bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective Changes of Pancreatic Iron in Thalassemia Major
Authors: Pepe Alessia , Pistoia Laura , Argento Crocetta , Rigoli Luciana , Benni Monica , Paci Cristina , Giovangrossi Piera , Maggio Aurelio , Restaino Gennaro , Riva Ada , Positano Vincenzo , Meloni Antonella 
Published: November 2021

Abstract
Introduction. Pancreatic iron deposition is a common finding in thalassemia major, being detected in more than one third of patients undergoing their first T2* Magnetic Resonance Imaging scan (MRI) for this purpose. However, no longitudinal studies on pancreatic iron are available in literature.
Aim: The aim of this multicenter study was to evaluate the changes in pancreatic iron overload in TM patients enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) Network who performed a baseline and a follow-up (FU) MRI scan at 18 months.
Methods. We considered 416 TM patients (37.77±10.46 years; 220 females) consecutively enrolled. Iron overload was quantified by the T2* technique. T2* measurements were performed over pancreatic head, body and tail and global value was the mean.
Results. Pancreatic iron overload (global pancreas T2*&lt;26 ms) was detected in 367 (88.2%) patients. Of them, only 14 (3.8%) improved at the FU. Out of the 49 (11.8%) patients without baseline pancreatic iron overload, 15 (30.6%) showed pancreatic iron overload at the FU MRI.
A significant inverse association was detected between % change in global pancreas T2*and baseline global pancreas T2* values (R=-0.369; P&lt;0.0001). Patients with baseline pancreatic iron overload showed significantly higher % changes in global pancreas T2* values (see Figure).
Changes (%) in global pancreas T2* were not associated with baseline serum ferritin levels or MRI liver iron concentration (LIC) values but were inversely correlated with % changes in serum ferritin levels (R=-0.199; P&lt;0.0001) and % changes in MRI LIC values (R=-0.255; P&lt;0.0001). A significant positive association was found between % changes in global pancreas and global heart T2* values (R=0.133; P=0.007).
At baseline MRI, 169 patients showed an alteration of glucidic metabolism: 32 had impaired fasting glucose, 65 impaired glucose tolerance, and 72 diabetes mellitus. These patients showed significantly higher % changes in global pancreas T2* than patients with a normal glucidic metabolism (33.06±79.48% vs 11.93±59.47%; P=0.003).
Conclusions. Our data showed that it is difficult to remove the iron from the pancreas and higher improvements were detected in more heavily loaded patients, with alterations of glucidic metabolism. The reduction in pancreatic iron was paralleled by a decrease in hepatic and cardiac iron.
Figure 1 Figure 1.

Disclosures
Pepe: Bayer S.p.A.: Other: no profit support; Chiesi Farmaceutici S.p.A: Other: no profit support. Maggio: Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Celgene Corp: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.
Contemporary Clinical Management and Course of ACUTE Pulmonary Embolism: The COPE Study
Authors: Becattini Cecilia , Agnelli Giancarlo , Maggioni Aldo P , Dentali Francesco , Fabbri Andrea , Enea Iolanda , Pomero Fulvio , Ruggeri Maria P , Di Lenarda Andrea , Cimini Ludovica A , Pepe Giuseppe , Cozzio Susanna , Diamanti Michele , Vanni Simone , Lucci Donata , Gulizia Michele M 
Published: November 2021

Abstract
Background. New management strategies, risk stratification procedures and treatments have become available over the last years for patients with acute pulmonary embolism (PE), leading to changes in clinical practice and potentially influencing patient's course and outcome.
Methods: The COntemporary management of Pulmonary Embolism (COPE) is an academical prospective, non-interventional, multicentre study in patients with confirmed acute symptomatic PE. In-hospital and 30-day mortality were the co-primary study outcomes. At first evaluation, patients were categorized at low-risk (simplified PESI [sPESI]=0), intermediate-risk (further classified based presence/absence of increased levels and right ventricle dysfunction [RVD] at echocardiography) and high-risk (shock or cardiac arrest).
Results. Among 5213 study patients, PE was confirmed by computed tomography in 96.3% and at least one test for risk stratification was obtained in more than 80% (81% echocardiography, 83% troponin, 56% brain natriuretic peptide/NT-pro BNP). Among 4885 patients entering the Emergency Department for acute PE, 1.2% were managed as outpatients and 5.8% by short-observation. In-hospital, 289 patients underwent reperfusion (5.5%); at discharge, 6.7% received a vitamin K antagonist and 75.6% a direct oral anticoagulant. Median duration of hospitalization was 7 days (IQR 5-12 days).
Overall in-hospital mortality was 3.4% (49% due to PE, 16% cancer and 4.5% major bleeding) and 30-day mortality 4.8% (36% PE, 28% cancer and 4% major bleeding). In-hospital major bleeding was 2.6%.
Death at 30 days occurred in 22.6% of 177 high-risk patients, in 6% of the 3281 intermediate-risk and in 0.5% of 1702 low-risk patients. Time to death at 30 days in patients at low, intermediate and high risk for death is reported in the Figure.
Conclusions: COPE is the largest ever cohort of patients with acute PE. In this contemporary scenario, the majority of patients received CT for diagnosis, at least one test for risk stratification and direct oral anticoagulants as long-term treatment. Short term death remains not negligible in patients with high and intermediate-risk PE.
Figure 1 Figure 1.

Disclosures
Becattini: Bristol Myers Squibb: Honoraria; Daiichi Sankyo: Honoraria; Bayer HealthCare: Honoraria. Agnelli: Bristol Myers Squibb: Honoraria; Pfizer: Honoraria; Daiichi Sankyo: Honoraria; Bayer HealthCare: Honoraria. Dentali: Daiichi Sankyo: Honoraria; Bayer: Honoraria; Sanofi: Honoraria; Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria; Novartis: Honoraria; Boehringer: Honoraria; Alfa Sigma: Honoraria.
Long-Term Efficacy of Psoralen Plus Ultraviolet a Irradiation and Low-Dose Interferon-Alpha Therapy According to Conventional and Emerging Clinical Endopoints of Early Stage Cutaneous T Cell Lymphoma
Authors: Rupoli Serena , Goteri Gaia , Morsia Erika , Torre Elena , Garvey Kimberly Blaine , Giantomassi Federica , Campanati Anna , Offidani Anna Maria , Brandozzi Giuliano , Giorgio Mozzicafreddo , Simonacci Marco , Olivieri Attilio 
Published: November 2021

Abstract

Introduction: Patients with early stage Cutaneous T cell Lymphoma (CTCL) usually have a benign and chronic disease course. Refractoriness under skin directed therapies and/or more extensive disease pose some therapeutic changes. Using the combination of psoralen plus ultraviolet A irradiation (PUVA) and low-dose Interferon-α (INF), the principal treatment goal is to keep confined the disease to the skin, preventing disease progression.
Methods: We carry out a prospective data on 87 patients with early stage IA to IIA MF treated with low-dose IFN-α2b and PUVA, enrolled from 1997 to 2010. We collected data regarding clinical characteristics of MF, efficacy and outcome. Subcutaneous IFN-α2b was administered 1.5 MU/day during the first week; in the second week the dose was increased to 3MU/day. PUVA irradiation was started on the 3th week with IFN-α2b 3 MU 3 times weekly until CR, of for a maximum of 2 months. During maintenance therapy, IFN-α2b was scheduled for 3 MU 3 times weekly for 2 months and subsequently 3 MU 2 times weekly for 10 months and PUVA was gradually reduced every 2 months over a period of 12 months. Diagnostic, risk and response assignments were according to EORTC criteria.
Results: Patient characteristics at time diagnosis, staging, response rates and overall outcome are shown in Table 1. Among the 87 patients, overall response rate (ORR) was 97.8% (n=85) and included complete remission (CR) in 70 patients (80.5%), very good partial remission in 5 patients (5.8%) and partial remission (PR) in another 10 (11.5%). The best response to therapy was seen after a median of 5 months (range, 1-30) and the 74.3% of patients who achieved a CR after induction therapy kept the complete response at the last follow up. Among the responders, 40 (47.1%) relapsed with minor event with in median time of 21 months (range, 0-71) and 7(8.2%) relapsed with major event in a median time of 6 months (range, 1-81).
After a median follow up of 207 months (range, 6-295), 25 (28.7) patients died, only 1 for progressive disease. Median overall survival (OS) for our cohort was not reached (95% CI; 235-NR months) and median time to next treatment (TTNT) was 38.5 months (95% CI, 33-46 months). Moreover, disease free survival (DFS) in CR patients was 210 months (95% CI; 200-226 months).
Conclusions: The long follow up of this study verifies our preliminary results and confirms the efficacy of INF-PUVA combination therapy in a real world setting, according conventional (OS and DFS) and emerging (TTNT) clinical endpoints of treatment efficacy.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Chromatin Accessibility Landscapes of Acute Lymphoblastic Leukemia
Authors: Barnett Kelly R. , Diedrich Jonathan D. , Bergeron Brennan P. , Yang Wenjian , Crews Kristine R. , Stock Wendy , Paietta Elisabeth M. , Kornblau Steven M. , Inaba Hiroto , Jeha Sima , Pui Ching-Hon , Relling Mary V. , Evans William E. , Yang Jun J. , Savic Daniel 
Published: November 2021

Abstract
Acute lymphoblastic leukemia (ALL) is the most common malignancy in pediatric patients spanning both B- and T-cell lineages. ALL also occurs less commonly in adults but with cure rates of only around 30%. Past work has characterized ALL into molecular subtypes spanning a range of aberrant chromosomal rearrangements and oncogene chimeric fusions driving malignancy. While transcriptional profiling of these subtypes has been extensively examined, the accompanying chromatin accessibility landscape and corresponding gene regulatory repertoire is not well characterized for many subtypes. To better profile the ALL epigenomic and gene regulatory repertoire we examined chromatin accessibility of 12 distinct molecular subtypes (BCR-ABL1, ETV6-RUNX1, Hyperdiploid, Hypodiploid, KMT2A rearranged, Ph-Like, PAX5, DUX4/ERG, TCF3-PBX1, T-ALL, Early T Precursor and B-other) across 189 primary patient samples of pediatric ALL (n = 106) and adult ALL (n = 83) origin using ATAC-seq. To our knowledge, this represents the largest collection of chromatin accessibility data in primary ALL samples spanning multiple molecular subtypes to date. Collectively, we identified over 600,000 accessible chromatin sites in the ALL genome with over 50,000 regions of differentially accessible chromatin encompassing both common and subtype-specific modalities. Further, transcription factor (TF) footprint profiling of ATAC-seq yielded tens of thousands of candidate TF binding events and identified key TF drivers within distinct molecular subtypes. We additionally performed H3K27ac ChIP-seq in a subset of 12 primary ALL patient samples, with integration of these histone data for select patient samples allowing inferences about candidate super-enhancer drivers of ALL molecular subtypes. Overall, these analyses and data offer a window into the gene regulatory and epigenetic landscape of ALL, and further highlight the complexity and heterogeneity of accessible chromatin landscapes among distinct molecular subtypes of ALL.

Disclosures
Stock: Pfizer: Consultancy, Honoraria, Research Funding; amgen: Honoraria; agios: Honoraria; jazz: Honoraria; kura: Honoraria; kite: Honoraria; morphosys: Honoraria; servier: Honoraria; syndax: Consultancy, Honoraria; Pluristeem: Consultancy, Honoraria. Pui: Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Data Monitoring Committee. Evans: Princess Máxima Center for Pediatric Oncology, Scientific Advisory Board, Chair: Membership on an entity's Board of Directors or advisory committees; St. Jude Children's Research Hospital, Emeritus Member (began Jan 2021): Ended employment in the past 24 months; BioSkryb, Inc.: Membership on an entity's Board of Directors or advisory committees.
Efficacy and safety of fremanezumab in clinical trial participants aged ≥60 years with episodic or chronic migraine: pooled results from 3 randomized, double-blind, placebo-controlled phase 3 studies
Authors: Nahas Stephanie J. , Naegel Steffen , Cohen Joshua M. , Ning Xiaoping , Janka Lindsay , Campos Verena Ramirez , Krasenbaum Lynda J. , Holle-Lee Dagny , Kudrow David , Lampl Christian 
Published: November 2021

AbstractBackgroundAlthough migraine is less common in older people, preventive treatment of migraine in these individuals may be more challenging due to the presence of multiple comorbidities and polypharmacy. Additionally, evidence for migraine treatment efficacy, safety, and tolerability is limited in this population. We evaluated efficacy, safety, and tolerability of fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene–related peptide (CGRP), in clinical trial participants aged ≥60 years with episodic migraine (EM) or chronic migraine (CM).MethodsThis analysis included data from 3 randomized, double-blind, placebo-controlled phase 3 studies: the HALO EM study, HALO CM study, and FOCUS study in participants with EM or CM and prior inadequate response to 2–4 migraine preventive medication classes. Participants in all studies were randomized 1:1:1 to receive 12 weeks of subcutaneous treatment with quarterly fremanezumab (Months 1/2/3: EM/CM, 675 mg/placebo/placebo), monthly fremanezumab (Months 1/2/3: EM, 225 mg/225 mg/225 mg; CM, 675 mg/225 mg/225 mg), or matched monthly placebo.ResultsThese pooled analyses included 246 participants aged ≥60 years. Reductions in monthly migraine days from baseline over 12 weeks were significantly greater with fremanezumab (least-squares mean change from baseline [standard error]: quarterly fremanezumab, − 4.3 [0.59]; monthly fremanezumab, − 4.6 [0.54]) versus placebo (placebo, − 2.3 [0.57]; bothP < 0.01 vs placebo). As early as Week 1, significant reductions from baseline in weekly migraine days were observed with fremanezumab versus placebo (bothP < 0.01). With fremanezumab treatment versus placebo, a significantly higher proportion of participants achieved ≥50% reduction in monthly migraine days, and significant improvements in disability and quality-of-life outcomes were observed (P < 0.05). Proportions of participants experiencing serious adverse events and adverse events leading to discontinuation were low and similar in the fremanezumab and placebo groups. Efficacy and safety results were comparable to the overall pooled population (N = 2843).ConclusionsThis pooled subgroup analysis demonstrates that fremanezumab treatment is efficacious and well-tolerated over 12 weeks in participants aged ≥60 years with EM or CM. These data may help healthcare providers with clinical decision making and preventive treatment selection for older patients with migraine.Trial registrationClinicalTrials.govidentifiers: HALO CM:NCT02621931; HALO EM:NCT02629861; FOCUS:NCT03308968.
Graphitic Carbon Nitride as a Platform for the Synthesis of Silver Nanoclusters
Authors: Starukh Halyna , Koštejn Martin , Matějka Vlastimil , Praus Petr 
Published: November 2021

Abstract
Graphitic carbon nitride (CN) synthetized by the thermal polycondensation of melamine at 550 °C for 4 h was further exfoliated by heating at 500 °C for 3 h. Silver cations were adsorbed on the exfoliated graphitic carbon nitride (CNE) and then reduced by sodium borohydride forming silver nanoclusters (NCs) with a size of less than 1 nm. The NCs were located on the CNE surface and did not change the CNE properties except for its pore size distribution and thereby specific surface area (SSA). The Ag NCs were able to collect the photoinduced electrons of CNE and thus reduce their recombination with the holes. It was also documented by the increase in the CNE photocatalytic activity in terms of the degradation of antibiotic Ofloxacin. This study demonstrates the ability of CNE to serve as a platform for a simple and fast synthesis of Ag NCs without any stabilizing compounds.

Graphic Abstract
Urinary peptidomics reveals proteases involved in idiopathic membranous nephropathy
Authors: Lin Baoxu , Liu Jianhua , Zhang Yue , Wu Yabin , Chen Shixiao , Bai Yibo , Liu Qiuying , Qin Xiaosong 
Published: November 2021

Abstract
Background
Idiopathic membranous nephropathy (IMN) is a cause of nephrotic syndrome that is increasing in incidence but has unclear pathogenesis. Urinary peptidomics is a promising technology for elucidating molecular mechanisms underlying diseases. Dysregulation of the proteolytic system is implicated in various diseases. Here, we aimed to conduct urinary peptidomics to identify IMN-related proteases.

Results
Peptide fingerprints indicated differences in naturally produced urinary peptide components among 20 healthy individuals, 22 patients with IMN, and 15 patients with other kidney diseases. In total, 1,080 peptide-matched proteins were identified, 279 proteins differentially expressed in the urine of IMN patients were screened, and 32 proteases were predicted; 55 of the matched proteins were also differentially expressed in the kidney tissues of IMN patients, and these were mainly involved in the regulation of proteasome-, lysosome-, and actin cytoskeleton-related signaling pathways. The 32 predicted proteases showed abnormal expression in the glomeruli of IMN patients based on Gene Expression Omnibus databases. Western blot revealed abnormal expression of calpain, matrix metalloproteinase 14, and cathepsin S in kidney tissues of patients with IMN.

Conclusions
This work shown the calpain/matrix metalloproteinase/cathepsin axis might be dysregulated in IMN. Our study is the first to systematically explore the role of proteases in IMN by urinary peptidomics, which are expected to facilitate discovery of better biomarkers for IMN.
Profile of gene expression changes during estrodiol-17β-induced feminization in the Takifugu rubripes brain
Authors: Shen Xufang , Yan Hongwei , Jiang Jieming , Li Weiyuan , Xiong Yuyu , Liu Qi , Liu Ying 
Published: November 2021

Abstract
Background
As the critical tissue of the central nervous system, the brain has been found to be involved in gonad development. Previous studies have suggested that gonadal fate may be affected by the brain. Identifying brain-specific molecular changes that occur during estrodiol-17β (E2) -induced feminization is crucial to our understanding of the molecular control of sex differentiation by the brains of fish.

Results
In this study, the differential transcriptomic responses of the Takifugu rubripes larvae brain were compared after E2 treatment for 55 days. Our results showed that 514 genes were differentially expressed between E2-treated-XX (E-XX) and Control-XX (C-XX) T. rubripes, while 362 genes were differentially expressed between E2-treated-XY (E-XY) and Control-XY (C-XY). For example, the expression of cyp19a1b, gnrh1 and pgr was significantly up-regulated, while st, sl, tshβ, prl and pit-1, which belong to the growth hormone/prolactin family, were significantly down-regulated after E2 treatment, in both sexes. The arntl1, bhlbe, nr1d2, per1b, per3, cry1, cipc and ciart genes, which are involved in the circadian rhythm, were also found to be altered. Differentially expressed genes (DEGs), which were identified between E-XX and C-XX, were significantly enriched in neuroactive ligand-receptor interaction, arachidonic acid metabolism, cytokine-cytokine receptor interaction and the calcium signaling pathway. The DEGs that were identified between E-XY and C-XY were significantly enriched in tyrosine metabolism, phenylalanine metabolism, arachidonic acid metabolism and linoleic acid metabolism.

Conclusion
A number of genes and pathways were identified in the brain of E2-treated T. rubripes larvae by RNA-seq. It provided the opportunity for further study on the possible involvement of networks in the brain-pituitary-gonadal axis in sex differentiation in T. rubripes.
Effects of minimally invasive and traditional surgeries on the quality of life of children with congenital heart disease: a retrospective propensity score-matched study
Authors: Tan Hui , Huang Erjia , Deng Xicheng , Li Dongping , Ouyang Shayuan 
Published: November 2021

Abstract
Background
The focus of clinical care after treating congenital heart disease (CHD) has shifted from saving patients’ lives to improving their quality of life. This study aimed to examine the influence of minimally invasive and traditional surgeries on the quality of life of children with CHD.

Methods
This was a retrospective cross-sectional study. A total of 459 children aged 2–18 years with CHD treated at Second Xiangya Hospital of Central South University from July 2016 to June 2017 were enrolled, among whom 219 underwent minimally invasive surgery and 240 traditional surgery. The quality of life of children with CHD after surgery was reported by the patients’ parents. We applied propensity score matching to correct for confounding factors and conducted multiple linear regression analysis to examine the related effects of minimally invasive and traditional surgeries on the quality of life of children with CHD.

Results
The scores of problems related to perceived physical appearance in children undergoing minimally invasive surgery was higher than those in those undergoing traditional surgery (p = 0.004). Different treatment modes were independent influencing factors for problems related to perceived physical appearance in children with CHD. There was no significant difference in average treatment effect scores of children undergoing different surgical procedures in other quality of life dimensions (problems related to cardiac symptoms and their treatment, drug treatment, anxiety regarding treatment, cognitive psychology, and communication), suggesting that different operation modes were not independent influencing factors for these related problems.

Conclusion
Compared with traditional surgery, minimally invasive surgery can significantly improve the physical appearance perception scores of children with CHD after surgery. Therefore, minimally invasive surgery can improve the quality of life of children with CHD.