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https://www.readbyqxmd.com/read/28634612/pd-0-catalyzed-intramolecular-arylative-dearomatization-of-%C3%AE-naphthols
#1
Ren-Qi Xu, Ping Yang, Shu-Li You
An efficient Pd(0)-catalyzed intramolecular arylative dearomatization of β-naphthols is described. Using Q-Phos as a ligand, the arylative dearomatization reaction proceeded smoothly affording excellent yields and chemoselectivity even when the catalyst loading was reduced to 0.1 mol%. This method offers an efficient access to a series of structurally diverse spirocarbocycles. Preliminary investigation indicates that an enantioselective reaction is feasible in the presence of a chiral phosphoramidite ligand...
June 21, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28631857/pd-catalyzed-hydroxylation-of-aryl-boronic-acids-using-in-situ-generated-hydrogen-peroxide
#2
Hong Yi, Aiwen Lei
In this work, we describe a benign and efficient palladium catalyzed in-situ generated hydrogen peroxide from carbon monoxide, water and oxygen under mild conditions. This novel methodology combines catalytic hydrogen peroxides production with aerobic oxidation process in a sole reaction system. This system shows good functional group tolerance and provides a benign and efficient access to a variety of functionalized phenols. Furthermore, the in-situ generated hydroperoxide can be well used for triphenylphosphine oxidation,in which the TON is up to 194...
June 20, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28631129/optimizing-the-deep-brain-stimulation-care-pathway-in-patients-with-parkinson-s-disease
#3
N J Thomas, P Mertens, T Danaila, G Polo, H Klinger, E Broussolle, S Thobois
Management of Parkinson's disease (PD) using deep brain stimulation (DBS) requires complex care in specialized, multidisciplinary centers. A well-organized, efficient patient flow is crucial to ensure that eligible patients can quickly access DBS. Delays or inefficiencies in patient care may impact a center's ability to meet demand, creating a capacity bottleneck. Analysis of the current practices within a center may help identify areas for improvement. After external audit of the DBS workflow of the Lyon Neurological Hospital and comparison with other European centers, manageable steps were suggested to restructure the care pathway...
June 19, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28607581/pembrolizumab-in-cervical-cancer-latest-evidence-and-clinical-usefulness
#4
REVIEW
Edith Borcoman, Christophe Le Tourneau
Cervical cancer is the fourth most common cause of cancer-related deaths in women worldwide. With the development of detection of precancerous lesions and preventive human papillomavirus (HPV) vaccination program, a survival improvement has been observed in these patients in developed countries, although disparities in accessibility to treatments exist across countries. While early-stage cervical cancer can be curable with surgery, prognosis of patients who recur remains poor, with limited treatment options...
June 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28606939/transcriptional-and-epigenetic-regulation-of-t-cell-hyporesponsiveness
#5
REVIEW
Renata M Pereira, Patrick G Hogan, Anjana Rao, Gustavo J Martinez
Naive CD8(+) T cells differentiate into effector and memory cytolytic T cells (CTLs) during an acute infection. In contrast, in scenarios of persistent antigen stimulation, such as chronic infections and cancer, antigen-specific CTLs show a gradual decrease in effector function, a phenomenon that has been termed CD8(+) T cell "exhaustion" or "dysfunction." Another hyporesponsive state, termed anergy, is observed when T cells are activated in the absence of positive costimulatory signals. Among the many negative regulators induced in hyporesponsive T cells are inhibitory cell-surface receptors, such as PD-1, LAG-3, CTLA-4, and TIM-3; "checkpoint blockade" therapies that involve treatment of patients with cancer with blocking antibodies to those receptors show considerable promise in the clinic because the blocking antibodies can mitigate hyporesponsiveness and promote tumor rejection...
June 12, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28605135/mechanistic-insight-leads-to-a-ligand-that-facilitates-the-pd-catalyzed-formation-of-2-hetero-arylaminooxazoles-and-4-hetero-arylaminothiazoles
#6
Esben P K Olsen, Pedro L Arrechea, Stephen L Buchwald
Using mechanistic insight, a new ligand (EPhos) for the Pd-catalyzed C-N cross-coupling between primary amines and aryl halides has been developed. Employing an isopropoxy group at the C3-position favors the C-bound isomer of ligand-supported Pd(II) complexes and leads to significantly improved reactivity. The use of a catalyst system based on EPhos with NaOPh as a mild homogeneous base proved to be very effective in the formation of 4-arylaminothiazoles and highly functionalized 2-arylaminooxazoles. Previously, these were not readily accessible using Pd-catalyzed methodology...
June 12, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28601879/outcomes-in-melanoma-patients-treated-with-braf-mek-directed-therapy-or-immune-checkpoint-inhibition-stratified-by-clinical-trial-versus-standard-of-care
#7
Chloe Goldman, Jeremy Tchack, Eric M Robinson, Sung Won Han, Una Moran, David Polsky, Russell S Berman, Richard L Shapiro, Patrick A Ott, Iman Osman, Hua Zhong, Anna C Pavlick, Melissa Ann Wilson
OBJECTIVES: Since 2011, metastatic melanoma treatment has evolved with commercial approval of BRAF- and MEK-targeted therapy and CTLA-4- and PD-1-blocking antibodies (immune checkpoint inhibitors, ICI). While novel therapies have demonstrated improved prognosis in clinical trials, few studies have examined the evolution of prognosis and toxicity of these drugs among an unselected population. We assess whether survival and toxicity reported in trials, which typically exclude most patients with brain metastases and poor performance status, are recapitulated within a commercial access population...
June 10, 2017: Oncology
https://www.readbyqxmd.com/read/28586388/a-prospective-pilot-study-of-genome-wide-exome-and-transcriptome-profiling-in-patients-with-small-cell-lung-cancer-progressing-after-first-line-therapy
#8
Glen J Weiss, Sara A Byron, Jessica Aldrich, Ashish Sangal, Heather Barilla, Jeffrey A Kiefer, John D Carpten, David W Craig, Timothy G Whitsett
BACKGROUND: Small cell lung cancer (SCLC) that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS) to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients. METHODS: Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment...
2017: PloS One
https://www.readbyqxmd.com/read/28582871/global-yet-incomplete-overview-of-cohort-studies-in-parkinson-s-disease
#9
Sebastian Heinzel, Stefanie Lerche, Walter Maetzler, Daniela Berg
BACKGROUND: Parkinson's disease (PD) is characterized by heterogeneity and multifactorial longitudinal changes. To identify PD subtypes and factors influencing the disease course, multiple cohort studies have been designed globally. Knowledge about existing cohorts is pivotal to foster collaboration, which may help to advance the understanding of PD. OBJECTIVE: To raise the awareness about PD cohorts and potential global collaboration opportunities. METHODS: Observational cohort studies in clinical PD were identified by a European working group (JPND BioLoC-PD) and through literature search...
May 31, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28582604/layer-by-layer-motif-architectures-programmed-electrochemical-syntheses-of-multilayer-mesoporous-metallic-films-with-uniformly-sized-pores
#10
Bo Jiang, Cuiling Li, Huayu Qian, Md Shahriar A Hossain, Victor Malgras, Yusuke Yamauchi
Although multilayer films have been extensively reported, most compositions have been limited to non-catalytically active materials (e.g. polymers, proteins, lipids, or nucleic acids). Herein, we report the preparation of binder-free multilayer metallic mesoporous films with sufficient accessibility for high electrocatalytic activity by using a programmed electrochemical strategy. By precisely tuning the deposition potential and duration, multilayer mesoporous architectures consisting of alternating mesoporous Pd layers and mesoporous PdPt layers with controlled layer thicknesses can be synthesized within a single electrolyte, containing polymeric micelles as soft templates...
June 5, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28578818/clinical-milestones-in-parkinson-s-disease-a-7-year-population-based-incident-cohort-study
#11
Anders Bjornestad, Kenn Freddy Pedersen, Ole-Bjorn Tysnes, Guido Alves
INTRODUCTION: Clinical staging of Parkinson's disease (PD) is important for patient management and prognosis. The non-motor and functional features visual hallucinations, recurrent falls, dementia and nursing home placement are currently not included in clinical staging schemes, but have been suggested as clinical milestones with important prognostic implications in advanced PD. In this study, we sought to evaluate the potential of these four milestone events for clinical staging and prognosis during the early years of the disease...
May 29, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28574254/direct-catalytic-desaturation-of-lactams-enabled-by-soft-enolization
#12
Ming Chen, Guangbin Dong
A direct catalytic method is described for the α,β-desaturation of N-protected lactams to their conjugated unsaturated counterparts under mildly acidic conditions. The reaction is consistently operated at room temperature and tolerates a wide range of functional groups, showing reactivity complementary to that of prior desaturation methods. Lactams with various ring sizes and substituents at different positions all reacted smoothly. The synthetic utility of this method is demonstrated in a concise synthesis of Rolipram...
June 6, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28571972/discovery-of-novel-and-potent-stearoyl-coenzyme-a-desaturase-1-scd1-inhibitors-as-anticancer-agents
#13
Keisuke Imamura, Naoki Tomita, Youichi Kawakita, Yoshiteru Ito, Kouji Ono, Noriyuki Nii, Tohru Miyazaki, Kazuko Yonemori, Michiko Tawada, Hiroyuki Sumi, Yoshihiko Satoh, Yukiko Yamamoto, Ikuo Miyahisa, Masako Sasaki, Yoshinori Satomi, Megumi Hirayama, Ryuichi Nishigaki, Hironobu Maezaki
A lead compound A was identified previously as an stearoyl coenzyme A desaturase (SCD) inhibitor during research on potential treatments for obesity. This compound showed high SCD1 binding affinity, but a poor pharmacokinetic (PK) profile and limited chemical accessibility, making it suboptimal for use in anticancer research. To identify potent SCD1 inhibitors with more promising PK profiles, we newly designed a series of 'non-spiro' 4, 4-disubstituted piperidine derivatives based on molecular modeling studies...
May 11, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28571532/rapid-access-to-oxazine-fused-furocoumarins-and-in-vivo-and-in-silico-studies-of-theirs-biological-activity
#14
Alla V Lipeeva, Dmitry S Baev, Margarita P Dolgikh, Tatijana G Tolstikova, Elvira E Shults
BACKGROUND: The synthesis of 1,2-oxazine-fused linear furocoumarins was performed involving the transition metal catalysis reaction of plant coumarin oreoselone derivatives. OBJECTIVE AND METHODS: The Pd-catalyzed desulfonative cross-coupling reactions of 2-(tosyl)oreoselone with terminal alkynes and the successive treatment of the obtained 2-(arylethynyl)furocoumarins with an excess of hydroxylamine gave the expected (Z,E)-3-(hydroxyimino)-2-(arylethynyl)furocoumarins with an (Z:E) ratio of about 1:0...
May 31, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28571267/effect-of-autologous-platelet-rich-fibrin-in-human-mandibular-molar-grade-ii-furcation-defects-a-randomized-clinical-trial
#15
Syed Asimuddin, Rekha Rani Koduganti, Veerendra Nath Reddy Panthula, Surya Prasanna Jammula, Rajashree Dasari, Himabindu Gireddy
INTRODUCTION: The Furcation of multirooted teeth is difficult region to gain access for treatment due to their complex anatomy. Modifications have been made in the periodontal instrument armamentarium to facilitate treatment of furcations. Moreover, many new materials have been introduced to attempt regeneration in the furcation defects. AIM: This study evaluated the role of Platelet Rich Fibrin (PRF) in comparison with allograft and Guided Tissue Regeneration (GTR) in the treatment of Grade II mandibular molar furcations...
April 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28567267/pd-ii-2l4-type-coordination-cages-up-to-three-nanometers-in-size
#16
Suzanne M Jansze, Matthew D Wise, Anna V Vologzhanina, Rosario Scopelliti, Kay Severin
The utilization of large ligands in coordination-based self-assembly represents an attractive strategy for the construction of supramolecular assemblies more than two nanometers in size. However, the implementation of this strategy is hampered by the fact that the preparation of such ligands often requires substantial synthetic effort. Herein, we describe a simple one-step protocol, which allows large bipyridyl ligands with a bent shape to be synthesized from easily accessible and/or commercially available starting materials...
March 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28561572/access-to-perfluoroalkyl-substituted-enones-and-indolin-2-ones-via-multicomponent-pd-catalyzed-carbonylative-reactions
#17
Hongfei Yin, Troels Skrydstrup
A simple method for accessing perfluoroalkyl-substituted enones is described applying a four-component palladium-catalyzed carbonylative coupling of aryl boronic acids together with terminal alkynes and perfluoroalkyl iodides in the presence of carbon monoxide. A wide range of highly functionalized enones can thus be prepared in a single operation in good yields. With 2-aminophenylalkynes, an intramolecular aminocarbonylation event overrules providing the indolin-2-one framework. Finally, adaptation of the two-chamber technology expands the method to the synthesis of the aforementioned structures with (13)C-isotope labeling...
June 8, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28560726/payment-reform-and-health-disparities-changes-in-dialysis-modality-under-the-new-medicare-dialysis-payment-system
#18
Marc Turenne, Regina Baker, Jeffrey Pearson, Chad Cogan, Purna Mukhopadhyay, Elizabeth Cope
OBJECTIVE: To evaluate the effect of the Medicare dialysis payment reform on potential disparities in the selection of peritoneal dialysis (PD) for the treatment of end-stage renal disease (ESRD). DATA SOURCES: Centers for Medicare & Medicaid Services (CMS) ESRD Medical Evidence Form, Medicare claims, and other CMS data for 2008-2013. STUDY DESIGN: We examined the association of patient age, race/ethnicity, urban/rural location, pre-ESRD care, comorbidities, insurance, and other factors with the selection of PD as initial dialysis modality across prereform (2008-2009), interim (2010), and postreform (2011-2013) time periods...
May 30, 2017: Health Services Research
https://www.readbyqxmd.com/read/28559209/short-post-weaning-social-isolation-induces-long-term-changes-in-the-dopaminergic-system-and-increases-susceptibility-to-psychostimulants-in-female-rats
#19
Carine Lampert, Danusa Mar Arcego, Natividade de Sá Couto-Pereira, Aline Dos Santos Vieira, Ana Paula Toniazzo, Rachel Krolow, Emily Garcia, Deusa Aparecida Vendite, Maria Elisa Calcagnotto, Carla Dalmaz
Childhood and adolescence are sensitive periods of development, marked by high brain maturation and plasticity. Exposure to early life stress, such as social isolation, is able to prompt changes in sensitive brain circuitries, essentially in the mesolimbic dopaminergic system and increase the risk for addictive behaviors later in life. Post-weaning social isolation can stimulate the consumption of rewarding substances, like drugs of abuse and palatable foods. However, most studies analyze long periods of social isolation and very little is known about the effects of a brief social isolation in a sensitive period of development and its association with palatable food on the reward system sensitization...
May 27, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28558794/assessment-of-physical-activity-capacity-and-nutritional-status-in-elderly-peritoneal-dialysis-patients
#20
Adamasco Cupisti, Claudia D'Alessandro, Viviana Finato, Claudia Del Corso, Battista Catania, Gian Marco Caselli, Maria Francesca Egidi
BACKGROUND: This study aimed to evaluate the prevalence of sedentarism, and to assess physical capacity and nutritional status in a cohort of older patients on peritoneal dialysis (PD), with respect to age-matched non-dialysis CKD population, using highly accessible, simple methods, namely the Rapid Assessment of Physical activity (RAPA) test and the 30″ Sit-to-stand (STS) test. METHODS: This cross-sectional multicenter study included 151 renal patients older than 60 years; 71 pts...
May 30, 2017: BMC Nephrology
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