myeloma targeting bone marrow microenvironment.

Disclosures
No relevant conflicts of interest to declare.
Association of Anticoagulant Use with COVID-19 Diagnosis
Authors: Kavecansky Juraj , Dusendang Jennifer R , Tavakoli Jahan , Schmittdiel Julie , Ho Gwendolyn , Loyles Jodi , Pai Ashok 
Published: February 2021

Background
The Coronavirus Disease 2019 (COVID-19) pandemic has challenged anticoagulation providers with providing optimal care while minimizing exposure risk, specifically in the management of patients on chronic warfarin. Here we provide data regarding our experience with managing patients on chronic anticoagulants, including warfarin, within Kaiser Permanente Northern California (KPNC), a large integrated healthcare delivery system serving more than 4 million patients.
Aim
To identify whether being on anticoagulation or antiplatelet agents correlates with an increased risk of contracting COVID-19.
Methods
We identified patients within KPNC electronic medical records on either warfarin, direct oral anticoagulation (DOAC) and/or antiplatelet agents between February 25 and July 3, 2020, as well as a randomly identified control group of patients not taking anticoagulation or antiplatelet. We looked for a correlation between taking anticoagulation and antiplatelets with the risk of testing positive for COVID-19.
Results/Conclusions
Among 188,438 patients on chronic anticoagulants or antiplatelets and 188,438 controls, 1,029 patients tested positive for COVID-19 during the study period. Being on chronic anticoagulants or antiplatelets was not associated with increased risk for a positive test. Patients on warfarin (N=30,242) also had no increased risk of developing COVID-19 compared to patients not on anticoagulation or antiplatelet therapy (odds ratio 0.87, 95% confidence interval 0.64-1.17). The time in the therapeutic range (TTR) of patients on warfarin during the COVID-19 pandemic remained near 72%, consistent with prior TTR, demonstrating persistent efficacy of anticoagulation despite measures to reduce COVID-19 transmission. Our data demonstrates the safety of continuing chronic warfarin in patients during the COVID-19 pandemic.

Disclosures
No relevant conflicts of interest to declare.