Lack of SMARCB1 expression characterizes a subset of human and murine peripheral T-cell lymphomas.

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of malignancies with poor outcome. Here, we identify a subgroup, PTCL-NOSSMARCB1-, which is characterized by the lack of the SMARCB1 protein and occurs more frequently in young patients. Human and murine PTCL-NOSSMARCB1- show similar DNA methylation profiles, with hypermethylation of T-cell-related genes and hypomethylation of genes involved in myeloid development. Single-cell analyses of human and murine tumors revealed a rich and complex network of interactions between tumor cells and an immunosuppressive and exhausted tumor microenvironment (TME). In a drug screen, we identified histone deacetylase inhibitors (HDACi) as a class of drugs effective against PTCL-NOSSmarcb1-. In vivo treatment of mouse tumors with SAHA, a pan-HDACi, triggered remodeling of the TME, promoting replenishment of lymphoid compartments and reversal of the exhaustion phenotype. These results provide a rationale for further exploration of HDACi combination therapies targeting PTCL-NOSSMARCB1- within the TME.

Inpatient palliative care in metastatic adrenocortical carcinoma: a retrospective analysis using the National Inpatient Sample database.

BACKGROUND: The use of inpatient palliative care (IPC) in advanced cancer patients represents a well-established guideline recommendation. This study examines the utilization rates and patterns of IPC among patients with metastatic adrenocortical carcinoma (mACC). METHODS: Relying on the Nationwide Inpatient Sample database (2007-2019), we tabulated IPC rates in mACC patients. Estimated annual percentage changes (EAPC) analyses as well as multivariable logistic regression models (MLRM) predicting IPC use were fitted. RESULTS: Of 2040 mACC patients, 238 (12%) received IPC. Overall, the rate of IPC increased from 3.7% to 19.1% between 2007 and 2019 (EAPC +9.6%, P=0.001). During the same period, in-hospital mortality remained unchanged from 12.1 to 13.8% (EAPC 0.1%; P=0.97). Younger age at admission (<60 years; MLRM OR=0.70, P=0.013), solitary metastatic site (OR=0.63; P=0.015), and non-brain metastases (OR=0.62; P=0.033) were all associated with lower IPC use. CONCLUSIONS: In mACC patients, IPC use has increased from a marginal 3.7% to a moderate annual value of 19.1% in the most recent study year. These rates were not driven by a concomitant increase in in-hospital mortality (12.1% to 13.8%; P=0.9). and may be interpreted as an improvement in quality of care. Despite this encouraging increase, some patient characteristics herald lower IPC use. In consequence, younger patients, those with solitary metastatic sites, and non-brain metastases should be carefully considered for IPC to decrease or completely reduce the IPC access barrier maximally.

Microwave vs radiofrequency ablation for small renal masses: perioperative and oncological outcomes.

OBJECTIVE: To conduct a comprehensive comparison of microwave ablation (MWA) vs radiofrequency ablation (RFA) outcomes in the treatment of small renal masses (SRMs), specifically: TRIFECTA ([i] complete ablation, [ii] absence of Clavien-Dindo Grade ≥III complications, and [iii] absence of ≥30% decrease in estimated glomerular filtration rate) achievement, operative time (OT), and local recurrence rate (LRR). PATIENTS AND METHODS: We retrospectively analysed 531 patients with SRMs (clinical T1a-b) treated with MWA or RFA at a single centre (2008-2022). First, multivariable logistic regression models were used for testing TRIFECTA achievement. Second, multivariable Poisson regression models were used to evaluate variables associated with longer OT. Finally, Kaplan-Meier plots depicted LRR over time. All analyses were repeated after 1:1 propensity score matching (PSM). RESULTS: Of 531 patients with SRMs, 373/531 (70.2%) underwent MWA and 158/531 (29.8%) RFA. MWA demonstrated superior TRIFECTA achievement (314/373 [84.2%]) compared to RFA (114/158 [72.2%], P = 0.001). These differences were driven by higher rates of complete ablation in MWA- vs RFA-treated patients (348/373 [93.3%] vs 137/158 [86.7%], P < 0.001). In multivariable logistic regression models, MWA was associated with higher TRIFECTA achievement, compared to RFA, before (odds ratio [OR] 1.92, P = 0.008) and after PSM (OR 1.99, P = 0.023). Finally, the median OT was shorter for MWA vs RFA (105 vs 115 min; P = 0.002). At Poisson regression analyses, MWA predicted shorter OT before (incidence rate ratio [IRR] 0.86, P < 0.001) and after PSM (IRR 0.85, P < 0.001). Local recurrence occurred in 17/373 (4.6%) MWA-treated patients and 21/158 (13.3%) RFA-treated patients (P = 0.29) after a median (interquartile range) follow-up of 24 (8-46) months. There were no differences in the LRR in Kaplan-Meier plots before (P = 0.29) and after PSM (P = 0.42). CONCLUSION: Microwave ablation provides higher TRIFECTA achievement, and shorter OT than RFA. No significant differences were found regarding the LRR.

Benchmark Study of Core-Ionization Energies with the Generalized Active Space-Driven Similarity Renormalization Group.

X-ray photoelectron spectroscopy (XPS) is a powerful experimental technique for probing the electronic structure of molecules and materials; however, interpreting XPS data requires accurate computational methods to model core-ionized states. This work proposes and benchmarks a new approach based on the generalized active space-driven similarity renormalization group (GAS-DSRG) for calculating core-ionization energies and treating correlation effects at the perturbative and nonperturbative levels. We tested the GAS-DSRG across three data sets. First, the vertical core-ionization energies of small molecules containing first-row elements are evaluated. GAS-DSRG achieves mean absolute errors below 0.3 eV, which is comparable to high-level coupled cluster methods. Next, the accuracy of GAS-DSRG is evaluated for larger organic molecules using the CORE65 data set, with the DSRG-MRPT3 level yielding a mean absolute error of only 0.34 eV for 65 core-ionization transitions. Insights are provided into the treatment of static and dynamic correlation, the importance of high-order perturbation theory, and notable differences from density functional theory in the predicted energy ordering of core-ionized states for specific molecules. Finally, vibrationally resolved XPS spectra of diatomic molecules (CO, N2, and O2) are simulated, showing excellent agreement with experimental data.

The SW480 cell line as a model of resident and migrating colon cancer stem cells.

Intra-tumor heterogeneity, i.e., the presence of diverse cell types and subpopulations within tumors, presents a significant obstacle in cancer treatment due to its negative consequences for resistance to therapy and disease recurrence. However, the mechanisms that underlie intra-tumor heterogeneity and result in the plethora of different cancer cells within a single lesion remain poorly understood. Here, we leverage the SW480 cell line as a model system to investigate the molecular and functional diversity of colon cancer cells. Through a combination of fluorescence-activated cell sorting (FACS) analysis and transcriptomic profiling, we identified three distinct subpopulations, namely resident cancer stem cells (rCSCs), migratory CSCs (mCSCs), and high-relapse cells (HRCs). These subpopulations show varying Wnt signaling levels and gene expression profiles mirroring their stem-like and functional properties. Examination of publicly available spatial transcriptomic data confirms the presence of these subpopulations in patient-derived cancers and reveals their distinct spatial distribution relative to the tumor microenvironment.

Differences in life expectancy of adrenocortical carcinoma patients vs. age­ and sex-matched population controls.

PURPOSE: To quantify to what extent the 5-year overall survival (OS) of adrenocortical carcinoma (ACC) patients differs from age- and sex-matched population-based controls, especially when stage is considered. METHODS: We relied on the Surveillance, Epidemiology, and End Results database (2004-2020) to identify newly diagnosed (2004-2014) ACC patients. Subsequently, we compared OS between ACC patients relative to simulated age- and sex-matched controls (Monte Carlo simulation), according to Social Security Administration Life Tables (2004-2020). RESULTS: Of all 742 ACC patients, 301 (41%) harbored localized stage, 173 (23%) locally advanced stage, and 268 (36%) metastatic stage. At 5-years follow-up, ACC patients' OS was 33%. After stratification for stage, the 5-years OS was 55 vs. 31 vs. 8% in localized, locally advanced, and metastatic stages, respectively. Conversely, after Monte Carlo simulation of age- and sex-matched controls, OS at five-years was 93% in the entire simulated cohort vs. 94% in the simulated localized cohort vs. 92 and 92% in locally advanced and metastatic stage, respectively. The resulting differences in OS between ACC patients and age- and sex-matched population-based controls were 60 vs. 39 vs. 61 vs. 84% respectively in the overall cohort vs. localized vs. locally advanced vs. metastatic stage. CONCLUSION: The most pronounced life expectancy detriment (84%) was recorded in metastatic ACC followed by locally advanced ACC patients (61%). Unfortunately, even in patients with localized ACC, life expectancy was 39% lower than that of the general population. Therefore, regardless of stage, ACC diagnosis results in a very pronounced detriment in life expectancy relative to the general population.

Forte: A suite of advanced multireference quantum chemistry methods.

Forte is an open-source library specialized in multireference electronic structure theories for molecular systems and the rapid prototyping of new methods. This paper gives an overview of the capabilities of Forte, its software architecture, and examples of applications enabled by the methods it implements.

Effect of race/ethnicity on survival in surgically treated intermediate/high risk non-metastatic clear cell renal carcinoma.

PURPOSE: It is unknown to what extent 10-year overall survival of radical nephrectomy treated intermediate/high-risk non-metastatic clear cell renal carcinoma patients differs from age- and sex-matched population-based controls, especially when race/ethnicity is considered (Caucasian vs. African American vs. Hispanic vs. Asian/Pacific Islander). METHODS: We relied on the SEER database (2004-2018) to identify newly diagnosed radical nephrectomy treated intermediate/high risk non-metastatic clear cell renal carcinoma patients. For each case, we simulated an age- and sex-matched control relying on Social Security Administration Life Tables with 10 years of follow-up. We compared overall survival between renal carcinoma cases and population-based controls. Multivariable competing risks regression models tested for predictors of cancer-specific mortality versus other-cause mortality. RESULTS: Of 6877 radical nephrectomy treated intermediate/high risk non-metastatic clear cell renal carcinoma patients, 5050 (73%) were Caucasian versus 433 (6%) African American versus 1002 (15%) Hispanic versus 392 (6%) Asian/Pacific Islanders. At 10 years, overall survival difference between radical nephrectomy treated intermediate/high risk non-metastatic clear cell renal carcinoma patients versus population-based controls was greatest in African Americans (51% vs. 81%, Δ = 30%), followed by Hispanics (54% vs. 80%, Δ = 26%), Asian/Pacific Islanders (56% vs. 80%, Δ = 24%) and Caucasians (52% vs. 74%, Δ = 22%). In competing risks regression, only African Americans exhibited significantly higher other cause mortality (hazard ratio = 1.3; 95% confidence interval = 1.1 - 1.6; p = 0.01) than others. CONCLUSION: Relative to Life Tables' derived sex- and age-matched controls, radical nephrectomy treated intermediate/high-risk non-metastatic clear cell renal carcinoma patients exhibit worse overall survival, with worst overall survival recorded in African Americans of all race/ethnicity groups.

Association between mpMRI detected tumor apparent diffusion coefficient and 5-year biochemical recurrence risk after radical prostatectomy.

PURPOSE: To assess the ability of tumor apparent diffusion coefficient (ADC) values obtained from multiparametric magnetic resonance imaging (mpMRI) to predict the risk of 5-year biochemical recurrence (BCR) after radical prostatectomy (RP). MATERIALS AND METHODS: This retrospective analysis included 1207 peripheral and 232 non-peripheral zone prostate cancer (PCa) patients who underwent mpMRI before RP (2012-2015), with the outcome of interest being 5-year BCR. ADC was evaluated as a continuous variable and as categories: low (< 850 µm2/s), intermediate (850-1100 µm2/s), and high (> 1100 µm2/s). Kaplan-Meier curves with log-rank testing of BCR-free survival, multivariable Cox proportional hazard regression models were formed to estimate the risk of BCR. RESULTS: Among the 1439 males with median age 63 (± 7) years, the median follow-up was 59 months, and 306 (25%) patients experienced BCR. Peripheral zone PCa patients with BCR had lower tumor ADC values than those without BCR (874 versus 1025 µm2/s, p < 0.001). Five-year BCR-free survival rates were 52.3%, 74.4%, and 87% for patients in the low, intermediate, and high ADC value categories, respectively (p < 0.0001). Lower ADC was associated with BCR, both as continuously coded variable (HR: 5.35; p < 0.001) and as ADC categories (intermediate versus high ADC-HR: 1.56, p = 0.017; low vs. high ADC-HR; 2.36, p < 0.001). In the non-peripheral zone PCa patients, no association between ADC and BCR was observed. CONCLUSION: Tumor ADC values and categories were found to be predictive of the 5-year BCR risk after RP in patients with peripheral zone PCa and may serve as a prognostic biomarker.

Synthesis and evaluation of chemical linchpins for highly selective CK2α targeting.

Casein kinase-2 (CK2) are serine/threonine kinases with dual co-factor (ATP and GTP) specificity, that are involved in the regulation of a wide variety of cellular functions. Small molecules targeting CK2 have been described in the literature targeting different binding pockets of the kinase with a focus on type I inhibitors such as the recently published chemical probe SGC-CK2-1. In this study, we investigated whether known allosteric inhibitors binding to a pocket adjacent to helix αD could be combined with ATP mimetic moieties defining a novel class of ATP competitive compounds with a unique binding mode. Linking both binding sites requires a chemical linking moiety that would introduce a 90-degree angle between the ATP mimetic ring system and the αD targeting moiety, which was realized using a sulfonamide. The synthesized inhibitors were highly selective for CK2 with binding constants in the nM range and low micromolar activity. While these inhibitors need to be further improved, the present work provides a structure-based design strategy for highly selective CK2 inhibitors.

Radiotherapy Versus Partial Penectomy for T1 Squamous Cell Carcinoma of the Penis.

BACKGROUND: Radiotherapy (RT) represents an alternative treatment option for patients with T1 squamous cell carcinoma of the penis (SCCP), with proven feasibility and tolerability. However, it has never been directly compared with partial penectomy (PP) using cancer-specific mortality (CSM) as an end point. METHODS: In the Surveillance, Epidemiology, and End Results database (2000-2020), T1N0M0 SCCP patients treated with RT or PP were identified. This study relied on 1:4 propensity score-matching (PSM) for age at diagnosis, tumor stage, and tumor grade. Subsequently, cumulative incidence plots as well as multivariable competing risks regression (CRR) models addressed CSM. Additionally, the study accounted for the confounding effect of other-cause mortality (OCM). RESULTS: Of 895 patients with T1N0M0 SCCP, 55 (6.1%) underwent RT and 840 (93.9%) underwent PP. The RT and PP patients had a similar age distribution (median age, 70 vs 70 years) and more frequently harbored grade I or II tumors (67.3% vs 75.8%) as well as T1a-stage disease (67.3% vs 74.3%). After 1:4 PSM, 55 (100%) of the 55 RT patients versus 220 (26.2%) of the 840 PP patients were included in the study. The 10-year CSM derived from the cumulative incidence plots was 25.4% for RT and 14.4% for PP. In the multivariable CRR models, RT independently predicted a higher CSM than PP (hazard ratio, 1.99; 95% confidence interval, 1.05-3.80; p = 0.04). CONCLUSION: For the T1N0M0 SCCP patients treated in the community, RT was associated with nearly a twofold higher CSM than PP. Ideally, a validation study based on tertiary care institution data should be conducted to test whether this CSM disadvantage is operational only in the community or not.

Toward Accurate Spin-Orbit Splittings from Relativistic Multireference Electronic Structure Theory.

Most nonrelativistic electron correlation methods can be adapted to account for relativistic effects, as long as the relativistic molecular spinor integrals are available, from either a four-, two-, or one-component mean-field calculation. However, relativistic multireference correlation methods remain a relatively unexplored area, with mixed evidence regarding the improvements brought by perturbative treatments. We report, for the first time, the implementation of state-averaged four-component relativistic multireference perturbation theories to second and third order based on the driven similarity renormalization group (DSRG). With our methods, named 4c-SA-DSRG-MRPT2 and 3, we find that the dynamical correlation included on top of 4c-CASSCF references can significantly improve the spin-orbit splittings in p-block elements and potential energy surfaces when compared to 4c-CASSCF and 4c-CASPT2 results. We further show that 4c-DSRG-MRPT2 and 3 are applicable to these systems over a wide range of the flow parameter, with systematic improvement from second to third order in terms of both improved error statistics and reduced sensitivity with respect to the flow parameter.

Merkel Cell Polyomavirus targets SET/PP2A complex to promote cellular proliferation and migration.

Merkel Cell Carcinoma (MCC) is a rare neuroendocrine skin cancer. In our previous work, we decoded genes specifically deregulated by MCPyV early genes as opposed to other polyomaviruses and established functional importance of NDRG1 in inhibiting cellular proliferation and migration in MCC. In the present work, we found the SET protein, (I2PP2A, intrinsic inhibitor of PP2A) upstream of NDRG1 which was modulated by MCPyV early genes, both in hTERT-HK-MCPyV and MCPyV-positive (+) MCC cell lines. Additionally, MCC dermal tumour nodule tissues showed strong SET expression. Inhibition of the SET-PP2A interaction in hTERT-HK-MCPyV using the small molecule inhibitor, FTY720, increased NDRG1 expression and inhibited cell cycle regulators, cyclinD1 and CDK2. SET inhibition by shRNA and FTY720 also decreased cell proliferation and colony formation in MCPyV(+) MCC cells. Overall, these results pave a path for use of drugs targeting SET protein for the treatment of MCC.

Shear wave propagation in a liquid crystal: An inelastic X-ray scattering study.

We investigated the spectrum of density fluctuations of a liquid crystal, CB7CB, in two different orientations by using high-resolution inelastic x-ray scattering. Our analysis, based on Bayesian principles, revealed that high-frequency collective excitations propagate through this mesoscale-ordered sample in a peculiar manner that lies somewhere between those observed in liquids and crystalline systems. Interestingly, when we probed longer length scales, a more pronounced solid-like response emerged. This was mainly characterized by anomalously sharp inelastic excitations and the onset of shear mode propagation. Comparison with previous x-ray diffraction results suggests a correlation between the observed behavior and the mesogen arrangement.

A Potent Sybody Selectively Inhibits α-Synuclein Amyloid Formation by Binding to the P1 Region.

Increasing research efforts focus on exploiting antibodies to inhibit the amyloid formation of neurodegenerative proteins. Nevertheless, it is challenging to discover antibodies that inhibit this process in a specific manner. Using ribosome display, we screened for synthetic single-domain antibodies, i.e., sybodies, of the P1 region of α-synuclein (residues 36-42), a protein that forms amyloid in Parkinson's disease and multiple-system atrophy. Hits were assessed for direct binding to a P1 peptide and the inhibition of amyloid formation. We discovered a sybody, named αSP1, that inhibits amyloid formation of α-synuclein at substoichiometric concentrations in a specific manner, even within highly crowded heterogeneous mixtures. Fluorescence resonance energy transfer-based binding assays and seeding experiments with and without αSP1 further demonstrate the importance of the P1 region for both primary and secondary nucleation mechanisms of amyloid assembly.

Evaluation of margins during radical prostatectomy: confocal microscopy vs frozen section analysis.

OBJECTIVES: To test the performance of ex vivo fluorescence confocal microscopy (FCM; Vivascope 2500M-G4), as compared to intra-operative frozen section (IFS) analysis, to evaluate surgical margins during robot-assisted radical prostatectomy (RARP), with final pathology as the reference standard. METHODS: Overall, 54 margins in 45 patients treated with RARP were analysed with: (1) ex vivo FCM; (2) IFS analysis; and (3) final pathology. FCM margins were evaluated by two different pathologists (experienced [M.I.: 10 years] vs highly experienced [G.R.: >30 years]) as strongly negative, probably negative, doubtful, probably positive, or strongly positive. First, inter-observer agreement (Cohen's κ) between pathologists was tested. Second, we reported the sensitivity, specificity, positive predictive (PPV) and negative predictive value (NPV) of ex vivo FCM. Finally, agreement between ex vivo FCM and IFS analysis (Cohen's κ) was reported. For all analyses, four combinations of FCM results were evaluated. RESULTS: At ex vivo FCM, the inter-observer agreement between pathologists ranged from moderate (κ = 0.74) to almost perfect (κ = 0.90), according to the four categories of results. Indeed, at ex vivo FCM, the highly experienced pathologist reached the best balance between sensitivity (70.5%) specificity (91.8%), PPV (80.0%) and NPV (87.1%). Conversely, on IFS analysis, the sensitivity, specificity, PPV and NPV were, respectively, 88.2% vs 100% vs 100% vs 94.8%. The agreement between the ex vivo FCM and IFS analyses ranged from moderate (κ = 0.62) to strong (κ = 0.86), according to the four categories of results. CONCLUSION: Evaluation of prostate margins at ex vivo FCM appears to be feasible and reliable. The agreement between readers encourages its widespread use in daily practice. Nevertheless, as of today, the performance of FCM seems to be sub-par when compared to the established standard of care (IFS analysis).

Thermal Ablation for Small Renal Masses: Identifying Anthropometric Factors for Predicting Perioperative and Oncological Outcomes.

OBJECTIVES: To test for specific anthropometric parameters to predict perioperative outcomes after thermal ablation (TA) for renal cell carcinoma (RCC). MATERIALS AND METHODS: Retrospective single center (2008-2022) analysis of 538 T1a-b RCC patients treated with TA. We tested for specific anthropometric parameters, namely skin to tumor distance (STTD), perirenal fat thickness (PFT), median psoas muscle axial area (PMAA) and median paravertebral muscle axial area (PVMAA), to predict TRIFECTA achievement: (1) absence of CLAVIEN-DINDO≥ 3 complications; (2) complete ablation; (3) absence of ≥ 30% decrease in eGFR. Univariable (ULRM) and multivariable logistic regression models (MLRM) were used for testing TRIFECTA achievement. RESULTS: Overall, 103 patients (19%) did not achieve TRIFECTA. Of all anthropometric factors, only lower PMAA was associated with no TRIFECTA achievement (10 vs. 11 cm2, P = .02). However, ULRMs and MLRMs did not confirmed the aforementioned association. We than tested for the 3 specific TRIFECTA items. In separate ULRM and MLRM predicting incomplete ablation, both continuously coded STTD (Odds Ratio [OR]: 1.02; CI: 1.01-1.03; P = .02) and STTD strata (STTD > 10 cm; OR: 2.1; CI: 1.1-4.1; P = .03) achieved independent predictor status. Conversely, in separate ULRM and MLRM predicting CLAVIEN-DINDO ≥3 complications, both continuously coded PFT (OR: 1.04; CI: 1.01-1.07; P = .01) and PFT strata (PFT ≥ 14 mm; OR: 3.3; CI: 1.6-10.2; P = .003) achieved independent predictor status. Last, none of the anthropometric parameters were associated with eGFR decrease ≥ 30%. CONCLUSION: None of the tested anthropometric parameters predicted TRIFECTA achievement. However, when the 3 specific TRIFECTA items were tested, STTD and PFT were associated with, respectively, incomplete ablation and CLAVIEN-DINDO ≥ 3 complications.

Frozen Natural Orbitals for the State-Averaged Driven Similarity Renormalization Group.

We present a reduced-cost implementation of the state-averaged driven similarity renormalization group (SA-DSRG) based on the frozen natural orbital (FNO) approach. The natural orbitals (NOs) are obtained by diagonalizing the one-body reduced density matrix from SA-DSRG second-order perturbation theory (SA-DSRG-PT2). We consider three criteria to truncate the virtual NOs for the subsequent electron correlation treatment beyond SA-DSRG-PT2. An additive second-order correction is applied to the SA-DSRG Hamiltonian to reintroduce correlation effects from the discarded orbitals. The FNO SA-DSRG method is benchmarked on 35 small organic molecules in the QUEST database. When keeping 98-99% of the cumulative occupation numbers, the mean absolute error in the vertical transition energies due to FNO is less than 0.01 eV. Using the same FNO threshold, we observe a speedup of 9 times compared to the conventional SA-DSRG implementation for nickel carbonyl with a quadruple-ζ basis set. The FNO approach enables nonperturbative SA-DSRG computations on chloroiron corrole [FeCl(C19H11N4)] with more than 1000 basis functions, surpassing the current limit of a conventional implementation.

Implementation of the Projective Quantum Eigensolver on a Quantum Computer.

We study the performance of our previously proposed projective quantum eigensolver (PQE) on IBM's quantum hardware in conjunction with error mitigation techniques. For a single qubit model of H2, we find that we are able to obtain energies within 4 millihartree (2.5 kcal/mol) of the exact energy along the entire potential energy curve, with the accuracy limited by both the stochastic error and the inconsistent performance of the IBM devices. We find that an optimization algorithm using direct inversion of the iterative subspace can converge swiftly, even to excited states, but stochastic noise can prompt large parameter updates. For the 4-site transverse-field Ising model at its critical point, PQE with an appropriate application of qubit tapering can recover 99% of the correlation energy, even after discarding several parameters. The large number of CNOT gates needed for the additional parameters introduces a concomitant error that, on the IBM devices, results in a loss of accuracy despite the increased expressivity of the trial state. Error extrapolation techniques and tapering or postselection are recommended to mitigate errors in PQE hardware experiments.