Search results for: Ruben Peralta
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 42

Search results for: Ruben Peralta

12 Exploring the Facets of Sexuality among Older Adults

Authors: Vivienne Cloude C. Bersabe, Nuelle Anne Castro, Christy P. Gonzales, Nathalie Ann D. Ocbo, Araceli Chuwaley C. Padcayan, Michelle Gaile Lianne S. Peralta, Cecile A. Perez, Eiden Mae A. Roque, Frances Bea S. Sabaten, Korina Louise A. Saculles, Jada Kristen O. Taska, Jose Reinhard C. Laoingco, Don Leonardo N. Dacumos

Abstract:

The rationale of the study: Since discussion about sexuality is considered taboo in the Filipino culture, provision of quality holistic care often lacks sexuality aspect. This research was conducted to highlight the need for nurses to incorporate sexuality in their care of older adults. Research Objectives: To measure the levels of older adults’ sexual desire, sexual behavior, and sexual intimacy and relate them to sex, living arrangement, educational level, and presence of chronic illness, whether with or without treatment. Methods: This study is of quantitative descriptive design that utilized purposive sampling. 400 older adults of Baguio City participated. The study used a 30 point researcher-made questionnaire, one-on-one interview and focused group discussion to gather data. Data were treated using weighted mean, t-test, F-test, and Scheffe's test. Results and Conclusions: The overall findings revealed that Filipino older adults have a low level of sexuality expressed by the participants’ sexual desire, behavior, and intimacy. Males have significantly higher level of sexual desire, behavior, and intimacy. Living arrangement does not seem to influence the level of sexuality in all its 3 facets. Sexual desire was significantly higher among those with tertiary education and without chronic illness. Recommendation: It is recommended that nurses carry out their assessment of clients to include the exploration of their sexuality especially the older adults. A similar study may be done to explore other variables like demographic location, i.e., rural or urban setting; socio-cultural factors; and functional performance status. It is also recommended that a similar study may be done exploring the different facets of sexuality among homosexual older persons.

Keywords: geriatrics, older adults, Philippines, sexuality

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11 EcoLife and Greed Index Measurement: An Alternative Tool to Promote Sustainable Communities and Eco-Justice

Authors: Louk Aourelien Andrianos, Edward Dommen, Athena Peralta

Abstract:

Greed, as epitomized by overconsumption of natural resources, is at the root of ecological destruction and unsustainability of modern societies. Presently economies rely on unrestricted structural greed which fuels unlimited economic growth, overconsumption, and individualistic competitive behavior. Structural greed undermines the life support system on earth and threatens ecological integrity, social justice and peace. The World Council of Churches (WCC) has developed a program on ecological and economic justice (EEJ) with the aim to promote an economy of life where the economy is embedded in society and society in ecology. This paper aims at analyzing and assessing the economy of life (EcoLife) by offering an empirical tool to measure and monitor the root causes and effects of unsustainability resulting from human greed on global, national, institutional and individual levels. This holistic approach is based on the integrity of ecology and economy in a society founded on justice. The paper will discuss critical questions such as ‘what is an economy of life’ and ‘how to measure and control it from the effect of greed’. A model called GLIMS, which stands for Greed Lines and Indices Measurement System is used to clarify the concept of greed and help measuring the economy of life index by fuzzy logic reasoning. The inputs of the model are from statistical indicators of natural resources consumption, financial realities, economic performance, social welfare and ethical and political facts. The outputs are concrete measures of three primary indices of ecological, economic and socio-political greed (ECOL-GI, ECON-GI, SOCI-GI) and one overall multidimensional economy of life index (EcoLife-I). EcoLife measurement aims to build awareness of an economy life and to address the effects of greed in systemic and structural aspects. It is a tool for ethical diagnosis and policy making.

Keywords: greed line, sustainability indicators, fuzzy logic, eco-justice, World Council of Churches (WCC)

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10 An Integrated Experimental and Numerical Approach to Develop an Electronic Instrument to Study Apple Bruise Damage

Authors: Paula Pascoal-Faria, Rúben Pereira, Elodie Pinto, Miguel Belbut, Ana Rosa, Inês Sousa, Nuno Alves

Abstract:

Apple bruise damage from harvesting, handling, transporting and sorting is considered to be the major source of reduced fruit quality, resulting in loss of profits for the entire fruit industry. The three factors which can physically cause fruit bruising are vibration, compression load and impact, the latter being the most common source of bruise damage. Therefore, prediction of the level of damage, stress distribution and deformation of the fruits under external force has become a very important challenge. In this study, experimental and numerical methods were used to better understand the impact caused when an apple is dropped from different heights onto a plastic surface and a conveyor belt. Results showed that the extent of fruit damage is significantly higher for plastic surface, being dependent on the height. In order to support the development of a biomimetic electronic device for the determination of fruit damage, the mechanical properties of the apple fruit were determined using mechanical tests. Preliminary results showed different values for the Young’s modulus according to the zone of the apple tested. Along with the mechanical characterization of the apple fruit, the development of the first two prototypes is discussed and the integration of the results obtained to construct the final element model of the apple is presented. This work will help to reduce significantly the bruise damage of fruits or vegetables during the entire processing which will allow the introduction of exportation destines and consequently an increase in the economic profits in this sector.

Keywords: apple, fruit damage, impact during crop and post-crop, mechanical characterization of the apple, numerical evaluation of fruit damage, electronic device

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9 A Mixed Methods Research Design for the Development of the Xenia Higher Education Institutions' Inclusiveness Index

Authors: Achilles Kameas, Eleni Georgakakou, Anna Lisa Amodeo, Aideen Quilty, Aisling Malone, Roberta Albertazzi, Moises Carmona, Concetta Esposito, Ruben David Fernandez Carrasco, Carmela Ferrara, Francesco Garzillo, Mojca Pusnik, Maria Cristina Scarano

Abstract:

While researchers, especially in academia, study and research the phenomena of inclusion of sexual minority and gender marginalized groups, seldom the European Higher Education Institutions (HEI) act on lowering the cultural and educational barriers to their proactive inclusion. The challenge in European HEIs is that gender, and sexual orientation discrimination remains an issue not adequately addressed. Following a mixed methods research design of quantitative and qualitative research techniques and tools, which is applied in five (5) European countries (Italy, Greece, Ireland, Slovenia, and Spain) and that combines desk research, evaluation, and weighting processes for a Matrix-based on Objective indicators and Survey for students and staff of the HEI to gauge the perception of inclusiveness in the HEI context, XENIA HEI Inclusiveness Index is an instrument that will allow universities to gauge and assess their inclusiveness in the domain of discrimination and exclusion based on gender identity and sexual orientation. The index will allow capturing the depth and reach of policies, programmes, and initiatives of HEIs in tackling the phenomena and dynamics of exclusion of LGBT+ (lesbian, gay, bisexual, trans, and other marginalized groups on the basis of gender and sexual identity) and cisgender women exposed to the risk of discrimination.

Keywords: gender identity, higher education, LGBT+ rights, XENIA inclusiveness index

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8 End-Users Tools to Empower and Raise Awareness of Behavioural Change towards Energy Efficiency

Authors: G. Calleja-Rodriguez, N. Jimenez-Redondo, J. J. Peralta Escalante

Abstract:

This research work aims at developing a solution to take advantage of the potential energy saving related to occupants behaviour estimated in between 5-30 % according to existing studies. For that purpose, the following methodology has been followed: 1) literature review and gap analysis, 2) define concept and functional requirements, 3) evaluation and feedback by experts. As result, the concept for a tool-box that implements continuous behavior change interventions named as engagement methods and based on increasing energy literacy, increasing energy visibility, using bonus system, etc. has been defined. These engagement methods are deployed through a set of ICT tools: Building Automation and Control System (BACS) add-ons services installed in buildings and Users Apps installed in smartphones, smart-TVs or dashboards. The tool-box called eTEACHER identifies energy conservation measures (ECM) based on energy behavioral change through a what-if analysis that collects information about the building and its users (comfort feedback, behavior, etc.) and carry out cost-effective calculations to provide outputs such us efficient control settings of building systems. This information is processed and showed in an attractive way as tailored advice to the energy end-users. Therefore, eTEACHER goal is to change the behavior of building´s energy users towards energy efficiency, comfort and better health conditions by deploying customized ICT-based interventions taking into account building typology (schools, residential, offices, health care centres, etc.), users profile (occupants, owners, facility managers, employers, etc.) as well as cultural and demographic factors. One of the main findings of this work is the common failure when technological interventions on behavioural change are done to not consult, train and support users regarding technological changes leading to poor performance in practices. As conclusion, a strong need to carry out social studies to identify relevant behavioural issues and to identify effective pro-evironmental behavioral change strategies has been identified.

Keywords: energy saving, behavioral bhange, building users, engagement methods, energy conservation measures

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7 Free Energy Computation of A G-Quadruplex-Ligand Structure: A Classical Molecular Dynamics and Metadynamics Simulation Study

Authors: Juan Antonio Mondragon Sanchez, Ruben Santamaria

Abstract:

The DNA G-quadruplex is a four-stranded DNA structure formed by stacked planes of four base paired guanines (G-quartet). Guanine rich DNA sequences appear in many sites of genomic DNA and can potential form G-quadruplexes, such as those occurring at 3'-terminus of the human telomeric DNA. The formation and stabilization of a G-quadruplex by small ligands at the telomeric region can inhibit the telomerase activity. In turn, the ligands can be used to down regulate oncogene expression making G-quadruplex an attractive target for anticancer therapy. Many G-quadruplex ligands have been proposed with a planar core to facilitate the pi–pi stacking and electrostatic interactions with the G-quartets. However, many drug candidates are impossibilitated to discriminate a G-quadruplex from a double helix DNA structure. In this context, it is important to investigate the site topology for the interaction of a G-quadruplex with a ligand. In this work, we determine the free energy surface of a G-quadruplex-ligand to study the binding modes of the G-quadruplex (TG4T) with the daunomycin (DM) drug. The complex TG4T-DM is studied using classical molecular dynamics in combination with metadynamics simulations. The metadynamics simulations permit an enhanced sampling of the conformational space with a modest computational cost and obtain free energy surfaces in terms of the collective variables (CV). The free energy surfaces of TG4T-DM exhibit other local minima, indicating the presence of additional binding modes of daunomycin that are not observed in short MD simulations without the metadynamics approach. The results are compared with similar calculations on a different structure (the mutated mu-G4T-DM where the 5' thymines on TG4T-DM have been deleted). The results should be of help to design new G-quadruplex drugs, and understand the differences in the recognition topology sites of the duplex and quadruplex DNA structures in their interaction with ligands.

Keywords: g-quadruplex, cancer, molecular dynamics, metadynamics

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6 The Impact of Task Type and Group Size on Dialogue Argumentation between Students

Authors: Nadia Soledad Peralta

Abstract:

Within the framework of socio-cognitive interaction, argumentation is understood as a psychological process that supports and induces reasoning and learning. Most authors emphasize the great potential of argumentation to negotiate with contradictions and complex decisions. So argumentation is a target for researchers who highlight the importance of social and cognitive processes in learning. In the context of social interaction among university students, different types of arguments are analyzed according to group size (dyads and triads) and the type of task (reading of frequency tables, causal explanation of physical phenomena, the decision regarding moral dilemma situations, and causal explanation of social phenomena). Eighty-nine first-year social sciences students of the National University of Rosario participated. Two groups were formed from the results of a pre-test that ensured the heterogeneity of points of view between participants. Group 1 consisted of 56 participants (performance in dyads, total: 28), and group 2 was formed of 33 participants (performance in triads, total: 11). A quasi-experimental design was performed in which effects of the two variables (group size and type of task) on the argumentation were analyzed. Three types of argumentation are described: authentic dialogical argumentative resolutions, individualistic argumentative resolutions, and non-argumentative resolutions. The results indicate that individualistic arguments prevail in dyads. That is, although people express their own arguments, there is no authentic argumentative interaction. Given that, there are few reciprocal evaluations and counter-arguments in dyads. By contrast, the authentically dialogical argument prevails in triads, showing constant feedback between participants’ points of view. It was observed that, in general, the type of task generates specific types of argumentative interactions. However, it is possible to emphasize that the authentically dialogic arguments predominate in the logical tasks, whereas the individualists or pseudo-dialogical are more frequent in opinion tasks. Nerveless, these relationships between task type and argumentative mode are best clarified in an interactive analysis based on group size. Finally, it is important to stress the value of dialogical argumentation in educational domains. Argumentative function not only allows a metacognitive reflection about their own point of view but also allows people to benefit from exchanging points of view in interactive contexts.

Keywords: sociocognitive interaction, argumentation, university students, size of the grup

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5 Internationalization Using Strategic Alliances: A Comparative Study between Family and Non-Family Businesses

Authors: Guadalupe Fuentes-Lombardo, Manuel Carlos Vallejo-Martos, Rubén Fernández-Ortiz, Miriam Cano-Rubio

Abstract:

The different ways in which companies enter foreign markets, exporting their products and direct investment and using strategic alliances or not, are influenced by a series of peculiarities specific to family businesses. In these companies, different systems, such as the family, property, and business overlap; giving them unique and specific characteristics which on occasions can enhance the development of cooperation agreements and in other situations can hinder them. Previous research has shown that these companies are more likely to enter into strategic alliances with certain specific features, and are more reluctant to take part in others in which some of the advantages of the family business are put at risk, such as control of ownership and decision-making over the company by the family, among others. These arguments show that there is a wide range of interesting aspects and peculiarities in the process of internationalization of the family business, although the research objectives of this paper focus on three in particular. Our first objective will be to discover why family businesses decide to establish or not strategic alliances in their internationalization processes in comparison with other companies that are not family owned. Secondly we will be identifying the idiosyncratic aspects of family businesses that favor or hinder the use of strategic alliances as a means of entering foreign markets. Our third and final objective will be to define the types of strategic alliance most commonly used by family businesses and the reasons why they choose these particular forms of alliance rather than others. We chose these research objectives for three main reasons. Firstly because research on this subject shows that alliances are the best way to begin the international expansion process, among other reasons because they provide the partners with different kinds of resources and capacity, so increasing the probability of successful internationalization. Secondly, because family and non-family businesses are often equipped with different types of resources and strategic alliances, offer them the chance to acquire resources less frequently found in family businesses. Thirdly, because the strengths and weaknesses of these companies could affect their decisions whether or not to use strategic alliances in their international expansion process and the success achieved in these alliances. As a result, these companies prefer to enter into cooperation agreements with conditions that do not put their specific status as family companies at risk.

Keywords: family business, internationalization, strategic alliances, olive-oil and wine industry

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4 Association of Body Composition Parameters with Lower Limb Strength and Upper Limb Functional Capacity in Quilombola Remnants

Authors: Leonardo Costa Pereira, Frederico Santos Santana, Mauro Karnikowski, Luís Sinésio Silva Neto, Aline Oliveira Gomes, Marisete Peralta Safons, Margô Gomes De Oliveira Karnikowski

Abstract:

In Brazil, projections of population aging follow all world projections, the birth rate tends to be surpassed by the mortality rate around the year 2045. Historically, the population of Brazilian blacks suffered for several centuries from the oppression of dominant classes. A group, especially of blacks, stands out in relation to territorial, historical and social aspects, and for centuries they have isolated themselves in small communities, in order to maintain their freedom and culture. The isolation of the Quilombola communities generated socioeconomic effects as well as the health of these blacks. Thus, the objective of the present study is to verify the association of body composition parameters with lower and upper limb strength and functional capacity in Quilombola remnants. The research was approved by ethics committee (1,771,159). Anthropometric evaluations of hip and waist circumference, body mass and height were performed. In order to verify the body composition, the relationship between stature and body mass (BM) was performed, generating the body mass index (BMI), as well as the dual-energy X-ray absorptiometry (DEXA) test. The Time Up and Go (TUG) test was used to evaluate the functional capacity, and a maximum repetition test (1MR) for knee extension and handgrip (HG) was applied for strength magnitude analysis. Statistical analysis was performed using the statistical package SPSS 22.0. Shapiro Wilk's normality test was performed. For the possible correlations, the suggestions of the Pearson or Spearman tests were adopted. The results obtained after the interpretation identified that the sample (n = 18) was composed of 66.7% of female individuals with mean age of 66.07 ± 8.95 years. The sample’s body fat percentage (%BF) (35.65 ± 10.73) exceeds the recommendations for age group, as well as the anthropometric parameters of hip (90.91 ± 8.44cm) and waist circumference (80.37 ± 17.5cm). The relationship between height (1.55 ± 0.1m) and body mass (63.44 ± 11.25Kg) generated a BMI of 24.16 ± 7.09Kg/m2, that was considered normal. The TUG performance was 10.71 ± 1.85s. In the 1MR test, 46.67 ± 13.06Kg and in the HG 23.93±7.96Kgf were obtained, respectively. Correlation analyzes were characterized by the high frequency of significant correlations for height, dominant arm mass (DAM), %BF, 1MR and HG variables. In addition, correlations between HG and BM (r = 0.67, p = 0.005), height (r = 0.51, p = 0.004) and DAM (r = 0.55, p = 0.026) were also observed. The strength of the lower limbs correlates with BM (r = 0.69, p = 0.003), height (r = 0.62, p = 0.01) and DAM (r = 0.772, p = 0.001). In this way, we can conclude that not only the simple spatial relationship of mass and height can influence in predictive parameters of strength or functionality, being important the verification of the conditions of the corporal composition. For this population, height seems to be a good predictor of strength and body composition.

Keywords: African Continental Ancestry Group, body composition, functional capacity, strength

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3 Parents' Motivating Factors for Their Deaf and Mute Children to Participate in Physical and Recreational Activities

Authors: Ruben L. Tagare, Jr

Abstract:

This study was conducted to determine the parents’ motivating factors for their deaf and mute children to participate in physical and recreational activities. Data were collected from the 17 parents of the deaf and mute children using a specifically designed survey questionnaire as the primary instrument used in the study. Data analysis and interpretation were done with the aid of descriptive statistics, such as frequency, percentage, weighted mean and multiple responses. Most of the respondents were female with a mean average age of 38 years old. The average age of their children was 10 years old. In terms of monthly income, the respondents had an average monthly income of PhP 13,945. Furthermore, most of the respondents lived in the urban area and were all Catholic by faith or religion. As to the factors that parents used to motivate their deaf and mute children to engage in physical and recreational activities, these included the followings: First; to make my child experience and explore more meaningful things through physical and recreational activities; second; to gain other’s respect; third; to build friendship and interact with his peers; fourth; to experience the feeling of belongingness; and fifth: to learn and discover new things. On the other hand, the least chosen factors were: first; to help achieve and maintain a healthy weight; second; to reduce fats and lowering blood pressure; third; to improve balance, coordination and strength; fourth; to improve posture; and fifth; to assist the child in the development of gross motor and fine motor skills. Based on the findings of the study, it is hereby recommended that since the first factor is 'to make my child experience and explore more meaningful things through physical and recreational activities' and the other top factors are more on social aspect, the school should design extra-curricular activities such as theatrical play and other similar activities that the students will find interesting while the parents will be more motivated to engage their children into physical and recreational activities. Also, since the least chosen factors are more on physical aspect, the school should organize or conduct a seminar for the parents to be aware of the benefits of participating in physical and recreational activities for their deaf and mute children. They can also conduct an information campaign to encourage the other parents of deaf and mute children, whom they keep only inside their home to enroll in the school and let their children be exposed to the natural world. Considering that parents are the primary motivators that can best help their children become more interested in physical and recreational activities for their own development, the school should always remain motivated by creating activities for the deaf and mute children with their parents. The study also recommends conducting further study on the level of knowledge/understanding of the parents on the benefits that can be derived from participating in physical and recreational activities.

Keywords: deaf and mute, participation, physical and recreational activities, adaptive PE

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2 Association between G2677T/A MDR1 Polymorphism with the Clinical Response to Disease Modifying Anti-Rheumatic Drugs in Rheumatoid Arthritis

Authors: Alan Ruiz-Padilla, Brando Villalobos-Villalobos, Yeniley Ruiz-Noa, Claudia Mendoza-Macías, Claudia Palafox-Sánchez, Miguel Marín-Rosales, Álvaro Cruz, Rubén Rangel-Salazar

Abstract:

Introduction: In patients with rheumatoid arthritis, resistance or poor response to disease modifying antirheumatic drugs (DMARD) may be a reflection of the increase in g-P. The expression of g-P may be important in mediating the effluence of DMARD from the cell. In addition, P-glycoprotein is involved in the transport of cytokines, IL-1, IL-2 and IL-4, from normal lymphocytes activated to the surrounding extracellular matrix, thus influencing the activity of RA. The involvement of P-glycoprotein in the transmembrane transport of cytokines can serve as a modulator of the efficacy of DMARD. It was shown that a number of lymphocytes with glycoprotein P activity is increased in patients with RA; therefore, P-glycoprotein expression could be related to the activity of RA and could be a predictor of poor response to therapy. Objective: To evaluate in RA patients, if the G2677T/A MDR1 polymorphisms is associated with differences in the rate of therapeutic response to disease-modifying antirheumatic agents in patients with rheumatoid arthritis. Material and Methods: A prospective cohort study was conducted. Fifty seven patients with RA were included. They had an active disease according to DAS-28 (score >3.2). We excluded patients receiving biological agents. All the patients were followed during 6 months in order to identify the rate of therapeutic response according to the American College of Rheumatology (ACR) criteria. At the baseline peripheral blood samples were taken in order to identify the G2677T/A MDR1 polymorphisms using PCR- Specific allele. The fragment was identified by electrophoresis in polyacrylamide gels stained with ethidium bromide. For statistical analysis, the genotypic and allelic frequencies of MDR1 gene polymorphism between responders and non-responders were determined. Chi-square tests as well as, relative risks with 95% confidence intervals (95%CI) were computed to identify differences in the risk for achieving therapeutic response. Results: RA patients had a mean age of 47.33 ± 12.52 years, 87.7% were women with a mean for DAS-28 score of 6.45 ± 1.12. At the 6 months, the rate of therapeutic response was 68.7 %. The observed genotype frequencies were: for G/G 40%, T/T 32%, A/A 19%, G/T 7% and for A/A genotype 2%. Patients with G allele developed at 6 months of treatment, higher rate for therapeutic response assessed by ACR20 compared to patients with others alleles (p=0.039). Conclusions: Patients with G allele of the - G2677T/A MDR1 polymorphisms had a higher rate of therapeutic response at 6 months with DMARD. These preliminary data support the requirement for a deep evaluation of these and other genotypes as factors that may influence the therapeutic response in RA.

Keywords: pharmacogenetics, MDR1, P-glycoprotein, therapeutic response, rheumatoid arthritis

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1 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients

Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

Abstract:

Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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