bluuebunny/crossref_metadata_2025 huggingface dataset:
Covalent adduct formation as strategy for efficient CO2 fixation in crotonyl-CoA carboxylases/reductases
Authors: Recabarren Rodrigo , Tinzl Matthias , Saez David , Gomez Aharon , Erb Tobias , Vöhringer-Martinez Esteban
Published: April 2023

Increasing levels of CO2 in the atmosphere have led to a growing interest into the various ways nature transforms this greenhouse gas into valuable organic compounds. Crotonyl-CoA carboxylases/reductases (Ccr's) are the most efficient biocatalysts for CO2 fixation because of their oxygen tolerance, their high catalytic rate constants and their high fidelity. The reaction mechanism involving hydride transfer from the NADPH cofactor and addition of CO2 to the reactive enolate, however, is not completely understood. In this study, we use computer simulations in combination with high-level ab initio calculations to trace the free energy landscape along two possible reaction paths: In the direct mechanism hydride transfer is immediately followed by CO2 addition whereas in the C2 mechanism a thermodynamically stable covalent adduct between the substrate and the NADPH cofactor is formed. This C2 adduct, which has been previously characterized experimentally, serves as a stable intermediate avoiding the reduction side reaction of the reactive enolate species and it is able to react with CO2 with similar kinetics as the direct reaction mechanism as confirmed by measured kinetic isotope effects. Thus, our results show that nature's most efficient CO2-fixing enzyme uses the formation of a covalent adduct as a strategy to store the reactive enolate species. The emerging microscopic picture of the CO2-fixing mechanism confirms previous experimental observations and provides new insights into how nature handles highly reactive intermediates to fix this inert greenhouse gas.
MLQD: A package for machine learning-based quantum dissipative dynamics
Authors: Ullah Arif , Dral Pavlo O.
Published: April 2023

Machine learning has emerged as a promising paradigm to study the quantum dissipative dynamics of open quantum systems. To facilitate the use of our recently published ML-based approaches for quantum dissipative dynamics, here we present an open-source Python package MLQD (https://github.com/Arif-PhyChem/MLQD), which currently supports the three ML-based quantum dynamics approaches: (1) the recursive dynamics with kernel ridge regression (KRR) method, (2) the non-recursive artificial-intelligence-based quantum dynamics (AIQD) approach and (3) the blazingly fast one-shot trajectory learning (OSTL) approach, where both AIQD and OSTL use the convolutional neural networks (CNN). This paper describes the features of the MLQD package, the technical details, optimization of hyperparameters, visualization of results, and the demonstration of the MLQD's applicability for two widely studied systems, namely the spin-boson model and the Fenna--Matthews--Olson (FMO) complex. To make MLQD more user-friendly and accessible, we have made it available on the Python Package Index (PyPi) platform and it can be installed via pip install mlqd. In addition, it is also available on the XACS cloud computing platform (https://XACScloud.com) via the interface to the MLATOM package (http://MLatom.com)
Sensitizer-free photochemical regeneration of benzimidazoline organohydride
Authors: Matsubara Ryosuke , Harada Tatsuhiro , Xie Weibin , Yabuta Tatsushi , Xu Jiasheng , Hayashi Masahiko
Published: April 2023

Organohydrides are an important class of organic compounds that can provide hydride anions for chemical and biochemical reactions, as demonstrated by reduced nicotinamide adenine dinucleotide serving as an important natural redox cofactor. The coupling of hydride transfer from the organohydride to the substrate and subsequent regeneration of the organohydride from its oxidized form can realize organohydride-catalyzed reduction reactions. Depending on the structure of the organohydride, its hydridicity and ease of regeneration vary. Benzimidazoline (BIH) is one of the strongest synthetic C–H hydride donors; however, its reductive regeneration requires highly reducing conditions. In this study, we synthesized various oxidized and reduced forms of BIH derivatives with aryl groups at the 2-position and investigated their photophysical and electrochemical properties. 4-(Dimethylamino)phenyl-substituted BIH exhibited salient red-shifted absorption compared to other synthesized BIH derivatives, and visible-light-driven regeneration without using an external photosensitizer was achieved. This knowledge has significant implications for the future development of solar-energy-based catalytic photoreduction technologies that utilize organohydride regeneration strategies.
Antibody-based Imaging of Bioreductive Prodrug Release in Hypoxia
Authors: Tosun Cagla , Mallerman Maxim , Wallabregue Antoine , Phillips Sarah , Edwards Claire , Conway Stuart , Hammond Ester
Published: April 2023

Regions of hypoxia occur in most tumors and predict for poor patient prognosis. Hypoxia-activated prodrugs provide an ideal strategy to target the aggressive, hypoxic fraction of a tumor while protecting the normal tissue from toxicity. A key challenge associated with the development of novel hypoxia-activated prodrugs, however, is the ability to visualize the delivery of the prodrug to hypoxic regions and determine where it has been activated. Here we report a modified version of the commonly used nitroimidazole bioreductive group that incorporates the fluoroethyl epitope of the antibody-based hypoxia imaging agent, EF5. Attachment of this group to the red fluorescent dye, DCM, enabled us to correlate release of the DCM dye with imaging of the reduced bioreductive group using the EF5 antibody. This study confirmed that the antibody was imaging reduction and fragmentation of the pro-fluorophore. We next employed the modified bioreductive group to synthesize a new prodrug of the KDAC inhibitor Panobinostat, EF5-Pano. Release of EF5-Pano in hypoxic multiple myeloma cells was imaged using the EF5 antibody, and the presence of an imaging signal correlated with apoptosis and a reduction in cell viability. Therefore, EF5-Pano is an imageable hypoxia-activated prodrug with proven cytotoxic effect in multiple myeloma, which could be utilized in future in vivo experiments.
Simulation of Conformality of ALD Growth Inside Lateral Channels: Comparison Between a Diffusion-Reaction Model and a Ballistic Transport-Reaction Model
Authors: Järvilehto Jänis , Velasco Jorge , Yim Jihong , Gonsalves Christine , Puurunen Riikka
Published: April 2023

Atomic layer deposition (ALD) has found significant use in the coating of high-aspect-ratio (HAR) structures. Approaches to model ALD film conformality in HAR structures can generally be classified into diffusion-reaction (DR) models, ballistic transport-reaction (BTR) models and Monte Carlo simulations. This work compares saturation profiles obtained using a DR model and a BTR model. The saturation profiles were compared qualitatively and quantitatively in terms of half-coverage penetration depth, slope at half-coverage penetration depth and adsorption front broadness. The results showed qualitative agreement between the models, except for a section of elevated surface coverage at the end of the structure, `trunk', observed in the BTR model. Quantitatively, the BTR model produced deeper penetration into the structure, lower absolute values of the slope at half-coverage penetration depth and broader adsorption fronts compared to the DR model. These differences affect the values obtained when extracting kinetic parameters from the saturation profiles.
Scalable all-inorganic halide perovskite photoanodes with >100 h operational stability containing Earth-abundant materials
Authors: Daboczi Matyas , Cui Junyi , Temerov Filipp , Eslava Salvador
Published: April 2023

The application of halide perovskites in photoelectrochemical generation of solar fuels and feedstocks is hindered by the instability of perovskites in aqueous electrolytes and the use of expensive electrode and catalyst materials, particularly in photoanodes driving kinetically slow water oxidation. Here, we incorporate solely Earth-abundant materials to fabricate a CsPbBr3-based photoanode that reaches a low onset potential of +0.4 VRHE and 8 mA cm-2 photocurrent density at +1.23 VRHE for water oxidation, close to the radiative efficiency limit of CsPbBr3. This photoanode retains 100% of its stabilized photocurrent density after >100 h continuous operation, that can be extended to weeks by replacing the inexpensive graphite sheet upon signs of deterioration. The improved performance is due to an efficiently electrodeposited NiFeOOH catalyst on a protective self-adhesive graphite sheet, and enhanced charge transfer achieved by phase engineering of CsPbBr3. Devices with >1cm2 area, and low-temperature processing demonstrate the potential for low capital cost, stable, and scalable perovskite photoanodes.
Magnesium(I) Reduction of Aluminum(III) Hydride Complexes: Generation of Mixed Valence Aluminum (AlI/Al0) Hydride Cluster Compounds, [Al6H8(NR3)2{Mg(-diketiminate)}4]
Authors: Jones Cameron , Mullassery Sneha , Yuvaraj K. , Dange Deepak , Jones Dafydd , Rajeshkumar Thayalan , Douair Iskander , Piltz Ross , Edwards Alison , Maron Laurent
Published: April 2023

Reduction of a range of amido- and aryloxy-aluminum dihydride complexes, e.g. [AlH2(NR3){N(SiMe3)2}] (NR3 = NMe3 or N-methylpiperidine (NMP)), with -diketiminato dimagnesium(I) reagents, [{(ArNacnac)Mg}2] (ArNacnac = [HC(MeCNAr)2]-, Ar = mesityl (Mes) or 2,6-xylyl (Xyl)), have afforded deep red mixed valence aluminum hydride cluster compounds, [Al6H8(NR3)2{Mg(ArNacnac)}4], which have an average Al oxidation state of +0.66, the lowest for any well-defined aluminum hydride compound. In the solid-state, the clusters are shown to have distorted octahedral Al6 cores, having zero-valent Al axial sites and mono-valent AlH2- equatorial units. Several novel by-products were isolated from the reactions that gave the clusters, including the Mg‒Al bonded magnesio-aluminate complexes, [(ArNacnac)(Me3N)Mg‒Al(-H)3[{Mg(ArNacnac)}2(-H)]]. Computational analyses of one aluminum hydride cluster revealed its Al6 core to be electronically delocalized, and to possess one unoccupied, and six occupied, skeletal molecular orbitals.
Viscosity-sensitive membrane dyes as tools to estimate the crystalline structure of lipid bilayers
Authors: Paez-Perez Miguel , Dent Michael R. , Brooks Nicholas J. , Kuimova Marina K.
Published: April 2023

Lipid membranes are crucial for cellular integrity and regulation, and tight control of their structural and mechanical properties is vital to ensure that they function properly. Fluorescent probes sensitive to the mem-brane’s microenvironment are useful for investigating lipid membrane properties, however, there is currently a lack of quantitative correlation between the exact parameters of lipid organization and a readout from these dyes. Here, we investigate this relationship for ‘molecular rotors’, or microviscosity sensors, by simultaneously measuring their fluorescence lifetime to determine the membrane viscosity, while using the X-Ray diffraction the determine the membrane’s structural properties. Our results reveal a phase-dependent correlation be-tween the membrane’s structural parameters and mechanical properties measured by a BODIPY-based mo-lecular rotor, giving excellent predictive power for the structural descriptors of the lipid bilayer. We also demonstrate that differences in membrane thickness between different lipid phases is not a prerequisite for formation of lipid microdomains and that this requirement can be disrupted by the presence of line-active molecules. Our results underpin the use of membrane-sensitive dyes as reporters of the structure of lipid membranes.
Ultrafast Transient Vibrational Action Spectroscopy of Cryogenically Cooled Ions
Authors: Chen Liangyi , Ma Zifan , Fournier Joseph
Published: April 2023

Ultrafast transient vibrational action spectra of cryogenically cooled Re(CO)3(CH3CN)3+ ions are presented. Nonlinear spectra were collected in the time domain by monitoring the photodissociation of a weakly-bound N2 messenger tag as a function of delay times and phases between a set of three infrared pulses. Frequency-resolved spectra in the carbonyl stretch region show relatively strong bleaching signals that oscillate at the difference frequency between the two observed transitions as a function of the pump-probe waiting time. This observation is consistent with the presence of nonlinear pathways resulting from underlying cross-peak signals between the coupled symmetric asymmetric C≡O stretch pair. The successful demonstration of frequency resolved ultrafast transient vibrational action spectroscopy of dilute molecular ion ensembles provides an exciting new framework for the study of molecular dynamics in isolated, complex molecular ion systems.
The first encounters of primary school students and parents in blended english classes
Authors: Semra Aydin , Ayfer Su-Bergil
Published: April 2023

This study investigates what blended English learning, the first of its kind at their school, means to primary school students and their parents. It aims to demonstrate how they experience and perceive blended English classes, particularly during their first encounter, in order to conceptualise the most commonly perceived benefits and to challenge the existing theoretical framework, Social Presence Theory. This study was conducted to help shareholders, specifically in a primarylevel English language education context, to exclude or reduce the barriers and maximise the benefits. To this end, a cross-sectional survey design was adopted, and 147 students and 138 parents participated in this study. Data was collected through questionnaires and calculated using the SPSS program. The data showed that primary school students and parents were generally pleased with their blended English class experiences. They found blended English learning experiences to be valuable and enhance their learning, especially in critical periods such as the COVID-19 pandemic. However, the face-to-face format is perceived more positively because of the limitations and challenges of blended and online English classes in terms of interactions and social elements. Based on the results, some implications and suggestions for further research are provided.
Emotional Intelligence Levels of IIT Students in India
Authors:   Indian Institute of Technology-Dhanbad, Dhanbad, India, Odame Christabel , Pandey Mrinalini ,   Indian Institute of Technology-Dhanbad, Dhanbad, India
Published: April 2023

Emotional Intelligence (EI) has been identified as a key competence that helps people to relate with one another easily. As such, EI coupled with IQ makes one a star performer at the workplace. Therefore, students need to possess both EI and IQ. For this reason, a descriptive study was conducted to assess the EI levels of IIT students at IIT (ISM)-Dhanbad, India. The analysis was done in two folds; first, to assess the EI levels of the participants. Secondly, to compare the EI levels of the participants using demographic variables. The purposive sampling technique was used to sample 200 engineering students from various engineering departments. The study results unveiled that students from IIT (ISM) Dhanbad were somewhat emotionally intelligent. Also, when the demographic variables were assessed, it was revealed that gender and age were not statistically significant on EI which means that gender and age does not affect a person’s EI. Albeit, in this study, work experience and family income were statistically significant on EI which implied that a person’s work experience and family income could affect their EI. When the EI levels of these participants are developed and improved, they will thrive and succeed both at the workplace, college and in life as a whole as their EI levels are significantly high.
Research the Future Teachers’ Digital Competence in the Context of Personality Pedagogy
Authors:   Immanuel Kant Baltic Federal University, Kaliningrad, Russia, Grebenyuk Tatyana , Nesyna Svetlana ,   Immanuel Kant Baltic Federal University, Kaliningrad, Russia, Ermakova Nadezhda ,   Immanuel Kant Baltic Federal University, Kaliningrad, Russia, Kaygorodova Olga ,   Immanuel Kant Baltic Federal University, Kaliningrad, Russia
Published: April 2023

The relevance of the study is explained by the digital transformation of society and the digitalization of education, its opportunities and risks. The key idea of the research is to reveal the phenomenon of students’ digital competence in the context of personality pedagogy. Namely, through the skills and competencies in the areas of individuality that arise when students apply digital technologies in their training. Data collection was carried out using self-assessment. Students assessed skills and competencies in the areas of individuality. The factor analysis showed that the digital competence of students is associated with the subject-practical sphere, existential sphere and the sphere of self-regulation.
Trends in the development of crop production that affect its resource provision
Authors: Lukomets Artem
Published: April 2023

In the development of crop production, a number of trends in the development of the industry were identified that affect its resource support, including quantitative and qualitative changes in land resources; violation of technological and agrotechnological processes; non-equivalence of exchange for the acquisition of a unit of basic crop resources; differentiated use of resources; increase in resource losses in the process of production, processing, storage, sale and consumption of crop products and food from crop raw materials, etc.
The Romani LGBTIAQ Movement and the Role of ARA ART
Authors: Tišer David
Published: April 2023

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Laura Corradi. 2018. Gypsy Feminism. Intersectional Politics, Alliances, Gender and Queer Activism. London: Routledge.
Authors: Bernacchi Erika
Published: April 2023

book review
Affective Politics and Alliances in ‘Queering the Gypsy’ and Facing Antigypsyism in the LGBT Milieu
Authors: Corradi Laura
Published: April 2023

This essay engages with issues of homophobia, lesbophobia, biphobia, and transphobia in  Romani/Gypsy/Traveller (RGT) communities. A lack of acceptance, marginalization, and at times expulsion of Queer people from RGT communities is a source of suffering for individuals and their families – with political consequences in terms of solidarity and alliances. Sexual minorities within marginalized ethnic and non-ethnic RGT minorities, when excluded, can be regarded as a threat to the social cohesion of the group and to internal social ties based on common struggles for economic and cultural justice. Acceptance for Queer people in RGT communities may also improve relations with social movements’ alliances, a sensible and necessary step –primarily in the anti-racist and feminist arenas, movements for social rights, i.e., jobs and housing.The paper discusses social (mis)representations of the ‘Gypsy Queer’ vs. self-representations emerging from activists’ experiences. In light of ‘affective politics’ – s conceptualized by Sara Ahmed – experiences of Homo-Lesbo-Bi-Trans-phobia in the RGT communities and ‘soft’ anti-gypsyism in Queer communities are addressed. In conclusion, affective politics are viewed in the frame suggested by Judith Okely around Roma-Gypsy-Traveller cultural identity “constructed through opposition, not isolation”; through the mirror of Jasbir Puar’s theory of identity created in the constant and aware, individual and collective, assemblage of parts of self; and as an element of ‘travelling activism’ – practice of “mobilizing hybrid forms of expertise and knowledge across space and difference” contesting both territorialization and ethnicization, as in Van Baar.
Fatal Coincidence: On the Root Causes of the Roma Holocaust
Authors: Kapralski Slawomir
Published: April 2023

This article puts forward a broad interpretive scheme to understand the deep causes of the Nazi persecution of Roma. It is argued that a reference to the interplay of modernity and colonialism is required to understand how Roma were constructed as different, how this difference became racialized, and how projects to eliminate this difference were drawn up. The author presents Roma as the main actors in the two most important European historical processes: modernization and colonization. Various modern strategies targeting Roma are described,together with the impact of the colonial experience that allowed Roma to be seen as the “savage within”, threatening the identity of German society. Finally, the similarities between colonial violence and persecution of Roma are brought into focus.
Representing/Roma/Holocaust: Exhibition Experiences in Europe and East Asia
Authors: Rosenhaft Eve , Lee Kyu Dong
Published: April 2023

This article reflects on two exhibitions, in 2018 and 2019, about the Nazi persecution of German Sinti and Roma. One was produced by an Anglo-German curatorial team and toured Britain and Continental Europe. The second was designed by South Korean curators and installed temporarily in a gallery in downtown Seoul. The two exhibitions drew on the same photographic archive, narrated the persecution histories of Romani subjects of the photographs, and used the story of their relationship with the non-Romani photographer to ask questions about responsibility and to prompt visitors to reflect on their own status as “implicated subjects” in contemporary forms of discrimination. Given different expectations of the level of knowledge that visitors bring to the exhibition and different communicative tools familiar to them (the Seoul curators included creative artists), the two curatorial teams took very different approaches to informing and moving their audiences – and to meeting the recognized challenges of representing Romani history and identity – not least in the ways in which the exhibition’s message was mediated in face-to-face conversations on site. The aesthetic approach adopted in Seoul did not fully succeed in maintaining the balance between explanation and exoticization. The evaluation relies on visitor surveys (quantitative and qualitative) and interviews with guides.
Between Antigypsyism and Human Rights Education: A Critical Discourse Analysis of the Representations of the Roma Holocaust in European Textbooks
Authors: Pecak Marko , Spielhaus Riem , Szakács-Behling Simona
Published: April 2023

This paper investigates representations of the Roma Holocaust in European textbooks on history, civics, and geography for pupils in upper primary to the end of secondary education. By applying critical discourse analysis (CDA) to a dataset of 472 passages and images referring to the Roma Holocaust from 869 textbooks, this paper reveals educational discourses of in/exclusion by focusing on narratives and linguistic tools, such as speech acts, level of detail and specificity, perspectives in semantic and grammatical forms, vocabulary and syntax. Most knowledge disseminated on the Roma Holocaust concerns numbers and technicalities of murder while Roma-specific details, survivor stories, and individual voices, as well as Romani terminology for the Holocaust (Porrajmos) are rare. Generally, the textbooks show little commitment to circulating knowledge about the Roma Holocaust, or specifically focusing on civic or human rights education. Portrayals of the Roma Holocaust are permeated by both explicitly and implicitly racist discourses, coupled with a distinct lack of critical tools withwhich to deconstruct these narratives. Overall, current textbook representations of the Roma Holocaust mirror social discourse and possibly serve to reproduce Romani exclusion and risk reinforcing antigypsyism attitudes.
Síndrome de hiper-IgM con afectación hepática temprana
Authors: Coronado Hernández Kareli Guadalupe , Campos Téllez Héctor Hugo , Macías Robles Ana Paola , Cortés Grimaldo Rosa María , Estrada García Carlos David , Barrios Díaz Britza , Ramírez Nepomuceno Adriana , Barreto Alcalá Marlén , Esparza Amaya David , Carvajal Alonso Hilda Lilian , Berrón Ruiz Laura
Published: April 2023

Introducción: El síndrome de hiper-IgM es un error innato de la inmunidad, caracterizado por un defecto en el cambio de isotipo de inmunoglobulina, con valores disminuidos de IgG, IgA e IgE, y concentraciones normales o elevadas de IgM. Predispone a procesos infecciosos en el sistema respiratorio y aparato gastrointestinal, además de enfermedades autoinmunes y neoplasias.
Reporte de caso: Paciente pediátrico de género masculino, de 5 años y 7 meses de edad, con antecedente de dos cuadros de neumonía (uno de estos grave) y diarrea crónica desde los 2 años. Neutropenia moderada persistente, disminución de la concentración de IgG y elevación de IgM. La citometría de flujo confirmó la ausencia de CD40L. Durante la evolución clínica tuvo afectación hepática temprana.
Conclusión: El síndrome de hiper-IgM predispone a daño hepático, por lo que se requiere la evaluación completa y el diagnóstico oportuno. El tratamiento antiinfeccioso activo y el control de la respuesta inflamatoria son factores decisivos para establecer el tratamiento del daño hepático.
Síndrome de Wiskott-Aldrich con plaquetas de tamaño normal y mutación c.295C>T en el gen WAS. Informe de caso
Authors: Cunha-Carneiro Maria Luiza , Xavier-Andrade Millena , Bacarini-Leite Luiz Fernando , Mosca Tainá , Carvalho Neves Forte Wilma
Published: April 2023

Antecedentes: El síndrome de Wiskott-Aldrich es un error innato de la inmunidad, distinguido por trombocitopenia, plaquetas pequeñas, eccema severo, infecciones recurrentes, y susceptibilidad a enfermedades autoinmunes y neoplasias. El diagnóstico es difícil de establecer, especialmente cuando las plaquetas son de tamaño normal.
Reporte de caso: Paciente masculino de 3 años, enviado al Hospital Universitario da Santa Casa de São Paulo, Brasil, por otitis media aguda, con evolución a sepsis por Haemophilus influenzae. Al mes de edad fue diagnosticado con trombocitopenia autoinmune, y a los 2 años se llevó a cabo explenectomía. Durante el seguimiento requirió tres hospitalizaciones: una por infección por Streptococcus pneumoniae, que evolucionó a sepsis; otra por exacerbación de eccema, aislándose S. epidermidis, y la última por fiebre de origen indeterminado. Las pruebas de laboratorio informaron: concentración de plaquetas dentro de los valores de referencia después de la esplenectomía, y de tamaño normal. A los 4 años se efectuaron nuevas pruebas, que reportaron: IgE 3128 kU/L; IgA, IgG y anticuerpos anti-polisacáridos normales; disminución de IgM y de CD19, TCD4, T y B vírgenes; aumento de TCD8; NK normales. Se sospechó el diagnóstico de síndrome de Wiskott-Aldrich. Mediante estudios de genética se identificó la mutación c.295C>T en el gen WAS.
Conclusiones: El caso aquí expuesto expresó una nueva mutación en el gen SWA, caracterizado por manifestaciones clínicas de fenotipo leve del síndrome de Wiskott-Aldrich, con trombocitopenia, plaquetas de tamaño normal y herencia ligada al cromosoma X. Es importante establecer el diagnóstico y tratamiento oportunos para ofrecer una mejor calidad de vida en estos pacientes.
SOMATIC MUTATIONAL LANDSCAPE CHARACTERIZATION OF METASTATIC BREAST CANCER IN BRAZIL
Authors: Bittencourt Yuri Cardoso Rodrigues Beckedorff , Almada Lucas Soares , Corrêa Tatiana Strava , Assad Daniele Xavier , Gonçalves Marina Sahade , Shimada Andrea Kazumi , Katz Artur , Barroso-Sousa Romualdo
Published: April 2023

Objective: Breast cancer (BC) is the most common malignancy among Brazilian women after non-melanoma skin cancer. The mutational landscape of BC in Brazil is unknown. This study describes the mutational profile of a cohort of patients with metastatic breast cancer (MBC) who had undergone next-generation sequencing (NGS) using a comprehensive somatic tumor panel. Methods: We retrospectively reviewed medical records from MBC patients. The mutational profile, clinical, and demographic characteristics were abstracted. Furthermore, the patterns of ordering the panel and its usefulness for a clinical decision were evaluated. Results: We found 54 female patients who fulfilled the above criteria. The median age was 58 years (32–86). Most tumors tested were hormone receptor-positive (74%), followed by triple-negative (20.3%), hormone receptor-positive/HER2-positive (3.7%), and HER-2 positive (1.85%). The median time between the diagnosis of metastatic disease and the NGS execution was 40 months (0–112), and only three patients (5.5%) had not received systemic treatment prior to the test recommendation. Somatic mutations were identified in 94.4% (n=51) of the patients, mainly in PIK3CA (48.1%), TP53 (42.5%), and ESR1 (18.5%) genes. Tumor burden mutation (TMB) was informed in 61.1% (n=33) somatic panels, and 15.1% (n=5) had tumors with TMB ≥10 mutations/megabase. Approved genome-driven cancer therapy was found in 54.9% (n=28), and eight patients (28.5%) received it. Conclusion: This study showed a high proportion of actionable somatic genomic alterations, and it reinforces the growing usefulness of a comprehensive NGS tumor somatic panel in managing patients with MBC.
FAT LOSS SOLUTIONS FOR OVERWEIGHT BREAST CANCER PATIENTS WITH SLEEP DISTURBANCES
Authors: Artene Diana
Published: April 2023

Objective: Obese breast cancer patients obtain lower pathological complete response rates and experience more neuropathy, anemia, fatigue, and depression during chemotherapy; have more surgical complications such as infection, seroma, implant loss, and lymphedema; more radiation dermatitis and esophagitis; lower disease-free survival and overall survival plus more grade 3 and 4 side effects under anti-HER2 treatments; lower Fulvestrant and Anastrozole efficacy; and more AET-related and Alpelisib side effects; the main impact coming from the fact that these are the main causes of treatment non-adherence and discontinuation. Due to the detrimental metabolic and behavioral impact, the quality of sleep is one of the important patient-related factors that needs to address when addressing obesity-related causes to improve oncologic outcomes. Methods: Seeking fat loss solutions for overweight ER+ breast cancer patients with sleep disturbances, we randomized 50 patients — of which 16 were depressive — to follow a high protein diet (D) or the diet and sleep journal interventions (D+SJ) for 8 weeks. Patients ate only when they were hungry, ate foods that were high in protein, calcium, omega-3, pre-, and probiotics, and wrote a daily food journal. Half of the patients were asked to write a 7-day SJ: the time it took them to fall asleep, the number of awakenings during the night, how much they slept, how much they stayed in bed, and self-perceived sleep quality. They were asked to set their sleeping and wake-up hours based on their SJ answers and to not sleep during the day. Eight patients from the D+SJ group left the study, five being depressive. We measured body composition with a bioelectrical impedance analysis scale. Results: The D group lost 2.31±2.86% of body fat (p=0.000) and 0.76±1.16% of visceral fat (p=0.000) with no differences between patients with or without depression. The D+SJ group improved sleep quality and lost 2.16±2.35% of body fat (p=0.002) and 0.86±1.24% of visceral fat (p=0.005); but depressive patients did not obtain statistically significant results, which may be because of the overtiring effect of the SJ intervention. So, both D and D+SJ interventions improve breast cancer patients’ body composition despite sleep disturbances. Conclusion: SJ interventions improve sleep quality in patients without depression, thereby decreasing weight regain risk.
OPPORTUNISTIC MAMMOGRAPHIC SCREENING INDICATORS IN A DECADE IN THE STATE OF GOIÁS: TECHNICAL, SOCIAL, AND ECONOMIC CHARACTERISTICS
Authors: Corrêa Rosangela da Silveira , Peixoto João Emílio , Rahal Rosemar Macedo Sousa , Rodrigues Danielle Cristina Netto , Marins Lucy Aparecida Parreira , Bastos Suzana Alves , Freitas Júnior Ruffo de
Published: April 2023

Objective: The aim of this study was to evaluate indicators of opportunistic mammographic screening performed in the state of Goiás, according to technical, social, and economic aspects. Methods: Ecological study, where the Diagnostic Centers that performed mammography, were observed. Data were collected on the characteristics of the equipment, production, value, and sources of payment for the examinations. For the 2019 data, the following variables were analyzed: imaging technology, availability of mammography devices and estimated production, mammography expenditures, and mammographic coverage in the female population aged 40–69 years. The ratio of non-Unified Health System (SUS) and SUS examinations and the Composite Annual Growth Rate (CAGR) were also calculated to compare the indicators of opportunistic screening between 2008 and 2019. Results: In 2019, 164 mammography machines were identified, and of these, 66 met the SUS. This year, 400,896 examinations were produced at a cost of R$41,931,120.00. The ratio of expenses between non-SUS and SUS care was 10.3, and the number of tests performed for non-SUS and SUS was 3.87. Opportunistic screening coverage was 69.8%, with the share of non-SUS services being 56.3% and SUS only 13.5%. When compared with the results of the 2008 study, a reduction in CAGR was observed: 16.3% for conventional mammography and 17% for digital mammography. The CAGR of the female population was 1.9%, and those aged 40–69 years showed an annual increase of 3.5%. There was an increase in the number of equipment used with a CAGR of 4.3% per year and an increase in the number of examinations of 2.5% per year; the CAGR of mammography coverage was -0.9% per year. Conclusion: The indicators show improvement in the technology park. The annual growth of the female population demonstrates an aging population, and the increase in the number of examinations was just enough to maintain mammography coverage.
STANDARDIZATION OF THE FICOLL GRADIENT TECHNIQUE FOR THE ISOLATION OF MONONUCLEAR CELLS FROM PERIPHERAL BLOOD
Authors: Santos Erick de Matos , Moreira Thayse Batista , Gomes Ana Luiza de Freitas Magalhães , Ramos Ana Paula Alvares , Queiroz Fábio Ribeiro , Salles Paulo Guilherme de Oliveira , Braga Letícia Conceição
Published: April 2023

Objective: The objective of this study was to standardize the Ficoll gradient technique for the circulating hematopoietic stem cell (HSC) isolation for the assembly of the peripheral blood mononuclear cell (PBMC) biorepository of breast cancer (BC) patients attended in the Clinical Oncology Service of Instituto Mário Penna. Methods: The study protocol was approved by the Ethics Committee of Instituto Mário Penna (CAEE 82703418.8.0000.5121). In recommended protocols, 15 mL of blood was used. At first, we adapted this volume due to the limited amounts of samples for research available. Blood was collected in a 9-mL sodium heparin tube. The experiments were performed in 50-mL conical tubes, but with reduced blood volume, and no PBMC ring was formed. It was necessary to change to 15 mL conical tubes. Finally, the remaining red blood cells were lysed with ammonium chloride. However, with the reduced volume, this solution lysed the PBMC too. Then, we decided to remove this step from the protocol. Results: We obtained 8.06×106 cells/mm3 with 80% viability. Data were confirmed by a Neubauer camera and an automatic cell counter. The HSCs were labeled with antibodies against CD34 and CD133 by flow cytometry. Conclusion: The characterization of HSCs is important to link tumor-associated HSCs with malignant and immunosuppressive phenotypes. Studies are in progress with this standardization, and they will permit us to perform the HSC characterization of BC patients with a better knowledge of tumor microenvironment.
EVALUATION OF CYP2D6 POLYMORPHISM IN PATIENTS WITH BREAST CANCER AND TAMOXIFEN USERS OF TWO BREAST SERVICES OF BELO HORIZONTE
Authors: Caetano Geovanna Cota , Rodrigues Julia Assis , Bellini Patrícia Aguiar , Lucena Clécio Ênio Murta de , Simões Renata Toscano , Sandrim Valéria Cristina
Published: April 2023

Objective: This study aimed to assess the CYP2D6*4 polymorphism and the association of this polymorphism with the evolution of breast cancer since the reduction of the CYP2D6 activity due to polymorphisms of the gene that encodes the enzyme or the use of inhibitory drugs has been linked to reduced levels of endoxifen (EDF) and worse prognosis in women treated with tamoxifen (TAM). The treatment is multidisciplinary; TAM is an established and important therapeutic modality. This drug is metabolized by the CYP2D6 enzyme into its active metabolites, 4-hydroxytamoxifen (HTF), and EDF. Methods: The study was approved by the local ethical committee (CEP) and registered as CEP number 065/2009. This is a prospective study in which interviews were conducted by graduated mastologists with 138 patients with breast cancer treated with TAM in two public outpatient clinics. The inclusion criteria were invasive breast cancer diagnosis and use of the TAM as part of the treatment. Clinical data and blood samples were collected for CYP2D6 genotyping with the Restriction Fragment Length Polymorphism technique. The statistical analysis was conducted through the STATA 10.3 program. Results: We observed that 14.5% of patients had a recurrence and 30% of premenopausal patients had menstrual cycles. The average disease-free survival was 43.6±45.7 months, and the average overall survival was 44.5±46.1 months. Regarding the polymorphism, 81.15% were extensive metabolizers (*1/*1), 16.66% were intermediate metabolizers (*1/*4), and 2.17% were poor metabolizers (*4/*4). The data corroborate with the literature in relation to CYP2D6 polymorphism. Conclusion: Considering the high incidence of BC and the wide use of TAM in the treatment of this tumor, conducting research addressing the pharmacogenetics of TAM is of great importance to assess the impact of CYP2D6 polymorphisms in the adjuvant treatment of BC.
TAMOXIFEN ADJUVANT INTERFERERS STUDY (TAIS STUDY): AN EXPLORATIVE ANALYSIS OF (Z)- ENDOXIFEN AND EARLY RECURRENCE OF BREAST CANCER IN A PROSPECTIVE BRAZILIAN STUDY
Authors: Rocha José Claudio Casali da , Almeida Thais , Schroth Werner , Nardin Jeanine , Mürdter Thomas , Winte Stefan , Hoppe Reiner , Brauch Hiltrud
Published: April 2023

Objective: Adherence to treatment and use of co-medication, molecular factors such as CYP2D6 genotype affect tamoxifen metabolism with consequences for early breast cancer (BC) prognosis. CYP2D6 polymorphisms have been promoted as potential biomarkers, yet they only partially explain the variability of plasma (Z)-endoxifen concentrations. The objective of this study was to evaluate whether plasma (Z)-endoxifen levels predicted early BC events (recurrence or death) within 5 years in patients receiving adjuvant tamoxifen treatment. The secondary aim was to evaluate whether (Z)-endoxifen levels were associated with clinical, pathological, and phenotypic CYP2D6 metabolism variables. Methods: In a prospective study on 149 tamoxifen-treated early-stage BC patients from Brazil followed up for 5 years, we investigated the association between the active tamoxifen metabolite (Z)-endoxifen at 3 months and event-free survival (EFS) adjusted for clinicopathological factors. We apply this approach to patients from a Brazilian prospective cohort (Tamoxifen Adjuvant Interferers Study) Results: In all, 25 (16.8%) patients had recurred or died at a median follow-up of 52.3 months. When we applied a putative 15 nM threshold used in previous independent studies, (Z)-endoxifen levels below the threshold showed an association with shorter EFS in an univariate analysis (p=0.045) and after adjustment for stage (HR 2.52; 95%CI 1.13–5.65; p=0.024). However, modeling of plasma concentrations with splines instead of dichotomization did not verify a significant association with EFS (univariate analysis: p=0.158; adjusted for stage: p=0.117). Hence, in this small exploratory study, the link between impaired tamoxifen metabolism and early BC recurrence could not be unanimously demonstrated. This inconsistency justifies larger modeling studies backed up by mechanistic pharmacodynamic analyses to shed new light on this suspected association and the stipulation of an appropriate predictive (Z)-endoxifen threshold. Conclusion: As expected, significant associations with CYP2D6 metabolism phenotypes were detected. In individual and grouped (PM+IM vs. NM+UM) comparisons, PM and IM phenotypes had lower median (Z)-endoxifen levels (7.7 and 16.3 nM, respectively) than patients with NM or UM phenotypes (27.6 and 38.0 nM, respectively; p <0.001). Using a putative clinical threshold concentration of 15 nM, low plasma (Z)-endoxifen levels were associated with a higher rate of early recurrence or death events during follow-up.
ADHERENCE TO ADJUVANT ENDOCRINE THERAPY AND ITS DETERMINING FACTORS IN PATIENTS WITH BREAST CANCER
Authors: Galvão Anna Luiza Zapalowski , Santos Danielle Laperche dos , Sousa Romualdo Barroso de , Suzuki Daniele Assad
Published: April 2023

Objective: This study aims to investigate the adherence rates to adjuvant hormone therapy in patients with early-stage breast cancer. Methods: Breast cancer patients with early invasive disease who are being treated with adjuvant hormone therapy for at least 6 months in a private oncology service were evaluated for adherence rates. Data collection was done using the RedCap software. The MMAS-8 scale was used to assess adherence to treatment, dividing patients into three groups as follows: low (<6 points), medium (6–8 points), or high adherence (8 points). Demographic and clinical characteristics were assessed for the three adherence groups. Results: From June to December 2021, a total of 60 patients were recruited. The median age was 60.3 years, and 23.3% were premenopause. About demographic statistics, 80% have a college degree, 35% live alone, and 30% have comorbidities. About breast cancer, 50% were in stage I, 50% received chemotherapy, 10% received HER2 blockade, and 26 patients (43.3%) used letrozole. Analyzing adherence, 45% had low/medium adhesion and 55% had high adhesion. There was no association between adherence rates and demographics, clinical and pathological characteristics, except for ECOG Performance Status (PS). All patients with PS ECOG 1 had low/medium adherence (p=0.036). More patients who live alone had low or medium adherence, whereas more patients who live together had high adherence. There was no difference in the type of hormonal treatment and adherence. Conclusion: Preliminary results show high adherence in only 55% of patients, lower than reported in previous studies. This result draws attention because it can compromise survival. We will continue the recruitment of patients in the private service and start in the public service to assess the rate of adherence in a larger population and the relationship with demographic characteristics.
VACUUM-ASSISTED EXCISION (VAE): A POTENTIALLY APPROACH FOR PERCUTANEOUS TREATMENT OF SMALL BREAST TUMORS
Authors: Valadares Carolina Nazareth , Couto Henrique Lima , Soares Aleida Nazareth , McIntosh Stuart A. , Sharma Nisha , Toppa Paola Hartung , Resende Vivian
Published: April 2023

Objective: The aim of this study was to evaluate vacuum-assisted excision (VAE) for percutaneous treatment of breast cancers. Methods: This is a retrospective analysis of 1061 vacuum-assisted biopsies (VAB) and VAE for the diagnostic purpose of suspicious breast lesions in a breast unit between April 13, 2017 and November 28, 2020. In total, 116 cases with complete data from VAB/VAE and surgical excision were evaluated. Excision following VAB/VAE was defined as complete resection (CR) if there was no residual tumor, minimal residual disease (MRD) if residual tumor was ≤3 mm, gross residual disease (GRD) if residual tumor was ≥3 mm, and upgrade from DCIS on VAB/VAE to invasive cancer. CR and MRD were combined as potentially resected and treated percutaneously (PRTP). The GRD and those with an upgrade to invasion were determined not suitable for percutaneous treatment. Results: The median age was 55.6 years (20–91; SD 12.27), and the median tumor size on imaging was 11.6 mm (4–88; SD 10.59). Of the 116 tumors, 29 (25%) were CR, 18 (15.5%) were MRD, 64 (55.2%) were GRD, and 5 (4.3%) were upgraded from DCIS to invasion. There were 47 (40.5%) tumors that were PRTP, of which 10 (21.3%) were DCIS and 37 (78.7%) were invasive diseases (12 pure invasive carcinoma [IC], 24 IC + DCIS, and 1 DCIS with microinvasion). In multivariate analysis, a VAE procedure (p=0.008, odds ratio [OR]: 4.4, 95%CI) with low/intermediate nuclear grade (p=0.000, OR: 12.5, 95%CI) and final T≤10 mm (p=0.000, OR: 50.1, 95%CI) were associated with PRTP. In this retrospective analysis, the probability of PRTP of low/intermediate grade tumors smaller than 10 mm undergoing VAE was 84.58%. Conclusion: These data suggest that low/intermediate grade pT1a/b breast tumors can be completely excised with percutaneous VAE. Based on this, small (≤10 mm) IC of low/intermediate grade could be considered for entry to prospective randomized trials of VAE for local treatment, with a long-term follow-up to assess recurrence rates. Standardization of the procedure should be recommended.
THE COVID-19 PANDEMIC AND LOSS OF BREAST RECONSTRUCTION SERVICES: HAS IT AFFECTED PATIENT QUALITY OF LIFE AND WELL-BEING?
Authors: Shepherd Jenna , Rodwell Sue , Moir Rachel , Fuller Mairi , Elsberger Beatrix , Masannat Yazan
Published: April 2023

Objective: Breast reconstruction has better postoperative quality of life (QoL) outcomes compared to mastectomy. The COVID-19 pandemic led to restrictions across the National Health Service, including breast reconstruction services. Breast reconstruction was unavailable in the Aberdeen Royal Infirmary from March to September 2020. This study aims to determine how many patients were affected and how this restriction has impacted patients’ physical, psychosocial, and sexual well-being. Methods: Patients who underwent mastectomy or breast reconstruction surgery in the Aberdeen Royal Infirmary from September 18, 2019 to September 18, 2020 were identified from admission lists. Breast-Q questionnaires were administered via post to all eligible individuals. Participants were asked if they would have preferred reconstruction had it been offered. QoL scores were compared between two groups: 1) patients who underwent breast reconstruction prior to the restriction of services and 2) patients who were not offered but would have preferred reconstruction. Data analysis was carried out using the SPSS statistical software. Results: In all, 164 patients underwent procedures during the period, of which 147 were eligible to participate. Of the 147 patients, 105 (71.4%) completed questionnaires were returned. Of those who had a procedure post-COVID-19 restrictions, 15 (27.8%) stated they would have preferred reconstruction had it been offered. Lower QoL scores were observed in group 2 compared to group 1 in both psychosocial well-being (medians 49 and 63, respectively, p=0.022) and sexual well-being (medians 37.5 and 51.5, respectively, p=0.026). Conclusion: The loss of breast reconstruction services affected 27.8% of patients. We demonstrate the negative impact this had on psychosocial and sexual well-being, which should inform decisions regarding service provision in the future.