bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of pharmacological agents for the treatment of non-infectious scleritis: a systematic review protocol
Authors: Ingaralingam Sathana , Rauz Saaeha , Murray Philip I. , Barry Robert J. 
Published: March 2020

Abstract
Background
Non-infectious scleritis is a potentially sight-threatening condition in which the sclera, the white outer layer of the eye, becomes inflamed. Whilst scleritis can be infective, the majority of cases are due to non-infectious causes, often occurring in association with an underlying systemic autoimmune or auto-inflammatory condition. Thorough systemic work-up is crucial to identify disease aetiology and exclude infection; however, a significant proportion of disease remains idiopathic with the underlying cause unknown. Non-infectious scleritis is normally managed with systemic corticosteroid and immunosuppression, yet there is no widely agreed consensus on the most appropriate therapy, and no national or international guidelines exist for treatment of non-infectious scleritis.

Methods
Standard systematic review methodology will be used to identify, select and extract data from comparative studies of pharmacological interventions used to treat patients with non-infectious scleritis. Searches of bibliographic databases (Cochrane Library, MEDLINE, CINAHL and EMBASE) and clinical trial registers will be employed. No restrictions will be placed on language or date of publication. Non-English articles will be translated where necessary. The primary outcome of interest will be disease activity measured by reduction in scleritis grading according to standardised grading systems. Secondary outcomes will include change in best corrected visual acuity, reduction in concurrent dose of systemic corticosteroid, time to treatment failure, adverse events and health-related quality of life. Risk of bias assessment will be conducted appropriate to each study design. Study selection, data extraction and risk of bias assessment will be completed by two reviewers independently. Data will be presented in a table and a narrative synthesis will be undertaken. Meta-analysis will be performed where methodological and clinical homogeneity exists. Subgroup and sensitivity analysis will be undertaken if appropriate.

Discussion
Many studies have investigated the effectiveness of pharmacological agents used in the management of non-infectious scleritis. A systematic review is needed to collate and analyse this evidence. Findings of this systematic review will help guide ophthalmologists managing patients with non-infectious scleritis and may form the basis for evidence-based recommendations for future clinical practice and encourage standardisation of treatment protocols.

Systematic review registration
PROSPERO CRD42019125198
New shrinking iterative methods for infinite families of monotone operators in a Banach space, computational experiments and applications
Authors: Wei Li , Chen Rui , Zhang Yanan , Agarwal Ravi P. 
Published: March 2020

AbstractNew shrinking iterative algorithms for approximating common zeros of two infinite families of maximal monotone operators in a real uniformly convex and uniformly smooth Banach space are designed. Two steps of multiple choices can be made in the new iterative algorithms, two groups of interactive containment sets $C_{n}$Cn and $Q_{n}$Qn are constructed and computational errors are considered, which are different from the previous ones. Strong convergence theorems are proved under mild assumptions and some new proof techniques can be found. Computational experiments for some special cases are conducted to show the effectiveness of the iterative algorithms and meanwhile some inequalities are proved to guarantee the strong convergence. Moreover, the applications of the abstract results on convex minimization problems and variational inequalities are exemplified.
A framework for assessing 16S rRNA marker-gene survey data analysis methods using mixtures.
Authors: Olson Nathan D. , Kumar M. Senthil , Li Shan , Braccia Domenick J. , Hao Stephanie , Timp Winston , Salit Marc L. , Stine O. Colin , Bravo Hector Corrada 
Published: March 2020

Abstract
Background
There are a variety of bioinformatic pipelines and downstream analysis methods for analyzing 16S rRNA marker-gene surveys. However, appropriate assessment datasets and metrics are needed as there is limited guidance to decide between available analysis methods. Mixtures of environmental samples are useful for assessing analysis methods as one can evaluate methods based on calculated expected values using unmixed sample measurements and the mixture design. Previous studies have used mixtures of environmental samples to assess other sequencing methods such as RNAseq. But no studies have used mixtures of environmental to assess 16S rRNA sequencing.

Results
We developed a framework for assessing 16S rRNA sequencing analysis methods which utilizes a novel two-sample titration mixture dataset and metrics to evaluate qualitative and quantitative characteristics of count tables. Our qualitative assessment evaluates feature presence/absence exploiting features only present in unmixed samples or titrations by testing if random sampling can account for their observed relative abundance. Our quantitative assessment evaluates feature relative and differential abundance by comparing observed and expected values. We demonstrated the framework by evaluating count tables generated with three commonly used bioinformatic pipelines: (i) DADA2 a sequence inference method, (ii) Mothur a de novo clustering method, and (iii) QIIME an open-reference clustering method. The qualitative assessment results indicated that the majority of Mothur and QIIME features only present in unmixed samples or titrations were accounted for by random sampling alone, but this was not the case for DADA2 features. Combined with count table sparsity (proportion of zero-valued cells in a count table), these results indicate DADA2 has a higher false-negative rate whereas Mothur and QIIME have higher false-positive rates. The quantitative assessment results indicated the observed relative abundance and differential abundance values were consistent with expected values for all three pipelines.

Conclusions
We developed a novel framework for assessing 16S rRNA marker-gene survey methods and demonstrated the framework by evaluating count tables generated with three bioinformatic pipelines. This framework is a valuable community resource for assessing 16S rRNA marker-gene survey bioinformatic methods and will help scientists identify appropriate analysis methods for their marker-gene surveys.
Image quality analysis of 44Sc on two preclinical PET scanners: a comparison to 68Ga
Authors: Rosar Florian , Buchholz Hans-Georg , Michels Sebastian , Hoffmann Manuela A. , Piel Markus , Waldmann Christopher M. , Rösch Frank , Reuss Stefan , Schreckenberger Mathias 
Published: March 2020

Abstract
Background
44Sc has been increasingly investigated as a potential alternative to 68Ga in the development of tracers for positron emission tomography (PET). The lower mean positron energy of 44Sc (0.63 MeV) compared to 68Ga (0.83 MeV) can result in better spatial image resolutions. However, high-energy γ-rays (1157 keV) are emitted at high rates (99.9%) during 44Sc decay, which can reduce image quality. Therefore, we investigated the impact of these physical properties and performed an unbiased performance evaluation of 44Sc and 68Ga with different imaging phantoms (image quality phantom, Derenzo phantom, and three-rod phantom) on two preclinical PET scanners (Mediso nanoScan PET/MRI, Siemens microPET Focus 120).

Results
Despite the presence of high-energy γ-rays in 44Sc decay, a higher image resolution of small structures was observed with 44Sc when compared to 68Ga. Structures as small as 1.3 mm using the Mediso system, and as small as 1.0 mm using the Siemens system, could be visualized and analyzed by calculating full width at half maximum. Full widths at half maxima were similar for both isotopes. For image quality comparison, we calculated recovery coefficients in 1–5 mm rods and spillover ratios in either air, water, or bone-equivalent material (Teflon). Recovery coefficients for 44Sc were significantly higher than those for 68Ga. Despite the lower positron energy, 44Sc-derived spillover ratio (SOR) values were similar or slightly higher to 68Ga-derived SOR values. This may be attributed to the higher background caused by the additional γ-rays. On the Siemens system, an overestimation of scatter correction in the central part of the phantom was observed causing a virtual disappearance of spillover inside the three-rod phantom.

Conclusion
Based on these findings, 44Sc appears to be a suitable alternative to 68Ga. The superior image resolution makes it an especially strong competitor in preclinical settings. The additional γ-emissions have a small impact on the imaging resolution but cause higher background noises and can effect an overestimation of scatter correction, depending on the PET system and phantom.
Single-site 123I-FP-CIT reference values from individuals with non-degenerative parkinsonism—comparison with values from healthy volunteers
Authors: Fahmi Rachid , Platsch Günther , Sadr Alexandre Bani , Gouttard Sylvain , Thobois Stephane , Zuehlsdorff Sven , Scheiber Christian 
Published: March 2020

Abstract
Purpose
Iodine 123-radiolabeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) SPECT can be performed to distinguish degenerative forms of movement disorders/parkinsonism/tremor from other entities such as idiopathic tremor or drug-induced parkinsonism. For equivocal cases, semi-quantification and comparison to reference values are a necessary addition to visual interpretation of 123I-FP-CIT scans. To overcome the challenges of multi-center recruitment and scanning of healthy volunteers, we generated 123I-FP-CIT reference values from individuals with various neurological conditions but without dopaminergic degeneration, scanned at a single center on the same SPECT-CT system following the same protocol, and compared them to references from a multi-center database built using healthy volunteers’ data.

Methods
From a cohort of 1884 patients, we identified 237 subjects (120 men, 117 women, age range 16–88 years) through a two-stage selection process. Every patient had a final clinical diagnosis after a mean follow-up of 4.8 ± 1.3 years. Images were reconstructed using (1) Flash3D with scatter and CT-based attenuation corrections (AC) and (2) filtered back projection with Chang AC. Volume-of-interest analysis was performed using a commercial software to calculate specific binding ratios (SBRs), caudate-to-putamen ratios, and asymmetry values on different striatal regions. Generated reference values were assessed according to age and gender and compared with those from the ENC-DAT study, and their robustness was tested against a cohort of patients with different diagnoses.

Results
Age had a significant negative linear effect on all SBRs. Overall, the reduction rate per decade in SBR was between 3.80 and 5.70%. Women had greater SBRs than men, but this gender difference was only statistically significant for the Flash3D database. Linear regression was used to correct for age-dependency of SBRs and to allow comparisons to age-matched reference values and “normality” limits. Generated regression parameters and their 95% confidence intervals (CIs) were comparable to corresponding European Normal Control Database of DaTscan (ENC-DAT) results. For example, 95% CI mean slope for the striatum in women is − 0.015 ([− 0.019, − 0.011]) for the Flash3D database versus − 0.015 ([− 0.021, − 0.009]) for ENC-DAT. Caudate-to-putamen ratios and asymmetries were not influenced by age or gender.

Conclusion
The generated 123I-FP-CIT references values have similar age-related distribution, with no increase in variance due to comorbidities when compared to values from a multi-center study with healthy volunteers. This makes it possible for sites to build their 123I-FP-CIT references from scans acquired during routine clinical practice.
Phase Ib study combining ibrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with CD20-positive B-cell non-Hodgkin lymphoma (NHL).
Authors: Younes Anas , Flinn Ian , Berdeja Jesus G. , Friedberg Jonathan W. , Alberti Sara , Thieblemont Catherine , Morschhauser Franck , Hellemans Peter , Hall Brett , Smit Johan , Skee Donna , de Vries Ronald , Todorovic Marija , Khan Imran , Fourneau Nele , Oki Yasuhiro 
Published: March 2020

8502 Background: Ibrutinib, a first-in-class oral Bruton’s tyrosine kinase inhibitor, has demonstrated single-agent activity in a variety of relapsed or refractory B-cell malignancies with limited toxicity, making it an appropriate drug to combine with standard R-CHOP chemotherapy in patients with previously untreated NHL. Methods: Patients received oral daily dose of ibrutinib (280, 420, or 560 mg) in combination with standard doses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, and vincristine on day 1, and prednisone on days 1 through 5 of each 21-day cycle for up to 6 cycles). The primary objective was to determine the recommended phase 2 dose (RP2D) of ibrutinib in combination with standard R-CHOP (IR-CHOP). The secondary objectives were to assess safety, overall response rate, pharmacokinetics, and pharmacodynamic biomarkers. Results: Seventeen patients (7, 4, and 6 in increasing ibrutinib doses) were enrolled: 59% male, median age 65 (range 46-81) years, diffuse large B-cell lymphoma 47%, mantle cell lymphoma 29% and follicular lymphoma 24%. In the 280 mg cohort, 2 patients had dose-limiting toxicity (DLT): 1 with transient syncope and 1 with periorbital cellulitis; at 560 mg, 1 patient had gastritis (grade 2). The RP2D was established at 560 mg ibrutinib. The most common (≥ 20% of patients) adverse events (AEs) were neutropenia (77%), thrombocytopenia (65%), vomiting (59%), anemia (53%), nausea (47%), fatigue (35%), headache (29%), constipation (24%), diarrhea (24%), and dizziness (24%). To date, 6 patients completed 6 cycles of treatment, and 2 patients discontinued treatment (1 due to noncompliance with the study drug and 1 due to non-DLT AE). At the time of this analysis, of the 10 patients had at least one post baseline tumor, the overall response rate was 100% (7 complete and 3 partial responses). Conclusions: The combination of IR-CHOP has an acceptable safety profile. No new toxicities were noted with adding ibrutinib to R-CHOP. An expansion cohort 560 mg ibrutinib (RP2D) is being opened to further explore the safety and efficacy of IR-CHOP in patients with newly diagnosed diffuse large B-cell lymphomas. Clinical trial information: NCT01569750.
Utility of post-therapy surveillance scans in DLBCL.
Authors: Thompson Carrie A. , Maurer Matthew J. , Ghesquieres Herve , Macon William R , Habermann Thomas Matthew , Witzig Thomas E. , Cerhan James Robert , Link Brian K. 
Published: March 2020

8504 Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma. The optimal follow-up strategy for patients (pts) in remission is not clear. The goal of this study is to determine the utility of surveillance scans in a large, prospective, multi-institutional cohort of DLBCL pts. Methods: Patients were enrolled in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER), a prospective cohort of newly diagnosed lymphoma pts. All pts were followed for events including relapse, re-treatment, and death with events verified by medical records. Patients eligible for this study had biopsy proven DLBCL and were treated with anthracycline based immunochemotherapy (IC). Initial and post-treatment management was per treating physician. Medical records were re-reviewed in pts with events for clinical details at relapse and relationship to planned follow-up visits and surveillance scans. Results: 644 pts with DLBCL treated with IC were enrolled in MER from 2002-2009. Median age was 63 years (range 18-92), 54% were men, and median f/u was 59 months (range 8-116). 537 pts entered post-treatment observation; 109 (20%) of the 537 pts relapsed and 41 died from other causes. 42% of relapses were in the first 12 months following diagnosis, 27% between 12-24 months, and 31% >24 months. In the 109 who relapsed, 62% of pts (62/100, 9 unknown) presented to their physician earlier than a planned follow-up visit due to symptoms. At the time of relapse, 68% were symptomatic, 42% of pts had abnormal physical exam, and 55% had elevated LDH; 87% of pts had ≥1 of these features. Of the 38 pts with relapse detected at a planned visit, 26 had clinical features of relapse and 12 pts had relapse detected solely by planned surveillance scan; 4 pts had relapse of low-grade or other subtype and 8 had DLBCL relapse (4 of whom had equivocal/positive PET at the end of IC). Thus, surveillance scanning detected DLBCL relapse prior to clinical manifestations in only 8/537 pts (1.5%) observed post DLBCL therapy. Conclusions: The vast majority of DLBCL relapses occur outside of planned follow-up visits and are accompanied by symptoms, physical exam, or laboratory abnormalities. Routine surveillance scans post-therapy add little to detection of DLBCL relapse.
Definition of a high-risk population among patients with AL amyloidosis not undergoing autologous stem cell transplantation using bone marrow plasmacytosis and the presence of CRAB.
Authors: Kourelis Taxiarchis , Gertz Morie , Lacy Martha , Buadi Francis , Hayman Suzanne R. , Kumar Shaji , Zeldenrust Steven R. , Leung Nelson , Kyle Robert A. , Russell Stephen , Dingli David , Lust John Anthony , Lin Yi , Kapoor Prashant , Rajkumar Vincent , Dispenzieri Angela 
Published: March 2020

8516 Background: There is consensus that light chain amyloidosis (AL) patients with CRAB criteria (abnormal calcium or renal function, anemia or lytic bone lesions) also have multiple myeloma (MM). These patients are typically excluded from AL trials; however, AL patients with >= 10% bone marrow plasma cells (BMPC) in the absence of CRAB are included in trials along with AL with < 10% BMPC. We postulated that the currently used dichotomy may be incorrect and examined the spectrum of AL with and without MM. Methods: We identified 1,272 patients with AL seen within 90 days of diagnosis, between January 1, 2000, and December 31, 2010. We defined the population of patients with coexisting MM based on the existence of CRAB (AL-CRAB-MM). Patients without CRAB were divided into two groups, AL-only (<10% BMPC) and AL-PC-MM (>=10% BMPC). Results: Among the 1,272 patients, 117 (9%) had AL-CRAB-MM, 476 (37%) had AL-PC-MM, and 679 (53%) had AL only. Their respective median overall survivals (OS) were 16.2, 15.8, and 28.4 months (p<0.0001). Autologous stem cell transplant (ASCT) was performed in 203 (30%), 138 (29%) and 23 (20%) patients respectively. Since the outcomes of AL-CRAB-MM and AL-PC-MM were similar, they were pooled for univariate and multivariate analyses. On multivariate analysis, AL-CRAB-MM and AL-PC-MM retained negative prognostic value independent of age, cardiac stage, prior autologous stem cell transplant (ASCT), beta 2 microglobulin, and dFLC. We next considered whether patients received ASCT as part of their treatment. For those patients who never received ASCT, the 5-year OS were 19%, 14%, and 31%, p<0.001, for AL-CRAB-MM, AL-PC-MM, and AL only respectively. In contrast, for those patients who received ASCT, the respective 5-year OS were 46%, 56%, and 73%, p<0.001. Conclusions: AL patients with >=10% BMPCs have a poor prognosis similar to patients with AL-CRAB-MM and should therefore be considered as AL with MM.
Updated results of a phase I first-in-human study of the BCL-2 inhibitor ABT-199 (GDC-0199) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL).
Authors: Davids Matthew Steven , Seymour John Francis , Gerecitano John F. , Kahl Brad S. , Pagel John M. , Wierda William G. , Anderson Mary Ann , Darden David E. , Nolan Cathy E. , Gressick Lori A. , Yang Jianning , Chyla Brenda J. , Busman Todd A. , Graham Alison M. , Cerri Elisa , Enschede Sari H. , Humerickhouse Rod A. , Roberts Andrew W 
Published: March 2020

8520 Background: BCL-2 is highly expressed in NHL, including mantle cell lymphoma (MCL), and is a promising therapeutic target as it is involved in NHL pathogenesis and mediates resistance to many cytotoxics. ABT-199 is a second generation inhibitor with 500-fold higher affinity for BCL-2 (Ki<0.10 nM) than BCL-XL (Ki=48 nM). Methods: Objectives of this Ph 1 dose-escalation study include evaluations of safety, pharmacokinetics and preliminary efficacy in patients (pts) with relapsed or refractory (R/R) NHL. A single oral dose (50-400 mg) was administered followed by 6 days off drug prior to the initiation of continuous once daily dosing. Due to concerns of potential tumor lysis syndrome (TLS), a 2 to 3 wk lead-in period with step-wise escalation to the target cohort dose was implemented. Dose cohorts up to 900 mg have been evaluated to date. Results: As of January 2013, 31 pts have been enrolled (median age 68 y (range 35-85); 20 males; median prior therapies 3 (range 1-7). 13 (42%) and 4 (13%) had bulky adenopathy (>5 and >10 cm, respectively). The most common AEs (≥15% of patients) were nausea (36%), diarrhea (26%), dyspepsia, vomiting, fatigue, pyrexia and cough (16% each). Gr 3/4 AEs occurring in >1 patient were anemia, neutropenia (4 pts each), and febrile neutropenia (2 pts). Two of 14 pts in cohort 5 experienced DLTs at the target dose of 600 mg: Gr 3 febrile neutropenia and Gr 4 neutropenia. Although Gr 3/4 thrombocytopenia was observed in 3 pts, it was not dose dependent. Gr 3 TLS was seen after the initial dose in 1 pt with very bulky MCL (>10 cm). With a median follow-up of 5 months (range 0.5-15), 17 have discontinued: 13 due to PD, 2 due to AEs and 2 who received a BMT. Of the 29 pts evaluable for efficacy, the overall best response rate was 55% with 1 DLBCL pt achieving a CR and 15 (52%) a PR (8/8 MCL, 3/3 Waldenstrom macroglobulinemia, 2/7 follicular lymphoma and 2/7 DLBCL pts). Conclusions: ABT-199 is highly active in R/R NHL, particularly in MCL. Additional dosing and scheduling modifications are currently being explored to optimize the efficacy/safety profile of this active new agent. ABT-199 warrants further single-agent and combination trials in NHL. Clinical trial information: NCT01328626.