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Integrally bladed disks, also known as blisks, are important components in the operation of gas turbines. To study the dynamics of these structures, several computational techniques approximate blisks as tuned systems, where all blades have the same characteristics. In reality, manufactured blades have small variations from their intended design, thus creating so-called mistuned systems. Previous work has shown that such small variations can cause high response amplifications that can result in blisk structural failure. Therefore, it is essential to identify mistuning to ensure the safe operation of these systems. Several methods utilize cantilever blade frequencies in their procedure to model mistuning and calculate blisk vibration response. A previously developed mistuning identification method uses mass detuning to isolate the cantilever blade frequencies and a set of influence coefficients to quantify the blade-to-blade couplings. However, the mistuning is calculated with respect to an arbitrary mistuning value that later needs to be identified through a trial-and-error procedure that can affect the accuracy of the final mistuning values. This paper focuses on updating the method to eliminate this additive error that cannot precisely be determined. Furthermore, the updated procedure is applied to an as-manufactured blisk using experimental ping test results. An additional analysis is performed on the effect of adding multiple sets of influence coefficients to capture the blade-to-blade couplings more accurately.

Background: It is currently unknown whether the addition of arthroscopic labral repair in the setting of periacetabular osteotomy (PAO) provides any clinical benefit. Purpose/Hypothesis: The purpose of this study was to compare outcomes of patients who underwent arthroscopic labral repair concomitantly with PAO versus patients who underwent PAO alone. We hypothesized that there would be no difference in patient-reported outcome measures (PROMs) between the cohorts. Study Design: Cohort study; Level of evidence, 3. Methods: Patients undergoing PAO from a single-center prospective hip preservation registry were eligible for this study if they completed pre- and postoperative PROMs (minimum, 1 year). PROMs were collected at 1 year, 2 years, and latest follow-up at 6.05 years for PAO group and 4.2 years for scope/PAO group. The study group consisted of 53 patients who underwent arthroscopic labral repair at the time of their PAO, and the comparison group consisted of 170 patients who underwent PAO alone. A subset of the PAO group who had radiologic evidence of a detached labral tear (n = 33) was also compared with the rest of the PAO-alone group. PROMs were compared at every time point for both groups as well as the subset of patients who underwent PAO alone despite a labral tear. Results: The mean follow-up of all patients was 2 years (range, 1-6 years). Overall, 85.2% of the PAO group and 85.7% of the scope/PAO group met the minimal clinically important difference for either the modified Harris Hip Score (mHHS) or the International Hip Outcome Tool (iHOT-33) at the most recent follow-up. There was no difference in improvement between groups (mHHS, P = .670; iHOT-33, P = .944). Patients who had a radiologically diagnosed detached labral tear and underwent PAO alone had no difference in outcomes when compared with the rest of the PAO cohort (mHHS, P = .981; iHOT-33, P = .909). Conclusion: There was no significant benefit measured by PROMs at follow-up for concomitant arthroscopic labral repair in the setting of PAO.

Men's emotions in intimate partner relationships have received little research attention. The current interpretive descriptive study included 30 Canadian-based men to address the research question: What are the connections between masculinities and men's emotions in and after intimate partner relationships? Three inductively derived themes included emergent distressing emotions wherein participants' predominance for holding in abeyance their concerns about the relationship manifested varying levels of emotional stoicism. Within this context most men denied or downplayed and did not express their emotions. When the relationship broke, men were overwhelmed by mixed and weighty break-up emotions comprising diverse and often-times discordant emotions, including sadness, shame, anger, regret and guilt, calling into question men's rationality for deciphering and expressing what was concurrently but inexplicably felt. Shame and anger were prominent emotions demanding the participant's attention to all that happened in and at the end of the relationship. In the third theme, understanding and transitioning after-burn emotions, participant's grief levered their efforts, including soliciting professional help for deconstructing, reframing and expressing their emotions in the aftermath of the partnership ending. The findings contextualise and in some instances counter claims about the utility of men's emotional stoicism by mapping participants' feelings in and after intimate partner relationships.

To evaluate the reliability, construct validity, and responsiveness of the lower extremity-specific Patient-Reported Outcomes Measurement Information System (PROMIS) Mobility (MO) bank in patients who underwent hip arthroscopic surgery for femoroacetabular impingement.Patients who underwent primary hip arthroscopic surgery at a large academic musculoskeletal specialty center between November 2019 and November 2020 completed the following baseline and 6-month measures: PROMIS MO, PROMIS Pain Interference (PI), PROMIS Physical Function (PF), modified Harris Hip Score, International Hip Outcome Tool 33, visual analog scale, and Single Assessment Numeric Evaluation. Construct validity was evaluated using Spearman correlation coefficients. The number of questions until completion was recorded as a marker of test burden. The percentage of patients scoring at the extreme high (ceiling) or low (floor) for each measure was recorded to measure inclusivity. Responsiveness was tested by comparing differences between baseline and 6-month measures, controlling for age and sex, using generalized estimating equations. Magnitudes of responsiveness were assessed through the effect size (Cohen d).In this study, 660 patients (50% female patients) aged 32 ± 14 years were evaluated. PROMIS MO showed a strong correlation with PROMIS PF (r = 0.84, P .001), the International Hip Outcome Tool 33 (r = 0.73, P.001), PROMIS PI (r = -0.76, P.001), and the modified Harris Hip Score (r = 0.73, P.001). Neither PROMIS MO, PROMIS PI, nor PROMIS PF met the conventional criteria for floor or ceiling effects (≥15%). The mean number of questions answered (± standard deviation) was 4.7 ± 2.1 for PROMIS MO, 4.1 ± 0.6 for PROMIS PI, and 4.1 ± 0.6 for PROMIS PF. From baseline to 6 months, the PROMIS and legacy measures exhibited significant responsiveness (P.05), with similar effect sizes between the patient-reported outcome measures.This longitudinal study reveals that in patients undergoing hip arthroscopy, PROMIS MO computerized adaptive testing maintains high correlation with legacy hip-specific instruments, significant responsiveness to change, and low test burden compared with legacy measures, with no ceiling or floor effects at 6-month postoperative follow-up.Level IV, retrospective case series.

Family caregivers of patients with cancer provide substantial physical, emotional, and functional care throughout the cancer trajectory. While caregiving can create employment and financial challenges, there is insufficient evidence to inform the development of caregiver-reported outcomes (CROs) that assess these experiences. The study purpose was to describe the occupational and financial consequences that were important to family caregivers of a patient with colorectal cancer (CRC) in the context of public health care, which represent potential considerations for CROs. In this qualitative Interpretive Description study, we analyzed interview data from 78 participants (25 caregivers, 37 patients, and 16 healthcare providers). Our findings point to temporary and long-term occupational and financial setbacks in the context of CRC. Caregiving for a person with CRC involved managing occupational implications, including (1) revamping employment arrangements, and (2) juggling work, family, and household demands. Caregiver financial struggles included (1) responding to financial demands at various stages of life, and (2) facing the spectre of lifelong expenses. Study findings offer novel insight into the cancer-related occupational and financial challenges facing caregivers, despite government-funded universal health care. Further research is warranted to develop CRO measures that assess the multifaceted nature of these challenges.

We report a single example of thermal spin crossover in a series of FeIII complexes, [FeIII(R-sal2323)]+, which typically stabilize the low-spin (S = 1/2) state. Single-crystal X-ray diffraction analysis of 53 such complexes with varying “R” groups, charge-balancing anions, and/or lattice solvation confirms bond lengths in line with an S = 1/2 ground state, with only the [FeIII(4-OMe-sal2323)]NO3 complex (1a) exhibiting longer bond lengths associated with a percentage of the spin sextet form at room temperature. Structural distortion parameters are investigated for the series. A magnetic susceptibility measurement of 1a reveals a gradual, incomplete transition, with T1/2 = 265 K in the solid state, while Evans method NMR reveals that the sample persists in the low-spin form in solution at room temperature. Computational analysis of the spin state preferences for the cations [FeIII(4-OMe-sal2323)]+ and [FeIII(sal2323)]+ confirmed the energetic preference for the spin doublet form in both, and the thermal spin crossover in complex 1a is therefore attributed to perturbation of the crystal packing on warming.

Background: Individualized risk prediction has become possible with machine learning (ML), which may have important implications in enhancing clinical decision making. We previously developed an ML algorithm to predict propensity for clinically meaningful outcome improvement after hip arthroscopy for femoroacetabular impingement syndrome. External validity of prognostic models is critical to determine generalizability, although it is rarely performed. Purpose: To assess the external validity of an ML algorithm for predicting clinically meaningful improvement after hip arthroscopy. Study Design: Cohort study; Level of evidence, 3. Methods: An independent hip preservation registry at a tertiary academic medical center was queried for consecutive patients/athletes who underwent hip arthroscopy for femoroacetabular impingement syndrome between 2015 and 2017. By assuming a minimal clinically important difference (MCID) outcome/event proportion of 75% based on the original study, a minimum sample of 132 patients was required. In total, 154 patients were included. Age, body mass index, alpha angle on anteroposterior pelvic radiographs, Tönnis grade and angle, and preoperative Hip Outcome Score–Sports Subscale were used as model inputs to predict the MCID for the Hip Outcome Score–Sports Subscale 2 years postoperatively. Performance was assessed using identical metrics to the internal validation study and included discrimination, calibration, Brier score, and decision curve analysis. Results: The concordance statistic in the validation cohort was 0.80 (95% CI, 0.71 to 0.87), suggesting good to excellent discrimination. The calibration slope was 1.16 (95% CI, 0.74 to 1.61) and the calibration intercept 0.13 (95% CI, –0.26 to 0.53). The Brier score was 0.15 (95% CI, 0.12 to 0.18). The null model Brier score was 0.20. Decision curve analysis revealed favorable net treatment benefit for patients with use of the algorithm as compared with interventional changes made for all and no patients. Conclusion: The performance of this algorithm in an independent patient population in the northeast region of the United States demonstrated superior discrimination and comparable calibration to that of the derivation cohort. The external validation of this algorithm suggests that it is a reliable method to predict propensity for clinically meaningful improvement after hip arthroscopy and is an essential step forward toward introducing initial use in clinical practice. Potential uses include integration into electronic medical records for automated prediction, enhanced shared decision making, and more informed allocation of resources to optimize patient outcomes.

Formalin-fixed, paraffin-embedded (FFPE) tissues are banked in large repositories to cost-effectively preserve valuable specimens for later study. With the rapid growth of spatial proteomics, FFPE tissues can serve as a more accessible alternative to more commonly used frozen tissues. However, extracting proteins from FFPE tissues is challenging due to cross-links formed between proteins and formaldehyde. Here, we have adapted the nanoPOTS sample processing workflow, which was previously applied to single cells and fresh-frozen tissues, to profile protein expression from FFPE tissues. Following the optimization of extraction solvents, times, and temperatures, we identified an average of 1312 and 3184 high-confidence master proteins from 10 μm thick FFPE-preserved mouse liver tissue squares having lateral dimensions of 50 and 200 μm, respectively. The observed proteome coverage for FFPE tissues was on average 88% of that achieved for similar fresh-frozen tissues. We also characterized the performance of our fully automated sample preparation and analysis workflow, termed autoPOTS, for FFPE spatial proteomics. This modified nanodroplet processing in one pot for trace samples (nanoPOTS) and fully automated processing in one pot for trace sample (autoPOTS) workflows provides the greatest coverage reported to date for high-resolution spatial proteomics applied to FFPE tissues. Data are available via ProteomeXchange with identifier PXD029729.

Objective Repetitive head impacts (RHIs) experienced during sports are gaining attention due to potential long-term neurological dysfunction, absent of a diagnosed concussion. One area susceptible to dysfunction is vision. The goal of this study was to evaluate changes in visual quality of life (VQOL) and functional vision scores from pre- to post-season among collision and non-collision athletes. Methods The Visual Functioning Questionnaire-25 and Neuro-Ophthalmic Supplement (NOS), as well as functional vision testing (Mobile Universal Lexicon Evaluation System – MULES) were completed pre- and post-season by three groups: collision athletes, non-collision athletes, and minimally active controls (MACs). Results There were 42 participants, with 41 (21 male, 20 female) completing both testing sessions, with a mean (standard deviation [SD]) age of 21 (2.46) years (collision group, n = 14; non-collision group, n = 13, MACs, n = 14). Baseline analyses revealed no significant differences between groups for VQOL or MULES scores. However, those with a family history of psychiatric disorder scored significantly worse on NOS. Post-season/follow-up testing revealed no significant differences between groups for VQOL scores. Non-collision athletes significantly improved on the MULES test by 2.46 ± 3.60 (SD) s (35.0 [95% confidence interval, 0.29–4.63]; p = .03). Change score results from pre- to post-season were not significant. Conclusion Although the groups were not significantly different from one another, non-collision athletes significantly improved MULES scores, whereas collision athletes performed the worst, suggesting exposure to RHIs may impact functional vision. Thus, further evaluation of RHIs and their impact on vision is warranted.

Background When fire intervals are shorter than the time required for plants to reproduce, plant populations are threatened by “immaturity risk.” Therefore, understanding how the time between fires influences plants can inform ecosystem management. Quantifying periods of immaturity risk requires investigating the influence of fire intervals across plant life stages, but most studies are indiscriminate of maturity. As fire regimes are multidimensional, it is also important to consider other characteristics of fires such as severity. We conducted a field study in heathy woodland that investigated how fire severity and fire interval influence immaturity risk to serotinous resprouter species, by examining if fire severity interacts with the time since the fire to influence the occurrence of mature individuals and relative abundance of three species: silver banksia (Banksia marginata Cav.), prickly teatree (Leptospermum continentale Joy Thomps), and heath teatree (Leptospermum myrsinoides Schitdl). Results Regression modeling revealed a strong, positive influence of time since the last fire on the proportion of quadrats at a site with mature plants, for all three species. We only detected a small and uncertain influence of fire severity on the proportion of quadrats with mature heath and prickly teatree, and did not observe an effect of fire severity on the maturity of silver banksia. Interestingly, no relationships were observed between time since fire and the relative abundance of plants. That is, only when plant life stages were considered did we detect an effect of fire on plants. Populations of the three species were mostly immature in the first 7 years post-fire, suggesting if sites were uniformly burnt in this time frame, there could be increased risk of local extinctions. Conclusions Our study highlights the importance of examining population processes, such as reproduction, in addition to plant relative abundance. Surprisingly, we did not detect strong differences in plant maturation across fire severity classes; low occurrence of mature plants in recently burnt areas indicated that immaturity risk was high, regardless of fire severity. Ecological studies that distinguish between plant life stages will help to predict the impacts of fire on populations and enhance decision-making. We recommend fire intervals of ≥ 8 years to protect serotinous resprouter plants in heathy woodland vegetation of southern Australia.

Orthopneumoviruses characteristically form membrane-less cytoplasmic inclusion bodies (IBs) wherein RNA replication and transcription occur. Herein, we report a strategy whereby the orthopneumoviruses sequester various components of the eiF4FInitiationComplex machinery into viral IBs to facilitate translation of their own mRNAs; pIC-pocketing. Mass spectrometry analysis of sub-cellular fractions from RSV-infected cells identified significant modification of the cellular translation machinery; however; interestingly, ribopuromycylation assays showed no changes to global levels of translation. Electron micrographs of RSV-infected cells revealed bi-phasic organisation of IBs; specifically, spherical “droplets” nested within the larger inclusion. Using correlative light and electron microscopy (CLEM), combined with fluorescence in situ hybridisation (FISH), we showed that the observed bi-phasic morphology represents functional compartmentalisation of the IB and that these domains are synonymous with the previously reported inclusion body associated granules (IBAGs). Detailed analysis demonstrated that IBAGs concentrate nascent viral mRNA, the viral M2-1 protein as well as many components of the eIF4F complex, involved in translation initiation. Interestingly, although ribopuromycylation-based imaging indicates the majority of viral mRNA translation likely occurs in the cytoplasm, there was some evidence for intra-IBAG translation, consistent with the likely presence of ribosomes in a subset of IBAGs imaged by electron microscopy. The mechanistic basis for this pathway was subsequently determined; the viral M2-1 protein interacting with eukaryotic translation initiation factor 4G (eIF4G) to facilitate its transport between the cytoplasm and the separate phases of the viral IB. In summary, our data shows that IBs function to spatially regulate early steps in viral translation within a highly selective biphasic liquid organelle.

Context Telehealth-delivered nutrition interventions are effective in practice; however, limited evidence exists regarding their cost-effectiveness. Objective To evaluate the cost-effectiveness of telehealth-delivered nutrition interventions for improving health outcomes in adults with chronic disease. Data sources PubMed, CENTRAL, CINAHL, and Embase databases were systematically searched from database inception to November 2021. Included studies were randomized controlled trials delivering a telehealth-delivered diet intervention conducted with adults with a chronic disease and that reported on cost-effectiveness or cost-utility analysis outcomes. Data extraction All studies were independently screened and extracted, and quality was appraised using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Data analysis All extracted data were grouped into subcategories according to their telehealth modality and payer perspective, and were analyzed narratively. Results Twelve randomized controlled trials comprising 5 phone-only interventions, 3 mobile health (mHealth), 2 online, and 1 each using a combination of phone–online or phone–mHealth interventions, were included in this review. mHealth interventions were the most cost-effective intervention in all studies. Across all telehealth interventions and cost analyses from health service perspectives, 60% of studies were cost-effective. From a societal perspective, however, 33% of studies reported that the interventions were cost-effective. Of the 10 studies using cost-utility analyses, 3 were cost saving and more effective, making the intervention dominant, 1 study reported no difference in costs or effectiveness, and the remaining 6 studies reported increased cost and effectiveness, meaning payers must decide whether this falls within an acceptable willingness-to-pay threshold for them. Quality of study reporting varied with between 63% to 92%, with an average of 77% of CHEERS items reported. Conclusion Telehealth-delivered nutrition interventions in chronic disease populations appear to be cost-effective from a health perspective, and particularly mHealth modalities. These findings support telehealth-delivered nutrition care as a clinically beneficial, cost-effective intervention delivery modality.

Deleterious effects of separation and divorce on men’s mental health are well-documented; however, little is known about their help-seeking when adjusting to these all-too-common life transitions. Employing interpretive descriptive methods, interviews with 47 men exploring their mental health help-seeking after a relationship break-up were analyzed in deriving three themes: (1) Solitary work and tapping established connections, (2) Reaching out to make new connections, and (3) Engaging professional mental health care. Men relying on solitary work and established connections accessed relationship-focused self-help books, online resources, and confided in friends and/or family. Some participants supplemented solitary work by reaching out to make new connections including peer-based men’s groups and education and social activities. Comprising first-time, returning, and continuing users, many men responded to relationship break-up crises by engaging professional mental health care. The findings challenge longstanding commentaries that men actively avoid mental health promotion by illuminating wide-ranging help resources.

Drug-impaired driving is a growing public safety issue. Addressing impairment due to drugs other than ethanol can be challenging for forensic toxicologists as many factors need to be considered including the type of drug(s), drug−drug interaction, the dose(s) and the individual’s physiological condition and drug use history. Interpretation of blood drug test results is additionally difficult as drug concentrations in impaired driving cases may overlap levels typically viewed as toxic. This study compares blood concentrations of drugs in impaired driving cases to those in postmortem cases in Houston, TX, from 2014 to 2020. Blood drug concentrations from driving while intoxicated (DWI) or driving under the influence of drugs (DUID) cases submitted to Houston Forensic Science Center (HFSC) and Harris County Institute of Forensic Sciences (HCIFS) were compared to postmortem blood test results from HCIFS. Eight DWI/DUID cases had drugs that exceeded impaired driving concentrations reported in the literature. These drugs included fentanyl (220 ng/mL), oxycodone (680 ng/mL), hydrocodone (310 and 490 ng/mL), clonazepam (330 ng/mL), methamphetamine (3,500 and 7,100 ng/mL) and tetrahydrocannabinol (THC) (160 ng/mL). For oxycodone and hydrocodone, the presented DWI/DUID cases exceeded 91% and 96% of postmortem concentrations, respectively. The 7,100 ng/mL methamphetamine DWI/DUID result was greater than 98% of postmortem cases. The presented DWI/DUID concentrations were higher than all but one postmortem case for clonazepam and higher than all postmortem cases for THC. This study demonstrates that extremely high drug concentrations in DWI/DUID casework blur the line between therapeutic/recreational and toxic concentrations.

High-Throughput Experimentation (HTE) workflows are efficient means of surveying a broad array of chiral catalysts in the development of catalytic asymmetric reactions. However, use of traditional HPLC-UV/vis methodology to determine enantiomeric excess (ee) from the resulting reactions is often hampered by co-elution of other reaction components, resulting in erroneous ee determination when crude samples are used, and ultimately requiring product isolation prior to ee analysis. In this study, using four published reactions selected as model systems, we demonstrate that the use of LC-MS, SFC-MS, and selected ion monitoring (SIM) mass chromatography provides a highly accurate means to determine ee of products in crude reaction samples using commonplace, low-cost MS detectors. By using ion selection, co-eluting signals can be deconvoluted to provide accurate integrations of the target analytes. We also show that this method is effective for samples lacking UV/vis chromophores, making it ideal for HTE workflows in asymmetric catalysis.

Context Nutrition care is an effective lifestyle intervention for the treatment and prevention of many noncommunicable diseases. Primary care is a high-value setting in which to provide nutrition care. Objective The objective of this review was to evaluate the cost-effectiveness of nutrition care interventions provided in primary care settings. Data Sources Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Central Register of Controlled Trials, EconLit, and the National Health Service Economic Evaluation Database (NHS EED) were searched from inception to May 2021. Data Extraction Data extraction was guided by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) reporting guidelines. Randomized trials of nutrition interventions in primary care settings were included in the analysis if incremental cost-effectiveness ratios were reported. The main outcome variable incremental cost-effectiveness ratios (ICERs) and reported interpretations were used to categorize interventions by the cost-effectiveness plane quadrant. Results Of 6837 articles identified, 10 were included (representing 9 studies). Eight of the 9 included studies found nutrition care in primary care settings to be more costly and more effective than usual care. High study heterogeneity limited further conclusions. Conclusion Nutrition care in primary care settings is effective, though it requires investment; it should, therefore, be considered in primary care planning. Further studies are needed to evaluate the long-term cost-effectiveness of providing nutrition care in primary care settings. Systematic review registration PROSPERO registration no. CRD42020201146.

Reversible proton‐induced spin state switching of an FeIII complex in solution is observed at room temperature. A reversible magnetic response was detected in the complex, [FeIII(sal2323)]ClO4 (1), using Evans’ method 1H NMR spectroscopy which indicated cumulative switching from low‐spin to high‐spin upon addition of one and two equivalents of acid. Infrared spectroscopy suggests a coordination‐induced spin state switching (CISSS) effect, whereby protonation displaces the metal‐phenoxo donors. The analogous complex, [FeIII(4‐NEt2‐sal2323)]ClO4 (2), with a diethylamino group on the ligand, was used to combine the magnetic change with a colorimetric response. Comparison of the protonation responses of 1 and 2 reveals that the magnetic switching is caused by perturbation of the immediate coordination sphere of the complex. These complexes constitute a new class of analyte sensor which operate by magneto‐modulation, and in the case of 2, also yield a colorimetric response.

Proton exchange membrane fuel cells, consuming hydrogen and oxygen to generate clean electricity and water, suffer acute liquid water challenges. Accurate liquid water modelling is inherently challenging due to the multi-phase, multi-component, reactive dynamics within multi-scale, multi-layered porous media. In addition, currently inadequate imaging and modelling capabilities are limiting simulations to small areas (2) or simplified architectures. Herein, an advancement in water modelling is achieved using X-ray micro-computed tomography, deep learned super-resolution, multi-label segmentation, and direct multi-phase simulation. The resulting image is the most resolved domain (16 mm2 with 700 nm voxel resolution) and the largest direct multi-phase flow simulation of a fuel cell. This generalisable approach unveils multi-scale water clustering and transport mechanisms over large dry and flooded areas in the gas diffusion layer and flow fields, paving the way for next generation proton exchange membrane fuel cells with optimised structures and wettabilities.

Isoprene is one of the most abundant and most frequently evaluated volatile organic compounds in exhaled breath. Recently, several individuals with background levels of exhaled isoprene have been identified. Here, case study data are provided for an individual, identified from a previous study, with this low prevalence phenotype. It is hypothesized that the individual will illustrate low levels of exhaled isoprene at rest and during exercise. At rest, the subject (7.1 ppb) shows background (μ = 14.2 ± 7.0 ppb) levels of exhaled isoprene while the control group illustrates significantly higher quantities (μ = 266.2 ± 72.3 ppb) via proton transfer reaction mass spectrometry (PTR-MS). The result, background levels of isoprene at rest, is verified by thermal desorption gas chromatography mass spectrometry (TD-GC-MS) collections with the individual showing −3.6 ppb exhaled isoprene while the room background contained μ= −4.1 ± 0.1 ppb isoprene. As isoprene has been shown previously to increase at the initiation of exercise, exercise bike experiments were performed with the individual identified with low isoprene, yielding low and invariant levels of exhaled isoprene (μ = 6.6 ± 0.1 ppb) during the exercise while control subjects illustrated an approximate 2.5-fold increase (pre μ = 286.3 ± 43.8 ppb, exercise μ = 573.0 ± 147.8 ppb) in exhaled isoprene upon exercise start. Additionally, exhaled breath bag data showed a significant decrease in isoprene (delta post/pre, p = 0.0078) of the control group following the exercise regimen. Finally, TD-GC-MS results for exhaled isoprene from the individual’s family (mother, father, sister and maternal grandmother) illustrated that the mother and father exhibited isoprene values (28.5 ppb, 77.2 ppb) below control samples 95% confidence interval (μ = 166.8 ± 43.3 ppb) while the individual’s sister (182.0 ppb) was within the control range. These data provide evidence for a large dynamic range in exhaled isoprene in this family. Collectively, these results provide additional data surrounding the existence of a small population of individuals with background levels of exhaled isoprene.

Direct profiling of biochemical expression within single cells provides insights into cellular processes that are lost when ensemble averages are measured across populations of cells. Advanced separations coupled with mass spectrometry (MS) can now quantify more than 1000 proteins within single cells. Further miniaturization of separations will greatly extend the reach of single-cell proteomics, metabolomics, and lipidomics, but key challenges in instrumentation, column technology, and ionization sources must be addressed.

The goal of proteomics is to identify and quantify the complete set of proteins in a biological sample. Single-cell proteomics specializes in the identification and quantitation of proteins for individual cells, often used to elucidate cellular heterogeneity. The significant reduction in ions introduced into the mass spectrometer for single-cell samples could impact the features of MS2 fragmentation spectra. As all peptide identification software tools have been developed on spectra from bulk samples and the associated ion-rich spectra, the potential for spectral features to change is of great interest. We characterize the differences between single-cell spectra and bulk spectra by examining three fundamental spectral features that are likely to affect peptide identification performance. All features show significant changes in single-cell spectra, including the loss of annotated fragment ions, blurring signal and background peaks due to diminishing ion intensity, and distinct fragmentation pattern, compared to bulk spectra. As each of these features is a foundational part of peptide identification algorithms, it is critical to adjust algorithms to compensate for these losses.

Multimodal mass spectrometry imaging (MSI) is a critical technique used for deeply investigating biological systems by combining multiple MSI platforms in order to gain the maximum molecular information about a sample that would otherwise be limited by a single analytical technique. The aim of this work was to create a multimodal MSI approach that measures metabolomic and proteomic data from a single biological organ by combining infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) for metabolomic MSI and nanodroplet processing in one pot for trace samples (nanoPOTS) LC-MS/MS for spatially resolved proteome profiling. Adjacent tissue sections of rat brain were analyzed by each platform, and each data set was individually analyzed using previously optimized workflows. IR-MALDESI data sets were annotated by accurate mass and spectral accuracy using HMDB, METLIN, and LipidMaps databases, while nanoPOTS-LC-MS/MS data sets were searched against the rat proteome using the Sequest HT algorithm and filtered with a 1% FDR. The combined data revealed complementary molecular profiles distinguishing the corpus callosum against other sampled regions of the brain. A multiomic pathway integration showed a strong correlation between the two data sets when comparing average abundances of metabolites and corresponding enzymes in each brain region. This work demonstrates the first steps in the creation of a multimodal MSI technique that combines two highly sensitive and complementary imaging platforms. Raw data files are available in METASPACE (https://metaspace2020.eu/project/pace-2021) and MassIVE (identifier: MSV000088211).