Systematic review and meta-analysis of vaginal natural orifice transluminal endoscopic surgery hysterectomy versus vaginal hysterectomy for benign indications.

Objective: As the second most common surgery performed on women in the United States, hysterectomy techniques are constantly examined for validity and superiority. The vaginal natural orifice transluminal endoscopic surgery (vNOTES) has increased in popularity since the first vNOTES hysterectomy was performed in 2012. We sought out to evaluate the safety and effectiveness of hysterectomy by vNOTES compared to conventional vaginal hysterectomy for various benign indications. Data sources: We searched Scopus, Medline, PubMed, ClinicalTrials.Gov, and the Cochrane Library. Our search included all studies from each respective database's inception until September 1, 2023. Study eligibility criteria: We included eligible studies that compare vNOTES hysterectomy versus conventional vaginal hysterectomy for various benign indications, and included at least one of our preselected outcomes. The main outcomes were estimated blood loss (mL), operation time (min), length of hospital stay (d), Visual Analogue Scale pain score at Day 1, intraoperative complications, and postoperative complications. Study appraisal and synthesis methods: We analyzed data of our continuous outcomes using RevMan 5.4.1. Continuous outcomes were analyzed using mean difference (MD) and 95% confidence intervals (CIs) under the inverse variance analysis method. We assessed the quality of the studies using the ROBINS-I assessment tool. Results: We found 4 eligible studies to include in our analysis. Surgeon declared estimated blood loss was found to be similar in both groups (MD=-44.70 [-99.97, 10.57]; P=.11). Also, the total length of hospital stay (in days) was found to be comparable in both groups (MD=-0.16 [-1.62, 1.30]; P=.83). We also found no other statistically significant difference between hysterectomy by vNOTES and vaginal hysterectomy in other studied outcomes, including the duration of the operation, the Visual Analogue Scale Pain score after 1 day, intraoperative complications, and postoperative complications. Conclusion: vNOTES seems to be associated with a nonsignificant lower surgeon declared estimated blood loss. We found no other significant differences in hospital stay, intraoperative, or postoperative outcomes. Further studies may clarify if other differences in safety or efficacy exist.

Photoaging and cosmeceutical solutions in sun-overexposed countries: The experience of Australia and Brazil.

Skin aging is the result of physiological changes determined by genetically driven processes and intrinsic factors, and exacerbated by a combination of multiple environmental factors, the main one being sun exposure. The effects of photoaging are particularly apparent on the face, where the appearance of aging signs can have a significant impact on the emotions conveyed and well-being. Photoprotection and facial skin care for managing photoaging signs are thus of particular importance for both physical and mental health. Countries, like Australia and Brazil, where the level of sun exposure is high and the populations have predominantly outdoor lifestyles, are particularly aware of the harms of photoaging and have implemented several measures to help reduce the risk of skin cancer in their populations. However, sun-seeking behaviours are difficult to change, and it takes time before interventions provide perceptible results. Australia still has some of the highest skin cancer incidence and mortality rates in the world. Solutions that target individuals can also be used for minimizing the clinical signs of facial aging and for improving skin quality, with the ultimate aim being not only to improve the appearance of the skin but also to mitigate the occurrence of pre-malignant and malignant lesions. This review summarizes the features of facial skin photoaging in photo-exposed populations, based on evidence gained from studies of Australian individuals, and discusses the various available solutions for skin photoaging, in particular those that are most popular in Brazil, which is a country with many years of experience in managing photoaged skin.

National survey of patient perspectives on cost discussions among recipients of copay assistance.

BACKGROUND: Individuals with cancer and other medical conditions often experience financial concerns from high costs-of-care and may utilize copay assistance programs (CAP). We sought to describe CAP recipients' experiences/preferences for cost discussions with clinicians. METHODS: We conducted a national, cross-sectional electronic-survey from 10/2022 to 11/2022 of CAP recipients with cancer or autoimmune conditions to assess patient perspectives on cost discussions. We used multivariable logistic regression models to explore associations of patient perspectives on cost discussions with patient characteristics and patient-reported outcomes (eg, financial toxicity, depression/anxiety, and health literacy). RESULTS: Among 1,566 participants, 71% had cancer and 29% had autoimmune conditions. Although 62% of respondents desired cost discussions, only 32% reported discussions took place. Additionally, 52% of respondents wanted their doctor to consider out-of-pocket costs when deciding the best treatment, and 61% of respondents felt doctors should ensure patients can afford treatment prescribed. Participants with depression symptoms were more likely to want doctors to consider out-of-pocket costs (OR = 1.54, P = .005) and to believe doctors should ensure patients can afford treatment (OR = 1.60, P = .005). Those with severe financial toxicity were more likely to desire cost discussions (OR = 1.65, P < .001) and want doctors to consider out-of-pocket costs (OR = 1.52, P = .001). Participants with marginal/inadequate health literacy were more likely to desire cost discussions (OR = 1.37, P = .01) and believe doctors should ensure patients can afford treatment (OR = 1.30, P = .036). CONCLUSIONS: In this large sample of CAP recipients with cancer and autoimmune conditions, most reported a desire for cost discussions, but under one-third reported such discussions took place.

Publication guidelines for human heart rate and heart rate variability studies in psychophysiology-Part 1: Physiological underpinnings and foundations of measurement.

This Committee Report provides methodological, interpretive, and reporting guidance for researchers who use measures of heart rate (HR) and heart rate variability (HRV) in psychophysiological research. We provide brief summaries of best practices in measuring HR and HRV via electrocardiographic and photoplethysmographic signals in laboratory, field (ambulatory), and brain-imaging contexts to address research questions incorporating measures of HR and HRV. The Report emphasizes evidence for the strengths and weaknesses of different recording and derivation methods for measures of HR and HRV. Along with this guidance, the Report reviews what is known about the origin of the heartbeat and its neural control, including factors that produce and influence HRV metrics. The Report concludes with checklists to guide authors in study design and analysis considerations, as well as guidance on the reporting of key methodological details and characteristics of the samples under study. It is expected that rigorous and transparent recording and reporting of HR and HRV measures will strengthen inferences across the many applications of these metrics in psychophysiology. The prior Committee Reports on HR and HRV are several decades old. Since their appearance, technologies for human cardiac and vascular monitoring in laboratory and daily life (i.e., ambulatory) contexts have greatly expanded. This Committee Report was prepared for the Society for Psychophysiological Research to provide updated methodological and interpretive guidance, as well as to summarize best practices for reporting HR and HRV studies in humans.

Effects of a monthly unconditional cash transfer starting at birth on family investments among US families with low income.

How does unconditional income for families in poverty affect parental investments for their young children? Mothers in four US metropolitan areas were randomized to receive a monthly unconditional cash transfer of either $333 per month (high) or $20 per month (low) for the first several years after childbirth. During the first 3 years, high-cash gift households spent more money on child-specific goods and more time on child-specific early learning activities than the low-cash gift group. Few changes were evident in other core household expenditures. Compared with low-cash gift families, high-cash gift families reported lower rates of public benefit receipt and fewer were residing in poverty, although mean income and wealth remain low for the majority of families by year 3. No statistically significant differences were evident in mothers' participation in paid work, children's time in childcare or mothers' subjective wellbeing.

HIV-1 with gag processing defects activates cGAS sensing.

BACKGROUND: Detection of viruses by host pattern recognition receptors induces the expression of type I interferon (IFN) and IFN-stimulated genes (ISGs), which suppress viral replication. Numerous studies have described HIV-1 as a poor activator of innate immunity in vitro. The exact role that the viral capsid plays in this immune evasion is not fully understood. RESULTS: To better understand the role of the HIV-1 capsid in sensing we tested the effect of making HIV-1 by co-expressing a truncated Gag that encodes the first 107 amino acids of capsid fused with luciferase or GFP, alongside wild type Gag-pol. We found that unlike wild type HIV-1, viral particles produced with a mixture of wild type and truncated Gag fused to luciferase or GFP induced a potent IFN response in THP-1 cells and macrophages. Innate immune activation by Gag-fusion HIV-1 was dependent on reverse transcription and DNA sensor cGAS, suggesting activation of an IFN response by viral DNA. Further investigation revealed incorporation of the Gag-luciferase/GFP fusion proteins into viral particles that correlated with subtle defects in wild type Gag cleavage and a diminished capacity to saturate restriction factor TRIM5α, likely due to aberrant particle formation. We propose that expression of the Gag fusion protein disturbs the correct cleavage and maturation of wild type Gag, yielding viral particles that are unable to effectively shield viral DNA from detection by innate sensors including cGAS. CONCLUSIONS: These data highlight the crucial role of capsid in innate evasion and support growing literature that disruption of Gag cleavage and capsid formation induces a viral DNA- and cGAS-dependent innate immune response. Together these data demonstrate a protective role for capsid and suggest that antiviral activity of capsid-targeting antivirals may benefit from enhanced innate and adaptive immunity in vivo.

Subclinical tuberculosis: a meta-analysis of prevalence and scoping review of definitions, prevalence and clinical characteristics.

BACKGROUND: This scoping review aimed to characterise definitions used to describe subclinical tuberculosis (TB), estimate the prevalence in different populations and describe the clinical characteristics and treatment outcomes in the scientific literature. METHODS: A systematic literature search was conducted using PubMed. We included studies published in English between January 1990 and August 2022 that defined "subclinical" or "asymptomatic" pulmonary TB disease, regardless of age, HIV status and comorbidities. We estimated the weighted pooled proportions of subclinical TB using a random-effects model by World Health Organization reported TB incidence, populations and settings. We also pooled the proportion of subclinical TB according to definitions described in published prevalence surveys. RESULTS: We identified 29 prevalence surveys and 71 other studies. Prevalence survey data (2002-2022) using "absence of cough of any duration" criteria reported higher subclinical TB prevalence than those using the stricter "completely asymptomatic" threshold. Prevalence estimates overlap in studies using other symptoms and cough duration. Subclinical TB in studies was commonly defined as asymptomatic TB disease. Higher prevalence was reported in high TB burden areas, community settings and immunocompetent populations. People with subclinical TB showed less extensive radiographic abnormalities, higher treatment success rates and lower mortality, although studies were few. CONCLUSION: A substantial proportion of TB is subclinical. However, prevalence estimates were highly heterogeneous between settings. Most published studies incompletely characterised the phenotype of people with subclinical TB. Standardised definitions and diagnostic criteria are needed to characterise this phenotype. Further research is required to enhance case finding, screening, diagnostics and treatment options for subclinical TB.

First and second-generation endometrial ablation devices: A network meta-analysis.

OBJECTIVE: First-generation and second-generation endometrial ablation (EA) techniques, along with medical treatment and invasive surgery, are considered successful lines of management for abnormal uterine bleeding (AUB). We set out to determine the efficacy of first and second-generation ablation techniques compared with medical treatment, invasive surgery and different modalities of the EA techniques themselves. DESIGN: Systematic review and network meta-analysis using a frequentist network. DATA SOURCES: We searched Medline (Ovid), PubMed, ClinicalTrials.gov, Cochrane CENTRAL, Web of Science, EBSCO and Scopus for all published studies up to 1 March 2021 using relevant keywords. ELIGIBILITY CRITERIA: We included all randomised controlled trials (RCTs) that compared premenopausal women with AUB receiving the intervention of second-generation EA techniques. DATA EXTRACTION AND SYNTHESIS: 49 high-quality RCTs with 8038 women were included. We extracted and pooled the data and then analysed to estimate the network meta-analysis models within a frequentist framework. We used the random-effects model of the netmeta package in R (V.3.6.1) and the 'Meta-Insight' website. RESULTS: Our network meta-analysis showed many varying results according to specific outcomes. The uterine balloon ablation had significantly higher amenorrhoea rates than other techniques in both short (hydrothermal ablation (risk ratio (RR)=0.51, 95% CI 0.37; 0.72), microwave ablation (RR=0.43, 95% CI 0.31; 0.59), first-generation techniques (RR=0.44, 95% CI 0.33; 0.59), endometrial laser intrauterine therapy (RR=0.18, 95% CI 0.10; 0.32) and bipolar radio frequency treatments (RR=0.22, 95% CI 0.15; 0.31)) and long-term follow-up (microwave ablation (RR=0.11, 95% CI 0.01; 0.86), bipolar radio frequency ablation (RR=0.12, 95% CI 0.02; 0.90), first generation (RR=0.12, 95% CI 0.02; 0.90) and endometrial laser intrauterine thermal therapy (RR=0.04, 95% CI 0.01; 0.36)). When calculating efficacy based only on calculated bleeding scores, the highest scores were achieved by cryoablation systems (p-score=0.98). CONCLUSION: Most second-generation EA systems were superior to first-generation systems, and statistical superiority between devices depended on which characteristic was measured (secondary amenorrhoea rate, treatment of AUB, patient satisfaction or treatment of dysmenorrhoea). Although our study was limited by a paucity of data comparing large numbers of devices, we conclude that there is no evidence at this time that any one of the examined second-generation systems is clearly superior to all others.

Radiation enhancement using focussed ultrasound-stimulated microbubbles for breast cancer: A Phase 1 clinical trial.

BACKGROUND: Preclinical studies have demonstrated that tumour cell death can be enhanced 10- to 40-fold when radiotherapy is combined with focussed ultrasound-stimulated microbubble (FUS-MB) treatment. The acoustic exposure of microbubbles (intravascular gas microspheres) within the target volume causes bubble cavitation, which induces perturbation of tumour vasculature and activates endothelial cell apoptotic pathways responsible for the ablative effect of stereotactic body radiotherapy. Subsequent irradiation of a microbubble-sensitised tumour causes rapid increased tumour death. The study here presents the mature safety and efficacy outcomes of magnetic resonance (MR)-guided FUS-MB (MRgFUS-MB) treatment, a radioenhancement therapy for breast cancer. METHODS AND FINDINGS: This prospective, single-center, single-arm Phase 1 clinical trial included patients with stages I-IV breast cancer with in situ tumours for whom breast or chest wall radiotherapy was deemed adequate by a multidisciplinary team (clinicaltrials.gov identifier: NCT04431674). Patients were excluded if they had contraindications for contrast-enhanced MR or microbubble administration. Patients underwent 2 to 3 MRgFUS-MB treatments throughout radiotherapy. An MR-coupled focussed ultrasound device operating at 800 kHz and 570 kPa peak negative pressure was used to sonicate intravenously administrated microbubbles within the MR-guided target volume. The primary outcome was acute toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Secondary outcomes were tumour response at 3 months and local control (LC). A total of 21 female patients presenting with 23 primary breast tumours were enrolled and allocated to intervention between August/2020 and November/2022. Three patients subsequently withdrew consent and, therefore, 18 patients with 20 tumours were included in the safety and LC analyses. Two patients died due to progressive metastatic disease before 3 months following treatment completion and were excluded from the tumour response analysis. The prescribed radiation doses were 20 Gy/5 fractions (40%, n = 8/20), 30 to 35 Gy/5 fractions (35%, n = 7/20), 30 to 40 Gy/10 fractions (15%, n = 3/20), and 66 Gy/33 fractions (10%, n = 2/20). The median follow-up was 9 months (range, 0.3 to 29). Radiation dermatitis was the most common acute toxicity (Grade 1 in 16/20, Grade 2 in 1/20, and Grade 3 in 2/20). One patient developed grade 1 allergic reaction possibly related to microbubbles administration. At 3 months, 18 tumours were evaluated for response: 9 exhibited complete response (50%, n = 9/18), 6 partial response (33%, n = 6/18), 2 stable disease (11%, n = 2/18), and 1 progressive disease (6%, n = 1/18). Further follow-up of responses indicated that the 6-, 12-, and 24-month LC rates were 94% (95% confidence interval [CI] [84%, 100%]), 88% (95% CI [75%, 100%]), and 76% (95% CI [54%, 100%]), respectively. The study's limitations include variable tumour sizes and dose fractionation regimens and the anticipated small sample size typical for a Phase 1 clinical trial. CONCLUSIONS: MRgFUS-MB is an innovative radioenhancement therapy associated with a safe profile, potentially promising responses, and durable LC. These results warrant validation in Phase 2 clinical trials. TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT04431674.

Synaptic injury in the inner plexiform layer of the retina is associated with progression in multiple sclerosis.

While neurodegeneration underlies the pathological basis for permanent disability in multiple sclerosis (MS), predictive biomarkers for progression are lacking. Using an animal model of chronic MS, we find that synaptic injury precedes neuronal loss and identify thinning of the inner plexiform layer (IPL) as an early feature of inflammatory demyelination-prior to symptom onset. As neuronal domains are anatomically segregated in the retina and can be monitored longitudinally, we hypothesize that thinning of the IPL could represent a biomarker for progression in MS. Leveraging our dataset with over 800 participants enrolled for more than 12 years, we find that IPL atrophy directly precedes progression and propose that synaptic loss is predictive of functional decline. Using a blood proteome-wide analysis, we demonstrate a strong correlation between demyelination, glial activation, and synapse loss independent of neuroaxonal injury. In summary, monitoring synaptic injury is a biologically relevant approach that reflects a potential driver of progression.

A review of the topical management of acne and its associated sequelae in the Asia-Pacific region with a spotlight on trifarotene.

Acne, a highly prevalent skin disease, can be particularly bothersome for patients of Asian background because of its impact on self-confidence and social interactions. In addition to active acne lesions, some patients may develop sequelae such as scarring, macular/postinflammatory hyperpigmentation, or erythema. The tendency of Asian skin to develop sequelae because of its increased susceptibility to irritation, cultural preferences for lighter skin phototypes, and differences in skincare regimens may all contribute to the increased burden of acne. Moreover, many Asia-Pacific countries do not have their own guidelines for acne management, and those that do often have no schedule in place for regular updates. In this article, we provide a critical review of the published guidance for the management of acne and its sequelae in the Asia-Pacific region, identifying gaps in current recommendations that could be addressed to enhance standards of acne care in Asia-Pacific countries. Along with highlighting the importance of a comprehensive skincare regimen to increase treatment efficacy and adherence, we discuss topical retinoids and retinoid combination options in the acne armamentarium that may be beneficial for sequelae prevention and management, such as adapalene 0.3% ± benzoyl peroxide 2.5%, tretinoin 0.05%, tazarotene 0.1%, and trifarotene 0.005%. In particular, trifarotene 0.005% has been observed to significantly reduce acne scar counts in a Phase 4 study. The recent data highlight the need to establish up-to-date guidance for acne and acne sequelae management in Asia-Pacific countries to provide optimal care to Asian patients.

Protocol for a construct and clinical validation study of MyCog Mobile: a remote smartphone-based cognitive screener for older adults.

INTRODUCTION: Annual cognitive screening in older adults is essential for early detection of cognitive impairment, yet primary care settings face time constraints that present barriers to routine screening. A remote cognitive screener completed on a patient's personal smartphone before a visit has the potential to save primary care clinics time, encourage broader screening practices and increase early detection of cognitive decline. MyCog Mobile is a promising new remote smartphone-based cognitive screening app for primary care settings. We propose a combined construct and clinical validation study of MyCog Mobile. METHODS AND ANALYSIS: We will recruit a total sample of 300 adult participants aged 65 years and older. A subsample of 200 healthy adult participants and a subsample of 100 adults with a cognitive impairment diagnosis (ie, dementia, mild cognitive impairment, cognitive deficits or other memory loss) will be recruited from the general population and specialty memory care centres, respectively. To evaluate the construct validity of MyCog Mobile, the healthy control sample will self-administer MyCog Mobile on study-provided smartphones and be administered a battery of gold-standard neuropsychological assessments. We will compare correlations between performance on MyCog Mobile and measures of similar and dissimilar constructs to evaluate convergent and discriminant validity. To assess clinical validity, participants in the clinical sample will self-administer MyCog Mobile on a smartphone and be administered a Mini-Cog screener and these data will be combined with the healthy control sample. We will then apply several supervised model types to determine the best predictors of cognitive impairment within the sample. Area under the receiver operating characteristic curve, accuracy, sensitivity and specificity will be the primary performance metrics for clinical validity. ETHICS AND DISSEMINATION: The Institutional Review Board at Northwestern University (STU00214921) approved this study protocol. Results will be published in peer-reviewed journals and summaries provided to the study's funders.

Increasing the impact of vertebrate scientific collections through 3D imaging: The openVertebrate (oVert) Thematic Collections Network.

The impact of preserved museum specimens is transforming and increasing by three-dimensional (3D) imaging that creates high-fidelity online digital specimens. Through examples from the openVertebrate (oVert) Thematic Collections Network, we describe how we created a digitization community dedicated to the shared vision of making 3D data of specimens available and the impact of these data on a broad audience of scientists, students, teachers, artists, and more. High-fidelity digital 3D models allow people from multiple communities to simultaneously access and use scientific specimens. Based on our multiyear, multi-institution project, we identify significant technological and social hurdles that remain for fully realizing the potential impact of digital 3D specimens.

Sustainability and impact of an intervention to improve initiation of tuberculosis preventive treatment: results from a follow-up study of the ACT4 randomized trial.

Background: In a cluster randomized trial (clinicaltrials.gov: NCT02810678) a flexible but comprehensive health system intervention significantly increased the number of household contacts (HHC) identified and started on tuberculosis preventive treatment (TPT). A follow-up study was conducted one year later to test the hypotheses that these effects were sustained, and were reproducible with a simplified intervention. Methods: We conducted a follow-up study from May 1, 2018 until April 30, 2019, as part of a multinational cluster randomized trial. Eight sites in 4 countries that had received the intervention in the original trial received no further intervention; eight other sites in the same countries that had not received the intervention (control sites in the original trial) now received a simplified version of the intervention. This consisted of repeated local evaluation of the Cascade of care for TB infection, and stakeholder decision making. The number of HHC identified and starting TPT were repeatedly measured at all 16 sites and expressed as rates per 100 newly diagnosed index TB patients. The sustained effect of the original intervention was estimated by comparing these rates after the intervention in the original trial with the last 6 months of the follow-up study. The reproducibility was estimated by comparing the pre-post intervention changes in rates at sites receiving the original intervention with the pre-post changes in rates at sites receiving the later, simplified intervention. Findings: With regard to the sustained impact of the original intervention, compared to the original post-intervention period, the number of HHC identified and treated per 100 newly diagnosed TB patients was 10 more (95% confidence interval: 84 fewer to 105 more), and 1 fewer (95% CI: 22 fewer to 20 more) respectively up to 14 months after the end of the original intervention. With regard to the reproducibility of the simplified intervention, at sites that had initially served as control sites, the number of HHC identified and treated per 100 TB patients increased by 33 (95% CI: -32, 97), and 16 (-69, 100) from 3 months before, to up to 6 months after receiving a streamlined intervention, although differences were larger, and significant if the post-intervention results were compared to all pre-intervention periods. Interpretation: Up to one year after it ended, a health system intervention resulted in sustained increases in the number of HHC identified and starting TPT. A simplified version of the intervention was associated with non-significant increases in the identification and treatment of HHC. Inferences are limited by potential bias due to other temporal effects, and the small number of study sites. Funding: Funded by the Canadian Institutes of Health Research (Grant number 143350).

Quantitative MALDI-MS and Imaging of Fungicide Pyrimethanil in Strawberries with 2-Nitrophloroglucinol as an Effective Matrix.

This work explores the use of 2-nitrophloroglucinol (2-NPG) as a matrix for quantitative analysis of the fungicide Pyrimethanil (PYM) in strawberries using matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and imaging. 2-NPG was selected for PYM analysis for optimum sensitivity and precision compared to common matrices α-cyano-4-hydroxylcinnamic acid (CHCA) and 2,5-dihydroxybenzoic acid (DHB). PYM-sprayed strawberries were frozen 0, 1, 3, and 4 days after treatment and sectioned for MALDI imaging. The remaining part of each strawberry was processed using quick easy cheap effective rugged and safe (QuEChERS) extraction and analyzed by MALDI-MS and ultraperformance liquid chromatography multireaction-monitoring (UPLC-MRM). MALDI-MS showed comparable performance to UPLC-MRM in calibration, LOD/LOQ, matrix effect, and recovery, with the benefit of fast analysis. The MALDI imaging results demonstrated that PYM progressively penetrated the interior of the strawberry over time and the PYM concentration on tissue measured by MALDI imaging correlated linearly with MALDI-MS and UPLC-MRM measurements and accounts for 79% MALDI-MS and 85% UPLC-MRM values on average. Additionally, quartz crystal microbalance (QCM) was introduced as a new approach to determine strawberry tissue mass per area for MALDI imaging absolute quantitation with sensitive, direct, and localized measurements. This work demonstrates the first example of absolute quantitative MALDI imaging of pesticides in a heterogeneous plant tissue. The novel use of the 2-NPG matrix in quantitative MALDI-MS and imaging could be applied to other analytes, and the new QCM tissue mass per area method is potentially useful for quantitative MALDI imaging of heterogeneous tissues in general.