Neural Sensitivity to Peer Feedback and Depressive Symptoms: Moderation by Executive Function.

Theories of adolescent development suggest that elevated neural sensitivity to social evaluation confers tradeoffs for adolescents' wellbeing, promoting adaptation to changing social contexts but increasing risk for emotional distress and depression. This study investigated whether the association between neural processing of peer feedback and depressive symptoms depends on teacher-reported executive function (EF) ability in adolescent girls. Girls showed activation to negative and positive peer feedback in regions implicated in social-emotional processing that interacted with EF to predict depressive symptoms. Specifically, activation predicted more depression in youth with poorer EF but less depression in youth with better EF, suggesting that the impact of increased social sensitivity may depend on youths' ability to regulate this sensitivity in adaptive ways.

Can Artificial Intelligence Chatbots Improve Mental Health?: A Scoping Review.

BACKGROUND AND OBJECTIVES: Mental health disorders, including anxiety and depression, are the leading causes of global health-related burden and have increased dramatically since the 1990s. Delivering mental healthcare using artificial intelligence chatbots may be one option for closing the gaps in mental healthcare access. The overall aim of this scoping review was to describe the use, efficacy, and advantages/disadvantages of using an artificial intelligence chatbot for mental healthcare (stress, anxiety, depression). METHODS: PubMed, PsycINFO, CINAHL, and Web of Science databases were searched. When possible, Medical Subject Headings terms were searched in combination with keywords. Two independent reviewers reviewed a total of 5768 abstracts. RESULTS: Fifty-four articles were chosen for further review, with 10 articles included in the final analysis. Regarding quality assessment, the overall quality of the evidence was lower than expected. Overall, most studies showed positive trends in improving anxiety, stress, and depression. DISCUSSION: Overall, using an artificial intelligence chatbot for mental health has some promising effects. However, many studies were done using rudimentary versions of artificial intelligence chatbots. In addition, lack of guardrails and privacy issues were identified. More research is needed to determine the effectiveness of artificial intelligence chatbots and to describe undesirable effects.

Human movement and environmental barriers shape the emergence of dengue.

Understanding how emerging infectious diseases spread within and between countries is essential to contain future pandemics. Spread to new areas requires connectivity between one or more sources and a suitable local environment, but how these two factors interact at different stages of disease emergence remains largely unknown. Further, no analytical framework exists to examine their roles. Here we develop a dynamic modelling approach for infectious diseases that explicitly models both connectivity via human movement and environmental suitability interactions. We apply it to better understand recently observed (1995-2019) patterns as well as predict past unobserved (1983-2000) and future (2020-2039) spread of dengue in Mexico and Brazil. We find that these models can accurately reconstruct long-term spread pathways, determine historical origins, and identify specific routes of invasion. We find early dengue invasion is more heavily influenced by environmental factors, resulting in patchy non-contiguous spread, while short and long-distance connectivity becomes more important in later stages. Our results have immediate practical applications for forecasting and containing the spread of dengue and emergence of new serotypes. Given current and future trends in human mobility, climate, and zoonotic spillover, understanding the interplay between connectivity and environmental suitability will be increasingly necessary to contain emerging and re-emerging pathogens.

Diagnostic and surgical treatment for traumatic bile peritonitis in dogs and cats.

OBJECTIVE: To describe short-term outcomes of dogs and cats undergoing surgery for traumatic bile peritonitis. ANIMALS: 13 dogs and 4 cats. METHODS: Multi-institutional, retrospective study. Medical records from 6 institutions were reviewed for cases of traumatic bile peritonitis between 2006 and 2022. Clinical presentation, additional injuries, surgical treatment, and outcome were recorded. RESULTS: Trauma occurred a median of 2 (range, 1 to 22) and 4 (range, 1 to 22) days prior to presentation in dogs and cats, respectively. Total bilirubin was increased in 11 of 13 dogs and 2 of 4 cats. Rupture occurred at the common bile duct (CBD) in 10 dogs and 1 cat, gallbladder in 3 dogs, cystic duct in 2 cats, and hepatic duct in 1 dog and 1 cat. The most common surgeries were cholecystoduodenostomy and CBD repair in dogs and cholecystectomy in cats. Eleven of 13 dogs and all cats survived to hospital discharge (88.2% overall survival). Median follow-up in surviving dogs and cats was 35 days (range, 14 to 401) and 30 days (range, 14 to 90), respectively. One dog that underwent cholecystectomy experienced recurrent bile peritonitis 20 days postoperatively. Short-term survival following surgical treatment of traumatic bile peritonitis was excellent and recurrence appears uncommon. The most frequent site of rupture was the CBD in dogs and the cystic duct in cats. CLINICAL RELEVANCE: Measurement of peritoneal bilirubin should be considered in dogs and cats with peritoneal effusion following trauma. Surgeons should be prepared to identify and address ruptures in locations other than the gallbladder.

Performance of EOM-CCSD(T)(a)*-Based Quartic Force Fields in Computing Fundamental, Anharmonic Vibrational Frequencies of Molecular Electronically Excited States with Application to the Ã1A″ State of :CCH2 (Vinylidene).

Highly accurate anharmonic vibrational frequencies of electronically excited states are not as easily computed as their ground electronic state counterparts, but recently developed approximate triple excited state methods may be changing that. One emerging excited state method is equation of motion coupled cluster theory at the singles and doubles level with perturbative triples computed via the (a)* formalism, EOMEE-CCSD(T)(a)*. One of the most employed means for the ready computation of vibrational anharmonic frequencies for ground electronic states is second-order vibrational perturbation theory (VPT2), a theory based on quartic force fields (QFFs),fourth-order Taylor series expansions of the potential portion of the internuclear Watson Hamiltonian. The combination of these two is herein benchmarked for its performance for use as a means of computing rovibrational spectra of electronically excited states. Specifically, the EOMEE-CCSD(T)(a)* approach employing a complete basis set extrapolation along with core electron inclusion and relativity (the so-called "CcCR" approach) defining the QFF produces anharmonic fundamental vibrational frequencies within 2.83%, on the average, of reported gas-phase experimentally assigned values for the test set including the A~1A″ states of HCF, HCCl, HSiF, HNO, and HPO. However, some states have exceptional accuracy in the fundamentals, most notably for ν2 of A~1A″ HCCl in which the CcCR QFF value is within 1.8 cm-1 at 927.9 cm-1 (or 0.2%) of the experiment. Additionally, this approach produces rotational constants to, on the absolute average, within 0.41% of available experimental data, showcasing notable accuracy in the computation of rovibronic spectral data. Furthermore, utilizing a hybrid approach composed of harmonic CcCR force constants along with a set of simple EOMEE-CCSD(T)(a)*/aug-cc-pVQZ QFF cubic and quartic force constants is faster than using pure CcCR and better represents those modes that suffer from numerical instability in the anharmonic portion of the QFF, implying that this so-called "CcCR + QZ" QFF approach may be the best for future applications. Finally, complete, rovibrational spectral data are provided for A~1A2 :CCH2, a molecule of potential astrochemical interest, in order to aid in its potential future experimental rovibronic characterization.

DFT + F12 QFFs for Cost-Effective Rovibrational Spectral Data Predictions of Ground and Excited Electronic States.

The quest for faster computation of anharmonic vibrational frequencies of both ground and excited electronic states has led to combining coupled cluster theory harmonic force constants with density functional theory cubic and quartic force constants for defining a quartic force field (QFF) utilized in conjunction with vibrational perturbation theory at second order (VPT2). This work shows that explicitly correlated coupled cluster theory at the singles, doubles, and perturbative triples levels [CCSD(T)-F12] provides accurate anharmonic vibrational frequencies and rotational constants when conjoined with any of B3LYP, CAM-B3LYP, BHandHLYP, PBE0, and ωB97XD for roughly one-quarter of the computational time of the CCSD(T)-F12 QFF alone for our test set. As the number of atoms in the molecule increases, however, the anharmonic terms become a greater portion of the QFF, and the cost comparison improves with HOCO+ and formic acid, requiring less than 15 and 10% of the time, respectively. In electronically excited states, PBE0 produces more consistently accurate results. Additionally, as the size of the molecule and, in turn, QFF increase, the cost savings for utilizing such a hybrid approach for both ground- and excited-state computations grows. As such, these methods are promising for predicting accurate rovibrational spectral properties for electronically excited states. In cases where well-behaved potentials for a small selection of targeted excited states are needed, such an approach should reduce the computational cost compared to that of methods requiring semiglobal potential surfaces or variational treatments of the rovibronic Hamiltonian. Such applications include spectral characterization of comets, exoplanets, or any situation in which gas phase molecules are being excited by UV-vis radiation.

COVID-19 risk communication gaps, needs, and strategies related to pandemic preparedness plans among vulnerable, Black American subgroups: A qualitative study.

OBJECTIVE: Improving current and future risk communication plans is critical to mitigate the COVID-19 pandemic and begin to prepare for future pandemics. Minority groups, particularly African Americans, have been limited in engagement to prepare these plans which has been demonstrated to be disadvantageous. We report findings from a qualitative study that describes gaps, needs, and strategies to improve communication among vulnerable, Black American subgroups during the COVID-19 pandemic. METHODS: Sixty-two Black Americans in uniquely, vulnerable subgroups participated in qualitative, semi-structured interviews from May to September 2020. Thematic analyses were used to identify themes. RESULTS: Participants were 16 essential workers, 16 parents, 15 young adults, and 15 individuals with underlying medical conditions. Emerging themes were: (1) Poor communication and miscommunication fueled fear and confusion; (2) Information sources and channels: How do I choose one?; (3) Communication needs were simple yet complex; (4) All information sources are not trusted information sources; (5) Preferred yet trusted channels and types of information; and (6) Dissemination of COVID Research: Why and How. Subgroups varied in information sources and processes for choosing the source, communication needs, and channels and types of information needed. They shared why they did and did not trust certain sources along with the importance of COVID research dissemination to promote informed decision-making throughout the pandemic. DISCUSSION: This study found that Black American subgroups had diverse, yet trusted and non-trusted messages, messengers, and strategies for communication and wanted research results disseminated. We describe multi-level stakeholders and strategies to help improve risk communication for pandemics, and potentially preparedness and health outcomes.

Early life adversity and psychopathology in preschoolers: mechanisms and moderators.

Developmental theories suggest that exposure to early life adversity (ELA) alters developing emotional response systems, predicting risk for psychopathology across the life span. The present study examines whether negative emotionality (NE), a trait-like measure of emotionality that develops during early childhood, mediates the association between ELA and psychopathology in a representative sample of 917 preschoolers (Mage = 3.84). Additionally, we explored whether cognitive control, which supports attentional focusing and inhibition and has been identified as a transdiagnostic protective factor, moderates the impact of heightened emotionality following adversity on psychopathology risk. We utilized parent report of adversity, psychopathology, and NE and parent report and task-based measures of cognitive control. Structural equation modeling of cross-sectional data revealed that NE partially mediated the link between ELA and psychopathology symptoms. Moreover, parent-reported cognitive control buffered this link such that the effect of ELA on psychopathology through NE was stronger in children with low versus high cognitive control. These results identify elevated NE as one mechanism linking ELA and psychopathology, specifically among children with poorer top-down control, informing our understanding of key risk and protective factors among adversity-exposed children.

Deletion of the inhibitory co-receptor CTLA-4 enhances and invigorates chimeric antigen receptor T cells.

Chimeric antigen receptor (CAR) T cell therapy targeting CD19 has achieved tremendous success treating B cell malignancies; however, some patients fail to respond due to poor autologous T cell fitness. To improve response rates, we investigated whether disruption of the co-inhibitory receptors CTLA4 or PD-1 could restore CART function. CRISPR-Cas9-mediated deletion of CTLA4 in preclinical models of leukemia and myeloma improved CAR T cell proliferation and anti-tumor efficacy. Importantly, this effect was specific to CTLA4 and not seen upon deletion of CTLA4 and/or PDCD1 in CAR T cells. Mechanistically, CTLA4 deficiency permitted unopposed CD28 signaling and maintenance of CAR expression on the T cell surface under conditions of high antigen load. In clinical studies, deletion of CTLA4 rescued the function of T cells from patients with leukemia that previously failed CAR T cell treatment. Thus, selective deletion of CTLA4 reinvigorates dysfunctional chronic lymphocytic leukemia (CLL) patient T cells, providing a strategy for increasing patient responses to CAR T cell therapy.

Genomic assessment of invasion dynamics of SARS-CoV-2 Omicron BA.1.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) now arise in the context of heterogeneous human connectivity and population immunity. Through a large-scale phylodynamic analysis of 115,622 Omicron BA.1 genomes, we identified >6,000 introductions of the antigenically distinct VOC into England and analyzed their local transmission and dispersal history. We find that six of the eight largest English Omicron lineages were already transmitting when Omicron was first reported in southern Africa (22 November 2021). Multiple datasets show that importation of Omicron continued despite subsequent restrictions on travel from southern Africa as a result of export from well-connected secondary locations. Initiation and dispersal of Omicron transmission lineages in England was a two-stage process that can be explained by models of the country's human geography and hierarchical travel network. Our results enable a comparison of the processes that drive the invasion of Omicron and other VOCs across multiple spatial scales.

Two cases of severe pulmonary toxicity from highly active mesothelin-directed CAR T cells.

Multiple clinical studies have treated mesothelin (MSLN)-positive solid tumors by administering MSLN-directed chimeric antigen receptor (CAR) T cells. Although these products are generally safe, efficacy is limited. Therefore, we generated and characterized a potent, fully human anti-MSLN CAR. In a phase 1 dose-escalation study of patients with solid tumors, we observed two cases of severe pulmonary toxicity following intravenous infusion of this product in the high-dose cohort (1-3 × 108 T cells per m2). Both patients demonstrated progressive hypoxemia within 48 h of infusion with clinical and laboratory findings consistent with cytokine release syndrome. One patient ultimately progressed to grade 5 respiratory failure. An autopsy revealed acute lung injury, extensive T cell infiltration, and accumulation of CAR T cells in the lungs. RNA and protein detection techniques confirmed low levels of MSLN expression by benign pulmonary epithelial cells in affected lung and lung samples obtained from other inflammatory or fibrotic conditions, indicating that pulmonary pneumocyte and not pleural expression of mesothelin may lead to dose-limiting toxicity. We suggest patient enrollment criteria and dosing regimens of MSLN-directed therapies consider the possibility of dynamic expression of mesothelin in benign lung with a special concern for patients with underlying inflammatory or fibrotic conditions.

Analysis of sunscreens and antibiotics in groundwater during the Covid-19 pandemic in the Riviera Maya, Mexico.

Tourism contributes to groundwater pollution, but quantifying its exact impact is challenging due to the presence of multiple pollution sources. However, the COVID-19 pandemic presented a unique opportunity to conduct a natural experiment and assess the influence of tourism on groundwater pollution. One such tourist destination is the Riviera Maya in Quintana Roo, Mexico (specifically Cancun). Here, water contamination occurs due to the addition of sunscreen and antibiotics during aquatic activities like swimming, as well as from sewage. In this study, water samples were collected during the pandemic and when tourists returned to the region. Samples were taken from sinkholes (cenotes), beaches, and wells then tested using liquid chromatography for antibiotics and active ingredients found in sunscreens. The data revealed that contamination levels from specific sunscreens and antibiotics persisted even when tourists were absent, indicating that local residents significantly contribute to groundwater pollution. However, upon the return of tourists, the diversity of sunscreen and antibiotics found increased, suggesting that tourists bring along various compounds from their home regions. During the initial stages of the pandemic, antibiotic concentrations were highest, primarily due to local residents incorrectly using antibiotics to combat COVID-19. Additionally, the research found that tourist sites had the greatest contribution to groundwater pollution, with sunscreen concentration increasing. Furthermore, installation of a wastewater treatment plant decreased overall groundwater pollution. These findings enhance our understanding of the pollution contributed by tourists in relation to other pollution sources.

Risk for Depressive Symptoms Among Adolescents with a History of Adversity: Unique Role of Stress Appraisals.

Lifetime social adversity predicts elevated depressive symptoms in adolescence. However, most adversity-exposed youth do not develop depression, highlighting the importance of examining risk and protective factors. The present study leveraged a multi-method approach, incorporating self-report, interview, and independent coding to examine whether appraisals of recent stressors moderate the effect of social adversity on depressive symptoms in 81 adolescent girls (Mage = 16.30 years, SD = .85). We utilized semi-structured interviews of lifetime adversity and recent stressors and semi-structured interviews and self-reports of depressive symptoms. Stress appraisals were calculated by regressing youths' subjective estimations of event stressfulness and dependence on estimations of independent coders. Lifetime social adversity predicted elevated depressive symptoms more strongly in girls who appraised interpersonal events as more stressful and dependent on their actions, providing insight into individual differences in depressive symptoms in adversity-exposed adolescents.

Correction: Development of a Tailored Mobile Phone-Based Intervention to Facilitate Parent-Child Communication and Build Human Papillomavirus Vaccine Confidence: Formative Qualitative Study.

[This corrects the article DOI: 10.2196/43041.].

F12+EOM Quartic Force Fields for Rovibrational Predictions of Electronically Excited States.

Quartic force fields (QFFs) constructed using a sum of ground-state CCSD(T)-F12b energies with EOM-CCSD excitation energies are proposed for computation of spectroscopic properties of electronically excited states. This is dubbed the F12+EOM approach and is shown to provide similar accuracy to previous methodologies at lower computational cost. Using explicitly correlated F12 approaches instead of canonical CCSD(T), as in the corresponding (T)+EOM approach, allows for 70-fold improvement in computational time. The mean percent difference between the two methods for anharmonic vibrational frequencies is only 0.10%. A similar approach is also developed herein which accounts for core correlation and scalar relativistic effects, named F12cCR+EOM. The F12+EOM and F12cCR+EOM approaches both match to within 2.5% mean absolute error of experimental fundamental frequencies. These new methods should help in clarifying astronomical spectra by assigning features to vibronic and vibrational transitions of small astromolecules when such data are not available experimentally.

Tissue-resident memory CAR T cells with stem-like characteristics display enhanced efficacy against solid and liquid tumors.

Chimeric antigen receptor (CAR) T cells demonstrate remarkable success in treating hematological malignancies, but their effectiveness in non-hematopoietic cancers remains limited. This study proposes enhancing CAR T cell function and localization in solid tumors by modifying the epigenome governing tissue-residency adaptation and early memory differentiation. We identify that a key factor in human tissue-resident memory CAR T cell (CAR-TRM) formation is activation in the presence of the pleotropic cytokine, transforming growth factor ß (TGF-ß), which enforces a core program of both "stemness" and sustained tissue residency by mediating chromatin remodeling and concurrent transcriptional changes. This approach leads to a practical and clinically actionable in vitro production method for engineering peripheral blood T cells into a large number of "stem-like" CAR-TRM cells resistant to tumor-associated dysfunction, possessing an enhanced ability to accumulate in situ and rapidly eliminate cancer cells for more effective immunotherapy.

Application of lean principles in a medicare insurance counseling service learning course.

BACKGROUND: Lean principles are increasingly applied in healthcare to improve quality and cost. A service-learning course providing Medicare insurance counseling requiring rapid transformation due to the COVID-19 pandemic provided an opportunity for pharmacy students to apply lean skills. EDUCATIONAL ACTIVITY: Students, already introduced to lean skills earlier in their curriculum, enrolled in the insurance education certificate during their third year in Fall 2020. Students were oriented to the mandated service delivery restrictions. After a review of lean principles, students analyzed existing process for in-person counseling using a value-stream map. Students worked in teams to complete a cause analysis and develop solutions. Collaboratively, students clarified the value of the Medicare insurance counseling services to the community, adapted these components to accommodate environmental risk, and developed standard work for client acquisition, communication procedures, and service delivery to optimize client satisfaction and safety. Outcomes compared before and after application of lean skills included number of pharmacy students completing insurance counselor training, number of clients counseled, and the mean out-of-pocket savings identified for Medicare beneficiaries. FINDINGS: Students applied lean skills to transform an insurance counseling service by developing and implementing a future state value-stream map and new standard work. Overall Medicare insurance counseling service metrics decreased compared to previous years, but the service was sustained despite pandemic restrictions. Application of lean skills and service redesign provided a method for students to provide services via telepharmacy. Application of lean principles increased student engagement with the course and provided an opportunity to practice quality improvement skills. Lean provides a flexible set of skills that can be introduced and applied in different pharmacy instructional settings.

Development of a Tailored Mobile Phone-Based Intervention to Facilitate Parent-Child Communication and Build Human Papillomavirus Vaccine Confidence: Formative Qualitative Study.

BACKGROUND: Human papillomavirus (HPV) vaccine hesitancy is on the rise, and provider communication is a first-line strategy to address parental concerns. The use of the presumptive approach and motivational interviewing by providers may not be enough to influence parental decision-making owing to the providers' limited time, self-efficacy, and skills to implement these strategies. Interventions to enhance provider communication and build parental HPV vaccine confidence have been undertested. Delivering tailored patient education to parents via mobile phones before they visit the health care provider may address time constraints during clinic visits and positively affect vaccine uptake. OBJECTIVE: This study aimed to describe the development and evaluate the acceptability of a mobile phone-based, family-focused intervention guided by theory to address concerns of HPV vaccine-hesitant parents before the clinic visit, as well as explore intervention use to facilitate parent-child communication. METHODS: The health belief model and theory of reasoned action guided intervention content development. A multilevel stakeholder engagement process was used to iteratively develop the HPVVaxFacts intervention, including a community advisory board review, a review by an advisory panel comprising HPV vaccine-hesitant parents, a health communications expert review, semistructured qualitative interviews with HPV vaccine-hesitant parents (n=31) and providers (n=15), and a content expert review. Inductive thematic analysis was used to identify themes in the interview data. RESULTS: The qualitative interviews yielded 4 themes: overall views toward mobile device use for health information, acceptability of HPVVaxFacts, facilitators of HPVVaxFacts use, and barriers to HPVVaxFacts use. In parent interviews after reviewing HPVVaxFacts prototypes, almost all parents (29/31, 94%) stated they intended to have their child vaccinated. Most of the parents stated that they liked the added adolescents' corner to engage in optional parent-child communication (ie, choice to share and discuss information with their child; 27/31, 87%) and shared decision-making in some cases (8/31, 26%). After incorporating all input, the final intervention consisted of a 10-item survey to identify the top 3 concerns of parents, followed by tailored education that was mapped to each of the following concerns: evidential messages, images or graphics to enhance comprehension and address low literacy, links to credible websites, a provider video, suggested questions to ask their child's physician, and an optional adolescents' corner to educate the patient and support parent-child communication. CONCLUSIONS: The multilevel stakeholder-engaged process used to iteratively develop this novel intervention for HPV vaccine-hesitant families can be used as a model to develop future mobile health interventions. This intervention is currently being pilot-tested in preparation for a randomized controlled trial aiming to increase HPV vaccination among adolescent children of vaccine-hesitant parents in a clinic setting. Future research can adapt HPVVaxFacts for other vaccines and use in other settings (eg, health departments and pharmacies).