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In this report, three patients were treated with a new treatment protocol for Invisalign to demonstrate that a variety of complex malocclusions can be successfully treated using this protocol, including correction of moderate crowding, correction of moderate Class II division 1, and deep overbite. Previous studies of Invisalign showed significant limitations for more complex orthodontic treatment, although a few recent case reports have shown successfully completed moderate to difficult orthodontic malocclusions. One reason for the discrepancy is that the earlier studies were done during the first four years of the appliance development (now ten years of clinical use), when significant problems existed with accomplishing bodily movement, torquing of roots, extrusions, and rotations of premolars and canines. The new protocol included new methods for anterior/posterior corrections, showing on the computer the effect of elastics for Class II treatment simulated as a one-stage anterior/posterior movement at the end of treatment. Staging for interproximal reduction (IPR) is now automatically staged when there is better access to interproximal contacts to avoid IPR where significant overlap between teeth is present to avoid performing IPR on surfaces that may be damaged by instruments such as burs, strips, and disks when cut on a sharp angle. Staging for tooth movements is now also done to enable combination movements to occur simultaneously for each tooth with the tooth that needs to move the most (the lead tooth) determining the minimum number of stages required. All other teeth move at a slower rate than the lead tooth throughout the duration of treatment. Attachments are now placed in the middle of the crown automatically for rotation and automatically sized in proportion to the clinical crown. Use of 1 mm thick (buccal-lingual dimension) horizontal beveled rectangular attachments is standard on premolars for retention of aligners during intrusive movements, such as leveling the lower curve of Spee in deep overbite for extrusions and for control of the tooth long axis during torquing movements. Staging of tooth movements now track linear and rotational velocities of teeth separately with the number of treatment stages determined by the lead tooth based on its rotational or linear maximum velocities at no more than two degrees of rotation per stage. Simultaneous movements are done for all teeth providing visible space (approximately 0.05 mm) between teeth during movements past other teeth using expansion instead of IPR as a primary way to increase space available for correction of crowding. [ABSTRACT FROM AUTHOR]

Using a novel cell suspension model we investigated the relative abilities of nominal peptide and variants thereof to modulate de novo positive selection of lymphocytic choriomeningitis virus (LCMV)-specific TCR transgenic T cells. Confirming our earlier findings intermediate concentrations (10-7 to 10-5 M) of the nominal agonist peptide, p33, induced CD8 co-receptor down-modulation at the level of the entire receptor and the CD8β chain as a consequence of high but non-deleting signal interactions. Agonist peptide variants caused down-modulation of the CD8β chain but to a lesser degree. An antagonist peptide capable of inducing positive selection did not cause such modifications of the co-receptor. The positively selected TCRhiCD8αα and TCRhiCD8- cells were functional but not as efficient as TCRhiCD8αβ cells, presumably due to lower avidity interactions in the absence of the CD8β chain or entire co-receptor. CD8β mRNA was absent in these cells and was not up-regulated when further stimulated with fresh antigen-presenting cells pulsed with 10-5 M p33. Effectively our data suggest that it is not the agonist or antagonist nature of a peptide per se but the overall strength of signaling that determines whether a cell will be positively or negatively selected, or die by neglect. Furthermore the agonist/antagonist properties of peptides defined at the level of mature T cell function do not unequivocally predict their effect on positive/negative selection. The ability of the T cell to down-modulate its CD8 co-receptor in response to high but non-deleting peptide interactions during positive selection allows the survival of T cells with a broader range of affinities and represents a possible mechanism by which low responsive but potentially autoreactive cells may escape into the periphery. [ABSTRACT FROM PUBLISHER]

Introduction: The objective of this pilot randomized clinical trial was to investigate the relative effectiveness of anchorage conservation of en-masse and 2-step retraction techniques during maximum anchorage treatment in patients with Angle Class I and Class II malocclusions. Methods: Sixty-four growing subjects (25 boys, 39 girls; 10.2-15.9 years old) who required maximum anchorage were randomized to 2 treatment techniques: en-masse retraction (n = 32) and 2-step retraction (n = 32); the groups were stratified by sex and starting age. Each patient was treated by a full-time clinic instructor experienced in the use of both retraction techniques at the orthodontic clinic of Peking University School of Stomatology in China. All patients used headgear, and most had transpalatal appliances. Lateral cephalograms taken before treatment and at the end of treatment were used to evaluate treatment-associated changes. Differences in maxillary molar mesial displacement and maxillary incisor retraction were measured with the before and after treatment tracings superimposed on the anatomic best fit of the palatal structures. Differences in mesial displacement of the maxillary first molar were compared between the 2 treatment techniques, between sexes, and between different starting-age groups. Results: Average mesial displacement of the maxillary first molar was slightly less in the en-masse group than in the 2-step group (mean, -0.36 mm; 95% CI, -1.42 to 0.71 mm). The average mesial displacement of the maxillary first molar for both treatment groups pooled (n = 63, because 1 patient was lost to follow-up) was 4.3 ± 2.1 mm (mean ± standard deviation). Boys had significantly more mesial displacement than girls (mean difference, 1.3 mm; P <0.03). Younger adolescents had significantly more mesial displacement than older adolescents (mean difference, 1.3 mm; P <0.02). Conclusions: Average mesial displacement of the maxillary first molar with 2-step retraction was slightly greater than that for en-masse retraction, but the difference did not reach statistical significance. This finding appears to contradict the belief of many clinicians that 2-step canine retraction is more effective than en-masse retraction in preventing clinically meaningful anchorage loss. [ABSTRACT FROM AUTHOR]

This article focuses on the chemical evaluation and initial treatment of patients with substance abuse problems who present to an emergency department. The importance of making an accurate differential diagnosis and consideration of all relevant biopsychosocial factors is highlighted. The authors offer a treatment algorithm for emergency department clinicians and psychiatrists working in an emergency department setting to consider when assessing patients with intoxication or withdrawal from drugs of abuse. As emergency departments serve an important triage function, level of care determinates are highlighted. Three important clinical federal guidelines developed by the Center for Substance Abuse Treatment are presented and discussed, which are relevant to all emergency department clinicians who evaluate patients who are intoxicated or in withdrawal. These include the following: First, never give medications to an intoxicated patient and immediately discharge them. Second, avoid discharging any intoxicated patient to the street. Last, differentiate between acute intoxication and withdrawal and assess the potential for self harm, intentional and non-intentional. [ABSTRACT FROM AUTHOR]

Objective: Employing automated language analysis, specifically Meaning Extraction Method (MEM) and Principal Component Analysis (PCA), to identify key factors in open-text responses about hearing aid experiences., Design: Exploratory, cross-sectional design, using an online questionnaire. Responses to a single open-ended question were analysed using MEM, PCA, regression, and correlation analyses., Study Sample: Participants (n = 538) included adult hearing aid users sampled from the Hearing Tracker website community and Lexie Hearing user databases in the United States., Results: The MEM-derived items revealed six factors related to hearing aid experiences: (1) life change, (2) social situation, (3) quality of life, (4) impact and speech understanding, (5) communication and interaction, and (6) music and environmental sounds. IOI-HA item 3 had the most statistically significant correlations with PCA factors. Quantile regression revealed that factors one and two significantly predicted the IOI-HA total score. Positive correlations were observed between self-reported hearing difficulty and factors one, four, and five, as well as between factor one and general health and factor two and physical activity., Conclusion: Natural language analysis of open-ended textual responses can offer valuable insights into hearing aid users' experiences. Future studies should aim to refine this methodology to enhance clinical relevance and generalisability.

The ways people use language can reveal clues to their emotions, social behaviours, thinking styles, cultures and the worlds around them. In the past two decades, research at the intersection of social psychology and computer science has been developing tools to analyse natural language from written or spoken text to better understand social processes and behaviour. The goal of this Review is to provide a brief overview of the methods and data currently being used and to discuss the underlying meaning of what language analyses can reveal in comparison with more traditional methodologies such as surveys or hand-scored language samples., (© 2024. Springer Nature Limited.)

Objectives: To compare vertical and transverse changes in mixed dentition patients treated with the Invisalign First System (IFS) to those treated with a banded hyrax expander with fixed appliances (Hyrax) and control groups, and to assess the efficiency rate of dental arch expansion with IFS., Materials and Methods: The study included 80 mixed dentition patients, with 40 in each group (IFS and Hyrax) and 40 controls from the American Association of Orthodontists Foundation Craniofacial Growth Legacy Collection. Skeletal and dental vertical dimension changes and arch width changes between pretreatment (T1) and posttreatment (T2) were evaluated., Results: Age at T1, time interval (T1-T2), sex, and Angle class did not significantly differ among the groups. Mandibular plane angle changes showed a similar reduction for the control and IFS groups, with no changes in the Hyrax group. However, the differences among the three groups did not reach statistical significance (P = .06). The Hyrax group showed significantly greater expansion in maxillary intermolar width compared to the IFS group, 4.4 vs 2.5 mm, respectively. The efficiency of maxillary expansion using IFS ranged from 52.3% to 76.87%., Conclusions: During the mixed dentition stage, no significant changes occurred in vertical dimensions among the control, Hyrax, and IFS groups. Although there was a trend suggesting a greater reduction in mandibular plane angle in the IFS group compared to the Hyrax group, this may not be clinically significant given the less than 1° difference. IFS can be a viable option for addressing mild arch width deficiencies, with a predictable increase in intermolar width of approximately 2.5 mm., (© 2024 by The EH Angle Education and Research Foundation, Inc.)

Purpose: Current monoclonal antibody-based treatment approaches for cutaneous T cell lymphoma (CTCL) rely heavily on the ability to identify a tumor specific target that is essentially absent on normal cells. Herein, we propose tumor associated glycoprotein-72 (TAG-72) as one such target. TAG-72 is a mucin-associated, truncated O-glycan that has been identified as a chimeric antigen receptor (CAR)-T cell target in solid tumor indications. To date, TAG-72 targeting has not been considered in the setting of hematological malignancies., Experimental Design: CD3 + cells from patients with CTCL were analyzed for TAG-72 expression by flow cytometry. Immunohistochemistry was used to assess TAG-72 expression in CTCL patient skin lesions and a TAG-72 ELISA was employed to assess soluble TAG-72 (CA 72-4) in patient plasma. TAG-72 CAR transduction was performed on healthy donor (HD) and CTCL T cells and characterized by flow cytometry. In vitro CAR-T cell function was assessed by flow cytometry and xCELLigence® using patient peripheral blood mononuclear cells and proof-of-concept ovarian cancer cell lines. In vivo CAR-T cell function was assessed in a proof-of-concept, TAG-72 + ovarian cancer xenograft mouse model., Results: TAG-72 expression was significantly higher on total CD3 + T cells and CD4 + subsets in CTCL donors across disease stages, compared to that of HDs. TAG-72 was also present in CTCL patient skin lesions, whereas CA 72-4 was detected at low levels in both CTCL patient and HD plasma with no differences between the two groups. In vitro cytotoxicity assays showed that anti-TAG-72 CAR-T cells significantly, and specifically reduced CD3 + TAG-72 + expressing CTCL cells, compared to culture with unedited T cells (no CAR). CTCL CAR-T cells had comparable function to HD CAR-T cells in vitro and CAR-T cells derived from CTCL patients eradicated cancer cells in vivo., Conclusion: This study shows the first evidence of TAG-72 as a possible target for the treatment of CTCL., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The research described in this paper was funded by Cartherics Pty Ltd. All authors except H.M.P., C.V.D.W. and R.T, are paid employees of Cartherics and hold options and/or equity in the company. R.L.B, A.O.T and I.T.N are key Cartherics executives and H.M.P. is a member of the company's Scientific Advisory Board. V.J.E, R.L.B, I.T.N, H.M.P and A.O.T are inventors on Cartherics-owned patent applications related to this work., (© 2024 The Authors. Published by Elsevier Ltd.)

Natural language processing (NLP)-previously the domain of a select few language and computer scientists-is undergoing an unprecedented surge in popularity across disciplines. The ubiquity of language data, alongside extremely rapid methodological innovations, has magnetized the field, attracting researchers with the promise of measuring, forecasting, and understanding the most central questions in business, psychology, biology, sociology, the humanities, and beyond. The power of language analysis to reveal insights into human thought, feeling, and behavior has become a core interest emerging from recent technological advances, which are being probed to unearth deeply embedded truths about the human condition. However, NLP research has reached a critical juncture, sitting at the cusp of societal transformation in many aspects of daily life. The details of how NLP research develops over the next 3-5 years will define this transformation. In this emerging, near-infinite space of NLP-driven research, we provide a critical frame of reference for how, when, and why these technologies should evolve in a particularly transdisciplinary manner. Specifically, we discuss (a) the urgency of pairing existing and emerging NLP research with existing scientific knowledge, theory, and principles from the behavioral sciences; (b) the coevolution of NLP technologies; and (c) the practical implications and ethical consequences of expanding language analysis using broader psychosocial theories of the human condition. While our discussion focuses principally on using language as a window in the individual mind, this topic holds substantial implications for other disciplines and lines of inquiry, including the dynamics of social interaction and beyond. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Health-related quality of life (HRQoL) assesses the perceived impact of health status across life domains. Although research has explored the relationship between specific conditions, including HIV, and HRQoL in low-resource settings, less attention has been paid to the association between multimorbidity and HRQoL. In a secondary analysis of cross-sectional data from the Vukuzazi ("Wake up and know ourselves" in isiZulu) study, which identified the prevalence and overlap of non-communicable and infectious diseases in the uMkhanyakunde district of KwaZulu-Natal, we (1) evaluated the impact of multimorbidity on HRQoL; (2) determined the relative associations among infectious diseases, non-communicable diseases (NCDs), and HRQoL; and (3) examined the effects of controlled versus non-controlled disease on HRQoL. HRQoL was measured using the EQ-5D-3L, which assesses overall perceived health, five specific domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and three levels of problems (no problems, some problems, and extreme problems). Six diseases and disease states were included in this analysis: HIV, diabetes, stroke, heart attack, high blood pressure, and TB. After examining the degree to which number of conditions affects HRQoL, we estimated the effect of joint associations among combinations of diseases, each HRQoL domain, and overall health. Then, in one set of ridge regression models, we assessed the relative impact of HIV, diabetes, stroke, heart attack, high blood pressure, and tuberculosis on the HRQoL domains; in a second set of models, the contribution of treatment (controlled vs. uncontrolled disease) was added. A total of 14,008 individuals were included in this analysis. Having more conditions adversely affected perceived health (r = -0.060, p<0.001, 95% CI: -0.073 to -0.046) and all HRQoL domains. Infectious conditions were related to better perceived health (r = 0.051, p<0.001, 95% CI: 0.037 to 0.064) and better HRQoL, whereas non-communicable diseases (NCDs) were associated with worse perceived health (r = -0.124, p<0.001, -95% CI: 0.137 to -0.110) and lower HRQoL. Particular combinations of NCDs were detrimental to perceived health, whereas HIV, which was characterized by access to care and suppressed viral load in the large majority of those affected, was counterintuitively associated with better perceived health. With respect to disease control, unique combinations of uncontrolled NCDs were significantly related to worse perceived health, and controlled HIV was associated with better perceived health. The presence of controlled and uncontrolled NCDs was associated with poor perceived health and worse HRQoL, whereas the presence of controlled HIV was associated with improved HRQoL. HIV disease control may be critical for HRQoL among people with HIV, and incorporating NCD prevention and attention to multimorbidity into healthcare strategies may improve HRQoL., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Stanton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The COVID-19 pandemic posed a global threat to nearly every society around the world. Individuals turned to their political leaders to safely guide them through this crisis. The most direct way political leaders communicated with their citizens was through official speeches and press conferences. In this report, we compare psychological language markers of four different heads of state during the early stage of the pandemic. Specifically, we collected all pandemic-related speeches and press conferences delivered by political leaders in the USA (Trump), UK (Johnson), Germany (Merkel), and Switzerland (Swiss Federal Council) between February 27th and August 31st, 2020. We used natural language analysis to examine language markers of expressed positive and negative emotions, references to the community (we-talk), analytical thinking, and authenticity and compare these language markers across the four nations. Level differences in the language markers between the leaders can be detected: Trump's language was characterized by a high expression of positive emotion, Merkel's by a strong communal focus, and Johnson's and the Swiss Federal Council by a high level of analytical thinking. Overall, these findings mirror different strategies used by political leaders to deal with the COVID-19 pandemic., (© 2024. The Author(s).)

Introduction: This study aimed to examine the stability of anterior open bite (AOB) treatment with clear aligners., Methods: This retrospective cohort study included 52 adult AOB patients (aged >18 years; 15 males, 37 females) who underwent nonextraction clear aligner treatment and were at least 1 year posttreatment. Eleven cephalometric measurements were evaluated at pretreatment, end of active treatment, and at least 1-year posttreatment. Overbite change, the primary outcome variable, and other cephalometric changes during treatment and retention were calculated, and repeated measures analysis of variance were performed. Stepwise multiple regression was used to make a prediction equation for open bite relapse., Results: The mean retention period was 2.1 ± 1.1 years. The mean change in overbite during treatment was 3.3 ± 1.5 mm; 6% of patients presented relapse at least 1 year after treatment completion. The mean change of overbite (0.2 ± 0.5 mm) during the retention period was not statistically significant (P = 0.59). None of the 11 cephalometric measurements showed significant change during the retention period. The prediction model showed that only the coefficient for a tongue posture issue at the initial examination was statistically significant., Conclusions: AOB was successfully corrected in all 52 patients using only clear aligners with no additional adjunctive aids such as microimplants. When retained with maxillary and mandibular fixed retainers and maxillary and mandibular vacuum-formed retainers, there was no significant change in cephalometric measurements during the short-term retention period., (Copyright © 2023 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Background: Mental health (MH) peer online forums offer robust support where internet access is common, but healthcare is not, e.g., in countries with under-resourced MH support, rural areas, and during pandemics. Despite their widespread use, little is known about who posts in such forums, and in what mood states. The discussion platform Reddit is ideally suited to study this as it hosts forums (subreddits) for MH and non-MH topics. In bipolar disorder (BD), where extreme mood states are core defining features, mood influences are particularly relevant., Objectives: This exploratory study investigated posting patterns of Reddit users with a self-reported BD diagnosis and the associations between posting and emotions, specifically: 1) What proportion of the identified users posts in MH versus non-MH subreddits? 2) What differences exist in the emotions that they express in MH or non-MH subreddit posts? 3) How does mood differ between those users who post in MH subreddits compared to those who only post in non-MH subreddits?, Methods: Reddit users were automatically identified via self-reported BD diagnosis statements and all their 2005-2019 posts were downloaded. First, the percentages of users who posted only in MH (non-MH) subreddits were calculated. Second, affective vocabulary use was compared in MH versus non-MH subreddits by measuring the frequency of words associated with positive emotions, anxiety, sadness, anger, and first-person singular pronouns via the LIWC text analysis tool. Third, a logistic regression distinguished users who did versus did not post in MH subreddits, using the same LIWC variables (measured from users' non-MH subreddit posts) as predictors, controlling for age, gender, active days, and mean posts/day., Results: 1) Two thirds of the identified 19,685 users with a self-reported BD diagnosis posted in both MH and non-MH subreddits. 2) Users who posted in both MH and non-MH subreddits exhibited less positive emotion but more anxiety and sadness and used more first-person singular pronouns in their MH subreddit posts. 3) Feminine gender, higher positive emotion, anxiety, and sadness were significantly associated with posting in MH subreddits., Conclusions: Many Reddit users who disclose a BD diagnosis use a single account to discuss MH and other concerns. Future work should determine whether users exhibit more anxiety and sadness in their MH subreddit posts because they more readily post in MH subreddits when experiencing lower mood or because they feel more able to express negative emotions in these spaces. MH forums may reflect the views of people who experience more extreme mood (outside of MH subreddits) compared to people who do not post in MH subreddits. These findings can be useful for MH professionals to discuss online forums with their clients. For example, they may caution them that forums may underrepresent people living well with BD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jagfeld et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The lymph node (LN) is home to resident macrophage populations that are essential for immune function and homeostasis, but key factors controlling this niche are undefined. Here, we show that fibroblastic reticular cells (FRCs) are an essential component of the LN macrophage niche. Genetic ablation of FRCs caused rapid loss of macrophages and monocytes from LNs across two in vivo models. Macrophages co-localized with FRCs in human LNs, and murine single-cell RNA-sequencing revealed that FRC subsets broadly expressed master macrophage regulator CSF1. Functional assays containing purified FRCs and monocytes showed that CSF1R signaling was sufficient to support macrophage development. These effects were conserved between mouse and human systems. These data indicate an important role for FRCs in maintaining the LN parenchymal macrophage niche., (© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

Borderline personality disorder (BPD) is characterized by severe interpersonal dysfunction, yet the underlying nature of such dysfunction remains poorly understood. The present study adopted a behavioral approach to more objectively describe the social-cognitive contributors to interpersonal dysfunction in BPD. Participants ( N = 530) completed an online survey comprising validated measures of BPD features and other problematic interpersonal traits (e.g., narcissism), as well as a writing prompt where they were asked to share their personal thoughts about relationships. Computerized language analysis methods were used to quantify various psychosocial dimensions of participants' writing, which were incorporated into a principal component analysis. Analyses revealed four core social dimensions of thought: (1) Connectedness/Intimacy; (2) Immediacy; (3) Social Rumination ; (4) Negative Affect . All four dimensions correlated with BPD features in intuitive ways, some of which were specific to BPD. This study highlights the value of natural language analysis to explore fundamental dimensions of personality disorder.

Background: Despite its growing prevalence, BDSM practice (bondage, discipline, dominance, submission, and sadomasochism) is still stigmatized, and little is known about the physical marks and injuries that individuals sustain from consensual BDSM-related activities., Aim: In this exploratory study, we examined BDSM sexual experiences and the physical marks and injuries resulting from these experiences in a convenience sample of 513 US adults., Methods: We examined the extent to which individuals at various stages of BDSM exploration engage with different types of BDSM and kink behaviors, along with the frequency with which they communicate about, inflict, and receive physical marks from these activities., Outcomes: Our main outcome measures were intentional and unintentional marks sustained from BDSM-related activities, BDSM experiences, and the use of safe words., Results: Results revealed that BDSM marks and injuries are common and quite varied (from small scratches to very large bruises) and unintentional and intentional marks differ in terms of typical size, place on body, and severity of injury. Additionally, BDSM experience is positively associated with the use of safe words and marking behaviors., Clinical Translation: Disclosure of marks and injuries, intentional and unintentional, may be improved if health care providers are aware of, and make efforts to reduce stigma surrounding, BDSM and rough sex activity., Strengths and Limitations: The findings of this study must be interpreted with acknowledgment of the limitations that it was a survey study with a convenience sample. However, as one of the few studies exploring the marks and injuries sustained from BDSM activities, the exploration of intentional and unintentional marks sustained provides a critical starting point for future examination of BDSM consequences that intersect with health care and the law., Conclusion: Marks and injuries from BDSM-related activities are common, and despite the greater use of safe words, practitioners with more BDSM experience inflict more marks than those with less BDSM experience., (© International Society for Sexual Medicine 2023.)

Emotional granularity is the ability to create differentiated and nuanced emotional experiences and is associated with positive health outcomes. Individual differences in granularity are hypothesized to reflect differences in emotion concepts, which are informed by prior experience and impact current and future experience. Greater variation in experience, then, should be related to the rich and diverse emotion concepts that support higher granularity. Using natural language processing methods, we analyzed descriptions of everyday events to estimate the diversity of contexts and activities encountered by participants. Across three studies varying in language (English, Dutch) and modality (written, spoken), we found that participants who referred to a more varied and balanced set of contexts and activities reported more differentiated and nuanced negative emotions. Experiential diversity was not consistently associated with granularity for positive emotions. We discuss the contents of daily life as a potential source and outcome of individual differences in emotion., Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-023-00185-2., Competing Interests: Conflicts of InterestThe authors declare no conflicts of interest., (© The Society for Affective Science 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

While experiencing the unpredictable events of the COVID-19 pandemic, we are likely to turn to people in order to regulate our emotions. In this research, we investigate how this interpersonal emotion regulation is connected to affective symptoms, above and beyond intra personal emotion regulation. Furthermore, we explore whether perceived psychosocial resources moderate these associations, i.e., if individuals reporting healthier social connections benefit differently from interpersonal emotion regulation. N = 1401 participants from the USA, UK, Germany, and Switzerland completed an online survey that included text samples. Affective symptoms (depression, adjustment disorder, fear of COVID-19) were examined based on self-reported as well as language-based indicators. As psychosocial resources, we examined social support, loneliness, attachment style, and trust. We defined latent variables for adaptive and maladaptive interpersonal emotion regulation and analyzed how they were associated with affective symptoms controlling for intrapersonal emotion regulation. Further, we analyzed how they interacted with psychosocial resources. Maladaptive interpersonal emotion regulation strategies were associated with affective symptoms. With lower psychosocial resources, the associations between interpersonal emotion regulation and depressive symptoms were more pronounced. The results highlight that maladaptive interpersonal emotion regulation is associated with worse mental health. These effects are not buffered by more psychosocial resources and are stronger for people with low psychosocial resources.

Despite the established health and ecological benefits of a plant-based diet, the decision to eschew meat and other animal-derived food products remains controversial. So polarising is this topic that anti-vegan communities - groups of individuals who stand vehemently against veganism - have sprung up across the internet. Much scholarship on veganism characterizes anti-vegans in passing, painting them as ill-informed, uneducated, or simply obstinate. However, little empirical work has investigated these communities and the individuals within them. Accordingly, we conducted a study using social media data from the popular platform, Reddit. Specifically, we collected all available submissions (∼3523) and comments (∼45,528) from r/AntiVegan subreddit users (N = 3819) over a five-year period. Using a battery of computerized text analytic tools, we examined the psychosocial characteristics of Reddit users who publicly identify as anti-vegan, how r/AntiVegan users discuss their beliefs, and how the individual user changes as a function of community membership. Results from our analyses suggest several individual differences that align r/AntiVegan users with the community, including dark entertainment, ex-veganism and science denial. Several topics were extensively discussed by r/AntiVegan members, including nuanced discourse on the ethicality and health implications of vegan diets, and the naturalness of animal death, which ran counter to our expectations and lay stereotypes of r/AntiVegan users. Finally, several longitudinal changes in language use were observed within the community, reflecting enhanced group commitment over time, including an increase in group-focused language and a decrease in cognitive processing. Implications for vegan-nonvegan relations are discussed., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Studies have shown age differences in adapting to the COVID-19 pandemic. The processes explaining these age differences remain unclear. Intrapersonal and interpersonal emotion regulation play an important role in psycho-social adjustment and develop across the lifespan. This study investigated whether differences in COVID-19-related adjustment disorder symptoms can be explained by age-differences in rumination in a multi-national sample. Furthermore, linguistic indicators of ruminative processing were examined with reference to age., Methods: N  = 1401 participants (from USA, UK, Switzerland, Germany, aged 18-88) completed an online survey and a writing task. Measures included brooding, co-brooding, adjustment disorder symptoms, and language indicators of negative self- and communal-focus ., Results: Older participants reported less adjustment disorder symptoms which was mediated by less (co-)brooding. Participants reporting more (co-)brooding wrote about COVID-19 more negatively. While in younger adults more self-focus was associated with higher ruminative brooding, in older adults it was associated with less brooding., Conclusion: These findings contribute to a better understanding of regulatory mechanisms that help explain age differences in mental health. They warrant further research considering age-related differences, as our results suggest not only more adaptive emotion regulation as resilience factor in older individuals but also different qualities of self-focus while processing stressful events.

Chimeric antigen receptor (CAR-) T cells are revolutionizing cancer treatment, as a direct result of their clinical impact on the treatment of hematological malignancies. However for solid tumors, CAR-T cell therapeutic efficacy remains limited, primarily due to the complex immunosuppressive tumor microenvironment, inefficient access to tumor cells and poor persistence of the killer cells. In this in vitro study, an injectable, gelatin-based micro-hydrogel system that can encapsulate and deliver effective CAR-T therapy is investigated. CAR-T cells targeting TAG-72, encapsulated in these microgels possessed high viability (> 87%) after 7 days, equivalent to those grown under normal expansion conditions, with retention of the T cell phenotype and functionality. Microgel recovered CAR-T cells demonstrated potent on-target cytotoxicity against human ovarian cancer in vitro and on three-dimensional tumor spheroids, by completely eliminating tumor cells. The gelatin-based micro-hydrogels have the potential to serve as carrier systems to augment CAR-T immunotherapeutic treatment of solid tumors., (Copyright © 2022. Published by Elsevier Inc.)

Background: This study was aimed at identifying key topics in online discussions about tinnitus by examining a large data set extracted from Reddit social media using a natural language processing technique., Method: A corpus of 113,215 posts about tinnitus was extracted from Reddit's application programming interface. After cleaning the data for duplications and posts without any text information, the sample was reduced to 101,905 posts, which was subjected to cluster analysis using the open-source IRaMuTeQ software to identify main topics based on the co-occurrence of texts. These clusters were named by a panel of tinnitus experts ( n = 9) by reading typical text segments within each cluster., Results: The cluster analysis identified 16 unique clusters that belong to two topics, which were named "tinnitus causes and consequences" and "tinnitus management and coping." Based on their characteristics, the clusters were named: tinnitus timeline (10%), tinnitus perception (9.7%), medical triggers and modulators (8.8%), hearing research (8.8%), attention and silence (8.6%), social media posts about tinnitus (7.4%), hearing protection (7.3%), interaction with hearing health care providers (6.7%), mental health and coping (5.8%), music listening (5.7%), hope for a cure (5.6%), interactions with people without tinnitus (5.4%), dietary supplements and alternative therapies (3.2%), sleep (3.9%), dietary effects (1.7%), and writing about tinnitus and being thankful to online community (1.4%)., Conclusions: Despite some limitations, tinnitus posts on Reddit provide rich real-world data to identify various issues and complaints that tinnitus patients and their significant others discuss in online communities. Some of the clusters identified here are novel (e.g., tinnitus timeline, interactions with people without tinnitus) and have not been much discussed in the tinnitus literature. The results suggest that individuals with tinnitus relay on social media for support and highlight the service delivery needs in providing social support through other means (e.g., support groups).

Chimeric antigen receptor (CAR)-T therapy has demonstrated remarkable outcomes for B cell malignancies, however, its application for T cell lymphoma, particularly cutaneous T cell lymphoma (CTCL), has been limited. Barriers to effective CAR-T cell therapy in treating CTCL include T cell aplasia in autologous transplants, CAR-T product contamination with leukemic T cells, CAR-T fratricide (when the target antigen is present on normal T cells), and tumor heterogeneity. To address these critical challenges, innovative CAR engineering by targeting multiple antigens to strike a balance between efficacy and safety of the therapy is necessary. In this review, we discuss the current obstacles to CAR-T cell therapy and highlight potential targets in treating CTCL. Looking forward, we propose strategies to develop more powerful dual CARs that are advancing towards the clinic in CTCL therapy., Competing Interests: All authors, except V.T, are paid employees or advisors of Cartherics Pty Ltd, and hold equity in the company. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2022 To, Evtimov, Jenkin, Pupovac, Trounson and Boyd.)

Introduction: Accurate landmark identification is a prerequisite for accurate and reliable biomedical image analysis. Orthodontic study models are valuable tools for diagnosis, treatment planning, and maintaining complete records. The purpose of this study was to evaluate the reliability and validity of a software program (Align Technology, Inc) as a tool for automatic landmark location., Methods: Using digital intraoral scans of 10 dental arches, 4 calibrated human judges independently located cusp tips and interproximal contacts. The same landmarks were automatically identified by the software. Intraclass correlation coefficient (Cronbach α), absolute mean errors, and regression analysis were calculated. In addition, Bland-Altman 95% confidence limits were also applied to the data to graphically display agreement on landmark identification between the human judges and the software., Results: The intraclass correlation coefficient between the software and the human judges' average for the x-, y-, and z-coordinates for all landmarks was excellent, at 1.0, 1.0, and 0.98, respectively. The regression analysis and Bland-Altman plots show no systematic errors for agreement on landmark identification between the human judges and the software., Conclusions: Landmark location was nearly identical between the software and the human judges, making the methods interchangeable., (Copyright © 2022. Published by Elsevier Inc.)

Objective: The primary aim of the study was to examine the automated linguistic analysis of the open-ended problem (PQ) and life-effects (LEQ) questionnaires to understand the psychological effects of tinnitus., Design: The study used a cross-sectional design. Participants completed online questionnaires which included demographic questions, several standardised patient-reported outcome measures (PROMs), and two open-ended questions focussing on PQ and LEQ related to tinnitus. The response to open-ended questions was analysed using the Linguistic Inquiry Word Count (LIWC) software to identify the frequency of text on various linguistic dimensions relevant to tinnitus., Study Sample: 336 individuals with tinnitus., Results: The study results point to two broad findings. First, although PQ and LEQ have some similarities with PROMs (e.g. the linguistic dimension negative emotions having a weak positive correlation with anxiety and depression), no correlation with the number of dimensions suggests that the open-ended questions identify additional elements that are not captured in PROMs. Second, more linguistic dimensions from the PQ correlate with PROMs compared to LEQ suggesting that the current PROMs are problem-oriented., Conclusions: The study results support the idea that the use of open-ended questions in addition to PROMs may help optimise the efforts in examining the effects of chronic conditions such as tinnitus.

Objective: The purpose of this study was to examine the effectiveness and mechanism of clear aligner therapy for the correction of anterior open bite in adult nonextraction cases., Methods: Sixty-nine adult patients with anterior open bite were enrolled and classified into Angle's Class I, II, and III groups. Fifty patients presented with skeletal open bite (mandibular plane angle [MPA] ≥ 38°), whereas 19 presented with dental open bite. Fifteen cephalometric landmarks were identified before (T1) and after (T2) treatment. The magnitudes of planned and actual movements of the incisors and molars were calculated., Results: Positive overbite was achieved in 94% patients, with a mean final overbite of 1.1 ± 0.8 mm. The mean change in overbite was 3.3 ± 1.4 mm. With clear aligners alone, 0.36 ± 0.58 mm of maxillary molar intrusion was achieved. Compared with the Class I group, the Class II group showed greater maxillary molar intrusion and MPA reduction. The Class III group showed greater mandibular incisor extrusion with no significant vertical skeletal changes., Conclusions: Clear aligners can be effective in controlling the vertical dimension and correcting mild to moderate anterior open bite in adult nonextraction cases. The treatment mechanism for Class III patients significantly differed from that for Class I and Class II patients. Maxillary incisor extrusion in patients with dental open bite and MPA reduction with mandibular incisor extrusion in patients with skeletal open bite are the most significant contributing factors for open bite closure.

The mental health of college students is a growing concern, and gauging the mental health needs of college students is difficult to assess in real-time and in scale. To address this gap, researchers and practitioners have encouraged the use of passive technologies. Social media is one such "passive sensor" that has shown potential as a viable "passive sensor" of mental health. However, the construct validity and in-practice reliability of computational assessments of mental health constructs with social media data remain largely unexplored. Towards this goal, we study how assessing the mental health of college students using social media data correspond with ground-truth data of on-campus mental health consultations. For a large U.S. public university, we obtained ground-truth data of on-campus mental health consultations between 2011-2016, and collected 66,000 posts from the university's Reddit community. We adopted machine learning and natural language methodologies to measure symptomatic mental health expressions of depression, anxiety, stress, suicidal ideation, and psychosis on the social media data. Seasonal auto-regressive integrated moving average (SARIMA) models of forecasting on-campus mental health consultations showed that incorporating social media data led to predictions with r = 0.86 and SMAPE = 13.30, outperforming models without social media data by 41%. Our language analyses revealed that social media discussions during high mental health consultations months consisted of discussions on academics and career, whereas months of low mental health consultations saliently show expressions of positive affect, collective identity, and socialization. This study reveals that social media data can improve our understanding of college students' mental health, particularly their mental health treatment needs., (© 2022. The Author(s).)

Background: It is critical for professionals to understand the discourse landscape within various online and social media outlets in order to support families of children with autism in treatment decision-making. This need is heightened when considering treatments that have garnered excitement and controversy, such as applied behavioral analysis (ABA) therapy. Method: The specific aims of this study were to identify the main themes in Reddit posts about ABA-based interventions for autism using topic modeling, to examine the linguistic aspects of Reddit conversations using the Linguistic Inquiry and Word Count (LIWC) analysis, and to examine the relationship between linguistic aspects and user category (i.e., pro- vs. anti-ABA vs. undecided, parent vs. professional vs. an individual with autism). Results: The topic modeling resulted in 11 themes that ranged across various elements, such as autism as a condition and its management, stakeholders, and consequences of autism and the support needed. The posts of individuals were focused on personal experiences and opinions as opposed to clinical and research information sharing. Linguistic analysis indicated that the posts reveal an intimate stance rather than an empirical stance. Conclusions: Results provide insight into perspectives of ABA. This type of research may help in developing and distributing appropriate and evidence-based information., Competing Interests: The 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 © 2022 Bellon-Harn, Boyd and Manchaiah.)

Linguistic features of a message necessarily shape its persuasive appeal. However, studies have largely examined the effect of linguistic features on persuasion in isolation and do not incorporate properties of language that are often involved in real-world persuasion. As such, little is known about the key verbal dimensions of persuasion or the relative impact of linguistic features on a message's persuasive appeal in real-world social interactions. We collected large-scale data of online social interactions from a social media website in which users engage in debates in an attempt to change each other's views on any topic. Messages that successfully changed a user's views are explicitly marked by the user themselves. We simultaneously examined linguistic features that have been previously linked with message persuasiveness between persuasive and non-persuasive messages. Linguistic features that drive persuasion fell along three central dimensions: structural complexity, negative emotionality, and positive emotionality. Word count, lexical diversity, reading difficulty, analytical language, and self-references emerged as most essential to a message's persuasive appeal: messages that were longer, more analytic, less anecdotal, more difficult to read, and less lexically varied had significantly greater odds of being persuasive. These results provide a more parsimonious understanding of the social psychological pathways to persuasion as it operates in the real world through verbal behavior. Our results inform theories that address the role of language in persuasion, and provide insight into effective persuasion in digital environments., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2021.)

Interpersonal relationships are vital to our well-being. In recent years, it has become increasingly common to seek relationship help through anonymous online platforms. Accordingly, we conducted a large-scale analysis of real-world relationship help-seeking to create a descriptive overview of the nature and substance of online relationship help-seeking. By analyzing the demographic characteristics and language of relationship help-seekers on Reddit ( N = 184,631), we establish the first-ever big data analysis of relationship help-seeking and relationship problems in situ among the general population. Our analyses highlight real-world relationship struggles found in the general population, extending beyond past work that is typically limited to counseling/intervention settings. We find that relationship problem estimates from our sample are closer to those found in the general population, providing a more generalized insight into the distribution and prevalence of relationship problems as compared with past work. Further, we find several meaningful associations between relationship help-seeking behavior, gender, and attachment. Notably, numerous gender differences in help-seeking and romantic attachment emerged. Our findings suggest that, contrary to more traditional contexts, men are more likely to seek help with their relationships online, are more expressive of their emotions (e.g., discussing the topic of "heartache"), and show language patterns generally consistent with more secure attachment. Our analyses highlight pathways for further exploration, providing even deeper insights into the timing, lifecycle, and moderating factors that influence who, what, why, and how people seek help for their interpersonal relationships., (© The Author(s) 2021.)

Background: Many patients with sudden sensorineural hearing loss may seek hearing health information and social support online, although little is known about the online information seeking behaviour., Objective: The present study aimed to examine the discussions around sudden sensorineural hearing loss in Reddit posts., Method: A total of 526 Reddit posts about sudden sensorineural hearing loss were extracted and analysed using qualitative and quantitative methods., Results: The content analysis identified eight main categories. Most of the posts were on topics of: sharing personal experiences (34 per cent), describing symptoms (31 per cent), discussing treatment options (36 per cent) and discussing possible causes (19 per cent) of sudden sensorineural hearing loss. The sudden sensorineural hearing loss Reddit posts varied significantly in terms of linguistic variables when compared to baseline Reddit posts. Reddit posts by individuals with sudden sensorineural hearing loss had significantly higher engagement, higher authenticity and made more references to their body when compared to other users., Conclusion: The study results provide insights that can be helpful for professionals during clinical interactions.

Chimeric antigen receptor (CAR) T cells have revolutionized blood cancer immunotherapy; however, their efficacy against solid tumors has been limited. A common mechanism of tumor escape from single target therapies is downregulation or mutational loss of the nominal epitope. Targeting multiple antigens may thus improve the effectiveness of CAR immunotherapies. We generated dual CAR-T cells targeting two tumor antigens: TAG-72 (tumor-associated glycoprotein 72) and CD47. TAG-72 is a pan-adenocarcinoma oncofetal antigen, highly expressed in ovarian cancers, with increased expression linked to disease progression. CD47 is ubiquitously overexpressed in multiple tumor types, including ovarian cancer; it is a macrophage "don't eat me" signal. However, CD47 is also expressed on many normal cells. To avoid this component of the dual CAR-T cells killing healthy tissue, we designed a truncated CD47 CAR devoid of intracellular signaling domains. The CD47 CAR facilitates binding to CD47 + cells, increasing the prospect of TAG-72 + cell elimination via the TAG-72 CAR. Furthermore, we could reduce the damage to normal tissue by monomerizing the CD47 CAR. Our results indicate that the co-expression of the TAG-72 CAR and the CD47-truncated monomer CAR on T cells could be an effective, dual CAR-T cell strategy for ovarian cancer, also applicable to other adenocarcinomas., Competing Interests: The research described in this paper was funded by Cartherics Pty Ltd. All authors are paid employees or advisors of Cartherics, and A.O.T., R.L.B., and P.J.H. hold equity in the company. Additionally, P.J.H. is a consultant to Avipep Pty, Ltd. and a Director of IsoClide Medical Pty, Ltd., whose products are entirely unrelated to Cartherics., (© 2021 Cartherics PL.)

Throughout history, scholars and laypeople alike have believed that our words contain subtle clues about what we are like as people, psychologically speaking. However, the ways in which language has been used to infer psychological processes has seen dramatic shifts over time and, with modern computational technologies and digital data sources, we are on the verge of a massive revolution in language analysis research. In this article, we discuss the past and current states of research at the intersection of language analysis and psychology, summarizing the central successes and shortcomings of psychological text analysis to date. We additionally outline and discuss a critical need for language analysis practitioners in the social sciences to expand their view of verbal behavior. Lastly, we discuss the trajectory of interdisciplinary research on language and the challenges of integrating analysis methods across paradigms, recommending promising future directions for the field along the way., Competing Interests: Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The huge power for social influence of digital media may come with the risk of intensifying common societal biases, such as gender and age stereotypes. Speaker's gender and age also behaviorally manifest in language use, and language may be a powerful tool to shape impact. The present study took the example of TED, a highly successful knowledge dissemination platform, to study online influence. Our goal was to investigate how gender- and age-linked language styles-beyond chronological age and identified gender-link to talk impact and whether this reflects gender and age stereotypes. In a pre-registered study, we collected transcripts of TED Talks along with their impact measures, i.e., views and ratios of positive and negative talk ratings, from the TED website. We scored TED Speakers' (N = 1,095) language with gender- and age-morphed language metrics to obtain measures of female versus male, and younger versus more senior language styles. Contrary to our expectations and to the literature on gender stereotypes, more female language was linked to higher impact in terms of quantity, i.e., more talk views, and this was particularly the case among talks with a lot of views. Regarding quality of impact, language signatures of gender and age predicted different types of positive and negative ratings above and beyond main effects of speaker's gender and age. The differences in ratings seem to reflect common stereotype contents of warmth (e.g., "beautiful" for female, "courageous" for female and senior language) versus competence (e.g., "ingenious", "informative" for male language). The results shed light on how verbal behavior may contribute to stereotypical evaluations. They also illuminate how, within new digital social contexts, female language might be uniquely rewarded and, thereby, an underappreciated but highly effective tool for social influence. WC = 286 (max. 300 words)., Competing Interests: The authors have declared that no competing interests exist.