Antimicrobial resistance has emerged as a huge challenge to the effective treatment of infectious diseases. Aside from a modest number of novel anti‐infective agents, very few new classes of ...antibiotics have been successfully developed for therapeutic use. Despite the research efforts of numerous scientists, the fight against antimicrobial (ATB) resistance has been a longstanding continued effort, as pathogens rapidly adapt and evolve through various strategies, to escape the action of ATBs. Among other mechanisms of resistance to antibiotics, the sophisticated envelopes surrounding microbes especially form a major barrier for almost all anti‐infective agents. In addition, the mammalian cell membrane presents another obstacle to the ATBs that target intracellular pathogens. To negotiate these biological membranes, scientists have developed drug delivery systems to help drugs traverse the cell wall; these are called “Trojan horse” strategies. Within these delivery systems, ATB molecules can be conjugated with one of many different types of carriers. These carriers could include any of the following: siderophores, antimicrobial peptides, cell‐penetrating peptides, antibodies, or even nanoparticles. In recent years, the Trojan horse‐inspired delivery systems have been increasingly reported as efficient strategies to expand the arsenal of therapeutic solutions and/or reinforce the effectiveness of conventional ATBs against drug‐resistant microbes, while also minimizing the side effects of these drugs. In this paper, we aim to review and report on the recent progress made in these newly prevalent ATB delivery strategies, within the current context of increasing ATB resistance.
This Minireview focuses on selected topics in the syntheses of bicyclo1.1.1pentane (BCP) analogues. A brief historical introduction was included. The content covers various synthetic routes of ...1‐substituted and 1,3‐disubstituted BCPs. Selective examples of synthetically useful building blocks are summarized for each category for synthetic organic chemists’ and medicinal chemists’ reference. A compare‐and‐contrast analysis is also applied to evaluate these routes and to demonstrate the progress of strategic functional group transformations using modern organic methodologies. By systematically analyzing the synthetic strategies to access these strained molecules, we also hope that this Minireview will provide inspirations for future developments in this area.
Like riding a bicyclopentane: In this Minireview, different synthetic strategies and novel organic methodologies to access bicyclo1.1.1pentane (BCP) analogues with diverse substitution patterns are discussed. In each section, these strategies are compared and contrasted, and selective examples of synthetically useful building blocks are provided.
Lymph node metastasis (LNM) is a significant prognostic factor in patients with head and neck cancer, and the ability to predict it accurately is essential to optimizing treatment. Positron emission ...tomography (PET) and computed tomography (CT) imaging are routinely used to identify LNM. Although large or highly active lymph nodes (LNs) have a high probability of being positive, identifying small or less reactive LNs is challenging. The accuracy of LNM identification strongly depends on the physician's experience, so an automatic prediction model for LNM based on CT and PET images is warranted to assist LMN identification across care providers and facilities. Radiomics and deep learning are the two promising imaging-based strategies for node malignancy prediction. Radiomics models are built based on handcrafted features, while deep learning learns the features automatically. To build a more reliable model, we proposed a hybrid predictive model that takes advantages of both radiomics and deep learning based strategies. We designed a new many-objective radiomics (MaO-radiomics) model and a 3D convolutional neural network (3D-CNN) that fully utilizes spatial contextual information, and we fused their outputs through an evidential reasoning (ER) approach. We evaluated the performance of the hybrid method for classifying normal, suspicious and involved LNs. The hybrid method achieves an accuracy (ACC) of 0.88 while XmasNet and Radiomics methods achieve 0.81 and 0.75, respectively. The hybrid method provides a more accurate way for predicting LNM using PET and CT.
Monitoring the conditions of machines is vital in the manufacturing industry. Early detection of faulty components in machines for stopping and repairing the failed components can minimize the ...downtime of the machine. In this article, we present a method for detecting failures in drill machines using drill sounds in Valmet AB, a company in Sundsvall, Sweden that supplies equipment and processes for the production of pulp, paper, and biofuels. The drill dataset includes two classes: anomalous sounds and normal sounds. Detecting drill failure effectively remains a challenge due to the following reasons. The waveform of drill sound is complex and short for detection. Furthermore, in realistic soundscapes, both sounds and noise exist simultaneously. Besides, the balanced dataset is small to apply state-of-the-art deep learning techniques. Due to these aforementioned difficulties, sound augmentation methods were applied to increase the number of sounds in the dataset. In this study, a convolutional neural network (CNN) was combined with a long-short-term memory (LSTM) to extract features from log-Mel spectrograms and to learn global representations of two classes. A leaky rectified linear unit (Leaky ReLU) was utilized as the activation function for the proposed CNN instead of the ReLU. Moreover, an attention mechanism was deployed at the frame level after the LSTM layer to pay attention to the anomaly in sounds. As a result, the proposed method reached an overall accuracy of 92.62% to classify two classes of machine sounds on Valmet's dataset. In addition, an extensive experiment on another drilling dataset with short sounds yielded 97.47% accuracy. With multiple classes and long-duration sounds, an experiment utilizing the publicly available UrbanSound8K dataset obtains 91.45%. Extensive experiments on our dataset as well as publicly available datasets confirm the efficacy and robustness of our proposed method. For reproducing and deploying the proposed system, an open-source repository is publicly available at https://github.com/thanhtran1965/DrillFailureDetection_SciRep2022 .
Pruritus is a common debilitating symptom experienced by hemodialysis patients. Treatment is difficult because the cause of uremic pruritus is not known. This study addressed the hypothesis that ...pruritus is caused by solutes that accumulate in the plasma when the kidneys fail. We sought to identify solutes responsible for uremic pruritus using metabolomic analysis to compare the plasma of hemodialysis patients with severe pruritus versus mild/no pruritus. Pruritus severity in hemodialysis patients was assessed using a 100-mm visual analogue scale (VAS), with severe pruritus defined as >70 mm and mild/no pruritus defined as <10 mm. Twelve patients with severe pruritus (Itch) and 24 patients with mild/no pruritus (No Itch) were included. Pre-treatment plasma and plasma ultrafiltrate were analyzed using an established metabolomic platform (Metabolon, Inc.). To identify solutes associated with pruritus, we compared the average peak area of each solute in the Itch patients to that of the No Itch patients using the false discovery rate (q value) and principal component analysis. Dialysis vintage, Kt/Vurea, and serum levels of calcium, phosphorus, PTH, albumin, ferritin, and hemoglobin were similar in the Itch and No Itch patients. Metabolomic analysis identified 1,548 solutes of which 609 were classified as uremic. No difference in the plasma or plasma ultrafiltrate levels of any solute or group of solutes was found between the Itch and No Itch patients. Metabolomic analysis of hemodialysis patients did not reveal any solutes associated with pruritus. A limitation of metabolomic analysis is that the solute of interest may not be included in the metabolomic platform's chemical library. A role for uremic solutes in pruritus remains to be established.
Despite the important contribution made by green human resource management (GHRM) towards organizational citizenship behavior for the environment (OCBE), few published studies have investigated this ...significant contemporary topic in the hospitality industry, which constitutes a major gap in the literature on the greening of the hospitality industry. Drawing on Ability-Motivation-Opportunity theory, this study develops and tests direct and interactive effects of GHRM practices on OCBE. A mixed methodology is applied, with a survey of 203 employees working in 4–5 star hotels being conducted first to test six hypotheses, followed by qualitative research into two specific cases. The results indicate a mixture of expected and unexpected findings, including: (i) the direct effects of GHRM practices on OCBE; (ii) the interaction of three GHRM practices (training, performance management and employee involvement), which can enhance employees' voluntary green behavior, dependent on the level of green performance management and green employee involvement; and (iii) that green training is seen as a key mechanism to boost employees’ voluntary green behavior. The originality of this manuscript is based on its status as one of the first mixed-methodology works on GHRM in the hospitality industry in an emerging economy.
•There is currently a lack of studies on green HRM in the hospitality industry.•We conducted a mixed-methods study on this topic.•We covered the direct influences of GHRM practices on OCBE.•We explored interactive influences of GHRM practices and OCBE.•We extended Ability-Motivation-Opportunities theory in the green context.
This paper examines the short-run and long-run effects of economic, sociological and energy factors on environmental degradation in 28 European countries. In so doing, we employ Panel Vector ...Autoregressive (PVAR) and Fully Modified OLS (FMOLS) approaches on data from 1990 to 2014 in a STIRPAT (Stochastic Impacts by Regression on Population, Affluence, and Technology) framework. Key empirical results indicate that these factors may contribute to environmental improvement in the short run; however, there are adverse implications in the long-run. Specifically, economic factors including economic growth, trade openness and foreign direct investment cause environmental degradation in the under-analysis economies. The sociological factors as measured by the population growth and the level of urbanization also show a negative impact on the environmental degradation in the short-run but in the long run, both population size and urbanization increase environmental degradation. These findings are in line with the concerns raised by Thomas Robert Malthus in his Essay on the Principle of Population. With regards to the energy factors, it indicates that the renewable energies help the European environment by reducing the level of carbon dioxide emissions whereas the higher energy intensity is an ecological threat. Our results remain robust in the EKC framework.
•STIRPAT (Stochastic Impacts by Regression on Population, Affluence, and Technology) framework.•Economic growth, trade openness and foreign direct investment cause environmental degradation.•Sociological factors (population growth and the level of urbanization) show a negative impact.•Our results are in line with the concerns raised by Thomas Robert Malthus in his Essay on the Principle of Population.•Our results remain robust in the EKC framework.
•Key roles of arginase in growth and control of cancer.•Interest in arginase inhibition for cancer therapy.•Relevant categories of arginase inhibitors and their anticancer activities.•Perspectives of ...arginase inhibitors as novel anticancer agents.
Arginase plays an important part in l-arginine metabolism. This metalloenzyme also regulates polyamine biosynthesis, nitric oxide production and the T-cell-mediated immune response, which are all involved in the growth and control of cancer. Research over the past decades has reported arginase as an attractive target for cancer treatment, and inhibition of arginase could be a promising strategy for cancer therapy. Herein, we present the available data on the role of arginase in cancer development. The principal synthetic and natural arginase inhibitors are outlined and followed by their mechanism of action. Among them, some molecules have shown their anticancer effects. The perspectives of arginase inhibitors as new anticancer agents will be discussed.
Early-stage glottic larynx squamous cell carcinoma (GLC) is a relatively common disease with excellent oncologic control, but treatment is associated with acute dysphagia and long-term voice quality ...changes. This phase 1 study of hypofractionated radiation therapy for early-stage GLC increased the fraction size while reducing the number of fractions until 5-fraction stereotactic ablative radiation therapy (SABR) was delivered.
Eligible patients had received a diagnosis of stage Tis to T2 GLC. Patients who had undergone prior curative-intent surgery were excluded. The equipotent dose levels were as follows: (1) level 0, 50 Gy in 15 fractions (n = 4); (2) level 1, 45 Gy in 10 fractions (n = 13); and (3) level 2, 42.5 Gy in 5 fractions (SABR level, n = 12). Grade 3 or 4 laryngeal edema, voice, dyspnea, stridor, or cough were the predefined dose-limiting toxicities.
Twenty-nine patients were enrolled from November 2013 to March 2017. The median and minimum follow-up times were 39.2 and 13 months, respectively. Two actively smoking patients, 1 treated in level 1 (grade 4 laryngeal edema, grade 3 dysphagia) and 1 treated in level 2 (grade 3 laryngeal necrosis, dysphagia), developed dose-limiting toxicities. The former patient soon developed a local recurrence, and the latter patient recovered. There were a total of 5 local recurrences: 2 in level 0 and 3 in level 1. The Voice Handicap Index results showed robust long-term voice quality with median values of 7 and 0 at 6 and 12 months, respectively.
Given the tolerability, excellent voice outcomes, and preliminary efficacy data of 5-fraction glottic larynx SABR, this regimen warrants further study.
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