bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incomplete COVID-19 Data: The Curation of Medical Health Data by the Virus Outbreak Data Network-Africa
Authors: Van Reisen Mirjam , Oladipo Francisca Onaolapo , Mpezamihigo Mouhamed , Plug Ruduan , Basajja Mariam , Aktau Aliya , Jati Putu Hadi Purnama , Nalugala Reginald , Folorunso Sakinat , Amare Samson Yohannes , Abdulahi Ibrahim , Afolabi Oluwole Olumuyiwa , Mwesigwa Ezra , Taye Getu Tadele , Kawu Abdulahi , Ghardallou Mariem , Liang Yan , Osigwe Obinna , Medhanyie Araya Abrha , Mawere Munyaradzi 
Published: August 2022

AbstractThe incompleteness of patient health data is a threat to the management of COVID-19 in Africa and globally. This has become particularly clear with the recent emergence of new variants of concern. The Virus Outbreak Data Network (VODAN)-Africa has studied the curation of patient health data in selected African countries and identified that health information flows often do not involve the use of health data at the point of care, which renders data production largely meaningless to those producing it. This modus operandi leads to disfranchisement over the control of health data, which is extracted to be processed elsewhere. In response to this problem, VODAN-Africa studied whether or not a design that makes local ownership and repositing of data central to the data curation process, would have a greater chance of being adopted. The design team based their work on the legal requirements of the European Union's General Data Protection Regulation (GDPR); the FAIR Guidelines on curating data as Findable, Accessible (under well-defined conditions), Interoperable and Reusable (FAIR); and national regulations applying in the context where the data is produced. The study concluded that the visiting of data curated as machine actionable and reposited in the locale where the data is produced and renders services has great potential for access to a wider variety of data. A condition of such innovation is that the innovation team is intradisciplinary, involving stakeholders and experts from all of the places where the innovation is designed, and employs a methodology of co-creation and capacity-building.
3M_BANTOR: A regression framework for multitask and multisession brain network distance metrics
Authors: Tomlinson Chal E. , Laurienti Paul J. , Lyday Robert G. , Simpson Sean L. 
Published: August 2022

Abstract
Brain network analyses have exploded in recent years and hold great potential in helping us understand normal and abnormal brain function. Network science approaches have facilitated these analyses and our understanding of how the brain is structurally and functionally organized. However, the development of statistical methods that allow relating this organization to phenotypic traits has lagged behind. Our previous work developed a novel analytic framework to assess the relationship between brain network architecture and phenotypic differences while controlling for confounding variables. More specifically, this innovative regression framework related distances (or similarities) between brain network features from a single task to functions of absolute differences in continuous covariates and indicators of difference for categorical variables. Here we extend that work to the multitask and multisession context to allow for multiple brain networks per individual. We explore several similarity metrics for comparing distances between connection matrices and adapt several standard methods for estimation and inference within our framework: standard F test, F test with scan-level effects (SLE), and our proposed mixed model for multitask (and multisession) BrAin NeTwOrk Regression (3M_BANTOR). A novel strategy is implemented to simulate symmetric positive-definite (SPD) connection matrices, allowing for the testing of metrics on the Riemannian manifold. Via simulation studies, we assess all approaches for estimation and inference while comparing them with existing multivariate distance matrix regression (MDMR) methods. We then illustrate the utility of our framework by analyzing the relationship between fluid intelligence and brain network distances in Human Connectome Project (HCP) data.
Citizen or City Diplomacy? Diplomatic Co-Production and the Middle Ground in Municipal Twinning Relationships
Authors: Harrison Scott Michael , Huang Quinton 
Published: August 2022

Summary
Since their early origins in the Cold War, municipal twinning relationships have relied on citizen initiative and participation. Where does the government end and the citizen begin? Using examples from Canada–Asia city twinning, we argue that municipal twinning relationships should be viewed as a co-produced diplomatic ‘middle ground’ formed by the interactions of official and domestic society actors. We map how the concept of a co-produced middle ground helps us better understand the identities, capacities, continuities, criteria and conceptions at the heart of municipal twinning relationships. These insights could inform a co-productive model for municipalities to approach the design and implementation of twinning relationships. As a preliminary examination of domestic society actors in municipal twinning using the interpretative framework of co-production, this article points towards possibilities for future avenues of research and policy-making that more carefully attend to the actors, sites and scales of subnational diplomacy.
Subdaily Rain-Rate Properties in Western Java Analyzed Using C-Band Doppler Radar
Authors: Lestari Sopia , Protat Alain , Louf Valentin , King Andrew , Vincent Claire , Mori Shuichi 
Published: August 2022

Abstract
Jakarta, a megacity in Indonesia, experiences recurrent floods associated with heavy rainfall. Characteristics of subdaily rainfall and the local factors influencing rainfall around Jakarta have not been thoroughly investigated, primarily because of data limitations. In this study, we examine the frequency and intensity of hourly and daily rain rate, including spatial characteristics and variations across time scales. We use 6-min C-band Doppler radar and 1-min in situ data during 2009–12 to resolve spatial rain-rate characteristics at higher resolution than previous studies. A reflectivity–rain rate (Z–R) relationship is derived (Z = 102.7R1.75) and applied to estimate hourly rain rate. Our results show that rain rate around Jakarta is spatially inhomogeneous. In the rainy season [December–February (DJF)], rain rate exhibits statistical properties markedly different from other seasons, with much higher frequency of rain, but, on average, less intense rain rate. In all seasons, there is a persistent higher hourly and daily mean rain rate found over mountainous areas, indicating the importance of local orographic effects. In contrast, for hourly rain-rate extremes, peaks are observed mostly over the coastal land and lowland areas. For the diurnal cycle of mean rain rate, a distinct afternoon peak is found developing earlier in DJF and later in the dry season. This study has implications for other analyses of mesoscale rain-rate extremes in areas of complex topography and suggests that coarse-grain products may miss major features of the rain-rate variability identified in our study.

Significance Statement
For many years, Jakarta and its surrounding regions have been repeatedly inundated by flooding triggered by short-duration heavy rainfall or rainfall accumulated over multiple days. Little is known about the distribution of local rainfall and how it differs between seasons. In this study, we used high-resolution C-band Doppler radar during 2009–12 to understand the characteristics of rainfall over this complex topography. The results demonstrate that the rainfall features vary spatially and seasonally. In the wet season, rainfall is more frequent but, on average, lighter relative to other seasons. In all seasons, the highest hourly and daily mean rain rate persistently occurs over the mountains, indicating the vital role of topography in generating rainfall in the region.
Observed Near-Inertial Waves Trapped in a Propagating Anticyclonic Eddy
Authors: Xu Xing , Zhao Wei , Huang Xiaodong , Hu Qianwen , Guan Shoude , Zhou Chun , Tian Jiwei 
Published: August 2022

Abstract
Near-inertial waves (NIWs) trapped in a propagating anticyclonic eddy (AE) are investigated along the eddy path at three areas spanning 660 km by using two mooring arrays and a cruise transect. In the upstream area, the reconstructed three-dimensional structure reveals that NIWs are concentrated within the eddy core with wave current amplitudes exceeding 0.2 m s−1; vertically, due to the critical layer effect caused by eddy baroclinicity, NIWs are trapped at depths around 200 and 315 m with frequencies estimated to be ω1 ≈ 0.918f and ω2 ≈ 0.985f, respectively. After the AE propagates southwestward for hundreds of kilometers, the NIWs of frequency ω1 are still detectable inside the AE, while NIWs of frequency ω2 are absent because of the equatorward migration of the AE on a beta plane. Meanwhile, the wave kinetic energy downstream is trapped closer to the eddy center in radial direction, with the wave amplitude decaying roughly in a Gaussian form along the eddy radius, and becomes more homogeneous in the azimuthal direction, showing a more regular trapping form in the three-dimensional view. Investigation on wind shows that trapped NIWs are likely to be generated by a typhoon but less affected by the wind during the eddy passage time. By an energy analysis, we find that enhanced wave dissipation near the critical layer is roughly balanced by the energy transfer from mean flows, and therefore the trapped wave kinetic energy is largely conserved during the long-distance migration.
A unique immune signature in blood separates therapy-refractory from therapy-responsive acute graft-versus-host disease
Authors: van Halteren Astrid G. S. , Suwandi Jessica S. , Tuit Sander , Borst Jelske , Laban Sandra , Tsonaka Roula , Struijk Ada , Wiekmeijer Anna-Sophia , van Pel Melissa , Roep Bart O. , Zwaginga Jaap Jan , Lankester Arjan C. , Schepers Koen , van Tol Maarten J. D. , Fibbe Willem E. 
Published: August 2022

Abstract
Acute graft-versus-host disease (aGVHD) is an immune cell‒driven, potentially lethal complication of allogeneic hematopoietic stem cell transplantation affecting diverse organs, including the skin, liver, and gastrointestinal (GI) tract. We applied mass cytometry (CyTOF) to dissect circulating myeloid and lymphoid cells in children with severe (grade III-IV) aGVHD treated with immune suppressive drugs alone (first-line therapy) or in combination with mesenchymal stromal cells (MSCs; second-line therapy). These results were compared with CyTOF data generated in children who underwent transplantation with no aGVHD or age-matched healthy control participants. Onset of aGVHD was associated with the appearance of CD11b+CD163+ myeloid cells in the blood and accumulation in the skin and GI tract. Distinct T-cell populations, including TCRγδ+ cells, expressing activation markers and chemokine receptors guiding homing to the skin and GI tract were found in the same blood samples. CXCR3+ T cells released inflammation-promoting factors after overnight stimulation. These results indicate that lymphoid and myeloid compartments are triggered at aGVHD onset. Immunoglobulin M (IgM) presumably class switched, plasmablasts, and 2 distinct CD11b– dendritic cell subsets were other prominent immune populations found early during the course of aGVHD in patients refractory to both first- and second-line (MSC-based) therapy. In these nonresponding patients, effector and regulatory T cells with skin- or gut-homing receptors also remained proportionally high over time, whereas their frequencies declined in therapy responders. Our results underscore the additive value of high-dimensional immune cell profiling for clinical response evaluation, which may assist timely decision-making in the management of severe aGVHD.
A tumor volume and performance status model to predict outcome before treatment in diffuse large B-cell lymphoma
Authors: Thieblemont Catherine , Chartier Loic , Dührsen Ulrich , Vitolo Umberto , Barrington Sally F. , Zaucha Jan M. , Vercellino Laetitia , Gomes Silva Maria , Patrocinio-Carvalho Ines , Decazes Pierre , Viailly Pierre-Julien , Tilly Herve , Berriolo-Riedinger Alina , Casasnovas Oliver , Hüttmann Andreas , Ilyas Hajira , Mikhaeel N. George , Dunn Joel , Cottereau Anne-Ségolène , Schmitz Christine , Kostakoglu Lale , Paulson Joseph N. , Nielsen Tina , Meignan Michael 
Published: August 2022

Abstract
Aggressive large B-cell lymphoma (LBCL) has variable outcomes. Current prognostic tools use factors for risk stratification that inadequately identify patients at high risk of refractory disease or relapse before initial treatment. A model associating 2 risk factors, total metabolic tumor volume (TMTV) &gt;220 cm3 (determined by fluorine-18 fluorodeoxyglucose positron emission tomography coupled with computed tomography) and performance status (PS) ≥2, identified as prognostic in 301 older patients in the REMARC trial (#NCT01122472), was validated in 2174 patients of all ages treated in 2 clinical trials, PETAL (Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas; N = 510) and GOYA (N = 1315), and in real-world clinics (N = 349) across Europe and the United States. Three risk categories, low (no factors), intermediate (1 risk factor), and high (2 risk factors), significantly discriminated outcome in most of the series. Patients with 2 risk factors had worse outcomes than patients with no risk factors in the PETAL, GOYA, and real-world series. Patients with intermediate risk also had significantly worse outcomes than patients with no risk factors. The TMTV/Eastern Cooperative Oncology Group-PS combination outperformed the International Prognostic Index with a positive C-index for progression-free survival and overall survival in most series. The combination of high TMTV &gt; 220 cm3 and ECOG-PS ≥ 2 is a simple clinical model to identify aggressive LBCL risk categories before treatment. This combination addresses the unmet need to better predict before treatment initiation for aggressive LBCL the patients likely to benefit the most or not at all from therapy.
Rational polypharmacological targeting of FLT3, JAK2, ABL, and ERK1 suppresses the adaptive resistance to FLT3 inhibitors in AML
Authors: Azhar Mohammad , Kincaid Zachary , Kesarwani Meenu , Menke Jacob , Schwieterman Joshua , Ansari Sekhu , Reaves Angela , Ahmed Arhama , Shehzad Rammsha , Khan Areeba , Syed Nuha , Amir Noor , Wunderlich Mark , Latif Tahir , Seibel William , Azam Mohammad 
Published: August 2022

Abstract
Despite significant advancements in developing selective FMS-like tyrosine kinase 3 (FLT3) inhibitors, resistance to treatment is common even on continued therapy. Acquisition of on-target mutations or adaptation to MAPK, JAK2, and ABL signaling pathways drive treatment failure and disease relapse. Although combinatorial targeting of all escape routes in preclinical models demonstrated its efficacy, the clinical application is challenging owing to drug-drug interaction and differing pharmacokinetics of the inhibitors. We reasoned that selective polypharmacological targeting could lead to a durable response with reduced toxicity. A cell-based screening was carried out to identify inhibitors targeting FLT3, RAS-MAPK, BCR-ABL, and JAK2 to target the adaptive resistance observed with FLT3 inhibitors. Here, we show that pluripotin is an equipotent inhibitor of FLT3, BCR-ABL, and JAK2 in addition to inhibiting Ras-GAP and extracellular signal-regulated kinase 1 (ERK1). Structural modeling studies revealed that pluripotin is a type II kinase inhibitor that selectively binds with inactive conformations of FLT3, ABL, and JAK2. Pluripotin showed potent inhibitory activity on both mouse and human cells expressing FLT3ITD, including clinically challenging resistant mutations of the gatekeeper residue, F691L. Likewise, pluripotin suppressed the adaptive resistance conferred by the activation of RAS-MAPK pathways, BCR-ABL, and JAK2 signaling. Treatment with pluripotin curbed the progression of acute myeloid leukemia (AML) in multiple in vivo models including patient-derived primary AML cells in mouse xenotransplants. As a proof of concept, we demonstrate that targeted polypharmacological inhibition of key signaling nodes driving adaptive resistance can provide a durable response.
Safety and efficacy of tisagenlecleucel plus pembrolizumab in patients with r/r DLBCL: phase 1b PORTIA study results
Authors: Jaeger Ulrich , Worel Nina , McGuirk Joseph P. , Riedell Peter A. , Fleury Isabelle , Du Yan , Han Xia , Pearson David , Redondo Santiago , Waller Edmund K. 
Published: August 2022

Abstract
Tisagenlecleucel demonstrated high response rates and a manageable safety profile in adults with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) in the JULIET trial. However, lack of response and chimeric antigen receptor (CAR) T-cell exhaustion were observed in patients with programmed cell death protein 1 (PD-1) overexpression. Hence, pembrolizumab, a PD-1 inhibitor, was hypothesized to improve efficacy and cellular expansion of CAR T-cells in vivo. Here, we report the final analysis of the PORTIA trial in adult patients with r/r DLBCL who had ≥2 prior lines of therapy and had an Eastern Cooperative Oncology Group performance status of ≤1. Patients received 1 tisagenlecleucel infusion on day 1. Pembrolizumab (200 mg) was given every 21 days, for up to 6 doses. Three cohorts initiated pembrolizumab on days 15 (n = 4), 8 (n = 4), or –1 (n = 4). Safety, efficacy, cellular kinetics, and biomarker analyses were included. Tisagenlecleucel plus pembrolizumab was feasible and showed a manageable safety profile, without dose-limiting toxicities. Emerging efficacy with tisagenlecleucel was observed when pembrolizumab was given the day before tisagenlecleucel; however, the limited patient sample and short follow-up do not allow for definitive conclusions. Adding pembrolizumab to tisagenlecleucel did not augment the cellular expansion of tisagenlecleucel but delayed peak expansion if given the day before tisagenlecleucel (NCT03630159).
Human acute leukemia uses branched-chain amino acid catabolism to maintain stemness through regulating PRC2 function
Authors: Kikushige Yoshikane , Miyamoto Toshihiro , Kochi Yu , Semba Yuichiro , Ohishi Maki , Irifune Hidetoshi , Hatakeyama Kiwamu , Kunisaki Yuya , Sugio Takeshi , Sakoda Teppei , Miyawaki Kohta , Kato Koji , Soga Tomoyoshi , Akashi Koichi 
Published: August 2022

Abstract
Cancer-specific metabolic activities play a crucial role in the pathogenesis of human malignancies. To investigate human acute leukemia–specific metabolic properties, we comprehensively measured the cellular metabolites within the CD34+ fraction of normal hematopoietic stem progenitor cells (HSPCs), primary human acute myelogenous leukemia (AML), and acute lymphoblastic leukemia (ALL) cells. Here, we show that human leukemia cells are addicted to the branched-chain amino acid (BCAA) metabolism to maintain their stemness, irrespective of myeloid or lymphoid types. Human primary acute leukemias had BCAA transporters for BCAA uptake, cellular BCAA, α-ketoglutarate (α-KG), and cytoplasmic BCAA transaminase-1 (BCAT1) at significantly higher levels than control HSPCs. Isotope-tracing experiments showed that in primary leukemia cells, BCAT1 actively catabolizes BCAA using α-KG into branched-chain α-ketoacids, whose metabolic processes provide leukemia cells with critical substrates for the trichloroacetic acid cycle and the synthesis of nonessential amino acids, both of which reproduce α-KG to maintain its cellular level. In xenogeneic transplantation experiments, deprivation of BCAA from daily diet strongly inhibited expansion, engraftment and self-renewal of human acute leukemia cells. Inhibition of BCAA catabolism in primary AML or ALL cells specifically inactivates the function of the polycomb repressive complex 2, an epigenetic regulator for stem cell signatures, by inhibiting the transcription of PRC components, such as zeste homolog 2 and embryonic ectoderm development. Accordingly, BCAA catabolism plays an important role in the maintenance of stemness in primary human AML and ALL, and molecules related to the BCAA metabolism pathway should be critical targets for acute leukemia treatment.
Absence of hyperfibrinolysis may explain lack of efficacy of tranexamic acid in hypoproliferative thrombocytopenia
Authors: Ilich Anton , Gernsheimer Terry B. , Triulzi Darrell J. , Herren Heather , Brown Siobhan P. , Holle Lori A. , Lucas Andrew T. , de Laat Bas , El Kassar Nahed , Wolberg Alisa S. , May Susanne , Key Nigel S. 
Published: August 2022

Abstract
The American Trial Using Tranexamic Acid (TXA) in Thrombocytopenia (A-TREAT, NCT02578901) demonstrated no superiority of TXA over placebo in preventing World Health Organization (WHO) grade 2 or higher bleeding in patients with severe thrombocytopenia requiring supportive platelet transfusion following myeloablative therapy for hematologic disorders. In this ancillary study, we sought to determine whether this clinical outcome could be explained on the basis of correlative assays of fibrinolysis. Plasma was collected from A-TREAT participants (n = 115) before the initiation of study drug (baseline) and when TXA was at steady-state trough concentration (follow-up). Global fibrinolysis was measured by 3 assays: euglobulin clot lysis time (ECLT), plasmin generation (PG), and tissue-type plasminogen activator (tPA)–challenged clot lysis time (tPA-CLT). TXA was quantified in follow-up samples by tandem mass spectrometry. Baseline samples did not demonstrate fibrinolytic activation by ECLT or tPA-CLT. Furthermore, neither ECLT nor levels of plasminogen activator inhibitor-1, tPA, plasminogen, alpha2-antiplasmin, or plasmin-antiplasmin complexes were associated with a greater risk of WHO grade 2+ bleeding. TXA trough concentrations were highly variable (range, 0.7-10 μg/mL) and did not correlate with bleeding severity, despite the fact that plasma TXA levels correlated strongly with pharmacodynamic assessments by PG (Spearman r, −0.78) and tPA-CLT (r, 0.74). We conclude that (1) no evidence of fibrinolytic activation was observed in these patients with thrombocytopenia, (2) trough TXA concentrations varied significantly between patients receiving the same dosing schedule, and (3) tPA-CLT and PG correlated well with TXA drug levels.