Hunter College

Understanding how peptide sequence relates to supramolecular dynamics and consequent solid-state material properties remains a central challenge for rational peptide materials design. Here, we use N-terminal proline as a strategic conformational constraint in minimalist tripeptides (PXX; P = proline, X = phenylalanine (F) or tryptophan (W)) to isolate side-chain contributions from backbone and show that simple aromatic exchange dictates crystallization pathways and solid-state dynamics. In this design, proline rigidifies the backbone, the central residue supports assembly, and the C-terminal aromatic residue dictates conformational adaptability. Combining molecular dynamics simulations with NMR and fluorescence spectroscopy, we show that peptides with W at the C-terminus, with a diverse interaction space, display shallow energy landscapes with multiple accessible states, whereas a C-terminal F, with a stringent hydrophobic nature and limited interaction space, restricts the peptide into fewer conformations. As a result, PXF peptides form soluble supramolecular aggregates, while PXW peptides access more adaptable conformations that promote crystallization. Solid-state characterization reveals that these sequence-encoded supramolecular dynamics directly influence bulk properties: W-containing peptides form stiff crystals with dynamic, wettable surfaces, whereas F analogues yield static, hydrophobic materials. Together, these results establish how aromatic-residues dictate supramolecular assembly and crystallization, offering a straightforward approach to engineering dynamic properties in solid-state peptide materials.

TP53mutations occur in 80-90% of triple-negative breast cancers (TNBCs) and drive genomic instability and metastatic progression. Poly (ADP-ribose) polymerase (PARP) is critical for DNA repair and replication fork stability. How oncogenic signaling influences PARP function to sustain proliferation during replication stress remains unclear. Mutant p53 (mtp53) R273H associates tightly with chromatin, forms complexes with PARP, and enhances PARP recruitment to replication forks [1–3]. The C-terminal region of mtp53 mediates mtp53-PARP and mtp53-Poly (ADP-ribose) (PAR) interactions that facilitate S phase progression [4, 5]. The PARP inhibitor talazoparib (TAL) combined with the alkylating agent temozolomide (TMZ) produces synergistic cytotoxicity selectively in mtp53, but not wild-type p53 (wtp53), breast cancer cells and organoids. Herein we evaluated the mechanism of mtp53-associated cell death and tested if this could translate to a preclinical xenograft model. We found that TMZ+TAL treatment induced elevated cleaved PARP and γH2AX and reduced the metastasis-promoting oncoprotein MDMX. In orthotopic xenografts expressing mtp53 R273H, but not wtp53, combination therapy significantly decreased circulating tumor cells (CTCs) and lung metastases. Transcriptomic profiling of tumors from combination treated animals demonstrated downregulation ofMDMX,VEGF,andNF-κB, consistent with the observed suppression of CTCs and lung metastasis, and increased γH2AX, indicative of replication stress in mtp53 xenografts. Inhibition of metastasis was also observed in mtp53 R273H WHIM25 and p53-undetectable WHIM6 TNBC patient-derived xenografts (PDX). The mtp53 C-terminal domain (347-393) demonstrated a critical tumor promoting function, as CRISPR-mediated deletion impaired replication fork progression, tumor growth, and metastatic dissemination. DNA fiber combing showed that expression of full-length mtp53 R273H, but not C-terminal deleted Δ347-393, supported sustained single-stranded DNA gaps (ssGAPs) following Poly (ADP-ribose) glycohydrolase (PARG) inhibition. These findings support that mtp53 uses C-terminal amino acids to exploit PARP to enable replication stress adaptation and that mtp53 is a predictive biomarker for combined PARP inhibitor and DNA damaging therapies targeting TNBC.Significance statementTP53mutations are the most common genetic alterations in TNBC and a major driver of replication stress and metastasis. This study shows that missense mutant p53 uses C-terminal amino acids to reprogram PARP activity to maintain tumor cell survival under replication stress. We demonstrate that p53 status governs the response to combined PARP inhibitor (PARPi) and DNA-damaging chemotherapy, establishing an additional molecular basis beyond BRCA1 mutations for treating TNBC with PARPi therapy. These findings reveal a previously unrecognized mechanism by which the mutant p53-PARP axis enables replication stress tolerance and drives cancer metastasis. We show mutation of p53 in TNBC provides an additional biomarker-guided framework to improve PARPi therapeutic outcomes.

/SummaryBackgroundWhile numerous studies have explored the relationship between COVID-19 and cancer, few have specifically examined the significant impact of the pandemic on cancer patients, particularly concerning their treatments and appointments.ObjectivesThis study aims to investigate cancer treatment behaviors during the COVID-19 pandemic.MethodsThis retrospective quantitative study utilized data from the Centers for Disease Control and Prevention’s National Health Interview Survey of 2020. The inclusion criteria were as follows: studies conducted within the United States; patients diagnosed with COVID-19 since the pandemic began; patients diagnosed with cancer within the United States; patients undergoing cancer treatment or in remission since the start of the pandemic; patients who experienced a change, delay, or cancellation of treatment due to the COVID-19 pandemic; patients who experienced a change or delay in cancer care due to the COVID-19 pandemic; patients with a weakened immune system due to prescriptions; and patients who took prescription medication within the past 12 months. The variables were analyzed against population characteristics, including age, race, gender, cancer type, and COVID-19 status. Python Jupyter Notebook (packaged by Anaconda Navigator in R Studio, version 6.4.8), Microsoft Excel for data cleaning and assessment, and SPSS were used for statistical analyses.ResultsChi-Square Analysis (p<.05) revealed significant associations between cancer treatment and gender (p=0.009), other cancer treatments and age (p<.001) and education (p<.001), changes in other cancer treatments and gender (p=0.045), race (p<.001), age (p<.001), and education (p=.013), and prescribed medication and gender (p=.009), family income (p<.001), and age (p<.001).ConclusionThe COVID-19 pandemic has significantly impacted cancer care in the U.S., affecting the delivery of treatments. Additional government funding is necessary to help medical facilities develop programs for off-site treatment delivery, to better prepare for future pandemics, and avoid repeating past challenges.

As generative artificial intelligence becomes more prolific in academic settings, its potential to enhance learning is somewhat overshadowed by concerns about the consequences of overreliance and ethical implications. This study explored the use of generative artificial intelligence, such as ChatGPT (OpenAI, San Francisco, CA), among undergraduate nursing students in a 4-year nursing program in the United States. In this study, 89% of students reported using artificial intelligence, and more than half had started using it before nursing school. Students reported using artificial intelligence to prepare for exams, draft assignments, and brainstorm presentations. Moreover, 84% of the students said it improved their coursework, and 65% reported that it made their learning more efficient. Despite the benefits, nearly 20% were unaware of their school's artificial intelligence policies, which raises concerns about plagiarism or cheating. This shows that clearer guidance and education on ethical artificial intelligence use are needed from institutions to prevent misuse, as well as distinct policies and guidelines. Future research should explore the long-term impact of artificial intelligence on clinical performance. Overall, artificial intelligence seems to be an important academic tool for nursing students, but its future implications remain unknown. To ensure competent nurses, training for both faculty and students on appropriate use of artificial intelligence is critical to ensure its use as a tool rather than a substitute for critical thinking.

Engagement in HIV care is essential for viral suppression, and care coordination programs have shown improved retention and adherence. In New York Medicaid HIV Special Needs Plans (SNP), health-homes provide enhanced care coordination for people with HIV (PWH) at risk of non-adherence; however, evidence of their impact on virologic outcomes is limited. Using a matched case-control design and 2016-2018 data from a New York City Medicaid HIV SNP, this study examined associations between health-homes and virologic failure. Cases had virologic failure, defined as two consecutive viral loads > 200 copies/mL. Controls matched 1:1 on age (18+), race, and second viral load date, had no virologic failure. Conditional logistic regression examined virologic failure and health-home use duration, Social Deprivation Index (SDI), gender identity, HIV-infection stage, SNP enrollment, comorbidities, and polypharmacy. There were 2,566 PWH (62% male, mean age 42.9 years, mean SDI 92.3). Virologic failure was associated with HIV Stage III (OR = 2.01, 95% CI: 1.61-2.49), substance use disorder (OR = 2.09, 95% CI: 1.68-2.58), and < 6 months of health-home use (OR = 2.08, 95% CI: 1.27-3.42). The association attenuated with 6 + months of health-home use (reference=none; OR = 0.98, 95% CI: 0.77-1.25). Polypharmacy (OR = 0.72, 95% CI: 0.59-0.89) and mental health diagnoses (OR = 0.74, 95% CI: 0.59-0.94) had lower odds of virologic failure. Although further research is needed to clarify the roles of polypharmacy and mental health care, sustained health-home use may reduce disparities in virologic failure among PWH at high risk of falling out of care.

Ordered leaf attachment, Phylo2Vec, and HOP are three recently introduced vector representations for rooted phylogenetic trees where the representation is determined by an ordering of the underlying leaf set X. Comparing the vectors of two rooted phylogenetic X-trees T and for a fixed ordering on X leads to polynomial-time computable measure for the dissimilarity of T and , albeit dependent on the choice of the leaf ordering. For each of ordered leaf attachment, Phylo2Vec, and HOP, we compare this measure with the rooted subtree prune and regraft distance (rSPR), the hybrid number, and the temporal tree-child hybrid number of T and . Although there is no direct relationship between rSPR and any of the three vector-based measures, we show that, when minimized over all orderings, the hybrid number is equal to HOP and is an upper bound on the other two. Moreover, when minimized over all orderings induced by common cherry-picking sequences of T and , the temporal tree-child hybrid number of T and is equal to each of the three vector-based measures.

This qualitative study used a phenomenological approach to study the lived experience of persons who participate in support groups for caregivers of persons with severe mental illness in Jamaica, West Indies. The findings of the study uncovered that caregiving is a frustrating responsibility with considerable financial burden, but support groups are helpful sites for learning of important information, and they create communities of support and encouragement that boost confidence in caring for others and oneself.

Identifying component skills necessary for the emergence of intraverbal tacts, or verbal responses under control of both a verbal and nonverbal antecedent stimulus, is important because the occasion for this skill often occurs in a child's everyday life. Previous research has begun to identify a sequence of component skills that may lead to the emergence of multiply controlled intraverbals. However, it remains unclear which component skills are necessary versus sufficient. The purpose of this study was to evaluate the effects of teaching a subset of component skills, element tact and intraverbal categorization, to identify the skills sufficient for emergence of intraverbal tacts. A multiple-probe design was used to assess intraverbal-tact emergence for five participants diagnosed with autism spectrum disorder during pre-and post-element-tact and intraverbal-categorization teaching sessions. Emergence of intraverbal tacts was also assessed during recombinative-generalization probes. Results indicated that intraverbal tacts emerged for all participants following acquisition of element tacts and intraverbal categorizations. As no other component skills were taught, these data suggest that these component skills may be sufficient for intraverbal tact emergence. Implications for identifying necessary component skills and directions for future research are discussed.