bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of capecitabine concentrations determined by microsampling versus plasma concentrations for therapeutic drug monitoring: a pilot study
Authors: Shafiei Mohsen , Galettis Peter , Beale Philip , Martin Jennifer H , McLachlan Andrew J , Blinman Prunella 
Published: December 2023

Abstract

Objectives
Therapeutic drug monitoring allows personalized dosing of chemotherapy, but is not well established for capecitabine. The aim of this study was to compare the concentrations of capecitabine and its metabolites obtained simultaneously by microsampling with plasma sampling and their acceptability to patients.

Methods
Adults taking capecitabine for cancer had paired (duplicate) microsampling at steady state (hour 2 post dose) using Mitra® devices and venous blood samples for analysis. Capecitabine and metabolites were measured using a validated mass spectrometry assay. Correlation between the sampling methods was determined. Patients’ preferences were elicited using a Likert numeric rating scale and pain by a Visual Analog Scale (range, 0–10).

Key findings
Capecitabine concentrations from 10 patients (60 paired samples) by microsampling and plasma sampling were highly correlated (Pearson correlation: 0.97, Coefficients of determination: 0.94, P &lt; 0.0001). Capecitabine concentrations in capillary sampling were consistently lower than the paired plasma concentration (median capecitabine capillary/plasma concentration ratio = 2851/3846 μg/l 75%). The agreement between sampling matrices showed a 28% bias (95% Cl, 4.02–52.00). Participant ratings showed microsampling was the preferred method by all 10 patients. Most participants reported no pain with microsampling (median 0, range 0–1).

Conclusion
Capecitabine concentration measured by microsampling and plasma sampling were highly correlated, but consistently lower in microsampling. Microsampling was the preferred method with minimal pain.
Outcomes of collagenase Clostridium histolyticum in men with ventral curvatures: an updated series
Authors: Larson Henry , Savage Joshua , Brearton Klint , Warner Riley , Ziegelmann Matthew , Kohler Tobias , Trost Landon 
Published: December 2023

Abstract

Background
The efficacy and safety of collagenase Clostridium histolyticum (CCH) have been demonstrated in the treatment of men with Peyronie’s disease (PD); however, the pivotal clinical trials excluded men with ventral penile curvature.

Aim
The study sought to evaluate outcomes of CCH treatment in men with ventral curvatures secondary to PD.

Methods
Men with PD treated with CCH were identified from a prospective database. Patients received up to 4 series of CCH injections using a progressively modified protocol over time. Results were compared between those with baseline ventral vs nonventral penile curvatures.

Outcomes
Changes in penile curvature, Peyronie’s Disease Questionnaire scores, International Index of Erectile Function scores, nonstandardized assessments, and adverse events.

Results
A total of 560 men with PD (85 ventral curvature, 475 nonventral curvature) were included in the analysis. Baseline median curvature was 60.0° (interquartile range, 48.8°-75.0°) in the ventral cohort and 65.0° (interquartile range, 45.0°-80.0°) in the nonventral cohort. Median change from baseline penile curvature was −25.0° in the ventral cohort vs −24.0° in the nonventral cohort (P = .08, between-group comparison), which corresponded to curvature reductions of 44.7% and 33.6%, respectively (P = .03). In the subset of patients who completed CCH treatment (ie, received 8 injections or discontinued early because of patient satisfaction with curvature reduction), median change from baseline was −35.0° in the ventral cohort vs −25.0° in the nonventral cohort (P &lt; .05); median percent improvement was 48.3% and 37.5%, respectively (P = .11). Median change from baseline in Peyronie’s Disease Questionnaire and International Index of Erectile Function domain scores and adverse events were similar between cohorts, with the exception of possibly higher hematoma rates in the nonventral group (50% vs 37%; P = .05). No urethral injuries were sustained in either cohort.

Clinical Implications
Data support the use of CCH for the treatment of ventral as well as nonventral penile curvatures in men with PD.

Strengths and Limitations
Study strengths are the inclusion of a general clinical population of men with PD, the prospective design, and the relatively large series of men with ventral curvature. Limitations include the single-center and observational nature of the study.

Conclusion
CCH was safe and effective in the treatment of both ventral and nonventral penile curvatures in men with PD.
Urine immunofixation electrophoresis and serum free light chain analyses benefit diagnosis of multiple myeloma in orthopedic patients with normal serum total proteins, creatinine, calcium, and hemoglobin
Authors: Jia Zhongwei , Xia Jinxing , Lu Qiong 
Published: December 2023

Abstract

Background
A substantial number of patients with multiple myeloma (MM) who have bone destruction are initially admitted into the orthopedic service at the hospital. However, routine laboratory testing usually fails to identify these patients, thus delaying optimal therapy. Therefore, there is a clear medical need for early diagnosis of MM in these patients.

Methods
Between 2019 and 2021, 42 patients receiving treatment for orthopedic conditions had normal hemoglobin (Hb), total protein (TP), albumin (ALB), creatinine (CREA), and blood calcium (Ca) levels before their surgical procedure(s) but were subsequently pathologically confirmed to have MM, based on their presenting orthopedic symptoms. During the same period, 52 patients with orthopedic conditions were pathologically excluded from the diagnosis of MM and were recruited into our control group. Serum free light chain (sFLC) testing was performed in 94 consecutive patients in the orthopedic service using Siemens N Latex FLC kits. The levels of Hb, TP, ALB, CREA, and Ca were also measured. All 42 patients with MM were divided into group A (n = 25: κ proliferation) and group B (n = 17: λ proliferation) by the pathology department.

Results
There were no significant differences in levels of Hb, TP, ALB, CREA, and Ca between group A and group B and the control group. However, the sFLC κ/λ ratio of group A and B was also significantly different from that of the control group (P &lt; .001). The results of serum immunofixation electrophoresis (IFE) testing demonstrated negative results in 14 cases (58.3%) in group A and 4 cases (25.0%) in group B.

Conclusions
Some patients with orthopedic conditions who do not have typical MM laboratory results, such as those with abnormal Hb, TP, ALB, CREA, and Ca levels before their operation(s), actually have MM. MM should be highly suspected in patients with unexplained bone lesions and with an abnormal sFLC κ/λ ratio. Further tissue or bone marrow biopsy is needed in these patients even if serum and urine IFE results are negative and light chain ratio is normal.
Switching Style towards Ease in a Medieval Textbook of Medicine: Revison of Constantine the African’s Pantegni, Theorica in Twelfth-Century Manuscripts
Authors: Kaltio Outi 
Published: December 2023

Abstract
The Pantegni of Constantine the African (d. by 1098/9) was the first ever comprehensive medical textbook written in Latin. It was translated and modified from an Arabic original in Salerno and in the monastery of Monte Cassino in south Italy. This article demonstrates that a large-scale stylistic revision of the Pantegni, or more precisely of its section Theorica, was carried out in the first half of the twelfth century at the latest. The existence of the revised version suggests there was a desire for Constantine’s translation to meet altered expectations and practical needs. Based on collation of a chapter from Book V and additional sample passages in both the standard version and the revised version of the Theorica, it is argued that the latter was compiled in order to simplify and clarify Constantine’s expression and make his train of thought as lucid as possible.
Given by Lady Joan Ingoldisthorpe: The Caxton Cordyal (1479) from a Library at Pott Chapel (Pott Shrigley, Cheshire), c. 1493, Identified
Authors: Harding Robert J D 
Published: December 2023

Abstract
This paper describes a copy of William Caxton’s printing of the Cordyal of the four last and final thinges (Westminster: 24 March 1479) recently acquired by the Brotherton Library, University of Leeds. It bears a gift inscription from Lady Joan Ingoldisthorpe (d. 1494) to the Downes Chantry Chapel at Pott Shrigley, Cheshire, which possessed a small library of books, including several others printed by Caxton, previously known only through an early inventory. It discusses the book’s ownership and provenance, the reception of Caxton’s printings beyond London, the possible patronage of his edition of John Tiptoft, earl of Worcester’s translations of Cicero and Buonaccorso da Montemagno printed by Caxton in 1481, and the early provenance of the unique copy of the Sarum Missal printed in Paris by Guillaume Maynyal for Caxton in 1487 owned by the National Trust at Lyme Park in Cheshire.
Counterfeiting Periodicals in Seventeenth-Century Europe: Engravings, Music, and Binding of the Dutch Mercure galant in the Austrian National Library (1678–1679)
Authors: Schuwey Christophe 
Published: December 2023

Abstract
This article analyses in detail a collection of seven counterfeit volumes of the Mercure galant—the main cultural periodical and principal propaganda machine of the late seventeenth-century—kept in the Austrian National Library in Vienna. These counterfeits, which have never been studied before, reveal the efforts and strategies undertaken by the Dutch bookseller Abraham Wolfgang to copy the text, engravings and music in each monthly issue. Analysing this set also reveals the financial and material constraints faced by the Parisian publishers of the original Mercure. Finally, the binding and bookplate reveal important clues regarding the international distribution and readership of Le Mercure galant, as well as its transformation from a periodical to an historical account.
Stellar rotations and the disentanglement of the Galactic thin and thick discs
Authors: da Silva M P , Alves-Brito A , do Nascimento J D 
Published: December 2023

ABSTRACT
The kinematics, mean α-elements, and ages of the stars reveal two distinct disc populations observed in the Solar neighbourhood. Although several studies have been carried out to characterize abundances of chemical elements and kinematic identifications in these populations, there are few studies that dealt with the analysis of stellar rotation and characteristics of populations focused on low-mass stars of the F and G types. In this work, we propose a new approach to classify stellar populations from the thin and thick disc for F and G dwarf stars by relating chemical abundance and rotation (v sin i) of these stars in the rotational–chemical–plane (v sin i–[α/Fe]–[Fe/H] plot). Our results show that the two rotational-chemical sequences disentangled, high- and low-[α/Fe] components, present properties (α-enhanced, ages, kinematics, space velocity gradients, local density ratio) closely linked to the stars of the chemically and kinematically defined as thin and thick disc components. This study has an impact on calibrations that relate ages to rotation (gyro-chronology) as well as age to chemical abundances (chemochronology), as well as sheds light on the understanding of the processes of Galactic disc formation.
A survey of molecular line emission towards Herbig Be star V645 Cyg
Authors: Gimalieva A D , Kirsanova M S , Salii S V , Kalenskii S V , Olofsson A O H , Topchieva A P 
Published: December 2023

ABSTRACT
We present a survey of molecular line emission towards the molecular cloud surrounding Herbig Be star V645 Cyg. The survey was performed with the 20-m Onsala space telescope at 3 and 4 mm. We detected emission lines of 33 molecules and their isotopologues from diatomic molecules to four COMs up to seven atoms. Using detected lines, we estimated molecular column densities and abundances relative to molecular hydrogen in local thermodynamic equilibrium (LTE) approximation for all molecules except for methanol, for which we obtained physical parameters using a non-LTE model. Moreover, in the basement of the non-LTE model of methanol line emission, we consider that there is a weak maser effect in the additional spectral component of 51–40 E methanol line at 84.521 GHz. We compared the molecular abundances with values found in several astrochemical templates: molecular clouds, hot cores, and photodissociation regions, and found that signatures of these different types can be found towards V645 Cyg. We also obtained maps of the cloud in several molecular emission lines. The peaks of CO and CH3OH emission are shifted from the direction of the star, but the CS, HCO+, HNC, HCN, and N2H+ emission peaks are observed directly towards the star. Exploring the gas kinematics around V645 Cyg, we found that velocity structure in the ambient molecular cloud on the scale ≈1.6–2.0 pc is not the same as within ≈0.5 pc found previously by other authors.
AGN-driven outflows in the OH absorber galaxy IRAS 19154+2704
Authors: Hekatelyne C , Storchi-Bergmann Thaisa , Riffel Rogemar A , Kharb Preeti , Cassanta Claudia M , Robinson Andrew , Sales Dinalva A 
Published: December 2023

ABSTRACT
We present a two-dimensional study of the gas distribution, excitation, and kinematics of the OH absorber galaxy IRAS 19154+2704 using Gemini Multi-Object Spectrograph integral field unit observations. Its continuum image shows a disturbed morphology indicative of a past or ongoing interaction. The ionized gas emission presents two kinematic components: a narrow (σ ≲ 300 km s−1) component that may be tracing the gas orbiting in the galaxy potential and a broad (σ ≳ 500 km s−1) component, which is produced by an active galactic nucleus (AGN)-driven outflow, with velocities reaching −500 km s−1, which may exceed the escape velocity of the galaxy. The emission-line ratios and Baldwin–Phillips–Terlevich diagrams confirm that the gas excitation in the inner ∼2 kpc is mainly due to the AGN, while in regions farther away, a contribution from star formation is observed. We estimate a mass-outflow rate of $\dot{M}_{\rm out}=4.0\pm 2.6$ M⊙ yr−1 at a distance of 850 pc from the nucleus. The corresponding outflow kinetic power, $\dot{E}_{\rm out} = (2.5\pm 1.6)\times 10^{42}$ erg s−1, is only 3 × 10−4 Lbol (the AGN luminosity), but the large mass-outflow rate, if kept for an ∼10 Myr AGN life cycle, will expel ≈108 M⊙ in ionized gas alone. This is the sixth of a series of papers in which we have investigated the kinematics of ultra-luminous infrared galaxies, most of which are interacting galaxies showing OH megamasers. IRAS 19154 shows the strongest signatures of an active AGN, supporting an evolutionary scenario: interactions trigger AGN that fully appears in the most advanced stages of the interaction.
Semi-reference based cell type deconvolution with application to human metastatic cancers
Authors: Lu Yingying , Chen Qin M , An Lingling 
Published: December 2023

Abstract
Bulk RNA-seq experiments, commonly used to discern gene expression changes across conditions, often neglect critical cell type-specific information due to their focus on average transcript abundance. Recognizing cell type contribution is crucial to understanding phenotype and disease variations. The advent of single-cell RNA sequencing has allowed detailed examination of cellular heterogeneity; however, the cost and analytic caveat prohibits such sequencing for a large number of samples. We introduce a novel deconvolution approach, SECRET, that employs cell type-specific gene expression profiles from single-cell RNA-seq to accurately estimate cell type proportions from bulk RNA-seq data. Notably, SECRET can adapt to scenarios where the cell type present in the bulk data is unrepresented in the reference, thereby offering increased flexibility in reference selection. SECRET has demonstrated superior accuracy compared to existing methods using synthetic data and has identified unknown tissue-specific cell types in real human metastatic cancers. Its versatility makes it broadly applicable across various human cancer studies.
Whole tumor analysis reveals early origin of the TERT promoter mutation and intercellular heterogeneity in TERT expression
Authors: Appin Christina L , Hong Chibo , Suwala Abigail K , Hilz Stephanie , Mathur Radhika , Solomon David A , Smirnov Ivan V , Stevers Nicholas O , Shai Anny , Wang Albert , Berger Mitchel S , Chang Susan M , Phillips Joanna J , Costello Joseph F 
Published: December 2023

Abstract

Background
The TERT promoter mutation (TPM) is acquired in most IDH-wildtype glioblastomas (GBM) and IDH-mutant oligodendrogliomas (OD) enabling tumor cell immortality. Previous studies on TPM clonality show conflicting results. This study was performed to determine whether TPM is clonal on a tumor-wide scale.

Methods
We investigated TPM clonality in relation to presumed early events in 19 IDH-wildtype GBM and 10 IDH-mutant OD using 3-dimensional comprehensive tumor sampling. We performed Sanger sequencing on 264 tumor samples and deep amplicon sequencing on 187 tumor samples. We obtained tumor purity and copy number estimates from whole exome sequencing. TERT expression was assessed by RNA-seq and RNAscope.

Results
We detected TPM in 100% of tumor samples with quantifiable tumor purity (219 samples). Variant allele frequencies (VAF) of TPM correlate positively with chromosome 10 loss in GBM (R = 0.85), IDH1 mutation in OD (R = 0.87), and with tumor purity (R = 0.91 for GBM; R = 0.90 for OD). In comparison, oncogene amplification was tumor-wide for MDM4- and most EGFR-amplified cases but heterogeneous for MYCN and PDGFRA, and strikingly high in low-purity samples. TPM VAF was moderately correlated with TERT expression (R = 0.52 for GBM; R = 0.65 for OD). TERT expression was detected in a subset of cells, solely in TPM-positive samples, including samples equivocal for tumor.

Conclusions
On a tumor-wide scale, TPM is among the earliest events in glioma evolution. Intercellular heterogeneity of TERT expression, however, suggests dynamic regulation during tumor growth. TERT expression may be a tumor cell-specific biomarker.
Developing a computable phenotype for glioblastoma
Authors: Yan Sandra , Melnick Kaitlyn , He Xing , Lyu Tianchen , Moor Rachel S F , Still Megan E H , Mitchell Duane A , Shenkman Elizabeth A , Wang Han , Guo Yi , Bian Jiang , Ghiaseddin Ashley P 
Published: December 2023

Abstract

Background
Glioblastoma is the most common malignant brain tumor, and thus it is important to be able to identify patients with this diagnosis for population studies. However, this can be challenging as diagnostic codes are nonspecific. The aim of this study was to create a computable phenotype (CP) for glioblastoma multiforme (GBM) from structured and unstructured data to identify patients with this condition in a large electronic health record (EHR).

Methods
We used the University of Florida (UF) Health Integrated Data Repository, a centralized clinical data warehouse that stores clinical and research data from various sources within the UF Health system, including the EHR system. We performed multiple iterations to refine the GBM-relevant diagnosis codes, procedure codes, medication codes, and keywords through manual chart review of patient data. We then evaluated the performances of various possible proposed CPs constructed from the relevant codes and keywords.

Results
We underwent six rounds of manual chart reviews to refine the CP elements. The final CP algorithm for identifying GBM patients was selected based on the best F1-score. Overall, the CP rule “if the patient had at least 1 relevant diagnosis code and at least 1 relevant keyword” demonstrated the highest F1-score using both structured and unstructured data. Thus, it was selected as the best-performing CP rule.

Conclusions
We developed and validated a CP algorithm for identifying patients with GBM using both structured and unstructured EHR data from a large tertiary care center. The final algorithm achieved an F1-score of 0.817, indicating a high performance, which minimizes possible biases from misclassification errors.
Responses to Real-World and Hypothetical E-Cigarette Flavor Bans Among US Young Adults Who Use Flavored E-Cigarettes
Authors: Tam Jamie , Jimenez-Mendoza Evelyn , Buckell John , Sindelar Jody , Meza Rafael 
Published: December 2023

Abstract

Introduction
E-cigarette flavor bans could reduce or exacerbate population health harms. To determine how US e-cigarette flavor restrictions might influence tobacco use behavior, this study assesses responses to real-world and hypothetical flavor bans among young adults who use flavored e-cigarettes.

Aims and Methods
An online, national survey of young adults ages 18–34 who use flavored e-cigarettes was conducted in 2021 (n = 1253), oversampling states affected by e-cigarette flavor restrictions. Participants were asked about their responses to real-world changes in the availability of flavored e-cigarettes. Unaffected participants were asked to predict their responses under a hypothetical federal e-cigarette flavor ban.

Results
The most common response to real-world changes in flavored e-cigarettes availability was to continue vaping (~80%). Among those who exclusively vaped, 12.5% switched to combustible tobacco. Quitting all forms of tobacco was selected by 5.3% of those exclusively vape versus 4.2% who dual use. Under a hypothetical federal ban, more than half of respondents stated they would continue vaping; 20.9% and 42.5% of those who exclusively vape versus dual use would use combustible tobacco. Quitting all tobacco products was endorsed by 34.5% and 17.2% of those who exclusively vape versus dual use.

Conclusions
Young adults who vape flavored e-cigarettes have mixed responses to e-cigarette flavor bans. Under both real-world and hypothetical e-cigarette flavor bans, most who use flavored e-cigarettes continue vaping. Under a real-world ban, the second most common response among those who exclusively vape is to switch to smoking; under a hypothetical federal ban, it is to quit all tobacco.

Implications
This is the first national survey to directly ask young adults who use flavored e-cigarettes about their responses to real-world changes in flavored e-cigarette availability due to state and local flavor restrictions. The survey also asked individuals to predict their responses under a hypothetical federal e-cigarette flavor ban. Most who use flavored e-cigarettes would continue vaping following e-cigarette flavor restrictions, but many would switch to or continue using combustible tobacco, highlighting potential negative public health consequences of these policies. Policymakers must consider the impact of e-cigarette flavor bans on both e-cigarette and cigarette use.