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Corona Virus Disease 2019 (COVID-19) is a new strain of coronavirus called SARS-CoV-2, which was identified in Wuhan, China, in December 2019. The rapid transmission of COVID-19 from human to human forced researchers to find a potent drug by setting aside the time-consuming traditional method in drug development. The molecular docking approach is one a reliable method to screening compound from chemical drug or by finding a compound from Indonesian herbal plants. The present study aimed to assess the potency of compounds from five medicinal plants as potential inhibitors of PLpro and 3CLpro from SARS-CoV-2 using molecular study. The molecular docking was performed using Protein-Ligand Ant System (PLANTS) to analyze the potential compounds by the docking score. Remdesivir triphosphate was used as a standard for the comparison of the test compounds. The docking score obtained from the docking of PLpro with native ligand, remdesivir triphosphate, curcumin, demethoxycurcumin, bisdemethoxycurcumin, luteolin, apigenin, quercetin, kaempferol, formononetin-7-O-glucuronide, andrographolide, and neoandrographolide were -111.441, -103.827, -103.609, -102.363, -100.27, -79.6655, -78.6901, -80.9337, -79.4686, -82.1124, -79.1789, and -97.2452, respectively. Meanwhile, docking score with 3CLpro for the same ligand were -64.0074, -86.1811, -81.428, -87.1625, -78.2899, -73.4345, -70.3368, -71.5539, -68.4321, -72.0154, -75.9777, and -93.7746. The docking score data suggest that curcumin was the most potential as a PLpro inhibitor, while neoandrographolide was the best as a 3CLpro inhibitor.

A scintillating bolometer based on a large cubic Li$_{2}$$^{100}$MoO$_4$ crystal (45 mm side) and a Ge wafer (scintillation detector) has been operated in the CROSS cryogenic facility at the Canfranc underground laboratory in Spain. The dual-readout detector is a prototype of the technology that will be used in the next-generation $0\nu2\beta$ experiment CUPID. The measurements were performed at 18 and 12 mK temperature in a pulse tube dilution refrigerator. This setup utilizes the same technology as the CUORE cryostat that will host CUPID and so represents an accurate estimation of the expected performance. The Li$_{2}$$^{100}$MoO$_4$ bolometer shows a high energy resolution of 6 keV FWHM at the 2615 keV $\gamma$ line. The detection of scintillation light for each event triggered by the Li$_{2}$$^{100}$MoO$_4$ bolometer allowed for a full separation ($\sim$8$\sigma$) between $\gamma$($\beta$) and $\alpha$ events above 2 MeV. The Li$_{2}$$^{100}$MoO$_4$ crystal also shows a high internal radiopurity with $^{228}$Th and $^{226}$Ra activities of less than 3 and 8 $\mu$Bq/kg, respectively. Taking also into account the advantage of a more compact and massive detector array, which can be made of cubic-shaped crystals (compared to the cylindrical ones), this test demonstrates the great potential of cubic Li$_{2}$$^{100}$MoO$_4$ scintillating bolometers for high-sensitivity searches for the $^{100}$Mo $0\nu2\beta$ decay in CROSS and CUPID projects., Comment: 19 pages, 7 figures, 1 table

O presente artigo tem como objetivo analisar a Gestão Pública e a qualidade no transporte coletivo, que é considerada uma das formas de locomoção mais usadas no Brasil, porém, não basta apenas oferecer o serviço, este precisa ser prestado com qualidade, mas essa não é a realidade de muitos estados da federação. Diante disso, pretende-se realizar uma pesquisa bibliográfica, baseada em livros, artigos, monografias, teses, dissertações indexados nas bases de dados Scielo e Google acadêmico, abrangendo um recorte temporal, de 2009 a 2019. Os resultados mostraram que a Gestão Pública precisa ser planejada para que a qualidade dos serviços públicos, como a oferta de transporte coletivo, para a população em geral seja satisfatória, ou seja, com ônibus novos, com acessibilidade, pois sabe-se que as pessoas com necessidades especiais são amparados legalmente pela CF de 1988, bem como pela Lei da Inclusão, atentando-se ao conforto e comodidade, bem como ao custo da tarifa. Diante dos resultados apresentados nas publicações selecionadas, em que as pesquisas foram realizadas no Distrito Federal, Natal e Bahia, evidenciou-se a insatisfação dos usuários pelos serviços prestados pelas empresas terceirizadas, pois o sucateamento dos ônibus, além das altas tarifas não, fiscalizadas pela contratante, no caso, as prefeituras. Serão apresentados alguns dados da capital amazonense que mostram a precariedade do serviço por causa da má gestão, e, com isso, interfere-se no tempo e distâncias das pessoas para chegarem em determinados locais.

Combination of CDK4/6 inhibitors and endocrine therapy improves clinical outcome in advanced oestrogen receptor (ER)-positive breast cancer, however relapse is inevitable. Here, we show in model systems that other than loss ofRB1few gene-copy number (CN) alterations are associated with irreversible-resistance to endocrine therapy and subsequent secondary resistance to palbociclib. Resistance to palbociclib occurred as a result of tumour cell re-wiring leading to increased expression ofEGFR, MAPK, CDK4, CDK2, CDK7, CCNE1andCCNE2. Resistance altered the ER genome wide-binding pattern, leading to decreased expression of ‘classical’ oestrogen-regulated genes and was accompanied by reduced sensitivity to fulvestrant and tamoxifen. Persistent CDK4 blockade decreased phosphorylation of tuberous sclerosis complex 2 (TSC2) enhancing EGFR signalling, leading to the re-wiring of ER. Kinome-knockdown confirmed dependency on ERBB-signalling and G2/M–checkpoint proteins such as WEE1, together with the cell cycle master regulator, CDK7. Noteworthy, sensitivity to CDK7 inhibition was associated with loss of ER andRB1CN. Overall, we show that resistance to CDK4/6 inhibitors is dependent on kinase re-wiring and the redeployment of signalling cascades previously associated with endocrine resistance and highlights new therapeutic networks that can be exploited upon relapse after CDK4/6 inhibition.

Rationale: Anaplastic large T-cell lymphoma (BI-ALCL) is a rare primitive lymphoma described in women with breast implant prostheses, which has been arousing interest in recent years due to its potentially high social impact. The difficult diagnosis associated with the high and increasing number of prosthetic implants worldwide has led to hypothesize an underestimation of the real impact of the disease among prosthesis-bearing women. The aim of this work is to search for specific radiological signs of disease linked to the chronic inflammatory pathogenetic mechanism. Patient concerns: This work describes a case of BI-ALCL in an American woman with no personal or family history of cancer, who underwent breast augmentation for esthetic purposes at our Institute. After about 10 years of relative well-being, the patient returned to our Institute with clear evidence of breast asymmetry due to the increase in volume of the right breast which had progressively become larger over a period of 6 months. There was no evidence of palpable axillary lymph nodes or other noteworthy signs. Diagnosis: The ultrasound and magnetic resonance (MR) tests indicated the presence of seroma with amorphous material in the exudate which was confirmed by indirect signs, visible in right breast mammography. Due to suspected cold seroma, an ultrasound-guided needle aspiration was performed for the cytological analysis of the effusion which highlighted the presence of a number of large-sized atypical cells with an irregular nucleus with CD30 immunoreactivity, leucocyte common antigen (CD45) compatible with the BI-ALCL diagnosis. Interventions: In our case, a capsulectomy was performed because the disease was limited inside the capsule and periprosthetic seroma. The final histological examination confirmed the stage. Lessons: The patient is being monitored and shows no signs of recurrence of disease >24 months after surgery. Conclusion: A diagnosis of BI-ALCL can be reached using new radiological indicators, such as fibrin, which is clearly visible by MR in the form of nonvascularized debris of amorphous material hypointense in all sequences, free flowing or adhered to the external surface of the prosthesis.

The dynamic contrast-enhanced MR imaging plays a crucial role in evaluating the effectiveness of neoadjuvant chemotherapy (NAC) even since its early stage through the prediction of the final pathological complete response (pCR). In this study, we proposed a transfer learning approach to predict if a patient achieved pCR (pCR) or did not (non-pCR) by exploiting, separately or in combination, pre-treatment and early-treatment exams from I-SPY1 TRIAL public database. First, low-level features, i.e., related to local structure of the image, were automatically extracted by a pre-trained convolutional neural network (CNN) overcoming manual feature extraction. Next, an optimal set of most stable features was detected and then used to design an SVM classifier. A first subset of patients, called fine-tuning dataset (30 pCR; 78 non-pCR), was used to perform the optimal choice of features. A second subset not involved in the feature selection process was employed as an independent test (7 pCR; 19 non-pCR) to validate the model. By combining the optimal features extracted from both pre-treatment and early-treatment exams with some clinical features, i.e., ER, PgR, HER2 and molecular subtype, an accuracy of 91.4% and 92.3%, and an AUC value of 0.93 and 0.90, were returned on the fine-tuning dataset and the independent test, respectively. Overall, the low-level CNN features have an important role in the early evaluation of the NAC efficacy by predicting pCR. The proposed model represents a first effort towards the development of a clinical support tool for an early prediction of pCR to NAC.

[EN] CRISPR/Cas ability to target several loci simultaneously (multiplexing) is a game-changer in plant breeding. Multiplexing not only accelerates trait pyramiding but also can unveil traits hidden by functional redundancy. Furthermore, multiplexing enhances dCas-based programmable gene expression and enables cascade-like gene regulation. However, the design and assembly of multiplex constructs comprising tandemly arrayed guide RNAs (gRNAs) requires scarless cloning and is still troublesome due to the presence of repetitive sequences, thus hampering a more widespread use. Here we present a comprehensive extension of the software-assisted cloning platform GoldenBraid (GB), in which, on top of its multigene cloning software, we integrate new tools for the Type IIS-based easy and rapid assembly of up to six tandemly-arrayed gRNAs with both Cas9 and Cas12a, using the gRNA-tRNA-spaced and the crRNA unspaced approaches, respectively. As stress tests for the new tools, we assembled and used for Agrobacterium-mediated stable transformation a 17 Cas9-gRNAs construct targeting a subset of the Squamosa-Promoter Binding Protein-Like (SPL) gene family in Nicotiana tabacum. The 14 selected genes are targets of miR156, thus potentially playing an important role in juvenile-to-adult and vegetative-to-reproductive phase transitions. With the 17 gRNAs construct we generated a collection of Cas9-free SPL edited T-1 plants harboring up to 9 biallelic mutations and showing leaf juvenility and more branching. The functionality of GB-assembled dCas9 and dCas12a-based CRISPR/Cas activators and repressors using single and multiplexing gRNAs was validated using a Luciferase reporter with the Solanum lycopersicum Mtb promoter or the Agrobacterium tumefaciens nopaline synthase promoter in transient expression in Nicotiana benthamiana. With the incorporation of the new web-based tools and the accompanying collection of DNA parts, the GB4.0 genome edition turns an all-in-one open platform for plant genome engineering., This work had been funded by EU Horizon 2020 Project Newcotiana Grant 760331 and PID2019-108203RB-100 Plan Nacional I+D, Spanish Ministry of Economy and Competitiveness. MV-V was recipient of aGeneralitat Valenciana and Fondo Social Europeo post-doctoral grant. JB-O and SS were recipients of FPI fellowships. CP was recipient of a Santiago Grisolia fellowship (Generalitat Valenciana).

BACKGROUND: The prevalence of current electronic cigarette (e-cigarette) use has increased dramatically among US youth. It is unknown how the impact of policies to curb e-cigarette use might differ across rural and urban areas. METHODS: Data were collected from an annual statewide survey of middle and high school students in Kansas. Multivariable logistic regression was performed to examine the temporal change in current e-cigarette use in 2018 and 2019 across rural and urban areas and across the areas with and without a Tobacco 21 (T21) policy that raises the minimum age of tobacco sales to 21 years. RESULTS: Of 132 803 participants, the prevalence of current e-cigarette use increased from 8.2% in 2018 to 12.6% in 2019. The increase was larger in rural areas (from 6.7% in 2018 to 13.4% in 2019, difference = 6.7%) than in urban areas (9.8%–11.9%, difference = 2.1%), with a significant interaction effect of year × urbanicity/T21 group (P < .0001). In urban areas, e-cigarette use increased significantly for middle school students in T21 areas (3.3%–4.5%; P = .01) and all students in non-T21 areas (8.1%–12.0%; P < .0001). In rural areas, the increase in e-cigarette use was significant in both T21 and non-T21 areas for all students, but the increase was smaller in T21 (7.9%–10.8%, difference = 3.0%) than in non-T21 areas (6.5%–13.7%, difference = 7.1%). CONCLUSIONS: In this study, we reported marked disparities in the increase of youth e-cigarette use, with a larger recent increase in rural than in urban areas. T21 policies appear to mitigate these increases in both rural and urban youth.

Objectives To identify correlations between family characteristics, nutritional parenting, and stunting in children under five in South Jakarta. Method This study used an observational, descriptive research design and a community-based cross-sectional approach. A total of 192 samples were included in the study, selected using the cluster sampling technique. Family Characteristics and Nutritional Parenting Tools contain the types of questions that were used to collect the data. A correlation data analysis was conducted using an independent t-test, chi-square, and multiple logistic regression prediction modeling. Results The results of the research showed a significant correlation between family characteristics and nutritional parenting with the occurrence of stunting in children under five in South Jakarta. Families whose incomes were below the regional minimum wage had a 6.625 times greater chance of observing stunting in children under five compared to families whose incomes were above the regional minimum wage with Wald value of 28.148. Conclusions Socioeconomic factors, especially household income, are the factors that are most responsible for influencing the incidence of stunting in children under five. Multisector and integrated programs are needed to increase household income, knowledge, and family skills to reduce the incidence of stunting in children under five.

Polydimethylsiloxane (PDMS) with two type viscosity that commonly used as vitreous humour substitutes in vitreoretinal surgery has been successfully synthesized by ring-opening polymerization. Optimization of synthesized parameters such as ratio of monomer and chain terminator, the amount of initiator, mixing temperature and reaction time was carried out to obtain PDMS materials having similar properties with commercial product. PDMS with viscosity of 1.17 Pas that very close to viscosity of commercial PDMS of 1.08 Pas, was successfully synthesized with a ratio of 26:10 monomer and terminator chain, 0.58 M of initiator KOH, 170 oC of mixing temperature and 35 minutes of reaction time. By changing reaction time to 40 minutes, PDMS was successfully synthesized with viscosity of 3.42 that similar to that of commercial one.

The mortality associated to breast cancer is in many cases related to metastasization and recurrence. Personalized treatment strategies are critical for the outcomes improvement of BC patients and the Clinical Decision Support Systems can have an important role in medical practice. In this paper, we present the preliminary results of a prediction model of the Breast Cancer Recurrence (BCR) within five and ten years after diagnosis. The main breast cancer-related and treatment-related features of 256 patients referred to Istituto Tumori “Giovanni Paolo II” of Bari (Italy) were used to train machine learning algorithms at the-state-of-the-art. Firstly, we implemented several feature importance techniques and then we evaluated the prediction performances of BCR within 5 and 10 years after the first diagnosis by means different classifiers. By using a small number of features, the models reached highly performing results both with reference to the BCR within 5 years and within 10 years with an accuracy of 77.50% and 80.39% and a sensitivity of 92.31% and 95.83% respectively, in the hold-out sample test. Despite validation studies are needed on larger samples, our results are promising for the development of a reliable prognostic supporting tool for clinicians in the definition of personalized treatment plans.

Contrast-enhanced spectral mammography (CESM) is an advanced instrument for breast care that is still operator dependent. The aim of this paper is the proposal of an automated system able to discriminate benign and malignant breast lesions based on radiomic analysis. We selected a set of 58 regions of interest (ROIs) extracted from 53 patients referred to Istituto Tumori “Giovanni Paolo II” of Bari (Italy) for the breast cancer screening phase between March 2017 and June 2018. We extracted 464 features of different kinds, such as points and corners of interest, textural and statistical features from both the original ROIs and the ones obtained by a Haar decomposition and a gradient image implementation. The features data had a large dimension that can affect the process and accuracy of cancer classification. Therefore, a classification scheme for dimension reduction was needed. Specifically, a principal component analysis (PCA) dimension reduction technique that includes the calculation of variance proportion for eigenvector selection was used. For the classification method, we trained three different classifiers, that is a random forest, a naïve Bayes and a logistic regression, on each sub-set of principal components (PC) selected by a sequential forward algorithm. Moreover, we focused on the starting features that contributed most to the calculation of the related PCs, which returned the best classification models. The method obtained with the aid of the random forest classifier resulted in the best prediction of benign/malignant ROIs with median values for sensitivity and specificity of 88.37% and 100%, respectively, by using only three PCs. The features that had shown the greatest contribution to the definition of the same were almost all extracted from the LE images. Our system could represent a valid support tool for radiologists for interpreting CESM images.

In early 2020, the COVID-19 pandemic was declared, which impacted music therapists in terms of employment, service delivery, and mental health. However, the extent of changes within the profession was unknown. The purpose of this study was to determine the impact of the pandemic on the employment, service delivery, stress, and hope of music therapy professionals in the United States. Music therapists (N = 1,196) responded to a 51-item survey including questions related to employment and service delivery. The study also included the Adult Hope Scale and the Perceived Stress Scale-10 (PSS-10). Results indicated that many music therapists experienced changes in their positions, including a decrease in client contact hours and an increase in using alternative services, such as telehealth. Changes in service hours and delivery were higher for individuals who worked in private practice than for other settings. Primary respondent concerns included being a carrier of COVID-19, being isolated from loved ones, and income loss. Compared with prior general population samples from the United States, respondents reported higher levels of hope, with a majority of respondents also reporting a high level of hope for the profession. Respondents also indicated a moderate level of perceived stress on the PSS-10. Open response comments provided additional insights into the situational stressors and feelings of hope at this time in the pandemic. The results of this study indicate that music therapists adapted to service delivery changes and continued to provide services to clients, despite the many difficulties faced during the pandemic.

Background Despite maximal therapy with surgery, chemotherapy, and radiotherapy, glioblastoma (GBM) patients have a median survival of only 15 months. Almost all patients inevitably experience symptomatic tumor recurrence. A hallmark of this tumor type is the large heterogeneity between patients and within tumors itself which relates to the failure of standardized tumor treatment. In this study, tissue samples of paired primary and recurrent GBM tumors were investigated to identify individual factors related to tumor progression. Methods Paired primary and recurrent GBM tumor tissues from 8 patients were investigated with a multiomics approach using transcriptomics, proteomics, and phosphoproteomics. Results In the studied patient cohort, large variations between and within patients are observed for all omics analyses. A few pathways affected at the different omics levels partly overlapped if patients are analyzed at the individual level, such as synaptogenesis (containing the SNARE complex) and cholesterol metabolism. Phosphoproteomics revealed increased STMN1(S38) phosphorylation as part of ERBB4 signaling. A pathway tool has been developed to visualize and compare different omics datasets per patient and showed potential therapeutic drugs, such as abobotulinumtoxinA (synaptogenesis) and afatinib (ERBB4 signaling). Afatinib is currently in clinical trials for GBM. Conclusions A large variation on all omics levels exists between and within GBM patients. Therefore, it will be rather unlikely to find a drug treatment that would fit all patients. Instead, a multiomics approach offers the potential to identify affected pathways on the individual patient level and select treatment options.

Background Raising the minimum legal age (MLA) of tobacco sales from 18 to 21 (Tobacco 21 [T21]) has recently been implemented nationwide as a method to reduce tobacco use, but empirical data on youth knowledge of T21 policies and related pathways to tobacco use are limited. Methods Data were collected from the 2018 Kansas Communities That Care Student Survey. Knowledge of the MLA was compared between T21 and non-T21 regions using a quasi-experimental design. Logistic regression and mediation analysis were conducted to assess the association between knowledge of the MLA, influencing factors, and intention to use tobacco. Results Of 16 949 students (aged between 11 and 18) completing the T21 survey, fewer students responded correctly about the MLA in T21 than in non-T21 regions (37.4% vs. 46.3% responded correctly, 27.6% vs. 24.2% responded incorrectly, respectively). In T21 regions, Hispanics and students who support T21 were more likely to respond correctly about the MLA. Among current non-tobacco users in T21 regions, students who responded correctly about the MLA were less likely to report intention to use tobacco (adjusted odds ratio [AOR] = 0.7, 95% confidence interval [CI]: [0.6–0.8]) than those who responded incorrectly. The pathway from knowledge of the MLA to intention to use tobacco was significantly mediated by increased support for T21 (p = .002), perceived difficulty in accessing cigarettes (p = .042), and reduced susceptibility to peer influence (p = .027). Conclusions Knowledge of the MLA was inversely associated with intention to use tobacco among youth. Educational campaigns to raise awareness and support for T21 among youth may improve the impact of T21 policies. Implications This study examined youth knowledge of the MLA to purchase tobacco products, and whether knowledge of the MLA was associated with reduced intention to use tobacco. It also examined other influencing factors (eg, perceived support for T21) and potential mediation pathways linking knowledge of the MLA with intention to use tobacco. Given the nationwide adoption of T21, educational campaigns to promote knowledge of the policy may improve its impact.

Aspergillus fumigatus is a human pathogen and the principal etiologic agent of invasive and chronic aspergillosis leading to several hundreds of thousands of deaths every year. Very few antifungals are available to treat infections caused by A. fumigatus, and resistance is developing to those we have. Our understanding of the molecular mechanisms that drive pathogenicity and drug resistance have been hampered by the lack of large mutant collections, which limits our ability to perform functional genomics analysis. Here we present a high-throughput gene knockout method that combines a highly reproducible fusion PCR method to enable generation of gene replacement cassettes with a multiwell format transformation procedure. This process can be used to generate 96 null mutants within 5 days by a single person at a cost of less than £18 ($24) per mutant and is being employed in our laboratory to generate a barcoded genome-wide knockout library in A. fumigatus. © 2019 The Authors.

Aspergillus fumigatus is an opportunistic human pathogenic mold. DNA extraction from this fungus is usually performed by mechanical perturbation of cells, as it possesses a rigid and complex cell wall. While this is not problematic for single isolates, it can be time consuming for large numbers of strains if using traditional DNA extraction procedures. Therefore, in this article we describe a fast and efficient thermal‐shock method to release DNA from spores of A. fumigatus and other filamentous fungi without the need for complex extraction methods. This is especially important for high‐throughput PCR analyses of mutants in 96‐ or 384‐well formats in a very short period of time without any concern about sample cross‐contamination. This method is currently being used to validate the protein‐coding gene and non‐coding RNA knockout libraries in A. fumigatus generated in our laboratory, and could be used in the future for diagnostics purposes. © 2019 The Authors.

The increased speed and sensitivity in mass spectrometry-based proteomics has encouraged its use in biomedical research in recent years. Large-scale detection of proteins in cells, tissues and whole organisms yields highly-complex quantitative data, the analysis of which poses significant challenges. Standardized proteomic workflows are necessary to ensure automated, sharable and reproducible proteomics analysis. Likewise, standardized data processing workflows are also essential for the overall reproducibility of results. To this purpose, we developed PaDuA, a Python package optimized for the processing and analysis of (phospho)proteomics data. PaDuA provides a collection of tools which can be used to build scripted workflows within Jupyter Notebooks, to facilitate bioinformatics analysis by both end-users and developers.

Background : Dengue hemorrhagic fever is one of the major global public health problems. Secondary prevention of dengue fever must be conducted to prevent high mortality rate by giving appropriate diagnosis and early management. This study was conducted to identify health-seeking behavior in dengue hemorrhagic patients and its related factors. Methods : This study involved 98 dengue hemorrhagic patients from four hospitals in Bandung region during July until November 2014. The hospitals were 2 public hospitals and 2 private hospitals. A questionnaire and in depth interview were used to collect the data. Results : Among 98 patients, 54 patients (55%) sought a right medical treatment timely, whereas 44 patients (45%) delayed. The first seeking behaviour to treat the disease was using over-the-counter drugs, followed by visiting a private clinic doctor. The second choice to seek health care was going to a private clinic doctor and hospital. Conclusions: Health-seeking behavior in dengue hemorrhagic patients in Bandung is inappropriate which can cause delay in treatment.

According to the National Institute of Deafness and other Communication Disorders 2012 report, the number of cochlear implant (CI) users is steadily increasing from 324,000 CI users worldwide. The cochlea, located in the inner ear, is a snail-like structure that exhibits a tonotopic geometry where acoustic waves are filtered spatially according to frequency. Throughout the cochlea, there exist hair cells that transduce sensed acoustic waves into an electrical signal that is carried by the auditory nerve to ultimately reach the auditory cortex of the brain. A cochlear implant bridges the gap if non-functional hair cells are present. Conventional CIs directly inject an electrical current into surrounding tissue via an implanted electrode array and exploit the frequency-to-place mapping of the cochlea. However, the current is dispersed in perilymph, a conductive bodily fluid within the cochlea, causing a spread of excitation. Magnetic fields are more impervious to the effects of the cochlear environment due to the material properties of perilymph and surrounding tissue, demonstrating potential to improve precision. As an alternative to conventional CI electrodes, the development and miniaturization of microcoils intended for micromagnetic stimulation of intracochlear neural elements is described. As a step toward realizing a microcoil array sized for cochlear implantation, human-sized coils were prototyped via aerosol jet printing. The batch reproducible aerosol jet printed microcoils have a diameter of 1800 μm, trace width and trace spacing of 112.5 μm, 12 μm thickness, and inductance values of approximately 15.5 nH. Modelling results indicate that the coils have a combined depolarization–hyperpolarization region that spans 1.5 mm and produce a more restrictive spread of activation when compared with conventional CI.

Intrinsic and/or acquired resistance represents one of the great challenges in targeted cancer therapy. A deeper understanding of the molecular biology of cancer has resulted in more efficient strategies, where one or multiple drugs are adopted in novel therapies to tackle resistance. This beneficial effect of using combination treatments has also been observed in colorectal cancer patients harboring the BRAF(V600E) mutation, whereby dual inhibition of BRAF(V600E) and EGFR increases antitumor activity. Notwithstanding this success, it is not clear whether this combination treatment is the only or most effective treatment to block intrinsic resistance to BRAF inhibitors. Here, we investigate molecular responses upon single and multi-target treatments, over time, using BRAF(V600E) mutant colorectal cancer cells as a model system. Through integration of transcriptomic, proteomic and phosphoproteomics data we obtain a comprehensive overview, revealing both known and novel responses. We primarily observe widespread upregulation of receptors tyrosine kinases and metabolic pathways upon BRAF inhibition. These findings point to mechanisms by which the drug-treated cells switch energy sources and enter a quiescent-like state as a defensive response, while additionally reactivating the MAPK pathway.

We report a sensitive amperometric dual glucose and lactate biosensor based on pyroloquinoline quinone glucose dehydrogenase (PQQ-GDH) and a lactate dehydrogenase (LDH) for the detection of glucose and lactate, respectively. The electrochemical sensing platform comprise multi-walled carbon nanotubes (MWCNTs) for the immobilization of the PQQ-GDH and LDH at the respective working electrodes. Platinum and Ag/AgCl counter and reference electrodes were integrated to construct a three-electrode system. The lactate biosensor component exhibited a linear response towards lactate over a concentration range of 1 to 10 mM lactate $(\mathbf{r}^{2}=\mathbf{0.998})$ and exhibit a sensitivity of $\mathbf{2.9}\mu \mathbf{A}$ mM−1 cm−2, whereas the glucose biosensor exhibited a linear response range of 1 to 10 mM glucose $(\mathbf{r}^{2}= \mathbf{0.990})$ and a sensitivity of $\mathbf{345.7}\ \mu \mathbf{A}$ mM−1 cm−2, These results show that the dual glucose and lactate biosensor possess important potential for application in clinical analysis and sports medicine.

Information Technology (TI) has a strong influence in the medical field, especially the pharmacy. Pharmacy is responsible for ensuring the effectiveness, safety, usage, and distribution of drugs. RSUD Dr Samratulangi Tondano starts to implement integration of drug producer or supplier because drug management and completeness are not always available on time. Beside for business, this is performed to minimize drug stock in the pharmacy, considering drugs are the main factor in treating patient. The researchers used SOA (Service Oriented Architecture) and ESB WSO2 models. The usage of SOA and ESB can help both the pharmacy and producers in communicating through a standard protocol to ease integration and exchange of pharmaceutical supply data. Based on the results of survey and analysis, it is concluded that the service of the pharmacy of RSUD DR Samratulangi Tondano was ineffective. Integration of pharmacy and drug manufacturers should be performed to improve service quality. SOA and ESB WSO2 models can meet the needs of pharmaceutical technology to improve the quality of pharmacy services in the community.