Miracle-dz/UniFAR-FTUs huggingface dataset:
Response by Schneider et al to Letter Regarding Article, "Treatment Effect of Drug-Coated Balloons Is Durable to 3 Years in the Femoropopliteal Arteries: Long-Term Results of the IN.PACT SFA Randomized Trial".

Dan et al describe paclitaxel as the pharmaceutical component of a coronary drug-eluting stent removed from the market because of safety and efficacy concerns. Paclitaxel has demonstrated a different clinical profile in the lower extremity, whether delivered by balloon or stent. The IN.PACT SFA trial studied the use of the IN.PACT Admiral drug-coated balloon (DCB) in the SFA and proximal popliteal arteries, and IN.PACT DEEP trial used the IN.PACT Amphirion DCB in the infrapopliteal arteries.1,2 These DCBs are completely different devices used in disparate populations for distinct conditions. IN.PACT Admiral is commercially available based on safety and efficacy in rigorously collected and adjudicated clinical trials and is coated with 3.5 μg/mm2 paclitaxel. IN.PACT Amphirion—a DCB with a different balloon material and coating methodology—is no longer on …
Endogenous Control Mechanisms of FAK and PYK2 and Their Relevance to Cancer Development

Focal adhesion kinase (FAK) and its close paralogue, proline-rich tyrosine kinase 2 (PYK2), are key regulators of aggressive spreading and metastasis of cancer cells. While targeted small-molecule inhibitors of FAK and PYK2 have been found to have promising antitumor activity, their clinical long-term efficacy may be undermined by the strong capacity of cancer cells to evade anti-kinase drugs. In healthy cells, the expression and/or function of FAK and PYK2 is tightly controlled via modulation of gene expression, competing alternatively spliced forms, non-coding RNAs, and proteins that directly or indirectly affect kinase activation or protein stability. The molecular factors involved in this control are frequently deregulated in cancer cells. Here, we review the endogenous mechanisms controlling FAK and PYK2, and with particular focus on how these mechanisms could inspire or improve anticancer therapies.
Multivariate CACE Analysis with an Application to Arthritis Health Journal Study

Treatment noncompliance is a common issue in randomized controlled trials that may plague the randomization settings and bias the treatment effect estimation. The complieraverage causal effect (CACE) model has become popular in estimating the method effectiveness under noncompliance. Performing multiple univariate CACE analysis separately fails to capture the potential correlations among multivariate outcomes, which will lead to biased estimates and significant loss of power in detecting actual treatment effect. Motivated by the Arthritis Health Journal Study, we propose a multivariate CACE model to better account for the correlations among outcomes. In our simulation study, the global likelihood ratio test is conducted to evaluate the treatment effect which fails to control the type I error for moderate sample sizes. So, we further perform a parametric bootstrap test to address this issue. Our simulation results suggest that the Multivariate CACE model outperforms multiple Univariate CACE models in the precision of estimation and statistical power in the case of correlated multivariate outcomes.
The Vaginal Microenvironment: The Physiologic Role of Lactobacilli

In addition to being a passage for sperm, menstruum, and the baby, the human vagina and its microbiota can influence conception, pregnancy, the mode and timing of delivery, and the risk of acquiring sexually transmitted infections. The physiological status of the vaginal milieu is important for the wellbeing of the host as well as for successful reproduction. High estrogen states, as seen during puberty and pregnancy, promote the preservation of a homeostatic (eubiotic) vaginal microenvironment by stimulating the maturation and proliferation of vaginal epithelial cells and the accumulation of glycogen. A glycogen-rich vaginal milieu is a haven for the proliferation of Lactobacilli facilitated by the production of lactic acid and decreased pH. Lactobacilli and their antimicrobial and anti-inflammatory products along with components of the epithelial mucosal barrier provide an effective first line defense against invading pathogens including bacterial vaginosis, aerobic vaginitis-associated bacteria, viruses, fungi and protozoa. An optimal host-microbial interaction is required for the maintenance of eubiosis and vaginal health. This review explores the composition, function and adaptive mechanisms of the vaginal microbiome in health and those disease states in which there is a breach in the host-microbial relationship. The potential impact of vaginal dysbiosis on reproduction is also outlined.
Successful re‐introduction of vitamin B12 after using isotretinoin to treat severe acne medicamentosa

after several months or even years without active intervention; however, relapses are common. MCND and habit-tic deformity are rare and remain poorly understood conditions of the nail. In both conditions, macrolunulae are seen in the affected thumbs but may also be present in other digits. Although these conditions are uncommon, the diagnosis, associated findings and potential predisposition to injury should be kept in mind by treating clinicians. Further evidence is required to definitively recognise an association, and we would encourage any clinicians working with nails to consider recording data in this context and consider publication.
Wearables in Medicine

Wearables as medical technologies are becoming an integral part of personal analytics, measuring physical status, recording physiological parameters, or informing schedule for medication. These continuously evolving technology platforms do not only promise to help people pursue a healthier life style, but also provide continuous medical data for actively tracking metabolic status, diagnosis, and treatment. Advances in the miniaturization of flexible electronics, electrochemical biosensors, microfluidics, and artificial intelligence algorithms have led to wearable devices that can generate real‐time medical data within the Internet of things. These flexible devices can be configured to make conformal contact with epidermal, ocular, intracochlear, and dental interfaces to collect biochemical or electrophysiological signals. This article discusses consumer trends in wearable electronics, commercial and emerging devices, and fabrication methods. It also reviews real‐time monitoring of vital signs using biosensors, stimuli‐responsive materials for drug delivery, and closed‐loop theranostic systems. It covers future challenges in augmented, virtual, and mixed reality, communication modes, energy management, displays, conformity, and data safety. The development of patient‐oriented wearable technologies and their incorporation in randomized clinical trials will facilitate the design of safe and effective approaches.
Intratumoral Delivery of an Adenoviral Vector Carrying the SOCS-1 Gene Enhances T-Cell–Mediated Antitumor Immunity By Suppressing PD-L1

Ovarian cancer is the leading cause of gynecologic cancer-related deaths and novel therapeutic strategies are required. Programmed cell death 1 and programmed cell death ligand 1 (PD-L1), which are key mediators of host immune tolerance, are associated with ovarian cancer progression. Recent evidence indicates the importance of IFNγ-induced PD-L1 for immune tolerance in ovarian cancer. This study aimed to reveal the therapeutic potential of suppressor of cytokine signaling 1 (SOCS-1), an endogenous inhibitor of the Janus kinase (JAK)–STAT signaling pathway, for the treatment of ovarian cancer. IHC assessment revealed that patients with ovarian cancer with high intratumoral STAT1 activation exhibited poor prognosis compared with patients with low STAT1 activation (P < 0.05). Stimulation of OVISE, OVTOKO, OV2944-HM-1 (HM-1), and CT26 cell lines with IFNγ induced STAT1 phosphorylation and PD-L1 expression. Adenovirus-mediated SOCS-1 gene delivery (AdSOCS-1) in HM-1 and CT26 cells in vitro potently inhibited IFNγ-induced STAT1 phosphorylation and PD-L1 upregulation, similar to the addition of JAK inhibitor I, but failed to inhibit their proliferation. Notably, intratumoral injection of AdSOCS-1, but not AdLacZ, significantly inhibited the tumor growth of HM-1 and CT26 cells subcutaneously transplanted in immunocompetent syngeneic mice. AdSOCS-1 reduced PD-L1 expression on tumors and restored the activation of tumor-infiltrating CD8+ T cells. Moreover, the antitumor effect of AdSOCS-1 was significantly attenuated by PD-L1 Fc-fusion protein administration in vivo, suggesting that the effect of AdSOCS-1 is mainly attributable to enhancement of tumor immunity. This study highlights the potential clinical utility of SOCS-1 as an immune checkpoint inhibitor. Mol Cancer Ther; 17(9); 1941–50. ©2018 AACR.
Left ventricular apical aneurysm in hypertrophic cardiomyopathy as a risk factor for sudden death at any age

In hypertrophic cardiomyopathy (HCM) aging has proved protective against sudden death (SD) risk and aggressive recommendations for prophylactic ICDs are uncommon in patients ≥60 years. Nevertheless, we present a patient with an unexpected but aborted sudden death event at the advanced age of 71 years due to a left ventricular apical aneurysm (LVAA) which has emerged as a novel SD marker. Subsequent reappraisal of the Tufts HCM database, specifically the 118 LVAA patients, showed that 36% of SD events occurred at ≥60 years. Of HCM patients ≥ 60 years, SD was 8‐fold more common with aneurysm than without aneurysms (16% vs 2%; P < 0.001). Risk in HCM with LVAA persists throughout life and senior LVAA patients should also be considered for primary prevention of SD with the ICD.
Parental Decision-Making on Childhood Vaccination

A growing number of parents delay vaccinations or are deciding not to vaccinate their children altogether. This increases the risk of contracting vaccine-preventable diseases and disrupting herd immunity, and also impairs the trust in the capacities of health care systems to protect people. Vaccine hesitancy is related to a range of both psychological and demographic determinants, such as attitudes toward vaccinations, social norms, and trust in science. Our aim is to understand those determinants in parents, because they are a special group in this issue—they act as proxy decision makers for their children, who are unable to decide for themselves. The fact that deciding to vaccinate is a socially forced choice that concerns a child's health makes vaccine-related decisions highly important and involving for parents. This high involvement might lead to parents overemphasizing the potential side effects that they know to be vaccine-related, and by amplifying those, parents are more focused on the potential outcomes of vaccine-related decisions, which can yield specific pattern of the outcome bias. We propose two related studies to investigate factors which promote vaccine hesitancy, protective factors that determine parental vaccination decisions, and outcome bias in parental vaccination intentions. We will explore demographic and psychological factors, and test parental involvement related to vaccine hesitancy using an online battery in a correlation panel design study. The second study is an experimental study, in which we will investigate the moderating role of parents' high involvement in the specific domain of vaccination decision making. We expect that higher involvement among parents, compared to non-parents, will shape the pattern of the proneness to outcome bias. The studies will be conducted across eight countries in Europe and Asia (Finland, Germany, Hong Kong, the Netherlands, Serbia, Slovenia, Spain, and the United Kingdom), rendering findings that will aid with understanding the underlying mechanisms of vaccine hesitancy and paving the way for developing interventions custom-made for parents.
Renal inpatient ward nurse experience and job satisfaction: A qualitative study.

AIMS AND OBJECTIVES To examine the experience of registered nurses working in renal inpatients wards at an acute National Health Service (NHS) hospital Trust. Nurse perceptions of their experience particularly in relation to job satisfaction were analysed. BACKGROUND Increased understanding of workplace organisation and culture can contribute to improved nurse work experience and better patient care. Worldwide many studies conducted on nurse experience and job satisfaction show that job satisfaction level varies across work settings so analysis of job satisfaction at a local level such as in a ward is important for producing useful analysis and recommendations. METHOD Using purposive sampling, semistructured individual interviews were conducted on twelve registered nurses working on renal inpatient wards. RESULTS The study identified three themes: safe care, organisational culture and work environment. Although staffing was identified as a key element to providing safe care maintaining adequate staffing levels remained a challenge. Whilst there were opportunities for professional development more support is needed for newly qualified nurses. CONCLUSIONS Findings highlighted that renal patients were complex. It is important to maintain adequate staffing levels. Good clinical leadership is required to support and develop the positive experience of nurses. RELEVANCE TO CLINICAL PRACTICE The high turnover of newly qualified nurses is a particular problem and nurse managers need to develop strategies to retain such nurses. Regular audits on staffing levels as part of improving workforce planning and patient safety need to be conducted.
Assessment of accuracy of out-of-field dose calculations by TiGRT treatment planning system in radiotherapy

Aim: The objective was to quantify the accuracy of dose calculation for out-of-field regions by the commercially available TiGRT version 1.2 (LinaTech, Sunnyvale, CA, USA) treatment planning system (TPS) for a clinical treatment delivered on a Siemens Primus with the single energy of 6 MV. Materials and Methods: Two tangential open fields were planned by TiGRT TPS to irradiate the left breast of a RANDO phantom. Dose values to out-of-field points were calculated by TiGRT TPS. A RANDO phantom was then irradiated, and dose values at set points were measured using thermoluminescent detectors-100 (TLDs-100) which were located within the phantom. Finally, the TLD-measured dose was compared to the TPS-calculated dose and the accuracy of TPS calculations at different distances from the field edge was quantified. Results: The measurements showed that TiGRT TPS generally underestimated the dose of out-of-field points and this underestimation worsened for regions relatively close to the treatment field edge. The mean underestimation of out-of-field doses was 39%. Nevertheless, the accuracy of dose calculation by this TPS for most in-field regions was within tolerance. Conclusion: This study highlights the limitations of TiGRT TPSs in calculating of the out-of-field dose. It should be noted that out-of-field data for this TPS should only be applied with a certain understanding of the accuracy of calculated dose outside the treatment field. Therefore, using the TPS-calculated dose could lead to an underestimation of secondary cancer risk as well as a weak clinical decision for patients with implantable cardiac pacemakers or pregnant patients.
Chiral behaviour for three wave guides at an exceptional point of third order

A simple matrix model that has been used to describe essential features of a PT symmetric set-up of three coupled wave guides is investigated. The emphasis of the study lies on the occurrence of an exceptional point of third order. It is demonstrated that the eigenfunctions in close vicinity of the exceptional point have a distinctive chiral behaviour. Using data describing realistic situations it is argued that such chiral behaviour can be tested experimentally.
Structure and mutagenic analysis of the lipid II flippase MurJ from Escherichia coli

Significance A peptidoglycan cell wall provides bacteria with protection from environmental stresses, and interfering with assembly of the cell wall is among the most effective strategies for antibiotic development. To build a cell wall, bacteria first synthesize lipid II on the inner leaflet of their membrane and then flip it across to the outer leaflet, where it is used to make peptidoglycan. Here, we report the structure of the lipid II flippase MurJ from Escherichia coli, and we use high-throughput mutagenesis to identify functionally important regions of the protein. Together with evolutionary covariation analysis, these data show that MurJ must exist in at least two discrete conformational states, providing a framework for understanding lipid II flipping. The peptidoglycan cell wall provides an essential protective barrier in almost all bacteria, defining cellular morphology and conferring resistance to osmotic stress and other environmental hazards. The precursor to peptidoglycan, lipid II, is assembled on the inner leaflet of the plasma membrane. However, peptidoglycan polymerization occurs on the outer face of the plasma membrane, and lipid II must be flipped across the membrane by the MurJ protein before its use in peptidoglycan synthesis. Due to its central role in cell wall assembly, MurJ is of fundamental importance in microbial cell biology and is a prime target for novel antibiotic development. However, relatively little is known regarding the mechanisms of MurJ function, and structural data for MurJ are available only from the extremophile Thermosipho africanus. Here, we report the crystal structure of substrate-free MurJ from the gram-negative model organism Escherichia coli, revealing an inward-open conformation. Taking advantage of the genetic tractability of E. coli, we performed high-throughput mutagenesis and next-generation sequencing to assess mutational tolerance at every amino acid in the protein, providing a detailed functional and structural map for the enzyme and identifying sites for inhibitor development. Lastly, through the use of sequence coevolution analysis, we identify functionally important interactions in the outward-open state of the protein, supporting a rocker-switch model for lipid II transport.
Pistachio‐Shuck‐Like MoSe2/C Core/Shell Nanostructures for High‐Performance Potassium‐Ion Storage

Potassium‐ion batteries (KIBs) have recently attracted intensive attention because of the abundant potassium resources and their low cost and high safety. However, the major challenge faced by KIBs lies in the lack of stable and high‐capacity materials for the intercalation/deintercalation of large‐size potassium ions. A unique pistachio‐shuck‐like MoSe2/C core/shell nanostructure (PMC) is synthesized herein as an advanced anode for boosting the performance of KIBs. This PMC is featured with a few layers of molybdenum selenide as the core with an expanded interlayer spacing of ≈0.85 nm, facilitating the intercalation/deintercalation of K ions, and a thin amorphous carbon as the shell, which can confine the active molybdenum selenide nanosheets during cycling for maintaining the high structural stability. Most importantly, as a whole, the PMC has the advantages of reducing the surplus hollow interior space for improving its packing density and buffering the volume expansion during the K‐ion intercalation for further enhancing the stability. As a consequence, the PMC shows a very high capacity of 322 mAh g−1 at 0.2 A g−1 over 100 cycles, and can still remain 226 mAh g−1 at 1.0 A g−1 for a long period of 1000 cycles, which is among the best‐reported KIBs anodes.
Spermatogenesis in the salps Thalia democratica and Cyclosalpa affinis (Tunicata: Thaliacea): An electron microscopic study

The fine structure of the male germinal cells in testes of two salps, Thalia democratica and Cyclosalpa affinis, is identical. The earliest germ cells seen were spermatocytes, located at the periphery of the testis and sometimes connected by cytoplasmic bridges. They are spherical with an anucleolate nucleus, a pair of centrioles, aboundant free ribosomes, sparse rough endoplasmic reticulum, and about five mitochondria. No Golgi complex was seen. The earliest spermatids, though similar to the spermatocytes, are smaller and have only one centriole. Spermatids develop (1) singly, (2) joined by cytoplasmic bridges, or (3) in syncytia. The next stage has a flagellum, a single large mitochondrion with dense material in some intracristal spaces, and a patch of highly condensed chromatin in the nucleus adjacent to the centriole. Subsequently the nucleus and the spermatid elongate. During elongation (1) the mitochondrion remains lateral to the nucleus and the amount of intracristal material enlarges, (2) the central core of condensed chromatin increases, and (3) the remainder of the chromatin becomes organized into dense strands. When elongation is 75% complete, the dense strands of chromatin appear to coalesce, to become homogeneous and denser than the core of chromatin, and the mitochondrion transforms into dense tubules. Finally, the mitochondrion wraps around the nucleus and extends its entire length, ultimately becoming a single tubule spiraled about 45 times around the nucleus. The mature sperm head is 18 μm long, tapering from 0.8 μm posteriorly to a tip about 0.14 μm wide. There is no acrosome. The single (distal) centriole of the sperm gives rise to a 9+2 flagellum with a fuzzy coat and dense material peripheral to each of the nine doublets. Spermiogenesis in T. democratica and C. affinis is similar to that in ascidians, and the sperm share many features with sperm of colonial ascidians in the suborder Didemnidae. The results, therefore, suggest that salps are closely related to ascidians and support the view that colonial ascidians gave rise to salps.
Values vs. Self-Interest as Determinants of Attitudes: Through a Construal Level Theory Lens, (Sometimes) Self-Interest Wins

The present study (n = 335) attempted to conceptually replicate Hunt, Kim, Borgida, and Chaiken (2010) with a high-powered design to investigate whether values and self-interest differentially impact attitudes depending on psychological distance. Participants were assigned to complete a task that made selfor other-focused values more accessible, then indicated their attitudes about a student fee increase at a university to fund scholarships the participants would not be eligible to receive (thus going against their own financial self-interest for the well being of someone else). The memo describing the fee increase was manipulated such that the increase would be occurring at either the socially proximal University of Arkansas (where the study was conducted), or socially distal University of Maine. Measures of financial strain we used as measures of self-interest, and an additional measure of values was collected prior to the values manipulation. Results showed that values (regardless of being measured or manipulated) had no significant effect on attitudes, but self-interest (when operationalized as objective financial strain) and construal did. As participants’ financial strain (i.e., self-interest) went up, support for the fee increase went down; and support for the fee increase was greater in the socially distal condition. Hunt and colleagues’ model did not replicate with the present data, as no interactions between these three variables were found.