bluuebunny/crossref_metadata_2025_split huggingface dataset:
Restrictive vs liberal red blood cell transfusion strategies in patients with acute myocardial infarction and anemia: Rationale and design of the REALITY trial
Authors: Ducrocq Gregory , Calvo Gonzalo , González‐Juanatey José Ramón , Durand‐Zaleski Isabelle , Avendano‐Sola Cristina , Puymirat Etienne , Lemesle Gilles , Arnaiz Joan Albert , Martínez‐Sellés Manuel , Rousseau Alexandra , Cachanado Marine , Vicaut Eric , Silvain Johanne , Karam Carma , Danchin Nicolas , Simon Tabassome , Steg Philippe Gabriel ,   REALITY investigators
Published: January 2021

AbstractBackgroundAnemia is common in patients with acute myocardial infarction (AMI), and is an independent predictor of mortality. The optimal transfusion strategy in these patients is unclear.HypothesisWe hypothesized that a “restrictive” transfusion strategy (triggered by hemoglobin ≤8 g/dL) is clinically noninferior to a “liberal” transfusion strategy (triggered by hemoglobin ≤10 g/dL), but is less costly.MethodsREALITY is an international, randomized, multicenter, open‐label trial comparing a restrictive vs a liberal transfusion strategy in patients with AMI and anemia. The primary outcome is the incremental cost‐effectiveness ratio (ICER) at 30 days, using the primary composite clinical outcome of major adverse cardiovascular events (MACE; comprising all‐cause death, nonfatal stroke, nonfatal recurrent myocardial infarction, or emergency revascularization prompted by ischemia) as the effectiveness criterion. Secondary outcomes include the ICER at 1 year, and MACE (and its components) at 30 days and at 1 year.ResultsThe trial aimed to enroll 630 patients. Based on estimated event rates of 11% in the restrictive group and 15% in the liberal group, this number will provide 80% power to demonstrate clinical noninferiority of the restrictive group, with a noninferiority margin corresponding to a relative risk equal to 1.25. The sample size will also provide 80% power to show the cost‐effectiveness of the restrictive strategy at a threshold of €50 000 per quality‐adjusted life year.ConclusionsREALITY will provide important guidance on the management of patients with AMI and anemia.
Physical fitness and modifiable cardiovascular disease risk factors in survivors of childhood cancer: A report from the SURfit study
Authors: Schindera Christina , Zürcher Simeon Joel , Jung Ruedi , Boehringer Sarah , Balder Jan Willem , Rueegg Corina Silvia , Kriemler Susi , von der Weid Nicolas Xavier 
Published: January 2021

BackgroundChildhood cancer survivors are at risk for cardiovascular disease (CVD) because of intensive cancer therapies often accompanied by an unhealthy lifestyle. This study was aimed at 1) describing modifiable CVD risk factors in survivors and 2) investigating the association between different aspects of physical fitness and CVD risk factors.MethodsThe authors analyzed cross‐sectional data from ≥5‐year survivors who were 16 years old or younger at their cancer diagnosis and 16 years old or older at the time of the study. Single CVD risk factors (waist circumference, blood pressure, fasting glucose, inverse high‐density lipoprotein, and triglycerides), a composite CVD risk score (combined z scores of all CVD risk factors), and metabolic syndrome were evaluated. Physical fitness measures included cardiopulmonary exercise testing (CPET), a handgrip test, and a 1‐minute sit‐to‐stand test (STS). Multivariable logistic regression was used for the association between fitness measures and CVD risk factors, with adjustments made for demographic factors and cancer therapy.ResultsThis study included 163 survivors with a median age at diagnosis of 7 years and a median age at the time of the study of 28 years. Among those survivors, 27% had a high waist circumference, 32% had high blood pressure, 19% had high triglycerides, 20% had an increased composite CVD risk score, and 10% had metabolic syndrome. A better performance during CPET, handgrip testing, and STS was associated with a lower probability of having a high waist circumference, high triglycerides, and metabolic syndrome.ConclusionsBetter aerobic fitness (CPET) and, to a lesser extent, handgrip and STS were associated with fewer CVD risk factors. Further investigations are warranted to investigate which fitness measures should preferably be used to screen survivors to promote physical activity in those with impaired test performance.Lay Summary

This study investigated the relationship between physical fitness of adult childhood cancer survivors and their risk factors for cardiovascular disease.

Cardiovascular risk factors such as high blood pressure, a high waist circumference, and high blood lipids were frequently found in childhood cancer survivors. Survivors with better physical fitness (measured by a cycling test or simple strength and endurance tests) had a lower chance of having cardiovascular risk factors.

This suggests that childhood cancer survivors could benefit from physical activity and general fitness by increasing their physical fitness and possibly decreasing their risk of cardiovascular disease.
Genetic Variation in Sodium‐glucose Cotransporter 2 and Heart Failure
Authors: Katzmann Julius L. , Mason Amy M. , März Winfried , Kleber Marcus E. , Niessner Alexander , Blüher Matthias , Speer Thimoteus , Laufs Ulrich 
Published: January 2021

Inhibition of sodium‐glucose cotransporter 2 (SGLT2) represents an emerging pharmaceutical approach for the treatment of heart failure. The mechanisms by which SGLT2 inhibitors reduce the risk of heart failure are not well understood. The objective of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in the SLC5A2 gene, encoding SGLT2, and heart failure, and to assess potential mediators of this association. Regression and mediation analyses were conducted with individual participant data of the UK Biobank (n = 416,737) and validated in the cardiovascular high‐risk cohort of the LUdwigshafen RIsk and Cardiovascular Health study (LURIC; n = 3316). Two intronic SNPs associated with SLC5A2 expression were included in a genetic score, which was associated with lower risk of heart failure in UK Biobank (odds ratio 0.97, 95% confidence interval, 0.95−0.99, P = 0.016). This association was also present in participants without type 2 diabetes or coronary artery disease (CAD). The associations of the genetic score with HbA1c, high‐density lipoprotein cholesterol, uric acid, systolic blood pressure, waist circumference, and body composition mediated 35% of the effect of the score on heart failure risk. No associations of the genetic SGLT2 score with atherosclerotic cardiovascular disease outcomes or markers of volume status were observed, which was confirmed in the LURIC study. Variations in the gene encoding SGLT2 were associated with the risk of prevalent or incident heart failure. This association was mediated by several mechanisms and did not depend on the presence of type 2 diabetes or previous CAD events.
A Multipurpose First‐in‐Human Study With the Novel CXCR7 Antagonist ACT‐1004‐1239 Using CXCL12 Plasma Concentrations as Target Engagement Biomarker
Authors: Huynh Christine , Henrich Andrea , Strasser Daniel S. , Boof Marie‐Laure , Al‐Ibrahim Mohamed , Meyer Zu Schwabedissen Henriette E. , Dingemanse Jasper , Ufer Mike 
Published: January 2021

The C‐X‐C chemokine receptor 7 (CXCR7) has evolved as a promising, druggable target mainly in the immunology and oncology fields modulating plasma concentrations of its ligands CXCL11 and CXCL12 through receptor‐mediated internalization. This “scavenging” activity creates concentration gradients of these ligands between blood vessels and tissues that drive directional cell migration. This randomized, double‐blind, placebo‐controlled first‐in‐human study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of ACT‐1004‐1239, a first‐in‐class drug candidate small‐molecule CXCR7 antagonist. Food effect and absolute bioavailability assessments were also integrated in this multipurpose study. Healthy male subjects received single ascending oral doses of ACT‐1004‐1239 (n = 36) or placebo (n = 12). At each of six dose levels (1–200 mg), repeated blood sampling was done over 144 hours for pharmacokinetic/pharmacodynamic assessments using CXCL11 and CXCL12 as biomarkers of target engagement. ACT‐1004‐1239 was safe and well tolerated up to the highest tested dose of 200 mg. CXCL12 plasma concentrations dose‐dependently increased and more than doubled compared with baseline, indicating target engagement, whereas CXCL11 concentrations remained unchanged. An indirect‐response pharmacokinetic/pharmacodynamic model well described the relationship between ACT‐1004‐1239 and CXCL12 concentrations across the full dose range, supporting once‐daily dosing for future clinical studies. At doses ≥ 10 mg, time to reach maximum plasma concentration ranged from 1.3 to 3.0 hours and terminal elimination half‐life from 17.8 to 23.6 hours. The exposure increase across the dose range was essentially dose‐proportional and no relevant food effect on pharmacokinetics was determined. The absolute bioavailability was 53.0% based on radioactivity data after oral vs. intravenous 14C‐radiolabeled microtracer administration of ACT‐1004‐1239. Overall, these comprehensive data support further clinical development of ACT‐1004‐1239.
Plasma cell‐rich bronchoalveolar lavage fluid: Could be a first clue to IgG4 plasma cell‐related lung disease
Authors: AbdullGaffar Badr , Abdelkareem Fatma 
Published: January 2021

AbstractPlasma cells are usually absent in normal bronchoalveolar lavage (BAL) fluids. Frequent plasma cells in BAL are always pathologically significant. They raise a rather narrow differential diagnosis, predominantly extrinsic allergic alveolitis and few other interstitial lung diseases. BAL is a key diagnostic procedure for certain lung diseases. Because plasma cells are uncommon in BAL fluids and usually associated with limited conditions compared to other more common interstitial lung diseases, the focus of cell count differentials in BAL fluids was on other mononuclear and granulocytic inflammatory cells. Recently, cases of IgG4 positive plasma cell‐related lung diseases have been reported in tissue specimens. This may raise the importance of cytologically recognizing plasma cells in BAL fluids. We report a case of a 16‐year‐old boy with clinical and radiologic features of diffuse interstitial lung disease. His BAL cytology showed frequent plasma cells. Endobronchial biopsy showed substantial infiltration by plasma cells confirmed by immunohistochemistry. After excluding other lung diseases, the possibility of IgG4 plasma cell‐related disease was raised. Blood tests showed elevated serum levels of IgG4. This case emphasizes the importance of including of IgG4 plasma cell‐related lung disease as a possible differential diagnosis. This should prompt proper serologic tests for confirmation and appropriate management. With increasing reports of IgG4‐related lung disease, cytopathologists should be aware of this possibility when examining BAL fluids. Measurement of IgG levels in BAL fluids and plasma cell immunophenotyping might be promising tools.
Comparing scraping cytology with touch imprint cytology and frozen section analysis in the intraoperative diagnosis of sentinel lymph node metastasis in breast cancer
Authors: Mohammadnia Avval Maryam , Hosseinzadeh Massood , Farahi Zahra , Mirtalebi Maryamsadat 
Published: January 2021

AbstractBackgroundBreast cancer is a common cancer in the female population. Sentinel lymph node (SLN) in breast cancer patients can be evaluated by different methods including intraoperative frozen section analysis (FSA), touch imprint cytology (TIC), and scraping cytology (SC). In this study, in addition to investigating TIC and FSA, we focused on SC to evaluate the diagnostic value of this almost new method.Materials and methodsIn this retrospective study, the quadrantectomy and sentinel lymph node resection of 150 specimens with mammography and core needle biopsy‐confirmed breast cancer were examined. Of the 150 participants, 77 and 73 had negative and positive results for the permanent pathology of SLN metastasis, respectively. Intra‐operative FSA, TIC, and SC for SLN were performed for the patients and all were confirmed by permanent pathology.ResultsAll the specimens were taken from females aged between 25 and 82 years. The sensitivity and specificity of TIC, FS, and SC were 73% and 50%, 92.6% and 50%, and 92.1% and 50%, respectively. Among the three techniques, TIC had the lowest positive and negative predictive values. However, FS had the highest positive predictive value whereas SC had the highest negative predictive value.ConclusionIn addition to FS and TIC as rapid, cost‐effective, and reliable diagnostic methods in SLN metastasis, SC is an acceptable and highly sensitive method. A combination of these methods may provide a more favorable diagnostic value for SLN assessment in breast cancer patients.
A comparison of two methods for estimating measurement repeatability in morphometric studies
Authors: Wylde Zachariah , Bonduriansky Russell 
Published: January 2021

Abstract

Measurement repeatability is often reported in morphometric studies as an index of the contribution of measurement error to trait measurements. However, the common method of remeasuring a mounted specimen fails to capture some components of measurement error and could therefore yield inflated repeatability estimates. Remounting specimens between successive measurements is likely to provide more realistic estimates of repeatability, particularly for structures that are difficult to measure.

Using measurements of 22 somatic and genitalic traits of the neriid fly Telostylinus angusticollis, we compared repeatability estimates obtained via remeasurement of a specimen that is mounted once (single‐mounted method) versus remeasurement of a specimen that is remounted between measurements (remounted method). We also asked whether the difference in repeatability estimates obtained via the two methods depends on trait size, trait type (somatic vs. genitalic), sclerotization, or sex.

Repeatability estimates obtained via the remounted method were lower than estimates obtained via the single‐mounted method for each of the 22 traits, and the difference between estimates obtained via the two methods was generally greater for small structures (such as genitalic traits) than for large structures (such as legs and wings). However, the difference between estimates obtained via the two methods did not depend on trait type (genitalic or somatic), tissue type (soft or sclerotized) or sex.

Remounting specimens between successive measurements can provide more accurate estimates of measurement repeatability than remeasuring from a single mount, especially for small structures that are difficult to measure.
Determination of acidity constants, ionic mobilities, and hydrodynamic radii of carborane‐based inhibitors of carbonic anhydrases by capillary electrophoresis
Authors: Šolínová Veronika , Brynda Jiří , Šícha Václav , Holub Josef , Grűner Bohumír , Kašička Václav 
Published: January 2021

AbstractCapillary electrophoresis (CE) has been applied for determination of the thermodynamic acidity constants (pKa) of the sulfamidoalkyl and sulfonamidoalkyl groups, the actual and limiting ionic mobilities and hydrodynamic radii of important compounds, eight carborane‐based inhibitors of carbonic anhydrases, which are potential new anticancer drugs. Two types of carboranes were investigated, (i) icosahedral cobalt bis(dicarbollide)(1‐) ion with sulfamidoalkyl moieties, and (ii) 7,8‐nido‐dicarbaundecaborate with sulfonamidoalkyl side chains. First, the mixed acidity constants, pKamix, of the sulfamidoalkyl and sulfonamidoalkyl groups of the above carboranes and their actual ionic mobilities were determined by nonlinear regression analysis of the pH dependences of their effective electrophoretic mobility measured by capillary electrophoresis in the pH range 8.00−12.25, at constant ionic strength (25 mM), and constant temperature (25°C). Second, the pKamix were recalculated to the thermodynamic pKas using the Debye–Hückel theory. The sulfamidoalkyl and sulfonamidoalkyl groups were found to be very weakly acidic with the pKas in the range 10.78−11.45 depending on the type of carborane cluster and on the position and length of the alkyl chain on the carborane scaffold. These pKas were in a good agreement with the pKas (10.67−11.27) obtained by new program AnglerFish (freeware at https://echmet.natur.cuni.cz), which provides thermodynamic pKas and limiting ionic mobilities directly from the raw CE data. The absolute values of the limiting ionic mobilities of univalent and divalent carborane anions were in the range 18.3−27.8 TU (Tiselius unit, 1 × 10−9 m2/Vs), and 36.4−45.9 TU, respectively. The Stokes hydrodynamic radii of univalent and divalent carborane anions varied in the range 0.34−0.52 and 0.42−0.52 nm, respectively.
Social Perceptions of Pediatric Hearing Aids
Authors: Qian Z. Jason , Nuyen Brian A. , Kandathil Cherian K. , Truong Mai‐Thy , Tribble Melissa S. , Most Sam P. , Chang Kay W. 
Published: January 2021

ObjectivesTo determine whether hearing aid (HA) use affects social perceptions of general public adults and age‐matched peers and if so, determine if effects are modulated by lack of societal representation of pediatric HAs.MethodsA 10‐year‐old boy was presented in six photographic conditions with and without HAs and eyeglasses (a worn sensory aid with wider societal representation). HAs were presented in neutral skin tone and bright blue colors. Photographic conditions were embedded into web‐based surveys with visual analog scales to capture social perceptions data and sourced to 206 adults (age 18–65) and 202 peers (age 10) with demographic characteristics representative of the general US population. Mean differences in scores for each condition compared to control images were computed using two‐tailed t‐tests.ResultsIn both adult and child respondents, HAs were associated with decreased athleticism, confidence, health, leadership, and popularity. Glasses were associated with decreased athleticism and popularity but increased intelligence, overall success, and in the child respondents, friendliness. When worn in combination, the beneficial effects of glasses were mitigated by brightly colored but not neutrally colored HAs.ConclusionNegative effects of pediatric HAs on social perceptions may be influenced by poor societal representation of HAs. These results suggest that greater representation of pediatric HAs is necessary to make society more inclusive for children with hearing loss.Level of Evidence4 Laryngoscope, 131:E2387–E2392, 2021
Factors Associated With Tolerance for In‐Office Laryngeal Laser Procedures
Authors: Zheng Melissa , Arora Nikhil , Bhatt Neel , O'Dell Karla , Johns Michael 
Published: January 2021

Objectives/HypothesisA variety of laryngeal pathologies are increasingly being managed with in‐office KTP laser (IOKTP) endoscopic procedures. The primary goal of this study was to identify patient characteristics and disease‐related features that correlated with tolerance for IOKTP.Study DesignRetrospective chart review.MethodsThe study was a retrospective review of adult patients undergoing office‐based laryngeal laser procedures between November 2016 and December 2019 at a tertiary care center. Two blinded otolaryngologist reviewers scored videotaped recordings of IOKTP procedures and assessed severity and distribution of disease using a modified Derkay score, and evaluated procedure tolerance using a visual analog scale.ResultsA total of 56 patients who received IOKTP procedures for laryngeal pathology were reviewed, 42 male and 14 female, with a mean age of 61 years. Gender, age, and BMI were not correlated with tolerance. There was a moderate, negative correlation between tolerance and total number of pathological anatomic laryngeal subsites (rs(56) = −0.35, P = .01). There was a weak, negative correlation between tolerance and total modified Derkay score (rs(56) = −0.29, P = .03). The median tolerance score was lower for patients with posterior lesions (Mdn = 6.4) compared with patients with non‐posterior lesions (Mdn = 7.4), P = .04, and lower for current or former smokers (Mdn = 6.5) compared with never smokers (Mdn = 7.3), P = .04.ConclusionPatients with large disease burden or posterior lesions and patients with smoking history may exhibit poorer tolerance of IOKTP procedures, factors which can help guide pre‐procedural counseling and management decisions.Level of EvidenceIV Laryngoscope, 131:E2292–E2297, 2021
Hematopoietic stem cell transplant referral patterns for children with sickle cell disease vary among pediatric hematologist/oncologists’ practice focus: A Sickle Cell Transplant Advocacy and Research Alliance (STAR) study
Authors: Meier Emily Riehm , Abraham Allistair A. , Ngwube Alex , Janson Isaac A. , Guilcher Gregory M.T. , Horan John , Kasow Kimberly A. 
Published: January 2021

AbstractBackgroundHematopoietic stem cell transplantation (HSCT) provides a curative therapy for children severely affected by sickle cell disease (SCD). Rejection‐free survival after matched sibling donor (MSD) HSCT is very high, but adoption of HSCT as a curative SCD therapy has been slow. In this study, we assess providers’ perceptions about MSD HSCT for children with variable SCD severity, and determine the influence of provider characteristics on HSCT referrals.ProcedureAfter our Institutional Review Board deemed the study exempt, American Society of Pediatric Hematology/Oncology Clinical Forum listserv subscribers and American Society of Hematology members who self‐identified as pediatric hematologists/oncologists (PHO) were emailed a survey. Analysis was performed to describe and evaluate correlations between participant demographics (including practice focus within PHO) and likelihood of HSCT referral for each scenario.ResultsSpearman's rank correlation analysis did not reveal any significant relationship between demographic characteristics except practice focus and likelihood to refer to HSCT for any scenarios. Providers focused on SCD and HSCT were more likely to refer a child who had never been admitted to the hospital or had suboptimal adherence to hydroxyurea than general PHOs. A significantly higher proportion of all respondents would refer a child with β‐thalassemia major (87%) than an asymptomatic child with HbSS (47%, P < .00001) or non‐HbSS variant (23%, P < .00001).ConclusionPSCD and HSCT physicians are more likely to refer for MSD HSCT in almost every condition than general PHO practitioners, likely because of increased awareness of long‐term effects of SCD and safety of MSD HSCT for children with SCD.