Correction: Digital Mental Health Interventions for Alleviating Depression and Anxiety During Psychotherapy Waiting Lists: Systematic Review.

[This corrects the article DOI: 10.2196/56650.].

Antifungal susceptibility, molecular epidemiology, and clinical risk factors of Candida glabrata in intensive care unit in a Chinese Tertiary Hospital.

Background: The increasing incidence and high mortality rate of Candida glabrata infection in ICU patients is an important issue. Therefore, it is imperative to investigate the antifungal susceptibility profiles and epidemiological characteristics in local regions. Methods: Herein, antifungal susceptibility testing was conducted to determine the minimum inhibitory concentrations (MICs) of eight antifungal drugs. Multilocus sequence typing (MLST) was used to study the strain genotype, geographical distribution, and susceptibility to antifungal agents among C. glabrata isolates. The mechanism of echinocandin resistance was explored by sequencing the FKS1 and FKS2 genes (encoding 1,3-ß-D-glucan synthases) of echinocandin-resistant C. glabrata strains. Moreover, we further investigated the clinical manifestations and the various risk factors of patients infected with C. glabrata in the ICU. Results: We selected 234 C. glabrata isolates from 234 patients in the ICU randomly for the follow-up study. Cross-resistance was found among the ICU C. glabrata isolates. Analysis using MLST showed that the genetic diversity among the C. glabrata isolates was low. Furthermore, sequence type showed no correlation with the antifungal resistance profiles, but was associated with geographical distribution. We also revealed novel mutations in FKS1 (S629P) and FKS2 (W1497stop) that mediated high-level echinocandin resistance (MIC >8 µg/mL). More than 14 days' stay in ICU (P=0.007), Acute Physiology and Chronic Health Evaluation II (APACHE-II) score (P=0.024), prior antifungal exposure (P=0.039) and lung disease (P=0.036) were significantly associated with antifungal resistant/non-wild-type C. glabrata infection. Conclusion: Our study shed light on the antifungal susceptibility, molecular epidemiology, and clinical risk factors of C. glabrata in the ICU of a Chinese Tertiary Hospital. Importantly, we revealed the molecular mechanism of echinocandin resistance. These results highlight the significance of continued surveillance in ICUs and provide data support for the treatment of C. glabrata in clinics.

Digital Mental Health Interventions for Alleviating Depression and Anxiety During Psychotherapy Waiting Lists: Systematic Review.

BACKGROUND: Depression and anxiety have become increasingly prevalent across the globe. The rising need for treatment and the lack of clinicians has resulted in prolonged waiting times for patients to receive their first session. Responding to this gap, digital mental health interventions (DMHIs) have been found effective in treating depression and anxiety and are potentially promising pretreatments for patients who are awaiting face-to-face psychotherapy. Nevertheless, whether digital interventions effectively alleviate symptoms for patients on waiting lists for face-to-face psychotherapy remains unclear. OBJECTIVE: This review aimed to synthesize the effectiveness of DMHIs for relieving depression and anxiety symptoms of patients on waiting lists for face-to-face therapy. This review also investigated the features, perceived credibility, and usability of DMHIs during waiting times. METHODS: In this systematic review, we searched PubMed, PsycINFO, Cochrane, and Web of Science for research studies investigating the effectiveness of DMHIs in reducing either depression or anxiety symptoms among individuals waiting for face-to-face psychotherapy. The search was conducted in June 2024, and we have included the studies that met the inclusion criteria and were published before June 6, 2024. RESULTS: Of the 9267 unique records identified, 8 studies met the eligibility criteria and were included in the systematic review. Five studies were randomized controlled trials (RCTs), and 3 studies were not. Among the RCTs, we found that digital interventions reduced depression and anxiety symptoms, but the majority of interventions were not more effective compared to the control groups where participants simply waited or received a self-help book. For the non-RCTs, the interventions also reduced symptoms, but without control groups, the interpretation of the findings is limited. Finally, participants in the included studies perceived the digital interventions to be credible and useful, but high dropout rates raised concerns about treatment adherence. CONCLUSIONS: Due to the lack of effective interventions among the reviewed studies, especially among the RCTs, our results suggest that waiting list DMHIs are not more effective compared to simply waiting or using a self-help book. However, more high-quality RCTs with larger sample sizes are warranted in order to draw a more robust conclusion. Additionally, as this review revealed concerns regarding the high dropout rate in digital interventions, future studies could perhaps adopt more personalized and human-centered functions in interventions to increase user engagement, with the potential to increase treatment adherence and effectiveness.

Integrated Framework to Model Microstructure Evolution and Decipher the Microstructure-Property Relationship in Polymeric Porous Materials.

Unraveling the microstructure-property relationship is crucial for improving material performance and advancing the design of next-generation structural and functional materials. However, this is inherently challenging because it requires both the comprehensive quantification of microstructural features and the accurate assessment of corresponding properties. To meet these requirements, we developed an efficient and comprehensive integrated modeling framework, using polymeric porous materials as a representative model system. Our framework generates microstructures using a physics-based phase-field model, characterizes them using various average and localized microstructural features, and evaluates microstructure-aware properties, such as effective diffusivity, using an efficient Fourier-based perturbation numerical scheme. Additionally, the framework incorporates machine learning methods to decipher the intricate microstructure-property relationships. Our findings indicate that the connectivity of phase channels is the most critical microstructural descriptor for determining effective diffusivity, followed by the domain shape represented by curvature distribution, while the domain size has a minor impact. This comprehensive approach offers a novel framework for assessing microstructure-property relationships in polymer-based porous materials, paving the way for the development of advanced materials for diverse applications.

Molecular, biological characterization and drug sensitivity of chidamide-resistant MCF7 cells.

Background: Chidamide (CHI) is a subtype-selective histone deacetylase inhibitor (HDACI) developed in China and approved as a second-line treatment combined with the aromatase inhibitor for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. However, drug resistance is commonly occurred after a long period of medication. This study aimed to investigate the characterization of induced resistance to CHI and explore the potential cross-resistance to chemotherapeutic agents. Methods: CHI with gradually increasing concentrations was added to breast cancer MCF7 cells to establish a CHI-resistant MCF7 (MCF7-CHI-R) cell line. Cell counting kit-8 (CCK-8) assays were performed to detect half-maximal inhibitory concentration (IC50) of CHI. Colony formation was used to determine the proliferation inhibition rate. Western blot analysis was conducted to detect expressions of protein related with cell cycle, apoptosis, ferroptosis, and histone deacetylase (HDAC). Flow cytometry was used to analyze apoptosis and cell cycle. Results: The IC50 value of CHI of MCF7-CHI-R cells was increased in comparison with MCF7 cells. And CHI led to cell cycle arrest and ferroptosis, which were not exhibited in MCF7-CHI-R cells. Moreover, HDAC activity decreased in MCF7-CHI-R cells in comparison with MCF7 cells, and HDAC1 and HDAC10 might be involved in the resistance to CHI. In addition, MCF7-CHI-R cells were resistant to gemcitabine (GEM), doxorubicin (ADM), docetaxel (DXT), albumin-bound paclitaxel (nab-PTX) and paclitaxel (PTX). Conclusions: The MCF7-CHI-R was established and the anti-ferroptosis pathway activation was involved in the resistance of MCF-CHI-R cells. Also, MCF7-CHI-R cells were resistant to GEM, ADM, DXT, nab-PTX and PTX.

The Effectiveness of Online Sensate Focus Exercises in Enhancing Sexual Function and Intimacy Among Chinese Heterosexual Couples: A Randomized Controlled Trial.

We investigated the effectiveness of online Sensate Focus exercises, delivered online as a series of 11 animation videos, in improving participants' sexual functioning and enhancing intimacy, relationship and sexual satisfaction. We studied 35 Chinese heterosexual couples, assessed them at pretest, post-test, and a three-month follow-up. Compared to the waitlist control group, the experimental group showed improvement in orgasm in women, and this was maintained at follow-up. Also, for those with a lower function at pretest, the intervention was possibly effective in improving erectile function among men, as well as overall sexual function and pain among women. These improvements were maintained at follow-up as well. Findings from the current study suggest that online Sensate Focus intervention has potential in treating sexual dysfunction of Chinese heterosexual couples. It may also serve as the first part of a stepped care approach or be integrated with other medication or cognitive behavioral therapy treatment.

Distinct patterns of electrophysiologic-neuroimaging correlations between Parkinson's disease and multiple system atrophy.

Due to a high degree of symptom overlap in the early stages, with movement disorders predominating, Parkinson's disease (PD) and multiple system atrophy (MSA) may exhibit a similar decline in motor areas, yet they differ in their spread throughout the brain, ultimately resulting in two distinct diseases. Drawing upon neuroimaging analyses and altered motor cortex excitability, potential diffusion mechanisms were delved into, and comparisons of correlations across distinct disease groups were conducted in a bid to uncover significant pathological disparities. We recruited thirty-five PD, thirty-seven MSA, and twenty-eight matched controls to conduct clinical assessments, electromyographic recording, and magnetic resonance imaging scanning during the "on medication" state. Patients with neurodegeneration displayed a widespread decrease in electrophysiology in bilateral M1. Brain function in early PD was still in the self-compensatory phase and there was no significant change. MSA patients demonstrated an increase in intra-hemispheric function coupled with a decrease in diffusivity, indicating a reduction in the spread of neural signals. The level of resting motor threshold in healthy aged showed broad correlations with both clinical manifestations and brain circuits related to left M1, which was absent in disease states. Besides, ICF exhibited distinct correlations with functional connections between right M1 and left middle temporal gyrus in all groups. The present study identified subtle differences in the functioning of PD and MSA related to bilateral M1. By combining clinical information, cortical excitability, and neuroimaging intuitively, we attempt to bring light on the potential mechanisms that may underlie the development of neurodegenerative disease.

A "What Matters Most" approach to investigating intersectional stigma toward HIV and cancer in Hanoi, Vietnam.

BACKGROUND: Vietnam is experiencing a growing burden of cancer, including among people living with HIV. Stigma acts as a sociocultural barrier to the prevention and treatment of both conditions. This study investigates how cultural notions of "respected personhood" (or "what matters most") influence manifestations of HIV-related stigma and cancer stigma in Hanoi, Vietnam. METHODS: Thirty in-depth interviews were conducted with people living with HIV in Hanoi, Vietnam. Transcripts were thematically coded via a directed content analysis using the What Matters Most conceptual framework. Coding was done individually and discussed in pairs, and any discrepancies were reconciled in full-team meetings. RESULTS: Analyses elucidated that having chu tín-a value reflecting social involvement, conscientiousness, and trustworthiness-and being successful (eg, in career, academics, or one's personal life) are characteristics of respected people in this local cultural context. Living with HIV and having cancer were seen as stigmatized and interfering with these values and capabilities. Intersectional stigma toward having both conditions was seen to interplay with these values in some ways that had distinctions compared with stigma toward either condition alone. Participants also articulated how cultural values like chu tín are broadly protective against stigmatization and how getting treatment and maintaining employment can help individuals resist stigmatization's most acute impacts. CONCLUSIONS: HIV-related and cancer stigma each interfere with important cultural values and capabilities in Vietnam. Understanding these cultural manifestations of these stigmas separately and intersectionally can allow for greater ability to measure and respond to these stigmas through culturally tailored intervention.

Wald χ2 Test for Differential Item Functioning Detection with Polytomous Items in Multilevel Data.

Identifying items with differential item functioning (DIF) in an assessment is a crucial step for achieving equitable measurement. One critical issue that has not been fully addressed with existing studies is how DIF items can be detected when data are multilevel. In the present study, we introduced a Lord's Wald χ2 test-based procedure for detecting both uniform and non-uniform DIF with polytomous items in the presence of the ubiquitous multilevel data structure. The proposed approach is a multilevel extension of a two-stage procedure, which identifies anchor items in its first stage and formally evaluates candidate items in the second stage. We applied the Metropolis-Hastings Robbins-Monro (MH-RM) algorithm to estimate multilevel polytomous item response theory (IRT) models and to obtain accurate covariance matrices. To evaluate the performance of the proposed approach, we conducted a preliminary simulation study that considered various conditions to mimic real-world scenarios. The simulation results indicated that the proposed approach has great power for identifying DIF items and well controls the Type I error rate. Limitations and future research directions were also discussed.

Efficacy and safety of gemcitabine plus raltitrexed or S-1 versus standard third-line therapies in metastatic colorectal cancer: a retrospective cohort study.

Background: After the failure of standard first- and second-line treatments, including oxaliplatin, irinotecan, and 5-fluorouracil (5-FU) combined with targeted drugs, the currently recommended third-line regimens for metastatic colorectal cancer (mCRC) include TAS-102, regorafenib, and fruquintinib. However, these regimens have the drawbacks of mediocre efficacy, substantive side effects, and high cost. Therefore, more effective, economical regimens with fewer side effects are needed in clinical practice. In this study, we assessed the efficacy and safety of gemcitabine plus raltitrexed or S-1 as a third- or later-line treatment in comparison to those of standard third-line therapies for patients with mCRC. Methods: Patients with previous failures of at least two lines of standard therapy with oxaliplatin, 5-FU, irinotecan, or capecitabine combined with targeted drugs were included. The participants received standard third-line therapies (including TAS-102, regorafenib, and fruquintinib) or gemcitabine plus raltitrexed or S-1 until disease progression, death, or intolerable toxicity arose. Imaging follow-up was performed every 3 months during their treatment. Progression-free survival (PFS) and overall survival (OS) were recorded. Cox regression analysis was used to investigate the potential predictors of survival. Results: From April 2018 to October 2022, 60 patients with mCRC were enrolled in our study. The numbers of patients in the chemotherapy, fruquintinib, regorafenib, and TAS-102 groups were 13, 15, 17, and 15, respectively; the median OS of the four groups was 7.4, 6.1, 8.3, and 6.7 months (P=0.384), respectively; the median PFS was 4.1, 3.4, 4.4, and 2.3 months (P=0.656), respectively; the overall response rate was 7.69%, 6.67%, 0.00%, and 13.33%, respectively; and the disease control rate was 61.54%, 60.00%, 70.59%, and 60.00%, respectively. Additionally, multivariate analysis revealed that primary lesion located in the rectum was adverse independent prognostic factors for OS. A typical case is presented in this article. Conclusions: The gemcitabine plus raltitrexed or S-1 regimen is a potential regimen with tolerable adverse reactions and low cost for patients with mCRC.

Psychometric exploration of the RAADS-R with autistic adults: Implications for research and clinical practice.

LAY ABSTRACT: Surveys used to screen for autism are being used much more by adults. Adults and clinicians want to be confident that the results from their surveys are accurate. If scores are not accurate, it is not possible to compare the scores of different groups of individuals. There are also concerns that these surveys do not accurately identify autistic individuals. This study explored the accuracy of two commonly used autism screening surveys for adults: the RAADS-R and the RAADS-14. The accuracy of these two screening tools was measured using a sample of 839 adults. Adults in the study were in one of the following categories: (1) diagnosed with autism, (2) adults who considered themselves to be autistic but had not been diagnosed, (3) adults who were unsure whether they were autistic, and (4) adults who did not consider themselves to be autistic and had not been diagnosed. The study found that the RAADS-R and the RAADS-14 are accurate. The study also found that a person's age, gender, autism diagnosis, or whether an individual considered themselves to be autistic did not impact how they understood the survey. Survey accuracy could be improved by changing the number of question responses from four to two. Importantly, individuals with a clinical diagnosis of autism and those who considered themselves to be autistic responded to survey items in a very similar way. Individuals with autism diagnoses and those who were unsure whether they were autistic were more different in their responses. Four specific survey items related to sensory experiences and social interaction identified key differences between autistic and non-autistic adults.

Approaches to Item-Level Data with Cross-Classified Structure: An Illustration with Student Evaluation of Teaching.

Student evaluation of teaching (SET) questionnaires are ubiquitously applied in higher education institutions in North America for both formative and summative purposes. Data collected from SET questionnaires are usually item-level data with cross-classified structure, which are characterized by multivariate categorical outcomes (i.e., multiple Likert-type items in the questionnaires) and cross-classified structure (i.e., non-nested students and instructors). Recently, a new approach, namely the cross-classified IRT model, was proposed for appropriately handling SET data. To inform researchers in higher education, in this article, the cross-classified IRT model, along with three existing approaches applied in SET studies, including the cross-classified random effects model (CCREM), the multilevel item response theory (MLIRT) model, and a two-step integrated strategy, was reviewed. The strengths and weaknesses of each of the four approaches were also discussed. Additionally, the new and existing approaches were compared through an empirical data analysis and a preliminary simulation study. This article concluded by providing general suggestions to researchers for analyzing SET data and discussing limitations and future research directions.

Disruption of H3K36 methylation provokes cellular plasticity to drive aberrant glandular formation and squamous carcinogenesis.

Chromatin organization is essential for maintaining cell-fate trajectories and developmental programs. Here, we find that disruption of H3K36 methylation dramatically impairs normal epithelial differentiation and development, which promotes increased cellular plasticity and enrichment of alternative cell fates. Specifically, we observe a striking increase in the aberrant generation of excessive epithelial glandular tissues, including hypertrophic salivary, sebaceous, and meibomian glands, as well as enhanced squamous tumorigenesis. These phenotypic and gene expression manifestations are associated with loss of H3K36me2 and rewiring of repressive H3K27me3, changes we also observe in human patients with glandular hyperplasia. Collectively, these results have identified a critical role for H3K36 methylation in both in vivo epithelial cell-fate decisions and the prevention of squamous carcinogenesis and suggest that H3K36 methylation modulation may offer new avenues for the treatment of numerous common disorders driven by altered glandular function, which collectively affect large segments of the human population.

A random item effects generalized partial credit model with a multiple imputation-based scoring procedure.

PURPOSE: Random item effects item response theory (IRT) models have received much attention for more than a decade. However, more research is needed on random item effects IRT models for polytomous data. Additionally, to improve the utility of this new class of IRT models, the scoring issue must be addressed. METHODS: We proposed a new random item effects generalized partial credit model (GPCM), which considers both random person and random item and category-specific effects. In addition, we introduced a multiple imputation (MI)-based scoring procedure that applies to various random item effects IRT models. To evaluate the proposed model and scoring procedure, we analyzed data from a Quality of Life (QoL) scale for the Chronically Mentally III and conducted a preliminary simulation study. RESULTS: In the empirical data analysis, we found that patient scores generated based on the proposed model and scoring procedure were almost identical to those obtained through the conventional GPCM and scoring method. However, the standard errors (SEs) associated with the scores were slightly larger when the proposed approach was utilized. In the simulation study, we observed adequate recovery of the model parameters and patient scores. CONCLUSION: The proposed model and MI-based scoring procedure contribute to the literature. The proposed model substantially reduces the number of free parameters in comparison to a conventional GPCM, which can be desired when sample sizes are small, e.g., special populations. In addition, the MI-based scoring procedure addresses the scoring issue and can be easily extended for scoring with other random item effects IRT models.

An Explanatory Multidimensional Random Item Effects Rating Scale Model.

Random item effects item response theory (IRT) models, which treat both person and item effects as random, have received much attention for more than a decade. The random item effects approach has several advantages in many practical settings. The present study introduced an explanatory multidimensional random item effects rating scale model. The proposed model was formulated under a novel parameterization of the nominal response model (NRM), and allows for flexible inclusion of person-related and item-related covariates (e.g., person characteristics and item features) to study their impacts on the person and item latent variables. A new variant of the Metropolis-Hastings Robbins-Monro (MH-RM) algorithm designed for latent variable models with crossed random effects was applied to obtain parameter estimates for the proposed model. A preliminary simulation study was conducted to evaluate the performance of the MH-RM algorithm for estimating the proposed model. Results indicated that the model parameters were well recovered. An empirical data set was analyzed to further illustrate the usage of the proposed model.

Single-cell transcriptomes reveal a molecular link between diabetic kidney and retinal lesions.

The occurrence of diabetic nephropathy (DN) and diabetic retinopathy (DR) are closely associated in patients with diabetes. However, the cellular and molecular linkage of DN and DR has not been elucidated, and further revelations are needed to improve mutual prognostic decisions and management. Here, we generate and integrate single-cell RNA sequencing profiles of kidney and retina to explore the cellular and molecular association of kidney and retina in both physiological and pathological conditions. We find renal mesangial cells and retinal pericytes share molecular features and undergo similar molecular transitions under diabetes. Furthermore, we uncover that chemokine regulation shared by the two cell types is critical for the co-occurrence of DN and DR, and the chemokine score can be used for the prognosis of DN complicated with DR. These findings shed light on the mechanism of the co-occurrence of DN and DR and could improve the prevention and treatments of diabetic microvascular complications.

Integration of spatial and single-cell data across modalities with weakly linked features.

Although single-cell and spatial sequencing methods enable simultaneous measurement of more than one biological modality, no technology can capture all modalities within the same cell. For current data integration methods, the feasibility of cross-modal integration relies on the existence of highly correlated, a priori 'linked' features. We describe matching X-modality via fuzzy smoothed embedding (MaxFuse), a cross-modal data integration method that, through iterative coembedding, data smoothing and cell matching, uses all information in each modality to obtain high-quality integration even when features are weakly linked. MaxFuse is modality-agnostic and demonstrates high robustness and accuracy in the weak linkage scenario, achieving 20~70% relative improvement over existing methods under key evaluation metrics on benchmarking datasets. A prototypical example of weak linkage is the integration of spatial proteomic data with single-cell sequencing data. On two example analyses of this type, MaxFuse enabled the spatial consolidation of proteomic, transcriptomic and epigenomic information at single-cell resolution on the same tissue section.

Mettl3-catalyzed m6A regulates histone modifier and modification expression in self-renewing somatic tissue.

N6-methyladenosine (m6A) is the most abundant modification on messenger RNAs (mRNAs) and is catalyzed by methyltransferase-like protein 3 (Mettl3). To understand the role of m6A in a self-renewing somatic tissue, we deleted Mettl3 in epidermal progenitors in vivo. Mice lacking Mettl3 demonstrate marked features of dysfunctional development and self-renewal, including a loss of hair follicle morphogenesis and impaired cell adhesion and polarity associated with oral ulcerations. We show that Mettl3 promotes the m6A-mediated degradation of mRNAs encoding critical histone modifying enzymes. Depletion of Mettl3 results in the loss of m6A on these mRNAs and increases their expression and associated modifications, resulting in widespread gene expression abnormalities that mirror the gross phenotypic abnormalities. Collectively, these results have identified an additional layer of gene regulation within epithelial tissues, revealing an essential role for m6A in the regulation of chromatin modifiers, and underscoring a critical role for Mettl3-catalyzed m6A in proper epithelial development and self-renewal.

Construction and validation of a prognostic model based on autophagy-related genes for hepatocellular carcinoma in the Asian population.

BACKGROUND AND OBJECTIVE: Hepatocellular carcinoma (HCC), which has a complex pathogenesis and poor prognosis, is one of the most common malignancies worldwide. Hepatitis virus B infection is the most common cause of HCC in Asian patients. Autophagy is the process of digestion and degradation, and studies have shown that autophagy-associated effects are closely related to the development of HCC. In this study, we aimed to construct a prognostic model based on autophagy-related genes (ARGs) for the Asian HCC population to provide new ideas for the clinical management of HCC in the Asian population. METHODS: The clinical information and transcriptome data of Asian patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) database, and 206 ARGs were downloaded from the human autophagy database (HADB). We performed differential and Cox regression analyses to construct a risk score model. The accuracy of the model was validated by using the Kaplan-Meier (K-M) survival curve, receiver operating characteristic (ROC) curve, and univariate and multivariate Cox independent prognostic analyses. The results Thirteen ARGs that were significantly associated with prognosis were finally identified by univariate and multivariate Cox regression analyses. The K-M survival curves showed that the survival rate of the low-risk group was significantly higher than that of the high-risk group (p < 0.001), and the multi-indicator ROC curves further demonstrated the predictive ability of the model (AUC = 0.877). CONCLUSION: The risk score model based on ARGs was effective in predicting the prognosis of Asian patients with HCC.

Actual and Desired Masturbation Frequency, Sexual Distress, and Their Correlates.

We investigated the prevalence of problematic masturbation using different criteria. We also investigated if masturbation-related distress was associated with sexual abuse history, family attitudes towards sexuality during childhood, and depression and anxiety symptoms. Here, 12,271 Finnish men and women completed a survey reporting masturbation frequency, desired masturbation frequency, sexual distress, childhood sexual abuse, sex-positive family background, as well as depression and anxiety symptoms. Among both sexes, those whose masturbation frequency did not match with desired frequency experienced more sexual distress. Different conceptualizations of problematic masturbation resulted in different proportions of individuals categorized as having it (i.e., 8.3% of men and 2.7% of women experienced self-perceived problematic masturbation, that is masturbating more than they desired and experiencing sexual distress; 2% of men and 0.6% of women masturbated more frequently than average and meanwhile experienced self-perceived problematic masturbation; 6.3% of men and 2.1% of women masturbated less frequently than average but still experienced self-perceived problematic masturbation). Moreover, among both sexes, self-perceived problematic masturbation was positively associated with childhood sexual abuse, depression, and anxiety, while negatively associated with a sex-positive family background. Our results point to the complexity of defining problematic masturbation. Causes of sexual distress related to masturbation need to be carefully examined case by case to choose an appropriate clinical approach.