Combined PD-1 and CTLA-4 Blockade in an International Cohort of Patients with Acral Lentiginous Melanoma.

BACKGROUND: Combination immune checkpoint blockade targeting PD-1 and CTLA-4 leads to high response rates and improved survival in advanced cutaneous melanoma (CM). Less is known about the efficacy of this combination in acral lentiginous melanoma (ALM). OBJECTIVES: To determine the efficacy of combination immune checkpoint blockade targeting PD-1 and CTLA-4 in a real-world, diverse population of ALM. METHODS: This multi-institutional retrospective study analyzed patients with histologically confirmed ALM treated with the combination of PD-1 and CTLA-4 inhibitors between 2010-2022. The primary objective of the study was objective response rate (ORR) per RECIST criteria. The secondary objectives were progression-free survival (PFS) and overall survival (OS). RESULTS: In total, 109 patients with advanced ALM treated with combined PD-1 and CTLA-4 blockade in any line of treatment were included. The majority of patients had stage IV disease (n=81, 74.2%). The ORR for the entire cohort was 18.3% (95% CI 11.6-26.9%), with 9 (8.3%) complete responses (CR) and 11 (10.1%) partial responses (PR). An additional 22 patients (20.2%) had stable disease (SD), and the disease control rate (DCR) was 38.5%. The median PFS was 4.2 months [95% CI 3.25-5.62], while the median OS was 17 months [95% CI 12.4%-23.1%]. A total of 95 patients (87.2%) had a treatment-related adverse event, with 40.4% (n=44/109) experiencing at least one grade 3 or 4 toxicity. Elevated LDH (p=.04), 2+ lines of prior therapy (p=.03), and Asian race/ethnicity (p=.04) were associated with worse OS, while Hispanic/Latino race/ethnicity was associated with better OS (p=.02). CONCLUSIONS: Combination of PD-1 and CTLA-4 blockade is less effective for ALM, as compared to CM, despite similar toxicity. Asian patients, in particular, appear to derive lower benefit from this regimen. Novel treatment approaches are needed for this rare melanoma subtype.

Homologous Recombination Deficiency (HRD) in Cutaneous Oncology.

Skin cancers, including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (SCC), and melanoma, are the most common malignancies in the United States. Loss of DNA repair pathways in the skin plays a significant role in tumorigenesis. In recent years, targeting DNA repair pathways, particularly homologous recombination deficiency (HRD), has emerged as a potential therapeutic approach in cutaneous malignancies. This review provides an overview of DNA damage and repair pathways, with a focus on HRD, and discusses major advances in targeting these pathways in skin cancers. Poly(ADP-ribose) polymerase (PARP) inhibitors have been developed to exploit HRD in cancer cells. PARP inhibitors disrupt DNA repair mechanisms by inhibiting PARP enzymatic activity, leading to the accumulation of DNA damage and cell death. The concept of synthetic lethality has been demonstrated in HR-deficient cells, such as those with BRCA1/2 mutations, which exhibit increased sensitivity to PARP inhibitors. HRD assessment methods, including genomic scars, RAD51 foci formation, functional assays, and BRCA1/2 mutation analysis, are discussed as tools for identifying patients who may benefit from PARP inhibitor therapy. Furthermore, HRD has been implicated in the response to immunotherapy, and the combination of PARP inhibitors with immunotherapy has shown promising results. The frequency of HRD in melanoma ranges from 18% to 57%, and studies investigating the use of PARP inhibitors as monotherapy in melanoma are limited. Further research is warranted to explore the potential of PARP inhibition in melanoma treatment.

Novel manifestations of immune dysregulation and granule defects in gray platelet syndrome.

Gray platelet syndrome (GPS) is a rare recessive disorder caused by biallelic variants in NBEAL2 and characterized by bleeding symptoms, the absence of platelet α-granules, splenomegaly, and bone marrow (BM) fibrosis. Due to the rarity of GPS, it has been difficult to fully understand the pathogenic processes that lead to these clinical sequelae. To discern the spectrum of pathologic features, we performed a detailed clinical genotypic and phenotypic study of 47 patients with GPS and identified 32 new etiologic variants in NBEAL2. The GPS patient cohort exhibited known phenotypes, including macrothrombocytopenia, BM fibrosis, megakaryocyte emperipolesis of neutrophils, splenomegaly, and elevated serum vitamin B12 levels. Novel clinical phenotypes were also observed, including reduced leukocyte counts and increased presence of autoimmune disease and positive autoantibodies. There were widespread differences in the transcriptome and proteome of GPS platelets, neutrophils, monocytes, and CD4 lymphocytes. Proteins less abundant in these cells were enriched for constituents of granules, supporting a role for Nbeal2 in the function of these organelles across a wide range of blood cells. Proteomic analysis of GPS plasma showed increased levels of proteins associated with inflammation and immune response. One-quarter of plasma proteins increased in GPS are known to be synthesized outside of hematopoietic cells, predominantly in the liver. In summary, our data show that, in addition to the well-described platelet defects in GPS, there are immune defects. The abnormal immune cells may be the drivers of systemic abnormalities such as autoimmune disease.

Cuticular Chemistry of the Queensland Fruit Fly Bactrocera tryoni (Froggatt).

The cuticular layer of the insect exoskeleton contains diverse compounds that serve important biological functions, including the maintenance of homeostasis by protecting against water loss, protection from injury, pathogens and insecticides, and communication. Bactrocera tryoni (Froggatt) is the most destructive pest of fruit production in Australia, yet there are no published accounts of this species' cuticular chemistry. We here provide a comprehensive description of B. tryoni cuticular chemistry. We used gas chromatography-mass spectrometry to identify and characterize compounds in hexane extracts of B. tryoni adults reared from larvae in naturally infested fruits. The compounds found included spiroacetals, aliphatic amides, saturated/unsaturated and methyl branched C12 to C20 chain esters and C29 to C33 normal and methyl-branched alkanes. The spiroacetals and esters were found to be specific to mature females, while the amides were found in both sexes. Normal and methyl-branched alkanes were qualitatively the same in all age and sex groups but some of the alkanes differed in amounts (as estimated from internal standard-normalized peak areas) between mature males and females, as well as between mature and immature flies. This study provides essential foundations for studies investigating the functions of cuticular chemistry in this economically important species.

Modulation of inhibitory and excitatory neurotransmissions by Zn2+ on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis in mice.

The substantia gelatinosa of the trigeminal subnucleus caudalis has been considered to be an essential location for the transference of orofacial sensory signals. The co-localization of inhibitory and excitatory neurotransmitters in the same substantia gelatinosa (SG) neurons has demonstrated their essential part in the modification of nociceptive transmission. Zn2+ is particularly numerous in the mammalian central nervous system. There are proofs demonstrating the role of Zn2+ in the modulation of voltage- and ligand-gated ion channels. However, little is known about what roles Zn2+ may play in the modulation of signal transmission in the SG neurons of the trigeminal subnucleus caudalis (Vc). Therefore, in this study, we used the whole-cell patch clamp technique to find out the effect of Zn2+ on the responses of three main neurotransmitters (glycine, GABA, and glutamate) on SG neurons of the Vc in mice. We have proved that Zn2+ induces a big potentiation of glycine receptor-mediated response but attenuates GABA- and glutamate-induced responses at micromolar concentrations, however, enhances glutamate-induced response at nanomolar concentration. Taken together, these data demonstrated that Zn2+ can modulate glycine, GABA and glutamate-mediated actions on the SG neurons of the Vc and support an important mechanism in spinal sensory information signaling.

Raspberry Ketone Trifluoroacetate, a New Attractant for the Queensland Fruit Fly, Bactrocera Tryoni (Froggatt).

Queensland fruit fly, Bactrocera tryoni (Q-fly), is a major pest of horticultural crops in eastern Australia. Lures that attract male Q-fly are important for detection of incursions and outbreaks, monitoring of populations, and control by mass trapping and male annihilation. Cuelure, an analog of naturally occurring raspberry ketone, is the standard Q-fly lure, but it has limited efficacy compared with lures that are available for some other fruit flies such as methyl eugenol for B. dorsalis. Melolure is a more recently developed raspberry ketone analog that has shown better attraction than cuelure in some field studies but not in others. A novel fluorinated analog of raspberry ketone, raspberry ketone trifluoroacetate (RKTA), has been developed as a potential improvement on cuelure and melolure. RKTA placed on laboratory cages containing 2-week-old Q-flies elicited strong behavioral responses from males. Quantification of Q-fly responses in these cages, using digital images to estimate numbers of flies aggregated near different lures, showed RKTA attracted and arrested significantly more flies than did cuelure or melolure. RKTA shows good potential as a new lure for improved surveillance and control of Q-fly.

The Mutational and Microenvironmental Landscape of Cutaneous Squamous Cell Carcinoma: A Review.

Cutaneous squamous cell carcinoma (cSCC) manifests through the complex interactions of UV-induced DNA damage, genetic mutations, and alterations in the tumor microenvironment. A high mutational burden is present in cSCC, as well as both cSCC precursors and normal skin, making driver genes difficult to differentiate. Despite this, several key driver genes have been identified, including TP53, the NOTCH family, CDKN2A, PIK3CA, and EGFR. In addition to mutations, the tumor microenvironment and the manipulation and evasion of the immune system play a critical role in cSCC progression. Novel therapeutic approaches, such as immunotherapy and EGFR inhibitors, have been used to target these dysregulations, and have shown promise in treating advanced cSCC cases, emphasizing the need for targeted interventions considering both genetic and microenvironmental factors for improved patient outcomes.

Insurance Status is Associated With Recurrence in Cutaneous Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: To identify socioeconomic factors influencing the presentation and outcomes of cutaneous head and neck squamous cell carcinoma (cHNSCC). STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic medical center with comprehensive cancer center. METHODS: Patients treated for cHNSCC at a single institution between 2008 and 2022 were included. Demographic, socioeconomic data and disease characteristics were obtained from medical record abstraction. Outcome measures included tumor stage, number of distinct primaries, recurrence, and disease-related death. χ2 and Mann-Whitney tests were implemented to evaluate clinicopathologic distributions across disease stages. Survival analyses were performed using Cox regression and Kaplan-Meier analysis. RESULTS: A total of 346 patients met the inclusion criteria. The median age at presentation and length of follow-up was 70.8 and 3.1 years, respectively. The majority of the cohort was white, male, and English-speaking. 13.3% of patients were underinsured and 27.5% were immunosuppressed. Patients who presented with advanced disease were more likely to be underinsured (21.7% vs 9.6%, P = .006) and have a history of homelessness (8.5% vs 2.1%, P = .014). Immunosuppressed patients were more likely to be underinsured (P = .009). Insurance status (1.97 [1.06-3.66], P = .032) and immune status (2.35 [1.30-4.26], P = .005) were independently associated with worse recurrence-free survival. CONCLUSION: Socioeconomic factors that influence access to care, such as insurance status, are associated with cHNSCC disease stage and disease recurrence. These factors may impose barriers that delay diagnosis and treatment. This may result in worse disease-related outcomes and greater treatment-associated morbidity for certain patients.

Evaluating the impact of a year-long external mentorship pilot program in classical hematology.

ABSTRACT: Effective mentorship is a pivotal factor in shaping the career trajectory of trainees interested in classical hematology (CH), which is of critical importance due to the anticipated decline in the CH workforce. However, there is a lack of mentorship opportunities within CH compared with medical oncology. To address this need, a year-long external mentorship program was implemented through the American Society of Hematology Medical Educators Institute. Thirty-five hematology/oncology fellows interested in CH and 34 academically productive faculty mentors from different institutions across North America were paired in a meticulous process that considered individual interests, experiences, and background. Pairs were expected to meet virtually once a month. Participation in a scholarly project was optional. A mixed-methods sequential explanatory design was used to evaluate the program using mentee and mentor surveys, a mentee interview, and a mentee focus group. Thirty-three mentee-mentor pairs (94.2%) completed the program. Sixty-three percent of mentee respondents worked on a scholarly project with their mentor; several mentees earned publications, grants, and awards. Mentee perception that their assigned mentor was a good match was associated with a perceived positive impact on confidence (P = .0423), career development (P = .0423), and professional identity (P = .0302). Furthermore, 23 mentees (66%) accepted CH faculty positions after fellowship. All mentor respondents believed that this program would increase retention in CH. This mentorship program demonstrates a productive, beneficial way of connecting mentees and mentors from different institutions to improve the careers of CH trainees, with the ultimate goal of increasing retention in CH.

ARID2 mutations may relay a distinct subset of cutaneous melanoma patients with different outcomes.

ARID genes encode subunits of SWI/SNF chromatin remodeling complexes and are frequently mutated in human cancers. We investigated the correlation between ARID mutations, molecular features, and clinical outcomes in melanoma patients. Cutaneous melanoma samples (n = 1577) were analyzed by next-generation sequencing. Samples were stratified by pathogenic/likely pathogenic mutation in ARID genes (ARID1A/2/1B/5B). PD-L1 expression was assessed using IHC (SP142; positive (+): ≥ 1%). Tumor mutation burden (TMB)-high was defined as ≥ 10 mutations/Mb. Transcriptomic signatures predictive of response to immune checkpoint inhibitors-interferon gamma and T-cell inflamed score were calculated. Real-world overall survival (OS) information was obtained from insurance claims data, with Kaplan-Meier estimates calculated from time of tissue collection until last date of contact. Mann-Whitney U, Chi-square, and Fisher exact tests were applied where appropriate, with p values adjusted for multiple comparisons. ARID2 mutations were more prevalent in cutaneous melanoma compared to ARID1A (11.0%: n = 451 vs 2.8%: n = 113), with concurrent ARID1A/ARID2 mutation in 1.1% (n = 46) of samples. ARID mutations were associated with a high prevalence of RAS pathway mutations-NF1 (ARID1A, 52.6%; ARID2, 48.5%; ARID1A/2, 63.6%; and ARID-WT, 13.3%; p < 0.0001) and KRAS (ARID1A, 3.5%; ARID2, 3.1%; ARID1A/2, 6.5%; and ARID-WT, 1.0%; p = 0.018)), although BRAF mutations were less common in ARID-mutated cohorts (ARID1A, 31.9%; ARID2, 35.6%; ARID1A/2, 26.1%; and ARID-WT, 50.4%; p < 0.0001). TMB-high was more common in ARID-mutated samples (ARID1A, 80.9%; ARID2, 89.9%; ARID1A/2, 100%; and ARID-WT, 49.4%; p < 0.0001), while PD-L1 positivity was similar across subgroups (ARID1A, 43.8%; ARID2, 51.1%; ARID1A/2, 52.5%; and ARID-WT, 44.9%; p = 0.109). Patients with ARID1A mutations had a higher prevalence of dMMR/MSI-H compared to those with ARID-WT (2.7% vs 0.2%, p = 0.030). Median IFN-γ and T-cell signatures were higher in ARID2-mutated samples compared to ARID-WT (IFN-γ: - 0.15 vs - 0.21, p = 0.0066; T-cell: 23.5 vs - 18.5, p = 0.041). ARID2-mutated patients had improved survival compared to ARID-WT; (HR: 1.22 (95% CI 1.0-1.5), p = 0.022). No additional OS benefit was observed with anti-PD-1 therapy for ARID2 mutation compared to ARID-WT. Melanoma patients with ARID mutations exhibited higher prevalence of markers associated with ICI response, including TMB-H, and immune-related signatures. Our data also suggests improved survival outcome in patients with ARID2 mutations, irrespective of anti-PD1 therapy.

Evolving Applications of Circulating Tumor DNA in Merkel Cell Carcinoma.

Circulating tumor DNA (ctDNA) is a subset of circulating cell-free DNA released by lysed tumor cells that can be characterized by its shorter strand length and tumor genome-specific information. The relatively short half-life of ctDNA allows it to provide a real-time measure of tumor burden which has potential prognostic and surveillance value as a tumor biomarker. Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer that requires close monitoring due to the high risk of relapse. There are currently no good tumor biomarkers for MCC patients, especially those who are negative for Merkel cell polyomavirus. ctDNA shows promise for improving the prognoses of MCC patients by monitoring tumor burden, identifying minimal residual disease (MRD), and stratifying patients by their likelihood of response to immune checkpoint inhibition or risk of relapse. In particular, bespoke ultra-sequencing platforms allow for the creation of patient-specific mutation panels that improve ctDNA detection, especially for patients with rare or uncharacteristic mutations. Leveraging bespoke ctDNA assays may improve physicians' ability to alter treatment plans for non-responsive or high-risk patients. In addition, ctDNA MRD monitoring may allow physicians to treat relapses early before clinically evident disease is present.

Pigmentary retinopathy associated with immune therapy for advanced cutaneous melanoma.

Purpose: To describe a case of bilateral retinal pigmentary changes in the setting of immune checkpoint inhibitor therapy (ICIT). Observations: A 69-year-old man with a history of advanced cutaneous melanoma was started on combination ICIT with nivolumab and ipilimumab and stereotactic body radiation therapy. Soon after, he developed photopsias and nyctalopia with findings of discrete retinal pigmentary changes bilaterally. Initial visual acuities were 20/20 and 20/30 in the right and left eye, respectively. Multi-modal imaging revealed sub-retinal deposits with progressive changes in pigmentation and autofluorescence, associated with decreased peripheral fields on formal perimetry. A full-field electroretinogram revealed attenuated and delayed a- and b-waves. Positive serum retinal autoantibodies were identified. The patient developed left-sided optic nerve edema and center-involving cystoid macular edema which improved after treatment with sub-tenon's triamcinolone. Conclusions: The use of ICIT has greatly expanded in oncologic practice with subsequent increases in immune related adverse events that pose significant systemic and ophthalmologic morbidities. We propose that the new retinal pigmentary changes seen in this case are the sequelae of an autoimmune inflammatory response against pigmented cells. This adds to the rare side effects that may occur after ICIT.

Genetic variation for rectal gland volatiles among recently collected isofemale lines and a domesticated strain of Queensland fruit fly, Bactrocera tryoni (Diptera: Tephritidae).

Divergence between populations in mating behaviour can function as a potent premating isolating mechanism and promote speciation. However, very few cases of inherited intraspecific variation in sexual signalling have been reported in tephritid fruit flies, despite them being a highly speciose family. We tested for such variation in one tephritid, the Queensland fruit fly, Bactrocera tryoni (Qfly). Qfly mating behaviour depends on volatiles secreted from male rectal glands but no role for the volatiles from female rectal glands has yet been reported. We previously detected over 100 volatile compounds in male rectal glands and identified over 30 of them. Similar numbers were recorded in females. However, many compounds showed presence/absence differences between the sexes and many others showed quantitative differences between them. Here we report inherited variation among 24 Qfly lines (23 isofemale lines established from recent field collections and one domesticated line) in the abundance of three esters, two alcohols, two amides, an aldehyde and 18 unidentified volatiles in male rectal glands. We did not find any compounds in female rectal glands that varied significantly among the lines, although this may at least partly reflect lower female sample numbers. Most of the 26 male compounds that differed between lines were more abundant in the domesticated line than any of the recently established isofemale lines, which concurs with other evidence for changes in mating behaviour during domestication of this species. There were also large differences in several of the 26 compounds among the isofemale lines, and some of these differences were associated with the regions from which the lines were collected. While some of the variation in different compounds was correlated across lines, much of it was not, implicating involvement of multiple genes. Our findings parallel reports of geographic variation in other Qfly traits and point to inherited differences in reproductive physiology that could provide a basis for evolution of premating isolation between ecotypes.

Multi-omic profiling reveals discrepant immunogenic properties and a unique tumor microenvironment among melanoma brain metastases.

Melanoma brain metastases (MBM) are clinically challenging to treat and exhibit variable responses to immune checkpoint therapies. Prior research suggests that MBM exhibit poor tumor immune responses and are enriched in oxidative phosphorylation. Here, we report results from a multi-omic analysis of a large, real-world melanoma cohort. MBM exhibited lower interferon-gamma (IFNγ) scores and T cell-inflamed scores compared to primary cutaneous melanoma (PCM) or extracranial metastases (ECM), which was independent of tumor mutational burden. Among MBM, there were fewer computationally inferred immune cell infiltrates, which correlated with lower TNF and IL12B mRNA levels. Ingenuity pathway analysis (IPA) revealed suppression of inflammatory responses and dendritic cell maturation pathways. MBM also demonstrated a higher frequency of pathogenic PTEN mutations and angiogenic signaling. Oxidative phosphorylation (OXPHOS) was enriched in MBM and negatively correlated with NK cell and B cell-associated transcriptomic signatures. Modulating metabolic or angiogenic pathways in MBM may improve responses to immunotherapy in this difficult-to-treat patient subset.

Oxidative arylation of isochroman.

We report the use of a previously intractable nucleophile, anisole, in an oxidative "cross-dehydrogenative coupling" (CDC) reaction with the cyclic ether isochroman, as well as derivatives of both components. Metal catalysis was required for the reaction to proceed efficiently, and the reaction is highly sensitive to modification of either coupling partner but is able to produce a range of novel compounds via what is a synthetic alternative to the traditional oxa-Pictet-Spengler reaction.

Diversity and sex differences in rectal gland volatiles of Queensland fruit fly, Bactrocera tryoni (Diptera: Tephritidae).

Rectal gland volatiles are key mediators of sexual interactions in tephritid fruit flies. We used solid-phase microextraction (SPME) plus gas chromatography-mass spectrometry (GC-MS) and gas chromatography-flame ionization detection (GC-FID) to substantially expand rectal gland chemical characterisation of the Queensland fruit fly (Bactrocera tryoni (Diptera: Tephritidae); Qfly). The SPME GC-MS analysis identified 24 of the 30 compounds previously recorded from Qfly rectal glands, plus another 21 compounds that had not previously been reported. A few amides and fatty acid esters dominated the chromatograms of males and females respectively, but we also found other esters, alcohols and aldehydes and a ketone. The GC-FID analyses also revealed over 150 others, as yet unidentified, volatiles, generally in lesser amounts. The GC-FID analyses also showed 49 and 12 compounds were male- and female-specific, respectively, both in single sex (virgin) and mixed sex (mostly mated) groups. Another ten compounds were male-specific among virgins but undetected in mixed sex groups, and 29 were undetected in virgins but male-specific in mixed sex groups. The corresponding figures for females were four and zero, respectively. Most short retention time peaks (including a ketone and an ester) were male-specific, whereas most female-biased peaks (including five fatty acid esters) had long retention times. Our results indicate previously unsuspected diversity of rectal gland volatiles that might have pheromone functions in males, but far fewer in females.

Neurotropic Cutaneous Malignancies: Case Report on Keratinocyte Derived Malignancies of the Head and Neck With Perineural Invasion.

Background: The recent addition of immunotherapy as a treatment modality to surgery and radiation has vastly improved disease control for patients with keratinocyte-derived carcinomas (KCs) that are incurable with local therapies alone. With the advent of immune checkpoint inhibitors (ICPis) in non-melanoma skin cancers comes diagnostic and therapeutic challenges when considering treatment strategies for patients presenting with clinical perineural invasion (cPNI) of locally advanced KC of the head and neck. Objectives: We report four cases that convey the diagnostic and therapeutic complexity of managing patients with neuropathic symptoms from cutaneous neurotropic carcinomas of the head and neck. We also discuss an updated review regarding immunotherapies and perineural invasion within KC management. Conclusion: Patients presenting with symptoms suspicious for cPNI warrant an expanded diagnostic evaluation to correlate neurological findings with neurotropic spread of disease. While nerve biopsies can be precarious in sensitive areas, a history of skin cancer and clinical presentation suggestive of neurotropism may be enough to pursue timely management in the form of surgery, radiation, and/or systemic therapy given each patient's individual priorities, comorbidities, and prognosis. When adding ICPi as a treatment modality for patients with disease not amenable to local therapies, the potential for immune-related adverse events must be considered. A multi-disciplinary review and approach to the management of patients with KC and cPNI is essential for obtaining optimal patient outcomes.

Clonal hematopoiesis in cancer.

Clonal hematopoiesis is a common premalignant condition defined by the abnormal expansion of clonally derived hematopoietic stem cells carrying somatic mutations in leukemia-associated genes. Apart from increasing age, this phenomenon occurs with higher frequency in individuals with lymphoid or solid tumors and is associated with exposures to genotoxic stress. Clonal hematopoiesis in this context confers a greater risk for developing therapy-related myeloid neoplasms and appears to contribute to adverse cancer-related survival through a variety of potential mechanisms. These include alterations of the bone marrow microenvironment, inflammatory changes in clonal effector cells and modulation of immune responses. Understanding how clonal hematopoiesis drives therapy-related myeloid neoplasm initiation and interactions with non-myeloid malignancies will inform screening and surveillance approaches and suggest targeted therapies in this vulnerable population. Here, we examine the clinical implications of clonal hematopoiesis in the cancer setting and discuss potential strategies to mitigate the adverse consequences of clonal expansion.

Vapor Pressures and Thermodynamic Properties of Phenylpropanoid and Phenylbutanoid Attractants of Male Bactrocera, Dacus, and Zeugodacus Fruit Flies at Ambient Temperatures.

We report on the vapor pressures at ambient temperatures of seven attractants of Bactrocera, Dacus, and Zeugodacus fruit flies-raspberry ketone, cuelure, raspberry ketone trifluoroacetate, methyl eugenol, methyl isoeugenol, dihydroeugenol, and zingerone-by a vapor saturation method. Dry nitrogen was passed over each compound at well-controlled temperatures. Entrained vapor from the compounds was trapped on Tenax GR tubes and analyzed by thermal desorption-gas chromatography-mass spectrometry. The measured attractant amounts on the traps were converted to vapor pressures. Data were subsequently fitted by the Antoine equation. From the Antoine equation parameters, thermodynamic properties for each compound were calculated at 298 K. The calculated vapor pressures were used to compare the volatility of the fruit fly attractants and to infer implications for field applications. Using ambient temperature readings yields far better estimates of vapor pressure values at temperatures relevant for insect control than do Antoine equation parameters derived from high-temperature readings.