Category: Nevin Manimala

WMJ. 2025;124(1):42-46.

ABSTRACT

INTRODUCTION: Implicit bias in patient care and outcomes is well documented. However, the presence of bias in hospital security interactions is a relatively new area of research. Flags placed on the electronic medical record identify patients considered high risk for negative outcomes, including those with security interactions.

OBJECTIVE: We sought to explore the types of flags and their frequency, differences among patients with flags, and their pattern over time.

METHODS: We conducted a retrospective chart review of flags placed on electronic medical records over 13 years of adults 18 years or older who were patients at a Midwest, tertiary, academic medical center. Descriptive statistics were used to explore patient demographic data. Chi-square tests were executed to compare patients with different flag types.

RESULTS: Three flag types were investigated: “communication alert,” “vulnerable/unsafe, behavior” and “risk management.” The communication alert flag was most common, although Black male patients were more likely to receive a vulnerable/unsafe behavior flag than a communication alert flag (P = 0.001). Patients who were prescribed anti-anxiety medications, antidepressants, antipsychotics, and psychotherapeutics also were more likely to receive a vulnerable/unsafe behavior flag than a communication alert flag (P = 0.001). The highest number of flags was placed during quarter 3 – the months of July, August, and September.

CONCLUSIONS: Records of patients with certain demographics and on certain medications were more likely to be labeled with vulnerable/unsafe behavior flags. There is no clear protocol to determine what behaviors elicit which flag. Standardized procedures could help provide transparency to this issue.

PMID:40262006

WMJ. 2025;124(1):17-21.

ABSTRACT

INTRODUCTION: People experiencing homelessness are more likely than the general population to have chronic health conditions and often encounter significant barriers to health care access. Many of these barriers can be affected by community-based factors, such as availability of reliable transportation, past experiences with health care systems, and community attitudes toward the unhoused population. This project aims to assess the needs and barriers to health care identified by people experiencing homelessness in a rural Midwestern city.

METHODS: The survey used was adapted from a survey previously conducted to assess the needs of the homeless population in Milwaukee, Wisconsin. Surveys were distributed during outreach around the city of Wausau, Wisconsin. Data were transcribed and reviewed, and descriptive statistics were calculated.

RESULTS: A total of 45 surveys were completed. Most participants identified as White, non-Hispanic males (n = 24, 53%) and were 46 to 55 years old (n = 14, 31%). Barriers to health care included lack of housing, cost, transportation, lack of a mailing address, inadequate hours, and disrespectful care. Eighty-six percent of participants (n = 38) reported having a mental health diagnosis, yet only 26% (n = 12) stated that they see a mental health professional.

CONCLUSIONS: Individuals experiencing homelessness in a rural community have broad and complex barriers to accessing health care. Given limited resources in smaller communities, innovative and holistic solutions should be considered when aiming to make care more equitable.

PMID:40262002

Sci Signal. 2025 Apr 22;18(883):eado3473. doi: 10.1126/scisignal.ado3473. Epub 2025 Apr 22.

ABSTRACT

Cellular plasticity mediates tissue development as well as cancer growth and progression. In breast cancer, a shift to a more epithelial phenotype (epithelialization) underlies a state of reversible cell growth arrest called tumor dormancy, which enables drug resistance, tumor recurrence, and metastasis. Here, we explored the mechanisms driving epithelialization and dormancy in aggressive mesenchymal-like breast cancer cells in three-dimensional cultures. Overexpressing either of the epithelial lineage-associated transcription factors OVOL1 or OVOL2 suppressed cell proliferation and migration and promoted transition to an epithelial morphology. The expression of OVOL1 (and of OVOL2 to a lesser extent) was regulated by steroid hormones and growth factors and was more abundant in tumors than in normal mammary cells. An uncharacterized and indirect target of OVOL1/2, C1ORF116, exhibited genetic and epigenetic aberrations in breast tumors, and its expression correlated with poor prognosis in patients. We further found that C1ORF116 was an autophagy receptor that directed the degradation of antioxidant proteins, including thioredoxin. Through C1ORF116 and unidentified mediators, OVOL1 expression dysregulated both redox homeostasis (in association with increased ROS, decreased glutathione, and redistribution of the transcription factor NRF2) and DNA damage and repair (in association with increased DNA oxidation and double-strand breaks and an altered interplay among the kinases p38-MAPK, ATM, and others). Because these effects, as they accumulate in cells, can promote metastasis and dormancy escape, the findings suggest that OVOLs not only promote dormancy entry and maintenance in breast cancer but also may ultimately drive dormancy exit and tumor recurrence.

PMID:40261955 | DOI:10.1126/scisignal.ado3473

Proc Natl Acad Sci U S A. 2025 Apr 29;122(17):e2417813122. doi: 10.1073/pnas.2417813122. Epub 2025 Apr 22.

ABSTRACT

Generic equilibria are derived for turbulent relaxing plasmas via an entropy-maximization procedure that accounts for the short-time conservation of certain collisionless invariants. The conservation of these collisionless invariants endows the system with a partial “memory” of its prior conditions but is imperfect on long time scales due to the development of a turbulent cascade to small scales, which breaks the precise conservation of phase volume, making this memory imprecise. The equilibria are still determined by the short-time collisionless invariants, but the invariants themselves are driven to a universal form by the nature of the turbulence. This is numerically confirmed for the case of beam instabilities in one-dimensional electrostatic plasmas, where sufficiently strong turbulence appears to cause the distribution function of particle energies to develop a universal power-law tail, with exponent -2.

PMID:40261929 | DOI:10.1073/pnas.2417813122

J Neuropathol Exp Neurol. 2025 Apr 22:nlaf034. doi: 10.1093/jnen/nlaf034. Online ahead of print.

ABSTRACT

Pituitary neuroendocrine tumors (PitNETs) are among the most common tumors encountered in neurooncology. While the majority of PitNETs demonstrate indolent behavior, a subset of tumors demonstrates aggressive behavior, including invasion into surrounding structures. As traditional imaging has limited capacity to distinguish tumor from post-operative changes, better methods of tumor delineation are needed to guide management. Somatotroph adenomas are known to express high levels of SSTR2, and SSTR2-targeting PET imaging has shown clinical utility in the management of neuroendocrine tumors and meningiomas. In this retrospective study of archival PitNETs (n = 271) and autopsy controls (AC) (n = 20), we show that although significant differences in SSTR2 immunostaining are appreciable between adenoma subtypes and ACs, high-staining cases are encountered in all subtypes. In ACs, females demonstrated significantly stronger SSTR2 staining than males. Weak age-related trends towards increasing labelling in females and decreasing labelling in males were noted but these did not reach statistical significance. Decreasing age-related trends were seen in gonadotrophs in both sexes; this was statistically significant in females. Our findings suggest that SSTR2-targeting imaging modalities may assist clinical management of a subset of PitNETs and that these results may need to be interpreted with consideration of patient age and sex.

PMID:40261909 | DOI:10.1093/jnen/nlaf034

PLOS Glob Public Health. 2025 Apr 22;5(4):e0004446. doi: 10.1371/journal.pgph.0004446. eCollection 2025.

ABSTRACT

Developing active ingredients for the global market requires substantial investment, often exceeding 300 million euros. This process takes an average of 12 years from initiation to commercialization. Despite this lengthy timeline, the industry frequently encounters significant restrictions and bans on active ingredients due to stringent international regulations and evolving environmental safety requirements. In this context, the analysis of regulatory lists using advanced machine learning and statistical modeling techniques becomes crucial for identifying the key parameters that influence the restriction and banning of active ingredients. This study aims to provide insights that enhance decision-making processes, thereby contributing to sustainability by reducing unnecessary environmental research and development efforts. The findings indicate that Governmental and Non-Governmental Organizations, as well as Blacklists, are key influencers in the restriction and ban of active ingredients for agricultural use, with Codex Alimentarius acting as a regional influencer depending on the specific country. Ultimately, the insights derived from this research can assist industries and policymakers in developing more effective regulatory strategies, promoting sustainable practices, and ensuring that new active ingredients are selected based on comprehensive and informed criteria that consider both safety and environmental impact.

PMID:40261900 | DOI:10.1371/journal.pgph.0004446

Conserv Biol. 2025 Apr 22:e70026. doi: 10.1111/cobi.70026. Online ahead of print.

ABSTRACT

Alternative protein interventions are common in conservation. They aim to reduce the hunting or consumption of wildlife by promoting substitutes. However, selecting suitable meat substitutes is challenging because many factors drive wild meat consumption. Palatability, one such factor, drives consumer food preference and is potentially crucial in determining meat substitutability in the context of alternative protein interventions. Nonetheless, there have been few assessments of wild meat palatability compared with other options. We collected data on the meat palatability of 96 animal species via a standardized questionnaire administered to 570 hunters, household members, and wild meat vendors (190 respondents in each group) in southeast Nigeria to examine the potential for wild meat substitution. We found positive correlations in the palatability of different species across pairs of respondent groups, highlighting preference similarities. We did not find a statistically significant difference in the average palatability of domestic meat, fish, invertebrates, or wild meat, suggesting scope for substitution based on palatability. Among mammalian orders, ungulates, carnivores, primates, and rodents had similar palatability, but pangolins (Phataginus sp. and Smutsia gigantea) had higher palatability than all orders except rodents. These findings suggest that substituting wild meat with other types of meat based on palatability might be appropriate, except for pangolins, which can only be suitably substituted with rodents.

PMID:40260657 | DOI:10.1111/cobi.70026

Ann Afr Med. 2025 Apr 22. doi: 10.4103/aam.aam_155_24. Online ahead of print.

ABSTRACT

CONTEXT: Seizures are challenging medical emergencies that can be difficult to diagnose, especially since no quick, reliable tests are available in an emergency setting. Approximately 10% of the general population will experience at least one seizure episode during their lifetime. Epilepsy mimics include several paroxysmal conditions that resemble epileptic seizures in their clinical presentation. Psychogenic nonepileptic seizures (PNES) are common mimics.

AIMS: Studies involving PNES in Saudi Arabia are limited. Therefore, this study aimed to investigate the prevalence of PNES and associated risk factors.

SETTINGS AND DESIGN: A cross-sectional study was conducted at our institution to assess the prevalence of psychogenic non-epileptic seizures in patients presenting with seizure.

METHODS: We retrospectively collected and analyzed the medical records of 260 patients who experienced seizures between 2019 and 2020.

STATISTICAL ANALYSIS USED: Data were analyzed using SPSS (version 27).

RESULTS: PNES was diagnosed in 9.2% of the participants, with females accounting for the majority of cases (70.8%). A statistically significant difference was observed between males and females (P < 0.05). The majority (95.8%) of patients with PNES had normal EEGs, and no abnormalities were found on computed tomography and/or magnetic resonance imaging in most patients (79.1%). In addition, 58.3% of patients with PNES reported taking antiepileptic drugs.

CONCLUSIONS: Determining the prevalence of psychogenic nonepileptic seizures is challenging. Our study revealed that the prevalence of PNES in patients with seizures was 9.2%. Female sex is a significant risk factor for PNES. Demographic characteristics and clinical data can help identify patients with PNES and guide appropriate management options.

PMID:40260645 | DOI:10.4103/aam.aam_155_24

Clin Cancer Res. 2025 Apr 21. doi: 10.1158/1078-0432.CCR-24-4105. Online ahead of print.

ABSTRACT

PURPOSE: Enabled by advancements in next-generation sequencing for hereditary cancer conditions, low allele frequency variants (LAFVs) are detected by testing laboratories. This study describes the frequency and clinical factors associated with LAFVs and reports results of follow-up testing when available.

PATIENTS AND METHODS: This retrospective study analyzed LAFV cases identified through multi-gene panel testing (MGPT) at a single high-volume germline genetic testing laboratory. LAFVs were defined as variant allele frequencies (VAF) between 10-30% as confirmed by Sanger sequencing. Comparative analyses were conducted between pathogenic variants (PVs) with a VAF of 30-60% (inferred heterozygous) and LAFV cohorts. Clinical characteristics were analyzed using descriptive statistics and logistic regression models. Ancillary testing was performed on alternative specimens or family members to determine if LAFVs were due to constitutional mosaicism.

RESULTS: Among 363,405 individuals undergoing MGPT, 965 (1.8%) had variants with VAF between 10-30%. Sanger sequencing confirmed 463 (0.1%) as LAFVs. Among the confirmed LAFVs, 262 (57.6%) were classified as PVs. The LAFV cohort compared to the control heterozygous cohort was significantly older, with a higher proportion of individuals > 50 years (84.1% vs. 54.9%; p<0.001). LAFVs were present in the following genes: TP53 (110;64.7%), NF1 (23;13.5%), CHEK2 (13;7.6%), ATM (12; 7.1%), and BRCA1 (4;2.4%). Ancillary testing performed on 62 cases with LAFVs confirmed 17.7% (11/62) as constitutional mosaicism.

CONCLUSION: LAFVs were infrequently detected in MGPT, representing 0.8% of the total variants and 0.1% of total tested. Ancillary testing is needed to understand the origins and clinical implications of LAFVs in patients and families.

PMID:40260637 | DOI:10.1158/1078-0432.CCR-24-4105

Mol Oncol. 2025 Apr 22. doi: 10.1002/1878-0261.70041. Online ahead of print.

ABSTRACT

Homologous recombination deficiency (HRD) leads to genomic instability, and patients with HRD can benefit from HRD-targeting therapies. Previous studies have primarily focused on identifying HRD biomarkers using data from a single technology. Here we integrated features from different genomic data types, including total copy number (CN), allele-specific copy number (ASCN) and single nucleotide variants (SNV). Using a semi-supervised method, we developed HRD classifiers from 1404 breast tumours across two datasets based on their BRCA1/2 status, demonstrating improved HRD identification when aggregating different data types. Notably, HRD-positive tumours in ER-negative disease showed improved survival post-adjuvant chemotherapy, while HRD status strongly correlated with neoadjuvant treatment response. Furthermore, our analysis of cell lines highlighted a sensitivity to PARP inhibitors, particularly rucaparib, among predicted HRD-positive lines. Exploring somatic mutations outside BRCA1/2, we confirmed variants in several genes associated with HRD. Our method for HRD classification can adapt to different data types or resolutions and can be used in various scenarios to help refine patient selection for HRD-targeting therapies that might lead to better clinical outcomes.

PMID:40260608 | DOI:10.1002/1878-0261.70041