Forecasting of emerging therapeutic monoclonal antibodies patents based on a decision model

Therapeutic monoclonal antibodies (mAbs) market is strongly contributing to the rising growth of the biotechnology industry. Despite the increasing number of inventions over time, a few therapeutic mAbs are currently marketed. This paper focuses on developing an emerging score to select/rank promising therapeutic mAbs patents, based on a hierarchical decision model using expert's opinion. Six attributes related to each factor concerning patent status, patent owner's profile and mAbs medical relevance were analyzed. The desirability levels of each attribute were also assessed. Our data shows the medical relevance factor as the most important, contributing 50% of the emerging score. Among the attributes, the most important under patent status was proper geographic coverage and wider patent scope; for organization's profile was the preexistence of approved drugs; and for medical relevance, the clinical phase performance. A group of 1053 patents related to therapeutic mAb were scored, and the most promising were concerning combination therapy using immune checkpoint inhibitors. The study has managerial implications related to patent portfolio management and patent valuation, and provides instructions to rank mAbs patents according to the emerging score defined by attribute's importance in order to improve the identification of future innovations pathways

The upper Hauterivian Barremian (Lower Cretaceous) Arrifes section (Algarve Basin, Southern Portugal): a palynostratigraphic and palaeoenvironmental approach

ABSTRACT: Integrated sedimentological, palynological, and palynofacies analyses of the Arrifes section in the central Algarve Basin (southern Portugal) provided new information on the age and environments of this Lower Cretaceous sequence. The sedimentary succession at the Arrifes section consists of fossiliferous interbedded limestones, marly limestones, and marls, dated as latest Hauterivian to late Barremian age (Lower Cretaceous) based on key dinoflagellate taxa. During this interval, the Arrifes area records climatic shifts and, multiple sea-level fluctuations; overall deposition was in shallow subtidal to intertidal settings, with deposition of carbonate and marly sediments. During the latest Hauterivian to earliest Barremian interval, an evident sea-level fall culminated in the subaerial exposure of the local carbonate ramp with increased influx of clastic sediments. However, during the Barremian, both sedimentological and palynological analyses suggest an overall deepening of the water depth towards the top of the section. These overall increase in the water column are confirmed by oscillation of terrestrial/marine palynomorph groups and supported by dinosaur track levels at the top of the succession; the latter indicate that sedimentation occurred in intertidal to subtidal environments. Finally, an attempt was made to correlate the Arrifes section with other sections from the Algarve Basin, as well as with broader region. These new data suggest a setting in the Tethyan basin influenced during the latest Hauterivian to the end of the Barremian. These new data allow local correlations and new palynological ages and paleoenvironmental interpretations for the Lower Cretaceous succession of the Algarve Basin.info:eu-repo/semantics/publishedVersio

Diarrhea-associated biofilm formed by enteroaggregative Escherichia coli and aggregative Citrobacter freundii: a consortium mediated by putative F pili

<p>Abstract</p> <p>Background</p> <p>Enteroaggregative <it>Escherichia coli </it>(EAEC) are enteropathogenic strains identified by the aggregative adhesion (AA) pattern that share the capability to form biofilms. <it>Citrobacter freundii </it>is classically considered as an indigenous intestinal species that is sporadically associated with diarrhea.</p> <p>Results</p> <p>During an epidemiologic study focusing on infantile diarrhea, aggregative <it>C. freundii </it>(EACF) and EAEC strains were concomitantly recovered from a severe case of mucous diarrhea. Thereby, the occurrence of synergic events involving these strains was investigated. Coinfection of HeLa cells with EACF and EAEC strains showed an 8-fold increase in the overall bacterial adhesion compared with single infections (P < 0.001). The synergic effect was mediated by physical interactions among the bacteria and primed in the absence of chemical signaling and without the participation of host cells. Thus, significant increases (2.7-fold on average) in bacterial adhesion were also observed during the formation of mixed biofilms on abiotic surfaces. Bacterial settling assays showed that EAEC strains harboring F-pili genes (<it>traA</it>) were capable of forming bacterial aggregates only in the presence of EACF. Scanning electronic microscopy analyses revealed that bacterial aggregates as well as enhanced biofilms formed by EACF and <it>traA</it>-positive EAEC were mediated by non-bundle forming, flexible pili. Moreover, mixed biofilms formed by EACF and <it>traA</it>-positive EAEC strains were significantly reduced using nonlethal concentration of zinc, a specific inhibitor of F pili. In addition, EAEC strains isolated from diarrheic children frequently produced single biofilms sensitive to zinc.</p> <p>Conclusions</p> <p>Putative F pili expressed by EAEC strains boosted mixed biofilm formation when in the presence of aggregative <it>C. freundii</it>.</p

Metabolic responses to high glycemic index and low glycemic index meals: a controlled crossover clinical trial

BACKGROUND: The consumption of low glycemic index (LGI) foods before exercise results in slower and more stable glycemic increases. Besides maintaining an adequate supply of energy during exercise, this response may favor an increase in fat oxidation in the postprandial period before the exercise compared to high glycemic index (HGI) foods. The majority of the studies that evaluated the effect of foods differing in glycemic index on substrate oxidation during the postprandial period before the exercise are acute studies in which a single meal is consumed right before the exercise. The purpose of this study was to investigate the effect of consuming two daily HGI or LGI meals for five consecutive days on substrate oxidation before the exercise and in the concentrations of glucose, insulin and free fatty acids before and during a high intensity exercise. METHODS: Fifteen male cyclists, aged 24.4 ± 3.8 years, with body mass index of 21.9 ± 1.4 kg.m(-2 )and a V(O2 max )of 70.0 ± 5.3 mL.kg(-1).min(-1), participated in this crossover study. All test meals were consumed in the laboratory. On days 1 and 5, substrate oxidation (30 minutes before and 90 minutes after breakfast (HGI or LGI)) and diet-induced thermogenesis (90 minutes postprandial) were assessed before the exercise. The levels of glucose, insulin, and free fatty acids were determined during 2 h after breakfast on these same days. Ninety minutes after breakfast, subjects completed a 30 min cycloergometric exercise at 85 to 95% of their maximum heart rate, during which lactate concentrations were assessed. RESULTS: The consumption of HGI meals resulted in higher areas under the glycemic and insulinemic curves in the postprandial period. However, glycemia did not differ by study treatment during exercise. There were no differences in free fatty acids in the postprandial period or in lactate levels during exercise. LGI meals resulted in lower fat oxidation and higher carbohydrate oxidation than the HGI meal in the postprandial period. CONCLUSIONS: The results do not support a differential glycemia according to glycemic index during exercise. The ingestion of LGI foods did not lead to higher fat oxidation relative to the ingestion of HGI foods. TRIAL REGISTRATION: ACTRN: ACTRN1260900052221

The age and depositional environments of the lower Karoo Moatize Coalfield of Mozambique: insights into the postglacial history of central Gondwana

ABSTRACT: The Moatize Coalfield belongs to a network of continental Karoo basins of central Mozambique, known as the Zambezi Basin. Palynological and sedimentological studies were performed on four coal exploration boreholes to determine the age, depositional settings, and overall geological evolution of its extensive coal deposits. Clastic formations recognised in this coalfield, in ascending order, are the Vúzi, Moatize and Matinde formations. Palynomorph assemblages indicate that the Moatize Coalfield succession ranges from Roadian (lower Guadalupian) to Changhsingian (upper Lopingian) in age. Two main depositional phases are identified, whose initiation and development are attributed to regional tectonic events and climate amelioration. The first phase formed towards the end of the deglacial period, characterised initially by fan deltas, represented by the upper Vúzi Formation, and the shift to lake–delta environments, represented by the lower part of the Moatize Formation. This phase took place from Roadian to the Wordian times. The lake–delta settings indicate a sediment aggradation trend with high subsidence rates in the lake basin, which, together with the associated post-glacial climate amelioration, led to the accumulation of coal deposits in swamps of the delta top and lake margins. The second depositional phase took place from Capitanian to Changhsingian times and related to fluvial environments initiated by uplift that reorganised the depocenter into alluvial plains characterised by bedload dominated rivers (braided) and overbank floodplains. Results obtained in this study provide critical information for the onset of the deglaciation events and the age of coal deposits in this part of Gondwana, important for wider stratigraphic correlation of these events in Africa and throughout the Gondwana.info:eu-repo/semantics/acceptedVersio

Effect of mesoporous silica under Neisseria meningitidis transformation process: environmental effects under meningococci transformation

<p>Abstract</p> <p>Background</p> <p>This study aimed the use of mesoporous silica under the naturally transformable <it>Neisseria meningitidis</it>, an important pathogen implicated in the genetic horizontal transfer of DNA causing a escape of the principal vaccination measures worldwide by the capsular switching process. This study verified the effects of mesoporous silica under <it>N. meningitidis </it>transformation specifically under the capsular replacement.</p> <p>Methods</p> <p>we used three different mesoporous silica particles to verify their action in <it>N. meningitis </it>transformation frequency.</p> <p>Results</p> <p>we verified the increase in the capsular gene replacement of this bacterium with the three mesoporous silica nanoparticles.</p> <p>Conclusion</p> <p>the mesouporous silica particles were capable of increasing the capsule replacement frequency in <it>N. meningitidis</it>.</p