bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality-of-care comparison of stroke: The reliability and robustness of ranking by process or outcome measures
Authors: Li Jingkun , Qu Peng , Wang Chao , Li Xi , Hou Shuang , Liu Meina 
Published: October 2021

Background and aim Discussion on the most rational types of performance measures for care quality comparisons has received increasing attention. The important consideration is to what extent will the measure detect a genuine difference in the underlying quality. In this study, we aimed to compare the ranking of hospitals on the performance of individual indicators, composite scores (CS, that were calculated by the method of opportunity-based score on patient-level), and in-hospital outcome of acute ischemic stroke across hospitals, and determined the reliability and robustness of the three types of ranking. Methods We analyzed data from 15,090 patients diagnosed with acute ischemic stroke who were treated at 184 large tertiary hospitals from January 2014 to May 2017. We ranked the hospital effects of recombinant tissue plasminogen activator (rt-PA) and CS and independence (modified Rankin Scale ≤2) at discharge based on fixed- and random-effects regression models before and after case-mix adjustment. We assessed the time-robustness of the hospital effects and calculated the rankability by relating the uncertainty within the hospital and the total hospital variation “beyond chance.” Results After case-mix and reliability adjustment, we estimated that 84.03% of the variance in CS between hospitals was due to true quality differences. The uncertainty within hospitals caused a poor (49.51%) rankability in rt-PA and moderate rankability (63.34%) in independence at discharge. The hospital rankings of CS were more robust across years compared with rt-PA and independence. Conclusions Our data indicated that CS is the optimal measure to indicate the quality-of-care variation of acute ischemic stroke between hospitals.
Zanubrutinib monotherapy for relapsed or refractory non-germinal center diffuse large B-cell lymphoma
Authors: Yang Haiyan , Xiang Bing , Song Yuqin , Zhang Huilai , Zhao Weili , Zou Dehui , Lv Fangfang , Guo Wei , Liu Aichun , Li Caixia , Tan Ziwen , Liu Yang , Fu Lina , Guo Haiyi , Novotny William , Huang Jane , Li Yufu 
Published: October 2021

AbstractThe non-germinal center B-cell like (non-GCB) subtype of diffuse large B-cell lymphoma (DLBCL) has poor clinical outcomes. Bruton tyrosine kinase (BTK) inhibitors have established therapeutic activity in B-cell malignancies, with modest activity in DLBCL. Zanubrutinib, a potent and selective BTK inhibitor, was evaluated in patients with relapsed or refractory (R/R) non-GCB DLBCL. The BGB-3111-207 study (NCT03145064) was a multicenter single-arm phase 2 study. Patients received twice-daily oral zanubrutinib, 160 mg, until disease progression or unacceptable toxicity. The primary end point was the overall response rate (ORR). Secondary end points included progression-free survival (PFS) and duration of response (DOR). Overall survival (OS) was an exploratory end point. Forty-one patients were enrolled in China after having progressed or not responded to prior therapy. At data cutoff, 4 patients continued treatment with 37 discontinuations. The median follow-up was 6.8 months, the ORR was 29.3%, and the complete response rate was 17.1%. Median DOR, PFS, and OS were 4.5, 2.8, and 8.4 months, respectively. Adverse events (AEs) leading to treatment discontinuation were reported in 4 patients, and grade ≥ 3 AEs were reported in 48.8% of patients. Major hemorrhage, atrial fibrillation, and/or flutter were not observed. Zanubrutinib demonstrated modest antitumor activity in non-GCB DLBCL, like other BTK inhibitors, as well as a safety profile consistent with previous studies. Through retrospective biomarker testing, potential antitumor activity was observed in patients with both CD79B and MYD88 mutations, who have inferior outcomes to immunochemotherapy. Future studies of zanubrutinib in R/R non-GCB DLBCL will focus on developing mechanism-based treatment combinations and biomarker-driven patient selection.
Anti-CD25 radioimmunotherapy with BEAM autologous hematopoietic cell transplantation conditioning in Hodgkin lymphoma
Authors: Herrera Alex F. , Palmer Joycelynne , Adhikarla Vikram , Yamauchi Dave , Poku Erasmus K. , Bading James , Yazaki Paul , Dandapani Savita , Mei Matthew , Chen Robert , Cao Thai , Karras Nicole , McTague Pamela , Nademanee Auayporn , Popplewell Leslie , Sahebi Firoozeh , Shively John E. , Simpson Jennifer , Smith D. Lynne , Song Joo , Spielberger Ricardo , Tsai Ni-Chun , Thomas Sandra H. , Forman Stephen J. , Colcher David , Wu Anna M. , Wong Jeffrey , Smith Eileen 
Published: October 2021

AbstractHigh-risk relapsed or refractory (R/R) classical Hodgkin lymphoma (HL) is associated with poor outcomes after conventional salvage therapy and autologous hematopoietic cell transplantation (AHCT). Post-AHCT consolidation with brentuximab vedotin (BV) improves progression-free survival (PFS), but with increasing use of BV early in the treatment course, the utility of consolidation is unclear. CD25 is often expressed on Reed-Sternberg cells and in the tumor microenvironment in HL, and we hypothesized that the addition of 90Y-antiCD25 (aTac) to carmustine, etoposide, cytarabine, melphalan (BEAM) AHCT would be safe and result in a transplantation platform that is agnostic to prior HL-directed therapy. Twenty-five patients with high-risk R/R HL were enrolled in this phase 1 dose-escalation trial of aTac-BEAM. Following an imaging dose of 111In-antiCD25, 2 patients had altered biodistribution, and a third developed an unrelated catheter-associated bacteremia; therefore, 22 patients ultimately received therapeutic 90Y-aTac-BEAM AHCT. No dose-limiting toxicities were observed, and 0.6 mCi/kg was deemed the recommended phase 2 dose, the dose at which the heart wall would not receive &gt;2500 cGy. Toxicities and time to engraftment were similar to those observed with standard AHCT, though 95% of patients developed stomatitis (all grade 1-2 per Bearman toxicity scale). Seven relapses (32%) were observed, most commonly in patients with ≥3 risk factors. The estimated 5-year PFS and overall survival probabilities among 22 evaluable patients were 68% and 95%, respectively, and non-relapse mortality was 0%. aTac-BEAM AHCT was tolerable in patients with high-risk R/R HL, and we are further evaluating the efficacy of this approach in a phase 2 trial. This trial was registered at www.clinicaltrials.gov as #NCT01476839.
Assessment of romiplostim immunogenicity in pediatric patients in clinical trials and in a global postmarketing registry
Authors: Bowers Charles , Mytych Daniel T. , Lawrence Tatiana , Wang Kejia , Barger Troy E. , Eisen Melissa , Bennett Carolyn M. , Tarantino Michael D. 
Published: October 2021

Abstract
Development of first-generation thrombopoietins (TPOs) was halted due to antibodies that neutralized endogenous TPO, causing protracted thrombocytopenia in some patients. The second-generation TPO receptor agonist romiplostim, having no homology to TPO, was developed to circumvent potential immunogenicity. We examined the development of binding and neutralizing antibodies to romiplostim and TPO among pediatric patients with primary immune thrombocytopenia (ITP) in 5 clinical trials and a global postmarketing registry. In the trials, 25 of 280 (8.9%) patients developed anti-romiplostim binding antibodies. The first positive result was detected 67 weeks (median) after romiplostim treatment was initiated. The median romiplostim dose was 8 µg/kg, and the median platelet count was 87 × 109/L. Most patients who developed anti-romiplostim binding antibodies (18 of 25 [72%]) had ≥90% of platelet assessments showing a response. Anti-romiplostim neutralizing antibodies developed in 8 of 280 (2.9%) patients. The development of anti-romiplostim neutralizing antibodies was unrelated to the romiplostim dose, and most patients who developed the antibodies (7 of 8 [88%]) had platelet response. Nine of 279 (3.2%) patients developed anti-TPO binding antibodies, and 1 (0.4%) developed transient anti-TPO neutralizing antibodies. In 8 patients who developed anti-romiplostim neutralizing antibodies, no TPO cross-reactivity was observed. In the postmarketing registry, 3 of 19 (15.8%) patients developed anti-romiplostim binding antibodies; 1 (5.3%) patient developed anti-romiplostim neutralizing antibodies. These results suggest that immunogenicity to romiplostim occurs infrequently in pediatric patients with ITP and is generally not associated with loss of platelet response or other negative clinical sequelae.
GATA2 deficiency phenotype associated with tandem duplication of GATA2 and overexpression of GATA2-AS1
Authors: Singh Preeti , Heer Maninder , Resteu Anastasia , Mikulasova Aneta , Reza Mojgan , Largeaud Laëtitia , Dufrechou Stéphanie , Prade Naïs , Dickinson Rachel E. , Bustamante Jacinta , Neven Bénédicte , Bigley Venetia , Delabesse Eric , Rico Daniel , Pasquet Marlène , Collin Matthew 
Published: October 2021

Abstract
A 3-year-old girl of nonconsanguineous healthy parents presented with cervical and mediastinal lymphadenopathy due to Mycobacterium fortuitum infection. Routine blood analysis showed normal hemoglobin, neutrophils, and platelets but profound mononuclear cell deficiency (monocytes &lt; 0.1 × 109/L; B cells 78/μL; NK cells 48/μL). A 548 902-bp region containing GATA2 was sequenced by targeted capture and deep sequencing. This revealed a de novo 187-kb duplication of the entire GATA2 locus, containing a maternally inherited copy number variation deletion of 25 kb (GRCh37: esv2725896 and nsv513733). Many GATA2-associated phenotypes have been attributed to amino acid substitution, frameshift/deletion, loss of intronic enhancer function, or aberrant splicing. Gene deletion has been described, but other structural variation has not been reported in the germline configuration. In this case, duplication of the GATA2 locus was paradoxically associated with skewed diminished expression of GATA2 messenger RNA and loss of GATA2 protein. Chimeric RNA fusion transcripts were not detected. A possible mechanism involves increased transcription of the anti-sense long noncoding RNA GATA2-AS1 (RP11-472.220), which was increased several fold. This case further highlights that evaluation of the allele count is essential in any case of suspected GATA2-related syndrome.
TheCADM1tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11
Authors: Lafage-Pochitaloff Marina , Gerby Bastien , Baccini Véronique , Largeaud Laetitia , Fregona Vincent , Prade Naïs , Juvin Pierre-Yves , Jamrog Laura , Bories Pierre , Hébrard Sylvie , Lagarde Stéphanie , Mansat-De Mas Véronique , Dovey Oliver M. , Yusa Kosuke , Vassiliou George S. , Jansen Joop H. , Tekath Tobias , Rombaut David , Ameye Geneviève , Barin Carole , Bidet Audrey , Boudjarane John , Collonge-Rame Marie-Agnès , Gervais Carine , Ittel Antoine , Lefebvre Christine , Luquet Isabelle , Michaux Lucienne , Nadal Nathalie , Poirel Hélène A. , Radford-Weiss Isabelle , Ribourtout Bénédicte , Richebourg Steven , Struski Stéphanie , Terré Christine , Tigaud Isabelle , Penther Dominique , Eclache Virginie , Fontenay Michaela , Broccardo Cyril , Delabesse, Eric 
Published: October 2021

AbstractMyelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis leading to peripheral cytopenias and in a substantial proportion of cases to acute myeloid leukemia. The deletion of the long arm of chromosome 11, del(11q), is a rare but recurrent clonal event in MDS. Here, we detail the largest series of 113 cases of MDS and myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) harboring a del(11q) analyzed at clinical, cytological, cytogenetic, and molecular levels. Female predominance, a survival prognosis similar to other MDS, a low monocyte count, and dysmegakaryopoiesis were the specific clinical and cytological features of del(11q) MDS. In most cases, del(11q) was isolated, primary and interstitial encompassing the 11q22-23 region containing ATM, KMT2A, and CBL genes. The common deleted region at 11q23.2 is centered on an intergenic region between CADM1 (also known as Tumor Suppressor in Lung Cancer 1) and NXPE2. CADM1 was expressed in all myeloid cells analyzed in contrast to NXPE2. At the functional level, the deletion of Cadm1 in murine Lineage-Sca1+Kit+ cells modifies the lymphoid-to-myeloid ratio in bone marrow, although not altering their multilineage hematopoietic reconstitution potential after syngenic transplantation. Together with the frequent simultaneous deletions of KMT2A, ATM, and CBL and mutations of ASXL1, SF3B1, and CBL, we show that CADM1 may be important in the physiopathology of the del(11q) MDS, extending its role as tumor-suppressor gene from solid tumors to hematopoietic malignancies.
Non-coding RNA in raw and commercially processed milk and putative targets related to growth and immune-response
Authors: Shome S. , Jernigan R. L. , Beitz D. C. , Clark S. , Testroet E. D. 
Published: October 2021

Abstract
Background
Bovine milk contains extracellular vesicles (EVs) that play a role in cellular communication, acting in either an autocrine, paracrine, or an exocrine manner. The unique properties of the EVs protect the cargo against degradation. We profiled the ncRNAs (non-coding RNA) present in the EVs from seven dairy products - raw whole milk, heat-treated skim milk, homogenized heat-treated skim milk, pasteurized homogenized skim milk, pasteurized heavy whipping cream, sweet cream buttermilk and cultured buttermilk with four replicates each, obtained at different processing steps from a commercial dairy plant. EVs and their cargo were extracted by using a validated commercial kit that has been shown to be efficient and specific for EVs. Further, to find the annotation of ncRNAs, we probed bovine and other organism repositories(such as miRBase, miRTarBase, Ensemble) to find homolog ncRNA annotation in case the annotations of ncRNA are not available in Bos Taurus database.

Results
Specifically, 30 microRNAs (miRNAs), were isolated throughout all the seven milk samples, which later when annotated with their corresponding 1546 putative gene targets have functions associated with immune response and growth and development. This indicates the potential for these ncRNAs to beneficially support mammary health and growth for the cow as well as neonatal gut maturation. The most abundant miRNAs were bta-miR-125a and human homolog miR-718 based on the abundance values of read count obtained from the milk samples.bta-miR-125a is involved in host bacterial and viral immune response, and human homolog miR-718 is involved in the regulation of p53, VEGF, and IGF signaling pathways, respectively.
Sixty-two miRNAs were up-regulated and 121 miRNAs were down-regulated throughout all the milk samples when compared to raw whole milk. In addition, our study explored the putative roles of other ncRNAs which included 88 piRNAs (piwi-interacting RNA), 64 antisense RNAs, and 105 lincRNAs (long-intergenic ncRNAs) contained in the bovine exosomes.

Conclusion
Together, the results indicate that bovine milk contains significant numbers of ncRNAs with putative regulatory targets associated with immune- and developmental-functions important for neonatal bovine health, and that processing significantly affects the ncRNA expression values; but statistical testing of overall abundance(read counts) of all miRNA samples suggests abundance values aren’t much affected. This can be attributed to the breakage of exosomal vesicles during the processing stages. It is worth noting, however, that these gene regulatory targets are putative, and further evidence could be generated through experimental validation.
Are morbidity and mortality estimates from randomized controlled trials externally valid? A comparison of outcomes among infants enrolled into an RCT or a cohort study in Botswana
Authors: Thivalapill Neil , Lockman Shahin , Powis Kathleen , Zash Rebecca , Leidner Jean , Ajibola Gbolahan , Mmalane Mompati , Makhema Joseph , Shapiro Roger L. 
Published: October 2021

Abstract
Background
The external validity of the randomized controlled trial (RCT) refers to the extent to which the results of the RCT apply to the relevant, non-trial population and is impacted by its eligibility criteria, its organization, and its delivery of the intervention. Here, we compared the outcomes of mortality and hospitalization between an RCT and a cohort study that concurrently enrolled HIV-exposed uninfected (HEU) newborns in Botswana.

Methods
The Mpepu Study (the RCT) was a clinical trial which determined that co-trimoxazole (CTX) provided no survival benefit for HEUs, allowing both arms of the RCT to be used. The Maikaelelo study (the cohort study) was a prospective observational study that enrolled HEU newborns with telephone follow-up and no in-person visits. Rates of death and hospitalization in the pooled population, were modeled using cox-proportional hazards models for time to death or time to first hospitalization, with study setting (RCT vs. cohort study) as an independent variable. The causal effect of study setting on morbidity and mortality was obtained through a treatment effects approach.

Results
In total, 4,010 infants were included; 1,306 were enrolled into the cohort study and 2,704 were enrolled into the RCT. No significant differences in mortality were observed between the two study settings (HR: 1.28, 95% CI: 0.76, 2.13), but RCT participants had a lower risk of hospitalization (HR: 0.72, 95% CI: 0.58, 0.89) that decreased with age. However, RCT participants had a higher risk of hospitalization within the first six months of life. The causal risk difference in hospitalizations attributable to the RCT setting was -0.03 (95% CI: -0.05, -0.01).

Conclusions
Children in an RCT with rigorous application of national standard of care guidelines experienced a significantly lower risk of hospitalization than children participating in a cohort study that did not alter clinical care. Future research is needed to further investigate outcome disparities when real-world results fail to mirror those achieved in a clinical trial.
Trial registration
The Mpepu Trial was funded by the U.S. National Institutes of Health (No. NCT01229761) and the Maikaelelo Study was funded primarily by the U.S. Centers for Disease Control and Prevention (32AI007433-21).
Predictive P-score for treatment ranking in Bayesian network meta-analysis
Authors: Rosenberger Kristine J. , Duan Rui , Chen Yong , Lin Lifeng 
Published: October 2021

Abstract
Background
Network meta-analysis (NMA) is a widely used tool to compare multiple treatments by synthesizing different sources of evidence. Measures such as the surface under the cumulative ranking curve (SUCRA) and the P-score are increasingly used to quantify treatment ranking. They provide summary scores of treatments among the existing studies in an NMA. Clinicians are frequently interested in applying such evidence from the NMA to decision-making in the future. This prediction process needs to account for the heterogeneity between the existing studies in the NMA and a future study.

Methods
This article introduces the predictive P-score for informing treatment ranking in a future study via Bayesian models. Two NMAs were used to illustrate the proposed measure; the first assessed 4 treatment strategies for smoking cessation, and the second assessed treatments for all-grade treatment-related adverse events. For all treatments in both NMAs, we obtained their conventional frequentist P-scores, Bayesian P-scores, and predictive P-scores.

Results
In the two examples, the Bayesian P-scores were nearly identical to the corresponding frequentist P-scores for most treatments, while noticeable differences existed for some treatments, likely owing to the different assumptions made by the frequentist and Bayesian NMA models. Compared with the P-scores, the predictive P-scores generally had a trend to converge toward a common value of 0.5 due to the heterogeneity. The predictive P-scores’ numerical estimates and the associated plots of posterior distributions provided an intuitive way for clinicians to appraise treatments for new patients in a future study.

Conclusions
The proposed approach adapts the existing frequentist P-score to the Bayesian framework. The predictive P-score can help inform medical decision-making in future studies.
GoodReports: developing a website to help health researchers find and use reporting guidelines
Authors: Struthers Caroline , Harwood James , de Beyer Jennifer Anne , Dhiman Paula , Logullo Patricia , Schlüssel Michael 
Published: October 2021

Abstract
Background
Th EQUATOR Network improves the quality and transparency in health research, primarily by promoting awareness and use of reporting guidelines. In 2018, the UK EQUATOR Centre launched GoodReports.org, a website that helps authors find and use reporting guidelines. This paper describes the tool’s development so far. We describe user experience and behaviour of using GoodReports.org both inside and outside a journal manuscript submission process. We intend to use our findings to inform future development and testing of the tool.

Methods
We conducted a survey to collect data on user experience of the GoodReports website. We cross-checked a random sample of 100 manuscripts submitted to a partner journal to describe the level of agreement between the tool’s checklist recommendation and what we would have recommended. We compared the proportion of authors submitting a completed reporting checklist alongside their manuscripts between groups exposed or not exposed to the GoodReports tool. We also conducted a study comparing completeness of reporting of manuscript text before an author received a reporting guideline recommendation from GoodReports.org with the completeness of the text subsequently submitted to a partner journal.

Results
Seventy percent (423/599) of survey respondents rated GoodReports 8 or more out of 10 for usefulness, and 74% (198/267) said they had made changes to their manuscript after using the website. We agreed with the GoodReports reporting guideline recommendation in 84% (72/86) of cases. Of authors who completed the guideline finder questionnaire, 14% (10/69) failed to submit a completed checklist compared to 30% (41/136) who did not use the tool. Of the 69 authors who received a GoodReports reporting guideline recommendation, 20 manuscript pairs could be reviewed before and after use of GoodReports. Five included more information in their methods section after exposure to GoodReports. On average, authors reported 57% of necessary reporting items before completing a checklist on GoodReports.org and 60% after.

Conclusion
The data suggest that reporting guidance is needed early in the writing process, not at submission stage. We are developing GoodReports by adding more reporting guidelines and by creating editable article templates. We will test whether GoodReports users write more complete study reports in a randomised trial targeting researchers starting to write health research articles.