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1.
JMIR Hum Factors ; 11: e54532, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38958216

RESUMO

Background: The National Research Mentoring Network (NRMN) is a National Institutes of Health-funded program for diversifying the science, technology, engineering, math, and medicine research workforce through the provision of mentoring, networking, and professional development resources. The NRMN provides mentoring resources to members through its online platform-MyNRMN. Objective: MyNRMN helps members build a network of mentors. Our goal was to expand enrollment and mentoring connections, especially among those who have been historically underrepresented in biomedical training and the biomedical workforce. Methods: To improve the ease of enrollment, we implemented the split testing of iterations of our user interface for platform registration. To increase mentoring connections, we developed multiple features that facilitate connecting via different pathways. Results: Our improved user interface yielded significantly higher rates of completed registrations (P<.001). Our analysis showed improvement in completed enrollments that used the version 1 form when compared to those that used the legacy form (odds ratio 1.52, 95% CI 1.30-1.78). The version 2 form, with its simplified, 1-step process and fewer required fields, outperformed the legacy form (odds ratio 2.18, 95% CI 1.90-2.50). By improving the enrollment form, the rate of MyNRMN enrollment completion increased from 57.3% (784/1368) with the legacy form to 74.5% (2016/2706) with the version 2 form. Our newly developed features delivered an increase in connections between members. Conclusions: Our technical efforts expanded MyNRMN's membership base and increased connections between members. Other platform development teams can learn from these efforts to increase enrollment among underrepresented groups and foster continuing, successful engagement.


Assuntos
Tutoria , Humanos , Tutoria/métodos , Estados Unidos , Design Centrado no Usuário , Diversidade Cultural , Pesquisa Biomédica , National Institutes of Health (U.S.) , Pesquisadores
2.
J Med Internet Res ; 26: e47560, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38885013

RESUMO

BACKGROUND: With an overarching goal of increasing diversity and inclusion in biomedical sciences, the National Research Mentoring Network (NRMN) developed a web-based national mentoring platform (MyNRMN) that seeks to connect mentors and mentees to support the persistence of underrepresented minorities in the biomedical sciences. As of May 15, 2024, the MyNRMN platform, which provides mentoring, networking, and professional development tools, has facilitated more than 12,100 unique mentoring connections between faculty, students, and researchers in the biomedical domain. OBJECTIVE: This study aimed to examine the large-scale mentoring connections facilitated by our web-based platform between students (mentees) and faculty (mentors) across institutional and geographic boundaries. Using an innovative graph database, we analyzed diverse mentoring connections between mentors and mentees across demographic characteristics in the biomedical sciences. METHODS: Through the MyNRMN platform, we observed profile data and analyzed mentoring connections made between students and faculty across institutional boundaries by race, ethnicity, gender, institution type, and educational attainment between July 1, 2016, and May 31, 2021. RESULTS: In total, there were 15,024 connections with 2222 mentees and 1652 mentors across 1625 institutions contributing data. Female mentees participated in the highest number of connections (3996/6108, 65%), whereas female mentors participated in 58% (5206/8916) of the connections. Black mentees made up 38% (2297/6108) of the connections, whereas White mentors participated in 56% (5036/8916) of the connections. Mentees were predominately from institutions classified as Research 1 (R1; doctoral universities-very high research activity) and historically Black colleges and universities (556/2222, 25% and 307/2222, 14%, respectively), whereas 31% (504/1652) of mentors were from R1 institutions. CONCLUSIONS: To date, the utility of mentoring connections across institutions throughout the United States and how mentors and mentees are connected is unknown. This study examined these connections and the diversity of these connections using an extensive web-based mentoring network.


Assuntos
Tutoria , Mentores , Humanos , Tutoria/métodos , Mentores/estatística & dados numéricos , Feminino , Masculino , Pesquisa Biomédica/estatística & dados numéricos , Estados Unidos , Grupos Minoritários/estatística & dados numéricos , Bases de Dados Factuais , Docentes/estatística & dados numéricos
3.
Hum Vaccin Immunother ; 20(1): 2340692, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38658140

RESUMO

The COVID-19 pandemic required the rapid development of COVID-19 vaccines and treatments, necessitating quick yet representative clinical trial enrollment to evaluate these preventive measures. However, misinformation around the COVID-19 pandemic and general concerns about clinical trial participation in the U.S. hindered clinical trial enrollment. This study assessed awareness of, willingness to participate in, and enrollment in COVID-19 vaccine and treatment clinical trials in Texas. A quota sample of 1,089 Texas residents was collected online from June - July 2022. Respondents were asked if they were aware of, willing to participate in, and had enrolled in clinical trials for COVID-19 vaccines or treatments. Overall, 45.8% of respondents reported being aware of clinical trials for COVID-19 treatments or vaccines, but only 21.7% knew how to enroll and only 13.2% had enrolled in a COVID-19 clinical trial. Respondents with bachelor's or graduate degrees were more likely to be aware of clinical trials, more likely to have enrolled in trials, and more willing to participate in treatment trials. Women were less willing to participate and less likely to have enrolled in COVID-19 clinical trials than men. Respondents aged 55 years and older were more willing to participate, but less likely to have enrolled in COVID-19 clinical trials than 18-to-24-year-olds. Common reasons given for not participating in clinical trials included concerns that COVID-19 treatments may not be safe, government distrust, and uncertainty about what clinical trial participation would entail. Substantial progress is needed to build community awareness and increase enrollment in clinical trials.


Assuntos
Vacinas contra COVID-19 , Ensaios Clínicos como Assunto , Conhecimentos, Atitudes e Prática em Saúde , Inquéritos e Questionários , COVID-19/prevenção & controle , Tamanho da Amostra , Texas , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Confiança , Segurança do Paciente , Incerteza , Seleção de Pacientes , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade
4.
J Biol Chem ; 300(3): 105680, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38272230

RESUMO

Migration and invasion enhancer 1 (MIEN1) overexpression characterizes several cancers and facilitates cancer cell migration and invasion. Leveraging conserved immunoreceptor tyrosine-based activation motif and prenylation motifs within MIEN1, we identified potent anticancer peptides. Among them, bioactive peptides LA3IK and RP-7 induced pronounced transcriptomic and protein expression changes at sub-IC50 concentrations. The peptides effectively inhibited genes and proteins driving cancer cell migration, invasion, and epithelial-mesenchymal transition pathways, concurrently suppressing epidermal growth factor-induced nuclear factor kappa B nuclear translocation in metastatic breast cancer cells. Specifically, peptides targeted the same signal transduction pathway initiated by MIEN1. Molecular docking and CD spectra indicated the formation of MIEN1-peptide complexes. The third-positioned isoleucine in LA3IK and CVIL motif in RP-7 were crucial for inhibiting breast cancer cell migration. This is evident from the limited migration inhibition observed when MDA-MB-231 cells were treated with scrambled peptides LA3IK SCR and RP-7 SCR. Additionally, LA3IK and RP-7 effectively suppressed tumor growth in an orthotopic breast cancer model. Notably, mice tolerated high intraperitoneal (ip) peptide doses of 90 mg/Kg well, surpassing significantly lower doses of 5 mg/Kg intravenously (iv) and 30 mg/Kg intraperitoneally (ip) used in both in vivo pharmacokinetic studies and orthotopic mouse model assays. D-isomers of LA3IK and RP-7 showed enhanced anticancer activity compared to their L-isomers. D-LA3IK remained stable in mouse plasma for 24 h with 75% remaining, exhibiting superior pharmacokinetic properties over D/L-RP-7. In summary, our findings mark the first report of short peptides based on MIEN1 protein sequence capable of inhibiting cancer signaling pathways, effectively impeding cancer progression both in vitro and in vivo.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Neoplasias , Animais , Camundongos , Movimento Celular/genética , Proliferação de Células , Transição Epitelial-Mesenquimal , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Simulação de Acoplamento Molecular , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Transdução de Sinais , Humanos , Linhagem Celular , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia
5.
PLOS Digit Health ; 2(6): e0000288, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37390116

RESUMO

Artificial intelligence and machine learning (AI/ML) tools have the potential to improve health equity. However, many historically underrepresented communities have not been engaged in AI/ML training, research, and infrastructure development. Therefore, AIM-AHEAD (Artificial Intelligence/Machine Learning Consortium to Advance Health Equity and Researcher Diversity) seeks to increase participation and engagement of researchers and communities through mutually beneficial partnerships. The purpose of this paper is to summarize feedback from listening sessions conducted by the AIM-AHEAD Coordinating Center in February 2022, titled the "AIM-AHEAD Community Building Convention (ACBC)." A total of six listening sessions were held over three days. A total of 977 people registered with AIM-AHEAD to attend ACBC and 557 individuals attended the listening sessions across stakeholder groups. Facilitators led the conversation based on a series of guiding questions, and responses were captured through voice and chat via the Slido platform. A professional third-party provider transcribed the audio. Qualitative analysis included data from transcripts and chat logs. Thematic analysis was then used to identify common and unique themes across all transcripts. Six main themes arose from the sessions. Attendees felt that storytelling would be a powerful tool in communicating the impact of AI/ML in promoting health equity, trust building is vital and can be fostered through existing trusted relationships, and diverse communities should be involved every step of the way. Attendees shared a wealth of information that will guide AIM-AHEAD's future activities. The sessions highlighted the need for researchers to translate AI/ML concepts into vignettes that are digestible to the larger public, the importance of diversity, and how open-science platforms can be used to encourage multi-disciplinary collaboration. While the sessions confirmed some of the existing barriers in applying AI/ML for health equity, they also offered new insights that were captured in the six themes.

6.
Vaccines (Basel) ; 11(4)2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-37112760

RESUMO

The COVID-19 pandemic has been a global public health concern since early 2020 and has required local and state-level responses in the United States. There were several Food and Drug Administration (FDA) approved vaccines available for the prevention of COVID-19 as of August 2022, yet not all states have achieved high vaccination coverage. Texas is a particularly unique state with a history of opposing vaccination mandates, as well as a large and ethnically/racially diverse population. This study explored the demographic and psychosocial correlates of COVID-19 vaccinations among a statewide sample in Texas. A quota sample of 1089 individuals was surveyed online from June-July 2022. The primary outcome in this study was COVID-19 vaccination status (fully vaccinated, partially vaccinated, or unvaccinated) and included independent variables related to demographics, COVID-19 infection/vaccine attitudes and beliefs, and challenges related to the COVID-19 pandemic. Hispanic/Latinx individuals were more likely than non-Hispanic White individuals to be partially vaccinated as opposed to unvaccinated. Higher education levels and confidence that the FDA would ensure a safe COVID-19 vaccine were strongly associated with a higher likelihood of being fully vaccinated. In addition, some challenges brought on by the pandemic and concerns about becoming infected or infecting others were associated with a higher likelihood of being partially or fully vaccinated. These findings emphasize the need to further investigate the interaction between individual and contextual factors in improving COVID-19 vaccination rates, especially among vulnerable and disadvantaged populations.

7.
Am J Cancer Res ; 13(3): 1082-1090, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37034219

RESUMO

Among the innate immune cells, natural killer cells (NK) serve its role in cytolytic targeting against infected and cancerous cells. NK function is regulated by an intricate balance of signals from interactions between activating and inhibitory NK receptors and ligands expressed on target cells. As an immune evasion strategy, cancer cells, particularly triple-negative breast cancer cells (TNBCs), express ligands that interact with NK receptors to inhibit NK cell cytolytic function. Our studies have revealed that Proliferating Cell Nuclear Antigen (PCNA), normally expressed in the nucleus with DNA replication and repair roles, was present on the cell surface of TNBC cell lines MDA-MB-231, -436, and -468. To elucidate the function of cell surface PCNA, we blocked PCNA on TNBCs with antibodies which both disrupted interaction with NKp44 and enhanced lysis by primary NK cells. Furthermore, a combinational antibody treatment of TNBCs with α-LLT1 and α-PCNA antibodies augments NK-mediated lysis. These results together suggest that cell surface PCNA on TNBCs enables evasion from cytolytic killing by NK cells. Blocking PCNA-NKp44 interaction with antibodies may potentially open an additional avenue in treatment of TNBCs.

8.
Pharmaceutics ; 15(2)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36839985

RESUMO

Bone-metastatic prostate cancer symbolizes the beginning of the later stages of the disease. We designed a cabazitaxel-loaded, poly (lactic-co-glycolic acid) (PLGA) nanoparticle using an emulsion-diffusion-evaporation technique. Bis (sulfosuccinimidyl) suberate (BS3) was non-covalently inserted into the nanoparticle as a linker for the conjugation of a bone-targeting moiety to the outside of the nanoparticle. We hypothesized that the nanoparticles would have the ability to inhibit the epithelial-to-mesenchymal transition (EMT), invasion, and migration in prostate cancer cells. Targeted, cabazitaxel-loaded nanoparticles attenuated the EMT marker, Vimentin, and led to an increased E-cadherin expression. These changes impart epithelial characteristics and inhibit invasive properties in cancer progression. Consequently, progression to distant sites is also mitigated. We observed the reduction of phosphorylated Src at tyrosine 416, along with increased expression of phosphorylated cofilin at serine 3. These changes could affect migration and invasion pathways in cancer cells. Both increased p-120 catenin and inhibition in IL-8 expression were seen in targeted, cabazitaxel-loaded nanoparticles. Overall, our data show that the targeted, cabazitaxel-loaded nanoparticles can act as a promising treatment for metastatic prostate cancer by inhibiting EMT, invasion, and migration, in prostate cancer cells.

9.
J Affect Disord Rep ; 11: 100472, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36624854

RESUMO

Background: In the United States, the COVID-19 pandemic has caused increased mental health symptoms and mental illness. Specific subgroups such as Asian Indians in the US have also been subject to additional stressors due to unprecedented loss of lives in their home country and increased Asian hate due to the misperception that Asians are to be blamed for the spread of the SARS-CoV-2. Objective: We examined the various factors including discrimination associated with COVID-19-related mental health symptoms among Asian Indians. Methods: We administered an online survey between May 2021 and July 2021 using convenient and snowball sampling methods to recruit Asian Indian adults (age > 18 years, N = 289). The survey included questions on mental health and the experience with unfair treatment in day-to-day life. Descriptive analysis and logistic regressions were performed. Results: Overall, 46.0% reported feeling down, depressed, or lonely and feeling nervous, tense, or worried due to the COVID-19 pandemic; 90.0% had received at least one dose of vaccination and 74.7% reported some form of discrimination. In the fully-adjusted logistic regression, age (AOR = 0.95; 95%CI- 0.92, 0.97;p < 0.01) and general health (AOR=0.84; 95%CI- 0.73, 0.97; p < 0.015) were negatively associated with mental health symptoms. Participants who experienced discrimination were more likely (AOR=1.26; 95%CI- 1.08, 1.46; p < 0.01) to report mental health symptoms. Conclusion: In this highly vaccinated group of Asian Indians discriminatory behaviors were associated with mental health symptoms suggesting the need for novel institutional level policy responses to reduce anti-Asian racism.

10.
Pharmaceutics ; 14(12)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36559179

RESUMO

The usage of peptide-based drugs to combat cancer is gaining significance in the pharmaceutical industry. The collateral damage caused to normal cells due to the use of chemotherapy, radiotherapy, etc. has given an impetus to the search for alternative methods of cancer treatment. For a long time, antimicrobial peptides (AMPs) have been shown to display anticancer activity. However, the immunomodulatory activity of anti-cancer peptides has not been researched very extensively. The interconnection of cancer and immune responses is well-known. Hence, a search and design of molecules that can show anti-cancer and immunomodulatory activity can be lead molecules in this field. A large number of anti-cancer peptides show good immunomodulatory activity by inhibiting the pro-inflammatory responses that assist cancer progression. Here, we thoroughly review both the naturally occurring and synthetic anti-cancer peptides that are reported to possess both anti-cancer and immunomodulatory activity. We also assess the structural and biophysical parameters that can be utilized to improve the activity. Both activities are mostly reported by different groups, however, we discuss them together to highlight their interconnection, which can be used in the future to design peptide drugs in the field of cancer therapeutics.

11.
Artigo em Inglês | MEDLINE | ID: mdl-36360949

RESUMO

The Community Engagement Alliance (CEAL) Against COVID-19 Disparities aims to conduct community-engaged research and outreach. This paper describes the Texas CEAL Consortium's activities in the first year and evaluates progress. The Texas CEAL Consortium comprised seven projects. To evaluate the Texas CEAL Consortium's progress, we used components of the RE-AIM Framework. Evaluation included estimating the number of people reached for data collection and education activities (reach), individual project goals and progress (effectiveness), partnerships established and partner engagement (adoption), and outreach and education activities (implementation). During the one-year period, focus groups were conducted with 172 people and surveys with 2107 people across Texas. Partners represented various types of organizations, including 11 non-profit organizations, 4 academic institutions, 3 civic groups, 3 government agencies, 2 grassroots organizations, 2 faith-based organizations, 1 clinic, and 4 that were of other types. The main facets of implementation consisted of education activities and the development of trainings. Key recommendations for future consortiums relate to funding and research logistics and the value of strong community partnerships. The lessons learned in this first year of rapid deployment inform ongoing work by the Texas CEAL Consortium and future community-engaged projects.


Assuntos
COVID-19 , Humanos , Texas/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Redes Comunitárias , Universidades , Grupos Focais
12.
J Clin Transl Sci ; 6(1): e64, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720963

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic requires urgent implementation of effective community-engaged strategies to enhance education, awareness, and inclusion of underserved communities in prevention, mitigation, and treatment efforts. The Texas Community-Engagement Alliance Consortium was established with support from the United States' National Institutes of Health (NIH) to conduct community-engaged projects in selected geographic locations with a high proportion of medically underserved minority groups with a disproportionate burden of COVID-19 disease and hospitalizations. The purpose of this paper is to describe the development of the Consortium. The Consortium organized seven projects with focused activities to address COVID-19 clinical and vaccine trials in highly affected counties, as well as critical statewide efforts. Five Texas counties (Bexar, Dallas, Harris, Hidalgo, and Tarrant) were chosen by NIH because of high concentrations of underserved minority communities, existing community infrastructure, ongoing efforts against COVID-19, and disproportionate burden of COVID-19. Policies and practices can contribute to disparities in COVID-19 risk, morbidity, and mortality. Community engagement is an essential element for effective public health strategies in medically underserved minority areas. Working with partners, the Consortium will use community engagement strategies to address COVID-19 disparities.

13.
BMC Med Educ ; 22(1): 391, 2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35597975

RESUMO

PURPOSE: Increased awareness and mitigation of one's unconscious bias is a critical strategy in diversifying the Science, Technology, Engineering, Mathematics, and Medicine (STEMM) disciplines and workforce. Greater management of unconscious bias can enhance diverse recruitment, persistence, retention, and engagement of trainees. The purpose of this study was to describe the implementation of an asynchronous course on unconscious bias for people in STEMM. Specifically, we explored who engaged with the course and reflections from participation. METHOD: A five-part, asynchronous Unconscious Bias Course was developed and was hosted on a national mentoring platform starting in July 2020. To examine course engagement, we assessed the demographics of course participants and completion. Participant responses to reflection questions after each module were also synthesized using qualitative methods. RESULTS: Overall, 977 people registered for the course and 42% completed all modules. In the reflection responses, participants reflected on their unconscious biases in their lived experiences and how it relates to actions, judgements, external factors, stereotypes, and un-intentionality. Participants also reflected on microaggressions, their impact on the recipients and others, and the relationship between microaggressions and unconscious bias. Participants reported four key strategies used by allies against unconscious bias: immediately acting (83%), reflection (46%), improving the organizational culture (30%), and individual-level ally-ship (44%). Strategies for self-awareness included: reflection, pausing/breathing, and self-observation. CONCLUSION: The assessment of the Unconscious Bias Course implementation revealed the course reached a wide cross-section of people in STEMM and demonstrated that participants were able to reflect on the underpinnings of the course. This course, and its suite of offerings, support a nationwide effort to mitigate bias and prepare individuals to be culturally competent in a diverse society in order to foster a STEMM environment that caters to individuals' success and diversification of these fields.


Assuntos
Medicina , Tutoria , Viés , Viés Implícito , Humanos , Mentores , Recursos Humanos
14.
Pharmaceutics ; 14(1)2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35057024

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and is the fourth leading cause of cancer-related deaths in the United States. Unfortunately, 80-85% of patients are diagnosed with unresectable, advanced stage tumors. These tumors are incurable and result in a median survival less than approximately six months and an overall 5-year survival rate of less than 7%. Whilst chemotherapy is a critical treatment, cure is not possible without surgical resection. The poor clinical outcomes in PDAC can be partially attributed to its dense desmoplastic stroma, taking up roughly 80% of the tumor mass. The stroma surrounding the tumor disrupts the normal architecture of pancreatic tissue leading to poor vascularization, high intratumoral pressure along with hypoxia and an acidic tumor microenvironment. This complicated microenvironment presents a significant challenge for drug delivery. The current manuscript discusses a novel approach to overcome many of these various obstacles. A complex of gemcitabine (GEM) and hemoglobin S (HbS) was formulated, which self-polymerizes under hypoxic and acidic conditions. When polymerized, HbS has the potential to break the tumor stroma, decrease intratumoral pressure, and therefore improve the treatment efficacy of standard therapy. Intratumoral injection of HbS with a fluorescent small molecule surrogate for GEM into a pancreatic tumor xenograft resulted in improved dissemination of the small molecule throughout the pancreatic tumor. The self-polymerization of HbS + GEM was significantly more effective than either agent individually at decreasing tumor size in an in vivo PDAC mouse model. These findings would suggest a clinical benefit from delivering the complex of GEM and HbS via direct injection by endoscopic ultrasound (EUS). With such a treatment option, patients with locally advanced disease would have the potential to become surgical candidates, offering them a chance for cure.

15.
J Neurosci Res ; 100(8): 1545-1550, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34085300

RESUMO

Research innovation that leads to discovery in the battle against neurological disease and disorders requires diverse ideas. The National Institute of Neurological Disorders and Stroke, one of the National Institutes of Health's 27 institutes and centers, strives to reduce the burden of neurological disease and disorders. The National Institutes of Neurologic Disorders and Stroke is very interested in increasing the diversity of researchers by addressing the existing barriers responsible for the low numbers of underrepresented populations from traditionally minority-serving institutions (MSIs) and non-minority serving institutions (non-MSIs). This commentary provides insight on the persistent underrepresentation of racial/ethnic minorities entering neuroscience research careers paths, focusing on multiples levels within the scientific academy and the supportive role that both MSIs and non-MSIs play in increasing diversity in the biomedical research workforce.


Assuntos
National Institute of Neurological Disorders and Stroke (USA) , Doenças do Sistema Nervoso , Humanos , Grupos Minoritários , Pesquisadores , Estados Unidos , Recursos Humanos
16.
Cancers (Basel) ; 15(1)2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36612209

RESUMO

Small extracellular vesicles (sEVs), mainly exosomes, are nanovesicles that shed from the membrane as intraluminal vesicles of the multivesicular bodies, serve as vehicles that carry cargo influential in modulating the tumor microenvironment for the multi-step process of cancer metastasis. Annexin A2 (AnxA2), a calcium(Ca2+)-dependent phospholipid-binding protein, is among sEV cargoes. sEV-derived AnxA2 (sEV-AnxA2) protein is involved in the process of metastasis in triple-negative breast cancer (TNBC). The objective of the current study is to determine whether sEV-AnxA2 protein and/or mRNA could be a useful biomarkers to predict the responsiveness of chemotherapy in TNBC. Removal of Immunoglobulin G (IgG) from the serum as well as using the System Bioscience's ExoQuick Ultra kit resulted in efficient sEV isolation and detection of sEV-AnxA2 protein and mRNA compared to the ultracentrifugation method. The standardized method was applied to the twenty TNBC patient sera for sEV isolation. High levels of sEV-AnxA2 protein and/or mRNA were associated with stage 3 and above in TNBC. Four patients who responded to neoadjuvant chemotherapy had high expression of AnxA2 protein and/or mRNA in sEVs, while other four who did not respond to chemotherapy had low levels of AnxA2 protein and mRNA in sEVs. Our data suggest that the sEV-AnxA2 protein and mRNA could be a combined predictive biomarker for responsiveness to chemotherapy in aggressive TNBC.

17.
Artigo em Inglês | MEDLINE | ID: mdl-36613095

RESUMO

During the COVID-19 pandemic, an increase in poor mental health among Asian Indians was observed in the United States. However, the leading predictors of poor mental health during the COVID-19 pandemic in Asian Indians remained unknown. A cross-sectional online survey was administered to self-identified Asian Indians aged 18 and older (N = 289). Survey collected information on demographic and socio-economic characteristics and the COVID-19 burden. Two novel machine learning techniques-eXtreme Gradient Boosting and Shapley Additive exPlanations (SHAP) were used to identify the leading predictors and explain their associations with poor mental health. A majority of the study participants were female (65.1%), below 50 years of age (73.3%), and had income ≥ $75,000 (81.0%). The six leading predictors of poor mental health among Asian Indians were sleep disturbance, age, general health, income, wearing a mask, and self-reported discrimination. SHAP plots indicated that higher age, wearing a mask, and maintaining social distancing all the time were negatively associated with poor mental health while having sleep disturbance and imputed income levels were positively associated with poor mental health. The model performance metrics indicated high accuracy (0.77), precision (0.78), F1 score (0.77), recall (0.77), and AUROC (0.87). Nearly one in two adults reported poor mental health, and one in five reported sleep disturbance. Findings from our study suggest a paradoxical relationship between income and poor mental health; further studies are needed to confirm our study findings. Sleep disturbance and perceived discrimination can be targeted through tailored intervention to reduce the risk of poor mental health in Asian Indians.


Assuntos
COVID-19 , Humanos , Adulto , Masculino , Feminino , Estados Unidos , Pessoa de Meia-Idade , COVID-19/epidemiologia , Saúde Mental , Estudos Transversais , Pandemias , Povo Asiático
18.
Ethn Dis ; 31(4): 559-566, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34720559

RESUMO

BACKGROUND: Eliminating the NIH funding gap among underrepresented minorities (URMs) remains a high priority for the National Institutes of Health. In 2014, the National Research Mentoring Network1 Steps Toward Academic Research (NRMN STAR) program recruited postdoctoral, early-stage and junior faculty to participate in a 12-month grant writing and professional development program. The expectation of the program was to increase the number of grant submissions and awards to URM researchers. Although receiving a grant award is the gold standard of NRMN STAR, instilling confidence for postdocs and early-stage faculty to submit an application is a critical first step. Based on our previous study, a sustained increase in trainee self-efficacy score over a 24-month period was observed after completing NRMN STAR. METHODS: The current study sought to determine the association between self-efficacy score and grant submissions among two cohorts of trainees. Grantsmanship Self-Efficacy was measured using a 19-item questionnaire previously described by and used in our own work, which was originally adapted from an 88-item Clinical Research Appraisal Inventory.2 A binary variable was created to identify trainees who submitted an initial or revised proposal vs those who abandoned their proposal or were still writing. Trainees were assessed prior to and following program completion with subsequent assessments at 6 and 12 months beyond participation. RESULTS: As of June 20, 2019, 12 of the 21 (57%) trainees had submitted a grant proposal (eg, NIH, other federal or non-federal grant). For every point increase in 12-month post assessments, Grantsmanship Self-Efficacy scores across all domains had a 44% higher prevalence of submitting a grant after controlling for race, sex, education level, academic rank, research experience, duration of postdoctoral training, institution type, and NRMN STAR cohort. CONCLUSIONS: Our findings demonstrate that NRMN STAR had a positive impact on trainees' confidence in grant writing and professional development activities, which resulted in higher grant submission rates.


Assuntos
Pesquisa Biomédica , Tutoria , Organização do Financiamento , Humanos , Tutoria/métodos , Pesquisadores/educação , Autoeficácia
19.
Int J Mol Sci ; 22(20)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34681689

RESUMO

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has infected >235 million people and killed over 4.8 million individuals worldwide. Although vaccines have been developed for prophylactic management, there are no clinically proven antivirals to treat the viral infection. Continuous efforts are being made all over the world to develop effective drugs but these are being delayed by periodic outbreak of mutated SARS-CoV-2 and a lack of knowledge of molecular mechanisms underlying viral pathogenesis and post-infection complications. In this regard, the involvement of Annexin A2 (AnxA2), a lipid-raft related phospholipid-binding protein, in SARS-CoV-2 attachment, internalization, and replication has been discussed. In addition to the evidence from published literature, we have performed in silico docking of viral spike glycoprotein and RNA-dependent RNA polymerase with human AnxA2 to find the molecular interactions. Overall, this review provides the molecular insights into a potential role of AnxA2 in the SARS-CoV-2 pathogenesis and post-infection complications, especially thrombosis, cytokine storm, and insulin resistance.


Assuntos
Anexina A2/metabolismo , COVID-19/patologia , Anexina A2/química , COVID-19/virologia , Síndrome da Liberação de Citocina/metabolismo , Síndrome da Liberação de Citocina/patologia , Humanos , Simulação de Acoplamento Molecular , RNA Polimerase Dependente de RNA/química , RNA Polimerase Dependente de RNA/metabolismo , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Trombose/metabolismo , Trombose/patologia , Internalização do Vírus
20.
Ethn Dis ; 31(3): 469-480, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34295135

RESUMO

Background: To address the need for diversifying the biomedical research workforce, the National Institutes of Health (NIH) established the Diversity Program Consortium (DPC) with the goal of developing, implementing, assessing, and disseminating interventions and programs to enhance the participation and persistence of individuals from underrepresented backgrounds in biomedical research careers. Intervention: As part of the DPC initiative, the NIH funded the National Research Mentoring Network (NRMN), which aimed to increase diversity of the biomedical research workforce through culturally responsive mentorship, networking, and professional development. In 2015, the NRMNet portal was developed to provide a broad-based network of mentors who are accessible to diverse mentees across the country. The portal also provides networking and professional development resources that support mentee transitions from one career stage to the next. Results: NRMNet is the gateway for career stage-specific mentorship, networking, resources, and professional development programs for trainees across the biomedical, behavioral, clinical, and social sciences. In the first five years, the NRMN strategic recruitment efforts resulted in an expanded network of nearly 13,000 diverse mentors and mentees with NRMN representation in all 50 states and Puerto Rico. Consistently, over the first five years, racial and ethnic diversity was reflected in composition of mentee and mentor groups: 66% of 6,526 mentees and 33% of 3,866 mentors were from underrepresented groups. Conclusions: The NRMNet portal is a promising effort for enhancing participation and continued engagement of undrerepresented individuals in biomedical research careers by providing culturally responsive mentorship, networking, and professional development for individuals at all career stages.


Assuntos
Pesquisa Biomédica , Tutoria , Etnicidade , Humanos , Mentores , Recursos Humanos
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