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https://www.readbyqxmd.com/read/29036404/the-value-of-prior-knowledge-in-machine-learning-of-complex-network-systems
#1
Dana Ferranti, David Krane, David Craft
Motivation: Our overall goal is to develop machine-learning approaches based on genomics and other relevant accessible information for use in predicting how a patient will respond to a given proposed drug or treatment. Given the complexity of this problem, we begin by developing, testing and analyzing learning methods using data from simulated systems, which allows us access to a known ground truth. We examine the benefits of using prior system knowledge and investigate how learning accuracy depends on various system parameters as well as the amount of training data available...
July 7, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29036385/the-latent-taxonicity-of-schizotypy-in-biological-siblings-of-probands-with-schizophrenia
#2
Richard J Linscott, Sarah E Morton
If schizotypy is a taxonic liability for schizophrenia with a general population prevalence of ~10%, it should also be taxonic among biological siblings of probands with schizophrenia. Moreover, assuming this is so, siblings' schizotypy class membership should be predicted by probands' familial load for psychotic disorder and clinical severity, consistent with a multifactorial polygenic threshold model of schizophrenia. We tested these hypotheses in the Genetic Risk and Outcome of Psychosis (GROUP) Study where siblings of probands (n = 792) and unaffected controls (n = 559) provided self-report ratings on the Community Assessment of Psychic Experiences (CAPE)...
October 4, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/29036309/chiral-analysis-of-methamphetamine-in-oral-fluid-samples-a-method-to-distinguish-licit-from-illicit-drug-use
#3
Damon Borg, Elizabeth Kolb, Cindy Lantigua, Richard Stripp
Methamphetamine (MAMP) is a popular illicit drug abused for its central nervous system stimulating effects. MAMP is also used therapeutically in the treatment of overeating disorders, narcolepsy, attention deficit disorder, in over-the-counter (OTC) products to ease nasal congestion. MAMP exists in two enantiomeric forms, dextrorotary (d-MAMP) or levorotary (l-MAMP). The compounds are similar in chemical structure, simply differing in the orientation of functional groups around the asymmetric carbon. In part because of the availability of l-MAMP in OTC nasal inhalers, forensic guidelines require a sample to contain greater than 20% d-MAMP to consider illicit drug use when interpreting results...
September 25, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/29036254/evaluation-of-risk-of-major-adverse-cardiovascular-events-with-biologic-therapy-in-patients-with-psoriasis
#4
Robert Bissonnette, Francisco Kerdel, Luigi Naldi, Kim Papp, Claudia Galindo, Wayne Langholff, K L Tang, Philippe Szapary, Steven Fakharzadeh, Bhaskar Srivastava, Kavitha Goyal, Alice B Gottlieb
BACKGROUND: Psoriasis is associated with increased risk of major adverse cardiovascular events (MACE). OBJECTIVES: Compare MACE risk with biologics vs topical/phototherapy use. METHODS: Psoriasis Longitudinal Assessment Registry (PSOLAR) is an international psoriasis registry of patients eligible to receive biologic/systemic treatments prospectively. MACE is defined as myocardial infarction, stroke, or cardiovascular death. Biologic cohorts, including tumor necrosis factor-alpha (TNF-α) inhibitors (ie, adalimumab, etanercept, and infliximab) and ustekinumab, combined and by class, were compared with a topical/phototherapy cohort...
October 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29036253/understanding-state-regulation-of-biosimilars-and-effect-on-prescribers
#5
Katerina Yale, Olabola Awosika, Monica Rengifo-Pardo, Alison Ehrlich
Biologics are a mainstay of treatment for many dermatologic conditions, however the high costs can be prohibitive for many patients. A growing market of biosimilar drugs is emerging with the hope of providing patients access to more affordable medications. While the FDA has created an abbreviated licensure pathway for these drugs, states are still in the process of creating regulations regarding their substitution for reference biologics. This article looks to raise awareness of the current federal regulations and the differences among state regulations regarding the use of biosimilars...
October 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29036249/cost-effectiveness-analysis-of-ixekizumab-vs-etanercept-and-their-manufacturer-recommended-dosing-regimens-in-moderate-to-severe-plaque-psoriasis
#6
Jeremy Udkoff, Lawrence F Eichenfield
INTRODUCTION: Biologic therapies have revolutionized the treatment of psoriasis; however, their use is limited by costs. Ixekizumab was more effective than etanercept in the UNCOVER trials, and the Food and Drug Administration (FDA) approved ixekizumab for treating psoriasis. Evaluating the cost-effectiveness of these therapies is crucial for medical decision making and our objective was to determine the cost-effectiveness of various ixekizumab dosing frequencies compared with etanercept...
October 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29036248/apremilast-and-narrowband-ultraviolet-b-combination-therapy-for-treating-moderate-to-severe-plaque-psoriasis
#7
Jerry Bagel, Elise Nelson, Brian R Keegan
BACKGROUND: Combining narrowband UVB (NB-UVB) phototherapy with biologics has been shown to enhance the therapeutic response of plaque psoriasis patients. The objective of this study was to evaluate the effectiveness of apremilast combined with NB-UVB in patients with moderate to severe plaque psoriasis. METHODS: This was a 12-week, open-label study of 29 patients diagnosed with moderate to severe psoriasis. Patients received apremilast 30 mg twice daily, and increasing doses of NB-UVB (310-312 nm) 3 times per week for 12 weeks...
October 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29036019/targeting-the-interleukin-4-and-interleukin-13-pathways-in-severe-asthma-current-knowledge-and-future-needs
#8
Amit D Parulekar, Christina C Kao, Zuzana Diamant, Nicola A Hanania
PURPOSE OF REVIEW: Severe asthma is a heterogeneous disease that can be classified into phenotypes and endotypes based upon clinical or biological characteristics. Interleukin (IL)-4 and IL-13 play a key role in type 2 (T2) asthma. This article reviews the signaling pathway of IL-4 and IL-13 and highlights its targeted therapy in severe asthma. RECENT FINDINGS: Several clinical trials of biologics targeting the IL-4/IL-13 pathway have recently been completed. In patients with severe, uncontrolled asthma, targeting IL-13 alone with biologics including lebrikizumab and tralokinumab has not shown consistent reduction in asthma exacerbations...
October 13, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/29035933/psoriatic-arthritis-new-evidence-for-old-concepts
#9
Enrique R Soriano, Josefina Marin, Maria L Acosta-Felquer
PURPOSE OF REVIEW: The review gives an updated overview of some of the new concepts in the management of psoriatic arthritis (PsA): early diagnosis, remission as an objective, treat-to-target, and treatment guidelines. RECENT FINDINGS: Early diagnosis, targeting remission as part of a treatment strategy, and new guidelines providing evidence-based support to these concepts are main topics in recent publications. SUMMARY: Dermatologists and rheumatologists should work together to reduce the number of patients remaining undiagnosed, and the time to do so...
October 13, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/29035761/lab-on-a-chip-systems-for-photodynamic-therapy-investigations
#10
REVIEW
Michał Chudy, Katarzyna Tokarska, Elżbieta Jastrzębska, Magdalena Bułka, Sławomir Drozdek, Łukasz Lamch, Kazimiera A Wilk, Zbigniew Brzózka
In recent years photodynamic therapy (PDT) has received widespread attention in cancer treatment due to its smaller surgical trauma, better selectivity towards tumor cells, reduced side effects and possibility of repeatable treatment. Since cancer is the second cause of death worldwide, scientists constantly seek for new potential therapeutic agents including nanotechnology-based photosensitizers used in PDT. The new-designed nanostructures must be carefully studied and well characterized what require analytically useful and powerful tools that enable real progress in nanoscience development...
October 7, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29035675/practical-considerations-in-clinical-strategy-to-support-the-development-of-injectable-drug-device-combination-products-for-biologics
#11
Zhaoyang Li, Rachael Easton
The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely...
October 16, 2017: MAbs
https://www.readbyqxmd.com/read/29035510/crispri-and-crispra-screens-in-mammalian-cells-for-precision-biology-and-medicine
#12
Martin Kampmann
Next-generation DNA sequencing technologies have led to a massive accumulation of genomic and transcriptomic data from patients and healthy individuals. The major challenge ahead is to understand the functional significance of the elements of the human genome and transcriptome, and implications for diagnosis and treatment. Genetic screens in mammalian cells are a powerful approach to systematically elucidate gene function in health and disease states. In particular, recently developed CRISPR/Cas9-based screening approaches have enormous potential to uncover mechanisms and therapeutic strategies for human diseases...
October 16, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29035502/binding-mechanism-of-model-charged-dye-carboxyfluorescein-to-hyaluronan-polylysine-multilayers
#13
Vladimir Z Prokopovic, Anna S Vikulina, David Sustr, Elena M Shchukina, Dmitry G Shchukin, Dmitry V Volodkin
Biopolymer-based multilayers become more and more attractive due to the vast span of biological application they can be used for, e.g. implant coatings, cell culture supports, scaffolds. Multilayers have demonstrated superior capability to store enormous amount of small charged molecules such as drugs and release them in a controlled manner, however, the binding mechanism for drug loading into the multilayers is still poorly understood. Here we focus on this mechanism using model hyaluronan/polylysine (HA/PLL) multilayers and a model charged dye carboxyfluorescein (CF)...
October 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29035303/optimization-of-bicomponent-electrospun-fibers-for-therapeutic-use-post-treatments-to-improve-chemical-and-biological-stability
#14
Antonio Papa, Vincenzo Guarino, Valentina Cirillo, Olimpia Oliviero, Luigi Ambrosio
Bicomponent electrospun nanofibers based on the combination of synthetic (i.e., aliphatic polyesters such as polycaprolactone (PCL)) and natural proteins (i.e., gelatin) have been extensively investigated as temporary platforms to instruct cells by the release of molecular/pharmaceutical signals for the regeneration of several tissues. Here, water soluble proteins (i.e., gelatin), strictly embedded to PCL, act as carriers of bioactive molecules, thus improving bioavailability and supporting cell activities during in vitro regeneration...
October 16, 2017: Journal of Functional Biomaterials
https://www.readbyqxmd.com/read/29035247/importance-of-land-snails-in-dicrocoeliosis-epidemiology
#15
Gözde Gürelli
Dicrocoeliosis is a helminthosis caused by the small liver fluke Dicrocoelium spp. (Trematoda, Dicrocoeliidae) parasitizing in the bile ducts and gall bladder of ruminants as well as many other animal species including humans. In the biological life cycle of Dicrocoelium, land snails are first intermediate hosts and ants are second intermediate hosts. Sporocysts and cercaria, which are larval stages, live in the hepatopancreas of land snails and metacercaria, which is also the larval stage, lives in the abdomen and brain of ants...
September 2017: Türkiye Parazitolojii Dergisi
https://www.readbyqxmd.com/read/29035081/biological-evaluation-of-novel-curcumin-pyrazole-mannich-derivative-active-against-drug-resistant-mycobacterium-tuberculosis
#16
Alok Kumar Singh, Pragya Yadav, Pratiksha Karaulia, Vinay Kumar Singh, Pushpa Gupta, Santosh Kumar Puttrevu, Sanjay Chauhan, Rabi S Bhatta, Narender Tadigoppula, Umesh D Gupta, Sidharth Chopra, Arunava Dasgupta
AIM: Our objective was to identify a more potent curcumin derivative with specific activity against Mycobacterium tuberculosis. MATERIALS & METHODS:  A total of 21 curcumin derivatives were synthesized and detailed bio-evaluation was carried out including determination of static/cidality, synergy with front-line antituberculosis drugs and determination of efficacy in the murine model of M. tuberculosis infection. RESULTS: We identified CPMD-6d dihydrochloride exhibiting concentration-dependent bactericidal activity against M...
October 16, 2017: Future Microbiology
https://www.readbyqxmd.com/read/29035049/exceptionally-high-proton-and-lithium-cation-gas-phase-basicity-of-the-anti-diabetic-drug-metformin
#17
Ewa Daniela Raczynska, Jean-Francois Gal, Pierre-Charles Maria, Piotr Michalec, Marcin Zalewski
Substituted biguanides are known for their biological effect and a few of them are used as drugs, the most prominent example being metformin (1,1-dimethylbiguanide, IUPAC name: N,N-dimethylimidodicarbonimidic diamide). Owing to the presence of hydrogen atoms at the amino groups, biguanides exhibit a multiple tautomerism. This aspect of their structures was examined in detail for unsubstituted biguanide and metformin in the gas phase. At the DFT level {essentially B3LYP/6-311+G(d,p)}, the most stable structures correspond to the conjugated, push-pull, system (NR2)(NH2)C=N-C(=NH)NH2 (R= H, CH3), further stabilized by an internal hydrogen bond...
October 16, 2017: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/29034942/guanidinium-based-molecular-glues-for-modulation-of-biomolecular-functions
#18
Rina Mogaki, P K Hashim, Kou Okuro, Takuzo Aida
Molecular adhesion based on multivalent interactions plays essential roles in various biological processes. Hence, "molecular glues" that can adhere to biomolecules may modulate biomolecular functions and therefore can be applied to therapeutics. This tutorial review describes design strategies for developing adhesive motifs for biomolecules based on multivalent interactions. We highlight a guanidinium ion-based salt-bridge as a key interaction for adhesion to biomolecules and discuss the application of molecular glues for manipulation of biomolecular assemblies, drug delivery systems, and modulation of biomolecular functions...
October 16, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/29034836/nanomedicine-for-intranasal-delivery-to-improve-brain-uptake
#19
Amit A Patel, Ravish J Patel, Shachi R Patel
Intranasal drug delivery system provide distinct advantage over conventional drug delivery system for a drug that is pharmacokenetically or biologically unstable. Major concern for treatment of central nervous system diseases are law concentration of therapeutically active molecule within brain as blood brain barrier is creating obstacle, where intranasal drug delivery provides direct transport of therapeutically active moiety into brain via olfactory or trigeminal pathway. Nasal mucosa provides distinct advantage like improved bioavailability, law dose and quick onset of action and high patient compliance, major disadvantage is residence time of drug and irreversible entrapment of drug...
October 13, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/29034831/graphene-oxide-based-metallic-nanoparticles-and-their-some-biological-and-environmental-application
#20
Aftab Aslam Parwaz Khan, Anish Khan, Abdullah M Asiri, Basma Galeb Alhogbia, Ghulam Md Ashraf
Recently the decoration of graphene with metallic nanoparticles by a synchronized reduction of graphene oxide (GO) and synthesis of metallic nanoparticles has gained energy. Metal-decorated carbon substrates, for example, carbon nanotubes and graphene oxide have been of mind boggling excitement to the scientific group all through the past three decades on account of different potential applications.The utilization of graphene oxide as the nano scale substrates for the formation of nanocomposites with metal oxides is a novel thought to acquire a hybrid which would show both the properties of GO as an interesting paper-shape material and the elements of single nano-sized metal particles...
October 16, 2017: Current Drug Metabolism
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