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Kinetic Sunyaev Zel'dovich (kSZ) tomography provides a powerful probe of the radial velocity field of matter in the Universe. By cross-correlating a high resolution cosmic microwave background (CMB) experiment like CMB-S4 and a galaxy survey like Dark Energy Spectroscopic Instrument (DESI) or Large Synoptic Survey Telescope (LSST), one can measure the radial velocity field with a very high signal-to-noise ratio over a large volume of the universe. In this paper we show how this measurement can be used to improve constraints on primordial non-Gaussianities of the local type. The velocity field provides a measurement of the unbiased matter perturbations on large scales, which can be cross-correlated with the biased large-scale galaxy density field. This results in sample variance cancellation for a measurement of scale-dependent bias due to a nonzero fNL. Using this method we forecast that CMB-S4 and LSST combined reach a sensitivity σfNL∼0.5, which is a factor of 3 improvement over the sensitivity using LSST alone (without internal sample variance cancellation). We take into account critical systematics like photometric redshifts, the kSZ optical depth degeneracy, and systematics affecting the shape of the galaxy auto-power spectrum and find that these have negligible impact, thus making kSZ tomography a robust probe for primordial non-Gaussianities. We also forecast the impact of mass binning on our constraints. The techniques proposed in this paper could be an important component of achieving the theoretically important threshold of σfNL 1 with future surveys.

We present results from spectroscopic follow-up observations of stars identified in the Kepler field and carried out by teams of the Kepler Follow-up Observation Program. Two samples of stars were observed over 6 yr (2009-2015): 614 standard stars (divided into "platinum" and "gold" categories) selected based on their asteroseismic detections and 2667 host stars of Kepler Objects of Interest (KOIs), most of them planet candidates. Four data analysis pipelines were used to derive stellar parameters for the observed stars. We compare the T eff, log(g), and [Fe/H] values derived for the same stars by different pipelines; from the average of the standard deviations of the differences in these parameter values, we derive error floors of ∼100 K, 0.2 dex, and 0.1 dex for T eff, log(g), and [Fe/H], respectively. Noticeable disagreements are seen mostly at the largest and smallest parameter values (e.g., in the giant star regime). Most of the log(g) values derived from spectra for the platinum stars agree on average within 0.025 dex (but with a spread of 0.1-0.2 dex) with the asteroseismic log(g) values. Compared to the Kepler Input Catalog (KIC), the spectroscopically derived stellar parameters agree within the uncertainties of the KIC but are more precise and thus an important contribution toward deriving more reliable planetary radii.

Chronic methamphetamine use poses potentially devastating consequences for directly affected individuals and for society. Lower dopamine D2-type receptor availability has been observed in striata of methamphetamine users as compared with controls, but an analogous comparison of D1-type receptors has been conducted only on post-mortem material, with no differences in methamphetamine users from controls in the caudate nucleus and putamen and higher D1-receptor density in the nucleus accumbens. Released from neurons when methamphetamine is self-administered, dopamine binds to both D1- and D2-type receptors in the striatum, with downstream effects on cortical activity. Thus, both receptor subtypes may contribute to methamphetamine-induced alterations in cortical morphology and behavior. In this study, 21 methamphetamine-dependent subjects and 23 healthy controls participated in positron emission tomography and structural magnetic resonance imaging for assessment of striatal D1- and D2-type receptor availability and cortical gray-matter thickness, respectively. Although D2-type receptor availability (BPnd) was lower in the methamphetamine group, as shown previously, the groups did not differ in D1-type BPnd. In the methamphetamine group, mean cortical gray-matter thickness was negatively associated with cumulative methamphetamine use and craving for the drug. Striatal D1-type but not D2-type BPnd was negatively associated with global mean cortical gray-matter thickness in the methamphetamine group, but no association was found between gray-matter thickness and BPnd for either dopamine receptor subtype in the control group. These results suggest a role of striatal D1-type receptors in cortical adaptation to chronic methamphetamine use.

Under what conditions do women participate in executive power in multiethnic societies? Previous research has examined how political institutions, socioeconomic factors, and cultural norms affect the appointment of women as cabinet ministers. However, no study has assessed the extent to which the politicization of ethnicity-a cleavage that shapes political life in many countries-affects women's cabinet appointments. Focusing on sub-Saharan Africa, we argue that women are less likely to become cabinet ministers where incumbents use such appointments to build patronage-based alliances with politicians who act as advocates for ethnic constituencies. Using an original dataset on the composition of cabinets in 34 African countries from 1980 to 2005, we show that women's share of cabinet appointments is significantly lower in countries where leaders must accommodate a larger number of politicized ethnic groups, but it rises with higher levels of democracy and greater representation of women in parliament. © 2013, Midwest Political Science Association.

Ninety-six parents in a preschool and pediatric clinic participated in a randomized study of a brief parenting intervention. The Attitudes Toward Spanking (ATS) scale was measured at baseline, and, on average, 4 months postintervention. Higher ATS scores are correlated with increased use of physical punishment. In the intervention group, there was a 2.7-point decrease in the ATS score at follow-up compared with baseline (P = 0.01). There was no decrease in the ATS in the control group. Brief interventions may shift parental attitudes toward using less physical punishment and have implications for improving anticipatory guidance within primary care and early education. [ABSTRACT FROM AUTHOR]

Bifidobacterium breve species of human intestinal origin have the ability to synthesize cis-9, trans-11 (c9, t11) conjugated linoleic acid (CLA) from free linoleic acid. In this study, the ability of Bifidobacterium species to isomerize C(18) polyunsaturated fatty acids was investigated, and the antiproliferative activities of the two main microbially produced CLA isomers were assessed. Linoleic acid was converted principally to c9, t11 CLA and lesser amounts of t9, t11 CLA, whereas c9, t11 CLA was converted mainly to t9, t11 CLA. Likewise, t10, c12 CLA was converted principally to t9, t11 CLA, which was incorporated into the bacterial cell membranes. To examine the antiproliferative effect of the two main CLA isomers formed, SW480 and HT-29 human colon cancer cells were cultured in the presence of c9, t11 CLA and t9, t11 CLA. The t9, t11 CLA had a more potent antiproliferative effect than c9, t11 CLA. It is tempting to suggest that the ability of Bifidobacterium to produce such bioactive metabolites may be associated with the beneficial effects of bifidobacteria present in the human gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Peripheral nerve entrapment syndromes of the upper extremities are well documented in musicians. Bowed string players are at risk for entrapment neuropathies in the upper extremities and are sensitive to mild neurologic deficits. The purpose of this study was to determine the presence of median and ulnar neuropathies in both upper extremities of university cellists. Fourteen volunteer cellists (ages 18-32 yrs) were recruited from the Belmont University School of Music and the Vanderbilt University Blair School of Music orchestras. Subjects completed a history form, were interviewed, and underwent a physical examination. Nerve conduction status of the median and ulnar nerves of both upper extremities was obtained by performing sensory, motor, and F-wave nerve conduction studies. After completion of the median and ulnar nerve conduction studies, the cellists were instructed in upper extremity injury prevention exercises. Descriptive statistics of the nerve conduction study variables were computed using Microsoft Excel. These subjects had normal upper extremity neural and musculoskeletal function based on extensive evaluation, including a history, physical examination, and nerve conduction studies. There was no evidence of median or ulnar neuropathy at or distal to the wrist, in the forearm, across the elbow, or in the arm of the tested subjects. [ABSTRACT FROM AUTHOR]

B-cell maturation antigen (BCMA) is the target of several investigational and approved drugs for multiple myeloma (MM). BCMA expressed on plasma cells (PCs) and MM cells is cleaved by the enzyme gamma secretase, reducing membrane-bound BCMA (mbBCMA) receptor density. Gamma secretase inhibitors (GSIs) have been shown to increase mbBCMA density and may enhance efficacy of BCMA-targeted therapies. The pharmacodynamic profile of the GSI nirogacestat was evaluated in MM cell lines and a phase 1 study in healthy volunteers. In MM cell lines, mbBCMA density and soluble BCMA (sBCMA) concentrations were measured before and after short-duration nirogacestat exposure and at serial timepoints following washout. In the phase 1 study, 23 participants were administered a single oral dose of nirogacestat 50, 150, or 300 mg or repeated doses of 100 mg every 12h for up to 48h; mbBCMA density on PCs (from whole blood and bone marrow) and nirogacestat plasma concentrations were measured at baseline and postdose. After single-dose administration, serum nirogacestat concentrations rapidly increased (Tmax ~1h), and a two-compartment model with linear absorption and clearance best described nirogacestat pharmacokinetics. In MM cells and healthy volunteers' PCs, nirogacestat resulted in rapid and robust increases in mbBCMA density, with increases up to 20-fold within 4-8h of exposure. Concomitant decreases in sBCMA were observed. Nirogacestat is currently being evaluated in combination with several BCMA-directed therapeutic agents in patients with MM. Elucidating the kinetics of BCMA in response to nirogacestat is key to guiding dosing and therapeutic strategies in MM.

Lytic cell death culminates in plasma membrane rupture (PMR), which releases large intracellular molecules to augment the inflammatory response. PMR is mediated by the effector membrane protein ninjurin-1 (NINJ1) 1 , which polymerises and ruptures the membrane via its hydrophilic face 1-4 . How NINJ1 is restrained under steady-state conditions to ensure cell survival remains a mystery. Here we describe the molecular underpinnings of NINJ1 inhibition. Using cryogenic electron microscopy, we determined the structure of inactive-state mouse NINJ1 bound to a newly-developed nanobody, Nb538. Inactive NINJ1 forms a face-to-face homodimer by adopting a 3-helix conformation with unkinked transmembrane helix 1 (TM1), in contrast to the 4-helix TM1-kinked active conformation 2-4 . Accordingly, endogenous NINJ1 from primary macrophages is a dimer under steady-state conditions. Inactive dimers sequester the PMR-inducing hydrophilic face of NINJ1 and occlude the binding site for kinked TM1 from neighbouring activated NINJ1 molecules. Mutagenesis studies in cells show that destabilisation of inactive face-to-face dimers leads to NINJ1-mediated cell death, whereas stabilisation of face-to-face dimers inhibits NINJ1 activity. Moreover, destabilising mutations prompt spontaneous TM1 kink formation, a hallmark of NINJ1 activation. Collectively, our data demonstrate that dimeric NINJ1 is autoinhibited in trans to prevent unprovoked PMR and cell death., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Dark photons that kinetically mix with the Standard Model photon give rise to new spectral anisotropies (patchy dark screening) in the cosmic microwave background (CMB) due to conversion of photons to dark photons within large-scale structure. We utilize predictions for this patchy dark screening signal to provide the tightest constraints to date on the dark photon kinetic mixing parameter [ϵ≲4.5×10^{-8} (95% confidence level)] over the mass range 10^{-13}  eV≲m_{A^{'}}≲10^{-11}  eV, almost an order of magnitude stronger than previous limits, by applying state-of-the-art component separation techniques to the cross-correlation of Planck CMB and unWISE galaxy survey data.

Competing Interests: M.S. is a member on the Society for Healthcare Epidemiology of America research and publications committees.

Purpose: Sixty percent of breast cancer patients develop persistent upper limb pain and dysfunction, but only limited knowledge exists about how these symptoms relate to rehabilitation access., Methods: A postal survey was sent to patients treated at a London University Teaching Hospital (2018-2020). Data were collected on pain (Pain Detect), shoulder function (Disability of Shoulder Arm and Hand (DASH)), quality-of-life (QoL) (EQ-5D-5L), and clinical characteristics, including treatment and access to rehabilitation. The free-text section invited patients' comments on upper limb symptoms and management strategies, which were analysed thematically. Quantitative data were analysed descriptively, and the medians were examined with Mann-Whitley U-Tests or Kruskal-Wallis Test., Results: Of 511 patients surveyed, 162 (32 %) questionnaires were returned and analysed. Respondents' mean age was 62 years (SD 11.3). The majority had Sentinel Node Biopsy 71 % (116/162) and mastectomy 61 % (99/162). 73 % (119/162) reported pain. Mean (SD) Pain Detect and DASH Score were respectively 11.07 (7) and 21.7 (21.5), with 51 % recording significant shoulder dysfunction, and only 28 % reporting access to rehabilitation. Individuals with neuropathic pain had significantly higher median (range) DASH score 60.8 (35.8, 75.0) p = 0.000. Median DASH score for sedentary individuals was significantly higher 22.9 (7.9, 31.8) p = 0.0009. Free-text analysis revealed persistent, progressive symptoms, mixed attitudes towards exercise and variations in access to rehabilitation and support., Conclusion: Two years following surgery many patients reported significant upper limb symptoms which adversely impact on QoL. However, approximately two thirds did not access potentially beneficial rehabilitation treatments. There is a need to improve pathways of care., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The prevalence of direct-to-consumer (DTC) advertising for prescription drugs has led to concerns about how consumers interpret the medical information conveyed in these ads. One strategy for improving lay understanding of medical information involves incorporating quantitative information about a treatment's potential benefits and risks., Objective: This literature review investigates laypersons' interpretations of statistical concepts, expanding on past reviews and including terms that may be used in DTC prescription drug advertising., Methods: We searched six databases for articles published from January 2000 to October 2021. Articles were included if they were in English and examined general or lay audiences' comprehension of quantitative or statistical concepts, without limiting the context of the studies to medical situations., Results: We identified 25 eligible articles. The evidence suggests that likelihood ratios, odds ratios, probabilities, numbers needed to treat/harm, and confidence intervals hinder comprehension of quantitative information. The results are mixed for information presented as frequencies, percentages, absolute risk reduction, and relative risk reduction. The mixed findings could be due to numeracy, framing as risks or benefits, and operationalization of the outcomes. We found no studies examining interpretations of minimum, maximum, central tendency, power, statistical significance, or hazard ratio., Conclusion: Studies spanning several decades have examined how laypeople interpret statistical concepts. While a few terms are consistently studied, many questions still remain on how to make risk information more understandable to lay audiences, particularly those with low numeracy., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier Inc.)

Wastewater-Based Epidemiology (WBE) is widely used to monitor the progression of SARS-CoV-2 pandemic. While there is a clear correlation between the number of COVID patients in a sewershed and the viral load in the wastewater, there is notable variability across different treatment plants. In particular, some facilities consistently exhibit higher viral content per diagnosed patient, implying a potential underestimation of the number of COVID patients, while others show a low viral load per diagnosed case, indicating potential attenuation of genetic material from the sewershed. In this study, we investigated the impact of nonylphenol ethoxylate (NPHE), linear alkylbenzene sulfonic acid (LABS), bisoctyl dimethyl ammonium chloride (BDAC), and didecyldimethylammonium chloride (DDAC), the surfactants that have been commonly used as detergents, emulsifiers, wetting agents on the stability of SARS-CoV-2 in wastewater. The results showed multiple and dynamic mechanisms, including degradation and desorption, can occur simultaneously during the interaction between SARS-CoV-2 and different chemicals depending on the physicochemical properties of each chemical. Through the elucidation of the dynamic interactions, the findings from this study could help the state health organizations and scientific community to optimize the SARS-CoV-2 wastewater-based epidemiology strategies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chung-Ho Lin reports financial support was provided by The Centers for Disease Control and prevention and the National Institute on Drug Abuse of the National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

There is much interest in targeting the activity in the oxytocin system to regulate social bonding. However, studies with exogenous administration of oxytocin face the caveats of its low stability, poor brain permeability and insufficient receptor specificity. The use of a small-molecule oxytocin receptor-specific agonist could overcome these caveats. Prior to testing the potential effects of a brain-penetrant oxytocin receptor agonist in clinical settings, it is important to assess how such an agonist would affect social bonds in animal models. The facultatively monogamous prairie voles (Microtus ochrogaster), capable of forming long-term social attachments between adult individuals, are an ideal rodent model for such testing. Therefore, in a series of experiments we investigated the effects of the recently developed oxytocin receptor-specific agonist LIT-001 on the acquisition and expression of partner preference, a well-established model of pair bonding, in prairie voles. LIT-001 (10 mg/kg, intraperitoneal), as expected, facilitated the acquisition of partner preference when administered prior to a 4hr cohabitation. In contrast, while animals injected with vehicle after the 4hr cohabitation exhibited significant partner preference, animals that were injected with LIT-001 did not show such partner preference. This result suggests that OXTR activation during expression of pair bonding can inhibit partner preference. The difference in effects of LIT-001 on acquisition versus expression was not due to basal differences in partner preference between the experiments, as LIT-001 had no significant effects on expression of partner preference if administered following a shorter (2hr-long) cohabitation. Instead, this difference agrees with the hypothesis that the activation of oxytocin receptors acts as a signal of presence of a social partner. Our results indicate that the effects of pharmacological activation of oxytocin receptors crucially depend on the phase of social attachments., (© 2024. The Author(s).)

SARS-CoV-2 causes persistent infections in a subset of individuals, which is a major clinical and public health problem that should be prioritised for further investigation for several reasons. First, persistent SARS-CoV-2 infection often goes unrecognised, and therefore might affect a substantial number of people, particularly immunocompromised individuals. Second, the formation of tissue reservoirs (including in non-respiratory tissues) might underlie the pathophysiology of the persistent SARS-CoV-2 infection and require new strategies for diagnosis and treatment. Finally, persistent SARS-CoV-2 replication, particularly in the setting of suboptimal immune responses, is a possible source of new, divergent virus variants that escape pre-existing immunity on the individual and population levels. Defining optimal diagnostic and treatment strategies for patients with persistent virus replication and monitoring viral evolution are therefore urgent medical and public health priorities., Competing Interests: Declaration of interests HMM was awarded funding for this work by the US National Institutes of Health (grant number T32AI055397). HMM, DHO'C, and TCF are funded by Centers for Disease Control and Prevention (CDC) contract 75D30121C11060. AMH and NDG are supported by CDC contract 75D30122C14697. DHO, TCF, and MCJ have a provisional patent on cryptic lineages covering methods for using viral sequences detected in wastewater to forecast and evaluate viral variants that might become dominant in the general population in the future. DHO has a pending patent on membrane-specific antibody responses that describes that the membrane ectodomain is a frequent target of SARS-CoV-2-specific antibodies and that this region could be used instead of or in addition to other serological diagnostics. JGW, PJH, JEL, AP, and WW declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Polymyxins are gram-negative antibiotics that target lipid A, the conserved membrane anchor of lipopolysaccharide in the outer membrane. Despite their clinical importance, the molecular mechanisms underpinning polymyxin activity remain unresolved. Here, we use surface plasmon resonance to kinetically interrogate interactions between polymyxins and lipid A and derive a phenomenological model. Our analyses suggest a lipid A-catalyzed, three-state mechanism for polymyxins: transient binding, membrane insertion, and super-stoichiometric cluster accumulation with a long residence time. Accumulation also occurs for brevicidine, another lipid A-targeting antibacterial molecule. Lipid A modifications that impart polymyxin resistance and a non-bactericidal polymyxin derivative exhibit binding that does not evolve into long-lived species. We propose that transient binding to lipid A permeabilizes the outer membrane and cluster accumulation enables the bactericidal activity of polymyxins. These findings could establish a blueprint for discovery of lipid A-targeting antibiotics and provide a generalizable approach to study interactions with the gram-negative outer membrane., (© 2024. The Author(s).)

We report a 14-month-old male with hypoplastic left heart syndrome, mitral stenosis, and aortic stenosis with native aortic root thrombus. He developed a wide complex ventricular tachycardia and ST-segment elevation myocardial infarction with troponin I levels peaking at 388 ng/mL. He was treated safely with systemic alteplase with a resolution of his regional wall motion abnormality 18 hours later.

HIV-1 relies extensively on host cell machinery for replication. Identification and characterization of these host-virus interactions is vital to our understanding of viral replication and the consequences of infection in cells. Several prior screens have identified host factors important for HIV replication but with limited replication of findings, likely due to differences in experimental design and conditions. Thus, unidentified factors likely exist. To identify novel host factors required for HIV-1 infection, we performed a genome-wide CRISPR/Cas9 screen using HIV-induced cell death as a partitioning method. We created a gene knockout library in TZM-GFP reporter cells using GeCKOv2, which targets 19,050 genes, and infected the library with a lethal dose of HIV-1 NL4-3 . We hypothesized that cells with a knockout of a gene critical for HIV infection would survive while cells with a knockout of a non-consequential gene would undergo HIV-induced death and be lost from the population. Surviving cells were analyzed by high throughput sequencing of the integrated CRISPR/Cas9 cassette to identify the gene knockout. Of the gene targets, an overwhelming majority of the surviving cells harbored the guide sequence for the AP-1 transcription factor family protein, JunB. Upon the generation of a clonal JunB knockout cell line, we found that HIV-1 NL4-3 infection was blocked in the absence of JunB. The phenotype resulted from downregulation of CXCR4, as infection levels were recovered by reintroduction of CXCR4 in JunB KO cells. Thus, JunB downmodulates CXCR4 expression in TZM-GFP cells, reducing CXCR4-tropic HIV infection., 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 © 2024 Schulze, Gregory, Johnson and Lange.)

Background: Excessive alcohol consumption leads to serious health problems. Mechanisms regulating the consumption of alcohol are insufficiently understood. Previous preclinical studies suggested that non-social environmental and social environmental complexities can regulate alcohol consumption in opposite directions. However, previous studies did not include all conditions and/or did not include female rodents. Therefore, in this study, we examined the effects of social versus single housing in standard versus non-standard housing conditions in male and female mice., Methods: Adult C57BL/6 J mice were housed in either standard shoebox cages or in automated Herdsman 2 (HM2) cages and exposed to a two-bottle choice procedure with 3% or 6% ethanol versus water for 5 days. The HM2 cages use radiotracking devices to measure the fluid consumption of individual mice in an undisturbed and automated manner. In both housing conditions, mice were housed either at one or at four per cage., Results: In standard cages, group housing of animals decreased alcohol consumption and water consumption. In HM2 cages, group housing significantly increased ethanol preference and decreased water intake. There were no significant differences in these effects between male and female animals. These observations were similar for 3 and 6% ethanol solutions but were more pronounced for the latter. The effects of social environment on ethanol preference in HM2 cages were accompanied by an increase in the number of approaches to the ethanol solution and a decrease in the number of approaches to water. The differences in ethanol intake could not be explained by differences in locomotor or exploratory activity as socially housed mice showed fewer non-consummatory visits to the ethanol solutions than single-housed animals. In addition, we observed that significant changes in behaviors measuring the approach to the fluid were not always accompanied by significant changes in fluid consumption, and vice versa, suggesting that it is important to assess both measures of motivation to consume alcohol., Conclusion: Our results indicate that the direction of the effects of social environment on alcohol intake in mice depends on the non-social housing environment. Understanding mechanisms by which social and non-social housing conditions modulate alcohol intake could suggest approaches to counteract environmental factors enhancing hazardous alcohol consumption., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Johnson, Zweig, Zhang and Ryabinin.)

Background: The origin of novel SARS-CoV-2 spike sequences found in wastewater, without corresponding detection in clinical specimens, remains unclear. We sought to determine the origin of one such cryptic wastewater lineage by tracking and characterising its persistence and genomic evolution over time., Methods: We first detected a cryptic lineage, WI-CL-001, in municipal wastewater in Wisconsin, USA, in January, 2022. To determine the source of WI-CL-001, we systematically sampled wastewater from targeted sub-sewershed lines and maintenance holes using compositing autosamplers. Viral concentrations in wastewater samples over time were measured by RT digital PCR. In addition to using metagenomic 12s rRNA sequencing to determine the virus's host species, we also sequenced SARS-CoV-2 spike receptor binding domains, and, where possible, whole viral genomes to identify and characterise the evolution of this lineage., Findings: We traced WI-CL-001 to its source at a single commercial building. There we detected the cryptic lineage at concentrations as high as 2·7 × 10 9 genome copies per L. The majority of 12s rRNA sequences detected in wastewater leaving the identified source building were human. Additionally, we generated over 100 viral receptor binding domain and whole-genome sequences from wastewater samples containing the cryptic lineage collected over the 13 consecutive months this virus was detectable (January, 2022, to January, 2023). These sequences contained a combination of fixed nucleotide substitutions characteristic of Pango lineage B.1.234, which circulated in humans in Wisconsin at low levels from October, 2020, to February, 2021. Despite this, mutations in the spike gene and elsewhere resembled those subsequently found in omicron variants., Interpretation: We propose that prolonged detection of WI-CL-001 in wastewater indicates persistent shedding of SARS-CoV-2 from a single human initially infected by an ancestral B.1.234 virus. The accumulation of convergent omicron-like mutations in WI-CL-001's ancestral B.1.234 genome probably reflects persistent infection and extensive within-host evolution. People who shed cryptic lineages could be an important source of highly divergent viruses that sporadically emerge and spread., Funding: The Rockefeller Foundation, Wisconsin Department of Health Services, Centers for Disease Control and Prevention, National Institute on Drug Abuse, and the Center for Research on Influenza Pathogenesis and Transmission., Competing Interests: Declaration of interests YK has received unrelated funding support from Daiichi Sankyo Pharmaceutical, Toyama Chemical, Tauns Laboratories, Shionogi, Otsuka Pharmaceutical, KM Biologics, Kyoritsu Seiyaku, Shinya Corporation, and Fuji Rebio. DHO, MCJ, and TCF have a provisional patent (US patent application number 63/394,159, Method for selecting antigenic viral vaccine and therapeutic sequences) that describes the use of cryptic lineage sequences in variant forecasting. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aquagenic syringeal keratoderma (ASK), rare in males, is characterized by the rapid onset of edematous palmar wrinkling with small white papules after brief contact with water or sweat. A 24-year-old atopic male presented with a 2-week subacute history of bilateral palmar edema with whitish-colored papules after exposure to water, 3 months after having had COVID-19 infection treated with a full course of ritonavir-boosted nirmatrelvir (PAXLOVID TM ). He had received 3 COVID-19 vaccines (Pfizer, New York, NY) about 12 months prior. Workup was negative. Initial spontaneous near-resolution 2 months after onset was temporary, with recurrence 1 month later. Treatment with 12% topical aluminum chloride was ineffective. Botulinum toxin injection to both palms led to resolution of symptoms that has been sustained for 7 months. The association between atopy and ASK remains weak. We present a case of new-onset ASK in an adult male 3 months following COVID-19 infection without a history of excessive handwashing. Our patient may have had a predisposition to recurrent ASK due to his history of atopy including atopic dermatitis and food allergy anaphylaxis combined with prior COVID-19 infection. It is possible that ASK is a novel manifestation of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC) infection or long COVID., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The subject of the case report is known and/or has a professional relationship with all authors.

Objective: Measurement of countertransference (CT) has proven challenging throughout the history of studying this construct. We sought to determine the potential value of using a common measure of transference, the Core Conflictual Relationship Theme (CCRT) method, as a means of studying CT., Method: The Relationship Anecdote Paradigm and the CCRT method were used to examine CT in two studies. In Study 1, we examined the correspondence between a therapist's wishes with significant people in her life (i.e., her parents and husband) and three long-term patients. In Study 2, we identified the interpersonal wishes of a different therapist and examined 14 of her sessions with 3 patients for evidence of how these wishes and needs were displayed in her clinical work., Results: Analyses revealed that specific wishes in therapists' personal lives could be detected from projective interviews and these wishes were similar, but not necessarily identical, to wishes in therapists' descriptions of, and actual work with, their patients. Evidence of both chronic wishes and patient-specific wishes was revealed., Conclusions: These findings support the idea that the origins of CT reside in therapists' interpersonal wishes and that the CCRT may be a promising means of identifying CT in research, practice, and supervision.

Recent trends in wildfire area burned have been characterized by large patches with high densities of standing dead trees, well outside of historical range of variability in many areas and presenting forest managers with difficult decisions regarding post-fire management. Post-fire tree harvesting, commonly called salvage logging, is a controversial management tactic that is often undertaken to recoup economic loss and, more recently, also to reduce future fuel hazard, especially when coupled with surface fuel reduction. It is unclear, however, whether the reductions in future fuels translate to meaningful changes to reburn fire behavior, particularly in the context of potentially detrimental effects of harvest on other ecosystem services. We used observed post-fire snag structure in four high severity burn scars located in the Western United States that had variable post-fire snag basal area (13.3-63.9 mg ha -2 ) to initialize a simulation study of future coarse and fine woody fuel hazard and associated reburn fire behavior and effects. We compared untreated controls to intensive and intermediate intensity harvest treatments, both simulated and actual. All treatments showed some number of years of extreme fire behavior during which flame lengths exceeded thresholds associated with wildfire resistance to control, implying that future fuel reductions achieved by the treatments did not translate to conditions conducive for effective reburn fire management. Harvested stands had less severe soil fire effects (soil heating and smoldering duration) than untreated controls, explained by lower predicted peak coarse woody fuels (CWD) in the harvested stands. At higher pre-treatment snag basal area, harvested stands better maintained CWD within the range desired to maintain ecosystem functions such as nutrient cycling and wildlife habitat. These simulation results indicate that, even with reduced fuel hazard, salvage treatments may still be associated with severe fire behavior for some time after wildfire, but achieved reductions in coarse woody fuels may also reduce some soil fire effects. Tradeoffs in the effects of post-fire harvest must be considered carefully in the context of forest regeneration, local conditions that govern salvage methods, snag fall and decomposition, and associated potential reburn fire effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The Centers for Medicare & Medicaid Services currently incentivizes hospitals to reduce postdischarge adverse events such as unplanned hospital readmissions for patients who underwent total joint arthroplasty (TJA). This study aimed to predict 90-day TJA readmissions from our comprehensive electronic health record data and routinely collected patient-reported outcome measures., Methods: We retrospectively queried all TJA-related readmissions in our tertiary care center between 2016 and 2019. A total of 104-episode care characteristics and preoperative patient-reported outcome measures were used to develop several machine learning models for prediction performance evaluation and comparison. For interpretability, a logistic regression model was built to investigate the statistical significance, magnitudes, and directions of associations between risk factors and readmission., Results: Given the significant imbalanced outcome (5.8% of patients were readmitted), our models robustly predicted the outcome, yielding areas under the receiver operating characteristic curves over 0.8, recalls over 0.5, and precisions over 0.5. In addition, the logistic regression model identified risk factors predicting readmission: diabetes, preadmission medication prescriptions (ie, nonsteroidal anti-inflammatory drug, corticosteroid, and narcotic), discharge to a skilled nursing facility, and postdischarge care behaviors within 90 days. Notably, low self-reported confidence to carry out social activities accurately predicted readmission., Conclusions: A machine learning model can help identify patients who are at substantially increased risk of a readmission after TJA. This finding may allow for health-care providers to increase resources targeting these patients. In addition, a poor response to the "social activities" question may be a useful indicator that predicts a significant increased risk of readmission after TJA., (© 2023 The Authors.)

Deep sequencing of wastewater to detect SARS-CoV-2 has been used during the COVID-19 pandemic to monitor viral variants as they appear and circulate in communities. SARS-CoV-2 lineages of an unknown source that have not been detected in clinical samples, referred to as cryptic lineages, are sometimes repeatedly detected from specific locations. We have continued to detect one such lineage previously seen in a Missouri site. This cryptic lineage has continued to evolve, indicating continued selective pressure similar to that observed in Omicron lineages., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gregory et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Twenty-five years after the first report that HIV-2 infection can reduce HIV-1-associated pathogenesis in dual-infected patients, the mechanisms are still not well understood. We explored these mechanisms in cell culture and showed first that these viruses can co-infect individual cells. Under specific conditions, HIV-2 inhibits HIV-1 through two distinct mechanisms, a broad-spectrum interferon response and an HIV-1-specific inhibition conferred by the HIV-2 TAR. The former could play a prominent role in dually infected individuals, whereas the latter targets HIV-1 promoter activity through competition for HIV-1 Tat binding when the same target cell is dually infected. That mechanism suppresses HIV-1 transcription by stalling RNA polymerase II complexes at the promoter through a minimal inhibitory region within the HIV-2 TAR. This work delineates the sequence of appearance and the modus operandi of each mechanism., Competing Interests: The authors declare no conflict of interest.

Background: Caregivers are often apprehensive about treating childhood atopic dermatitis (AD) with topical corticosteroids but may find comfort if treatments are presented in a patient-centered manner., Objective: We assessed caregivers' willingness to treat AD with either a "topical steroid," "topical medication," or "treatment, similar to the all-natural signals produced by the adrenal glands in the body.", Methods: A survey randomized 874 caregivers of children with AD to receive a "topical steroid," "topical medication," or "treatment, similar to the all-natural signals produced by the adrenal glands in the body." A scenario-only dataset received these descriptions, while a descriptive heading dataset and expanded scale dataset also received headings of "Topical Steroid Use," "Topical Medication Use," and "All-Natural Treatment Use," respectively. Responses were recorded on a 6-point Likert scale or 0-100 slider scale. Whole and dichotomized responses were evaluated using 2-tailed, independent sample t-tests., Results: For the descriptive heading and expanded scale datasets, those presented with a "topical medication" reported greater willingness to treat than those presented with a "topical steroid" and "all-natural treatment" in the descriptive heading dataset (P<0.05). For the dichotomized scenario-only dataset, those presented with a "treatment, similar to the all-natural signals produced by the adrenal glands in the body," reported greater willingness than those presented with a "topical medication" (P<0.05)., Conclusion: Initially presenting caregivers with a "topical medication" rather than a "topical steroid" may improve willingness to treat AD for some caregivers. However, tailoring the discussion to best fit caregivers’ understanding of treatment may be the most beneficial approach. J Drugs Dermatol. 2023;22(12):1216-1219. doi:10.36849/JDD.5746.

Background: Rett syndrome (RTT) is a developmental encephalopathy disorder that is associated with a high incidence of sudden death presumably from cardiorespiratory etiologies. Electrocardiogram (ECG) abnormalities, such as prolonged heart-rate corrected QT (QTc) interval, are markers of cardiac repolarization and are associated with potentially lethal ventricular arrhythmias. This study investigates the cardiac repolarization characteristics of RTT patients, including QTc and T-wave morphology characteristics., Methods: A retrospective quantitative analysis on 110 RTT patients and 124 age and sex-matched healthy controls was conducted., Results: RTT patients had longer QTc, more abnormal T-wave morphology, and greater heterogeneity of cardiac repolarization parameters compared to controls. Even RTT patients without prolonged QTc had more abnormal ECG and T-wave characteristics than controls. Among RTT patients, MECP2 patients had prolonged QTc compared to CDKL5 and FOXG1 patients. A subset of five RTT patients who died had normal QTc, but more abnormal T-wave morphology than the remaining RTT patients., Conclusions: Cardiac repolarization abnormalities are present in RTT patients, even without long QTc. T-wave morphology is related to RTT genotype and may be predictive of mortality. These findings could be used to help the management and monitoring of RTT patients., Competing Interests: Each author declares that they do not have any competing interests pertaining to this study., (Copyright 2023, Collins et al.)

Background: Antimicrobial stewardship programs (ASPs) are vital to improving patient safety and ensuring quality of care but are often underresourced, limiting their effectiveness and reach. While barriers to ASP success have been well documented, approaches to address these barriers with limited resources are needed. Stewardship networks and collaboratives have emerged as possible solutions. In January 2020, 5 US Department of Veterans Affairs facilities created a regional ASP collaborative. In this article, we describe the impact of this collaborative on the productivity of the facilities' ASPs., Methods: ASP annual reports for each of the 5 facilities provided retrospective data. Reports from fiscal year (FY) 2019 and reports from FY 2020-2022 were reviewed. Staffing, inpatient and outpatient stewardship reporting, individual and collaborative initiatives, and publications data were collected to measure productivity. Yearly results were trended for each facility and for the region. Additionally, the COVID-19 antibiotic use dashboard and upper respiratory infection dashboard were used to review the impact of initiatives on antibiotic prescribing during the collaborative., Results: Regular reporting of outpatient metrics increased; 27% of measures showed improvement in 2019 and increased to 60% in 2022. For all 5 facilities, ASP initiatives increased from 33 in 2019 to 41 in 2022 (24% increase) with a corresponding increase in collaborative initiatives from 0 to 6. Likewise, publications increased from 2 in 2019 to 17 in 2022 (750% increase). Rates of reporting and improvement in inpatient metrics did not change significantly., Conclusions: The ASP collaborative aided in efficiency and productivity within the region by sharing improvement practices, distributing workload for initiatives, and increasing publications., Competing Interests: Author disclosures: The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article., (Copyright © 2023 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

Using an extensive database of every resident death in Virginia from 2005 to 2020, climate-mortality relationships are examined for 12 climatically homogeneous regions within the Commonwealth. Each region is represented by a first-order weather station from which archived temperature and humidity data are used to generate a variety of biometeorologically relevant indices. Using these indices and other variables (such as air quality and heat and cold waves), daily mortality and climate relationships are modeled for each region over a 21-day lag period utilizing generalized additive models and distributed lag non-linear models. Optimal models are identified for each region, and a consensus model was also run based on maximum temperature to facilitate inter-regional comparisons. The relative risk of mortality varies markedly as a function of climate between regions, with U-shaped, J-shaped, and inverse linear relationships evident. Cold mortality exceeds heat mortality across most of Virginia (typical relative risks are 1.10 for cold and 1.03 for heat), with cold risks strongest at lags 3 to 10. Low temperatures (or low humidity) are protective at lags 0-2 days except in the colder, western parts of state. Heat mortality occurs at short lags (0-2 days) for three-fourths of the stations, but the spatial pattern is random. Mortality displacement is evident for most regions for several days following the heat-related spike. Although the use of region-specific models is justified, the simple consensus model based on a consistent set of predictors provides similar results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Bacteria use a diverse arsenal of anti-phage immune systems, including CRISPR-Cas and restriction enzymes. Recent advances in anti-phage system discovery and annotation tools have unearthed many unique systems, often encoded in horizontally transferred defense islands, which can be horizontally transferred. Here, we developed Hidden Markov Models (HMMs) for defense systems and queried microbial genomes on the NCBI database. Out of the 30 species with >200 completely sequenced genomes, our analysis found Pseudomonas aeruginosa exhibits the greatest diversity of anti-phage systems, as measured by Shannon entropy. Using network analysis to identify the common neighbors of anti-phage systems, we identified two core defense hotspot loci (cDHS1 and cDHS2). cDHS1 is up to 224 kb (median: 26 kb) with varied arrangements of more than 30 distinct immune systems across isolates, while cDHS2 has 24 distinct systems (median: 6 kb). Both cDHS regions are occupied in a majority of P. aeruginosa isolates. Most cDHS genes are of unknown function potentially representing new anti-phage systems, which we validated by identifying a novel anti-phage system (Shango) commonly encoded in cDHS1. Identifying core genes flanking immune islands could simplify immune system discovery and may represent popular landing spots for diverse MGEs carrying anti-phage systems., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Plasma membrane rupture (PMR) in dying cells undergoing pyroptosis or apoptosis requires the cell-surface protein NINJ1 1 . PMR releases pro-inflammatory cytoplasmic molecules, collectively called damage-associated molecular patterns (DAMPs), that activate immune cells. Therefore, inhibiting NINJ1 and PMR may limit the inflammation that is associated with excessive cell death. Here we describe an anti-NINJ1 monoclonal antibody that specifically targets mouse NINJ1 and blocks oligomerization of NINJ1, preventing PMR. Electron microscopy studies showed that this antibody prevents NINJ1 from forming oligomeric filaments. In mice, inhibition of NINJ1 or Ninj1 deficiency ameliorated hepatocellular PMR induced with TNF plus D-galactosamine, concanavalin A, Jo2 anti-Fas agonist antibody or ischaemia-reperfusion injury. Accordingly, serum levels of lactate dehydrogenase, the liver enzymes alanine aminotransaminase and aspartate aminotransferase, and the DAMPs interleukin 18 and HMGB1 were reduced. Moreover, in the liver ischaemia-reperfusion injury model, there was an attendant reduction in neutrophil infiltration. These data indicate that NINJ1 mediates PMR and inflammation in diseases driven by aberrant hepatocellular death., (© 2023. The Author(s).)

Background: Infection is one of the challenging complications after open reduction and internal fixation for ankle fractures. Previously published case series conclude that Staphylococcus aureus is the most frequent causative microorganism. An unexpected increase in Enterobacter cloacae infections after this surgery was observed in a preliminary analysis of data at the promoting center of the study. In traumatology, its incidence has been reported in chronic osteomyelitis, prosthetic infections, septic osteoarthritis, open fractures in children and adults, and fractures other than the ankle. Because of this unexpected finding, we decided to perform this study to analyze the demographic and microbiological variables of acute osteosynthesis infection after ankle fracture and determine the distinctive features of the patients with E cloacae infection., Methods: We performed a retrospective multicenter study including 4 university hospitals. All patients diagnosed with acute osteosynthesis infection after ankle fracture fixation between January 2015 and December 2018 were included. We analyzed demographic data, type of fracture, surgical technique, and microorganisms responsible for the infection. We performed a descriptive statistical analysis of the variables. Univariate and multivariate regression analysis were performed to compare patients with E cloacae infection to patients with infection caused by other microorganisms., Results: A total of 65 patients were included. A predominance of polymicrobial infections (24.62%), followed by infections caused by S aureus (23.07%) and E cloacae (23.07%) was observed. When E cloacae isolated in polymicrobial infections were added, the incidence of E cloacae as a causative microorganism increased to 32.3%. Patients with E cloacae infection were older (64/53, P  = .008) and had a higher requirement of negative-pressure therapy after surgical debridement (71%/40%, P  = .017)., Conclusion: A high incidence of E cloacae infections was observed. Patients with E cloacae infection were generally older and required a higher use of negative-pressure therapy after debridement., Level of Evidence: Level V, mechanism-based reasoning.

Context: Hispanic or Latino men who have sex with men (HLMSM) are disproportionately affected by the HIV/AIDS epidemic in New York State (NYS) and nationally. In 2019, HLMSM comprised 13% of all new diagnoses and 21% of new diagnoses among men who have sex with men (MSM) in NYS excluding New York City. HIV home testing programs are effective methods for increasing HIV testing., Objective: This pilot sought to determine whether the NYS HIV Home Test Giveaway (HHTG) can effectively reach priority populations, specifically HLMSM/transgender/gender nonconforming persons who have sex with men, to increase uptake of HIV home testing services and identify new HIV infections., Design/setting: We recruited participants using media campaigns linked to a brief self-administered eligibility survey. Eligible participants provided their e-mail address to receive a code for a free HIV home test and were sent a self-administered follow-up survey 4 to 11 weeks after eligibility survey completion., Participants: The 2018 and 2019 NYS HHTG reached 1214 and 1340 participants, respectively. A total of 606 participants in 2018 and 736 participants in 2019 were eligible to receive the HHTG home test kit., Main Outcome Measures: HHTG utilization and test results., Results: Hispanic or Latino persons participated at higher rates (34.8% and 25.4% in 2018 and 2019, respectively) than the percentage of Hispanic men in prioritized zip codes (15.7% and 15.6% in 2018 and 2019, respectively). The majority of participants who received HHTG test kits used them to test themselves (87.5% in 2018 and 90.6% in 2019). Across both rounds, 4 participants reported new HIV-positive results, for a seropositivity rate of approximately 1%., Conclusion: Geospatial prioritization was successful in reaching Hispanic or Latino priority populations for HIV testing. HIV self-testing programs such as the HHTG are beneficial methods to reach priority populations for state and national Ending the HIV Epidemic initiatives., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc.)

The purpose of this study was to explore how group leader affect impacted facilitation of a career education program. Through a case study design, data were gathered via focus groups and blog posts from 16 program staff members. Five major themes were derived, highlighting group leader affect and experience: Emotions During Intervention, Flexibility, Student Engagement and Connections, Support from Program Staff, and School Culture. The findings encouraged career educators to remain flexible when delivering programming, to consider regular evaluations of affect throughout career programming, and to acknowledge the reciprocity of engagement, affect, and programmatic buy-in between facilitators and participants., Competing Interests: Conflict of interest We have no known conflict of interest to disclose.