bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health Impact and Cost-Effectiveness of Achieving the National Salt and Sugar Reduction Initiative Voluntary Sugar Reduction Targets in the United States: A Microsimulation Study
Authors: Shangguan Siyi , Mozaffarian Dariush , Sy Stephen , Lee Yujin , Liu Junxiu , Wilde Parke E. , Sharkey Andrea L. , Dowling Erin A. , Marklund Matti , Abrahams-Gessel Shafika , Gaziano Thomas A. , Micha Renata 
Published: August 2021

Background:
High intake of added sugar is linked to weight gain and cardiometabolic risk. In 2018, the US National Salt and Sugar Reduction Initiative proposed government-supported voluntary national sugar reduction targets. This intervention’s potential effects and cost-effectiveness are unclear.

Methods:
A validated microsimulation model, CVD-PREDICT (Cardiovascular Disease Policy Model for Risk, Events, Detection, Interventions, Costs, and Trends), coded in C++, was used to estimate incremental changes in type 2 diabetes, cardiovascular disease (CVD), quality-adjusted life-years (QALYs), costs, and cost-effectiveness of the US National Salt and Sugar Reduction Initiative policy. The model was run at the individual level, incorporating the annual probability of each person’s transition between health statuses on the basis of risk factors. The model incorporated national demographic and dietary data from the National Health and Nutrition Examination Survey across 3 cycles (2011 through 2016), added sugar-related diseases from meta-analyses, and policy costs and health-related costs from established sources. A simulated nationally representative US population was created and followed until age 100 years or death, with 2019 as the year of intervention start. Findings were evaluated over 10 years and a lifetime from health care and societal perspectives. Uncertainty was evaluated in a 1-way analysis by assuming 50% industry compliance and probabilistic sensitivity analyses through a second-order Monte Carlo approach. Model outputs included averted diabetes cases, CVD events and CVD deaths, QALYs gained, and formal health care cost savings, stratified by age, race, income, and education.

Results:
Achieving the US National Salt and Sugar Reduction Initiative sugar reduction targets could prevent 2.48 million CVD events, 0.49 million CVD deaths, and 0.75 million diabetes cases; gain 6.67 million QALYs; and save $160.88 billion net costs from a societal perspective over a lifetime. The policy became cost-effective (<150 000/QALYs) at 6 years, highly cost-effective (<50 000/QALYs) at 7 years, and cost-saving at 9 years. Results were robust from a health care perspective, with lower (50%) industry compliance, and in probabilistic sensitivity analyses. The policy could also reduce disparities, with greatest estimated health gains per million adults among Black or Hispanic individuals, lower income, and less educated Americans.

Conclusions:
Implementing and achieving the US National Salt and Sugar Reduction Initiative sugar reformation targets could generate substantial health gains, equity gains, and cost savings.
Authority in the Classical Ḥanafī School: the Emergence & Evolution of Ẓāhir al-Riwāya
Authors: Younas Salman 
Published: August 2021

Abstract
The madhhab in its classical form was an authoritative entity with substantive boundaries that established the outer limits of the school and its authoritative doctrine. The latter involved, among other things, confronting the plurality of opinions found within the school. In this essay, I will analyse the manner in which Ḥanafī jurists attempted to limit this plurality through an authorizing discourse that created a taxonomy of legal doctrine ranking different opinions present in the corpus juris of their school. Specifically, I will examine the most authoritative corpus in this taxonomy, namely ẓāhir al-riwāya, in five parts: the first part will investigate the concept of legal authority prior to ẓāhir al-riwāya; the second part will identify the earliest usage of the term ẓāhir al-riwāya; the third and fourth parts will analyse the popularization of this doctrine, its spread, and earliest theorization; the final part will briefly investigate what ẓāhir al-riwāya denoted.
Imagining a New Volk: German-American Nationalism in the Age of the Revolution
Authors: Kinney Brandon 
Published: August 2021

Abstract
German colonists who participated in the American Revolution did so in a number of ways that were comparable to their Anglo-American neighbors. Yet German Patriots also had a unique method of expressing American nationalism: their vocabulary. While using the German language in the New World was often a means of preserving identity and cultural institutions, it also provided an avenue through which they could assert a hybrid German-American identity: the word Volk. This paper focuses primarily on the changes in the writings of Henry Miller, the foremost German-American who cast his lot with the Patriot cause. It tracks a shift in his use of language during the American Revolution and demonstrates how he used the concept of Volk first to assert a distinct colonial identity and later to invent an America nation for German consumption.
Histoire des sciences, histoire concrète de l’abstraction (1998)
Authors: Perrot Jean-Claude 
Published: August 2021

Résumé
Comment une histoire matérielle de l’abstraction peut-elle servir l’histoire intellectuelle ou bien l’histoire des sciences, cela à l’encontre de l’histoire des idées et des généalogies rétrospectives ? L’objet est ici l’œuvre de connaissance telle qu’elle est ancrée dans son cadre historique. Cette histoire intellectuelle déborde les coupes disciplinaires. L’article en offre plusieurs exemples qui partent de la recherche de différenciations explicables entre des pratiques intellectuelles d’abstraction. Une séquence s’ouvre alors avec l’émergence d’une conception, puis la formation de théories et finalement la consolidation d’un corpus de choses tenues pour évidentes. Toutes les activités cognitives qui précédent le savoir constitué sont ici visées.
A Hyperactive End to the Atlantic Hurricane Season October–November 2020
Authors: Klotzbach Philip J. , Wood Kimberly M. , Bell Michael M. , Blake Eric S. , Bowen Steven G. , Caron Louis-Philippe , Collins Jennifer M. , Gibney Ethan J. , Schreck Carl J. , Truchelut Ryan E. 
Published: August 2021

Abstract
The active 2020 Atlantic hurricane season produced 30 named storms, 14 hurricanes, and 7 major hurricanes (category 3+ on the Saffir–Simpson hurricane wind scale). Though the season was active overall, the final two months (October–November) raised 2020 into the upper echelon of Atlantic hurricane activity for integrated metrics such as accumulated cyclone energy (ACE). This study focuses on October–November 2020, when 7 named storms, 6 hurricanes, and 5 major hurricanes formed and produced ACE of 74 × 104 kt2 (1 kt ≈ 0.51 m s−1). Since 1950, October–November 2020 ranks tied for third for named storms, first for hurricanes and major hurricanes, and second for ACE. Six named storms also underwent rapid intensification (≥30 kt intensification in ≤24 h) in October–November 2020—the most on record. This manuscript includes a climatological analysis of October–November tropical cyclones (TCs) and their primary formation regions. In 2020, anomalously low wind shear in the western Caribbean and Gulf of Mexico, likely driven by a moderate-intensity La Niña event and anomalously high sea surface temperatures (SSTs) in the Caribbean, provided dynamic and thermodynamic conditions that were much more conducive than normal for late-season TC formation and rapid intensification. This study also highlights October–November 2020 landfalls, including Hurricanes Delta and Zeta in Louisiana and in Mexico and Hurricanes Eta and Iota in Nicaragua. The active late season in the Caribbean would have been anticipated by a statistical model using the July–September-averaged ENSO longitude index and Atlantic warm pool SSTs as predictors.
Evaluation of IMERG satellite precipitation over the land-coast-ocean continuum – Part I: Detection
Authors: Derin Yagmur , Kirstetter Pierre-Emmanuel , Gourley Jonathan J. 
Published: August 2021

AbstractAs a fundamental water flux, quantitative understanding of precipitation is important to understand and manage water systems under a changing climate, especially in transition regions such as the coastal interface between land and ocean. This work aims to assess the uncertainty in precipitation detection over the land-coast-ocean continuum in the Integrated Multi-satellitE Retrievals for Global Precipitation Measurement (IMERG) V06B. It is examined over three coastal regions of the U.S., i.e. the West Coast, the Gulf of Mexico, and the East Coast, each of which are characterized by different topographies and precipitation climatologies. Detection capabilities are contrasted over different surfaces (land, coast, ocean). A novel and integrated approach traces the IMERG detection performance back to its components (passive microwave, infrared, and morphing-based estimates). The analysis is performed by using high-resolution, high-quality Ground Validation Multi-Radar/Multi-Sensor (GV-MRMS) rainfall estimates as ground reference. The best detection performances are reported with PMW estimates (hit rates in the range of [25-39]%), followed by morphing ([20-34]%), morphing+IR ([17-27]%) and IR ([11-16]%) estimates. Precipitation formation mechanisms play an important role, especially in the West Coast where orographic processes challenge detection. Further, precipitation typology is shown to be a strong driver of IMERG detection. Over the ocean, IMERG detection is generally better but suffers from false alarms ([10-53]%). Overall, IMERG displays nonhomogeneous precipitation detection capabilities tracing back to its components. Results point toward a similar behavior across various land-coast-ocean continuum regions of the CONUS, which suggests that results can be potentially transferred to other coastal regions of the world.
Understanding China’s New Dual Circulation Development Strategy: A Marxian Input-Output Analysis
Authors: Su Lijun , Liang Junshang 
Published: August 2021

The Chinese government has proposed a new development model called Dual Circulation, which, we argue, is a response to the upsurge of trade protectionism in recent years, as well as an acceleration of China’s long-planned restructuring of its economy. Our input-output analysis reveals the inferior global distributional position of China and the dire consequences it faces from a counterfactual US-China trade decoupling. Specifically, China on average transferred out about 9 percent of its abstract labor during 2010–14, and it stands to lose 2.5 percentage points in its growth rate and over 10 million jobs if the United States and China completely transfer their bilateral trade to other partners. JEL classification: B51, O24, D57
KDM5A suppresses PML-RARα target gene expression and APL differentiation through repressing H3K4me2
Authors: Xu Siyuan , Wang Siqing , Xing Shenghui , Yu Dingdang , Rong Bowen , Gao Hai , Sheng Mengyao , Tan Yun , Zhang Yifan , Sun Xiaojian , Wang Kankan , Xue Kai , Shi Zhennan , Lan Fei 
Published: August 2021

Abstract
Epigenetic abnormalities are frequently involved in the initiation and progression of cancers, including acute myeloid leukemia (AML). A subtype of AML, acute promyelocytic leukemia (APL), is mainly driven by a specific oncogenic fusion event of promyelocytic leukemia–RA receptor fusion oncoprotein (PML-RARα). PML-RARα was reported as a transcription repressor through the interaction with nuclear receptor corepressor and histone deacetylase complexes leading to the mis-suppression of its target genes and differentiation blockage. Although previous studies were mainly focused on the connection of histone acetylation, it is still largely unknown whether alternative epigenetics mechanisms are involved in APL progression. KDM5A is a demethylase of histone H3 lysine 4 di- and tri-methylations (H3K4me2/3) and a transcription corepressor. Here, we found that the loss of KDM5A led to APL NB4 cell differentiation and retarded growth. Mechanistically, through epigenomics and transcriptomics analyses, KDM5A binding was detected in 1889 genes, with the majority of the binding events at promoter regions. KDM5A suppressed the expression of 621 genes, including 42 PML-RARα target genes, primarily by controlling the H3K4me2 in the promoters and 5′ end intragenic regions. In addition, a recently reported pan-KDM5 inhibitor, CPI-455, on its own could phenocopy the differentiation effects as KDM5A loss in NB4 cells. CPI-455 treatment or KDM5A knockout could greatly sensitize NB4 cells to all-trans retinoic acid–induced differentiation. Our findings indicate that KDM5A contributed to the differentiation blockage in the APL cell line NB4, and inhibition of KDM5A could greatly potentiate NB4 differentiation.
Analysis of biological models to predict clinical outcomes based on HLA-DPB1 disparities in unrelated transplantation
Authors: Buhler Stéphane , Baldomero Helen , Ferrari-Lacraz Sylvie , Mamez Anne-Claire , Masouridi-Levrat Stavroula , Heim Dominik , Halter Jörg , Nair Gayathri , Chalandon Yves , Schanz Urs , Güngör Tayfun , Nicoloso Grazia , Passweg Jakob R. , Villard Jean ,   on behalf of the Swiss Blood Stem Cell Transplantation Group
Published: August 2021

Abstract
HLA compatibility is a key factor for survival after unrelated hematopoietic stem cell transplantation (HSCT). HLA-A, -B, -C, -DRB1, and -DQB1 are usually matched between donor and recipient. By contrast, HLA-DPB1 mismatches are frequent, although it is feasible to optimize donor selection and DPB1 matching with prospective typing. Because classical DPB1 allele mismatches are often unavoidable, however, several biological models have been developed to predict the optimal DPB1 mismatch combination for less graft-versus-host disease (GVHD) and better overall survival. In 909 recipient/donor pairs, we analyzed the role of 3 biological models: T-cell epitopes (TCEs) based on the immunogenicity of DPB1, cell surface expression of DPB1 molecules based on a single-nucleotide polymorphism located in the 3′ untranslated region, and the Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) model based on the presentation of allogeneic peptides derived from mismatched HLA, compared with the classical allele mismatch. Matching for both DPB1 alleles remains the best option to prevent acute GVHD. In the situation of one DPB1 allele mismatch, the donor associated with the lowest acute GVHD risks is mismatched for an allele with a low expression profile in the recipient, followed by a permissive TCE3/4 mismatch and/or the absence of PIRCHE II potential against the recipient. In the context of 2 DPB1 mismatches, the same considerations apply for a permissive TCE3/4 mismatch and no PIRCHE II. By combining the biological models, the most favorable DPB1 constellation can be defined. This approach will help optimize donor selection and improve post-HSCT complications and patient prognosis.
Predicting mortality from intracranial hemorrhage in patients who undergo allogeneic hematopoietic stem cell transplantation
Authors: Ren Xiying , Huang Qiusha , Qu Qingyuan , Cai Xuan , Fu Haixia , Mo Xiaodong , Wang Yu , Zheng Yawei , Jiang Erlie , Ye Yishan , Luo Yi , Chen Shaozhen , Yang Ting , Zhang Yuanyuan , Han Wei , Tang Feifei , Mo Wenjian , Wang Shunqing , Li Fei , Liu Daihong , Zhang Xiaoying , Zhang Yicheng , Feng Shuqing , Gao Feng , Yuan Hailong , Wang Dao , Wan Dingming , Chen Huan , Chen Yao , Wang Jingzhi , Chen Yuhong , Wang Ying , Xu Kailin , Lang Tao , Wang Xiaomin , Meng Hongbin , Li Limin , Wang Zhiguo , Fan Yanling , Chang Yingjun , Xu Lanping , Huang Xiaojun , Zhang Xiaohui 
Published: August 2021

Abstract
Intracranial hemorrhage (ICH) is a rare but fatal central nervous system complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, factors that are predictive of early mortality in patients who develop ICH after undergoing allo-HSCT have not been systemically investigated. From January 2008 to June 2020, a total of 70 allo-HSCT patients with an ICH diagnosis formed the derivation cohort. Forty-one allo-HSCT patients with an ICH diagnosis were collected from 12 other medical centers during the same period, and they comprised the external validation cohort. These 2 cohorts were used to develop and validate a grading scale that enables the prediction of 30-day mortality from ICH in all-HSCT patients. Four predictors (lactate dehydrogenase level, albumin level, white blood cell count, and disease status) were retained in the multivariable logistic regression model, and a simplified grading scale (termed the LAWS score) was developed. The LAWS score was adequately calibrated (Hosmer-Lemeshow test, P &gt; .05) in both cohorts. It had good discrimination power in both the derivation cohort (C-statistic, 0.859; 95% confidence interval, 0.776-0.945) and the external validation cohort (C-statistic, 0.795; 95% confidence interval, 0.645-0.945). The LAWS score is the first scoring system capable of predicting 30-day mortality from ICH in allo-HSCT patients. It showed good performance in identifying allo-HSCT patients at increased risk of early mortality after ICH diagnosis. We anticipate that it would help risk stratify allo-HSCT patients with ICH and facilitate future studies on developing individualized and novel interventions for patients within different LAWS risk groups.
Multicenter analysis of geriatric fitness and real-world outcomes in older patients with classical Hodgkin lymphoma
Authors: Orellana-Noia Victor M. , Isaac Krista , Malecek Mary-Kate , Bartlett Nancy L. , Voorhees Timothy J. , Grover Natalie S. , Hwang Steven R. , Bennani N. Nora , Hu Rachel , Hill Brian T. , Mou Eric , Advani Ranjana H. , Carter Jordan , David Kevin A. , Ballard Hatcher J. , Svoboda Jakub , Churnetski Michael C. , Magarelli Gabriela , Feldman Tatyana A. , Cohen Jonathon B. , Evens Andrew M. , Portell Craig A. 
Published: August 2021

Abstract
We performed a multicenter retrospective analysis across 10 US academic medical centers to evaluate treatment patterns and outcomes in patients age ≥60 years with classic Hodgkin lymphoma (cHL) from 2010-2018. Among 244 eligible patients, median age was 68, 63% had advanced stage (III/IV), 96% had Eastern Cooperative Oncology Group performance status (PS) 0-2, and 12% had documented loss of ≥1 activity of daily living (ADL). Medical comorbidities were assessed by the Cumulative Illness Rating Scale–Geriatric (CIRS-G), where n = 44 (18%) had total scores ≥10. Using multivariable Cox models, only ADL loss predicted shorter progression-free (PFS; hazard ratio [HR] 2.13, P = .007) and overall survival (OS; HR 2.52, P = .02). Most patients (n = 203, 83%) received conventional chemotherapy regimens, including doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD; 56%), AVD (14%), and AVD with brentuximab vedotin (BV; 9%). Compared to alternative therapies, conventional regimens significantly improved PFS (HR 0.46, P = .0007) and OS (HR 0.31, P = .0003). Survival was similar following conventional chemotherapy in those ages 60-69 vs ≥70: PFS HR 0.88, P = .63; OS HR 0.73, P = .55. Early treatment discontinuation due to toxicity was more common with CIRS-G ≥10 (28% vs 12%, P = .016) or documented geriatric syndrome (28% vs 13%, P = .02). A competing risk analysis demonstrated improved disease-related survival with conventional therapy (HR 0.29, P = .02) and higher mortality from causes other than disease or treatment with high CIRS-G or geriatric syndromes. This study suggests conventional chemotherapy regimens remain a standard of care in fit older patients with cHL, and highlights the importance of geriatric assessments in defining fitness for cHL therapy going forward.
Identification of coagulation factor IX variants with enhanced activity through ancestral sequence reconstruction
Authors: Knight Kristopher A. , Coyle Christopher W. , Radford Caelan E. , Parker Ernest T. , Fedanov Andrew , Shields Jordan M. , Szlam Fania , Purchel Anatolii , Chen Michelle , Denning Gabriela , Sniecinski Roman M. , Lollar Pete , Spencer H. Trent , Gaucher Eric A. , Doering Christopher B. 
Published: August 2021

Abstract
Orthologous proteins contain sequence disparity guided by natural selection. In certain cases, species-specific protein functionality predicts pharmacological enhancement, such as greater specific activity or stability. However, immunological barriers generally preclude use of nonhuman proteins as therapeutics, and difficulty exists in the identification of individual sequence determinants among the overall sequence disparity. Ancestral sequence reconstruction (ASR) represents a platform for the prediction and resurrection of ancient gene and protein sequences. Recently, we demonstrated that ASR can be used as a platform to facilitate the identification of therapeutic protein variants with enhanced properties. Specifically, we identified coagulation factor VIII (FVIII) variants with improved specific activity, biosynthesis, stability, and resistance to anti-human FVIII antibody–based inhibition. In the current study, we resurrected a panel of ancient mammalian coagulation factor IX (FIX) variants with the goal of identifying improved pharmaceutical candidates. One variant (An96) demonstrated 12-fold greater FIX activity production than human FIX. Addition of the R338L Padua substitution further increased An96 activity, suggesting independent but additive mechanisms. after adeno-associated virus 2 (AAV2)/8-FIX gene therapy, 10-fold greater plasma FIX activity was observed in hemophilia B mice administered AAV2/8-An96–Padua as compared with AAV2/8-human FIX–Padua. Furthermore, phenotypic correction conferred by the ancestral variant was confirmed using a saphenous vein bleeding challenge and thromboelastography. Collectively, these findings validate the ASR drug discovery platform as well as identify an ancient FIX candidate for pharmaceutical development.