Parents' anti-Black messages, empathic reactions toward racism, fear of Black individuals, and perceived ability to engage in anti-racism advocacy among Asian American emerging adults.

Asian Americans, historically oppressed and influenced by White supremacist norms, may internalize anti-Blackness (beliefs of behaviors that minimize, marginalize, or devalue Black individuals) as they navigate White-dominated environments to survive and seek acceptance. However, there is limited research addressing the intergenerational socialization of anti-Blackness within Asian American communities and its impact as a barrier to cross-racial solidarity and involvement in anti-racism efforts. Thus, we tested whether parents' anti-Black messages were associated with fear of Black individuals and lack of empathic reactions to anti-Black racism, and in turn, related to hindrance in the perceived ability to engage in anti-racism advocacy among Asian American emerging adults. With data from 205 participants (Mage = 19.92, SD = 2.64, online convenience sample), we conducted a path analysis of parents' anti-Black messages indirectly associated with perceived ability in advocacy against anti-Black racism through fear of Black individuals and empathic reactions to anti-Black racism. Parents' anti-Black messages were associated with greater fear of Black individuals, which was associated with lower empathic reactions to racism, and in turn, ultimately associated with a lower perceived ability to engage in advocacy against anti-Black racism. This pathway was the best-fitting model compared with an alternative parallel model (fear and empathy as separate mediators) and a model with empathy as the first mediator. Our study suggests that clinicians, educators, and researchers should target parents' anti-Black messages and Asian American emerging adults' emotional responses (fear, empathy) to anti-Black racism in disrupting anti-Blackness at parental/family and individual levels.

Gendered Racial Microaggressions and Depressive Symptoms Among Emerging Adult Asian American Women: Racial/Ethnic Differences Among Asian and White Romantic Partners.

Discrimination can contribute to adverse mental health outcomes among individuals in romantic partnerships. However, research has yet to examine how differences in partner race/ethnicity can shape the link between gendered racial microaggressions, an intersectional form of discrimination, and depressive symptoms among Asian American women. Accordingly, we assessed the link between gendered racial microaggressions and depressive symptoms, and whether partner race/ethnicity (White vs. Asian) moderated the link. Using a sample of 156 Asian American women (Mage = 26.5, SD = 5.33), we conducted multiple regressions to assess the main effects between four gendered racial microaggression stress subscale factors and depressive symptoms. We then examined partner race/ethnicity as a moderator in these associations. All four gendered racial microaggression stress subscale factors of ascribed submissiveness, assumptions of universal appearance, Asian fetishism, and media invalidation significantly predicted greater depressive symptoms. However, only Asian fetishism experiences maintained a significant and positive association with depressive symptoms for Asian American women with White male partners. The association between Asian fetishism and depressive symptoms was no longer significant for Asian American women with Asian male partners. Results indicate that Asian fetishization may be a uniquely oppressive experience for Asian American women with White partners that can contribute to greater depressive symptoms. These findings demonstrate an increased need for the development of critical consciousness in individual and couples counseling sessions to help Asian American women and their romantic partners identify and mitigate the negative effects of gendered racial microaggressions.

Treatment Effects in Randomized and Nonrandomized Studies of Pharmacological Interventions: A Meta-Analysis.

Importance: Randomized clinical trials (RCTs) are widely regarded as the methodological benchmark for assessing clinical efficacy and safety of health interventions. There is growing interest in using nonrandomized studies to assess efficacy and safety of new drugs. Objective: To determine how treatment effects for the same drug compare when evaluated in nonrandomized vs randomized studies. Data Sources: Meta-analyses published between 2009 and 2018 were identified in MEDLINE via PubMed and the Cochrane Database of Systematic Reviews. Data analysis was conducted from October 2019 to July 2024. Study Selection: Meta-analyses of pharmacological interventions were eligible for inclusion if both randomized and nonrandomized studies contributed to a single meta-analytic estimate. Data Extraction and Synthesis: For this meta-analysis using a meta-epidemiological framework, separate summary effect size estimates were calculated for nonrandomized and randomized studies within each meta-analysis using a random-effects model and then these estimates were compared. The reporting of this study followed the Guidelines for Reporting Meta-Epidemiological Methodology Research and relevant portions of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Main Outcome and Measures: The primary outcome was discrepancies in treatment effects obtained from nonrandomized and randomized studies, as measured by the proportion of meta-analyses where the 2 study types disagreed about the direction or magnitude of effect, disagreed beyond chance about the effect size estimate, and the summary ratio of odds ratios (ROR) obtained from nonrandomized vs randomized studies combined across all meta-analyses. Results: A total of 346 meta-analyses with 2746 studies were included. Statistical conclusions about drug benefits and harms were different for 130 of 346 meta-analyses (37.6%) when focusing solely on either nonrandomized or randomized studies. Disagreements were beyond chance for 54 meta-analyses (15.6%). Across all meta-analyses, there was no strong evidence of consistent differences in treatment effects obtained from nonrandomized vs randomized studies (summary ROR, 0.95; 95% credible interval [CrI], 0.89-1.02). Compared with experimental nonrandomized studies, randomized studies produced on average a 19% smaller treatment effect (ROR, 0.81; 95% CrI, 0.68-0.97). There was increased heterogeneity in effect size estimates obtained from nonrandomized compared with randomized studies. Conclusions and Relevance: In this meta-analysis of treatment effects of pharmacological interventions obtained from randomized and nonrandomized studies, there was no overall difference in effect size estimates between study types on average, but nonrandomized studies both overestimated and underestimated treatment effects observed in randomized studies and introduced additional uncertainty. These findings suggest that relying on nonrandomized studies as substitutes for RCTs may introduce additional uncertainty about the therapeutic effects of new drugs.

TOPORS E3 ligase mediates resistance to hypomethylating agent cytotoxicity in acute myeloid leukemia cells.

Hypomethylating agents (HMAs) are frontline therapies for Myelodysplastic Neoplasms (MDS) and Acute Myeloid Leukemia (AML). However, acquired resistance and treatment failure are commonplace. To address this, we perform a genome-wide CRISPR-Cas9 screen in a human MDS-derived cell line, MDS-L, and identify TOPORS as a loss-of-function target that synergizes with HMAs, reducing leukemic burden and improving survival in xenograft models. We demonstrate that depletion of TOPORS mediates sensitivity to HMAs by predisposing leukemic blasts to an impaired DNA damage response (DDR) accompanied by an accumulation of SUMOylated DNMT1 in HMA-treated TOPORS-depleted cells. The combination of HMAs with targeting of TOPORS does not impair healthy hematopoiesis. While inhibitors of TOPORS are unavailable, we show that inhibition of protein SUMOylation with TAK-981 partially phenocopies HMA-sensitivity and DDR impairment. Overall, our data suggest that the combination of HMAs with inhibition of SUMOylation or TOPORS is a rational treatment option for High-Risk MDS (HR-MDS) or AML.

Catalase produced by Candida albicans protects Streptococcus mutans from H2O2 stress-one more piece in the cross-kingdom synergism puzzle.

Co-infection with Streptococcus mutans and Candida albicans is associated with dental caries, and their co-cultivation results in enhanced biofilm matrix production that contributes to increased virulence and caries risk. Moreover, the catalase-negative S. mutans demonstrates increased oxidative stress tolerance when co-cultivated in biofilms with C. albicans, a catalase-producing yeast. Here, we sought to obtain mechanistic insights into the increased H2O2 tolerance of S. mutans when co-cultivated with clinical isolates of Candida glabrata, Candida tropicalis, and C. albicans. Additionally, the C. albicans SC5314 laboratory strain, its catalase mutant (SC5314Δcat1), and S. mutans UA159 and its glucosyltransferase B/C mutant (UA159ΔgtfB/C) were grown as single- and dual-species biofilms. Time-kill assays revealed that upon acute H2O2 challenge, the survival rates of S. mutans in dual-species biofilms with the clinical isolates and C. albicans SC5314 were greater than when paired with SC5314Δcat1 or as a single-species biofilm. Importantly, this protection was independent of glucan production through S. mutans GtfB/C. Transwell assays and treatment with H2O2-pre-stimulated C. albicans SC5314 supernatant revealed that this protection is contact-dependent. Biofilm stability assays with sublethal H2O2 or peroxigenic Streptococcus A12 challenge resulted in biomass reduction of single-species S. mutans UA159 and dual-species with SC5314Δcat1 biofilms compared to UA159 biofilms co-cultured with C. albicans SC5314. S. mutans oxidative stress genes were upregulated in single-species biofilms when exposed to H2O2, but not when S. mutans was co-cultivated with C. albicans SC5314. Here, we uncovered a novel, contact-dependent, synergistic interaction in which the catalase of C. albicans protects S. mutans against H2O2. IMPORTANCE It is well established that co-infection with the gram-positive caries-associated bacterium Streptococcus mutans and the yeast pathobiont Candida albicans results in aggressive forms of caries in humans and animal models. Together, these microorganisms form robust biofilms through enhanced production of extracellular polysaccharide matrix. Further, co-habitation in a biofilm community appears to enhance these microbes' tolerance to environmental stressors. Here, we show that catalase produced by C. albicans protects S. mutans from H2O2 stress in a biofilm matrix-independent manner. Our findings uncovered a novel synergistic trait between these two microorganisms that could be further exploited for dental caries prevention and control.

Protein-protein interactions between tenascin-R and RPTPζ/phosphacan are critical to maintain the architecture of perineuronal nets.

Neural plasticity, the ability to alter the structure and function of neural circuits, varies throughout the age of an individual. The end of the hyperplastic period in the central nervous system coincides with the appearance of honeycomb-like structures called perineuronal nets (PNNs) that surround a subset of neurons. PNNs are a condensed form of neural extracellular matrix that include the glycosaminoglycan hyaluronan and extracellular matrix proteins such as aggrecan and tenascin-R (TNR). PNNs are key regulators of developmental neural plasticity and cognitive functions, yet our current understanding of the molecular interactions that help assemble them remains limited. Disruption of Ptprz1, the gene encoding the receptor protein tyrosine phosphatase RPTPζ, altered the appearance of nets from a reticulated structure to puncta on the surface of cortical neuron bodies in adult mice. The structural alterations mirror those found in Tnr-/- mice, and TNR is absent from the net structures that form in dissociated cultures of Ptprz1-/- cortical neurons. These findings raised the possibility that TNR and RPTPζ cooperate to promote the assembly of PNNs. Here, we show that TNR associates with the RPTPζ ectodomain and provide a structural basis for these interactions. Furthermore, we show that RPTPζ forms an identical complex with tenascin-C, a homolog of TNR that also regulates neural plasticity. Finally, we demonstrate that mutating residues at the RPTPζ-TNR interface impairs the formation of PNNs in dissociated neuronal cultures. Overall, this work sets the stage for analyzing the roles of protein-protein interactions that underpin the formation of nets.

Preparing for Colonoscopy in People with Diabetes: A Review with Suggestions for Clinical Practice.

People with diabetes have an increased risk of adverse events during the peri-colonoscopy period, including hypoglycemia, lactic acidosis, diabetic ketoacidosis and acute kidney injury. This is secondary to inadequate dietary modification, the bowel preparation and antihyperglycemic agent modification. With the availability of many new diabetes agents, endoscopists need updated guidance. This review of current literature provides a practical approach to antihyperglycemic agent modification in the context of colonoscopy preparation, as well as guidelines on dietary changes, the bowel preparation itself and glucose monitoring.

Medical School Interview Preference in the Post-COVID-19 Era: A Single Institution Experience.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic presented unforeseen obstacles to prospective medical students such as Medical College of Admission Test (MCAT) scheduling postponements and technical challenges during virtual interviews. Students were also faced with difficult decisions post-submission such as having to choose a program without ever visiting a school in person. The primary objective of the present study is to assess the changes in medical school interview preferences and experiences in the post-COVID-19 era. METHODS: A retrospective survey of the class of 2024 (in-person interview group) and class of 2025 (virtual interview group) at an allopathic medical school was conducted in the Fall of 2021 via the Qualtrics XM online survey software (Qualtrics, Provo, UT, USA). RESULTS: There were 195 survey respondents: 77 students from the in-person interview group and 89 students from the virtual group. More students in the virtual cohort had to reschedule their MCAT compared to the in-person cohort (56.1% versus 14.3%; p<0.001). The in-person group had higher travel-related expenses (>$500) compared to the group who interviewed virtually (65.1% versus 2.4%; p<0.001). More students from the in-person cohort preferred the in-person interview format compared to the virtual cohort (85.7% versus 22.5%; p<0.001). Lastly, 87% of the in-person group and 24.7% of the virtual group felt they were able to gather a clear impression of the atmosphere and culture of a school from the interview trail alone (p<0.001). CONCLUSION: Matriculated medical students at an allopathic medical school who applied during the COVID-19 pandemic had more pre-application hurdles when compared to the cohort who applied just prior to the pandemic. Students who primarily had virtual interviews during the pandemic had less travel-related costs but felt more limited in their experience of a school's culture and ability to establish rapport with interviewers. Despite this, however, the virtual group still expressed a preference for virtual interviews.

Hierarchical Materials from High Information Content Macromolecular Building Blocks: Construction, Dynamic Interventions, and Prediction.

Hierarchical materials that exhibit order over multiple length scales are ubiquitous in nature. Because hierarchy gives rise to unique properties and functions, many have sought inspiration from nature when designing and fabricating hierarchical matter. More and more, however, nature's own high-information content building blocks, proteins, peptides, and peptidomimetics, are being coopted to build hierarchy because the information that determines structure, function, and interfacial interactions can be readily encoded in these versatile macromolecules. Here, we take stock of recent progress in the rational design and characterization of hierarchical materials produced from high-information content blocks with a focus on stimuli-responsive and "smart" architectures. We also review advances in the use of computational simulations and data-driven predictions to shed light on how the side chain chemistry and conformational flexibility of macromolecular blocks drive the emergence of order and the acquisition of hierarchy and also on how ionic, solvent, and surface effects influence the outcomes of assembly. Continued progress in the above areas will ultimately usher in an era where an understanding of designed interactions, surface effects, and solution conditions can be harnessed to achieve predictive materials synthesis across scale and drive emergent phenomena in the self-assembly and reconfiguration of high-information content building blocks.

Multispecies facial detection for individual identification of wildlife: a case study across ursids.

To address biodiversity decline in the era of big data, replicable methods of data processing are needed. Automated methods of individual identification (ID) via computer vision are valuable in conservation research and wildlife management. Rapid and systematic methods of image processing and analysis are fundamental to an ever-growing need for effective conservation research and practice. Bears (ursids) are an interesting test system for examining computer vision techniques for wildlife, as they have variable facial morphology, variable presence of individual markings, and are challenging to research and monitor. We leveraged existing imagery of bears living under human care to develop a multispecies bear face detector, a critical part of individual ID pipelines. We compared its performance across species and on a pre-existing wild brown bear Ursus arctos dataset (BearID), to examine the robustness of convolutional neural networks trained on animals under human care. Using the multispecies bear face detector and retrained sub-applications of BearID, we prototyped an end-to-end individual ID pipeline for the declining Andean bear Tremarctos ornatus. Our multispecies face detector had an average precision of 0.91-1.00 across all eight bear species, was transferable to images of wild brown bears (AP = 0.93), and correctly identified individual Andean bears in 86% of test images. These preliminary results indicate that a multispecies-trained network can detect faces of a single species sufficiently to achieve high-performance individual classification, which could speed-up the transferability and application of automated individual ID to a wider range of taxa. Supplementary Information: The online version contains supplementary material available at 10.1007/s42991-021-00168-5.

Building the Plant SynBio Toolbox through Combinatorial Analysis of DNA Regulatory Elements.

While the installation of complex genetic circuits in microorganisms is relatively routine, the synthetic biology toolbox is severely limited in plants. Of particular concern is the absence of combinatorial analysis of regulatory elements, the long design-build-test cycles associated with transgenic plant analysis, and a lack of naming standardization for cloning parts. Here, we use previously described plant regulatory elements to design, build, and test 91 transgene cassettes for relative expression strength. Constructs were transiently transfected into Nicotiana benthamiana leaves and expression of a fluorescent reporter was measured from plant canopies, leaves, and protoplasts isolated from transfected plants. As anticipated, a dynamic level of expression was achieved from the library, ranging from near undetectable for the weakest cassette to a ∼200-fold increase for the strongest. Analysis of expression levels in plant canopies, individual leaves, and protoplasts were correlated, indicating that any of the methods could be used to evaluate regulatory elements in plants. Through this effort, a well-curated 37-member part library of plant regulatory elements was characterized, providing the necessary data to standardize construct design for precision metabolic engineering in plants.

The cellular function of ROP GTPase prenylation is important for multicellularity in the moss Physcomitrium patens.

A complete picture of how signaling pathways lead to multicellularity is largely unknown. Previously, we generated mutations in a protein prenylation enzyme, GGB, and showed that it is essential for maintaining multicellularity in the moss Physcomitrium patens. Here, we show that ROP GTPases act as downstream factors that are prenylated by GGB and themselves play an important role in the multicellularity of P. patens. We also show that the loss of multicellularity caused by the suppression of GGB or ROP GTPases is due to uncoordinated cell expansion, defects in cell wall integrity and the disturbance of the directional control of cell plate orientation. Expressing prenylatable ROP in the ggb mutant not only rescues multicellularity in protonemata but also results in development of gametophores. Although the prenylation of ROP is important for multicellularity, a higher threshold of active ROP is required for gametophore development. Thus, our results suggest that ROP activation via prenylation by GGB is a key process at both cell and tissue levels, facilitating the developmental transition from one dimension to two dimensions and to three dimensions in P. patens.

High-Throughput Transfection and Analysis of Soybean (Glycine max ) Protoplasts.

With the advent of plant synthetic biology, there is an urgent need to develop plant-based systems that are able to effectively enhance the speed of design-build-test cycles to screen large numbers of synthetic constructs. Thus far, protoplasts have served to fill this need, with cell suspension cultures serving as the primary source tissue to enable high-throughput protoplast experimentation. The possibility to use low-cost food-grade enzymes for cell wall digestion along with polyethylene glycol (PEG)-mediated transfection makes protoplasts particularly suited to automation and high-throughput screening. In other systems for which synthetic biology is well established (model bacteria and yeast), libraries of components, i.e., promoters, 5' untranslated regions, 3' untranslated regions, terminators, and transcription factors, serve as the basis for the design of complex genetic circuits. In order for synthetic biology to make similar strides in plant biology, well-characterized libraries of functional genetic parts for plants are required, necessitating the need for high-throughput protoplast assays.In this chapter, we describe an optimized method for the preparation of soybean (Glycine max ) dark-grown cell suspension cultures, followed by protoplast isolation, automated transfection , and subsequent screening.

Amphiphilic Peptoid-Directed Assembly of Oligoanilines into Highly Crystalline Conducting Nanotubes.

It is reported herein the synthesis of a novel amphiphilic diblock peptoid bearing a terminal conjugated oligoaniline and its self-assembly into small-diameter (D ≈ 35 nm) crystalline nanotubes with high aspect ratios (>30). It is shown that both tetraaniline (TANI)-peptoid and bianiline (BANI)-peptoid triblock molecules self-assemble in solution to form rugged highly crystalline nanotubes that are very stable to protonic acid doping and de-doping processes. The similarity of the crystalline tubular structure of the nanotube assemblies revealed by electron microscopy imaging, and X-ray diffraction analysis of the nanotube assemblies of TANI-functionalized peptoids and nonfunctionalized peptoids showed that the peptoid is an efficient ordered structure directing motif for conjugated oligomers. Films of doped TANI-peptoid nanotubes has a dc conductivity of ca. 95 mS cm-1 , while the thin films of doped un-assembled TANI-peptoids show a factor of 5.6 lower conductivity, demonstrating impact of the favorable crystalline ordering of the assemblies on electrical transport. These results demonstrate that peptoid-directed supramolecular assembly of tethered π-conjugated oligo(aniline) exemplify a novel general strategy for creating rugged ordered and complex nanostructures that have useful electronic and optoelectronic properties.

Online digital storytelling video on promoting men's intentions to seek counselling for depression: The role of empathy.

BACKGROUND: Applying the narrative transportation theory, we sought to test the role of a male-sensitive digital storytelling video as a source to persuade men to develop greater intentions to seek counselling based on their empathic reactions to the storyteller. METHODS: Using a post-test only design, a total of 247 diverse adult men (M = 35.86, SD = 12.75) were randomly assigned to either the brochure or video condition and subsequently reported on their state empathy, perceived persuasiveness, and intentions to seek counselling. Controlling for previous counselling experience, a three-way interaction analysis was conducted to assess the significance of the relationship between persuasiveness and intentions to seek counselling across the two conditions, and whether empathy moderated this association in each condition. RESULTS: For men who viewed the brochure, greater persuasiveness was linked to lower intentions to seek counselling at all levels of empathy; although, at high empathy, the relationship was not significant. A similar trend was observed for men who viewed the video at low and mean empathy levels. However, for men who reported high empathy after viewing the video, greater persuasiveness was significantly linked to greater intentions to seek counselling. CONCLUSION: Empathy may play a viable role in promoting intentions to seek counselling among men who view persuasive digital storytelling content on depression. However, more research needs to be conducted on the conditions that make it favourable for men to have empathic reactions to the contents. Implications for research and the potential for intervention are discussed.

The use of nonrandomized evidence to estimate treatment effects in health technology assessment.

Health technology assessment (HTA) is increasingly informed by nonrandomized studies, but there is limited guidance from HTA bodies on expectations around evidence quality and study conduct. We developed recommendations to support the appropriate use of such evidence based on a pragmatic literature review and a workshop involving 16 experts from eight countries as part of the EU's Horizon-2020 IMPACT-HTA program (work package six). To ensure HTA processes remain rigorous and robust, HTA bodies should demand clear, extensive and structured reporting of nonrandomized studies, including an in-depth assessment of the risk of bias. In recognition of the additional uncertainty imparted by nonrandomized designs in estimates of treatment effects, HTA bodies should strengthen early scientific advice and engage in collaborative efforts to improve use of real-world data.

Effects of a single-entry intake system on access to outpatient visits to specialist physicians and allied health professionals: a systematic review.

BACKGROUND: Canada lags behind other countries with respect to wait times for specialist physician and allied health professional consultations. We conducted a systematic review to assess the effects of a single-entry model on waiting time, referral volume and the satisfaction of patients and health care providers. METHODS: We searched MEDLINE, Embase, Cochrane CENTRAL and CINAHL databases from inception to December 2019. We included studies from countries in the Organisation for Economic Co-operation and Development that reported on the effects of a single-entry model on the time between referral to first assessment by a specialist physician or allied health professional, termed wait time 1 (WT1). Patient volume and the satisfaction of providers and patients were secondary outcomes. We conducted a narrative synthesis using descriptive statistics. RESULTS: Of the 4637 citations identified, 17 met the eligibility criteria, and we included 10 of these in the final analysis. All of the included studies reported an absolute reduction in WT1 after implementation of the single-entry model. The average percent reduction in WT1 across specialties was greatest for surgical referrals (57%) and urgent internal medicine referrals (40%). Higher initial WT1 was associated with a greater absolute reduction in WT1 after implementation of the single-entry model (p = 0.002). Patient and provider satisfaction with the single-entry model was high in all studies. The effect estimates from all included studies were at high risk of bias. INTERPRETATION: Single-entry models were associated with an absolute reduction in time from referral from primary care to consultation. These models represent a promising option to improve access to a range of health services, but there is a need for rigorous prospective evaluations to inform policy. PROSPERO REGISTRATION: CRD42018100395.

Characterization of a novel roseophage and the morphological and transcriptional response of the sponge symbiont Ruegeria AU67 to infection.

Sponges have recently been recognized to contain complex communities of bacteriophages; however, little is known about how they interact with their bacterial hosts. Here, we isolated a novel phage, called Ruegeria phage Tedan, and characterized its impact on the bacterial sponge symbiont Ruegeria AU67 on a morphological and molecular level. Phage Tedan was structurally, genomically and phylogenetically characterized to be affiliated with the genus Xiamenvirus of the family Siphoviridae. Through microscopic observations and transcriptomic analysis, we show that phage Tedan upon infection induces a process leading to metabolic and morphological changes in its host. These changes would render Ruegeria AU67 better adapted to inhabit the sponge holobiont due to an improved utilization of ecologically relevant energy and carbon sources as well as a potential impediment of phagocytosis by the sponge through cellular enlargement. An increased survival or better growth of the bacterium in the sponge environment will likely benefit the phage reproduction. Our results point towards the possibility that phages from host-associated environments require, and have thus evolved, different strategies to interact with their host when compared to those phages from free-living or planktonic environments.