bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inter-pathologist Agreement on Structured Histopathology Reporting in Chronic Rhinosinusitis
Authors: Ganti Ashwin , Brown Hannah J. , Gattuso Paolo , Ghai Ritu , Papagiannopoulos Peter , Batra Pete S. , Tajudeen Bobby A. 
Published: January 2021

Background: Structured histopathology reporting is increasingly being utilized in rhinology to characterize endotypes in chronic rhinosinusitis and guide management decisions after sinus surgery. Objective: The goal of this investigation is to evaluate inter-observer agreement in structured histopathology reporting. Methods: Two experienced head and neck pathologists independently compiled structured histopathology reports for tissue samples collected during functional endoscopic sinus surgery. Cohen’s standard kappa (κ) coefficients were calculated for each histopathologic variable to assess inter-pathologist agreement. Results: A total of 92 cases were analyzed. Substantial inter-pathologist agreement was reached on tissue eosinophil count (κ = 0.64, P < .001), the presence of eosinophil aggregates (κ = 0.62, P < .001), and the presence of fungal elements (κ = 0.74, P < .001). There was moderate agreement on the degree of inflammation (κ = 0.56, P < .001) and the presence of squamous metaplasia (κ = 0.46, P < .001). There was fair agreement on the presence of neutrophil infiltrates (κ = 0.33, P < .001), the presence of hyperplastic changes (κ = 0.40, P < .001), and the presence of fibrosis (κ = 0.24, P = .022). There was only slight agreement on the degree of subepithelial edema (κ = 0.20, P = .008). The κ coefficients for basement membrane thickening and mucosal ulceration were not statistically significant. Conclusion: High inter-pathologist agreement was demonstrated for several salient histopathologic variables, including tissue eosinophil count and the presence of eosinophil aggregates. However, refining the definitions of certain histopathologic variables may improve the reproducibility of structured histopathology reporting.
Determination of a Beckman Coulter AU turbidometric method-specific caeruloplasmin reference interval
Authors: Kaye Olivia E , Cook Paul 
Published: January 2021

Background Method-dependent variation of caeruloplasmin measurement is significant and necessitates the requirement for assay-specific reference intervals. Local determination becomes necessary in the absence of suitable published or manufacturer-quoted reference intervals. Methods Applicability of the Beckman Coulter AU-quoted reference interval was determined by assay of 20 surplus serum samples from patients attending the medical renal stones clinic at University Hospital Southampton. Subsequently, 60 additional samples were collected for local reference interval determination. Samples were analysed for caeruloplasmin using the Beckman Coulter AU turbidometric kit on an AU680 analyser. Outliers were removed, and non-parametric rank analysis of the results was performed. Results The Beckman Coulter-quoted reference interval of 200–600 mg/L was unsuitable with 40% of the verification samples falling below 200 mg/L. A caeruloplasmin reference interval of 150–320 mg/L was established. Conclusion Users should be aware the quoted Beckman Coulter AU turbidometric reference interval may not be appropriate. We have established a method-specific adult reference interval for routine use.
Electron microscopy study of 496 cases of lupus nephritis: A single-center experience
Authors: Bagheri Bahar , Owji Seyed Mohammad , Torabinezhad Simin , Raeisi Shahraki Hadi , Kamalinia Amirhossein , Owji Seyed Hossein , Dehghani Farshad 
Published: January 2021

Introduction Renal involvement is seen in about 40-82% of systemic lupus erythematosus (SLE) Asian patients. The exact diagnosis and classification of lupus nephritis are important for treatment and prognosis. This study aimed to investigate the value of electron microscopy (EM) in the diagnosis and classification of lupus nephritis compared with light microscopy. Method In this cross-sectional referral-center 16-year study of lupus nephritis, the final diagnosis was based on the EM study. Primary light microscopy findings were compared with EM diagnosis. Moreover, Immunofluorescence patterns distribution was assessed. Results From 496 patients diagnosed with lupus nephritis based on EM, 225(45.4%) of patients were categorized in class IV, followed by 98(19.7%), 93(18.8%), 46(9.3%), and 14(2.8%) who were categorized into classes of II, III, V, and VI respectively. Only 1(0.2%) patient belonged to class I, and 19(3.8%) cases were diagnosed with mixed two classes. Using EM was essential for diagnosing 25.6% of cases taking the correct classification by light microscopy into account; however, disregarding correct classification, this could change to a 7.4% contribution rate of EM. The most common cause of misdiagnosis, disregarding incorrect classification, was inadequate or wrong tissue. Positive associations were detected between tubular atrophy and interstitial fibrosis of both electron and light microscopy with different classes (P < 0.001). Conclusion While light microscopy is highly accurate for diagnosing lupus nephritis regardless of correct classification, EM contributes substantially to the correct classification of lupus nephritis types.
Macular fibrosis in Coats’ disease demonstrated by Optical Coherence Tomography Angiography – new data toward pathophysiology
Authors: Chwiejczak Katarzyna , Biswas Susmito , Tsamis Emmanouil , Siso-Fuertes Irene , Kasbia Shakti , Stanga Paulo E 
Published: January 2021

Purpose: To analyze if Segmented Swept-Source Optical Coherence Tomography Angiography (SS OCT-A) can provide additional information on morphology and pathophysiology of macular fibrosis in Coats’ patients. Methods: A consecutive case series of three male patients (5, 7 and 15 years old), with Coats’ disease-related macular fibrosis (stage 2b-2 patients, 3b-1 patient). SS OCT-A 3×3 mm macular scans of affected eyes were performed. Results: In all three cases the inner portion of macular fibrosis displayed a dense network of vessels, continuing into deeper layers. This structure was similar to that observed in retinal angiomatous proliferations (RAP). There was associated loss of the foveal avascular zone. In one case we observed evolution of the lesion. Conclusion: SS-OCT imaging of macular fibrosis in Coats’ disease reveals a distinct intralesional vascular structure with elements resembling RAP, probably developing as a secondary process.
Accuracy of apparent diffusion coefficient in differentiation of glioblastoma from metastasis
Authors: Beig Zali Sanaz , Alinezhad Farbod , Ranjkesh Mahnaz , Daghighi Mohammad H , Poureisa Masoud 
Published: January 2021

Background Brain metastasis and glioblastoma multiforme are two of the most common malignant brain neoplasms. There are many difficulties in distinguishing these diseases from each other. Purpose The purpose of this study was to determine whether the mean apparent diffusion coefficient and absolute standard deviation derived from apparent diffusion coefficient measurements can be used to differentiate glioblastoma multiforme from brain metastasis based on cellularity levels. Material and methods Magnetic resonance images of 34 patients with histologically verified brain tumors were evaluated retrospectively. Apparent diffusion coefficient and standard deviation values were measured in the enhancing tumor, peritumoral region, and contralateral healthy white matter. Then, to determine whether there was a statistical difference between brain metastasis and glioblastoma multiforme, we analyzed different variables between the two groups. Results Neither mean apparent diffusion coefficient values and ratios nor standard deviation values and ratios were significantly different between glioblastoma multiforme and brain metastasis. Receiver operating characteristic curve analysis of the logistic model with backward stepwise feature selection yielded an area under the curve of 0.77, a specificity of 84%, a sensitivity of 67%, a positive predictive value of 83.33%, and a negative predictive value of 78.26% for distinguishing between glioblastoma multiforme and brain metastasis. The absolute standard deviation and standard deviation ratios were significantly higher in the peritumoral edema compared to the tumor region in each case. Conclusion Apparent diffusion coefficient values and ratios, as well as standard deviation values and ratios in peritumoral edema, cannot be used to differentiate edema with infiltration of tumor cells from vasogenic edema. However, standard deviation values could successfully characterize areas of peritumoral edema from the tumoral region in each case.
Hrabákite, Ni9PbSbS8, a new member of the hauchecornite group from Příbram, Czech Republic
Authors: Sejkora Jiří , Škácha Pavel , Plášil Jakub , Dolníček Zdeněk , Ulmanová Jana 
Published: January 2021

AbstractThe new mineral hrabákite (IMA2020-034) was found in siderite–sphalerite gangue with minor dolomite–ankerite at the dump of shaft No. 9, one of the mines in the abandoned Příbram uranium and base-metal district, central Bohemia, Czech Republic. Hrabákite is associated with Pb-rich tučekite, Hg-rich silver, stephanite, nickeline, millerite, gersdorffite, sphalerite and galena. The new mineral occurs as rare prismatic crystals up to 120 μm in size and allotriomorphic grains. Hrabákite is grey with a brownish tint. Mohs hardness isca. 5–6; the calculated density is 6.37 g.cm–3. In reflected light, hrabákite is grey with a brown hue. Bireflectance is weak and pleochroism was not observed. Anisotropy under crossed polars is very weak (brownish tints) to absent. Internal reflections were not observed. Reflectance values of hrabákite in air (Rmin–Rmax, %) are: 39.6–42.5 at 470 nm, 45.0–47.5 at 546 nm, 46.9–49.2 at 589 nm and 48.9–51.2 at 650 nm). The empirical formula for hrabákite, based on electron-microprobe analyses (n= 11), is (Ni8.91Co0.09Fe0.03)9.03(Pb0.94Hg0.04)0.98(Sb0.91As0.08)0.99S7.99. The ideal formula is Ni9PbSbS8, which requires Ni 47.44, Pb 18.60, Sb 10.93 and S 23.03, total of 100.00 wt.%. Hrabákite is tetragonal,P4/mmm,a= 7.3085(4),c= 5.3969(3) Å, withV= 288.27(3) Å3andZ= 1. The strongest reflections of the calculated powder X-ray diffraction pattern [d, Å (I)(hkl)] are: 3.6543(57)(200); 3.2685(68)(210); 2.7957(100)(211); 2.3920(87)(112); 2.3112(78)(310); 1.8663(74)(222); and 1.8083(71)(302). According to the single-crystal X-ray diffraction data (Rint= 0.0218), the unit cell of hrabákite is undoubtedly similar to the cell reported for tučekite. The structure contains four metal cation sites, two Sb (Sb1 dominated by Pb2+) and two Ni (with minor Co2+content) sites. The close similarity in metrics between hrabákite and tučekite is due to similar bond lengths of Pb–S and Sb–S pairs. Hrabákite is named after Josef Hrabák, the former professor of the Příbram Mining College.
New arsenate minerals from the Arsenatnaya fumarole, Tolbachik volcano, Kamchatka, Russia. XV. Calciojohillerite, NaCaMgMg2(AsO4)3, a member of the alluaudite group
Authors: Pekov Igor V. , Koshlyakova Natalia N. , Agakhanov Atali A. , Zubkova Natalia V. , Belakovskiy Dmitry I. , Vigasina Marina F. , Turchkova Anna G. , Sidorov Evgeny G. , Pushcharovsky Dmitry Yu. 
Published: January 2021

AbstractThe new alluaudite-group mineral calciojohillerite is one of the major arsenates in sublimates of the Arsenatnaya fumarole at the Second scoria cone of the Northern Breakthrough of the Great Tolbachik Fissure Eruption, Tolbachik volcano, Kamchatka, Russia. In middle zones of the fumarole, calciojohillerite is associated with hematite, tenorite, johillerite, nickenichite, bradaczekite, badalovite, tilasite, lammerite, ericlaxmanite, aphthitalite-group sulfates, langbeinite, calciolangbeinite, anhydrite, sanidine, fluorophlogopite, fluoborite, cassiterite, pseudobrookite, rutile, sylvite and halite. In deep zones it occurs in association with anhydrite, diopside, hematite, svabite, berzeliite, schäferite, forsterite, magnesioferrite, ludwigite, rhabdoborite-group fluoroborates, powellite, baryte, fluorapatite, udinaite, arsenudinaite and paraberzeliite. Calciojohillerite forms prismatic crystals up to 1 cm long, their aggregates and crystal crusts up to 0.5 m2. It is transparent, colourless, pale green, pale yellow, light blue, pale lilac or pink, with vitreous lustre. The mineral is brittle, with imperfect cleavage. The Mohs hardness is 3½. Dcalc is 3.915 g cm–3. Calciojohillerite is optically biaxial (–), α = 1.719(3), β = γ = 1.732(3); 2Vmeas. = 15(10)°. Chemical composition (wt.%, electron-microprobe; holotype) is: Na2O 7.32, K2O 0.10, CaO 6.82, MgO 20.31, MnO 0.68, CuO 0.27, ZnO 0.02, Al2O3 0.56, Fe2O3 3.53, TiO2 0.01, SiO2 0.03, P2O5 1.25, V2O5 0.10, As2O5 58.77, SO3 0.13, total 99.90. The empirical formula based on 12 O atoms is (Na1.30K0.01Ca0.67Mg2.78Mn0.05Cu0.02Al0.06Fe3+0.24)Σ5.13(As2.83P0.10S0.01V0.01)Σ2.95O12. Calciojohillerite is monoclinic, C2/c, a = 11.8405(3), b = 12.7836(2), c = 6.69165(16) Å, β = 112.425(3)°, V = 936.29(4) Å3 and Z = 4. The crystal structure was solved from single-crystal X-ray diffraction data, R1 = 0.0227. Calciojohillerite is isostructural with other alluaudite-group minerals. Its simplified crystal chemical formula is A(1)CaA(1)′□A(2)□A(2)′NaM(1)MgM(2)Mg2(AsO4)3 (□ = vacancy). The idealised formula is NaCaMg3(AsO4)3, or, according to the nomenclature of alluaudite-group arsenates, NaCaMgMg2(AsO4)3. Calciojohillerite is named as an analogue of johillerite NaCu2+MgMg2(AsO4)3 with species-defining Ca instead of Cu in the ideal formula.
The use of luspatercept for thalassemia in adults
Authors: Cappellini Maria Domenica , Taher Ali T. 
Published: January 2021

AbstractLuspatercept is an activin receptor ligand trap that has been shown to enhance late-stage erythropoiesis in animal models of β-thalassemia. A multicenter, international, phase 2 dose-finding study was initiated in adult patients with β-thalassemia, either non–transfusion-dependent thalassemia (NTDT) or transfusion-dependent thalassemia (TDT). Positive results of the phase 2 study paved the way to a randomized phase 3 clinical trial (BELIEVE) to assess the efficacy and safety of luspatercept. The BELIEVE trial is a randomized, double-blind, placebo-controlled phase 3 trial. Three hundred thirty-six patients aged ≥18 years with TDT (regularly transfused, 6-20 red blood cell units within 24 weeks before randomization) were included in the trial. Patients received luspatercept or placebo subcutaneously every 21 days for ≥48 weeks and best supportive care. Forty-eight of 224 patients (21.4%) in the luspatercept group achieved the primary end points (≥33% reduction in transfusion burden) compared with those in the placebo group (4.5%; P &lt; .001). Moreover, more patients had a ≥33% reduction in transfusion burden during any rolling 12-week interval (70.5% vs 29.5%) or any 24-week interval (41.1% vs 2.7%) with luspatercept than with the placebo. Transfusion independence was achieved by 11% of patients in the luspatercept group. Transient adverse events were more frequent with luspatercept than with placebo, but were manageable. Luspatercept was approved by the US Food and Drug Administration in 2019 and by the European Medicines Agency in 2020. The luspatercept trial is registered on www.clinicaltrials.gov at #NCT01749540 and the BELIEVE trial at #NCT02604433.
Overcoming resistance to targeted therapies in chronic lymphocytic leukemia
Authors: Skånland Sigrid S. , Mato Anthony R. 
Published: January 2021

Abstract
Insight into the critical role of B-cell receptor signaling for the pathogenesis of chronic lymphocytic leukemia (CLL) led to the development of targeted therapies directed at key regulators of cell survival. Agents targeting B-cell lymphoma-2 protein, Bruton’s tyrosine kinase (BTK), and phosphatidylinositol 3-kinase are approved for treatment of CLL, and have significantly improved the disease management. Nevertheless, acquired resistance to the targeted therapies is a challenge still to be resolved. The mechanisms underlying resistance are becoming clearer, and include secondary mutations within the drug target and activation of bypass pathways. This knowledge has allowed development of strategies to prevent and overcome treatment resistance. Approaches to prevent resistance include targeting bypass mechanisms by combination therapies, temporally sequencing of therapies, improved clinical trial designs, and real-time monitoring of patient response. A rational design of drug sequencing may secure effective treatment options at the relapsed setting. Next-generation inhibitors and bispecific antibodies have the potential to overcome resistance to the BTK inhibitor ibrutinib. Immunotherapy, including chimeric antigen receptor-modified T-cell therapy, is explored for relapsed CLL. Here, recent advances that have contributed to the understanding of resistance to targeted therapies in CLL are discussed. Strategies for managing resistance are reviewed, including translational, real-world, and clinical perspectives.
A-to-I editing of miR-200b-3p in airway cells is associated with moderate-to-severe asthma
Authors: Magnaye Kevin M. , Naughton Katherine A. , Huffman Janel , Hogarth D. Kyle , Naureckas Edward T. , White Steven R. , Ober Carole 
Published: January 2021

BackgroundAsthma is a chronic lung disease characterised by persistent airway inflammation. Altered microRNA (miRNA)-mediated gene silencing in bronchial epithelial cells (BECs) has been reported in asthma, yet adenosine deaminase acting on RNA (ADAR)-mediated miRNA editing in asthma remains unexplored.MethodsWe first identified adenosine to inosine (A-to-I) edited sites in miRNAs in BECs from 142 adult asthma cases and controls. A-to-I edited sites were tested for associations with asthma severity and clinical measures of asthma. Paired RNA sequencing data were used to perform pathway enrichments and test for associations with bioinformatically predicted target genes of the unedited and edited miRNAs.ResultsOf 19 A-to-I edited sites detected in these miRNAs, one site at position 5 of miR-200b-3p was edited less frequently in cases compared with controls (pcorrected=0.013), and especially compared with cases with moderate (pcorrected=0.029) and severe (pcorrected=3.9×10−4), but not mild (pcorrected=0.38), asthma. Bioinformatic prediction revealed 232 target genes of the edited miR-200b-3p, which were enriched for both interleukin-4 and interferon-γ signalling pathways, and included theSOCS1(suppressor of cytokine signalling 1) gene.SOCS1was more highly expressed in moderate (pcorrected=0.017) and severe (pcorrected=5.4×10−3) asthma cases compared with controls. Moreover, both miR-200b-3p editing andSOCS1were associated with bronchoalveolar lavage eosinophil levels.ConclusionsReduced A-to-I editing of position 5 of miR-200b-3p in lower airway cells from moderate-to-severe asthmatic subjects may lead to overexpression ofSOCS1and impaired cytokine signalling. We propose ADAR-mediated editing as an epigenetic mechanism contributing to features of moderate-to-severe asthma in adulthood.
Exercise-induced bronchoconstriction and bronchodilation: investigating the effects of age, sex, airflow limitation and FEV1
Authors: Satia Imran , Priel Eldar , Al-Khazraji Baraa K. , Jones Graham , Freitag Andy , O'Byrne Paul M. , Killian Kieran J. 
Published: January 2021

Exercise-induced bronchoconstriction (EIBc) is a recognised response to exercise in asthmatic subjects and athletes but is less well understood in an unselected broad population. Exercise-induced bronchodilation (EIBd) has received even less attention. The objective of this study was to investigate the effects of age, sex, forced expiratory volume in 1 s (FEV1) and airflow limitation (FEV1/forced vital capacity (FVC) <0.7) on the prevalence of EIBc and EIBd.This was a retrospective study based on incremental cardiopulmonary exercise testing on cycle ergometry to symptom limitation performed between 1988 and 2012. FEV1was measured before and 10 min after exercise. EIBc was defined as a percentage fall in FEV1post-exercise below the 5th percentile, while EIBd was defined as a percentage increase in FEV1above the 95th percentile.35 258 subjects aged 6–95 years were included in the study (mean age 53 years, 60% male) and 10.3% had airflow limitation (FEV1/FVC <0.7). The lowest 5% of subjects demonstrated a ≥7.6% fall in FEV1post-exercise (EIBc), while the highest 5% demonstrated a >11% increase in FEV1post-exercise (EIBd). The probability of both EIBc and EIBd increased with age and was highest in females across all ages (OR 1.76, 95% CI 1.60–1.94; p<0.0001). The probability of EIBc increased as FEV1% pred declined (<40%: OR 4.38, 95% CI 3.04–6.31; p<0.0001), with a >2-fold increased likelihood in females (OR 2.31, 95% CI 1.71–3.11; p<0.0001), with a trend with airflow limitation (p=0.06). The probability of EIBd increased as FEV1% pred declined, in the presence of airflow limitation (OR 1.55, 95% CI 1.24–1.95; p=0.0001), but sex had no effect.EIBc and EIBd can be demonstrated at the population level, and are influenced by age, sex, FEV1% pred and airflow limitation.
Treatable cardiac disease in hospitalised COPD exacerbations
Authors: Leong Paul , MacDonald Martin I. , King Paul T. , Osadnik Christian R. , Ko Brian S. , Landry Shane A. , Hamza Kais , Kugenasan Ahilan , Troupis John M. , Bardin Philip G. 
Published: January 2021

IntroductionAcute exacerbations of COPD (AECOPD) are accompanied by escalations in cardiac risk superimposed upon elevated baseline risk. Appropriate treatment for coronary artery disease (CAD) and heart failure with reduced ejection fraction (HFrEF) could improve outcomes. However, securing these diagnoses during AECOPD is difficult, so their true prevalence remains unknown, as does the magnitude of this treatment opportunity. We aimed to determine the prevalence of severe CAD and severe HFrEF during hospitalised AECOPD using dynamic computed tomography (CT).MethodsA cross-sectional study of 148 patients with hospitalised AECOPD was conducted. Dynamic CT was used to identify severe CAD (Agatston score ≥400) and HFrEF (left ventricular ejection fraction ≤40% and/or right ventricular ejection fraction ≤35%).ResultsSevere CAD was detected in 51 of 148 patients (35%), left ventricular systolic dysfunction was identified in 12 cases (8%) and right ventricular systolic dysfunction was present in 18 (12%). Clinical history and examination did not identify severe CAD in approximately one-third of cases and missed HFrEF in two-thirds of cases. Elevated troponin and brain natriuretic peptide did not differentiate subjects with severe CAD from nonsevere CAD, nor distinguish HFrEF from normal ejection fraction. Undertreatment was common. Of those with severe CAD, only 39% were prescribed an antiplatelet agent, and 53% received a statin. Of individuals with HFrEF, 50% or less received angiotensin blockers, beta blockers or antimineralocorticoids.ConclusionDynamic CT detects clinically covert CAD and HFrEF during AECOPD, identifying opportunities to improve outcomesviawell-established cardiac treatments.