Miracle-dz/UniFAR-FTUs huggingface dataset:
Current status of human rabies prevention: remaining barriers to global biologics accessibility and disease elimination

ABSTRACT Introduction: Rabies is a serious, neglected tropical disease. Zoonotic agents are RNA viruses (Genus Lyssavirus, Family Rhabdoviridae), global in distribution. As an acute, progressive, incurable encephalitis, rabies has the highest case fatality of any infectious disease. Warm-blooded vertebrates are susceptible hosts. Major mammalian reservoirs include mesocarnivores and bats. Given wildlife perpetuation, rabies is not eradicable, but is preventable and controllable, especially under newly available international guidelines. Areas covered: Literature review over the past 5 years reveals development of sensitive, specific diagnostic tests and safe and highly effective human and veterinary vaccines. Yet, tens of thousands of human fatalities occur annually, usually in Africa and Asia, primarily after canine exposure. Human and domestic animal vaccination, before or after exposure, is the single greatest preventative strategy following a rabid animal bite. Expert opinion: Significant progress occurred during the twenty-first century regarding vaccine development, doses, and schedules. Remaining barriers to widespread rabies vaccination include an inter-related set of economic, cultural, social, educational, ecological and technological factors. A basic understanding of local and regional root causes of cases historically allows for broader accessibility to vaccination in a trans-disciplinary fashion to meet the global elimination of human rabies caused via dogs (GEHRD) by 2030.
Inward-facing conformation of a multidrug resistance MATE family transporter

Significance Active efflux of drugs and toxic compounds carried out by multidrug and toxic compound extrusion (MATE) family transporters is one of the strategies developed by bacterial pathogens to confer multidrug resistance. To elucidate the underlying steps of the MATE transport cycle, structures of distinct intermediates are required; however, only structures in outward-facing conformations have been available. Our approach of using native lipids allowed trapping and visualization of the MATE transporter from Pyrococcus furiosus in an inward-facing conformation. This work highlights the importance of native lipids and opens an alternative view on the function and mechanism of action for the MATE family transporters. Multidrug and toxic compound extrusion (MATE) transporters mediate excretion of xenobiotics and toxic metabolites, thereby conferring multidrug resistance in bacterial pathogens and cancer cells. Structural information on the alternate conformational states and knowledge of the detailed mechanism of MATE transport are of great importance for drug development. However, the structures of MATE transporters are only known in V-shaped outward-facing conformations. Here, we present the crystal structure of a MATE transporter from Pyrococcus furiosus (PfMATE) in the long-sought-after inward-facing state, which was obtained after crystallization in the presence of native lipids. Transition from the outward-facing state to the inward-facing state involves rigid body movements of transmembrane helices (TMs) 2–6 and 8–12 to form an inverted V, facilitated by a loose binding of TM1 and TM7 to their respective bundles and their conformational flexibility. The inward-facing structure of PfMATE in combination with the outward-facing one supports an alternating access mechanism for the MATE family transporters.
Intelligent Modelling and Multi-Objective Optimisation of Laser Beam Cutting of Nickel Based Superalloy Sheet

In the present study, a novel technique, namely, evolutionary non-dominated sorting genetic algorithm-II (NSGA-II) was used in conjunction with developed artificial neural network (ANN) model to select optimal process parameters for achieving the better process performance in LBC. First, ANN with backpropagation algorithm was used to model the LBC of nickel based superalloy sheets. The input process parameters taken were oxygen pressure, pulse width, pulse frequency and cutting speed. The performance characteristics of interest in nickel based superalloy thin sheet cutting are average kerf taper and surface roughness. The ANN model was trained and tested using the experimental data obtained through experimentation on pulsed Nd-YAG laser beam machining system. The 4-10-11-2 backpropagation architecture was found more accurate and generalized for given problem with good prediction capability. The results show that the developed modelling and optimization tool is effective for process parameter optimization in LBC process. The optimization of the process suggests that for achieving high cut quality characteristics the pulse width, pulse frequency and cutting speed are set to lower limit within the available range and gas pressure is set to a level which is sufficient to remove the molten metal from the kerf.
Indirect Force Control of a Cable-Driven Parallel Robot: Tension Estimation using Artificial Neural Network trained by Force Sensor Measurements

In a cable-driven parallel robot (CDPR), force sensors are utilized at each winch motor to measure the cable tension in order to obtain the force distribution at the robot end-effector. However, because of the effects of friction in the pulleys and the unmodeled cable properties of the robot, the measured cable tensions are often inaccurate, which causes force-control difficulties. To overcome this issue, this paper presents an artificial neural network (ANN)-based indirect end-effector force-estimation method, and its application to CDPR force control. The pulley friction and other unmodeled effects are considered as black-box uncertainties, and the tension at the end-effector is estimated by compensating for these uncertainties using an ANN that is developed using the training datasets from CDPR experiments. The estimated cable tensions at the end-effector are used to design a P-controller to track the desired force. The performance of the proposed ANN model is verified through comparisons with the forces measured directly at the end-effector. Furthermore, cable force control is implemented based on the compensated tensions to evaluate the performance of the CDPR in wrench space. The experimental results show that the proposed friction-compensation method is suitable for application in CDPRs to control the cable force.
Revision Stapes Surgery in a Tertiary Referral Center: Surgical and Audiometric Outcomes

Objectives: To evaluate pure-tone audiometric results in otosclerosis patients undergoing revision stapes surgery following previous middle ear interventions. Methods: A retrospective cohort study was performed in a tertiary referral center. Consecutive otosclerosis patients who underwent revision stapes surgeries, following previous middle ear interventions, for persistent conductive hearing loss, recurrent conductive hearing loss, or vertigo and had available postoperative pure-tone audiometry were included. Mean pre- and postoperative air conduction, bone conduction, and air-bone gap averaged over 0.5, 1, 2, and 3 kHz were obtained. Audiometric outcomes were obtained at 7 weeks postoperatively. Results: In total, 63 consecutive otosclerosis patients who underwent 66 revision stapes surgeries were included. Air-bone gap improved significantly with a mean gain of 19 dB (95% CI, 15-22). Air conduction improved significantly with a mean gain of 18 dB (95% CI, 14-23). Bone conduction did not change significantly, with a mean deterioration of 0 dB (95% CI, –2 to 1). Air-bone gap closure to 10 dB or less was achieved in 38% of cases and to 20 dB or less in 80% of cases. Indication for surgery, previous type of procedure, primary cause of failure, and current surgical technique were not significantly associated with air-bone gap closure to 10 dB or less. Indication for surgery and primary cause of failure were associated with one another. Conclusions: Compared to the available literature, a slightly larger gain in air conduction and air-bone gap was achieved in our study. Air-bone gap closure to 10 dB or less was achieved less often in our study.
Dual-Specificity Phosphatases in Immunity and Infection: An Update

Kinase activation and phosphorylation cascades are key to initiate immune cell activation in response to recognition of antigen and sensing of microbial danger. However, for balanced and controlled immune responses, the intensity and duration of phospho-signaling has to be regulated. The dual-specificity phosphatase (DUSP) gene family has many members that are differentially expressed in resting and activated immune cells. Here, we review the progress made in the field of DUSP gene function in regulation of the immune system during the last decade. Studies in knockout mice have confirmed the essential functions of several DUSP-MAPK phosphatases (DUSP-MKP) in controlling inflammatory and anti-microbial immune responses and support the concept that individual DUSP-MKP shape and determine the outcome of innate immune responses due to context-dependent expression and selective inhibition of different mitogen-activated protein kinases (MAPK). In addition to the canonical DUSP-MKP, several small-size atypical DUSP proteins regulate immune cells and are therefore also reviewed here. Unexpected and complex findings in DUSP knockout mice pose new questions regarding cell type-specific and redundant functions. Another emerging question concerns the interaction of DUSP-MKP with non-MAPK binding partners and substrate proteins. Finally, the pharmacological targeting of DUSPs is desirable to modulate immune and inflammatory responses.
A Fuzzy Logic Framework to Estimate the Angular Turn Rate for High-Performance Target Tracking

Most tracking algorithms are model based because knowledge of target motion is available. A successful target tracking depends on the choice of a good model of the target; which facilitates the extraction of useful information about the target's state from observations. A good model-based tracking algorithm will outperform any model-free tracking algorithm to a great extent if the underlying model turns out to be a good one. In this paper, we propose a fuzzy logic framework to expect the angular turn rate and, thus, the appropriate model for target tracking using the particle filter. The coordinate turn (CT) model with unknown turn rate is used to calculate the expected angular turn rate. The fuzzy logic system is comprised of double-input single-output; which is presented by fuzzy relational equations. A canonical-rule based form is used to express each of these fuzzy relational equations. The dynamics of the high-performance target are modeled by multiple switching (jump Markov) systems. The proposed algorithm showed better performance in tracking a maneuvering target in relative slow scan periods compared to fuzzy integrated multiple models (FIMM).
Local Cytokine Expression Profiling in Patients with Specific Autoimmune Uveitic Entities

ABSTRACT Purpose: To evaluate expression of cytokines GM-CSF, IL-11, IL-12p40, IL-12p70, IL-27p28, IL-35, APRIL, BAFF, TWEAK, and LIGHT in uveitis. Methods: Aqueous humor samples from patients with active uveitis associated with Behçet’s disease (BD), sarcoidosis, HLA-B27-related inflammation, and Vogt-Koyanagi-Harada (VKH) disease and control patients were assayed with a multiplex assay. Results: Comparing all patients to controls, GM-CSF, IL-11, IL-12p40, APRIL, and BAFF were significantly increased, whereas LIGHT was significantly decreased. IL-11 and BAFF were the most strongly upregulated, being elevated 19.7-fold and 14.1-fold, respectively, compared with controls. IL-11 was significantly highest in HLA-B27 uveitis. GM-CSF, IL-11, and IL-12p40 were significantly higher in nongranulomatous uveitis (BD and HLA-B27) than in granulomatous uveitis (sarcoidosis and VKH), whereas APRIL and TWEAK were significantly higher in granulomatous uveitis. Conclusions: IL-11-driven immune responses might be more potent in nongranulomatous uveitis, particularly in HLA-B27 uveitis. BAFF and APRIL might contribute to B cell-driven autoimmune response in uveitis.
Partial Surface Modification of Low Generation Polyamidoamine Dendrimers: Gaining Insight into their Potential for Improved Carboplatin Delivery

Carboplatin (CAR) is a second generation platinum-based compound emerging as one of the most widely used anticancer drugs to treat a variety of tumors. In an attempt to address its dose-limiting toxicity and fast renal clearance, several delivery systems (DDSs) have been developed for CAR. However, unsuitable size range and low loading capacity may limit their potential applications. In this study, PAMAM G3.0 dendrimer was prepared and partially surface modified with methoxypolyethylene glycol (mPEG) for the delivery of CAR. The CAR/PAMAM G3.0@mPEG was successfully obtained with a desirable size range and high entrapment efficiency, improving the limitations of previous CAR-loaded DDSs. Cytocompatibility of PAMAM G3.0@mPEG was also examined, indicating that the system could be safely used. Notably, an in vitro release test and cell viability assays against HeLa, A549, and MCF7 cell lines indicated that CAR/PAMAM G3.0@mPEG could provide a sustained release of CAR while fully retaining its bioactivity to suppress the proliferation of cancer cells. These obtained results provide insights into the potential of PAMAM G3.0@mPEG dendrimer as an efficient delivery system for the delivery of a drug that has strong side effects and fast renal clearance like CAR, which could be a promising approach for cancer treatment.
Etoricoxib-induced acute generalized exanthematous pustulosis.

Sir, Acute generalized exanthematous pustulosis (AGEP) is a rapid-onset skin syndrome consisting of generalized non-follicular small pustules on erythematous skin and systemic symptoms. In most cases AGEP is induced by drugs (1). Etoricoxib, a non-steroidal anti-inflammatory drug (NSAID) cyclo-oxygenase-2 (COX-2) inhibitor, is nowadays widely used due to its lower rate of gastrointestinal irritation. We report here the first documented case of etoricoxib-induced AGEP. The diagnosis was confirmed by typical clinical symptoms, histopathological findings and positive patch tests.
Observations and possible function of the striking anterior coloration pattern of Galathea intermedia (Crustacea: Decapoda: Anomura)

Galathea intermedia is common, but cryptic, on Clyde maerl deposits where it lives in small groups of mixed sex and age, sharing shelters (typically dead Dosinia shells) to avoid predation. Its appearance is marked by six iridescent blue spots which may play an important role in intra- or interspecific interactions.
Molecular Carcinogenesis

Funding information Siying Wang, Grant/Award Number: 81472330; National Science Foundation of China Abstract The Helicobacter pylori (H. pylori) cytotoxin‐associated gene A (CagA) and Krüppel‐like transcription factor (KLF4) were both closely associated with the development and progression of gastric cancer (GC). However, the nature of the interactions between CagA and KLF4 in GC development has not been elucidated. Therefore, we focused on the CagA‐mediated promotion of the malignant transformation of gastric epithelial cells. Herein, we first examined the expression of KLF4 in both human cancer and paracarcinoma tissues with or without H. pylori infection and found that KLF4 expression was significantly decreased in H. pylori‐positive GC cells compared with the H. pylori‐negative GC cells. Further functional studies revealed that the increased expression of CagA could suppress KLF4 expression and promote the malignant transformation of normal epithelial cells. Subsequently, we found that CagA could upregulate miR‐155 and further restrict the expression of downstream KLF4. More importantly, the overexpression of miR‐155 in GES‐1 promoted epithelial‐mesenchymal transition and eventually facilitated tumor growth in vivo. Overall, the identification of the CagA/miR‐155/KLF4 signaling pathway provided a new insight into the development and treatment of GC.
Fretting studies of nanocrystalline Pd, Pd-Ag and Pd-Y films

In the present work, the effects of fretting on the contact resistance behavior of nanocrystalline Pd, Pd/sub 90/Y/sub 10/ and Pd/sub 60/Ag/sub 40/ films deposited on phosphorous-nickel and phosphorous-bronze plates was investigated. The wires used were bare copper, tin-plated copper and silver-copper (Ag/sub 90/Cu/sub 10/). Some of the wires were also coated with the same nanostructured films. The contact resistance was used to monitor the interaction between the wires and the plates. Following the fretting experiments, the surface of the contact regions was examined using scanning electron microscopy with energy dispersive X-ray detection and by Auger spectroscopy. The microstructure of the different films, as well as the effect of thermal annealing of the film/plate combination were investigated. This study shows that nanostructured films have a large technological potential in the improvement of low current electrical connections.
Physiologically Relevant In Vitro-In Vivo Correlation (IVIVC) Approach for Sildenafil with Site-Dependent Dissolution

This study aimed to establish a physiologically relevant in vitro-in vivo correlation (IVIVC) model reflecting site-dependent dissolution kinetics for sildenafil based on population-pharmacokinetic (POP-PK) modeling. An immediate release (IR, 20 mg) and three sustained release (SR, 60 mg) sildenafil tablets were prepared by wet granulation method. In vitro dissolutions were determined by the paddle method at pH 1.2, 4.5, and 6.8 media. The in vivo pharmacokinetics were assessed after oral administration of the prepared IR and SR formulations to Beagle dogs (n = 12). The dissolution of sildenafil from SR formulations was incomplete at pH 6.8, which was not observed at pH 1.2 and pH 4.5. The relative bioavailability was reduced with the decrease of the dissolution rate. Moreover, secondary peaks were observed in the plasma concentration-time curves, which may result from site-dependent dissolution. Thus, a POP-PK model was developed to reflect the site-dependent dissolution by separately describing the dissolution and absorption processes, which allowed for estimation of the in vivo dissolution of sildenafil. Finally, an IVIVC was established and validated by correlating the in vitro and in vivo dissolution rates. The present approach may be applied to establish IVIVC for various drugs with complex dissolution kinetics for the development of new formulations.
Differences in beliefs and attitudes toward Depression and Schizophrenia in Russia and the United States

Background: Cross-cultural studies find that culture shapes people’s understanding of mental illnesses, particularly Depression and Schizophrenia. Aims: To compare individuals’ beliefs and attitudes toward Depression and Schizophrenia in Russia and the United States. Method: Participants (N=607) were presented with vignettes of two diagnostically unlabeled psychiatric case histories and then answered questions regarding mental health literacy (MHL) and attitudes toward the person and the illness. Results: Our findings indicate that Depression was most often attributed to psychosocial stress while Schizophrenia was thought to be caused by biological factors. People from both countries considered those suffering from Schizophrenia to be unpredictable and dangerous. US participants were more likely to endorse lay and professional help for both disorders than their Russian counterparts. Russian participants reported being less likely to turn to someone they trust and more likely to deal with problems on their own. Russian participants were also more likely to view those with Depression as ‘weak-willed’ and leading an ‘immoral lifestyle’. Conclusion: Our findings further inform cultural understandings of these mental illnesses in an often neglected national group. Patterns suggest that both groups may benefit from exposure to corrective information about Depression and Schizophrenia.
Risk factors for prescription drug diversion among people living with HIV: a systematic scoping review.

BACKGROUND In addition to numerous infections and frequent pain constantly affecting people living with HIV (PLWH), various risk factors might contribute to prescription drug diversion. The purpose of the study is to map existing evidence on risk factors contributing to prescription drug diversion among PLWH. METHODS Arksey and O'Malley's framework and the recommendation by Levac et al. (2010) guided this study. We searched for relevant literature from the following databases: PubMed; Google Scholar; EBSCOhost (Academic Search Complete, MEDLINE and Newspaper Source), Cochrane, WHO, HIV, ScienceDirect and Open Access Theses and Dissertations. Studies reporting evidence on risk factors contributing to prescription drug diversion and published in the period January 1996 to July 2017 were included. Thematic content analysis was performed to summarize the findings. RESULTS The search identified 734 studies. After full-text screening of the eligible studies, risk factors contributing to prescription drug diversion among PLWH were reported in 20 included studies. It was found that there is limited research on prescription drug diversion among PLWH in low-middle-income countries (LMICs). Risk factors contributing to prescription drug diversion were being a substance user or substance dependent; being male; young in age; being stigmatized; not disclosed HIV status; diagnosed with mental health problems; being HIV infected; poor health and well being; being White; being homeless or not owing a home; having low educational level; having history of diversion, misuse or abuse; in possession of addictive prescriptions; being unemployed and living in high neighbourhood disorder. CONCLUSION Evidence shows that there is limited research on prescription drug diversion among PLWH in LMICs. The study findings show that the risk factors contributing to prescription drug diversion are related with risk factors for HIV transmission and infection. PROSPERO REGISTRATION NUMBER CRD42017074076.