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1.
Methods Mol Biol ; 2814: 209-222, 2024.
Article in English | MEDLINE | ID: mdl-38954208

ABSTRACT

Identifying the mechanisms of action of existing and novel drugs is essential for the development of new compounds for therapeutic and commercial use. Here we provide a technique to identify these mechanisms through isolating mutant cell lines that show resistance to drug-induced phenotypes using Dictyostelium discoideum REMI libraries. This approach provides a robust and rapid chemical-genetic screening technique that enables an unbiased approach to identify proteins and molecular pathways that control drug sensitivity. Mutations that result in drug resistance often occur in target proteins thus identifying the specific protein targets for drugs and bioactive natural products. Following the identification of a list of putative molecular targets user selected compound targets can be analyzed to confirm and validate direct inhibitory effects.


Subject(s)
Dictyostelium , Mutation , Dictyostelium/genetics , Dictyostelium/metabolism , DNA Restriction Enzymes/metabolism , Gene Library , Drug Resistance/genetics , Small Molecule Libraries/pharmacology
3.
Angew Chem Int Ed Engl ; : e202404539, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38970305

ABSTRACT

We report a rapid, room-temperature mechanochemical synthesis of 2- and 3-dimensional boroxine covalent organic frameworks (COFs), enabled by using trimethylboroxine as a dehydrating additive to overcome the hydrolytic sensitivity of boroxine-based COFs. The resulting COFs display high porosity and crystallinity, with COF-102 being the first example of a mechanochemically prepared 3D COF, exhibiting a surface area of ca. 2,500 m2 g-1. Mechanochemistry enabled a >20-fold reduction in solvent use and ~100-fold reduction in reaction time compared with solvothermal methods, providing target COFs quantitatively with no additional work-up besides vacuum drying. Real-time Raman spectroscopy permitted the first quantitative kinetic analysis of COF mechanosynthesis, while transferring the reaction design to Resonant Acoustic Mixing (RAM) enabled synthesis of multi-gram amounts of the target COFs (tested up to 10 g).

4.
Fam Med ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39012292

ABSTRACT

BACKGROUND AND OBJECTIVES: Physicians have long been considered valued members of a solid US health care system. Significant changes in medical education, health care, and society at-large suggest that current medical students may face a different future. To help guide educators and policy makers, we set out to understand medical students' perceptions of the future of health care and their place in it. METHODS: In year one of a longitudinal study, we conducted in-depth interviews of Case Western Reserve University medical students. A multidisciplinary team performed iterative thematic analyses and sampling until reaching saturation on major themes. RESULTS: Eleven medical student participants described social and health care issues as major influences on their professional futures. Concerns included health care system failings, unsustainable costs, climate change, demographic shifts, disinformation, and public distrust in health care. Students looked forward to team practice and using technology, data, and artificial intelligence in care delivery. They hoped for greater access and equity in health care, with a focus on prevention and social, behavioral, and environmental drivers of health. Most students expected to be employed rather than in private practice and sought time/flexibility for professional and personal interests. Paying off medical school debt and advocating for patients and change were priorities. Many saw primary care as important, but fewer envisioned it as their career path of choice. CONCLUSIONS: Medical students envision a future shaped by health care systems and social issues. These findings can inform those helping students prepare for uncertainty and rapid change in their careers, their lives, and the lives of their patients.

5.
J Pediatr Psychol ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38994892

ABSTRACT

OBJECTIVE: This study tested a randomized controlled trial of RVA Breathes, a community asthma program, in reducing asthma-related healthcare utilization among children living in an area with a high poverty rate. METHODS: Participants included 250 caregivers (78% African American/Black; 73.3% household income<$25,000/year) and their children with asthma (5-11 years). Inclusion criteria included an asthma-related emergency department (ED) visit, hospitalization, unscheduled doctor's visit, or systemic steroids in the past 2 years. Families were randomized to a full active intervention (asthma education with community health workers [CHWs], home remediation with home assessors, and a school nurse component; n = 118), partial active intervention (asthma education and home remediation; n = 69), or a control group (n = 63) for 9 months. Measures on healthcare utilization and asthma-related factors were collected. Follow-up assessments occurred across a 9-month period. RESULTS: Although we did not find any significant effects, there was a trend toward significance for a group by time effect with objective healthcare utilization as the outcome (F4,365 = 2.28, p = .061). The full intervention group experienced a significant decrease from baseline to 9-month follow-up compared with the other groups (p < .001). Only the full intervention group experienced a significant increase in reported asthma action plans across time (no significant group effect). CONCLUSIONS: In the context of the unprecedented COVID-19 pandemic, which led to a substantial global decrease in healthcare utilization, the study's main hypotheses were not supported. Nevertheless, findings support the benefit of community asthma programs that integrate care across multiple settings and connect families with CHWs.

6.
Int J Mol Sci ; 25(12)2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38928292

ABSTRACT

Tanshinone IIA (T2A) is a bioactive compound that provides promise in the treatment of glioblastoma multiforme (GBM), with a range of molecular mechanisms including the inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) and the induction of autophagy. Recently, T2A has been demonstrated to function through sestrin 2 (SESN) to inhibit mTORC1 activity, but its possible impact on autophagy through this pathway has not been investigated. Here, the model system Dictyostelium discoideum and GBM cell lines were employed to investigate the cellular role of T2A in regulating SESN to inhibit mTORC1 and activate autophagy through a GATOR2 component MIOS. In D. discoideum, T2A treatment induced autophagy and inhibited mTORC1 activity, with both effects lost upon the ablation of SESN (sesn-) or MIOS (mios-). We further investigated the targeting of MIOS to reproduce this effect of T2A, where computational analysis identified 25 novel compounds predicted to strongly bind the human MIOS protein, with one compound (MIOS inhibitor 3; Mi3) reducing cell proliferation in two GBM cells. Furthermore, Mi3 specificity was demonstrated through the loss of potency in the D. discoideum mios- cells regarding cell proliferation and the induction of autophagy. In GBM cells, Mi3 treatment also reduced mTORC1 activity and induced autophagy. Thus, a potential T2A mimetic showing the inhibition of mTORC1 and induction of autophagy in GBM cells was identified.


Subject(s)
Abietanes , Autophagy , Dictyostelium , Glioblastoma , Mechanistic Target of Rapamycin Complex 1 , Glioblastoma/drug therapy , Glioblastoma/metabolism , Glioblastoma/pathology , Abietanes/pharmacology , Humans , Mechanistic Target of Rapamycin Complex 1/metabolism , Mechanistic Target of Rapamycin Complex 1/antagonists & inhibitors , Autophagy/drug effects , Cell Line, Tumor , Dictyostelium/drug effects , Dictyostelium/metabolism , Cell Proliferation/drug effects , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/antagonists & inhibitors , Sestrins
7.
Body Image ; 51: 101747, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38875992

ABSTRACT

There has been an assumption in the literature that the three concepts of ideal body shape (personal ideal, cultural ideal, and the most attractive body shape) are effectively the same percept. To test this presumption, 554 participants completed either a between- or within-subjects condition using a matrix of 32 bodies varying in two dimensions: muscle and adiposity. Three separate groups of participants were recruited to the between-subjects design and made only one of these judgements, whilst participants in the within-subjects version completed all three of these judgments. These bodies are based on 3D scans of 221 women's bodies and so accurately represent the change in size and shape caused by changing body composition. The participants also completed a set of psychometric questionnaires to index the degree to which external concepts of body image have been internalised. The results show that in both conditions, all three judgements collapse onto the same average preferred body shape, with low adiposity and relatively high muscularity. However, this masked systematic differences in responses between personal ideals and the other body judgements, which may be explained by a difference in how information directly related to oneself is processed relative to more abstract third person judgements.

8.
Evol Appl ; 17(5): e13695, 2024 May.
Article in English | MEDLINE | ID: mdl-38721593

ABSTRACT

Recent developments within the IUCN and the Convention on Biological Diversity have affirmed the increasingly key role that effective population size (N e) and the effective size: census size ratio (N e/N) play in applied conservation and management of global biodiversity. This paper reviews and synthesizes information regarding the definition of N e and demographic and genetic methods for estimating effective size, census size, and their ratio. Emphasis is on single-generation estimates of contemporary N e/N, which are the most informative for practical applications. It is crucial to clearly define which individuals are included in the census size (N). Defining N as the number of adults alive at a given time facilitates comparisons across species. For a wide range of applications and experimental designs, inbreeding N e is simpler to calculate and interpret than variance N e. Effects of skewed sex ratio are generally modest, so most reductions to N e/N arise from overdispersed (greater-than-Poisson) variance in offspring number (σk2). Even when fecundity changes with age, overdispersed within-age variance generally contributes most to overall σk2, and both random and deterministic (mediated by selection) factors can be important. Most species are age-structured, so it is important to distinguish between effective size per generation (N e) and the effective number of breeders in one season or year (N b). Both N e and N b are important for applied conservation and management. For iteroparous species, a key metric is variance in lifetime reproductive success (σk•2), which can be affected by a variety of additional factors, including variation in longevity, skip or intermittent breeding, and persistent individual differences in reproductive success. Additional factors that can be important for some species are also discussed, including mating systems, population structure, sex reversal, reproductive compensation, captive propagation, and delayed maturity.

9.
Mol Ecol ; : e17415, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38785346

ABSTRACT

vonHoldt et al. ((2024), Molecular Ecology, 33, e17231) (vH24) used low-coverage (average ~ 7X read depth) restriction site-associated DNA sequence data to estimate individual inbreeding and heterozygosity, and recent effective population size (Ne), in Great Lakes (GL) and Northern Rocky Mountain (RM) wolves. They concluded that RM heterozygosity rapidly declined between 1991 and 2020, and that Ne declined substantially in GL and RM over the last 50 generations. Here, we evaluate the effects of low sequence coverage and sampling strategy on vH24's findings and provide general recommendations for using sequence data to evaluate inbreeding, heterozygosity and Ne. Low-coverage sequencing resulted in downwardly biased estimates of individual inbreeding and heterozygosity, and an erroneous large temporal decline in RM heterozygosity due to declining read depth through time. Additionally, vH24's sampling strategy-which combined individuals from several genetically differentiated populations and across at least eight wolf generations-is expected to have resulted in severe downward bias in estimates of recent Ne for RM. We recommend using high-coverage sequence data ( ≥ $$ \ge $$ 15-20X) to estimate inbreeding and heterozygosity. Carefully filtering individuals, loci and genotypes, and using genotype imputation or likelihoods can help to minimise bias when low-coverage sequence data must be used. For estimation of contemporary Ne, the marginal benefits of using more than 103-104 loci are small, so aggressive filtering of loci with low average read depth potentially can retain most individuals without sacrificing much precision. Individuals are relatively more valuable than loci because analyses of contemporary Ne should focus on roughly single-generation samples from local breeding populations.

10.
Perception ; : 3010066241256221, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38778780

ABSTRACT

Perceiving facial attractiveness is an important behaviour across psychological science due to these judgments having real-world consequences. However, there is little consensus on the measurement of this behaviour, and practices differ widely. Research typically asks participants to provide ratings of attractiveness across a multitude of different response scales, with little consideration of the psychometric properties of these scales. Here, we make psychometric comparisons across nine different response scales. Specifically, we analysed the psychometric properties of a binary response, a 0-100 scale, a visual analogue scale, and a set of Likert scales (1-3, 1-5, 1-7, 1-8, 1-9, 1-10) as tools to measure attractiveness, calculating a range of commonly used statistics for each. While certain properties suggested researchers might choose to favour the 1-5, 1-7 and 1-8 scales, we generally found little evidence of an advantage for one scale over any other. Taken together, our investigation provides consideration of currently used techniques for measuring facial attractiveness and makes recommendations for researchers in this field.

11.
J Pediatr Psychol ; 2024 May 16.
Article in English | MEDLINE | ID: mdl-38752579

ABSTRACT

OBJECTIVE: Suboptimal nutritional adherence in adolescents with cystic fibrosis (awCF) has been associated with lower lung function. AwCF often have more independence in dietary decisions than younger children, yet little research has examined how adolescent decision-making relates to nutritional adherence. This study explored whether components of adolescent decision-making involvement facilitate enzyme and caloric adherence in awCF. METHODS: 37 families participated and completed study procedures. AwCF and caregivers completed electronic surveys, including the Decision-Making Involvement Scale (DMIS). The DMIS evaluated awCF behaviors during nutrition-related decision-making/discussions with caregivers using DMIS subscales: Child Seek (asking for help/advice from caregivers), Child Express (awCF stating opinions) and Joint/Options (awCF participating in joint decision-making or caregiver providing options). AwCF completed 2, 24-hr diet recalls via videoconferencing/phone to estimate adherence. Chart reviews collected medical information. DMIS subscales were regressed onto enzyme and caloric adherence. RESULTS: 43% of awCF met calorie recommendations; 48.6% took all enzymes as prescribed. Caloric adherence was positively correlated with adolescent- and parent-reported Child Seek (r = 0.53; r = 0.36) and adolescent-reported Joint/Options (r = 0.41). Per adolescent-report, the caloric adherence regression model was significant, with Child Seek contributing unique variance in caloric adherence (ß = .62, p = .03). Parent-reported adolescent-decision-making involvement significantly predicted caloric adherence, but none of the subscales contributed unique variance. No other regressions were significant. CONCLUSIONS: When awCF participated in nutrition-related discussions with a caregiver, especially with questions, caloric adherence was better. Future research should examine whether family factors influence these results. AwCF are encouraged to ask questions in nutrition discussions.

12.
Women Birth ; 37(4): 101622, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38744163

ABSTRACT

PROBLEM: The COVID-19 pandemic hindered access to routine healthcare globally, prompting concerns about possible increases in pregnancy loss and perinatal death. BACKGROUND: PUDDLES is an international collaboration exploring the impact of the COVID-19 pandemic on parents who experience pregnancy loss and perinatal death in seven countries, including Aotearoa New Zealand. AIM: To explore parents' experiences of access to healthcare services and support following baby loss during the COVID-19 pandemic in Aotearoa New Zealand. METHODS: We conducted in-depth, semi-structured interviews with 26 bereaved parents, including 20 birthing mothers, and six non-birthing parents (one mother and five fathers). Types of loss included 15 stillbirths, four late miscarriages, and one neonatal death. Participant ethnicities were broadly representative of Aotearoa New Zealand's multi-ethnic society. Data were analysed using Template Analysis. FINDINGS: Analysis revealed five themes relating to pandemic impact on bereaved parent's experiences. These were: 'Distanced and Impersonal care'; 'Navigating Hospital Rules'; Exclusion of Non-birthing Parents; 'Hindered Access to Social Support'; and 'Continuity of Relational Care'. DISCUSSION: The COVID-19 pandemic exacerbated isolation of bereaved parents through perceived impersonal care by healthcare professionals and restrictions on movement hindered access to social and cultural support. Compassionate bending of the rules by healthcare professionals and community postnatal visits by continuity of care midwives following the bereavement appeared to be mitigating factors. CONCLUSION: Social isolation is an added challenge for parents experiencing baby loss during a pandemic, which may be mitigated by flexible and compassionate care from healthcare professionals, especially continuity of care midwives.


Subject(s)
COVID-19 , Parents , Qualitative Research , SARS-CoV-2 , Social Support , Stillbirth , Humans , COVID-19/epidemiology , COVID-19/prevention & control , New Zealand , Female , Pregnancy , Adult , Male , Stillbirth/psychology , Parents/psychology , Interviews as Topic , Bereavement , Health Services Accessibility , Infant, Newborn , Perinatal Death , Pandemics , Physical Distancing , Abortion, Spontaneous/psychology
13.
Qual Life Res ; 33(6): 1719-1734, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38632146

ABSTRACT

PURPOSE: Caregiver burden (CB) is typically self-assessed by caregivers. However, an emerging concept is assessment of CB by the recipients of care, i.e., the patient. The specific objectives are (1) to assess the level of agreement between care recipients' and caregivers' view on CB, across financial, physical, emotional, and social domains; (2) to explore two care recipient perspectives: their self-perceived burden (CR-SPB), and their interpretation of the caregiver's view (Proxy-CB). METHODS: Data were collected from 504 caregiver-care recipient dyads in the U.S. using an online Qualtrics panel. The survey assessed caregiver burden using CarerQol and newly developed items. The level of agreement between responses was quantified using weighted kappa (κ) coefficients for individual items and intraclass correlation coefficients (ICC) for index/summary scores. RESULTS: The average age of caregivers was 49.2 years, and 62.7 years for care recipients. Dyads most commonly consisted of spouses/partners (34.5%); 68.3% lived together. Proxy-CB aligned more closely with caregiver's view, with moderate to substantial agreement across CB domains (from κ = 0.48 for emotional to κ = 0.66 for financial). In the same perspective, the CarerQol-7D Index showed moderate agreement (ICC = 0.58) and the summary score of CB items substantial agreement (ICC = 0.76). Care recipients generally overestimated  CB in the Proxy-CB perspective, while they underestimated it in the CR-SPB perspective. CONCLUSION: Results demonstrate there is a difference between perspectives. Strong agreement in Proxy-CB perspective suggests that care recipients can potentially substitute for caregivers depending on the domain. CR-SPB agrees less with caregivers and may provide complementary information.


Subject(s)
Caregiver Burden , Caregivers , Quality of Life , Humans , Male , Female , Middle Aged , Caregivers/psychology , Caregiver Burden/psychology , Surveys and Questionnaires , Adult , Aged , United States , Psychometrics
14.
Ecol Evol ; 14(3): e11102, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38524913

ABSTRACT

Genetics is a fast-moving field, and for conservation practitioners or ecologists, it can be bewildering. The choice of marker used in studies is fundamental; in the literature, preference has recently shifted from microsatellites to single nucleotide polymorphism (SNP) loci. Understanding how marker type affects estimates of population genetic parameters is important in the context of conservation, especially because the accuracy of estimates has a bearing on the actions taken to protect threatened species. We compare parameter estimates between seven microsatellites, 3761 SNP loci, and a random subset of 100 SNPs for the exact same 324 individual swift parrots, Lathamus discolor, and also use 457 additional samples from subsequent years to compare SNP estimates. Both marker types estimated a lower H O than H E. We show that microsatellites and SNPs mainly indicate a lack of spatial genetic structure, except when a priori collection locations were used on the SNP data in a discriminant analysis of principal components (DAPC). The 100-SNP subset gave comparable results to when the full dataset was used. Estimates of effective population size (N e) were comparable between markers when the same individuals were considered, but SNPs had narrower confidence intervals. This is reassuring because conservation assessments that rely on population genetic estimates based on a few microsatellites are unlikely to be nullified by the general shift toward SNPs in the literature. However, estimates between markers and datasets varied considerably when only adult samples were considered; hence, including samples of all age groups is recommended to be used when available. The estimated N e was higher for the full SNP dataset (2010-2019) than the smaller comparison data (2010-2015), which might be a better reflection of the species status. The lower precision of microsatellites may not necessarily be a barrier for most conservation applications; however, SNPs will improve confidence limits, which may be useful for practitioners.

15.
Plant Commun ; 5(6): 100846, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38460510

ABSTRACT

Allelochemicals represent a class of natural products released by plants as root, leaf, and fruit exudates that interfere with the growth and survival of neighboring plants. Understanding how allelochemicals function to regulate plant responses may provide valuable new approaches to better control plant function. One such allelochemical, Myrigalone A (MyA) produced by Myrica gale, inhibits seed germination and seedling growth through an unknown mechanism. Here, we investigate MyA using the tractable model Dictyostelium discoideum and reveal that its activity depends on the conserved homolog of the plant ethylene synthesis protein 1-aminocyclopropane-1-carboxylic acid oxidase (ACO). Furthermore, in silico modeling predicts the direct binding of MyA to ACO within the catalytic pocket. In D. discoideum, ablation of ACO mimics the MyA-dependent developmental delay, which is partially restored by exogenous ethylene, and MyA reduces ethylene production. In Arabidopsis thaliana, MyA treatment delays seed germination, and this effect is rescued by exogenous ethylene. It also mimics the effect of established ACO inhibitors on root and hypocotyl extension, blocks ethylene-dependent root hair production, and reduces ethylene production. Finally, in silico binding analyses identify a range of highly potent ethylene inhibitors that block ethylene-dependent response and reduce ethylene production in Arabidopsis. Thus, we demonstrate a molecular mechanism by which the allelochemical MyA reduces ethylene biosynthesis and identify a range of ultrapotent inhibitors of ethylene-regulated responses.


Subject(s)
Arabidopsis , Ethylenes , Pheromones , Ethylenes/biosynthesis , Ethylenes/metabolism , Pheromones/pharmacology , Pheromones/metabolism , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis/drug effects , Germination/drug effects
16.
Value Health ; 27(7): 967-977, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38492925

ABSTRACT

OBJECTIVES: Several measures have been used or developed to capture the health and well-being of caregivers, including the EQ Health and Well-being (EQ-HWB) and its short form, EQ-HWB-S. This study aimed to evaluate the psychometric properties and construct validity of the EQ-HWB/EQ-HWB-S in a US caregiver population. METHODS: A cross-sectional survey was conducted involving 504 caregivers. Eligible participants were 18+ years old, provided unpaid care to a relative/friend aged 18+ in the past 6 months, and spent on average of at least 1 hour per week caregiving. Survey included the following measures: EQ-HWB, Adult Social Care Outcomes Toolkit for Carers-Carer, CarerQol, and EQ-5D-5L. Psychometric properties were assessed using response distributions, floor/ceiling effects, Spearman's correlation for convergent validity, and effect sizes (ES) for known-group validity based on caregiving situations and intensity. RESULTS: The average age of caregivers was 49.2 (SD = 15.4), with 57.5% being female. More than half (54.4%) reported high caregiving intensity, and 68.3% lived with the care recipient. The EQ-HWB-S index showed a strong positive correlation with the EQ-5D-5L (rs = 0.72), Adult Social Care Outcomes Toolkit for Carers (rs = 0.54), and CarerQol (rs = 0.54) indices. Notably, the EQ-HWB-S index showed the largest ES among measures in differentiating caregiving scenarios with a large ES for caregiver's general health (d = 1.00) and small ES for caregiving intensity (d = 0.39). CONCLUSIONS: Results support construct validity of EQ-HWB and EQ-HWB-S as measures for assessing health and well-being of adult informal caregivers in comparison with other validated instruments. Differing levels of known-group validity across anchors emphasize the importance of selecting appropriate measures for caregivers, depending on research question and/or intervention aims.


Subject(s)
Caregivers , Psychometrics , Quality of Life , Humans , Caregivers/psychology , Middle Aged , Male , Female , Cross-Sectional Studies , Adult , United States , Surveys and Questionnaires , Aged , Reproducibility of Results , Health Status , Young Adult
17.
Pathologie (Heidelb) ; 45(2): 124-132, 2024 Mar.
Article in German | MEDLINE | ID: mdl-38372762

ABSTRACT

OBJECTIVE: Artificial intelligence (AI) holds the potential to make significant advancements in pathology. However, its actual implementation and certification for practical use are currently limited, often due to challenges related to model transferability. In this context, we investigate the factors influencing transferability and present methods aimed at enhancing the utilization of AI algorithms in pathology. MATERIALS AND METHODS: Various convolutional neural networks (CNNs) and vision transformers (ViTs) were trained using datasets from two institutions, along with the publicly available TCGA-MIBC dataset. These networks conducted predictions in urothelial tissue and intrahepatic cholangiocarcinoma (iCCA). The objective was to illustrate the impact of stain normalization, the influence of various artifacts during both training and testing, as well as the effects of the NoisyEnsemble method. RESULTS: We were able to demonstrate that stain normalization of slides from different institutions has a significant positive effect on the inter-institutional transferability of CNNs and ViTs (respectively +13% and +10%). In addition, ViTs usually achieve a higher accuracy in the external test (here +1.5%). Similarly, we showcased how artifacts in test data can negatively affect CNN predictions and how incorporating these artifacts during training leads to improvements. Lastly, NoisyEnsembles of CNNs (better than ViTs) were shown to enhance transferability across different tissues and research questions (+7% Bladder, +15% iCCA). DISCUSSION: It is crucial to be aware of the transferability challenge: achieving good performance during development does not necessarily translate to good performance in real-world applications. The inclusion of existing methods to enhance transferability, such as stain normalization and NoisyEnsemble, and their ongoing refinement, is of importance.


Subject(s)
Artificial Intelligence , Neural Networks, Computer , Algorithms , Artifacts
18.
Fam Community Health ; 47(2): 176-190, 2024.
Article in English | MEDLINE | ID: mdl-38372334

ABSTRACT

INTRODUCTION: The US Food and Drug Administration is poised to restrict the availability of menthol cigarettes and flavored cigars, products disproportionately used by Black/African American (B/AA) individuals. We examined B/AA youth and adult perceptions regarding factors contributing to tobacco use, as well as prevention/cessation resources. METHODS: In 2 mixed-methods studies in Richmond, Virginia, we conducted cross-sectional surveys among youth (n = 201) and adult (n = 212) individuals who were primarily B/AA and reported past 30-day cigar smoking or nontobacco use, followed by focus groups with a subset (youth: n = 30; adults: n = 24). Focus groups were analyzed using a thematic analysis framework, and descriptive survey data provided context to themes. RESULTS: Among focus group participants, 20% of youth and 75% of adults reported current cigar smoking. Six themes emerged across the groups: advertising/brands, sensory experiences, costs, social factors, youth-related factors, and dependence/cessation. Youth and adults perceived cigars as popular; cigar use was attributed to targeted advertising, flavors, affordability, and accessibility. While adults expressed concern regarding youth tobacco use, youth did not perceive tobacco prevention programs as helpful. Adults and youth reported limited access to community tobacco prevention/cessation programs. DISCUSSION: Expanded tobacco prevention and cessation resources for B/AA people who smoke could leverage federal regulatory actions to ban tobacco products targeted toward this group and decrease disparities in tobacco-related morbidity and mortality.


Subject(s)
Black or African American , Tobacco Use , Adult , Humans , Adolescent , Virginia , Cross-Sectional Studies , Surveys and Questionnaires
19.
BMC Genomics ; 25(1): 202, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38383295

ABSTRACT

BACKGROUND: Transitions from sexual to asexual reproduction are common in eukaryotes, but the underlying mechanisms remain poorly known. The pea aphid-Acyrthosiphon pisum-exhibits reproductive polymorphism, with cyclical parthenogenetic and obligate parthenogenetic lineages, offering an opportunity to decipher the genetic basis of sex loss. Previous work on this species identified a single 840 kb region controlling reproductive polymorphism and carrying 32 genes. With the aim of identifying the gene(s) responsible for sex loss and the resulting consequences on the genetic programs controlling sexual or asexual embryogenesis, we compared the transcriptomic response to photoperiod shortening-the main sex-inducing cue-of a sexual and an obligate asexual lineage of the pea aphid, focusing on heads (where the photoperiodic cue is detected) and embryos (the final target of the cue). RESULTS: Our analyses revealed that four genes (one expressed in the head, and three in the embryos) of the region responded differently to photoperiod in the two lineages. We also found that the downstream genetic programs expressed during embryonic development of a future sexual female encompass ∼1600 genes, among which miRNAs, piRNAs and histone modification pathways are overrepresented. These genes mainly co-localize in two genomic regions enriched in transposable elements (TEs). CONCLUSIONS: Our results suggest that the causal polymorphism(s) in the 840 kb region somehow impair downstream epigenetic and post-transcriptional regulations in obligate asexual lineages, thereby sustaining asexual reproduction.


Subject(s)
Aphids , Female , Animals , Aphids/physiology , Pisum sativum , Parthenogenesis/genetics , Reproduction, Asexual/genetics , Gene Expression Profiling
20.
Sch Psychol ; 39(1): 1-3, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38330320

ABSTRACT

School Psychology is an outlet for research on children, youth, educators, and families that has scientific, practice, and policy implications for education and educational systems. In this editorial, annual updates are provided regarding journal impact, award winners, special topics, and editorial leadership, as well as reflections on how the journal engages in the open science process to promote transparency, rigor, and reproducibility in the science produced in the field of school psychology. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Awards and Prizes , Psychology, Educational , Adolescent , Child , Humans , Reproducibility of Results , Schools
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