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There is a need to identify biomarkers predictive of response to neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC). We previously obtained evidence that a polyamine signature in the blood is associated with TNBC development and progression. In this study, we evaluated whether plasma polyamines and other metabolites may identify TNBC patients who are less likely to respond to NACT. Pre-treatment plasma levels of acetylated polyamines were elevated in TNBC patients that had moderate to extensive tumor burden (RCB-II/III) following NACT compared to those that achieved a complete pathological response (pCR/RCB-0) or had minimal residual disease (RCB-I). We further applied artificial intelligence to comprehensive metabolic profiles to identify additional metabolites associated with treatment response. Using a deep learning model (DLM), a metabolite panel consisting of two polyamines as well as nine additional metabolites was developed for improved prediction of RCB-II/III. The DLM has potential clinical value for identifying TNBC patients who are unlikely to respond to NACT and who may benefit from other treatment modalities.

This article draws on data from interviews with sex workers in Welsh massage parlours and individuals involved in the provision of support to migrant sex workers in Wales and England. Drawing on concepts of xeno-racism and ‘everyday ordering’, it illustrates the ways in which policies and state institutions enable violence against sex workers in a way that is increasingly mediated and compounded by race and immigration status. It argues that an awareness of regular and hostile policing practices, coupled with fears of deportation, among a sample of primarily Romanian migrant sex workers is exposing them to increased risks of harm and exploitation.

BackgroundIn the era of big data, artificial intelligence (AI), and the Internet of Things (IoT), digital data have become essential for our everyday functioning and in health care services. The sensitive nature of health care data presents several crucial issues such as privacy, security, interoperability, and reliability that must be addressed in any health care data management system. However, most of the current health care systems are still facing major obstacles and are lacking in some of these areas. This is where decentralized, secure, and scalable databases, most notably blockchains, play critical roles in addressing these requirements without compromising security, thereby attracting considerable interest within the health care community. A blockchain can be maintained and widely distributed using a large network of nodes, mostly computers, each of which stores a full replica of the data. A blockchain protocol is a set of predefined rules or procedures that govern how the nodes interact with the network, view, verify, and add data to the ledger. ObjectiveIn this article, we aim to explore blockchain technology, its framework, current applications, and integration with other innovations, as well as opportunities in diverse areas of health care and clinical research, in addition to clarifying its future impact on the health care ecosystem. We also elucidate 2 case studies to instantiate the potential role of blockchains in health care. MethodsTo identify related existing work, terms based on Medical Subject Headings were used. We included studies focusing mainly on health care and clinical research and developed a functional framework for implementation and testing with data. The literature sources for this systematic review were PubMed, Medline, and the Cochrane library, in addition to a preliminary search of IEEE Xplore. ResultsThe included studies demonstrated multiple framework designs and various implementations in health care including chronic disease diagnosis, management, monitoring, and evaluation. We found that blockchains exhibit many promising applications in clinical trial management such as smart-contract application, participant-controlled data access, trustless protocols, and data validity. Electronic health records (EHRs), patient-centered interoperability, remote patient monitoring, and clinical trial data management were found to be major areas for blockchain usage, which can become a key catalyst for health care innovations. ConclusionsThe potential benefits of blockchains are limitless; however, concrete data on long-term clinical outcomes based on blockchains powered and supplemented by AI and IoT are yet to be obtained. Nonetheless, implementing blockchains as a novel way to integrate EHRs nationwide and manage common clinical problems in an algorithmic fashion has the potential for improving patient outcomes, health care experiences, as well as the overall health and well-being of individuals.

Background Citrulline post-translational modification of proteins is mediated by protein arginine deiminase (PADI) family members and has been associated with autoimmune diseases. The role of PADI-citrullinome in immune response in cancer has not been evaluated. We hypothesized that PADI-mediated citrullinome is a source of neoantigens in cancer that induces immune response.Methods Protein expression of PADI family members was evaluated in 196 cancer cell lines by means of indepth proteomic profiling. Gene expression was assessed using messenger RNA data sets from The Cancer Genome Atlas. Immunohistochemical analysis of PADI2 and peptidyl-citrulline was performed using breast cancer tissue sections. Citrullinated 12–34-mer peptides in the putative Major Histocompatibility Complex-II (MHC-II) binding range were profiled in breast cancer cell lines to investigate the relationship between protein citrullination and antigen presentation. We further evaluated immunoglobulin-bound citrullinome by mass spectrometry using 156 patients with breast cancer and 113 cancer-free controls.Results Proteomic and gene expression analyses revealed PADI2 to be highly expressed in several cancer types including breast cancer. Immunohistochemical analysis of 422 breast tumor tissues revealed increased expression of PADI2 in ER− tumors (p

PurposeThe purpose of this study was to use a mouse model of diet-induced obesity to determine if corneal dysfunction begins prior to the onset of sustained hyperglycemia and if the dysfunction is ameliorated by diet reversal.MethodsSix-week-old male C57BL/6 mice were fed a high fat diet (HFD) or a normal diet (ND) for 5-15 weeks. Diet reversal (DiR) mice were fed a HFD for 5 weeks, followed by a ND for 5 or 10 weeks. Corneal sensitivity was determined using aesthesiometry. Corneal cytokine expression was analyzed using a 32-plex Luminex assay. Excised corneas were prepared for immunofluorescence microscopy to evaluate diet-induced changes and wound healing. For wounding studies, mice were fed a HFD or a ND for 10 days prior to receiving a central 2mm corneal abrasion.ResultsAfter 10 days of HFD consumption, corneal sensitivity declined. By 10 weeks, expression of corneal inflammatory mediators increased and nerve density declined. While diet reversal restored nerve density and sensitivity, the corneas remained in a heightened inflammatory state. After 10 days on the HFD, corneal circadian rhythms (limbal neutrophil accumulation, epithelial cell division and Rev-erbα expression) were blunted. Similarly, leukocyte recruitment after wounding was dysregulated and accompanied by delays in wound closure and nerve recovery.ConclusionIn the mouse, obesogenic diet consumption results in corneal dysfunction that precedes the onset of sustained hyperglycemia. Diet reversal only partially ameliorated this dysfunction, suggesting a HFD diet may have a lasting negative impact on corneal health that is resistant to dietary therapeutic intervention.

This study hypothesizes and tests whether the degree to which managers exercise earnings discretion relates to their value system (i.e., culture) as well as the institutional features (i.e., legal environment) of their country. We find that uncertainty avoidance and individualism dimensions of national culture explain managers' earnings discretion across countries, and that this association varies with the strength of investor protection. This study extends prior literature by documenting that both national culture and institutional structure are important factors that explain corporate managers' earnings discretion practices around the world, and that the influences of these factors on earnings discretion are conditional on each other. [ABSTRACT FROM AUTHOR]

This paper demonstrates a novel quadstable monolithic mechanism (QsMM), which provides four stable equilibrium positions within its planar operation range. The QsMM has been realized from the use of both X- and Y-directional bistable structures, which utilize curved snapping beams. Two pairs of curved beams were attached to an inner frame in both X and Y directions to present an independent bistable behavior in the directions. It was found out that the design of the inner frame is crucial for the quadstability and dynamic responses of the mechanism. A millimeter-scale brass mechanism was actually fabricated by ultraprecision milling to test the quadstability and the force-displacement behavior. The prototype clearly demonstrates four distinct stable positions in its millimeter-scale operation range. The design concept, finite element simulation, fabrication, and experimental measurement of the proposed multistable mechanism have been presented. The mechanical multistability of the proposed QsMM can be utilized for multiple switching and optical networking applications, yielding low power consumption operations. [ABSTRACT FROM AUTHOR]

Octopamine and tyramine, both biogenic amines, are bioactive chemicals important in diverse physiological processes in invertebrates. In insects, octopamine and tyramine operate analogously to epinephrine and norepinephrine in the vertebrates. Octopamine and tyramine bind to G-protein coupled receptors (GPCRs) leading to changes in second messenger levels and thereby modifying the function in target tissues and insect behavior. In this paper, we report the cDNA sequences of two GPCRs, RhoprOctβ2-R, and RhoprTyr1-R, have been cloned and functionally characterized from Rhodnius prolixus. Octopamine and tyramine each activate RhoprOctβ2-R and RhoprTyr1-R in a dose-dependent manner. Octopamine is one order of magnitude more potent than tyramine in activating RhoprOctβ2-R. Tyramine is two orders of magnitude more potent than octopamine in activating RhoprTyr1-R. Phentolamine and gramine significantly antagonize RhoprOctβ2-R, whereas yohimbine and phenoxybenzamine are effective blockers of RhoprTyr1-R. The transcripts of both receptors are enriched in the central nervous system (CNS) and are expressed throughout the adult female reproductive system. It has been shown in other insects that Octβ2-R is essential for processes such as ovulation and fertilization. We previously reported that octopamine and tyramine modulate oviducts and bursa contractions in R. prolixus. Our data confirm the importance of octopamine and tyramine signaling in the reproductive system of R. prolixus.

Background: The mechanisms underlying the initiation of sustained ventricular tachycardia (VT) have not been fully elucidated. The extent to which reentry, abnormal automaticity, and triggered activity play a role in VT differs depending on the etiology of left ventricular dysfunction. By analyzing electrograms from implantable cardioverter defibrillator (ICD), we sought to determine whether there were differences in VT initiation patterns between patients with ischemic and nonischemic cardiomyopathy. Methods: We analyzed ICD electrograms in patients with ejection fractions < 40% who had sustained VT over a 27‐month period. The trigger for VT onset was classified as a ventricular premature beat (VPB), supraventricular tachycardia, or of “sudden onset.” The baseline cycle length, VT cycle length, coupling interval, and prematurity ratio were recorded for each event. The prematurity ratio was calculated as the coupling interval of the VT initiator divided by the baseline cycle length. Results: Sixty‐three VT events in 14 patients met the inclusion criteria. A VPB initiated the VT in 58 episodes (92%), 1 episode (2%) was initiated by a supraventricular tachycardia, and 4 episodes (6%) were sudden onset. The prematurity ratio was significantly higher (P < 0.05) in patients with ischemic cardiomyopathy (0.751 ± 0.068) as compared to patients with nonischemic cardiomyopathy (0.604 ± 0.139). Conclusion: VPBs initiated most sustained VT episodes. A significantly higher prematurity ratio was observed in the ischemic heart disease group. This may represent different mechanisms of VT initiation in patients with ischemic versus nonischemic heart disease.

This article describes an interesting case of automated implantable cardioverter defibrillator (AICD) extrusion fifteen months after implantation. The case report is followed by a discussion of the causes and treatment of skin erosion following pacemaker/AICD insertion.

A 67 year old man presented with a serum potassium of 7.7 mEq/L and slow atrial flutter with variable A-V block and peaked T waves. Initial treatment for hyperkalemia was followed by an increase in the atrial flutter rate to 300 beats per minute. After hemodialysis the rhythm converted to sinus.

Background: Cardiac Resynchronization Therapy (CRT) is indicated for the treatment of advanced heart failure with severe systolic dysfunction and intraventricular conduction delay. Patient selection for this technology is vital, though it remains unclear which patients benefit most from CRT. We tested the hypothesis that patients with non-ischemic cardiomyopathy have a superior mortality benefit from CRT than ischemic cardiomyopathy patients. Methods: We evaluated 95 CRT patients to determine which factors predict mortality.Results: Patients with non-ischemic cardiomyopathy had a significantly better prognosis than patients with ischemic cardiomyopathy.Conclusion: Larger prospective studies can substantiate this finding and better delineate which patients benefit most from CRT.

The following article presents an unusual case of atrial tachycardia, initially misdiagnosed due to a lack of clear P waves. The diagnosis was eventually confirmed using the atrial electrogram from the patients pacemaker.

Tumor-derived, circulating proteins are potentially useful as biomarkers for detection of cancer, for monitoring of disease progression, regression and recurrence, and for assessment of therapeutic response. Here we interrogated how a protein's stability, cellular localization, and abundance affect its observability in blood by mass-spectrometry-based proteomics techniques. We performed proteomic profiling on tumors and plasma from two different xenograft mouse models. A statistical analysis of this data revealed protein properties indicative of the detection level in plasma. Though 20% of the proteins identified in plasma were tumor-derived, only 5% of the proteins observed in the tumor tissue were found in plasma. Both intracellular and extracellular tumor proteins were observed in plasma; however, after normalizing for tumor abundance, extracellular proteins were seven times more likely to be detected. Although proteins that were more abundant in the tumor were also more likely to be observed in plasma, the relationship was nonlinear: Doubling the spectral count increased detection rate by only 50%. Many secreted proteins, even those with relatively low spectral count, were observed in plasma, but few low abundance intracellular proteins were observed. Proteins predicted to be stable by dipeptide composition were significantly more likely to be identified in plasma than less stable proteins. The number of tryptic peptides in a protein was not significantly related to the chance of a protein being observed in plasma. Quantitative comparison of large versus small tumors revealed that the abundance of proteins in plasma as measured by spectral count was associated with the tumor size, but the relationship was not one-to-one; a 3-fold decrease in tumor size resulted in a 16-fold decrease in protein abundance in plasma. This study provides quantitative support for a tumor-derived marker prioritization strategy that favors secreted and stable proteins over all but the most abundant intracellular proteins.

Due to the increasing use of polypropylene-based nonwoven dust masks and air filters, environmental problems that occur due to the plastic pollution resulting from the disposal of these materials have also increased. Hence, an eco-friendly air filter based on PVA nanofibers (NFs) was fabricated by electrospinning on a nonwoven fabric, and its performance was evaluated as a filter capable of blocking or capturing particulate matter. The quality factor of the optimized PVA NF-based air filter was found to be 0.010606 Pa−1, which is lower than that of a HEPA filter (0.015394 Pa−1), but higher than that of a cabin air filter (0.010517 Pa−1) and a dust mask (0.009102 Pa−1). The contamination level of the PVA NF-based filter was analyzed by optical and structural analyses of the filter surface. Finally, the filter was soaked in water to selectively remove the contaminated PVA NF layer, and the remaining nonwoven fabric was able to be reused to make the filter.