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Background and Aims: Endoscopic mucosal resection (EMR) of large colorectal lesions can be challenging, and residual lesions after EMR can progress to colorectal cancer. We aimed to assess the efficacy and safety of adding thermal ablation of margins [using argon plasma coagulation (APC) or snare tip soft coagulation (STSC)] in reducing recurrence rates after EMR., Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) identified from PubMed, Cochrane Library, and Embase. The primary outcome was the recurrence rate. Secondary outcomes were overall adverse events (AEs) and delayed bleeding. We pre-specified subgroup analyses by lesion size, thermal ablation technique, and resection type. The random-effects model was used to calculate the pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed using the Cochran's Q test and I 2 statistics., Results: We included four RCTs (815 patients and 872 colorectal lesions). Thermal ablation reduced recurrence rates [RR 0.31; 95%CI (0.20-0.47); I 2  = 0%], while the risk of overall AEs [RR 0.93; 95%CI (0.73-1.17); I 2  = 0%] was similar between both groups. The results were consistent in subgroup analyses of APC, STSC, polyps > 20 mm, and piece-meal resection., Conclusion: Thermal ablation of margins following EMR reduced recurrence rates while maintaining a comparable safety profile., Competing Interests: Declarations. Disclosures: Paula Santo, Gilmara Coelho Meine, Erica Uchoa Holanda, Eduardo Cerchi Barbosa, Stefano Baraldo, Angelica Luciana Nau, and Karollyna Maria Henry Moore have no conflicts of interest or financial ties to disclose., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ethylene glycol dinitrate (EGDN) is a nitrate ester explosive widely used in military ordnance and missile systems. This study investigates the decomposition dynamics of the EGDN cation using a comprehensive approach that combines femtosecond time-resolved mass spectrometry (FTRMS) experiments with ab initio electronic structure and molecular dynamics computations. We identify three distinct dissociation time scales for the metastable EGDN cation of approximately 40-60 fs, 340-450 fs, and >2 ps. The observed dissociation time scales are rationalized by electronic and geometric relaxation of multiple EGDN conformers. These insights are crucial for advancing knowledge of the initial molecular decomposition processes that are central to the detonation physics of nitrate esters, which can lead to improving safety protocols and optimizing the performance of nitrate ester explosives in various applications.

Introduction: This paper developed and used practice vignettes to understand sexual assault nurse examiners' perceptions of self-confidence to provide care for Black, Indigenous, and transgender sexual violence survivors. Sexual assault nurse examiners are uniquely positioned to provide patient-centered postsexual violence health care but not all sexual assault nurse examiners receive culturally specific and identity-affirming training. Black/African American, Indigenous, and/or transgender people disproportionately experience sexual violence but may receive poorer health care after sexual violence compared with white cisgender people. Understanding sexual assault nurse examiner confidence to provide this care is paramount to improving sexual assault nurse examiner training and patient outcomes., Methods: In collaboration with a nurse advisory board, researchers developed and validated 3 case vignettes that manipulated the race or gender of the patient. A fourth previously validated vignette that assessed sexual assault nurse examiner care for a transgender patient also was administered. Sexual assault nurse examiners then answered questions about their confidence to provide (1) a patient-centered safety plan, (2) patient-centered referrals, and (3) care without personal biases influencing care. The current study used a cross-sectional online self-report survey with 4 sexual assault nurse examiner patient vignettes randomized across a convenience sample of 70 sexual assault nurse examiners recruited from a midwestern state., Results: On average, sexual assault nurse examiners rated the vignettes as realistic. Sexual assault nurse examiners reported lower confidence to develop a patient-centered safety plan, provide care without allowing personal biases to influence that care, and provide patient-centered referrals for Black, Indigenous, and/or transgender survivors compared with white cisgender survivors., Discussion: Training and mentorship programs could improve sexual assault nurse examiner confidence to provide trauma- and violence-informed care for Black, Indigenous, and transgender survivors, and vignettes could be used to measure changes in confidence owing to training., (Copyright © 2024 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Despite advances in obstetric care, postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. Prior reviews of studies published through 2016 suggest an association of antidepressant use during late pregnancy and increased risk of PPH. However, a causal link between prenatal antidepressants and PPH remains controversial. Objectives: This systematic literature review aimed to synthesize the empirical evidence on the association of antidepressant exposure in late pregnancy with the risk of PPH, including studies published before and after 2016. Methods: A systematic literature search was conducted using PubMed, OVID Medline, EMBASE, SCOPUS, PsycINFO, and CINAHL from inception to September 9, 2023. Original, peer-reviewed studies (published in English) that reported on the frequency or risk of PPH in women with evidence of antidepressant use during pregnancy and included at least one control group were included. Results: Twenty studies (eight published after 2016) met inclusion criteria, most of which focused on the risks of PPH associated with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). The main findings from the individual studies were mixed, but the majority documented statistically significant associations of PPH with late prenatal exposure, especially for exposures occurring within 30 days of delivery, compared with unexposed deliveries. Fourteen studies addressed underlying antidepressant indications or their correlates. Few studies focused on prenatal antidepressants and the risk of well-defined severe PPH or on antidepressant dose changes and general PPH risk. None examined competing risks of antidepressant discontinuation on mental health outcomes. Conclusions: Late pregnancy exposure to antidepressants may be a minor risk factor for PPH, but it is unclear to what extent reported associations are causal in nature, as opposed to correlational (effects related to nonpharmacological factors including maternal indication). For patients needing antidepressants during pregnancy, current evidence does not favor routinely discontinuing antidepressants specifically to reduce the risk of PPH.

Pulsed laser ablation in organic solvents is widely used to produce oxide-free metal and metal carbide nanoparticles, often with carbon coatings resulting from laser-induced reactions in the organic solvent. To gain insight into how the molecular structure of the solvent affects these reaction pathways, this work investigates ablation of the C 6 H 14 isomers n -hexane, 2-methylpentane, and 3-methylpentane through characterization of the gas and liquid products with mass spectrometry. Ablation of each C 6 H 14 isomer produces a distinct distribution of product molecular weights and isomers. 2-methylpentane preferentially produces C 3 and C 9 , whereas 3-methylpentane produces C 2 , C 4 , C 8 , and C 10 products. These preferential product distributions, along with the lack of such selectivity in n -hexane, arise from differences in the most favorable C-C bond scission pathways in each C 6 H 14 isomer. Moreover, the particular isomers of C 8 H 18 , C 9 H 20 , C 10 H 22 , and C 12 H 26 produced by ablation of each C 6 H 14 isomer indicate that the vast majority of reaction pathways involve addition reactions between a fragment radical and parent C 6 H 14 or between two C 6 H 14 molecules, without molecular rearrangement. This propensity toward direct addition suggests that the chemical reactions induced by ultrashort pulsed laser ablation proceed on faster time scales than those of radical rearrangements.

Introduction: Lithium remains a gold standard treatment for bipolar disorder including during peripartum. Historically, guidelines advised against breastfeeding while taking lithium though recent data suggest it is acceptable for a healthy infant. Lack of awareness of acceptability contributes to decreased patient and clinician comfort and low breastfeeding rates. We report current breastfeeding rates, monitoring practices, and infant outcomes with lithium exposure in breastmilk at our institution. Methods: A retrospective chart review was conducted at a single academic medical center using records from 2013 to 2023. Electronic medical records were queried to identify patients prescribed lithium postpartum. Data were collected on timing of lithium initiation, lithium dose and concentration, breastfeeding status, and infant outcomes. Results: A total of 18 cases of lithium use in the postpartum period were identified. A total of 39% ( n = 7) of patients taking lithium postpartum breastfed. Most patients, 61% ( n = 11), initiated lithium prior to pregnancy, 11% ( n = 2) initiated during pregnancy and 27% ( n = 5) started postpartum. Four infant charts were reviewed with no reports of adverse events. Of these infants, average maternal lithium dose was 750 mg daily, with an average maternal serum lithium concentration of 0.62 mmol/L and average infant serum lithium concentration of 0.16 mmol/L. Conclusion: Our data demonstrate most patients using lithium postpartum have been taking lithium long-term and are not breastfeeding. Lithium exposure in breastmilk appears to be tolerated by healthy infants. There is a need for ongoing research and education on acceptability and infant monitoring recommendations to support patients who would like to breastfeed while on lithium.

Waning immunity and the emergence of immune evasive SARS-CoV-2 variants jeopardize vaccine efficacy leading to breakthrough infections. We have previously shown that innate immune cells play a critical role in controlling SARS-CoV-2. To investigate the innate immune response during breakthrough infections, we modeled breakthrough infections by challenging low-dose vaccinated mice with a vaccine-mismatched SARS-CoV-2 Beta variant. We found that low-dose vaccinated infected mice had a 2-log reduction in lung viral burden, but increased immune cell infiltration in the lung parenchyma, characterized by monocytes, monocyte-derived macrophages, and eosinophils. Single cell RNA-seq revealed viral RNA was highly associated with eosinophils that corresponded to a unique IFN-γ biased signature. Antibody-mediated depletion of eosinophils in vaccinated mice resulted in increased virus replication and dissemination in the lungs, demonstrating that eosinophils in the lungs are protective during SARS-CoV-2 breakthrough infections. These results highlight the critical role for the innate immune response in vaccine mediated protection against SARS-CoV-2.

Background: Intimate Partner Violence (IPV) is a significant public health concern that disproportionately impacts Indigenous American women more than any other ethnic/racial group in the United States., Purpose: This study aims to inform the work of nurses and allied health professionals by providing insight into the lived realities of Indigenous women in urban areas and how IPV manifests in the lives of Indigenous women., Methods: Postcolonial and Indigenous feminist frameworks informed this qualitative study. Using thematic analysis, we analyzed data from semi-structured individual interviews with 34 Indigenous women in large urban areas in the upper Midwest., Findings: This manuscript discusses one broad theme: experiences of IPV during pregnancy and the devastating impacts on women and their children in the form of intergenerational trauma. Under this broad theme, we identified two sub-themes: impacts of IPV on individual pregnancy experiences and linkages to adverse pregnancy-related outcomes related to physical IPV during the childbearing years., Conclusion: This Indigenous-led study informs the development of effective Indigenous-specific interventions to minimize barriers to accessing prenatal care and help-seeking when experiencing IPV to reduce the devastating consequences for Indigenous women and their families., Competing Interests: Declaration of competing interest The authors have disclosed that they have no significant relationships with or financial interest in any commercial companies pertaining to this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The effects of immunodeficiency associated with chronic HIV infection on COVID-19 disease and viral persistence have not been directly addressed in a controlled setting. In this pilot study, we exposed two pigtail macaques (PTMs) chronically infected with SIVmac239, exhibiting from very low to no CD4 T cells across all compartments, to SARS-CoV-2. We monitored the disease progression, viral replication, and evolution, and compared these outcomes with SIV-naïve PTMs infected with SARS-CoV-2. No overt signs of COVID-19 disease were observed in either animal, and the SARS-CoV-2 viral kinetics and evolution in the SIVmac239 PTMs were indistinguishable from those in the SIV-naïve PTMs in all sampled mucosal sites. However, the single-cell RNA sequencing of bronchoalveolar lavage cells revealed an infiltration of functionally inert monocytes after SARS-CoV-2 infection. Critically, neither of the SIV-infected PTMs mounted detectable anti-SARS-CoV-2 T-cell responses nor anti-SARS-CoV-2 binding or neutralizing antibodies. Thus, HIV-induced immunodeficiency alone may not be sufficient to drive the emergence of novel viral variants but may remove the ability of infected individuals to mount adaptive immune responses against SARS-CoV-2.

Background: Forensic nurse examiners, including sexual assault nurse examiners, provide care for survivors holistically through healthcare, emotional support, connection to follow-up care, safety planning, and, if desired, evidence collection to aid in the prosecution of sexual assault. There is increasing recognition that trauma-informed care must also include an understanding of the impacts of structural violence on minoritized patients to ensure health equity., Aim: To help address this guidance gap, we expanded Campbell and colleagues' empowering care model using a trauma- and violence-informed care (TVIC) lens., Methods: We used an iterative discussion-based process that included five joint meetings between a seven-member transdisciplinary research team and a five-member nurse advisory board., Results: In a TVIC-informed empowering care model, we propose behavioral examples for forensic nurses for each of Campbell et al.'s five key domains of empowering care for forensic nurse examinations (i.e., build rapport and establish trust, show compassion, provide patient-directed care, convey professionalism, and provide resource referral and follow-up)., Conclusions: These behavioral examples for nurses can help guide forensic nurse training and practice to reduce disparities in treatment and follow-up support. Structures and systems are needed that enable forensic nurses to provide trauma- and violence-informed empowering care to survivors of sexual assault and, over time, increase the accessibility of forensic nurse examinations and improve patient outcomes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 International Association of Forensic Nurses.)

Zika virus (ZIKV) is a mosquito-borne flavivirus that caused an epidemic in the Americas in 2016 and is linked to severe neonatal birth defects, including microcephaly and spontaneous abortion. To better understand the host response to ZIKV infection, we adapted the 10× Genomics Chromium single-cell RNA sequencing (scRNA-seq) assay to simultaneously capture viral RNA and host mRNA. Using this assay, we profiled the antiviral landscape in a population of human monocyte-derived dendritic cells infected with ZIKV at the single-cell level. The bystander cells, which lacked detectable viral RNA, expressed an antiviral state that was enriched for genes coinciding predominantly with a type I interferon (IFN) response. Within the infected cells, viral RNA negatively correlated with type I IFN-dependent and -independent genes (the antiviral module). We modeled the ZIKV-specific antiviral state at the protein level, leveraging experimentally derived protein interaction data. We identified a highly interconnected network between the antiviral module and other host proteins. In this work, we propose a new paradigm for evaluating the antiviral response to a specific virus, combining an unbiased list of genes that highly correlate with viral RNA on a per-cell basis with experimental protein interaction data., Importance: Zika virus (ZIKV) remains a public health threat given its potential for re-emergence and the detrimental fetal outcomes associated with infection during pregnancy. Understanding the dynamics between ZIKV and its host is critical to understanding ZIKV pathogenesis. Through ZIKV-inclusive single-cell RNA sequencing (scRNA-seq), we demonstrate on the single-cell level the dynamic interplay between ZIKV and the host: the transcriptional program that restricts viral infection and ZIKV-mediated inhibition of that response. Our ZIKV-inclusive scRNA-seq assay will serve as a useful tool for gaining greater insight into the host response to ZIKV and can be applied more broadly to the flavivirus field., Competing Interests: The authors declare no conflict of interest.

Background: Psychiatric disorders differ in their prevalence, symptom profiles, and disease courses in men and women. However, sex differences in psychiatric disorders have not received enough attention to guide treatment recommendations. This systematic review aims to summarize sex differences in the treatment responses and adverse effects of mood stabilizers and antipsychotics transdiagnostically., Methods: We conducted a systematic review following the PRISMA 2020 statement (CRD42020212478). A literature search was conducted using MEDLINE, Embase, Cochrane Central, PsycINFO, Web of Science Core Collection, and Scopus databases. Studies comparing mood stabilizer or antipsychotic treatment outcomes in men and women were included. JBI critical appraisal checklists were used to assess bias risk., Results: Out of 4866 records, 129 reports (14 on mood stabilizers, 115 on antipsychotics) with varying designs were included. Sample sizes ranged from 17 to 22,774 participants (median = 147). The most common psychiatric diagnoses were schizophrenia spectrum (n = 109, 84.5 %) and bipolar disorders (n = 38, 29.5 %). Only four studies explored sex differences in mood stabilizer treatment response. In 40 articles on antipsychotic treatment response, 18 indicated no sex difference, while 16 showed females had better outcomes. Women had more adverse effects with both mood stabilizers and antipsychotics. The risk of bias was low in 84 (65.1 %) of studies., Limitations: Substantial heterogeneity among the studies precluded performing a meta-analysis., Conclusion: Number of studies focusing on sex differences in treatment outcomes of mood stabilizers is limited. Women may respond better to antipsychotics than men, but also experience more side effects. The impact of pharmacokinetics on sex differences warrants more attention., Competing Interests: Declaration of competing interest ME's spouse is an employee of Sanofi. MAF has received grant support from Assurex Health and Mayo Foundation, received CME travel and honoraria from Carnot Laboratories and American Physician Institute, and has Financial Interest / Stock ownership / Royalties from Chymia LLC. All other authors report no financial relationships with commercial interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

0rtho -Nitroaniline (ONA) is a model for the insensitive high explosive 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) that shares strong hydrogen bonding character between adjacent nitro and amino groups. This work reports femtosecond time-resolved mass spectrometry (FTRMS) measurements and theoretical calculations that explain the high stability of the ONA cation compared with related nitroaromatic molecules. Ab initio calculations found that the lowest-lying electronic excited state of the ONA cation, D 1 , lies more than 2 eV above the ground state, and the energetic barriers to rearrangement and dissociation reactions exceed this D 1 energy. These theoretical results were confirmed by FTRMS pump-probe measurements showing that (1) fragment ions represented less than 30% of the total ion yield when a 10 14 W cm -2 , 1300 nm, 20 fs pump pulse was used to ionize ONA; and (2) 3.1 eV (400 nm) photons were required to induce dissociation of the ONA cation. Stronger coupling between the ground D 0 and excited D 4 states of the ONA cation at the geometry of neutral ONA resulted in a transient enhancement of fragment ion yields at <300 fs pump-probe delay times, prior to relaxation of the ONA cation to its optimal geometry.

There is increasing interest in individualizing treatment selection for more than 25 regulatory approved treatments for major depressive disorder (MDD). Despite an inconclusive efficacy evidence base, antidepressants (ADs) are prescribed for the depressive phase of bipolar disorder (BD) with oftentimes, an inadequate treatment response and or clinical concern for mood destabilization. This study explored the relationship between antidepressant response in MDD and antidepressant-associated treatment emergent mania (TEM) in BD. We conducted a genome-wide association study (GWAS) and polygenic score analysis of TEM and tested its association in a subset of BD-type I patients treated with SSRIs or SNRIs. Our results did not identify any genome-wide significant variants although, we found that a higher polygenic score (PGS) for antidepressant response in MDD was associated with higher odds of TEM in BD. Future studies with larger transdiagnostic depressed cohorts treated with antidepressants are encouraged to identify a neurobiological mechanism associated with a spectrum of depression improvement from response to emergent mania., (© 2024. The Author(s).)

We report a chemically motivated, single-step method to enhance metal deposition onto silicon laser-induced periodic surface structures (LIPSSs) using reactive laser ablation in liquid (RLAL). Galvanic replacement (GR) reactions were used in conjunction with RLAL (GR-RLAL) to promote the deposition of Au and Cu nanostructures onto a Si LIPSS. To increase the deposition of Au, sacrificial metals Cu, Fe, and Zn were used; Fe and Zn also enhanced the deposition of Cu. We show that the deposited metal content, surface morphology, and metal crystallite size can be tuned based on the difference in electrochemical potentials of the deposited and sacrificial metal. Compared to the Au and Cu reference samples, GR more than doubled the metal content on the LIPSS and reduced metal crystallite sizes by up to 20%. The ability to tune the metal content and crystalline domain size simultaneously makes GR-RLAL a potentially useful approach in the manufacturing of functional metal-LIPSS materials such as surface-enhanced Raman spectroscopy substrates.

Imipramine class tricyclic antidepressants have low ionization efficiencies that make them difficult to detect by using secondary ion mass spectrometry. Ultraviolet picosecond laser desorption postionization (ps-LDPI-MS) is examined here for the detection of four tricyclic antidepressants: imipramine, desipramine, amitriptyline, and clomipramine. About 30 ps laser pulses at either 213 nm (5.8 eV) or 355 nm (3.5 eV) are used for desorption of samples under vacuum, 7.9 eV (157 nm) fluorine laser pulses are used for post-ionization, and the ions so formed are detected by time-of-flight mass spectrometry. Detection of imipramine by 213 nm ps-LDPI-MS shows less fragmentation than either 355 nm ps-LDPI-MS or prior results from 800 nm fs-LDPI-MS. Ionization energies of imipramine, desipramine, amitriptyline, and clomipramine are predicted using density functional theory calculations and used to explain the corresponding ps-LDPI-MS data for these four compounds as resulting from single-photon ionization. The experimental observation of low-mass amine-containing fragments with calculated ionization energies below 7.9 eV is attributed mostly to dissociation during laser desorption, followed by single-photon ionization of the neutral fragments rather than the more traditional mechanism of unimolecular dissociation following single-photon ionization of the parent molecule.

Persistent and uncontrolled SARS-CoV-2 replication in immunocompromised individuals has been observed and may be a contributing source of novel viral variants that continue to drive the pandemic. Importantly, the effects of immunodeficiency associated with chronic HIV infection on COVID-19 disease and viral persistence have not been directly addressed in a controlled setting. Here we conducted a pilot study wherein two pigtail macaques (PTM) chronically infected with SIVmac239 were exposed to SARS-CoV-2 and monitored for six weeks for clinical disease, viral replication, and viral evolution, and compared to our previously published cohort of SIV-naïve PTM infected with SARS-CoV-2. At the time of SARS-CoV-2 infection, one PTM had minimal to no detectable CD4+ T cells in gut, blood, or bronchoalveolar lavage (BAL), while the other PTM harbored a small population of CD4+ T cells in all compartments. Clinical signs were not observed in either PTM; however, the more immunocompromised PTM exhibited a progressive increase in pulmonary infiltrating monocytes throughout SARS-CoV-2 infection. Single-cell RNA sequencing (scRNAseq) of the infiltrating monocytes revealed a less activated/inert phenotype. Neither SIV-infected PTM mounted detectable anti-SARS-CoV-2 T cell responses in blood or BAL, nor anti-SARS-CoV-2 neutralizing antibodies. Interestingly, despite the diminished cellular and humoral immune responses, SARS-CoV-2 viral kinetics and evolution were indistinguishable from SIV-naïve PTM in all sampled mucosal sites (nasal, oral, and rectal), with clearance of virus by 3-4 weeks post infection. SIV-induced immunodeficiency significantly impacted immune responses to SARS-CoV-2 but did not alter disease progression, viral kinetics or evolution in the PTM model. SIV-induced immunodeficiency alone may not be sufficient to drive the emergence of novel viral variants.

Mice were immunized with a combination of self-amplifying (sa) RNA constructs for the F1 and V antigens of Yersinia pestis at a dose level of 1 μg or 5 μg or with the respective protein sub-units as a reference vaccine. The immunization of outbred OF1 mice on day 0 and day 28 with the lowest dose used (1 μg) of each of the saRNA constructs in lipid nanoparticles protected 5/7 mice against subsequent sub-cutaneous challenge on day 56 with 180 cfu (2.8 MLD) of a 2021 clinical isolate of Y. pestis termed 10-21/S whilst 5/7 mice were protected against 1800cfu (28MLD) of the same bacteria on day 56. By comparison, only 1/8 or 1/7 negative control mice immunized with 10 μg of irrelevant haemagglutin RNA in lipid nanoparticles (LNP) survived the challenge with 2.8 MLD or 28 MLD Y. pestis 10-21/S, respectively. BALB/c mice were also immunized with the same saRNA constructs and responded with the secretion of specific IgG to F1 and V, neutralizing antibodies for the V antigen and developed a recall response to both F1 and V. These data represent the first report of an RNA vaccine approach using self-amplifying technology and encoding both of the essential virulence antigens, providing efficacy against Y. pestis . This saRNA vaccine for plague has the potential for further development, particularly since its amplifying nature can induce immunity with less boosting. It is also amenable to rapid manufacture with simpler downstream processing than protein sub-units, enabling rapid deployment and surge manufacture during disease outbreaks., 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 © 2023 Shattock, Andrianaivoarimanana, McKay, Randriantseheno, Murugaiah, Samnuan, Rogers, Tregoning, Rajerison, Moore, Laws and Williamson.)

Omicron SARS-CoV-2 variants escape vaccine-induced neutralizing antibodies and cause nearly all current COVID-19 cases. Here, we compared the efficacy of three booster vaccines against Omicron BA.5 challenge in rhesus macaques: mRNA-1273, the Novavax ancestral spike protein vaccine (NVX-CoV2373), or Omicron BA.1 spike protein version (NVX-CoV2515). All three booster vaccines induced a strong BA.1 cross-reactive binding antibody and changed immunoglobulin G (Ig) dominance from IgG1 to IgG4 in the serum. All three booster vaccines also induced strong and comparable neutralizing antibody responses against multiple variants of concern, including BA.5 and BQ.1.1, along with long-lived plasma cells in the bone marrow. The ratio of BA.1 to WA-1 spike-specific antibody-secreting cells in the blood was higher in NVX-CoV2515 animals compared with NVX-CoV2373 animals, suggesting a better recall of BA.1-specific memory B cells by the BA.1 spike-specific vaccine compared with the ancestral spike-specific vaccine. Further, all three booster vaccines induced low levels of spike-specific CD4 but not CD8 T cell responses in the blood. After challenge with SARS-CoV-2 BA.5 variant, all three vaccines showed strong protection in the lungs and controlled virus replication in the nasopharynx. In addition, both Novavax vaccines blunted viral replication in nasopharynx at day 2. The protection against SARS-CoV-2 BA.5 infection in the upper respiratory airways correlated with binding, neutralizing, and ADNP activities of the serum antibody. These data have important implications for COVID-19 vaccine development, because vaccines that lower nasopharyngeal virus may help to reduce transmission.

Abstract: The STEERR Mentoring Framework, grounded in decolonized and feminist mentorship approaches, integrates foundational principles of mentoring with the unique and complex characteristics of the role of the forensic nurse. The primary objective of the program is to support a competent, sustainable, and resilient forensic nursing workforce. In this article, we describe the development process, framework structure, and evaluation approach implemented within a 1-year pilot initiative focused on forensic nurses in the sexual assault nurse examiner role. We reflect on strategies for broader application and replication in forensic nursing programs across the United States., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 International Association of Forensic Nurses.)

The present study aimed to describe the personality and psychopathology dimensions reported by veterans seeking organ transplantation, as well as to identify those dimensions associated with subsequent presurgical recommendations and transplant outcomes. Data were collected from 245 veterans undergoing a pretransplant psychological evaluation that included the MMPI-2-RF. Three treatment recommendations resulting from these evaluations, three recommendation adherence variables, and two transplant outcomes were extracted from electronic medical records. The sample's MMPI-2-RF scale scores were compared to the normative sample and two other presurgical samples and contrasted across subgroups defined by organ transplanted. Point-biserial correlations and logistic regression analyses examined associations between MMPI-2-RF scale scores and the eight measured outcomes. Results indicated that over-reporting, internalizing tendencies, negative emotionality, and a lack of positive emotions were uniquely predictive of mental health treatment recommendation, whereas somatic over-reporting, externalizing tendencies, and disinhibition were predictive of substance use treatment recommendation. Veterans who reported higher levels of activation were less likely to initiate mental health treatment. Finally, veterans with greater somatic preoccupation were less likely to be listed for organ transplant. More suspicious and mistrustful veterans were less likely to receive the transplant. These findings offer support for the role of the MMPI-2-RF in veteran pretransplant evaluations.

The influenza A virus causes substantial morbidity and mortality worldwide every year and poses a constant threat of an emergent pandemic. Seasonal influenza vaccination strategies fail to provide complete protection against infection due to antigenic drift and shift. A universal vaccine targeting a conserved influenza epitope could substantially improve current vaccination strategies. The ectodomain of the matrix 2 protein (M2e) of influenza is a highly conserved epitope between virus strains but is also poorly immunogenic. Administration of M2e and the immunostimulatory stimulator of interferon genes (STING) agonist 3'3'-cyclic guanosine-adenosine monophosphate (cGAMP) encapsulated in microparticles made of acetalated dextran (Ace-DEX) has previously been shown to be effective for increasing the immunogenicity of M2e, primarily through T-cell-mediated responses. Here, the immunogenicity of Ace-DEX MPs delivering M2e was further improved by conjugating the M2e peptide to the particle surface in an effort to affect B-cell responses more directly. Conjugated or encapsulated M2e co-administered with Ace-DEX MPs containing cGAMP were used to vaccinate mice, and it was shown that two or three vaccinations could fully protect against a lethal influenza challenge, while only the surface-conjugated antigen constructs could provide some protection against lethal challenge with only one vaccination. Additionally, the use of a reducible linker augmented the T-cell response to the antigen. These results show the utility of conjugating M2e to the surface of a particle carrier to increase its immunogenicity for use as the antigen in a universal influenza vaccine.

Laser synthesis in liquids is often carried out in organic solvents to prevent oxidation of metals during nanoparticle generation and to produce tailored carbon-based nanomaterials. This work investigates laser ablation of neat organic liquids acetone, ethanol, n -hexane, and toluene with pulse widths ranging from 30 fs to 4 ps through measurements of reaction kinetics and characterization of the ablation products with optical spectroscopy and mass spectrometry. Increasing the pulse width from 30 fs to 4 ps impacts both the reaction kinetics and product distributions, suppressing the formation of solvent molecule dimers and oxidized molecules while enhancing the yields of gaseous molecules, sp -hybridized carbons, and fluorescent carbon dots. The observed trends are explained in the context of established ionization mechanisms and cavitation bubble dynamical processes that occur during ultrashort pulsed laser ablation of liquid media. The results of this work have important implications both for controlling the formation of carbon shells around metal nanoparticles during the ablation of solid targets in liquid and producing carbon nanomaterials directly from the ablation of organic liquids without a solid target.

Laser-induced reduction of metal ions is attracting increasing attention as a sustainable route to ligand-free metal nanoparticles. In this work, we investigate the photochemical reactions involved in reduction of Ag + and [AuCl 4 ] - upon interaction with lasers with nanosecond and femtosecond pulse duration, using strong-field ionization mass spectrometry and spectroscopic assays to identify stable molecular byproducts. Whereas Ag + in aqueous isopropyl alcohol (IPA) is reduced through plasma-mediated mechanisms upon femtosecond laser excitation, low-fluence nanosecond laser excitation induces electron transfer from IPA to Ag + . Both nanosecond and femtosecond laser excitation of aqueous [AuCl 4 ] - produce reactive chlorine species by Au-Cl bond homolysis. Formation of numerous volatile products by IPA decomposition during both femtosecond and nanosecond laser excitation of [AuCl 4 ] - is attributed to enhanced optical breakdown by the Au nanoparticle products of [AuCl 4 ] - reduction. These mechanistic insights can inform the design of laser synthesis procedures to improve control over metal nanoparticle properties and enhance byproduct yields.

Despite calls recognizing the need for culturally sensitive responses to minimize the occurrence of secondary victimization for African American women following an experience of sexual assault, few studies have focused on hearing from African American women survivors about their experiences receiving healthcare services in a hospital setting following sexual assault. Employing critical ethnography as our methodology and using intersectionality theory as a lens, we centered the voices of African American women survivors about their experiences receiving nursing care in urban acute care or hospital settings in the Upper Midwest of the United States following sexual assault. In this qualitative study, 30 African American women survivors were interviewed using in-depth, semi-structured interviews about their post-sexual assault care. Interviews were analyzed using thematic analysis. An important theme identified focused on survivors' experiences of dehumanization when receiving healthcare services following sexual assault. These experiences included: discrediting, dismissing, shaming, and blaming. To mitigate and prevent secondary victimization in the future, we present practice and education change recommendations for nurses, and healthcare providers more broadly, based on the voices of African American female survivors of sexual assault., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Tau plays a key role in Alzheimer's disease (AD) pathophysiology, and accumulating evidence suggests that lowering tau may reduce this pathology. We sought to inhibit MAPT expression with a tau-targeting antisense oligonucleotide (MAPT Rx ) and reduce tau levels in patients with mild AD. A randomized, double-blind, placebo-controlled, multiple-ascending dose phase 1b trial evaluated the safety, pharmacokinetics and target engagement of MAPT Rx . Four ascending dose cohorts were enrolled sequentially and randomized 3:1 to intrathecal bolus administrations of MAPT Rx or placebo every 4 or 12 weeks during the 13-week treatment period, followed by a 23 week post-treatment period. The primary endpoint was safety. The secondary endpoint was MAPT Rx pharmacokinetics in cerebrospinal fluid (CSF). The prespecified key exploratory outcome was CSF total-tau protein concentration. Forty-six patients enrolled in the trial, of whom 34 were randomized to MAPT Rx and 12 to placebo. Adverse events were reported in 94% of MAPT Rx -treated patients and 75% of placebo-treated patients; all were mild or moderate. No serious adverse events were reported in MAPT Rx -treated patients. Dose-dependent reduction in the CSF total-tau concentration was observed with greater than 50% mean reduction from baseline at 24 weeks post-last dose in the 60 mg (four doses) and 115 mg (two doses) MAPT Rx groups. Clinicaltrials.gov registration number: NCT03186989 ., (© 2023. The Author(s).)

Objective: To describe the lived experience of nursing staff and nurse leaders working in COVID-19 devoted units (intensive care or medical unit) prior to vaccine availability., Research Design: Qualitative phenomenological design with a focus group approach., Methods: The study team recruited a convenience sample of nursing staff (nurses, and nursing assistants/nurse technicians) and nurse leaders (managers, assistant nurse managers, clinical nurse specialists, and nurse educators) at an academic medical center in the midwestern United States. Focus groups and individual interviews were conducted to encourage participants to describe their (1) experiences as nursing professionals, (2) coping strategies, and (3) perspectives about supportive resources. Moral distress was measured with the moral distress thermometer and qualitative data were analyzed with Giorgi-style phenomenology., Results: We conducted 10 in-person focus groups and five one-on-one interviews ( n   =  44). Seven themes emerged: (1) the reality of COVID-19: we are sprinting in a marathon; (2) acute/critical care nurse leaders experience unique burdens; (3) acute/critical care staff nurses experience unique burdens; (4) meaning of our lived experience; (5) what helped us during the pandemic; (6) what hurt us during the pandemic; and (7) we are not okay. Participants reported a moderate level of moral distress ( M   =  5.26 SD   =  2.31). They emphasized that peer support was preferred over other types of support offered by the healthcare organization. Participants expressed positive feedback about the focus group experience and commented that group processing validated their experiences and helped them "feel heard.", Conclusion: These findings affirm the need for trauma-informed care and grief support for nurses, interventions that increase meaning in work, and efforts to enhance primary palliative communication skills. Study findings can inform efforts to tailor existing interventions and develop new, more comprehensive resources to meet the psychosocial needs of nursing staff and nurse leaders practicing during a pandemic., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Objective: To explore Australian chiropractors' and final year students' readiness to identify and support patient's experiencing intimate partner violence (IPV)., Methods: This cross-sectional study used the Chiro-PREMIS, an adaptation of the Physician Readiness to Manage Intimate Partner Violence Survey (PREMIS) to explore chiropractors' and final year students' readiness. Survey responses were analyzed through a lens of Miller's framework for developing clinical competence and chiropractic graduate competencies., Results: One hundred forty participants completed the online survey (n = 99 chiropractors and n = 41 students). Reports of practice over the 4 weeks prior to completing the survey showed 21% of chiropractors and 20% of students consulted with patients who had disclosed they were involved in IPV. Thirty-three percent of chiropractors and 27% of students suspected a patient was involved, but that patient did not disclose. Participants report meager training in IPV. Many are unclear about appropriate questioning techniques, documentation, referrals, identifying available resources, and legal literacy. Overall, participants do not "know" about IPV, they do not "know how" to and may not be able to "show how" or "do" when it comes to managing IPV-related clinical scenarios. Further studies are needed to confirm if chiropractors have the appropriate clinical capabilities., Conclusion: With proper preparation, chiropractors have an opportunity to make a positive contribution to this social problem. We anticipate chiropractic-specific discourse surrounding these escalating growing social concerns will highlight the intent of the chiropractic profession to make a substantial contribution to the health care of the Australian public. More studies are needed.

Introduction: Bipolar Disorder (BD) is known to be equally distributed among males and females. The well-documented increased risk of medical comorbidities in patients with BD, in comparison to BD patients without medical comorbidities, shows a negative impact on the course of illness. There is some evidence suggesting that women with BD have higher psychiatric and medical comorbidities in comparison to men with BD, however there is no evidence in comparison to women without BD or other major psychiatric illness. These comorbidities, along with various psychosocial factors, are known to affect the course of BD., Methods: We aimed to systematically review the literature on cardiovascular, metabolic and endocrine comorbidities in women with BD in comparison to men with BD and control women. A comprehensive search of electronic databases including PubMed, PsycINFO, Embase, and SCOPUS was conducted, and a total of 61 identified studies were included in this review., Results: Women with BD had higher rates of cardiovascular risk factors/mortality, diabetes mellitus II and thyroid disorders compared to women in the general population. In comparison to men with BD, women with BD had comparable cardiovascular risk but higher prevalence of metabolic and thyroid disorders., Limitations: Gender specific data was limited in multiple studies., Conclusions: Results present a need for gender-specific screening and interventions for various medical comorbidities in patients with BD., Competing Interests: Conflict of interest M.F. receives commercial funding from Merck. All other authors report no financial relationships with commercial interests. All 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 Elsevier B.V. All rights reserved.)

Pelizaeus-Merzbacher disease is a rare X-linked leukodystrophy accompanied by central nervous system hypomyelination with a spectrum of clinical phenotypes. This is the first survey of caregivers of individuals with Pelizaeus-Merzbacher disease to investigate the presenting symptoms, path to diagnosis, identity and impact of most bothersome symptoms, and needs that future treatment should address. One hundred participants completed the survey. Results from this survey demonstrate that the majority of Pelizaeus-Merzbacher disease symptoms manifest before 2 years of age and commonly include deficits in gross and fine motor skills, speech, and communication. Caregivers rated difficulty crawling, standing, or walking as the most bothersome symptoms due to Pelizaeus-Merzbacher disease, with constipation and difficulty with sleep, manual dexterity, and speech and communication rated nearly as high. The most important treatment goals for caregivers were improved mobility and communication. The survey findings present a caregiver perspective of the impact of symptoms in Pelizaeus-Merzbacher disease and provide helpful guidance to affected families, physicians, and drug developers on the often-long path to diagnosis and the unmet medical needs of this patient population.

Although seasonal influenza disease spread is a spatio-temporal phenomenon, public surveillance systems aggregate data only spatially, and are rarely predictive. We develop a hierarchical clustering-based machine learning tool to anticipate flu spread patterns based on historical spatio-temporal flu activity, where we use historical influenza-related emergency department records as a proxy for flu prevalence. This analysis replaces conventional geographical hospital clustering with clusters based on both spatial and temporal distance between hospital flu peaks to generate a network illustrating whether flu spreads between pairs of clusters (direction) and how long that spread takes (magnitude). To overcome data sparsity, we take a model-free approach, treating hospital clusters as a fully-connected network, where arcs indicate flu transmission. We perform predictive analysis on the clusters' time series of flu ED visits to determine direction and magnitude of flu travel. Detection of recurrent spatio-temporal patterns may help policymakers and hospitals better prepare for outbreaks. We apply this tool to Ontario, Canada using a five-year historical dataset of daily flu-related ED visits, and find that in addition to expected flu spread between major cities/airport regions, we were able to illuminate previously unsuspected patterns of flu spread between non-major cities, providing new insights for public health officials. We showed that while a spatial clustering outperforms a temporal clustering in terms of the direction of the spread (81% spatial v. 71% temporal), the opposite is true in terms of the magnitude of the time lag (20% spatial v. 70% temporal).

Purpose: Long-term lithium therapy (LTLT) has been associated with chronic kidney disease (CKD). We investigated changes in clinical characteristics, pharmacotherapeutic treatments for medical/psychiatric disorders, and outcomes among patients with bipolar disorder (BD) and CKD on LTLT in a 2-year mirror-image study design., Methods: Adult BD patients on LTLT for ≥1 year who enrolled in the Mayo Clinic Bipolar Disorder Biobank and developed CKD (stage 3) were included, and our study was approved by the Mayo Clinic Institutional Review Board. The primary outcome was the time to the first mood episode after CKD diagnosis among the lithium (Li) continuers and discontinuers. Cox proportional hazards models were used to estimate the time to the first mood episode. We tested for differences in other medication changes between the Li continuers and discontinuers group using Mantel-Haenszel χ2 tests (linear associations)., Results: Of 38 BD patients who developed CKD, 18 (47%) discontinued Li, and the remainder continued (n = 20). The median age of the cohort was 56 years (interquartile range [IQR], 48-67 years), 63.2% were female, and 97.4% were White. As compared with continuers, discontinuers had more psychotropic medication trials (6 [IQR, 4-6] vs 3 [IQR, 2-5], P = 0.02), a higher rate of 1 or more mood episodes (61% vs 10%, P = 0.002), and a higher risk of a mood episode after CKD diagnoses (Hazard Ratio, 8.38; 95% confidence interval, 1.85-38.0 [log-rank P = 0.001]]., Conclusions: Bipolar disorder patients on LTLT who discontinued Li had a higher risk for relapse and a shorter time to the first mood episode, suggesting a need for more thorough discussion before Li discontinuation after the CKD diagnosis., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To inform continued development of the novel immune agent GEN-1, we compared ovarian cancer patients' end points from a neoadjuvant single-arm phase IB study with those of similar historic clinical trial (HCT) patients who received standard neoadjuvant chemotherapy., Methods: Applying OVATION-1 trial (ClinicalTrials.gov identifier: NCT02480374) inclusion and exclusion criteria to Medidata HCT data, we identified historical trial patients for comparison. Integrating patient-level Medidata historic trial data (N = 41) from distinct neoadjuvant ovarian phase I-III trials with patient-level OVATION-1 data (N = 18), we selected Medidata patients with similar baseline characteristics as OVATION-1 patients using propensity score methods to create an external control arm (ECA)., Results: Fifteen OVATION-1 patients (15 of 18, 83%) were matched to 15 (37%, 15 of 41) Medidata historical trial control patients. Matching attenuated preexisting differences in attributes between the groups. The median progression-free survival time was not reached by the OVATION-1 group and was 15.8 months (interquartile range, 11.40 months to nonestimable) for the ECA. The hazard of progression was 0.53 (95% CI, 0.16 to 1.73), favoring GEN-1 patients. Compared with ECA patients, OVATION-1 patients had more nausea, fatigue, chills, and infusion-related reactions., Conclusion: Comparing results of a single-arm early-phase trial to those of a rigorously matched HCT ECA yielded insights regarding comparative efficacy prior to a randomized controlled trial. The effect size estimate itself informed both the decision to continue development and the randomized phase II trial (ClinicalTrials.gov identifier: NCT03393884) sample size. The work illustrates the potential of HCT data to inform drug development.

Purpose: To examine COVID-19 mRNA vaccine-induced binding and neutralizing antibody responses in patients with non-small-cell lung cancer (NSCLC) to SARS-CoV-2 614D (wild type [WT]) strain and variants of concern after the primary 2-dose and booster vaccination., Methods: Eighty-two patients with NSCLC and 53 healthy volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2-specific binding and neutralizing antibody responses were evaluated by Meso Scale Discovery assay and live virus Focus Reduction Neutralization Assay, respectively., Results: A majority of patients with NSCLC generated binding and neutralizing antibody titers comparable with the healthy vaccinees after mRNA vaccination, but a subset of patients with NSCLC (25%) made poor responses, resulting in overall lower (six- to seven-fold) titers compared with the healthy cohort ( P = < .0001). Although patients age > 70 years had lower immunoglobulin G titers ( P = < .01), patients receiving programmed death-1 monotherapy, chemotherapy, or a combination of both did not have a significant impact on the antibody response. Neutralizing antibody titers to the B.1.617.2 (Delta), B.1.351 (Beta), and in particular, B.1.1.529 (Omicron) variants were significantly lower ( P = < .0001) compared with the 614D (WT) strain. Booster vaccination led to a significant increase ( P = .0001) in the binding and neutralizing antibody titers to the WT and Omicron variant. However, 2-4 months after the booster, we observed a five- to seven-fold decrease in neutralizing titers to WT and Omicron viruses., Conclusion: A subset of patients with NSCLC responded poorly to the SARS-CoV-2 mRNA vaccination and had low neutralizing antibodies to the B.1.1.529 Omicron variant. Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant.

Objective: This is the second phase of a project. The aim was to explore Australian chiropractic and osteopathic new graduates' readiness for transition to practice concerning their clinical skills, professional behaviors, and interprofessional abilities. Phase 1 explored final year students' self-perceptions, and this part uncovered their opinions after 6 months or more in practice., Methods: Interviews were conducted with a self-selecting sample of phase 1 participant graduates from 2 Australian chiropractic and 2 osteopathic programs. Results of the thematic content analysis of responses were compared to the Australian Chiropractic Standards and Osteopathic Capabilities, the authority documents at the time of the study., Results: Interviews from graduates of 2 chiropractic courses (n = 6) and 2 osteopathic courses (n = 8) revealed that the majority had positive comments about their readiness for practice. Most were satisfied with their level of clinical skills, verbal communication skills, and manual therapy skills. Gaps in competence were identified in written communications such as case notes and referrals to enable interprofessional practice, understanding of professional behaviors, and business skills. These identified gaps suggest that these graduates are not fully cognizant of what it means to manage their business practices in a manner expected of a health professional., Conclusion: This small study into clinical training for chiropractic and osteopathy suggests that graduates lack some necessary skills and that it is possible that the ideals and goals for clinical education, to prepare for the transition to practice, may not be fully realized or deliver all the desired prerequisites for graduate practice., (© 2022 Association of Chiropractic Colleges.)

This work explores Coulomb explosion (CE) dissociation pathways in multiply charged cations of para -nitrotoluene (PNT), a model compound for nitroaromatic energetic molecules. Experiments using strong-field ionization and mass spectrometry indicate that metastable cations PNT 2+ and PNT 3+ undergo CE to produce NO 2 + and NO + . The experimentally measured kinetic energy release from CE upon formation of NO 2 + and NO + agrees qualitatively with the kinetic energy release predicted by computations of the reaction pathways in PNT 2+ and PNT 3+ using density functional theory (DFT). Both DFT computations and mass spectrometry identified additional products from CE of highly charged PNT q + cations with q > 3. The dynamical timescales required for direct CE of PNT 2+ and PNT 3+ to produce NO 2 + were estimated to be 200 and 90 fs, respectively, using ultrafast disruptive probing measurements.

We describe rapid detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant using targeted spike single-nucleotide polymorphism polymerase chain reaction and viral genome sequencing. This case occurred in a fully vaccinated and boosted returning traveler with mild symptoms who was identified through community surveillance rather than clinical care., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objectives: Recognizing bipolar disorder as a multi-system metabolic condition driven, in part, by binge eating behavior and atypical depressive symptoms, this study aimed to quantify diet quality and evaluate clinical correlates in a bipolar disorder cohort., Methods: Participants from the Mayo Clinic Bipolar Disorder Biobank (n = 734) completed the Rapid Eating Assessment for Participants - Shortened version (REAP-S) to determine diet quality. The average REAP-S score for a U.S. omnivorous diet is 32 (range 13 to 39) with higher scores indicating healthier diet. Demographic variables were collected in a standardized clinical questionnaire. Depressive symptoms were assessed by the Bipolar Inventory of Symptoms Scale. Cardiometabolic variables were retrieved from the electronic health record. Associations between continuous variables and REAP-S scores (total, 'healthy foods' and 'avoidance of unhealthy foods') were assessed using linear regression., Results: Overall, our sample had a mean REAP-S score of 27.6 (4.9), suggestive of a lower diet quality than the average general population in the US. There was a significant inverse relationship between mean REAP-S lower scores with increased BMI, waist circumference, disordered eating and depression. All these associations were significantly stronger in female participants., Limitations: EHR cross-sectional data., Conclusions: Our data suggest unhealthy diet quality in bipolar disorder is associated with depression, obesity and cardiometabolic abnormalities. Additional work is encouraged to prospectively track mood and diet quality to further understand the bidirectional relationship and clarify if dietary interventions can positively impact mood. Further delineating potential sex differences in diet quality and depression may provide greater appreciation of modifiable risk factors for future cardiometabolic burden., (Copyright © 2022. Published by Elsevier B.V.)

A zinc-carnosine (ZnCar) metal-organic coordination polymer was fabricated in biologically relevant N -(2-hydroxyethyl)piperazine- N '-ethanesulfonic acid (HEPES) buffer for use as a vaccine platform. In vitro , ZnCar exhibited significantly less cytotoxicity than a well-established zeolitic imidazolate framework (ZIF-8). Adsorption of CpG on the ZnCar surface resulted in enhanced innate immune activation compared to soluble CpG. The model antigen ovalbumin (OVA) was encapsulated in ZnCar and exhibited acid-sensitive release in vitro . When injected intramuscularly on days 0 and 21 in C57BL/6 mice, OVA-specific serum total IgG and IgG1 were significantly greater in all groups with ZnCar and antigen compared to soluble controls. Th1-skewed IgG2c antibodies were significantly greater in OVA and CpG groups delivered with ZnCar for all time points, regardless of whether the antigen and adjuvant were co-formulated in one material or co-delivered in separate materials. When broadly acting Computationally Optimized Broadly Reactive Antigen (COBRA) P1 influenza hemagglutinin (HA) was ligated to ZnCar via its His-tag, significantly greater antibody levels were observed at all time points compared to soluble antigen and CpG. ZnCar-formulated antigen elicited increased peptide presentation to B3Z T cells in vitro and production of IL-2 after ex vivo antigen recall of splenocytes isolated from vaccinated mice. Overall, this work displays the formation of a zinc-carnosine metal-organic coordination polymer that can be applied as a platform for recombinant protein-based vaccines.

Highly pathogenic avian influenza (HPAI) is a serious disease affecting multiple organ systems and resulting in high levels of mortality in domestic poultry and may also be a serious zoonotic condition. In July-August 2020, HPAI was confirmed on 3 egg-laying chicken farms in Victoria, Australia, while a further two turkey farms and one emu farm were diagnosed with low pathogenicity viruses. All six farms were depopulated and decontaminated by 26 November 2020 and Australia declared regained freedom from HPAI on 26 February 2021. As part of the follow-up surveillance in support of claiming HPAI freedom, a scenario-tree model was developed to estimate the population sensitivity of passive surveillance for the detection of HPAI in the Victorian commercial poultry industry, and to also estimate the confidence of freedom from HPAI provided by passive surveillance, predicted over a 2-year period. Risk factors included in the model were industry sector (breeder, broiler, layer and other), flock size: small commercial (50 ≤ 5000 birds) or large commercial (> 5000 birds) and housing type (cage, barn or free-range). A detection cascade was also modelled, with probabilities allocated, to estimate the flock sensitivity for flocks in each risk stratum. System sensitivity and confidence of freedom were then estimated across all flocks in the industry. Design prevalence was set at 1, 2, 5 or 10 infected flocks and prior confidence of freedom at 0.5. Other model inputs were entered as probability distributions and the model was simulated for 10,000 iterations. Outputs were expressed as median and 95% probability intervals (PI), with the time period for analysis set at 1 month. Median system sensitivity was 0.58 (95% PI: 0.47-0.69) per time period for a single infected flock, increasing to 0.81, 0.985 and 0.9998 for 2, 5 and 10 infected flocks respectively. Median confidence of freedom was > 0.7 (95% PI: 0.65-0.76) after one time period and exceeded 0.95 and 0.99 after 4 and 7 months, respectively for one infected flock and 2 and 3 months respectively for 2 infected flocks. These results support the conclusion that passive surveillance is a highly effective tool for the detection of HPAI in commercial poultry and add further weight to evidence that HPAI has been successfully eradicated from the Victorian poultry industry and that the industry has regained HPAI free status., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Bipolar disorder (BD) with co-occurring attention deficit-hyperactivity disorder (ADHD) is associated with an unfavorable course of illness. We aimed to identify potential clinical and genetic correlates of BD with and without ADHD., Methods: Among patients with BD ( N = 2,198) enrolled in the Mayo Clinic Bipolar Biobank we identified those with ADHD diagnosed in childhood (BD+cADHD; N = 350), those with adult-onset attention deficit symptoms (BD+aAD; N = 254), and those without ADHD ( N = 1,594). We compared the groups using linear or logistic regression adjusting for age, sex, and recruitment site. For genotyped patients ( N = 1,443), logistic regression was used to compare ADHD and BD polygenic risk scores (PRSs) between the BD groups, as well as to non-BD controls ( N = 777)., Results: Compared to the non-ADHD BD group, BD+cADHD patients were younger, more often men and had a greater number of co-occurring anxiety and substance use disorders (all p < 0.001). Additionally, BD+cADHD patients had poorer responses to lithium and lamotrigine ( p = 0.005 and p = 0.007, respectively). In PRS analyses, all BD patient subsets had greater genetic risk for BD and ADHD when compared to non-BD controls ( p < 0.001 in all comparisons). BD+cADHD patients had a higher ADHD-PRS than non-ADHD BD patients ( p = 0.012). However, BD+aAD patients showed no evidence of higher ADHD-PRS than non-ADHD BD patients ( p = 0.38)., Conclusions: BD+cADHD was associated with a greater number of comorbidities and reduced response to mood stabilizing treatments. The higher ADHD PRS for the BD+cADHD group may reflect a greater influence of genetic factors on early presentation of ADHD symptoms., Competing Interests: JV reports a grant-in-kind from Assurex, unrelated to the current study. PC has received research support from Neuronetics, Inc., NeoSync, Inc., and Pfizer. He has received grant-in-kind equipment and laboratory support for research studies from Assurex Health, Neuronetics, Inc. and MagVenture, Inc. He has served as a consultant for Myriad Neuroscience and Procter & Gamble. BS received grant support from Clinical and Translational Science CCaTS Small Grants Award, and Mayo Clinic. SM is or has been a consultant to or member of the scientific advisory boards of Avanir, Allergan now AbbVie, Bracket now Signant Health, Naurex, Idorsia, Intra-Cellular Therapies, Inc., Shire now Takeda, Sunovion, and Takeda. She is or has been a principal or co-investigator on studies sponsored by the Agency for Healthcare Research & Quality AHRQ, Avenir, AstraZeneca, Cephalon, Forest, Marriott Foundation, Medibio, National Institute of Mental Health, Orexigen Therapeutics, Inc., Jazz, Shire now Takeda, Sunovian, and Takeda Pharmaceutical Company Ltd. She is also an inventor on United States Patent No. 6,323,236 B2, Use of Sulfamate Derivatives for Treating Impulse Control Disorders, and along with the patent's assignee, University of Cincinnati, Cincinnati, Ohio, has received payments from Johnson & Johnson, which has exclusive rights under the patent. MF has received grant support from Assurex Health, Myriad, Pfizer, National Institute of Mental Health RO1 MH079261, National Institute of Alcohol Abuse and Alcoholism P20AA017830, Mayo Foundation; has been a consultant to Janssen Global Services, LLC, Mitsubishi Tanabe Pharma Corporation, Myriad, Sunovion, and Teva Pharmaceuticals; has received CME/Travel Support/presentation from CME Outfitters Inc. and Sunovian; Mayo Clinic has a financial interest in AssureRx and OneOme. 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 © 2022 Nunez, Coombes, Romo-Nava, Bond, Vande Voort, Croarkin, Leibman, Gardea Resendez, Veldic, Betcher, Singh, Colby, Cuellar-Barboza, Prieto, Moore, Ozerdem, McElroy, Frye and Biernacka.)

We report on pump-probe control schemes to manipulate fragmentation product yields in p -nitrotoluene (PNT) cation. Strong field ionization of PNT prepares the parent cation in the ground electronic state, with coherent vibrational excitation along two normal modes: the C-C-N-O torsional mode at 80 cm -1 and the in-plane ring-stretching mode at 650 cm -1 . Both vibrational wave packets are observed as oscillations in parent and fragment ion yields in the mass spectrum upon optical excitation. Excitation with 650 nm selectively fragments the PNT cation into C 7 H 7 + , whereas excitation with 400 nm selectively produces C 5 H 5 + and C 3 H 3 + . In both cases the ion yield oscillations result from torsional wave packet excitation, but 650 and 400 nm excitation produce oscillations with opposite phases. Ab initio calculations of the ground and excited electronic potential energy surfaces of PNT cation along the C-C-N-O dihedral angle reveal that 400 nm excitation accesses an allowed transition from D 0 to D 6 at 0° dihedral angle, whereas 650 nm excitation accesses a strongly allowed transition from D 0 to D 4 at a dihedral angle of 90°. This ability to access different electronic excited states at different locations along the potential energy surface accounts for the selective fragmentation observed with different probe wavelengths. The ring-stretching mode, only observed using 800 nm excitation, is attributed to a D 0 to D 2 transition at a geometry with 90° dihedral angle and elongated C-N bond length. Collectively, these results demonstrate that strong field ionization induces multimode coherent excitation and that the vibrational wave packets can be excited with specific photon energies at different points on their potential energy surfaces to induce selective fragmentation., 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 López Peña, Shusterman, Ampadu Boateng, Lao and Tibbetts.)

The dynamics of the dimethyl methylphosphonate (DMMP) radical cation after production by strong field adiabatic ionization have been investigated. Pump-probe experiments using strong field 1300 nm pulses to adiabatically ionize DMMP and a 800 nm non-ionizing probe induce coherent oscillations of the parent ion yield with a period of about 45 fs. The yields of two fragments, PO 2 C 2 H 7 + and PO 2 CH 4 + , oscillate approximately out of phase with the parent ion, but with a slight phase shift relative to each other. We use electronic structure theory and nonadiabatic surface hopping dynamics to understand the underlying dynamics. The results show that while the cation oscillates on the ground state along the P=O bond stretch coordinate, the probe excites population to higher electronic states that can lead to fragments PO 2 C 2 H 7 + and PO 2 CH 4 + . The computational results combined with the experimental observations indicate that the two conformers of DMMP that are populated under experimental conditions exhibit different dynamics after being excited to the higher electronic states of the cation leading to different dissociation products. These results highlight the potential usefulness of these pump-probe measurements as a tool to study conformer-specific dynamics in molecules of biological interest.

Clinical management of gynecological cancer begins by optimal debulking with first-line platinum-based chemotherapy. However, in ~80% patients, ovarian cancer will recur and is lethal. Prognostic gene signature panel identifying platinum-resistance enables better patient stratification for precision therapy. Retrospectively collected serum from 11 "poor" (<6 months progression free interval [PFI]) and 22 "favorable" (>24 months PFI) prognosis patients, were evaluated using circulating cell-free DNA (cfDNA). DNA from both groups showed 50 to 10 000 bp fragments. Pairwise analysis of sequenced cfDNA from patients showed that gene dosages were higher for 29 genes and lower for 64 genes in poor than favorable prognosis patients. Gene ontology analysis of higher dose genes predominantly grouped into cytoskeletal proteins, while lower dose genes, as hydrolases and receptors. Higher dosage genes searched for cancer-relatedness in Reactome database indicated 15 genes were referenced with cancer. Among them 3 genes, TGFBR2, ZMIZ2, and NRG2, were interacting with more than 4 cancer-associated genes. Protein expression analysis of tumor samples indicated that TGFBR2 was downregulated and ZMIZ2 was upregulated in poor prognosis patients. Our results indicate that the cfDNA gene dosage combined with protein expression in tumor samples can serve as gene signature panel for prognosis determination amongst ovarian cancer patients., 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 Author(s) 2022.)