Miracle-dz/UniFAR-FTUs huggingface dataset:
Effectiveness of Adjunctive Analgesics in Head and Neck Cancer Patients Receiving Curative (Chemo-) Radiotherapy: A Systematic Review.

OBJECTIVE Our aim was to give an overview of the effectiveness of adjunctive analgesics in head and neck cancer (HNC) patients receiving (chemo-) radiotherapy. DESIGN Systematic review. INTERVENTIONS This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched for studies concerning "head neck cancer," "adjunctive analgesics," "pain," and "radiotherapy. " OUTCOME MEASURES Pain outcome, adverse events, and toxicity and other reported outcomes, for example, mucositis, quality of life, depression, etc. RESULTS Nine studies were included in our synthesis. Most studies were of low quality and had a high risk of bias on several domains of the Cochrane Collaboration tool. Only two studies comprised high-quality randomized controlled trials in which pregabalin and a doxepin rinse showed their effectiveness for the treatment of neuropathic pain and pain from oral mucositis, respectively, in HNC patients receiving (chemo-) radiotherapy. CONCLUSIONS More high-quality trials are necessary to provide clear evidence on the effectiveness of adjunctive analgesics in the treatment of HNC (chemo-) radiation-induced pain.
Protein Expression in Metastatic Melanoma and the Link to Disease Presentation in a Range of Tumor Phenotypes

Malignant melanoma is among the most aggressive skin cancers and it has among the highest metastatic potentials. Although surgery to remove the primary tumor is the gold standard treatment, once melanoma progresses and metastasizes to the lymph nodes and distal organs, i.e., metastatic melanoma (MM), the usual outcome is decreased survival. To improve survival rates and life span, advanced treatments have focused on the success of targeted therapies in the MAPK pathway that are based on BRAF (BRAF V600E) and MEK. The majority of patients with tumors that have higher expression of BRAF V600E show poorer prognosis than patients with a lower level of the mutated protein. Based on the molecular basis of melanoma, these findings are supported by distinct tumor phenotypes determined from differences in tumor heterogeneity and protein expression profiles. With these aspects in mind, continued challenges are to: (1) deconvolute the complexity and heterogeneity of MM; (2) identify the signaling pathways involved; and (3) determine protein expression to develop targeted therapies. Here, we provide an overview of the results from protein expression in MM and the link to disease presentation in a variety of tumor phenotypes and how these will overcome the challenges of clinical problems and suggest new promising approaches in metastatic melanoma and cancer therapy.
The miR-9b microRNA mediates dimorphism and development of wing in aphids

Significance Evolution of various wings plays an important role in the success of insects in environmental adaptation. During evolution, aphids deploy a wing dimorphism strategy to escape unfavorable conditions. This strategy also poses high risks to crops by distant transmission of viral diseases vectored by aphids. Thus, it is important to understand how aphids perceive environmental cues in triggering wing dimorphism and exploit specific approaches to target this process. Here, we report a microRNA (miR-9b)-mediated signal cascade that controls high-population-density–induced wing dimorphism in aphids. This finding highlights that small RNAs are important in regulating signal transduction of insect phenotypic plasticity when insects face environmental challenges, which may provide an alternative for the development of dispersal restriction-based pest control. Wing dimorphism is a phenomenon of phenotypic plasticity in aphid dispersal. However, the signal transduction for perceiving environmental cues (e.g., crowding) and the regulation mechanism remain elusive. Here, we found that aci-miR-9b was the only down-regulated microRNA (miRNA) in both crowding-induced wing dimorphism and during wing development in the brown citrus aphid Aphis citricidus. We determined a targeted regulatory relationship between aci-miR-9b and an ABC transporter (AcABCG4). Inhibition of aci-miR-9b increased the proportion of winged offspring under normal conditions. Overexpression of aci-miR-9b resulted in decline of the proportion of winged offspring under crowding conditions. In addition, overexpression of aci-miR-9b also resulted in malformed wings during wing development. This role of aci-miR-9b mediating wing dimorphism and development was also confirmed in the pea aphid Acyrthosiphon pisum. The downstream action of aci-miR-9b-AcABCG4 was based on the interaction with the insulin and insulin-like signaling pathway. A model for aphid wing dimorphism and development was demonstrated as the following: maternal aphids experience crowding, which results in the decrease of aci-miR-9b. This is followed by the increase of ABCG4, which then activates the insulin and insulin-like signaling pathway, thereby causing a high proportion of winged offspring. Later, the same cascade, “miR-9b-ABCG4-insulin signaling,” is again involved in wing development. Taken together, our results reveal that a signal transduction cascade mediates both wing dimorphism and development in aphids via miRNA. These findings would be useful in developing potential strategies for blocking the aphid dispersal and reducing viral transmission.
Slc43a3 is a regulator of free fatty acid flux1

Adipocytes take up long chain FAs through diffusion and protein-mediated transport, whereas FA efflux is considered to occur by diffusion. To identify potential membrane proteins that are involved in regulating FA flux in adipocytes, the expression levels of 55 membrane transporters without known function were screened in subcutaneous adipose samples from obese patients before and after bariatric surgery using branched DNA methodology. Among the 33 solute carrier (SLC) transporter family members screened, the expression of 14 members showed significant changes before and after bariatric surgery. One of them, Slc43a3, increased about 2.5-fold after bariatric surgery. Further investigation demonstrated that Slc43a3 is highly expressed in murine adipose tissue and induced during adipocyte differentiation in primary preadipocytes and in OP9 cells. Knockdown of Slc43a3 with siRNA in differentiated OP9 adipocytes reduced both basal and forskolin-stimulated FA efflux, while also increasing FA uptake and lipid droplet accumulation. In contrast, overexpression of Slc43a3 decreased FA uptake in differentiated OP9 cells and resulted in decreased lipid droplet accumulation. Therefore, Slc43a3 seems to regulate FA flux in adipocytes, functioning as a positive regulator of FA efflux and as a negative regulator of FA uptake.
Emerging Mechanisms of Cardiovascular Protection for the Omega-3 Fatty Acid Eicosapentaenoic Acid

Patients with well-controlled LDL (low-density lipoprotein) levels still have residual cardiovascular risk associated with elevated triglycerides. Epidemiological studies have shown that elevated fasting triglyceride levels associate independently with incident cardiovascular events, and abundant recent human genetic data support the causality of TGRLs (triglyceride-rich lipoproteins) in atherothrombosis. Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lower blood triglyceride concentrations but likely exert additional atheroprotective properties at higher doses. Omega-3 fatty acids modulate T-cell differentiation and give rise to various prostaglandins and specialized proresolving lipid mediators that promote resolution of tissue injury and inflammation. The REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial) with an EPA-only formulation lowered a composite of cardiovascular events by 25% in patients with established cardiovascular disease or diabetes mellitus and other cardiovascular risk factors. This clinical benefit likely arises from multiple molecular mechanisms discussed in this review. Indeed, human plaques readily incorporate EPA, which may render them less likely to trigger clinical events. EPA and DHA differ in their effects on membrane structure, rates of lipid oxidation, inflammatory biomarkers, and endothelial function as well as tissue distributions. Trials that have evaluated DHA-containing high-dose omega-3 fatty acids have thus far not shown the benefits of EPA alone demonstrated in REDUCE-IT. This review will consider the mechanistic evidence that helps to understand the potential mechanisms of benefit of EPA.
Hepatitis C: looking into the future

ABSTRACT Introduction The recent availability of highly effective hepatitis C medications, with a cure rate approaching 100%, has created a wide range of questions and uncertainties. Areas covered The most recent data around hepatitis C virus (HCV) elimination will be reviewed. In addition, the impact of HCV cure or sustained virologic response (SVR) on the risk for hepatocellular carcinoma (HCC) development will be discussed. Although the terms ‘SVR’ and ‘cure’ are used interchangeably, there are little data to support that they are actually the same. In this review, we will shed some light on the status of HCV vaccine development, obstacles, and published experience. Finally, in the face of decreasing HCV patients needing transplantation, and increasing available organs from donors infected with HCV, the question is that, is it possible to transplant an organ infected with HCV to a patient who is not infected? The pros and cons of transplanting HCV-positive organs to HCV-negative recipients will be discussed. Expert opinion Although the new advances in HCV treatment have solved many problems, it created several new issues which the medical community has to deal with and which will likely remain in the near future.
Measurement of the x-ray effective focal spot size with edge response analysis using digital detectors

Abstract. Purpose: For the focal spot measurement of x-ray tubes, we propose a practical method in which only a metal edge and a digital detector are used, together with a process of removing detector blur inherently associated. Approach: The evaluation was made through the optical transfer function (OTF) measurements using the edge response of a 1-mm-thick tungsten plate. First, we made the acquisition of a geometrically magnified edge response, which consists of focal spot penumbra and detector blur, followed by the acquisition of nonmagnified edge response, which includes only detector blur. Then the detector blur was removed by taking the ratio of the two OTFs. Finally, the focal spot profile was obtained by the inverse Fourier transform of this ratio. Results: Resultant full widths at the half-maximum of a small focus profile were 0.529 ± 0.005 mm for the proposed method and 0.527 ± 0.020 mm for the conventional slit method with film, indicating excellent agreement between both methods. Comparing between results obtained using two flat panel detectors with different pixel pitches (0.143 and 0.175 mm) confirmed no differences with these variations. Conclusion: Through the whole study, the accuracy and the practicality of the proposed method were demonstrated, indicating a possibility of the method to be widely used to evaluate the effective focal spot size and profile of x-ray systems.
Validation and identification of reference genes in Chinese hamster ovary cells for Fc-fusion protein production

Chinese hamster ovary cells are the predominant cell lines used for bio-therapeutic production. Real-time quantitative PCR (RT-qPCR) and transcriptomics are powerful tools to understand and optimize the Chinese hamster ovary cells for higher productivity or better control of product qualities. Reliable reference genes, which were proved to be experiment-specific, are critical yardsticks. In this study, we compared expression stability of 20 candidate reference genes at mRNA level, including commonly used housekeeping genes, previous literature reported genes in Chinese hamster ovary cells producing an intact antibody, and new candidates suggested by our RNA-seq transcriptomic database, in RT-qPCR reactions in Fc-fusion protein-producing Chinese hamster ovary cells with various productivity during long-term cultivation and fed-batch cultures at 26 different conditions. geNorm, NormFinder, BestKeeper, and ΔCt programs and methods were utilized to analyze the gene expression stability and gave an overall ranking. Akr1a1, Gpx1, and Aprt in long-term cultivation and Akr1a1, Rps16 in fed-batch culture, which have not been reported previously, exhibited the highest stability of gene expression, while Pabpn1, Hirip3, and Actb in both sets of experiments together with Atp5f1 in long-term passage process showed the weakest stability. The results were then validated using GLP1-Fc (Glucagon-like peptide-1 Fc fusion protein) gene as the target with determined expression level which were doubly confirmed by both absolute RT-qPCR and confocal microscopy. These new references should be considered for the investigations on Chinese hamster ovary cells in related research. Impact statement In order to reveal potential genotype-phenotype relationship, RT-qPCR reactions are frequently applied which require validated and reliable reference genes. With the investigation on long-term passage and fed-batch cultivation of CHO cells producing an Fc-fusion protein, four new reference genes–Akr1a1, Gpx1, Aprt, and Rps16, were identified from 20 candidates with the aid of geNorm, NormFinder, BestKeeper, and ΔCt programs and methods. This article provided more verified options in reference gene selection in related research on CHO cells.
Evaluating Mobile Apps and Biosensing Devices to Monitor Physical Activity and Respiratory Function in Smokers With and Without Respiratory Symptoms or Chronic Obstructive Pulmonary Disease: Protocol for a Proof-of-Concept, Open-Label, Feasibility Study

Background Chronic obstructive pulmonary disease (COPD) is a global public health problem, and continuous monitoring is essential for both its management as well as the management of other chronic diseases. Telemonitoring using mobile health (mHealth) devices has the potential to promote self-management, improve control, increase quality of life, and prevent hospital admissions. Objective This study aims to demonstrate whether a large-scale study assessing the use of mHealth devices to improve the treatment, assessment, compliance, and outcomes of chronic diseases, particularly COPD and cardio-metabolic syndrome, is feasible. This will allow our team to select the appropriate design and characteristics for our large-scale study. Methods A total of 3 cohorts, with 9 participants in each, will use mHealth devices for 90 days while undergoing the current standard of care. These groups are: 9 “non-COPD,” otherwise healthy, smokers; 9 “grey zone” smokers (forced expiratory volume in 1 second/ forced vital capacity ≥0.70 after bronchodilator treatment; COPD Assessment Test ≥10); and 9 smokers diagnosed with Stage 1-3 COPD. Rates of recruitment, retention, and adherence will be measured. Overall, two mHealth devices will be utilized in the study: the AnaMed Original Equipment Manufacturer device (measures distance, energy expenditure, heart rate, and heart rate variability) and the Air Next mobile spirometry device. The mHealth devices will be compared against industry standards. Additionally, a questionnaire will be administered to assess the participants’ perceptions of the mHealth technologies used. Results The inclusion of participants started in June 2019. Study results will be published in peer-reviewed scientific journals. Conclusions This study will demonstrate whether a large-scale study to assess the use of mHealth devices to improve the treatment, assessment, compliance, and outcomes of chronic diseases, particularly COPD and cardio-metabolic syndrome, is feasible. It will also allow the research team to select the appropriate design and characteristics for the large-scale study. Trial Registration ClinicalTrials.gov NCT04081961; https://clinicaltrials.gov/ct2/show/NCT04081961 International Registered Report Identifier (IRRID) DERR1-10.2196/16461
Evaluation of RAPNO criteria in medulloblastoma and other leptomeningeal seeding tumors using MRI and clinical data.

BACKGROUND Although the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group has made recommendations for response assessment in patients with medulloblastoma (MBL) and leptomeningeal seeding tumors, these criteria have yet to be evaluated. METHODS We examined MR imaging and clinical data in a multicenter retrospective cohort of 269 patients diagnosed with MBL, high grade glioma, embryonal tumor, germ cell tumor, or choroid plexus papilloma. Inter-observer agreement, objective response rates (ORRs) and progression-free survival (PFS) were calculated. Landmark analyses were performed for objective response (OR) and progression status at 0.5, 1.0, and 1.5 years after treatment initiation. Cox proportional hazard models were used to determine the associations between OR and progression with overall survival (OS). Subgroup analyses based on tumor subgroup and treatment modality were performed. RESULTS The median follow-up time was 4.0 years. In all patients, the ORR was 0.565 [95% confidence interval (CI), 0.505-0.625] by RAPNO. The inter-observer agreement of OR determination between two raters (a neuroradiologist and a neuro-oncologist) for the RAPNO criteria in all patients was 83.8% (k statistic=0.815; P<0.001). At 0.5-, 1.0-, and 1.5-year landmarks, both OR status and PFS determined by RAPNO were predictive of OS [hazard ratios for 1-year landmark (OR HR=0.079, P <0.001; PFS HR=10.192, P<0.001)]. In subgroup analysis, OR status and PFS were predictive of OS for all tumor subtypes and treatment modalities. CONCLUSION RAPNO criteria showed excellent consistency in the treatment response evaluation of MBL and other leptomeningeal seeding tumors. OR and PFS determined by RAPNO criteria correlated with OS.
Tropical pyomyositis: an update

Tropical pyomyositis (TP) is a life‐threatening bacterial infection of the skeletal muscle that occurs particularly among children, young adults and those with immunocompromised conditions. The appropriate diagnosis and treatment are often delayed due to its non‐specific signs, leading to fatal consequences. Staphylococcus aureus, especially methicillin‐susceptible S. aureus, is responsible for most TP cases. However, other bacteria (i.e. streptococci, Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp., Candida spp., Mycobacterium spp.) have been reported. This narrative review provides an update on the epidemiology and clinical course of TP. A special focus is laid on the role of toxins (i.e. Panton‐Valentine Leucocidin and α‐toxin) in the pathogenesis of TP and their implication for the clinical management of infection.
Solving Large-Scale Multiobjective Optimization Problems With Sparse Optimal Solutions via Unsupervised Neural Networks

Due to the curse of dimensionality of search space, it is extremely difficult for evolutionary algorithms to approximate the optimal solutions of large-scale multiobjective optimization problems (LMOPs) by using a limited budget of evaluations. If the Pareto-optimal subspace is approximated during the evolutionary process, the search space can be reduced and the difficulty encountered by evolutionary algorithms can be highly alleviated. Following the above idea, this article proposes an evolutionary algorithm to solve sparse LMOPs by learning the Pareto-optimal subspace. The proposed algorithm uses two unsupervised neural networks, a restricted Boltzmann machine, and a denoising autoencoder to learn a sparse distribution and a compact representation of the decision variables, where the combination of the learnt sparse distribution and compact representation is regarded as an approximation of the Pareto-optimal subspace. The genetic operators are conducted in the learnt subspace, and the resultant offspring solutions then can be mapped back to the original search space by the two neural networks. According to the experimental results on eight benchmark problems and eight real-world problems, the proposed algorithm can effectively solve sparse LMOPs with 10000 decision variables by only 100000 evaluations.
An Updated Analysis of Utilization of Epidural Procedures in Managing Chronic Pain in the Medicare Population from 2000 to 2018.

BACKGROUND With increasing costs of health care in the United States, attention is focused on expensive conditions. Musculoskeletal disorders with low back and neck pain account for the third highest amount of various disease categories. Minimally invasive interventional techniques for managing spinal pain, including epidural injections, have been considered to be growing rapidly. However, recent analyses of utilization of interventional techniques from 2000 to 2018 has shown a decline of 2.6% and a decline of 21% from 2009 to 2018 for epidural and adhesiolysis procedures. OBJECTIVES The objectives of this analysis of epidural procedures from 2000 to 2018 are to provide an update on utilization of epidural injections in managing chronic pain in the fee-for-service (FFS) Medicare population, with a comparative analysis of 2000 to 2009 and 2009 to 2018. STUDY DESIGN Utilization patterns and variables of epidural injections in managing chronic spinal pain from 2000 to 2009 and from 2009 to 2018 in the FFS Medicare population in the United States. METHODS This analysis was performed by utilizing master data from CMS, physician/supplier procedure summary from 2000 to 2018. The analysis was performed by the assessment of utilization patterns using guidance from Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). RESULTS Overall, epidural procedures declined at a rate of 20.7% per 100,000 Medicare enrollees in FFS Medicare in the United States from 2009 to 2018, with an annual decline of 2.5%. However, from 2000 to 2009, there was an increase of 89.2%, with an annual increase of 7.3%. This analysis showed a decline in all categories, with an annual decrease of 4.7% for lumbar interlaminar and caudal epidural injections, 4.7% decline for cervical/thoracic transforaminal epidural injections, 1.1% decline for lumbar/sacral transforaminal epidural injections, and finally 0.4% decline for cervical/thoracic interlaminar epidural injections. Overall declines from 2009 to 2018 were highest for cervical and thoracic transforaminal injections with 35.1%, followed by lumbar interlaminar and caudal epidural injections of 34.9%, followed by 9.4% for lumbar/sacral transforaminal epidurals, and 3.5% for cervical and thoracic interlaminar epidurals. LIMITATIONS This analysis was limited by noninclusion of Medicare Advantage plans, which constitutes almost 30% of the Medicare population. In addition, utilization data for individual states continues to be sparse and may not be accurate or representative of the population. CONCLUSIONS The declining utilization of epidural injections in all categories with an annual of 2.5% and overall decrease of 20.7% from 2009 to 2018 compared with annual increases of 7.3% and overall increase of 89.2% from 2000 to 2009 shows a slow decline of utilization of all epidural injections. KEY WORDS Chronic spinal pain, interlaminar epidural injections, caudal epidural injections, transforaminal epidural injections, utilization patterns.