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This case study of one university's students and their support-seeking behaviors offers an initial explanation of what types of social support students sought during the pandemic and if their needs were met. This study fills a gap in the literature, as it addresses where students actually sought support during this time of crisis, and based on this analysis, we offer applications for how universities can be ready to support students even more effectively the next time an unexpected crisis occurs. Implications for institutional social support services at universities and more accessible opportunities for institutional support are discussed. As universities continue to evolve to meet holistic student needs during this stressful time, the evaluation of students' access to support is discussed. Thus, this investigation bridges a divide between college students' COVID-related stress and support services by measuring their support-seeking behaviors during the pandemic. [ABSTRACT FROM AUTHOR]

Over the past 40 years fundamental and application research into Surface-Enhanced Raman Scattering (SERS) has been explored by academia, industry, and government laboratories. To date however, SERS has achieved little commercial success as an analytical technique. Researchers are tackling a variety of paths to help break through the commercial barrier by addressing the reproducibility in both the SERS substrates and SERS signals as well as continuing to explore the underlying mechanisms. To this end, investigators use a variety of methodologies, typically studying strongly binding analytes such as aromatic thiols and azarenes, and report SERS enhancement factor calculations. However a drawback of the traditional SERS enhancement factor calculation is that it does not yield enough information to understand substrate reproducibility, application potential with another analyte, or the driving factors behind the molecule–metal interaction. Our work at the US Army Edgewood Chemical Biological Center has focused on these questions and we have shown that thermodynamic principles play a key role in the SERS response and are an essential factor in future designs of substrates and applications. This work will discuss the advantages and disadvantages of various experimental techniques used to report SERS enhancement with planar SERS substrates and present our alternative SERS enhancement value. We will report on three types of analysis scenarios that all yield different information concerning the effectiveness of the SERS substrate, practical application of the substrate, and finally the thermodynamic properties of the substrate. We believe that through this work a greater understanding for designing substrates will be achieved, one that is based on both thermodynamic and plasmonic properties as opposed to just plasmonic properties. This new understanding and potential change in substrate design will enable more applications for SERS based methodologies including targeting molecules that are traditionally not easily detected with SERS due to the perceived weak molecule–metal interaction of substrates. [ABSTRACT FROM AUTHOR]

A sensitive chemical aerosol Raman detector (CARD) has been developed for the trace detection and identification of chemical particles in the ambient atmosphere. CARD includes an improved aerosol concentrator with a concentration factor of about 40 and a CCD camera for improved detection sensitivity. Aerosolized isovanillin, which is relatively safe, has been used to characterize the performance of the CARD. The limit of detection (SNR = 10) for isovanillin in 15 s has been determined to be 1.6 pg/cm³, which corresponds to 6.3 × 109 molecules/cm³ or 0.26 ppb. While less sensitive, CARD can also detect gases. This paper provides a more detailed description of the CARD hardware and detection algorithm than has previously been published. [ABSTRACT FROM AUTHOR]

The records of 335 patients admitted to the general medicine wards and to the medical intensive and coronary care unit (MICCU) at Brooke Army Medical Center were retrospectively reviewed to assess the frequency of advance directives and "do not resuscitate" (DNR) designations. Two hundred sixty-seven (79.7%) were admitted to the ward and 68 (20.3%) were admitted to the MICCU. Advance directives were executed in 14.9% of patients. DNR designations were made for 21 (7.9%) patients on the ward and 11 (16.2%) patients in the MICCU (p = 0.064). There were no statistical differences in mean length of stay, presence of advance directives, or documentation of advance directives in ward versus MICCU patients. However, there was a statistical difference in the number of deaths in the MICCU as compared with that on the ward (9.7 vs. 2.7%, p < 0.05). The frequency of advance directives and DNR designations did not differ between ward and MICCU patients in this population, although there was a trend for greater DNR designations in the MICCU environment. [ABSTRACT FROM AUTHOR]

Land-based mazes that require spatial cues to identify the location of a hiding-place are a low-stress method to evaluate learning rate and memory retention in mice. One version, the Barnes maze, allows quantification of naturalistic exploratory behaviors not evident in water-based tasks. As the task relies on innate behaviors, it does not require overtraining, making it more feasible to examine early learning and non-memory executive functions that are characteristic of some non-amnestic dementias. However, because it is difficult to hide odor cues in the traditional version of the maze, learning rate during individual trials can be difficult to interpret. We designed and tested the use of 3D-printed escape shuttles that can be made in duplicate, as well as a docking tunnel that allows mice to self-exit the maze to improve reproducibility and limit experimenter influence. In combination with maze turning and escape tunnel caps, we show our shuttles mitigate the possibility of undesired cues. We then compare use of our 4-day protocol across several mouse models of cognitive impairment. We demonstrate an additional stage, the STARR protocol (Spatial Training and Rapid Reversal), to better challenge executive functions such as working memory and behavioral flexibility. We examine commonly used outcome measures across mice with and without access to spatial cues, as well as across mouse models of cognitive impairment to demonstrate the use of our 4-day protocol. Overall, this protocol provides detailed instructions to build and perform a robust spatial maze that can help expand the range of deficits identified. Our findings will aid in interpretation of traditional protocols, as well as provide an updated method to screen for both amnestic and non-amnestic cognitive changes.

Hydrogen peroxide (H 2 O 2 ) is a highly effective decontaminant against chemical warfare agents (CWAs) when present both in a liquid and as a solid powder. For the latter, this can be in the form of H 2 O 2 being complexed to a polymer, such as polyvinylpyrrolidone (PVP). While a H 2 O 2 -PVP complex is indeed effective at decontaminating CWAs, it is vulnerable to environmental conditions such as high relative humidities (RH), which can dissociate the H 2 O 2 from the complex before it is given the opportunity to react with CWAs. In this paper, we demonstrate that the cross-linked version of PVP forms a highly stable complex with H 2 O 2 , which can withstand both high (40 °C) and low (-20 °C) temperatures as well as maintain stability at high RH up to 90% over several days. Collectively, this lays the framework for processing the H 2 O 2 -PVP complex in a variety of form factors that can maintain efficacy under a wide range of real-world environmental conditions.

Cancer therapy often results in heterogeneous responses in different metastatic lesions in the same patient. Inter- and intratumor heterogeneity in signaling within various tumor compartments and its impact on therapy are not well characterized due to the limited sensitivity of single-cell proteomic approaches. To overcome this barrier, we applied single-cell mass cytometry with a customized 26-antibody panel to PTEN-deleted orthotopic prostate cancer xenograft models to measure the evolution of kinase activities in different tumor compartments during metastasis or drug treatment. Compared with primary tumors and circulating tumor cells (CTC), bone metastases, but not lung and liver metastases, exhibited elevated PI3K/mTOR signaling and overexpressed receptor tyrosine kinases (RTK) including c-MET protein. Suppression of c-MET impaired tumor growth in the bone. Intratumoral heterogeneity within tumor compartments also arose from highly proliferative EpCAM-high epithelial cells with increased PI3K and mTOR kinase activities coexisting with poorly proliferating EpCAM-low mesenchymal populations with reduced kinase activities; these findings were recapitulated in epithelial and mesenchymal CTC populations in patients with metastatic prostate and breast cancer. Increased kinase activity in EpCAM-high cells rendered them more sensitive to PI3K/mTOR inhibition, and drug-resistant EpCAM-low populations with reduced kinase activity emerged over time. Taken together, single-cell proteomics indicate that microenvironment- and cell state-dependent activation of kinase networks create heterogeneity and differential drug sensitivity among and within tumor populations across different sites, defining a new paradigm of drug responses to kinase inhibitors., Significance: Single-cell mass cytometry analyses provide insights into the differences in kinase activities across tumor compartments and cell states, which contribute to heterogeneous responses to targeted therapies., (©2022 American Association for Cancer Research.)

Behavioral flexibility requires the prefrontal cortex and striatum, but it is unclear if these structures play similar or distinct roles in adapting to novel circumstances. Here, we investigate neuronal ensembles in the medial frontal cortex (MFC) and the dorsomedial striatum (DMS) during one form of behavioral flexibility: learning a new temporal interval. We studied corticostriatal neuronal activity as rodents trained to respond after a 12-s fixed interval (FI12) learned to respond at a shorter 3-s fixed interval (FI3). On FI12 trials, we found that a key form of temporal processing-time-related ramping activity-decreased in the MFC but did not change in the DMS as animals learned to respond at a shorter interval. However, while MFC and DMS ramping was stable with successive days of two-interval performance, temporal decoding by DMS ensembles improved on FI3 trials. Finally, when comparing FI12 versus FI3 trials, we found that more DMS neurons than MFC neurons exhibited differential interval-related activity early in two-interval performance. These data suggest that the MFC and DMS play distinct roles during temporal learning and provide insight into corticostriatal circuits., (© The Author(s) 2020. Published by Oxford University Press.)

Tumor-stromal communication within the microenvironment contributes to initiation of metastasis and may present a therapeutic opportunity. Using serial single-cell RNA sequencing in an orthotopic mouse prostate cancer model, we find up-regulation of prolactin receptor as cancer cells that have disseminated to the lungs expand into micrometastases. Secretion of the ligand prolactin by adjacent lung stromal cells is induced by tumor cell production of the COX-2 synthetic product prostaglandin E2 (PGE2). PGE2 treatment of fibroblasts activates the orphan nuclear receptor NR4A (Nur77), with prolactin as a major transcriptional target for the NR4A-retinoid X receptor (RXR) heterodimer. Ectopic expression of prolactin receptor in mouse cancer cells enhances micrometastasis, while treatment with the COX-2 inhibitor celecoxib abrogates prolactin secretion by fibroblasts and reduces tumor initiation. Across multiple human cancers, COX-2, prolactin, and prolactin receptor show consistent differential expression in tumor and stromal compartments. Such paracrine cross-talk may thus contribute to the documented efficacy of COX-2 inhibitors in cancer suppression., Competing Interests: Conflict of interest statement: Massachusetts General Hospital has filed for patent protection for the circulating tumor cell inertial focusing (iChip) technology., (Copyright © 2019 the Author(s). Published by PNAS.)

Blood-based biomarkers are critical in metastatic prostate cancer, where characteristic bone metastases are not readily sampled, and they may enable risk stratification in localized disease. We established a sensitive and high-throughput strategy for analyzing prostate circulating tumor cells (CTC) using microfluidic cell enrichment followed by digital quantitation of prostate-derived transcripts. In a prospective study of 27 patients with metastatic castration-resistant prostate cancer treated with first-line abiraterone, pretreatment elevation of the digital CTC M score identifies a high-risk population with poor overall survival (HR = 6.0; P = 0.01) and short radiographic progression-free survival (HR = 3.2; P = 0.046). Expression of HOXB13 in CTCs identifies 6 of 6 patients with ≤12-month survival, with a subset also expressing the ARV7 splice variant. In a second cohort of 34 men with localized prostate cancer, an elevated preoperative CTC L score predicts microscopic dissemination to seminal vesicles and/or lymph nodes ( P < 0.001). Thus, digital quantitation of CTC-specific transcripts enables noninvasive monitoring that may guide treatment selection in both metastatic and localized prostate cancer. Significance: There is an unmet need for biomarkers to guide prostate cancer therapies, for curative treatment of localized cancer and for application of molecularly targeted agents in metastatic disease. Digital quantitation of prostate CTC-derived transcripts in blood specimens is predictive of abiraterone response in metastatic cancer and of early dissemination in localized cancer. Cancer Discov; 8(3); 288-303. ©2018 AACR. See related commentary by Heitzer and Speicher, p. 269 This article is highlighted in the In This Issue feature, p. 253 ., (©2018 American Association for Cancer Research.)

Metastasis-competent circulating tumour cells (CTCs) experience oxidative stress in the bloodstream, but their survival mechanisms are not well defined. Here, comparing single-cell RNA-Seq profiles of CTCs from breast, prostate and lung cancers, we observe consistent induction of β-globin (HBB), but not its partner α-globin (HBA). The tumour-specific origin of HBB is confirmed by sequence polymorphisms within human xenograft-derived CTCs in mouse models. Increased intracellular reactive oxygen species (ROS) in cultured breast CTCs triggers HBB induction, mediated through the transcriptional regulator KLF4. Depletion of HBB in CTC-derived cultures has minimal effects on primary tumour growth, but it greatly increases apoptosis following ROS exposure, and dramatically reduces CTC-derived lung metastases. These effects are reversed by the anti-oxidant N-Acetyl Cysteine. Conversely, overexpression of HBB is sufficient to suppress intracellular ROS within CTCs. Altogether, these observations suggest that β-globin is selectively deregulated in cancer cells, mediating a cytoprotective effect during blood-borne metastasis.

The neurotransmitter dopamine acts via two major classes of receptors, D1-type and D2-type. D1 receptors are highly expressed in the striatum and can also be found in the cerebral cortex. Here we review the role of D1 dopamine signaling in two major domains: L-DOPA-induced dyskinesias in Parkinson's disease and cognition in neuropsychiatric disorders. While there are many drugs targeting D2-type receptors, there are no drugs that specifically target D1 receptors. It has been difficult to use selective D1-receptor agonists for clinical applications due to issues with bioavailability, binding affinity, pharmacological kinetics, and side effects. We propose potential therapies that selectively modulate D1 dopamine signaling by targeting second messengers downstream of D1 receptors, allosteric modulators, or by making targeted modifications to D1-receptor machinery. The development of therapies specific to D1-receptor signaling could be a new frontier in the treatment of neurological and psychiatric disorders., Competing Interests: Compliance with ethics guidelines 1) Conflict of Interest Young-Cho Kim, Stephanie L. Alberico, Eric Emmons, and Nandakumar S. Narayanan declare that they have no conflict of interest.

Cationic and anionic residues of the extracellular matrices (ECM) of bone play synergistic roles in recruiting precursor ions and templating the nucleation, growth and crystalline transformations of calcium apatite in natural biomineralization. We previously reported that zwitterionic sulfobetaine ligands can template extensive 3-dimensional (3-D) hydroxyapaptite (HA)-mineralization of photo-crosslinked polymethacrylatehydrogels. Here, we compared the potency of two other major zwitterionic ligands, phosphobetaine and carboxybetaine, with that of the sulfobetaine in mediating 3-D mineralization using the crosslinked polymethacrylate hydrogel platform. We confirmed that all three zwitterionic hydrogels were able to effectively template 3-D mineralization, supporting the general ability of zwitterions to mediate templated mineralization. Among them, however, sulfobetaine and phosphobetaine hydrogels templated denser 3-D mineralizationthan the carboxybetaine hydrogel, likely due to their higher free water fractions and better maintenance of zwitterionic nature throughout the pH-changes during the in vitro mineralization process. We further demonstrated that the extensively mineralized zwitterionic hydrogels could be exploited for efficient retention (e.g. 99% retention after 24-h incubation in PBS) of osteogenic growth factor recombinant bone morphogenetic protein-2 (rhBMP-2) and subsequent sustained local release with retained bioactivity. Combined with the excellent cytocompatibility of all three zwitterionic hydrogels and the significantly improved cell adhesive properties of their mineralized matrices, these materials could find promising applications in bone tissue engineering.

Raman chemical imaging (RCI) has been used to detect and identify explosives in contaminated fingerprints. Bright-field imaging is used to identify regions of interest within a fingerprint, which can then be examined to determine their chemical composition using RCI and fluorescence imaging. Results are presented where explosives in contaminated fingerprints are identified and their spatial distributions are obtained. Identification of explosives is obtained using Pearson's cosine cross-correlation technique using the characteristic region (500-1850 cm(-1)) of the spectrum. This study shows the ability to identify explosives nondestructively so that the fingerprint remains intact for further biometric analysis. Prospects for forensic examination of contaminated fingerprints are discussed.

High-pressure Raman spectroscopy and X-ray diffraction of THV 500, a terpolymer of tetrafluoroethylene-hexafluoropropylene-vinylidene fluoride, were performed using diamond anvil cells (DAC). Changes in the interatomic spacing as well as shifts of several of the vibrational bands as a function of pressure were measured up to approximately 10 GPa. The changes in interatomic spacing and shifts of the vibrational bands are compared to those of polytetrafluoroethylene, showing the effects of copolymerization and reduced crystallinity. The high-pressure behavior of polymers is a relatively unexplored field but is becoming increasingly important due to applications where polymers experience extreme conditions.

Neutral C60 is well known to exhibit a giant resonance in its photon absorption spectrum near 20 eV. This is associated with a surface plasmon, where delocalized electrons oscillate as a whole relative to the ionic cage. Absolute photoionization cross-section measurements for C+60, C2+60, and C3+60 ions in the 17-75 eV energy range show an additional resonance near 40 eV. Time-dependent density functional calculations confirm the collective nature of this feature, which is characterized as a dipole-excited volume plasmon made possible by the special fullerene geometry.

Objective: To determine how often screening electrocardiograms (EKGs), which are required by military regulation, change management or disclose cardiac disease in healthy people., Methods: A total of 1,718 consecutive EKG interpretations, whether or not the screening EKG led to further testing, disclosed serious or potentially serious cardiac disease, or changed management or disposition of the patient, were prospectively recorded., Results: Thirty-four percent of the screening EKGs was abnormal. Seven (0.67%) of these abnormal EKGs altered management by leading to further consultation or testing. No screening EKG disclosed serious underlying cardiac disease. Two cases of potentially serious cardiac disease were discovered by the screening EKGs. At an average follow-up time of 34 months, neither of these two patients has developed serious cardiac disease. Our findings are similar to studies of other populations., Conclusion: Screening EKGs rarely caused a change in management. No adverse outcome would have occurred nor would serious cardiac disease have been missed if the routine screening EKG were not performed. The military should consider abandoning practice of performing screening EKGs in young, healthy individuals.

During the deployment of U.S. troops to the former Republic of Yugoslavia in support of Operation Joint Endeavor and the Dayton Peace Accords from December 1995 to December 1996, members of a deployed field hospital were exposed to a case of active tuberculosis from a local civilian worker. Tuberculin skin testing of civilian contacts of the index patient revealed 76% reactivity. Testing of exposed unit members revealed a 1.3% conversion rate upon redeployment, versus a 2.0% conversion rate for redeployed soldiers as a whole. More importantly, tuberculin skin testing of locally hired civilian workers as a whole revealed a 44% background positive rate, raising significant force-protection concerns and highlighting the role of occupational medicine and the need for screening of civilian employees in operations other than war.