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Guidelines identifying best practices for harvesting tissues that lead to optimal DNA preservation are few but are important curatorial concerns for genetic resource collections. We conducted a temporal study to establish rate of DNA degradation of tissue samples extracted from field-caught museum specimens. Five individuals of Sigmodon hispidus were collected and their liver and muscle tissues were harvested. Each tissue type was sectioned into 15 subsamples, and each was preserved in liquid nitrogen at different time intervals (2, 4, 8, 16, and 32 min; 1, 2, 4, 8, and 16 h; and 1, 2, 4, 8, and 16 days) following death. DNA was extracted using an automated robotic instrument and molecular mass profiles were determined fluorometrically. Postmortem DNA degradation was continuous and dependent on time, but also was significantly affected by differences among individual cotton rats. DNA fragments of ≥10,000 base pairs in length were present in muscle samples across all time intervals, whereas DNA fragments of this size in liver samples were no longer present after 8–16 h postmortem. DNA molecular mass profiles showed that muscle samples retained 80% of their longest fragments (≥10,000 base pairs) until 1 day postmortem, whereas liver samples retained the same percentage only until 8 min after death. Although rates of decay were measured from samples in a laboratory (not field) setting, rates of decay presented here can guide field and museum workers in best practices. Results suggest that opportunistic samples, such as those from roadkill specimens, are more likely to be of use for a variety of molecular methods when muscle is preserved. Considerations of differences in rates of degradation may also guide selection of tissue types housed in genetic resource collections, especially under space-limited circumstances.

Phenotypic variability is ubiquitous. This is especially true in bats, where families such as Phyllostomidae encompass as much phenotypic variability as some entire orders of mammals. Typically, phenotypic variability is characterized based on cranial morphology, with studies of other functionally important aspects of the phenotype, such as legs, feet and wings, being less frequent. We examined patterns of secondary sexual dimorphism and allometry of wing elements of the fringed fruit-eating bat (Artibeus fimbriatus) and examined, for the first time, the modularity of bat wings. Patterns were based on 13 wing measurements taken from 21 females and 15 males from eastern Paraguay. From a multivariate perspective, A. fimbriatus exhibited significant secondary sexual dimorphism. Females were larger than males for all 13 wing characteristics, with significant differences involving the last phalanx of the fourth and fifth digits. Female wings were also relatively larger than male wings from a multivariate perspective, as was the last phalanx of the fourth and fifth digits, after adjusting for wing size based on forearm length. Wing elements were highly variable regarding allometric relationships, with some exhibiting no allometric patterns and others exhibiting isometry or hyperallometry, depending on the element. Wings exhibited significant modularity, with metacarpals, proximal phalanges and distal phalanges each representing a discrete module. The wings of A. fimbriatus exhibit substantive patterns of dimorphism, allometry and modularity. Although the big mother hypothesis is a strong theoretical construct to explain wing dimorphism, there is not yet any sound theoretical basis for the patterns of allometry and modularity of the wing. Further investigation is required to understand the determinants of variation in wing morphology.

ObjectiveIntracranial pressure (ICP) is a vital waveform used to assess the conditions of patients with intracranial pathologies, such as traumatic brain injury. The current standard for monitoring ICP requires a catheter to be inserted into the brain, which is extremely invasive and increases the risk of hemorrhage and infection. We hypothesize that ICP can be inferred from extracranial waveforms routinely measured in the Intensive Care Unit (ICU), such as invasive arterial blood pressure (ABP), photoplethysmography (PPG), and electrocardiography (ECG).MethodsWe extracted 600 hours of simultaneous ABP, EKG, PPG, and ICP waveforms (125 Hz) across 10 different patients from the MIMIC III Waveform Database. These concurrent recordings were broken into 10 second windows to train on long-short term memory (LSTM) and temporal convolutional network (TCN) models to predict ICP using ABP, EKG, and PPG as input features. These models were evaluated in both a single-patient analysis and multi-patient analysis study.ResultsIn the single-patient analysis study, TCN’s median mean average error (MAE) test loss was 1.60 mmHg in comparison to a median MAE test loss of 1.88 mmHg for LSTM. TCN was used in the multi-patient analysis study, reporting a test MAE loss of 5.44 mmHg.ConclusionsThese novel results indicate that it is possible to predict ICP waveforms from extracranial waveforms in a real-time, continuous, and non-invasive manner. This approach could potentially eliminate the risks associated with invasive monitoring and allow for more timely treatment of patients with intracranial pathologies with further follow-up studies.

Introduction Sexual anxiety is one of the root causes of female sexual dysfunction (Pyke, 2020). Increased anxiety during sexual intercourse can cause women to avoid sexual activity altogether (Gerrier et al., 2015; Sanoff, 2016), experience reduced sexual satisfaction (Brassard et al., 2015), and lead to sexual difficulties such as anorgasmia, lack of arousal, and lack of sexual desire (McCabe, 2005). However, little is known about sexual anxiety beyond the narrow White male-focused quantitative research on sexual performance anxiety. Research fails to account for intersecting sociocultural oppression Black women face that may precipitate anxiety within a sexual context. For Black women, who experience sexual stereotypes about their sexual prowess (Collins, 2000), pressures to conform Eurocentric body standards (Awad et al., 2015), and reproductive health disparities that often precipitate sexual pain (Eltoukhi et al., 2014), examining sexual anxiety requires an intersectional lens, from onset to treatment (Hargons et al., 2022). Objective To counter the deficit-based narratives of Black women’s sexualities this study takes an intersectional approach and is rooted in Black feminist perspectives to center the voices of Black women in sex science and advance the research on Black women’s sexuality through a holistic lens. The purpose of this study is to understand Black women’s experiences of sexual anxiety using a phenomenological approach. This study makes a unique contribution to the literature by being the first study to our knowledge to 1) explore Black women’s experiences of sexual anxiety, including their self-reported precipitants and coping strategies, and 2) develop a working definition of sexual anxiety for Black women that capture the nuances of this phenomenon among them. Methods Data comes from Phase 2 of a larger explanatory mixed methods study on Black women’s sexual pain and sexual pleasure. To be eligible for Phase 1, participants had to be 1) premenopausal, 2) under the age of 50, 4) identify as a cisgender Black woman, and 5) live in the Southern region of the US. N=24 Participants completed a 60-min Zoom interview in April 2021. Interview data was analyzed using an interpretative phenomenological analysis. Results Participants reported three components of sexual anxiety as a phenomenon: 1) causes of sexual anxiety, 2) characteristics of sexual anxiety, and 3) coping strategies (see Figure 1). Causes of sexual anxiety contained five elements: partner unfamiliarity, oppressive body standards, rape culture and fears of sexual violence, pressure to meet societal sexual expectations, and anticipation of sexual pain. Characteristics of sexual anxiety included elements such as somatic, emotional, and cognitive symptoms and resultant behaviors. Coping strategies ranged from individual-level strategies to partnered coping strategies. Additionally, we composed a working description of sexual anxiety based on participant responses which account for sociocultural factors distinct for Black women. Conclusions This study highlights the importance of investigating, preventing, and treating barriers that exacerbate sexual difficulties, such as sexual anxiety, so Black women can engage in pleasurable sex and feel safe, mentally present, and confident during sexual experiences. Implications for intersectionality-informed interventions and suggestions for mental health professionals and partners will be discussed. Disclosure No

BackgroundGiven the clinical heterogeneity of COVID-19 infection, we hypothesize the existence of subphenotypes based on early inflammatory responses that are associated with mortality and additional complications.MethodsFor this cross-sectional study, we extracted electronic health data from adults hospitalized patients between March 1, 2020 and May 5, 2021, with confirmed primary diagnosis of COVID-19 across five Johns Hopkins Hospitals. We obtained all electronic health records from the first 24h of the patient’s hospitalization. Mortality was the primary endpoint explored while myocardial infarction (MI), pulmonary embolism (PE), deep vein thrombosis (DVT), stroke, delirium, length of stay (LOS), ICU admission and intubation status were secondary outcomes of interest. First, we employed clustering analysis to identify COVID-19 subphenotypes on admission with only biomarker data and assigned each patient to a subphenotype. We then performed Chi-Squared and Mann-Whitney-U tests to examine associations between COVID-19 subphenotype assignment and outcomes. In addition, correlations between subphenotype and pre-existing comorbidities were measured using Chi-Squared analysis.ResultsA total of 7076 patients were included. Analysis revealed three distinct subgroups by level of inflammation: hypoinflammatory, intermediate, and hyperinflammatory subphenotypes. More than 25% of patients in the hyperinflammatory subphenotype died compared to less than 3% hypoinflammatory subphenotype (pConclusionWe identify three distinct inflammatory subphenotypes that predict a range of outcomes, including mortality, MI, DVT, PE, stroke, delirium, ICU admission and LOS. The three subphenotypes are easily identifiable and may aid in clinical decision making.

Supplemental Figure 1. Expression of FASN, SPHK1 and SPHK2 in CRC.

Metastasis is the most common cause of death in colorectal cancer patients. Fatty acid synthase (FASN) and sphingosine kinase-1 and -2 (SPHK1 and 2) are overexpressed in many cancers, including colorectal cancer. However, the contribution of FASN-mediated upregulation of sphingolipid metabolism to colorectal cancer metastasis and the potential of these pathways as targets for therapeutic intervention remain unknown. This study determined that sphingosine kinases (SPHK) are overexpressed in colorectal cancer as compared with normal mucosa. FASN expression significantly correlated with SPHK2 expression in data sets from The Cancer Genome Atlas (TCGA) and a colorectal cancer tumor microarray. FASN, SPHK1, and SPHK2 colocalized within invadopodia of primary colorectal cancer cells. Moreover, FASN inhibition decreased SPHK2 expression and the levels of dihydrosphingosine 1-phosphate (DH-S1P) and sphingosine 1-phosphate (S1P) in colorectal cancer cells and tumor tissues. Inhibition of FASN using TVB-3664 and sphingolipid metabolism using FTY-720 significantly inhibited the ability of primary colorectal cancer cells to proliferate, migrate, form focal adhesions, and degrade gelatin. Inhibition of the FASN/SPHK/S1P axis was accompanied by decreased activation of p-MET, p-FAK, and p-PAX. S1P treatment rescued FASN-mediated inhibition of these proteins, suggesting that FASN promotes metastatic properties of colorectal cancer cells, in part, through an increased sphingolipid metabolism. These data demonstrate that upregulation of the FASN/SPHK/S1P axis promotes colorectal cancer progression by enhancing proliferation, adhesion, and migration.Implications:This study provides a strong rationale for further investigation of the interconnection of de novo lipogenesis and sphingolipid metabolism that could potentially lead to the identification of new therapeutic targets and strategies for colorectal cancer.

We report on the development of a diagnostic to measure the time-resolved column density and Doppler temperature of atomic vapors produced by laser ablation. The diagnostic is based on the strong frequency dependence of the atomic susceptibility near an electronic transition in the interrogated atomic species. Interference on the face of a fast photodetector between the several frequency components present in a sinusoidally phase-modulated probe beam will produce a time signature uniquely determined by the column density of atoms in the probed atomic state and the Doppler temperature of the atomic vapor. With the extensive, high precision atomic spectroscopy data available in the literature, it is possible to model the vapor and extract the desired parameters through comparison of the model result with the experimental data.

OBJECTIVE To determine the rate of survival to hospital discharge and identify indicators associated with poor outcomes among female dogs (bitches) with pyometra treated with ovariohysterectomy (OHE) in a nonspecialized setting. ANIMALS 405 bitches diagnosed with pyometra at the American Society for the Prevention of Cruelty to Animals Animal Hospital from January 1, 2017, to February 8, 2019. PROCEDURES For this retrospective study, medical records were searched and data collected including patient history, clinical signs, serum biochemical analyses results, and outcome (survival to hospital discharge, length of hospital stay, and uterine rupture). Logistic regression models were used to assess multivariable associations and identify potential predictive variables. RESULTS The rate of survival to hospital discharge for bitches with pyometra treated with OHE was 97% (394/405); 44% (174/394) stayed in the hospital ≥ 2 nights, and 3% (11/390) had a ruptured uterus. Bitches with a high BUN concentration or heart murmur had greater odds of death after OHE; however, the model had low predictive power. Those with uterine rupture, inappetence, high concentrations of BUN or serum creatinine, low PCV, or dehydration had greater odds of hospitalization ≥ 2 nights. There were no significant predictors of uterine rupture. CLINICAL RELEVANCE The rate of survival to hospital discharge was high for bitches with pyometra treated with OHE in a nonspecialized setting; therefore, general practitioners could expect similar outcomes. With this important procedure widely available in general practices, more pets can receive treatment for this life-threatening disease.

This proceedings article presents actionable research targets on the basis of the presentations and discussions at the 2nd Curing Coma National Institutes of Health (NIH) symposium held from May 3 to May 5, 2021. Here, we summarize the background, research priorities, panel discussions, and deliverables discussed during the symposium across six major domains related to disorders of consciousness. The six domains include (1) Biology of Coma, (2) Coma Database, (3) Neuroprognostication, (4) Care of Comatose Patients, (5) Early Clinical Trials, and (6) Long-term Recovery. Following the 1st Curing Coma NIH virtual symposium held on September 9 to September 10, 2020, six workgroups, each consisting of field experts in respective domains, were formed and tasked with identifying gaps and developing key priorities and deliverables to advance the mission of the Curing Coma Campaign. The highly interactive and inspiring presentations and panel discussions during the 3-day virtual NIH symposium identified several action items for the Curing Coma Campaign mission, which we summarize in this article.

Background: Polystemma (Apocynaceae subfamily Asclepiadoideae) is a small genus currently with seven species characterized by having white glandular trichomes becoming crystalline in age; filiform corona appendages; and fusiform, smooth, mottled follicles. Exploration in the Balsas Depression of Michoacán, Mexico resulted in the discovery of an unknown species of Polystemma . Questions: Are the unknown Polystemma plants occurring in the Balsas Depression of Michoacán new to science? If so, how are they distinguished from other species of the genus, what are their ecological preferences, what is their distribution, and are they endangered? Studied species: Species of Polystemma . Study site and dates: Balsas Depression, Michoacán, México; 2001, 2003, 2004, 2014. Methods: Fieldwork to collect herbarium specimens and photograph plants; review of literature on Polystemma to determine taxonomic status; preparation of a morphological description; evaluation of conservation status using IUCN Redlist criteria. Results: Polystemma fishbeiniana is proposed as a new species and illustrated with photographs. It occurs at two locations in the xeric scrub and open thorn forest of the Zicuirán-Infiernillo Biosphere Reserve, at elevations from 275 to 400 m. Flowering occurs from June to September, with mature fruits present from October to March; dehisced fruits can persist on the plants for almost a year. Its conservation status is assessed as Endangered, EN B1ab(iii)+2ab(iii). Conclusions: Polystemma fishbeiniana is distinguished from congeners by its suffrutescent habit, small leaves, and flowers abaxially yellowish with a blackish to dark burgundy red margin and central line with short lateral extensions.These traits are otherwise unknown in the genus. Translate stop Translate stop

In the United States, Black men and women who are incarcerated bear a disproportionate and inequitable burden of HIV infection. While HIV knowledge does not consistently predict HIV risk behaviors, HIV knowledge can inform one’s perceptions of their risk for HIV. We examined gender differences in HIV knowledge and perceived risk of contracting HIV ( N = 424) among Black men and women who were incarcerated and nearing community reentry from seven prisons in Kentucky. Our results demonstrated that women reported greater levels of HIV knowledge and perceived greater risk for contracting HIV than their male counterparts. Implications for HIV prevention interventions are discussed.

Figure S4. Loss of Erbin does not significantly alter the expression of genes associated with intestinal stem cells and differentiation in normal intestinal organoids. (A) Representative phase contrast images of intestinal organoids derived WT and Erbin-/- (KO) mice grown in 3D Matrigel for 5 days. Scale bar, 200μm. (B) Intestinal organoids from WT, Erbin+/- (Het) and Erbin-/- (KO) mice were grown in 3D Matrigel and collected after 5 days. Total RNA were prepared and used for qRT-PCR analysis for the expression of genes associated with intestinal stem and progenitor cells (Lgr5, Axin2 and Cd44), cell proliferation (Ccnd1 and Ki67) and intestinal cell differentiation (Alpi, Chga, Muc2 and Cdh1). (C) MEF cells generated from WT and Erbin KO mice were stimulated with EGF (10ng/mL) for the indicated times and analyzed for the activation of Akt and RAS/RAF signaling by western blot.

Table S1. The mutation status of cancer genes in CRC cell lines used in this study. Data were obtained from reference (25) and COSMIC, the Catalogue of Somatic Mutations in Cancer (http://cancer.sanger.ac.uk).

Erbin belongs to the LAP (leucine-rich repeat and PDZ domain) family of scaffolding proteins that plays important roles in orchestrating cell signaling. Here, we show that Erbin functions as a tumor suppressor in colorectal cancer. Analysis of Erbin expression in colorectal cancer patient specimens revealed that Erbin was downregulated at both mRNA and protein levels in tumor tissues. Knockdown of Erbin disrupted epithelial cell polarity and increased cell proliferation in 3D culture. In addition, silencing Erbin resulted in increased amplitude and duration of signaling through Akt and RAS/RAF pathways. Erbin loss induced epithelial–mesenchymal transition, which coincided with a significant increase in cell migration and invasion. Erbin interacted with kinase suppressor of Ras 1 (KSR1) and displaced it from the RAF/MEK/ERK complex to prevent signal propagation. Furthermore, genetic deletion of Erbin in Apc knockout mice promoted tumorigenesis and significantly reduced survival. Tumor organoids derived from Erbin/Apc double knockout mice displayed increased tumor initiation potential and activation of Wnt signaling. Results from gene set enrichment analysis revealed that Erbin expression associated positively with the E-cadherin adherens junction pathway and negatively with Wnt signaling in human colorectal cancer. Taken together, our study identifies Erbin as a negative regulator of tumor initiation and progression by suppressing Akt and RAS/RAF signaling in vivo.Significance: These findings establish the scaffold protein Erbin as a negative regulator of EMT and tumorigenesis in colorectal cancer through direct suppression of Akt and RAS/RAF signaling. Cancer Res; 78(17); 4839–52. ©2018 AACR.