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A response from the author of the article "Self-injurious thoughts and behaviors as risk factors for future suicide ideation, attempts, and death: a meta-analysis of longitudinal studies" in 2016 issue is presented.

Importance: With a recent surge in anti-lesbian, gay, bisexual, transgender, or queer (LGBTQ+) policies and associated news and media coverage, there is a need to study the association of LGBTQ+ focused news or media exposure and short-term changes in suicidal ideation (SI) among LGBTQ+ youth., Objective: To examine within-person direct and indirect associations between exposure to general and LGBTQ+ negative news or media and SI intensity through expectations of rejection., Design, Setting, and Participants: This intensive longitudinal cohort study used a smartphone-based ecological momentary assessment (EMA) protocol wherein participants responded to EMAs 3 times per day for 28 consecutive days. Young adults aged 18 to 24 years who self-identified as LGBTQ+, resided in Tennessee, and had past-year SI and at least mild depression (defined as a score ≥5 on the Patient Health Questionnaire-9) were eligible for inclusion. Participants were recruited through social media advertisements, LGBTQ+ community organizations, and mental and behavioral health clinics. Participants were recruited between March 30, 2023, and August 23, 2023, and data analyses were conducted from August 28, 2023, through April 20, 2024., Exposures: At each EMA, participants reported on recent exposure to negative news or media. A 3-level categorical exposure variable denoted (1) no news or media exposure (reference); (2) exposure to general negative news or media; and (3) exposure to LGBTQ+ negative news or media. Each EMA also assessed expectations of rejection due to LGBTQ+ identity on a scale of 0 (not at all) through 10 (very much)., Main Outcomes and Measures: Three primary outcomes assessed current (ie, "right now") intensity of active SI, passive SI, and self-harm ideation, each measured on a scale from 0 (not at all) to 10 (very strong). Multilevel modeling approaches were used to account for the hierarchical structure of EMA data, with assessments (level 1) nested within people (level 2). Linear mixed models and multilevel mediation models were used to examine within-person associations between exposure to negative news or media and the 3 primary outcomes, as well as the mediating role of expectations of rejection., Results: Of 31 total participants, 22 were assigned female sex at birth (71%), and 16 (52%) self-identified as transgender or gender diverse. The median (IQR) participant age was 21 (18-22) years, and a total of 2189 EMAs were completed, with a median (range) compliance of 90.5% (41.7%-100%). At the within-person level, recent exposure to LGBTQ+ negative news or media was significantly associated with increased active SI (estimate [b], 0.14; 95% CI, 0.04-0.25; P = .009), passive SI (b, 0.23; 95% CI, 0.04-0.41; P = .02), and self-harm ideation (b, 0.13; 95% CI, 0.02-0.23; P = .02). No statistically significant associations were detected for exposure to general negative news or media. In multilevel mediation models, heightened expectations of rejection explained some of the total effect of exposure to LGBTQ+ negative news or media on active SI (23%) and passive SI (37%)., Conclusions and Relevance: This intensive longitudinal cohort study found that SI intensity modestly increased in the hours immediately following exposure to LGBTQ+ negative news or media among LGBTQ+ young adults. These findings have timely implications for research and intervention, particularly within sociopolitical and geographic contexts where news or media coverage about LGBTQ+ topics is intensified.

Although the literature suggests trait-like differences in affective and cognitive vulnerabilities between individuals with and without a history of nonsuicidal self-injury (NSSI), little is known about how these dispositional differences are experienced in the natural environment. The present study compares the intensity, inertia, interaction, and variability of affective (negative and positive affect) and cognitive states (rumination, self-criticism) in the everyday lives of individuals who do and do not engage in NSSI. Using experience sampling methodology (ESM), 60 emerging adults (ages = 18-22 years) with and without past-year NSSI (equally distributed) completed eight questionnaires per day for 12 days (in total, 96 questionnaires per participant), resulting in 4,587 assessments (median compliance = 83.3%; IQR = 71.9-91.7). In a dynamic structural equation modeling framework, dynamic parameters (i.e., mean intensity, carryover effects, spillover effects, and within-person variability) were evaluated using multilevel vector autoregressive models. Emerging adults who engage in NSSI experience higher intensity and greater variability of negative affect, rumination, and self-criticism, whereas those who do not engage in NSSI experience higher intensity and lower variability of positive affect. In addition, past-year NSSI predicted stronger affective-cognitive interactions over time, with stronger spillover effects of negative and positive affect on subsequent rumination and self-criticism in individuals who engage in NSSI. Depressive symptoms and trait levels of emotion dysregulation and self-criticism partially negated these differences. Our findings provide evidence that emerging adults who self-injure experience more negative affective-cognitive states in daily life and point to the potential relevance of boosting positive emotions to buffer negative cognitions., (Copyright © 2023 Association for Behavioral and Cognitive Therapies. Published by Elsevier Ltd. All rights reserved.)

Lay Abstract: Adaptive behavior is a broad set of skills needed to function in everyday life. The Vineland Adaptive Behavior Scales (VABS-3) is commonly used to measure adaptive behavior. It divides adaptive behavior into three domains, Communication, Daily Living Skills, and Socialization, each of which are split into subdomains. Analyses of this three-part structure of the first version of VABS used the instrument as an interview, but now it is done as a questionnaire as well. The structure has not been well supported in samples of autistic people, who often have different strengths and challenges in adaptive behavior compared with non-autistic people. Because adaptive behavior is an important concept in autism research and online-administered questionnaires are increasingly common, it is important to ensure the structure of the VABS-3 Comprehensive Parent/Caregiver Form (VABS-3:CPCF; a questionnaire) works well for autistic individuals across a range of abilities. This study aimed to investigate whether VABS-3:CPCF measures adaptive behavior similarly in verbal and minimally verbal autistic people. However, the data didn't fit the structure in the first step of the analysis, so this could not be investigated. The next analyses also found the three-domain structure didn't fit in different age and language groups. In addition, the data didn't fit a structure combining all the domains into 1 (unidimensional). These results suggest that neither the three-factor or unidimensional structure fit the VABS-3:CPCF, cautioning against interpretation of domain or overall adaptive behavior composite scores in autistic individuals and further encouraging careful consideration of administration format., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: V.H.B receives research funding from Western Psychological Services and has received consulting fees from Regeneron and Janssen Research & Development LLC; all projects are unrelated to this work.

Objective: Suicidal ideation and suicidal behaviors are major public health concerns in the United States and are difficult to treat and predict. Risk factors that are incrementally informative are needed to improve prediction and inform prevention of suicidal thoughts and behaviors. Uncontrollability of suicidal ideation, one parameter of suicidal ideation, is one such candidate., Method: In the current study, we assessed the predictive power of uncontrollability of suicidal ideation, over and above overall suicidal ideation, for future suicidal ideation in a large sample of active-duty service members. A total of 1044 suicidal military service members completed baseline assessments, of whom 664 (63.6%) completed 3-month follow-up assessments., Results: While baseline overall suicidal ideation itself was the strongest predictor of future suicidal ideation, uncontrollability of suicidal ideation added some incremental explanatory power., Conclusion: Further study of uncontrollability of suicidal thought is needed to elucidate its impact on suicidal outcomes., (© 2023 Wiley Periodicals LLC.)

The mouse Igh locus is organized into a developmentally regulated topologically associated domain (TAD) that is divided into subTADs. Here we identify a series of distal V H enhancers (E VH s) that collaborate to configure the locus. E VH s engage in a network of long-range interactions that interconnect the subTADs and the recombination center at the D H J H gene cluster. Deletion of E VH 1 reduces V gene rearrangement in its vicinity and alters discrete chromatin loops and higher order locus conformation. Reduction in the rearrangement of the V H 11 gene used in anti-PtC responses is a likely cause of the observed reduced splenic B1 B cell compartment. E VH 1 appears to block long-range loop extrusion that in turn contributes to locus contraction and determines the proximity of distant V H genes to the recombination center. E VH 1 is a critical architectural and regulatory element that coordinates chromatin conformational states that favor V(D)J rearrangement., (© 2023. The Author(s).)

Objectives: Suicidal ideation is a pervasive and painful experience that varies considerably in its phenomenology. Here, we consider how one key risk variable might inform our understanding of variation in suicidal ideation: emotion-related impulsivity, the trait-like tendency towards unconstrained speech, behaviour, and cognition in the face of intense emotions. We hypothesized that emotion-related impulsivity would be tied to specific features, including severity, perceived lack of controllability, more rapidly fluctuating course, higher scores on a measure of acute suicidal affective disturbance, and more emotional and cognitive disturbance as antecedents., Methods: We recruited two samples of adults (Ns = 421, 221) through Amazon Mechanical Turk (MTurk), with oversampling of those with suicidal ideation. Both samples completed psychometrically sound self-report measures online to assess emotion- and non-emotion-related dimensions of impulsivity and characteristics of suicidal ideation., Results: One form of emotion-related impulsivity related to the severity, uncontrollability, dynamic course, and affective and cognitive precursors of ideation., Conclusions: Despite limitations of the cross-sectional design and self-report measures, the current findings highlight the importance of specificity in considering key dimensions of impulsivity and suicidal ideation., (© 2022 British Psychological Society.)

While apoptosis plays a role in B-cell self-tolerance, its significance in preventing autoimmunity remains unclear. Here, we report that dysregulated B cell apoptosis leads to delayed onset autoimmune phenotype in mice. Our longitudinal studies revealed that mice with B cell-specific deletion of pro-apoptotic Bim ( BBim fl/fl ) have an expanded B cell compartment with a notable increase in transitional, antibody secreting and recently described double negative (DN) B cells. They develop greater hypergammaglobulinemia than mice lacking Bim in all cells and accumulate several autoantibodies characteristic of Systemic Lupus Erythematosus (SLE) and related Sjögren's Syndrome (SS) including anti-nuclear, anti-Ro/SSA and anti-La/SSB at a level comparable to NODH2h4 autoimmune mouse model. Furthermore, lymphocytes infiltrated the tissues including submandibular glands and formed follicle-like structures populated with B cells, plasma cells and T follicular helper cells indicative of ongoing immune reaction. This autoimmunity was ameliorated upon deletion of Bruton's tyrosine kinase (Btk) gene, which encodes a key B cell signaling protein. These studies suggest that Bim-mediated apoptosis suppresses and B cell tyrosine kinase signaling promotes B cell-mediated autoimmunity., Competing Interests: Authors GC, LC, and TM are employed by AstraZeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wright, Bazile, Clark, Carlesso, Boucher, Kleiman, Mahmoud, Cheng, López-Rodríguez, Satterthwaite, Altman, Greidinger and Khan.)

Objective: Gratitude, or thankfulness for positive aspects of life, is related to psychosocial well-being and decreased psychopathology, and may reduce suicide risk. We explored four potential hypotheses purported to explain the beneficial outcomes of gratitude (schematic, positive affect, broaden-and-build, and coping), hypothesizing that hopelessness (schematic), depression (positive affect), social support (broaden-and-build), and substance use (coping) would mediate the gratitude-suicide linkage. Participants: 913 undergraduate students from a mid-size, southeastern U.S. university. Methods: Respondents completed online self-report questionnaires including the Suicidal Behaviors Questionnaire-Revised, Gratitude Questionnaire, Beck Hopelessness Scale, Beck Depression Inventory, Duke Social Support Index, Alcohol Use Disorders Identification Test, and Drug Abuse Screening Test. Results: Supporting theory and hypotheses, gratitude was related to less suicide risk via beneficial associations with hopelessness, depression, social support, and substance misuse. Conclusions: The linkage between gratitude and suicide risk appears to be predicated on the beneficial association of gratitude to negative mood and interpersonal functioning.

Extracellular adenosine suppresses T cell immunity in the tumor microenvironment and in vitro treatment of memory T cells with adenosine can suppress antigen-mediated memory T cell expansion. We describe utilizing the recall antigen assay platform to screen small molecule drug off-target effects on memory T cell expansion/function using a dosing regimen based on adenosine treatment. As a proof of principle, we show low dose GS-5734, a monophosphoramidate prodrug of an adenosine analog, does not alter memory T cell recall at lower doses whereas toxicity observed at high dose favors antigen-specific memory T cell survival/proliferation over non-specific CD8 + T cells. Conversely, parent nucleoside GS-441524 at high dosage does not result in cellular toxicity and reduces antigen-specific T cell recall in most donors. Despite similar chemical structure, these drugs displayed opposing effects on memory T cell expansion and viability highlighting the sensitivity of this assay setup in screening compounds for off-target effects.

The Defective Self Model of nonsuicidal self-injury (NSSI) proposes that some people engage in NSSI to punish themselves and/or to respond to self-critical cognitions. Although there is a growing body of research to support this theory, there has been a lack of ecologically valid approaches employed to critically examine its tenets. The current study aimed to fill this gap in the literature. A sample of 64 undergraduates with a history of repetitive NSSI were recruited and completed an ecological momentary assessment (EMA) protocol. At baseline, participants completed trait measures of self-criticism and self-punishment cognitions. Over the EMA period, participants reported their experience of self-critical and self-punitive cognitions, and NSSI urge intensity three times daily. Our between-persons level findings suggest that trait and aggregated state self-punishment, but not self-critical cognitions, predict NSSI urges experienced over the EMA period. Our findings additionally provide evidence that both momentary self-critical and self-punishment cognitions are concomitantly and prospectively associated with NSSI urge intensity as measured in real-time and modeled at a within-persons level. However, after adjusting for concurrent NSSI urge intensity in prospective models, these within-persons level findings do not hold. Nevertheless, our findings provide greater support for the Defective Self Model of NSSI., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Wearable physiological monitoring devices enable the continuous measurement of human behavior and psychophysiology in the real world. Although such monitors are promising, their availability does not guarantee that participants will continuously wear and interact with them, especially during times of psychological distress., Objective: This study aimed to evaluate the feasibility and acceptability of using a wearable behavioral and physiological monitor, the Empatica E4, to continuously assess a group of suicidal adolescent inpatients., Methods: Participants (n=50 adolescent inpatients) were asked to wear an Empatica E4 on their wrist for the duration of their inpatient stay. In addition to assessing behavioral metadata (eg, hours worn per day), we also used qualitative interviews and self-report measures to assess participants' experience of wearing the monitor., Results: Results supported the feasibility and acceptability of this approach. Participants wore the monitor for an average of 18 hours a day and reported that despite sometimes finding the monitor uncomfortable, they did not mind wearing it. Many of the participants noted that the part of the study they enjoyed most was contributing to scientific understanding, especially if it could help people similar to them in the future., Conclusions: These findings provide promising support for using wearable monitors in clinical samples in future studies, especially if participants are invested in being part of a research study., (©Evan Kleiman, Alexander J Millner, Victoria W Joyce, Carol C Nash, Ralph J Buonopane, Matthew K Nock. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 24.09.2019.)

Objective: Eating disordered (ED) behaviors (i.e., binge eating, compensatory behaviors, restrictive eating) and nonsuicidal self-injury (NSSI; intentional and nonsuicidal self-harm) are highly comorbid and share several similarities, including consequent pain and physical damage. However, whereas NSSI is considered direct self-harm, ED behaviors are considered indirect self-harm. These distinctions stem from theoretical understanding that NSSI is enacted to cause physical harm in the moment, whereas ED behaviors are enacted for other reasons, with consequent physical harm occurring downstream of the behaviors. We sought to build on these theoretically informed classifications by assessing a range of self-harming intentions across NSSI and ED behaviors., Method: Study recruitment was conducted via online forums. After screening for inclusion criteria, 151 adults reported on their intent to and knowledge of causing physical harm in the short- and long-term and suicide and death related cognitions and intentions when engaging in NSSI and specific ED behaviors., Results: Participants reported engaging in ED and NSSI behaviors with intent to hurt themselves physically in the moment and long-term, alongside thoughts of suicide, and with some hope and knowledge of dying sooner due to these behaviors. Distinctions across behaviors also emerged. Participants reported greater intent to cause physical harm in the moment via NSSI and in the long-run via restrictive eating. NSSI and restrictive eating were associated with stronger endorsement of most suicide and death-related intentions than binge eating or compensatory behaviors., Conclusions: Findings shed light on classification of self-harming behaviors, casting doubt that firm boundaries differentiate direct and indirectly self-harming behaviors., (© 2019 Wiley Periodicals, Inc.)

The genome is organized into topologically associated domains (TADs) that enclose smaller subTADs. Here, we identify and characterize an enhancer that is located in the middle of the V gene region of the immunoglobulin kappa light chain (Igκ) locus that becomes active preceding the stage at which this locus undergoes V(D)J recombination. This enhancer is a hub of long-range chromatin interactions connecting subTADs in the V gene region with the recombination center at the J genes. Deletion of this element results in a highly altered long-range chromatin interaction pattern across the locus and, importantly, affects individual V gene utilization locus-wide. These results indicate the existence of an enhancer-dependent framework in the Igκ locus and further suggest that the composition of the diverse antibody repertoire is regulated in a subTAD-specific manner. This enhancer thus plays a structural role in orchestrating the proper folding of the Igκ locus in preparation for V(D)J recombination., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Igκ locus contraction and Vκ gene usage are controlled by Cer, a cis -acting sequence in the Vκ-Jκ intervening region. This effect is attributed to two CTCF-binding sites within Cer that are oriented toward the Vκ gene region. However, the importance of Cer CTCF orientation in regulating VκJκ rearrangement is unknown. We used CRISPR/Cas9 editing to delete and invert Cer in murine Abl pro-B cell lines. This revealed that Cer orientation is critical because clones with either an inverted or deleted Cer element show skewing toward Jκ-proximal Vκ gene usage. However, only Cer deletion increased Jκ-proximal Vκ germline transcription, suggesting an insulating function of Cer. Lastly, circularized chromosome conformation capture interaction data show that Cer CTCF orientation regulates long-range interactions with inversion clones displaying fewer interactions with regions in the middle and distal parts of the Vκ locus and more interactions to downstream regions compared with wild-type or deletion clones., (Copyright © 2018 by The American Association of Immunologists, Inc.)

To date there has not been a study directly comparing relative Igκ rearrangement frequencies obtained from genomic DNA (gDNA) and cDNA and since each approach has potential biases, this is an important issue to clarify. Here we used deep sequencing to compare the unbiased gDNA and RNA Igκ repertoire from the same pre-B cell pool. We find that ~20% of Vκ genes have rearrangement frequencies ≥2-fold up or down in RNA vs. DNA libraries, including many members of the Vκ3, Vκ4, and Vκ6 families. Regression analysis indicates Ikaros and E2A binding are associated with strong promoters. Within the pre-B cell repertoire, we observed that individual Vκ genes rearranged at very different frequencies, and also displayed very different Jκ usage. Regression analysis revealed that the greatly unequal Vκ gene rearrangement frequencies are best predicted by epigenetic marks of enhancers. In particular, the levels of newly arising H3K4me1 peaks associated with many Vκ genes in pre-B cells are most predictive of rearrangement levels. Since H3K4me1 is associated with long range chromatin interactions which are created during locus contraction, our data provides mechanistic insight into unequal rearrangement levels. Comparison of Igκ rearrangements occurring in pro-B cells and pre-B cells from the same mice reveal a pro-B cell bias toward usage of Jκ-distal Vκ genes, particularly Vκ10-96 and Vκ1-135. Regression analysis indicates that PU.1 binding is the highest predictor of Vκ gene rearrangement frequency in pro-B cells. Lastly, the repertoires of iEκ -/- pre-B cells reveal that iEκ actively influences Vκ gene usage, particularly Vκ3 family genes, overlapping with a zone of iEκ-regulated germline transcription. These represent new roles for iEκ in addition to its critical function in promoting overall Igκ rearrangement. Together, this study provides insight into many aspects of Igκ repertoire formation.

Recent studies suggest that a ruminative response style may contribute to the development and maintenance of Bulimia nervosa. However it is not clear what factors may contribute to the relationship between rumination and BN. One factor may be self-control, as studies suggest that BN symptomatology relates to deficits in self-control. In the present study, we hypothesized that the association between rumination and BN symptomatology would be the strongest among individuals with lower self-control relative to those with higher self-control. Participants were 353 students at a large university. Participants completed measures of self-control, rumination, and eating disorder symptomology as part of an online study. A hierarchical regression supported an interaction between rumination and self-control predicting bulimic symptomatology, controlling for BMI. Individuals with higher levels of rumination presented more bulimic symptoms if they also had lower levels of self-control, supporting our hypothesis. Based on these findings, assessing rumination in conjunction with self-control among individuals who present with eating concerns may help to direct treatment. Additionally, clinical interventions increasing self-control may also alleviate some BN symptoms in ruminators., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Ying Yang 1 (YY1) is a ubiquitously expressed transcription factor shown to be essential for pro-B-cell development. However, the role of YY1 in other B-cell populations has never been investigated. Recent bioinformatics analysis data have implicated YY1 in the germinal center (GC) B-cell transcriptional program. In accord with this prediction, we demonstrated that deletion of YY1 by Cγ1-Cre completely prevented differentiation of GC B cells and plasma cells. To determine if YY1 was also required for the differentiation of other B-cell populations, we deleted YY1 with CD19-Cre and found that all peripheral B-cell subsets, including B1 B cells, require YY1 for their differentiation. Transitional 1 (T1) B cells were the most dependent upon YY1, being sensitive to even a half-dosage of YY1 and also to short-term YY1 deletion by tamoxifen-induced Cre. We show that YY1 exerts its effects, in part, by promoting B-cell survival and proliferation. ChIP-sequencing shows that YY1 predominantly binds to promoters, and pathway analysis of the genes that bind YY1 show enrichment in ribosomal functions, mitochondrial functions such as bioenergetics, and functions related to transcription such as mRNA splicing. By RNA-sequencing analysis of differentially expressed genes, we demonstrated that YY1 normally activates genes involved in mitochondrial bioenergetics, whereas it normally down-regulates genes involved in transcription, mRNA splicing, NF-κB signaling pathways, the AP-1 transcription factor network, chromatin remodeling, cytokine signaling pathways, cell adhesion, and cell proliferation. Our results show the crucial role that YY1 plays in regulating broad general processes throughout all stages of B-cell differentiation.

Splenic transitional B-cells (T1 and T2) are selected to avoid self-reactivity and to safeguard against autoimmunity, then differentiate into mature follicular (FO-I and FO-II) and marginal zone (MZ) subsets. Transcriptomic analysis by RNA-seq of the five B-cell subsets revealed T1 cell signature genes included RAG suggesting a potential for receptor revision. T1 to T2 B-cell differentiation was marked by a switch from Myb to Myc, increased expression of the PI3K adapter DAP10 and MHC class II. FO-II may be an intermediate in FO-I differentiation and may also become MZ B-cells as suggested by principle component analysis. MZ B-cells possessed the most distinct transcriptome including down-regulation of CD45 phosphatase-associated protein (CD45-AP/PTPRC-AP), as well as upregulation of IL-9R and innate molecules TLR3, TLR7, and bactericidal Perforin-2 (MPEG1). Among the endosomal TLRs, stimulation via TLR3 further enhanced Perforin-2 expression exclusively in MZ B-cells. Using gene-deleted and overexpressing transgenic mice we show that IL-9/IL-9R interaction resulted in rapid activation of STAT1, 3, and 5, primarily in MZ B-cells. Importantly, CD45-AP mutant mice had reduced transitional and increased mature MZ and FO B-cells, suggesting that it prevents premature entry of transitional B-cells to the mature B-cell pool or their survival and proliferation. Together, these findings suggest, developmental plasticity among splenic B-cell subsets, potential for receptor revision in peripheral tolerance whereas enhanced metabolism coincides with T2 to mature B-cell differentiation. Further, unique core transcriptional signatures in MZ B-cells may control their innate features.