bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spectrometric Determination of the Total Concentration of Single-Type Analytes Using Conventional Multidimensional Calibrations
Authors: Vlasova I. V. , Vershinin V. I. 
Published: February 2022

Abstract
Multidimensional calibrations can be used for the spectrometric determination of the total concentration (cΣ) of similar substances; these calibrations relate the generalized signals (AΣ)j measured at different wavelengths (λj) with the concentrations of these analytes (ci) and their absorption coefficients (kij). Such calibrations are conventionally used for the separate determination of analytes, while the ci values are calculated using chemometric algorithms. To find cΣ, one should only take a sum of the found ci values. Despite the simplicity of this type of group analysis, it is rarely used, and its capabilities have not been studied. It is unclear how the accuracy of the cΣ estimate depends on the number of analytical wavelengths (AWLs), the number of standards, and other factors. The purpose of this study was to obtain relevant information using an example of model mixtures of arenes. The absorption spectra of arene mixtures were recorded in the region 230–280 nm, where these spectra are additive. We analyzed 55 hexane solutions containing three to six arenes with a total concentration of 0.1–0.5 mg/mL. The qualitative composition of the model mixtures was considered to compose the matrix of absorption coefficients of individual arenes. The ci values were found by multiple linear regression (MLR, direct calibration). With a sufficiently large number of AWLs, the found ci values were close to zero for arenes absent in the sample and close to the actual ci values for the present arenes. The summation of the found ci gave approximately correct estimates of cΣ (±5%). The single errors of the group analysis were, as a rule, smaller than the errors of the determination of the mixture components. The complication of the model (the introduction of “extra” standards and an increase in the number of AWLs) did not affect the accuracy of the results of group analysis, and the simplification of the model increased errors. If only the most typical standards were used to form the model, the values of kij of which covered the entire range of possible values of kij, the presence of components in the sample that were not taken into account by the simplified model did not lead to a noticeable increase in errors.
Early prediction of treatment response in rheumatoid arthritis by quantitative macrophage PET
Authors: Verweij Nicki , Zwezerijnen Gerben , ter Wee Marieke , de Jongh Jerney , Yaqub Maqsood , van Schaardenburg Dirkjan , Lammertsma Adriaan , Voskuyl Alexandre , Lems Willem , Boers Maarten , van der Laken Conny 
Published: February 2022

ObjectiveTo determine whether macrophage positron emission tomography (PET)/computed tomography (CT) imaging using (R)-[11C]PK11195 at 0 and 2 weeks is associated with clinical response at 13 weeks in patients with early rheumatoid arthritis (RA).MethodsWhole-body (R)-[11C]PK11195 PET/CT scans were performed at baseline and after 2 weeks of COBRA-light (combination therapy of methotrexate and prednisone) treatment in 35 patients with clinically active early RA. Clinical assessment (Disease Activity Score of 44 joints (DAS44)) was performed at 0, 2 and 13 weeks of treatment. PET/CT scans were assessed visually by two blinded, experienced readers, and by calculating standardised uptake values (SUVs) for shoulders, elbows, hips, knees, and hand and feet joints. Clinical and PET variables were compared using (multivariate) linear regression.Results18 males and 17 females were included (baseline DAS44=3.2 ± 1.0). 171 out of 1470 joints were visually PET positive at baseline, decreasing to 100 joints after 2 weeks. In general, small feet joints showed the highest uptake at baseline, and the largest decrease after 2 weeks (Δ0-2). Neither baseline nor Δ0-2 PET measures correlated with DAS44 at 13 weeks. However, at 2 weeks, average SUV of the feet significantly correlated with DAS44 at 13 weeks (R2=0.14, p=0.04). In a multivariable model, DAS44 and average SUV of the feet at 2 weeks showed substantial combined predictive value (combined R2=0.297, p<0.01).ConclusionQuantitative macrophage PET assessment of feet joints, together with DAS44, after 2 weeks of COBRA light treatment in patients with early RA correlates with clinical response after 3 months of treatment.
Coastal processes and landforms
Authors: Spencer Tom , French Jon R. 
Published: February 2022

Abstract
This chapter charts developments in the study of coastal processes and landforms in the period between the 1960s and the end of the millennium, focusing on efforts to understand better sandy beaches, barriers and barrier islands, deltas and estuaries, tidal flats and marshes, and coral reefs. The period saw the emergence of a dual focus on, first, the elucidation of landscape history from morphological and, later, stratigraphic evidence; and, second, the relationships between shoreline morphology and processes of sediment movement. Particularly noteworthy was the integration of a broad spectrum of space scales and timescales in a conceptual framework that became known as ‘coastal morphodynamics’.
Sorting in Memristive Memory
Authors: Alam Mohsen Riahi , Najafi M. Hassan , Taherinejad Nima 
Published: February 2022

Sorting data is needed in many application domains. Traditionally, the data is read from memory and sent to a general-purpose processor or application-specific hardware for sorting. The sorted data is then written back to the memory. Reading/writing data from/to memory and transferring data between memory and processing unit incur significant latency and energy overhead. In this work, we develop the first architectures for in-memory sorting of data to the best of our knowledge. We propose two architectures. The first architecture is applicable to the conventional format of representing data, i.e., weighted binary radix. The second architecture is proposed for developing unary processing systems, where data is encoded as uniform unary bit-streams. As we present, each of the two architectures has different advantages and disadvantages, making one or the other more suitable for a specific application. However, the common property of both is a significant reduction in the processing time compared to prior sorting designs. Our evaluations show on average 37 × and 138× energy reduction for binary and unary designs, respectively, compared to conventional CMOS off-memory sorting systems in a 45 nm technology. We designed a 3×3 and a 5×5 Median filter using the proposed sorting solutions, which we used for processing 64×64 pixel images. Our results show a reduction of 14× and 634× in energy and latency, respectively, with the proposed binary, and 5.6× and 152×10
3
in energy and latency with the proposed unary approach compared to those of the off-memory binary and unary designs for the 3 × 3 Median filtering system.
Phase 1b Clinical Trial with Alpelisib plus Olaparib for Patients with Advanced Triple-Negative Breast Cancer
Authors: Batalini Felipe , Xiong Niya , Tayob Nabihah , Polak Madeline , Eismann Julia , Cantley Lewis C. , Shapiro Geoffrey I. , Adalsteinsson Viktor , Winer Eric P. , Konstantinopoulos Panagiotis A. , D'Andrea Alan , Swisher Elizabeth M. , Matulonis Ursula A. , Wulf Gerburg M. , Mayer Erica L. 
Published: February 2022

Abstract

Purpose:
We had previously reported on the safety and the recommended phase 2 dose (RP2D) of olaparib in combination with the PI3Kα-specific inhibitor alpelisib in patients with high-grade serous ovarian cancer as studied in a phase 1b trial (NCT01623349). Here, we report on the breast cancer cohort from that study.

Patients and Methods:
Eligible patients had recurrent triple-negative breast cancer (TNBC) or recurrent breast cancer of any subtype with a germline BRCA mutation and were enrolled to a dose-escalation or -expansion cohort. After definition of the RP2D, secondary end points included safety and objective response rate (ORR). Exploratory analyses were performed using circulating-free DNA (cfDNA).

Results:
Seventeen patients with TNBC were enrolled with a median of three prior lines of chemotherapy. The most common treatment-related grade 3–4 adverse events were hyperglycemia (18%) and rash (12%). The ORR was 18% (23% for patients treated at the RP2D) and 59% had disease control. The median duration of response was 7.4 months. Analysis of cfDNA tumor fractions (TFx) revealed that patients with TFx &lt; 15% after completion of the first cycle had a longer progression-free survival compared with those with TFx ≥ 15% (6.0 vs. 0.9 months; P = 0.0001).

Conclusions:
Alpelisib in combination with olaparib is tolerable in patients with pre-treated TNBC, with evidence of activity in non-BRCA carriers. cfDNA provided important prognostic information. Results highlight potential synergistic use of a PI3K inhibitor to sensitize HR-proficient (BRCA wild-type) TNBC to PARP inhibition and suggest the potential to expand the use of PARP inhibition beyond BRCA-mutant tumors.
PET-Based Radiogenomics Supports mTOR Pathway Targeting for Hepatocellular Carcinoma
Authors: An Jihyun , Oh Minyoung , Kim Seog-Young , Oh Yoo-Jin , Oh Bora , Oh Ji-Hye , Kim Wonkyung , Jung Jin Hwa , Kim Ha Il , Kim Jae-Seung , Sung Chang Ohk , Shim Ju Hyun 
Published: February 2022

Abstract

Purpose:
This work aimed to explore in depth the genomic and molecular underpinnings of hepatocellular carcinoma (HCC) with increased 2[18F]fluoro-2-deoxy-d-glucose (FDG) uptake in PET and to identify therapeutic targets based on this imaging-genomic surrogate.

Experimental Design:
We used RNA sequencing and whole-exome sequencing data obtained from 117 patients with HCC who underwent hepatic resection with preoperative FDG-PET/CT imaging as a discovery cohort. The primary radiogenomic results were validated with transcriptomes from a second cohort of 81 patients with more advanced tumors. All patients were allocated to an FDG-avid or FDG–non-avid group according to the PET findings. We also screened potential drug candidates targeting FDG-avid HCCs in vitro and in vivo.

Results:
High FDG avidity conferred worse recurrence-free survival after HCC resection. Whole transcriptome analysis revealed upregulation of mTOR pathway signals in the FDG-avid tumors, together with higher abundance of associated mutations. These clinical and genomic findings were replicated in the validation set. A molecular signature of FDG-avid HCCs identified in the discovery set consistently predicted poor prognoses in the public-access datasets of two cohorts. Treatment with an mTOR inhibitor resulted in decreased FDG uptake followed by effective tumor control in both the hyperglycolytic HCC cell lines and xenograft mouse models.

Conclusions:
Our PET-based radiogenomic analysis indicates that mTOR pathway genes are markedly activated and altered in HCCs with high FDG retention. This nuclear imaging biomarker may stimulate umbrella trials and tailored treatments in precision care of patients with HCC.
PhAc-ALGP-Dox, a Novel Anticancer Prodrug with Targeted Activation and Improved Therapeutic Index
Authors: Casazza Andrea , Van Helleputte Lawrence , Van Renterghem Britt , Pokreisz Peter , De Geest Natalie , De Petrini Marzia , Janssens Tom , Pellens Marijke , Diricx Marjan , Riera-Domingo Carla , Wozniak Agnieszka , Mazzone Massimiliano , Schöffski Patrick , Defert Olivier , Reyns Geert , Kindt Nele 
Published: February 2022

Abstract
Clinical use of doxorubicin (Dox) is limited by cumulative myelo- and cardiotoxicity. This research focuses on the detailed characterization of PhAc-ALGP-Dox, a targeted tetrapeptide prodrug with a unique dual-step activation mechanism, designed to circumvent Dox-related toxicities and is ready for upcoming clinical investigation. Coupling Dox to a phosphonoacetyl (PhAc)-capped tetrapeptide forms the cell-impermeable, inactive compound, PhAc-ALGP-Dox. After extracellular cleavage by tumor-enriched thimet oligopeptidase-1 (THOP1), a cell-permeable but still biologically inactive dipeptide-conjugate is formed (GP-Dox), which is further processed intracellularly to Dox by fibroblast activation protein-alpha (FAPα) and/or dipeptidyl peptidase-4 (DPP4). In vitro, PhAc-ALGP-Dox is effective in various 2D- and 3D-cancer models, while showing improved safety toward normal epithelium, hematopoietic progenitors, and cardiomyocytes. In vivo, these results translate into a 10-fold higher tolerability and 5-fold greater retention of Dox in the tumor microenvironment compared with the parental drug. PhAc-ALGP-Dox demonstrates 63% to 96% tumor growth inhibition in preclinical models, an 8-fold improvement in efficacy in patient-derived xenograft (PDX) models, and reduced metastatic burden in a murine model of experimental lung metastasis, improving survival by 30%. The current findings highlight the potential clinical benefit of PhAc-ALGP-Dox, a targeted drug-conjugate with broad applicability, favorable tissue biodistribution, significantly improved tolerability, and tumor growth inhibition at primary and metastatic sites in numerous solid tumor models.
MYC Promotes Tyrosine Kinase Inhibitor Resistance in ROS1-Fusion-Positive Lung Cancer
Authors: Iyer Sudarshan R. , Odintsov Igor , Schoenfeld Adam J. , Siau Evan , Mattar Marissa S. , de Stanchina Elisa , Khodos Inna , Drilon Alexander , Riely Gregory J. , Ladanyi Marc , Somwar Romel , Davare Monika A. 
Published: February 2022

Abstract

Targeted therapy of ROS1-fusion-driven non–small cell lung cancer (NSCLC) has achieved notable clinical success. Despite this, resistance to therapy inevitably poses a significant challenge. MYC amplification was present in ∼19% of lorlatinib-resistant ROS1-driven NSCLC. We hypothesized that MYC overexpression drives ROS1-TKI resistance. Using complementary approaches in multiple models, including a MYC-amplified patient-derived cell line and xenograft (LUAD-0006), we established that MYC overexpression induces broad ROS1-TKI resistance. Pharmacologic inhibition of ROS1 combined with MYC knockdown were essential to completely suppress LUAD-0006 cell proliferation compared with either treatment alone. We interrogated cellular signaling in ROS1-TKI-resistant LUAD-0006 and discovered significant differential regulation of targets associated with cell cycle, apoptosis, and mitochondrial function. Combinatorial treatment of mitochondrial inhibitors with crizotinib revealed inhibitory synergism, suggesting increased reliance on glutamine metabolism and fatty-acid synthesis in chronic ROS1-TKI treated LUAD-0006 cells. In vitro experiments further revealed that CDK4/6 and BET bromodomain inhibitors effectively mitigate ROS1-TKI resistance in MYC-overexpressing cells. Notably, in vivo studies demonstrate that tumor control may be regained by combining ROS1-TKI and CDK4/6 inhibition. Our results contribute to the broader understanding of ROS1-TKI resistance in NSCLC.

Implications:
This study functionally characterizes MYC overexpression as a novel form of therapeutic resistance to ROS1 tyrosine kinase inhibitors in non–small cell lung cancer and proposes rational combination treatment strategies.
Methylated Septin9 (mSEPT9): A Promising Blood-Based Biomarker for the Detection and Screening of Early-Onset Colorectal Cancer
Authors: Loomans-Kropp Holli A. , Song Yurong , Gala Manish , Parikh Aparna R. , Van Seventer Emily E. , Alvarez Rocio , Hitchins Megan P. , Shoemaker Robert H. , Umar Asad 
Published: February 2022

Early-onset colorectal cancer (EOCRC), defined as a diagnosis under age 50, is an emerging public health burden. As many of these individuals fall outside of screening guidelines, the development of a minimally invasive, accurate screening modality for this population is warranted. We evaluated the FDA-approved blood-based biomarker methylated Septin9 (mSEPT9) test as screening tool for EOCRC. EOCRC plasma, healthy plasma, and serum-free conditioned media from cancer cell lines were collected. Cell-free DNA (cfDNA) was isolated and bisulfite converted for use in the assay. mSEPT9 and ACTB measured using Epi proColon V2.0. EOCRC plasma was collected at Massachusetts General Hospital (2005–2019) and controls were collected at the NIH and by ZenBio Inc. (prior to 2019). Twenty-seven EOCRC cases, 48 healthy controls &lt;50 years old, and 39 healthy controls ≥50 years old were included in this study. mSEPT9 was detected more frequently in EOCRC cases (88.9%) compared with healthy controls age &lt;50 (4.2%) and ≥50 (15.4%), respectively (P &lt; 0.001). The sensitivity, specificity, positive predictive value, and negative predictive values of the mSEPT9 assay to detect EOCRC was 90.8% (95% CI, 84.7%–96.9%), 88.9% (95% CI, 77.0%–100.0%), 96.3% (95% CI, 92.3%–100.0%), and 75.0% (95% CI, 60.0%–90.0%), respectively, compared with all healthy controls. mSEPT9 cfDNA level was an independent predictor of survival (P = 0.02). mSEPT9 is a sensitive and specific biomarker for EOCRC detection. These results suggest that mSEPT9 may be useful in the detection of EOCRC, providing a minimally invasive method for screening in this growing population of patients with colorectal cancer.Significance:mSEPT9 may be a novel biomarker for the detection of early-onset colorectal cancer, as it demonstrated high sensitivity and specificity in our study.
The Iron Age Cyclades and Crete: Different Approaches to Connectivity Speculatively Related to Food Security
Authors: Forsyth Doug 
Published: February 2022

This paper offers a case study of some of the Cycladic Islands examining connectivity and insularity between 1000 – 500 BCE. In the Cyclades, evidence of interaction with areas outside of the archipelago and of intra-island connectivity is observable on many of the islands. It will be argued that environmental factors, predominantly low rainfall, may be at least part of the explanation for the adoption of a strategy of reaching out beyond an island’s shores. Cycladic islanders plausibly sought to develop strong networks of affiliation with trading partners from other regions perhaps to serve as buffer zones to rely on during periods of poor food productivity. Compared to Cycladic material, the archaeological evidence of Cretan items found outside Crete is not as robust. This paper speculatively suggests that Cretans, living in a more fertile environment, did not feel the same need as Cycladic islanders to establish networks of affiliation for purposes of food security.
A Poética simbolista da joia “Fin de Siècle”
Authors: Coupeau Charline 
Published: February 2022

Tradução de Bruno Anselmi Matangrano & Caroline MicaeliaJoias escritas, descritas, pintadas, poetizadas ou cinzeladas, o universo destes pequenos objetos preciosos nos desperta para um mundo de sentidos e sentimentos. Num cosmos marcado por percepções e admirações, a joia simbolista do fim do século XIX aperfeiçoa sua linguagem do mundo intermediário, o do imaginário e dos sonhos. Esse microcosmo é apreendido graças à interação de diversas disciplinas artísticas, as quais, por múltiplas correspondências criadoras, permitem à joalheria a identificação da estética fin de siècle e de sua relação com o mundo, com o tempo que passa. Assim como a literatura, a poesia ou a pintura, a joalheria do final do século XIX sabe, portanto, captar as impressões, bem como produzi-las. Graças a seu potencial simbólico, a joia mediadora lírica se inscreve numa tentativa de descentralização tendo por objetivo nos transpor numa autarquia poética.
Les Impressionnistes et Stéphane Mallarmé
Authors: Illouz Jean-Nicolas 
Published: February 2022

Ami des peintres impressionnistes, Mallarmé pose sur leur art un regard d’une extrême acuité, qui tend à faire de l’impressionnisme l’indice d’une triple crise, à la fois métaphysique, esthétique, et politique : – métaphysique, parce que le traitement que l’impressionnisme fait subir à la lumière vaut comme une conversion de celle-ci à l’immanence ; – esthétique, parce que les leçons que Mallarmé retient des peintres éclairent sa propre recherche poétique, quand il travaille lui-même à changer la langue sur le motif ; – politique, enfin parce que l’impressionnisme apparaît comme l’art des temps démocratiques, en ceci que sa « valeur » réside dans le jugement purement « spéculatif » de la foule, qu’il s’agit d’éveiller à une conscience toujours plus haute de son propre génie symbolique.MOTS-CLÉS : Mallarmé ; peinture impressionniste ; impressionnisme littéraire ; poésie et peinture ; Edouard Manet ; Berthe Morisot
‘Ejemplos’ indígenas, el Covi-cho y algunos tips anti fines de mundo
Authors: Medrano Celeste 
Published: February 2022

El objetivo del presente ensayo es poner en diálogo ciertas perspectivas de fines de mundo narradas por los indígenas qom del Gran Chaco Argentino y los sucesos desplegados por la actual pandemia de Covid-19. Con el fin de ‘amansar’ al virus, lo llamaremos Covi-cho y lo situaremos en tensión con los ‘modelos’ y ‘ejemplos’ que el antropólogo Viveiros de Castro propuso en un manuscrito del 2019. Como mostraremos, los fines del mundo para los colectivos indígenas de Argentina se han presentado una y varias veces, al ritmo de la creación de la nación moderna. No obstante esto, ellos siguen ahí, resistiendo en sus devenires. En un contexto como el contemporáneo, donde los Estados ensayan ‘modelos’ para proteger la salud de los ciudadanos, nos preguntaremos: ¿pueden estos ‘ejemplos’ indígenas enseñarnos algo sobre la actual crisis sanitaria global?
Number of Affected Relatives, Age, Smoking, and Hypertension Prediction Score for Intracranial Aneurysms in Persons With a Family History for Subarachnoid Hemorrhage
Authors: Zuurbier Charlotte C.M. , Bourcier Romain , Constant Dit Beaufils Pacôme , Redon Richard , Desal Hubert ,   The ICAN Investigators, Bor Anne S.E. , Lindgren Antti E. , Rinkel Gabriel J.E. , Greving Jacoba P. , Ruigrok Ynte M. 
Published: February 2022

Background:
Persons with a positive family history of aneurysmal subarachnoid hemorrhage are at increased risk of aneurysmal subarachnoid hemorrhage. Preventive screening for intracranial aneurysms (IAs) in these persons is cost-effective but not very efficient. We aimed to develop and externally validate a model for predicting the probability of an IA at first screening in persons with a positive family history of aneurysmal subarachnoid hemorrhage.

Methods:
For model development, we studied results from initial screening for IA in 660 prospectively collected persons with ≥2 affected first-degree relatives screened at the University Medical Center Utrecht. For validation, we studied results from 258 prospectively collected persons screened in the University Hospital of Nantes. We assessed potential predictors of IA presence in multivariable logistic regression analysis. Predictive performance was assessed with the C statistic and a calibration plot and corrected for overfitting.

Results:
IA were present in 79 (12%) persons in the development cohort. Predictors were number of affected relatives, age, smoking, and hypertension (NASH). The NASH score had a C statistic of 0.68 (95% CI, 0.62–0.74) and showed good calibration in the development data. Predicted probabilities of an IA at first screening varied from 5% in persons aged 20 to 30 years with two affected relatives, without hypertension who never smoked, up to 36% in persons aged 60 to 70 years with ≥3 affected relatives, who have hypertension and smoke(d). In the external validation data IA were present in 67 (26%) persons, the model had a C statistic of 0.64 (95% CI, 0.57–0.71) and slightly underestimated IAs risk.

Conclusions:
For persons with ≥2 affected first-degree relatives, the NASH score improves current predictions and provides risk estimates for an IA at first screening between 5% and 36% based on 4 easily retrievable predictors. With the information such persons can now make a better informed decision about whether or not to undergo preventive screening.