bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement properties of the Dutch–Flemish patient-reported outcomes measurement information system (PROMIS) physical function item bank and instruments: a systematic review
Authors: Abma Inger L. , Butje Bas J. D. , ten Klooster Peter M. , van der Wees Philip J. 
Published: February 2021

AbstractBackgroundLimitations in physical functioning are a big concern especially for patients with chronic or musculoskeletal diseases. Therefore, physical functioning is often used as a core outcome of treatments. The generic patient-reported outcomes information system (PROMIS) physical function (PF) item bank has shown potential to measure PF with better precision, interpretability and lower respondent burden compared with traditional patient-reported outcome measures. This study provides an overview of the current evidence on the quality of the measurement properties of the translated Dutch–Flemish PROMIS-PF item bank and its subdomains, and their derived short forms and computer adaptive tests (CATs).MethodsPubMed was searched up to June 17th 2020 for validation studies of Dutch–Flemish PROMIS-PF in Dutch and Flemish adults. Quality assessment of the included studies was conducted using the COSMIN Risk of bias checklist. The COSMIN criteria for good measurement properties were used to judge the results of the studies, which were adjusted and added to where needed for this review, in the context of IRT instruments and item banks. The quality of evidence was summarized for each measurement property based on the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach.ResultsEleven studies were included, evaluating the PROMIS-PF item bank, the Upper Extremity (UE) subdomain, and/or their derived short forms and CATs in different clinical populations. There is evidence for sufficient structural validity, measurement precision, construct validity, and cross-cultural validity of the Dutch–Flemish PROMIS-PF item bank. The upper extremity subdomain item bank shows high quality evidence for structural validity and measurement precision. Content validity of these item banks has not been thoroughly demonstrated in a Dutch–Flemish population. Furthermore, the derived instruments have far less robust evidence: there are fewer validation studies available and none examined their performance as stand-alone administered instruments.ConclusionsThe first studies into the Dutch–Flemish PROMIS-PF item bank and the UE subdomain show promising results, with especially high quality evidence for sufficient structural validity and measurement precision. However, more studies, and with higher methodological quality, are needed to study the instruments derived from these item banks. These studies should also evaluate content validity, reliability and responsiveness.
Whole blood RNA sequencing reveals a differential transcriptomic profile associated with cervical insufficiency: a pilot study
Authors: Son Ga-Hyun , Choi So Yeon , Ju Yeon-Ji , Lee Keun-Young , Lee Jae Jun , Song Ji-Eun , Kim Youngmi , Park Sung Taek 
Published: February 2021

Abstract
Background
The uterine cervix is a mechanical and immunological barrier against ascending infection during pregnancy. Cervical insufficiency (CI), a painless cervical dilation that occurs in the mid-trimester, is an important cause of extremely preterm birth. We hypothesized that women with CI have a differential transcriptomic profile. Therefore, we compared the transcriptomic profile of peripheral blood in women with CI and that of controls.

Methods
RNA sequencing was used to generate the global gene expression profiles of 11 women with CI and 4 controls, and differential expression analysis was performed to identify genes showing significant expression changes between the CI (n = 11) and control (n = 4) groups as well as between the CI-preterm (n = 7) and CI-term (n = 4) groups. Gene set enrichment was assessed in terms of Gene Ontology processes, and a subset of differentially expressed genes in CI was validated in a different sample-set by qRT-PCR and ELISA.

Results
Thirty genes were differentially expressed between the CI and control groups. Differentially upregulated genes in the CI group included neutrophil-mediated immunity-associated (DEFA3 and ELANE) and bicarbonate transport-related genes. The serum concentration of alpha defensin 3 was significantly higher in women with CI than in controls (P = 0.014). Analysis of differential gene expression according to pregnancy outcomes revealed 338 differentially expressed genes between the CI-term and CI-preterm groups. Immune and defense response to organism-associated genes and influenza A and NOD-like receptor signaling pathways were upregulated in the CI-term group.

Conclusions
Our results revealed significant differences in the whole blood transcriptomic profiles of women with CI compared to those of controls. Different immune responses in women with CI may affect pregnancy outcomes.
Abelson kinase’s intrinsically disordered region plays essential roles in protein function and protein stability
Authors: Rogers Edward M. , Allred S. Colby , Peifer Mark 
Published: February 2021

AbstractBackgroundThe non-receptor tyrosine kinase Abelson (Abl) is a key player in oncogenesis, with kinase inhibitors serving as paradigms of targeted therapy. Abl also is a critical regulator of normal development, playing conserved roles in regulating cell behavior, brain development and morphogenesis. Drosophila offers a superb model for studying Abl’s normal function, because, unlike mammals, there is only a single fly Abl family member. In exploring the mechanism of action of multi-domain scaffolding proteins like Abl, one route is to define the roles of their individual domains. Research into Abl’s diverse roles in embryonic morphogenesis revealed many surprises. For instance, kinase activity, while important, is not crucial for all Abl activities, and the C-terminal F-actin binding domain plays a very modest role. This turned our attention to one of Abl’s least understood features—the long intrinsically-disordered region (IDR) linking Abl’s kinase and F-actin binding domains. The past decade revealed unexpected, important roles for IDRs in diverse cell functions, as sites of posttranslational modifications, mediating multivalent interactions and enabling assembly of biomolecular condensates via phase separation. Previous work deleting conserved regions in Abl’s IDR revealed an important role for a PXXP motif, but did not identify any other essential regions.MethodsHere we extend this analysis by deleting the entire IDR, and asking whether Abl∆IDR rescues the diverse roles of Abl in viability and embryonic morphogenesis inDrosophila.ResultsThis revealed that the IDR is essential for embryonic and adult viability, and for cell shape changes and cytoskeletal regulation during embryonic morphogenesis, and, most surprisingly, revealed a role in modulating protein stability.ConclusionOur data provide new insights into the role of the IDR in an important signaling protein, the non-receptor kinase Abl, suggesting that it is essential for all aspects of protein function during embryogenesis, and revealing a role in protein stability. These data will stimulate new explorations of the mechanisms by which the IDR regulates Abl stability and function, both in Drosophila and also in mammals. They also will stimulate further interest in the broader roles IDRs play in diverse signaling proteins.
Phosphoinositides signaling modulates microglial actin remodeling and phagocytosis in Alzheimer’s disease
Authors: Desale Smita Eknath , Chinnathambi Subashchandrabose 
Published: February 2021

AbstractAlzheimer’s disease is one of the neurodegenerative diseases, characterized by the accumulation of abnormal protein deposits, which disrupts signal transduction in neurons and other glia cells. The pathological protein in neurodegenerative diseases, Tau and amyloid-β contribute to the disrupted microglial signaling pathways, actin cytoskeleton, and cellular receptor expression. The important secondary messenger lipids i.e., phosphatidylinositols are largely affected by protein deposits of amyloid-β in Alzheimer’s disease. Phosphatidylinositols are the product of different phosphatidylinositol kinases and the state of phosphorylation at D3, D4, and D5 positions of inositol ring. Phosphatidylinositol 3,4,5-triphosphate (PI 3, 4, 5-P3) involves in phagocytic cup formation, cell polarization, whereas Phosphatidylinositol 4,5-bisphosphate (PI 4, 5-P2)-mediates the process of phagosomes formation and further its fusion with early endosome.. The necessary activation of actin-binding proteins such as Rac, WAVE complex, and ARP2/3 complex for the actin polymerization in the process of phagocytosis, migration is regulated and maintained by PI 3, 4, 5-P3 and PI 4, 5-P2. The ratio and types of fatty acid intake can influence the intracellular secondary lipid messengers along with the cellular content of phaphatidylcholine and phosphatidylethanolamine. The Amyloid-β deposits and extracellular Tau seeds disrupt phosphatidylinositides level and actin cytoskeletal network that hamper microglial-signaling pathways in AD. We hypothesize that being a lipid species intracellular levels of phosphatidylinositol would be regulated by dietary fatty acids. Further we are interested to understand phosphoinositide-based signaling cascades in phagocytosis and actin remodeling.
Distinguishing active pediatric COVID-19 pneumonia from MIS-C
Authors: Reiff Daniel D. , Mannion Melissa L. , Samuy Nichole , Scalici Paul , Cron Randy Q. 
Published: February 2021

Abstract
Importance
Active pediatric COVID-19 pneumonia and MIS-C are two disease processes requiring rapid diagnosis and different treatment protocols.

Objective
To distinguish active pediatric COVID-19 pneumonia and MIS-C using presenting signs and symptoms, patient characteristics, and laboratory values.

Design
Patients diagnosed and hospitalized with active COVID-19 pneumonia or MIS-C at Children’s of Alabama Hospital in Birmingham, AL from April 1 through September 1, 2020 were identified retrospectively. Active COVID-19 and MIS-C cases were defined using diagnostic codes and verified for accuracy using current US Centers for Disease Control case definitions. All clinical notes were reviewed for documentation of COVID-19 pneumonia or MIS-C, and clinical notes and electronic medical records were reviewed for patient demographics, presenting signs and symptoms, prior exposure to or testing for the SARS-CoV-2 virus, laboratory data, imaging, treatment modalities and response to treatment.

Findings
111 patients were identified, with 74 classified as mild COVID-19, 8 patients as moderate COVID-19, 8 patients as severe COVID-19, 10 as mild MIS-C and 11 as severe MIS-C. All groups had a male predominance, with Black and Hispanic patients overrepresented as compared to the demographics of Alabama. Most MIS-C patients were healthy at baseline, with most COVID-19 patients having at least one underlying illness. Fever, rash, conjunctivitis, and gastrointestinal symptoms were predominant in the MIS-C population whereas COVID-19 patients presented with predominantly respiratory symptoms. The two groups were similar in duration of symptomatic prodrome and exposure history to the SARS-CoV-2 virus, but MIS-C patients had a longer duration between presentation and exposure history. COVID-19 patients were more likely to have a positive SAR-CoV-2 PCR and to require respiratory support on admission. MIS-C patients had lower sodium levels, higher levels of C-reactive protein, erythrocyte sedimentation rate, d-dimer and procalcitonin. COVID-19 patients had higher lactate dehydrogenase levels on admission. MIS-C patients had coronary artery changes on echocardiography more often than COVID-19 patients.

Conclusions and relevance
This study is one of the first to directly compare COVID-19 and MIS-C in the pediatric population. The significant differences found between symptoms at presentation, demographics, and laboratory findings will aide health-care providers in distinguishing the two disease entities.
Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial
Authors:   the Study 1053 investigators, Kreitman Robert J. , Dearden Claire , Zinzani Pier Luigi , Delgado Julio , Robak Tadeusz , le Coutre Philipp D. , Gjertsen Bjørn T. , Troussard Xavier , Roboz Gail J. , Karlin Lionel , Gladstone Douglas E. , Kuptsova-Clarkson Nataliya , Liu Shiyao , Patel Priti , Rotolo Federico , Mitry Emmanuel , Pastan Ira , Giles Francis 
Published: February 2021

Abstract
Background
Moxetumomab pasudotox is a recombinant CD22-targeting immunotoxin. Here, we present the long-term follow-up analysis of the pivotal, multicenter, open-label trial (NCT01829711) of moxetumomab pasudotox in patients with relapsed/refractory (R/R) hairy cell leukemia (HCL).

Methods
Eligible patients had received ≥ 2 prior systemic therapies, including ≥ 2 purine nucleoside analogs (PNAs), or ≥ 1 PNA followed by rituximab or a BRAF inhibitor. Patients received 40 µg/kg moxetumomab pasudotox intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles. Disease response and minimal residual disease (MRD) status were determined by blinded independent central review. The primary endpoint was durable complete response (CR), defined as achieving CR with hematologic remission (HR, blood counts for CR) lasting > 180 days.

Results
Eighty adult patients were treated with moxetumomab pasudotox and 63% completed six cycles. Patients had received a median of three lines of prior systemic therapy; 49% were PNA-refractory, and 38% were unfit for PNA retreatment. At a median follow-up of 24.6 months, the durable CR rate (CR with HR > 180 days) was 36% (29 patients; 95% confidence interval: 26–48%); CR with HR ≥ 360 days was 33%, and overall CR was 41%. Twenty-seven complete responders (82%) were MRD-negative (34% of all patients). CR lasting ≥ 60 months was 61%, and the median progression-free survival without the loss of HR was 71.7 months. Hemolytic uremic and capillary leak syndromes were each reported in ≤ 10% of patients, and ≤ 5% had grade 3–4 events; these events were generally reversible. No treatment-related deaths were reported.

Conclusions
Moxetumomab pasudotox resulted in a high rate of durable responses and MRD negativity in heavily pre-treated patients with HCL, with a manageable safety profile. Thus, it represents a new and viable treatment option for patients with R/R HCL, who currently lack adequate therapy.

Trial registration

ClinicalTrials.gov identifier: NCT01829711; first submitted: April 9, 2013. https://clinicaltrials.gov/ct2/show/NCT01829711
Exosome-mediated transfer of CD44 from high-metastatic ovarian cancer cells promotes migration and invasion of low-metastatic ovarian cancer cells
Authors: Shen Xiameng , Wang Conghui , Zhu Huihui , Wang Yaping , Wang Xinyu , Cheng Xiaodong , Ge Wanzhong , Lu Weiguo 
Published: February 2021

Abstract
Objective
To investigate the detailed roles and mechanisms of tumor-derived exosomes in progression and metastasis of ovarian cancer in vitro.

Methods
Exosomes were isolated by differential centrifugation method; the morphology, size and biological markers of exosomes were separately defined by transmission electron microscopy, nanoS90 and Western blotting; Trans-well chambers assay was used to assess the ability of migration and invasion of recipient cells uptaking the exosomes from HO8910PM cells. The downstream molecule was screened by mass spectrometry.CD44 was identified by western blotting and the function of CD44 was identified by trans-well chambers assay and CCK8 assay.

Results
Exosomes derived from HO8910PM cells could be transferred to HO8910 cells and promote cell migration and invasion in the recipient cells of ovarian cancer. And CD44 could be transferred to the HO8910 cells through exosomes from HO8910PM cells and influence the migration and invasion ability of HO8910 cells.

Conclusion
The more aggressive subpopulation can transfer a metastatic phenotype to the less one via secreting exosomes within a heterogeneous tumor. CD44 may be a potential therapeutic approach for ovarian cancer.
Whole blood and blood components from vertebrates differentially affect egg formation in three species of anautogenous mosquitoes
Authors: Harrison Ruby E. , Brown Mark R. , Strand Michael R. 
Published: February 2021

AbstractBackgroundMost female mosquitoes are anautogenous and must blood feed on a vertebrate host to produce eggs. Prior studies show that the number of eggs females lay per clutch correlates with the volume of blood ingested and that protein is the most important macronutrient for egg formation. In contrast, how whole blood, blood fractions and specific blood proteins from different vertebrates affect egg formation is less clear. Since egg formation is best understood inAedes aegypti,we examined how blood and blood components from different vertebrates affect this species and two others: the malaria vectorAnopheles gambiaeand arbovirus vectorCulex quinquefasciatus.MethodsAdult female mosquitoes were fed blood, blood fractions and purified major blood proteins from different vertebrate hosts. Markers of reproductive response including ovary ecdysteroidogenesis, yolk deposition into oocytes and number of mature eggs produced were measured.ResultsAe. aegypti, An. gambiaeandC. quinquefasciatusresponded differently to meals of whole blood, plasma or blood cells from human, rat, chicken and turkey hosts. We observed more similarities between the anthropophilesAe. aegyptiandAn. gambiaethan the ornithophileC. quinquefasciatus.Focusing onAe. aegypti,the major plasma-derived proteins (serum albumin, fibrinogen and globulins) differentially stimulated egg formation as a function of vertebrate host source. The major blood cell protein, hemoglobin, stimulated yolk deposition when from pigs but not humans, cows or sheep. Serum albumins from different vertebrates also variably affected egg formation. Bovine serum albumin (BSA) stimulated ovary ecdysteroidogenesis, but more weakly induced digestive enzyme activities than whole blood. In contrast, BSA-derived peptides and free amino acids had no stimulatory effects on ecdysteroidogenesis or yolk deposition into oocytes.ConclusionsWhole blood, blood fractions and specific blood proteins supported egg formation in three species of anautogenous mosquitoes but specific responses varied with the vertebrate source of the blood components tested.Graphical Abstract
Single-cell transcriptomic profiling and characterization of endothelial progenitor cells: new approach for finding novel markers
Authors: Abdelgawad Mohamed Essameldin , Desterke Christophe , Uzan Georges , Naserian Sina 
Published: February 2021

AbstractBackgroundEndothelial progenitor cells (EPCs) are promising candidates for the cellular therapy of peripheral arterial and cardiovascular diseases. However, hitherto there is no specific marker(s) defining precisely EPCs. Herein, we are proposing a new in silico approach for finding novel EPC markers.MethodsWe assembled five groups of chosen EPC-related genes/factors using PubMed literature and Gene Ontology databases. This shortened database of EPC factors was fed into publically published transcriptome matrix to compare their expression between endothelial colony-forming cells (ECFCs), HUVECs, and two adult endothelial cell types (ECs) from the skin and adipose tissue. Further, the database was used for functional enrichment on Mouse Phenotype database and protein-protein interaction network analyses. Moreover, we built a digital matrix of healthy donors’ PBMCs (33 thousand single-cell transcriptomes) and analyzed the expression of these EPC factors.ResultsTranscriptome analyses showed that BMP2, 4, and ephrinB2 were exclusively highly expressed in EPCs; the expression of neuropilin-1 and VEGF-C were significantly higher in EPCs and HUVECs compared with other ECs; Notch 1 was highly expressed in EPCs and skin-ECs; MIR21 was highly expressed in skin-ECs; PECAM-1 was significantly higher in EPCs and adipose ECs. Moreover, functional enrichment of EPC-related genes on Mouse Phenotype and STRING protein database has revealed significant relations between chosen EPC factors and endothelial and vascular functions, development, and morphogenesis, where ephrinB2, BMP2, and BMP4 were highly expressed in EPCs and were connected to abnormal vascular functions. Single-cell RNA-sequencing analyses have revealed that among the EPC-regulated markers in transcriptome analyses, (i) ICAM1 and Endoglin were weekly expressed in the monocyte compartment of the peripheral blood; (ii) CD163 and CD36 were highly expressed in the CD14+ monocyte compartment whereas CSF1R was highly expressed in the CD16+ monocyte compartment, (iii) L-selectin and IL6R were globally expressed in the lymphoid/myeloid compartments, and (iv) interestingly, PLAUR/UPAR and NOTCH2 were highly expressed in both CD14+ and CD16+ monocytic compartments.ConclusionsThe current study has identified novel EPC markers that could be used for better characterization of EPC subpopulation in adult peripheral blood and subsequent usage of EPCs for various cell therapy and regenerative medicine applications.
Defining, conceptualizing, and measuring perceived maternal care quality in low- to high-income countries: a scoping review protocol
Authors: Brown Kyrah K. , Boateng Godfred O. , Ossom-Williamson Peace , Haygood Laura 
Published: February 2021

Abstract
Background
Health practitioners and researchers must be able to measure and assess maternal care quality in facilities to monitor, intervene, and reduce global maternal mortality rates. On the global scale, there is a general lack of consensus on how maternal care quality is defined, conceptualized, and measured. Much of the literature addressing this problem has focused primarily on defining, conceptualizing, and measuring clinical indicators of maternal care quality. Less attention has been given in this regard to perceived maternal care quality among women which is known to influence care utilization and adherence. Therefore, there is a need to map the literature focused on defining, conceptualizing, and measuring perceived maternal care quality across low-, middle-, and high-income country contexts.

Methods
This scoping review protocol will follow the Arksey and O’Malley methodological framework. A comprehensive search strategy will be used to search for articles published from inception to 2020 in Ovid MEDLINE, Embase, AMED, and WHO Global Index Medicus. Gray literature will be included. Two independent reviewers will screen articles by title and abstract, then by full-text based on pre-determined inclusion/exclusion criteria. A third reviewer will arbitrate any discrepancies. This protocol outlines a four-step analytic approach that includes numerical, graphical, tabular, and narrative summaries to provide a comprehensive description of the body of literature.

Discussion
The findings from this scoping review will provide a comprehensive overview of the existing evidence on perceived maternal care quality. The findings are expected to inform future work on building consensus around the definition and conceptualization of perceived maternal care quality, and lay the groundwork for future research aimed at developing measures of perceived maternal care quality that can be applied across country contexts. Consequently, this review may aid in facilitating coordinated efforts to measure and improve maternal care quality across diverse country contexts (i.e., low-, middle-, and high-income country contexts).

Review registration
This scoping review has been registered in the Open Science Framework (osf.io/k8nqh).