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Abstract Background There is evidence indicating that chemoresistance in tumor cells is mediated by the reconfiguration of the tricarboxylic acid cycle, leading to heightened mitochondrial activity and oxidative phosphorylation (OXPHOS). Previously, we have shown that ovarian cancer cells that are resistant to chemotherapy display increased OXPHOS, mitochondrial function, and metabolic flexibility. To exploit this weakness in chemoresistant ovarian cancer cells, we examined the effectiveness of the mitochondrial inhibitor CPI-613 in treating preclinical ovarian cancer. Methods Chemosensitive OVCAR3, and chemoresistant CAOV3 and F2 ovarian cancer cells lines and their xenografts in nude mice were used. Functional metabolic studies were performed using Seahorse instrument. Metabolite quantification was performed using LC/MS/MS. Results Mice treated with CPI-613 exhibited a notable increase in overall survival and a reduction in tumor development and burden in OVCAR3, F2, and CAOV3 xenografts. CPI-613 suppressed the activity of pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complex, which are two of its targets. This led to a reduction in OXPHOS and tricarboxylic acid cycle activity in all 3 xenografts. The addition of CPI-613 enhanced the responsiveness of chemotherapy in the chemoresistant F2 and CAOV3 tumors, resulting in a notable improvement in survival rates and a reduction in tumor size as compared to using chemotherapy alone. CPI-613 reduced the chemotherapy-induced OXPHOS in chemoresistant tumors. The study revealed that the mechanism by which CPI-613 inhibits tumor growth is through mitochondrial collapse. This is evidenced by an increase in superoxide production within the mitochondria, a decrease in ATP generation, and the release of cytochrome C, which triggers mitochondria-induced apoptosis. Conclusion Our study demonstrates the translational potential of CPI-613 against chemoresistant ovarian tumors.

Several protein expression platforms exist for a wide variety of biopharmaceutical needs. A substantial proportion of research and development into protein expression platforms and their optimization since the mid-1900s is a result of the production of viral antigens for use in subunit vaccine research. This review discusses the seven most popular forms of expression systems used in the past decade—bacterial, insect, mammalian, yeast, algal, plant and cell-free systems—in terms of advantages, uses and limitations for viral antigen production in the context of subunit vaccine research. Post-translational modifications, immunogenicity, efficacy, complexity, scalability and the cost of production are major points discussed. Examples of licenced and experimental vaccines are included along with images which summarize the processes involved.

Abstract The design of cereblon-binding molecular glues (MGs) that selectively recruit a desired protein while excluding teratogenic SALL4 is an area of significant interest when designing therapeutic agents. Previous studies show that SALL4 is degraded in the presence of IKZF1 degraders pomalidomide, and to a lesser extent by CC-220. To expand our understanding of the molecular basis for the interaction of SALL4 with cereblon, we performed biophysical and structural studies demonstrating that SALL4 zinc finger domains one and two (ZF1-2) interact with cereblon (CRBN) in a unique manner. ZF1 interacts with the N-terminal domain of cereblon and ZF2 binds as expected in the C-terminal IMiD-binding domain. Both ZF1 and ZF2 contribute to the potency of the interaction of ZF1-2 with CRBN:MG complexes and the affinities of SALL4 ZF1-2 for the cereblon:CC-220 complex are less potent than for the corresponding pomalidomide complex. Structural analysis provides a rationale for understanding the reduced affinity of SALL4 for cereblon in the presence of CC-220, which engages both ZF1 and ZF2. These studies further our understanding of the molecular glue-mediated interactions of zinc finger-based proteins with cereblon and may provide structural tools for the prospective design of compounds with reduced binding and degradation of SALL4.

Several pieces of literature have been written on the status of heterosexual college student attitudes toward homosexuality, homosexual students, and homophobia (D'Augelli, 1989; D'Augelli & Rose, 1990; Ficarrotto,1990; Goldberg, 1982; Grieger & Ponterotto, 1988; McDevitt, 1987; Spees, 1987; Wells & Franken, 1987; Yarber & Yee, 1983). Conversely, limited research outlines the impact that this heterosexual perspective has on homosexual (gay/lesbian) students. Furthermore, little research has been presented in the specific area of addressing the needs of homosexual and bisexual students (Baker, 1991; Scott, 1988). Due to the minimal attention focusing on gay/lesbian/bisexual students, and more specifically the issues that they face on our college campuses, this study attempts to extend the existing research. This article originally appeared in the CSPA Journal in 1994 and presented literature on LGBT students, particularly noting the lack of research at that time. It also presents findings from a qualitative project talking to LGBT students at that time about their experience.

Abstract Background Transgender and gender diverse (TGD) individuals disproportionately experience disparate health outcomes compared to their cisgender peers. This study aimed to collect qualitative data from a sample of TGD community health center patients on health research priorities to inform future TGD-centered research in the field of TGD health. Methods Between September–November of 2018, four focus groups (two groups in Boston MA, two in New York NY; n = 28 individuals) were held to evaluate community-identified TGD health research priorities with a sample of patients from two community health centers. Thematic analyses were conducted and restricted to social factors impacting health. Findings were incorporated into the development of The LEGACY Project, a longitudinal cohort of TGD patients, assessing the impact of gender-affirming care on health outcomes. Results Cross-cutting themes about TGD research priorities pertaining to social factors and health included: (1) Embodiment: understanding and investigating the complex and intersectional lived experiences of TGD individuals; (2) Social determinants of health: the impact of structural and interpersonal stigma on TGD health; and (3) Resiliency and health promoting factors: the need to expand public health research beyond disparities to assess resiliency and health promotion in TGD communities. Conclusions Participants identified investigating the impact of social influences on health as a research priority for TGD patients. Recalibrating field norms from individual researcher priorities to TGD population-driven research will help ensure investigators address topics that may otherwise be missed or overlooked and may optimize the reach and impact of research in TGD health.

We developed a dataset consisting of outbreak data collected from official, open-source surveillance reports representing more than 170 pathogens, 237 countries and territories, and more than 3300 events that occurred primarily between 1963 and 2023. Here we present and analyze a subset of these data, comprising a dataset of human epidemic events with onset between 2015 and 2020. Structuring of epidemiological data in the dataset follows a specific methodology to ensure consistency across all events. This methodology has been designed to produce the most reliable spatiotemporal view of an outbreak as possible. To ensure data are true-to-source, the structured data undergoes multiple rounds of both manual and automated review and validation. The extensive and standardized nature of the dataset makes it well-suited for both descriptive epidemiology and exploring outbreak dynamics and disease emergence. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review summarizes recent evidence linking experiences of discrimination and anticipated discrimination with cardiovascular health outcomes. Recent Findings: Experiences of discrimination were consistently associated with increased risk of nicotine exposure, poor sleep health, obesity, diabetes, hypertension, and subclinical cardiovascular disease. Evidence is mixed for cardiovascular disease diagnoses and cardiovascular mortality. Although research is limited, anticipated discrimination is an independent risk factor for poor sleep health and subclinical cardiovascular disease. Key methodological limitations included the limited use of gold-standard objective measures of health behaviors and well-validated self-report measures, inadequate consideration of intersectionality, and lack of robust examinations of psychological, behavioral, and physiological mechanisms linking discrimination with cardiovascular health outcomes. Summary: There is substantial evidence linking experiences of discrimination with cardiovascular outcomes. Yet, before translating these findings into clinical practice, more rigorous studies are needed to address methodological limitations and uncover mechanisms by which discrimination influences cardiovascular health. There is a need for studies to inform the development of evidence-based interventions focused on reducing the influence of discrimination-related stressors on cardiovascular health outcomes. Findings have important implications for future work to advance cardiovascular health equity. [ABSTRACT FROM AUTHOR]

A 27-year-old woman presented with bilateral blurry vision for 2 weeks. She had a presumed diagnosis of idiopathic intracranial hypertension given her bilateral disc edema; however, bilateral disc and retinal infiltration was noted on ophthalmoscopy. This report presents a rare case of chronic myelogenous leukemia (CML) in the non-blast phase presenting as bilateral optic disc infiltration, indicating central nervous system involvement at the time of diagnosis. The patient had no other clinical symptoms at the time of diagnosis and was promptly treated with orbital radiation and a tyrosine kinase inhibitor, resulting in 20/20 vision in both eyes. [Ophthalmic Surg Lasers Imaging Retina 2025;56:102–107.] [ABSTRACT FROM AUTHOR]

Combining cytarabine and mitoxantrone with the tricarboxylic acid cycle inhibitor devimistat has been reported in a phase I clinical trial with relapsed or refractory acute myeloid leukaemia (AML). Here, the authors report the outcomes of a phase II study, analyse samples from both phases and perform preclinical analyses that show mitochondrial fission or autophagy inhibition sensitizes AML cells to devimistat.

BackgroundThe sexual health of transmasculine (TM) people—those who identify as male, men, or nonbinary and were assigned a female sex at birth—is understudied. One barrier to conducting HIV- and sexually transmitted infection (STI)–related research with this population is how to best capture sexual risk data in an acceptable, gender-affirming, and accurate manner. ObjectiveThis study aimed to report on the community-based process of developing, piloting, and refining a digitally deployed measure to assess self-reported sexual behaviors associated with HIV and STI transmission for research with TM adults. MethodsA multicomponent process was used to develop a digital-assisted self-interview to assess HIV and STI risk in TM people: gathering input from a Community Task Force; working with an interdisciplinary team of content experts in transgender medicine, epidemiology, and infectious diseases; conducting web-based focus groups; and iteratively refining the measure. We field-tested the measure with 141 TM people in the greater Boston, Massachusetts area to assess HIV and STI risk. Descriptive statistics characterized the distribution of sexual behaviors and HIV and STI transmission risk by the gender identity of sexual partners. ResultsThe Transmasculine Sexual Health Assessment (TM-SHA) measures the broad range of potential sexual behaviors TM people may engage in, including those which may confer risk for STIs and not just for HIV infection (ie, oral-genital contact); incorporates gender-affirming language (ie, genital or frontal vs vaginal); and asks sexual partnership characteristics (ie, partner gender). Among 141 individual participants (mean age 27, SD 5 years; range 21-29 years; n=21, 14.9% multiracial), 259 sexual partnerships and 15 sexual risk behaviors were reported. Participants engaged in a wide range of sexual behaviors, including fingering or fisting (receiving: n=170, 65.6%; performing: n=173, 66.8%), oral-genital sex (receiving: n=182, 70.3%; performing: n=216, 83.4%), anal-genital sex (receptive: n=31, 11.9%; insertive: n=9, 3.5%), frontal-genital sex (receptive: n=105, 40.5%; insertive: n=46, 17.8%), and sharing toys or prosthetics during insertive sex (n=62, 23.9%). Overall barrier use for each sexual behavior ranged from 10.9% (20/182) to 81% (25/31). Frontal receptive sex with genitals and no protective barrier was the highest (21/42, 50%) with cisgender male partners. In total, 14.9% (21/141) of participants reported a lifetime diagnosis of STI. The sexual history tool was highly acceptable to TM participants. ConclusionsThe TM-SHA is one of the first digital sexual health risk measures developed specifically with and exclusively for TM people. TM-SHA successfully integrates gender-affirming language and branching logic to capture a wide array of sexual behaviors. The measure elicits sexual behavior information needed to assess HIV and STI transmission risk behaviors. A strength of the tool is that detailed partner-by-partner data can be used to model partnership-level characteristics, not just individual-level participant data, to inform HIV and STI interventions.

Abstract Background The purpose of this formative study was to assess barriers and facilitators to participation of transgender and gender diverse (TGD) patients in clinical research to solicit specific feedback on perceived acceptability and feasibility of research methods to inform creation of a multisite longitudinal cohort of primary care patients engaged in care at two community health centers. Method Between September–November 2018, four focus groups (FGs) were convened at two community health centers in Boston, MA and New York, NY (N = 28 participants across all 4 groups; 11 in Boston and 17 in New York). FG guides asked about patient outreach, acceptability of study methods and measures, and ideas for study retention. FGs were facilitated by TGD study staff, lasted approximately 90 min in duration, were audio recorded, and then transcribed verbatim by a professional transcription service. Thematic analyses were conducted by two independent analysts applying a constant comparison method. Consistency and consensus were achieved across code creation and application aided by Dedoose software. Results Participants were a mean age of 33.9 years (SD 12.3; Range 18–66). Participants varied in gender identity with 4 (14.3%) men, 3 (10.7%) women, 8 (28.6%) transgender men, 10 (35.7%) transgender women, and 3 (10.7%) nonbinary. Eight (26.6%) were Latinx, 5 (17.9%) Black, 3 (10.7%) Asian, 3 (10.7%) another race, and 5 (17.9%) multiracial. Motivators and facilitators to participation were: research creating community, research led by TGD staff, compensation, research integrated into healthcare, research applicable to TGD and non-TGD people, and research helping TGD communities. Barriers were: being research/healthcare averse, not identifying as TGD, overlooking questioning individuals, research coming from a ‘cisgender lens”, distrust of how the research will be used, research not being accessible to TGD people, and research being exploitative. Conclusion Though similarities emerged between the perspectives of TGD people and research citing perspectives of other underserved populations, there are barriers and facilitators to research which are unique to TGD populations. It is important for TGD people to be involved as collaborators in all aspects of research that concerns them.

Several protein expression platforms exist for a wide variety of biopharmaceutical needs. A substantial proportion of research and development into protein expression platforms and their optimization since the mid-1900s is a result of the production of viral antigens for use in subunit vaccine research. This review discusses the seven most popular forms of expression systems used in the past decade—bacterial, insect, mammalian, yeast, algal, plant and cell-free systems—in terms of advantages, uses and limitations for viral antigen production in the context of subunit vaccine research. Post-translational modifications, immunogenicity, efficacy, complexity, scalability and the cost of production are major points discussed. Examples of licenced and experimental vaccines are included along with images which summarize the processes involved. [ABSTRACT FROM AUTHOR]

Background: There is evidence indicating that chemoresistance in tumor cells is mediated by the reconfiguration of the tricarboxylic acid cycle, leading to heightened mitochondrial activity and oxidative phosphorylation (OXPHOS). Previously, we have shown that ovarian cancer cells that are resistant to chemotherapy display increased OXPHOS, mitochondrial function, and metabolic flexibility. To exploit this weakness in chemoresistant ovarian cancer cells, we examined the effectiveness of the mitochondrial inhibitor CPI-613 in treating preclinical ovarian cancer. Methods: Chemosensitive OVCAR3, and chemoresistant CAOV3 and F2 ovarian cancer cells lines and their xenografts in nude mice were used. Functional metabolic studies were performed using Seahorse instrument. Metabolite quantification was performed using LC/MS/MS. Results: Mice treated with CPI-613 exhibited a notable increase in overall survival and a reduction in tumor development and burden in OVCAR3, F2, and CAOV3 xenografts. CPI-613 suppressed the activity of pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complex, which are two of its targets. This led to a reduction in OXPHOS and tricarboxylic acid cycle activity in all 3 xenografts. The addition of CPI-613 enhanced the responsiveness of chemotherapy in the chemoresistant F2 and CAOV3 tumors, resulting in a notable improvement in survival rates and a reduction in tumor size as compared to using chemotherapy alone. CPI-613 reduced the chemotherapy-induced OXPHOS in chemoresistant tumors. The study revealed that the mechanism by which CPI-613 inhibits tumor growth is through mitochondrial collapse. This is evidenced by an increase in superoxide production within the mitochondria, a decrease in ATP generation, and the release of cytochrome C, which triggers mitochondria-induced apoptosis. Conclusion: Our study demonstrates the translational potential of CPI-613 against chemoresistant ovarian tumors. [ABSTRACT FROM AUTHOR]

Patterns of cohort decline are key demographic traits that provide a unique temporal perspective vital to understanding population dynamics. The discovery of multidecadal lifespans in tropical surgeonfishes in the 1990s created a paradigm shift to the notion that they are highly vulnerable species with low population recovery rates; however, research into the mortality patterns of surgeonfishes (Acanthuridae) has been sparse until recently. Recent studies on this family have demonstrated an unusual (possibly unique), two‐phase pattern of adult catch‐at‐age, whereby there is a population‐level shift from higher‐than‐expected rates of decline early in life to lower‐than‐expected decline rates for the remainder of the lifespan. To examine the geographic and phylogenetic ubiquity of this pattern, we compiled age‐based information from demographic samples of 70 populations of 25 tropical species spanning the Indo‐Central Pacific and Central‐Western Atlantic. Overall, we found that 79% of populations exhibited strong biphasic patterns, including 88% of populations across the Indo‐Central Pacific. By accounting for empirical relationships instead of using linear catch curves or classical assumptions of natural population decay based on lifespan, we demonstrate that surgeonfishes have turnover times that are two to four times faster than previously believed. Faster turnover times may suggest a higher level of sustainability for surgeonfish fisheries throughout the global tropics than previously estimated. [ABSTRACT FROM AUTHOR]

Getting synthetic biology circuit-based sensors into field applications is still a challenge. Here the authors combine a circuit sensor with a glucose meter for small analyte and nucleic acid detection.

Abstract We have previously developed and validated a one-step assay based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) for rapid detection of the Zika virus (ZIKV) from mosquito samples. Patient diagnosis of ZIKV is currently carried out in centralized laboratories using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR), which, while the gold standard molecular method, has several drawbacks for use in remote and low-resource settings, such as high cost and the need of specialized equipment. Point-of-care (POC) diagnostic platforms have the potential to overcome these limitations, especially in low-resource countries where ZIKV is endemic. With this in mind, here we optimized and validated our RT-LAMP assay for rapid detection of ZIKV from patient samples. We found that the assay detected ZIKV from diverse sample types (serum, urine, saliva, and semen) in as little as 20 min, without RNA extraction. The RT-LAMP assay was highly specific and up to 100 times more sensitive than RT-qPCR. We then validated the assay using 100 patient serum samples collected from suspected cases of arbovirus infection in the state of Pernambuco, which was at the epicenter of the last Zika epidemic. Analysis of the results, in comparison to RT-qPCR, found that the ZIKV RT-LAMP assay provided sensitivity of 100%, specificity of 93.75%, and an overall accuracy of 95.00%. Taken together, the RT-LAMP assay provides a straightforward and inexpensive alternative for the diagnosis of ZIKV from patients and has the potential to increase diagnostic capacity in ZIKV-affected areas, particularly in low and middle-income countries.

Abstract Background To date, research assessing discrimination has employed primarily explicit measures (i.e., self-reports), which can be subject to intentional and social desirability processes. Only a few studies, focusing on sex and race/ethnicity discrimination, have relied on implicit measures (i.e., Implicit Association Test, IAT), which permit assessing mental representations that are outside of conscious control. This study aims to advance measurement of discrimination by extending the application of implicit measures to multiple types of discrimination and optimizing the time required for the administration of these instruments. Methods Between September 27th 2019 and February 9th 2020, we conducted six experiments (984 participants) to assess implicit and explicit discrimination based on race/ethnicity, sex, gender identity, sexual orientation, weight, and age. Implicit discrimination was measured by using the Brief-Implicit Association Test (B-IAT), a new validated version of the IAT developed to shorten the time needed (from ≈15 to ≈2 min) to assess implicit mental representations, while explicit discrimination was assessed using self-reported items. Results Among participants (mean age = 37.8), 68.6% were White Non-Hispanic; 69% were females; 76.1% were heterosexual; 90.7% were gender conforming; 52.8% were medium weight; and 41.5% had an advanced level of education. Overall, we found implicit and explicit recognition of discrimination towards all the target groups (stronger for members of the target than dominant groups). Some exceptions emerged in experiments investigating race/ethnicity and weight discrimination. In the racism experiment, only people of Color showed an implicit recognition of discrimination towards the target group, while White people were neutral. In the fatphobia experiment, participants who were not heavy showed a slight implicit recognition of discrimination towards the dominant group, while heavy participants were neutral. Conclusions This study provides evidence that the B-IAT is a valuable tool for quickly assessing multiple types of implicit discrimination. It shows also that implicit and explicit measures can display diverging results, thus indicating that research would benefit from the use of both these instruments. These results have important implications for the assessment of discrimination in health research as well as in social and psychological science.

Abstract The global spread of SARS-CoV-2 has shaken our health care and economic systems, prompting re-evaluation of long-held views on how best to deliver care. This is especially the case for our global diagnostic strategy. While current laboratory-based centralized RT-qPCR will continue to serve as a gold standard diagnostic into the foreseeable future, the shortcomings of our dependence on this method have been laid bare. It is now clear that a robust diagnostics pandemic response strategy, like any disaster planning, must include adaptive, diverse and de-centralized solutions. Here we look at how the COVID-19 pandemic, and previous outbreaks, have set the stage for a new innovative phase in diagnostics and a re-thinking of pandemic preparedness.