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Background: Programmed cell death-1 (PD-1) and PD ligand-1 (PD-L1) expression predict the biological behaviour, aggressiveness, and response to immune checkpoint inhibitors in different cancers. We reviewed the published data on PD-L1 expression in pituitary tumours from the perspective of its biological role and prognostic usefulness. Summary: A literature review focused on PD-L1 expression in pituitary tumours was performed. Six immunohistochemistry-based studies which assessed PD-L1 positivity in pituitary tumours were included, encompassing 704 patients. The cohort consisted of 384 (54.5%) nonfunctioning tumours and 320 (43.5%) functioning pituitary tumours. PD-L1 expression was positive in 248 cases (35.2%). PD-L1 positivity rate was higher in functioning than in nonfunctioning tumours (46.3% vs. 26.0%; p < 0.001) but also higher in growth hormone-secreting tumours (56.7%) and prolactinomas (53.6%) than in thyrotroph (33.3%) or corticotroph tumours (20.6%). While proliferative pituitary tumours showed higher rate of PD-L1 positivity than non-proliferative tumours (p < 0.001), no association with invasion or recurrence was found. Key Messages: PD-L1 is expressed in a substantial number of pituitary tumours, predominantly in the functioning ones. PD-L1 positivity rates were significantly higher in proliferative pituitary tumours in comparison to non-proliferative tumours, but no differences were found concerning invasive or recurrent pituitary tumours. More studies following homogeneous and standardised methodologies are needed to fully elucidate the role and usefulness of PD-L1 expression in pituitary tumours. [ABSTRACT FROM AUTHOR]

Palaeoseismological studies play a crucial role in the seismic characterization of regions with slow-moving faults. This is the case in the central Betic Cordillera, a highly populated area for which the record of prehistoric earthquakes is very limited, despite being one of the regions with the greatest seismic hazard in Spain. We present here a palaeoseismological characterization of the Galera Fault, one of the active faults accommodating deformation in the central Betic Cordillera. We excavated and analysed several trenches along the fault trace. We quantitatively correlate the results from these trenches, resulting in a surface rupture history involving seven or eight events (accounting for the epistemic uncertainties) during the last ca. 24 000 years, with recurrence intervals ranging from 1520 to 1720 years. Further analysis of this surface rupture history seems to indicate that the Galera Fault is prone to producing earthquake clusters as we recorded five events in ∼ 400 years (ca. 1536–1126 BCE) and only two events in the ∼ 3200 years that followed. Using the fault geometry and palaeoseismological data, we also carried out a seismogenic characterization of the fault. This analysis yielded a maximum expected magnitude of 6.7 ± 0.3 and a recurrence interval of 1857 years. Furthermore, we also present a geodetic rupture scenario for the maximum expected event, involving displacements of up to 0.5 m. Finally, we discuss the possible impact of the deduced palaeoearthquakes on the development of Bronze Age human settlements located in the vicinity of the fault. In addition to their intrinsic value, our results will provide the basis for future seismic-hazard assessments carried out in the central Betic Cordillera. [ABSTRACT FROM AUTHOR]

Commuting road accidents have a direct impact on workers as well as companies. Therefore, analyzing the characteristics of commuting to and from work and workers' perceptions of their potential risk is necessary. This study analyzes these factors in a sample of employees in a large Spanish company. A questionnaire was distributed to a total of 665 workers, assessing variables such as means of transport used and preferred in this type of commuting, perceived risks, assessment of preventive measures, involvement in a road accident during commuting, and road safety training received by the company, among others. There is a difference between preferred and used modes of transport, with factors limiting the use of soft modes. People who have experienced an accident on the way to work have a higher risk perception of this type of journey. The time and distance of the journey also have a significant influence on the perceived risk. The most highly rated preventive actions are mainly related to the accessibility and comfort of the workers' daily commute, which helps minimize the time spent on journeys. This analysis provides relevant information on the social acceptability of different measures for the development and implementation of future actions of the prevention services that contribute to reducing this type of accident and designing strategies to promote more sustainable commuting mobility. [ABSTRACT FROM AUTHOR]

Palaeoseismological studies play a crucial role in the seismic characterization of regions with slow moving faults. This is the case of the Central Betic Cordillera, a highly populated area where the record of prehistoric earthquakes is very scarce, despite of being one of the regions with the highest seismic hazard in Spain. We present here a palaeoseismological characterization of the Galera Fault, one of the active faults accommodating deformation in the Central Betic Cordillera. We excavated and analysed several trenches along the fault trace. We quantitatively correlate the results from these trenches, resulting in a surface rupture history involving 7 or 8 events (accounting for the epistemic uncertainties) during the last ca. 24000 yr, with a recurrence interval ranging between 1520 and 1720 yr. Further analysis of this surface rupture history seems to indicate that the Galera Fault is prone to produce earthquakes clusters, as we recorded five events in ca. 400 yr (ca. 1536–1126 BC), and only two events in the next ca. 3200 yr. Using the fault geometry and palaeoseismological data, we also carried out a seismogenic characterization of the fault. This analysis yielded a maximum expected magnitude of 6.7 ± 0.3 and a recurrence interval of 1857 yr. Furthermore, we also present a geodetic rupture scenario for the maximum expected event, involving displacements of up to 0.5 m. Finally, we discuss the possible impact of the deduced palaeoearthquakes in the development of Bronze Age human settlements located in the vicinity of the fault. Other than their intrinsic value, our results will be the basis for future seismic hazard assessment carried out in the Central Betic Cordillera. [ABSTRACT FROM AUTHOR]

The cellular mechanism(s) linking macrophages to norepinephrine (NE)-mediated regulation of thermogenesis have been a topic of debate. Here we identify sympathetic neuron-associated macrophages (SAMs) as a population of cells that mediate clearance of NE via expression of solute carrier family 6 member 2 (SLC6A2), an NE transporter, and monoamine oxidase A (MAOA), a degradation enzyme. Optogenetic activation of the sympathetic nervous system (SNS) upregulates NE uptake by SAMs and shifts the SAM profile to a more proinflammatory state. NE uptake by SAMs is prevented by genetic deletion of Slc6a2 or inhibition of the encoded transporter. We also observed an increased proportion of SAMs in the SNS of two mouse models of obesity. Genetic ablation of Slc6a2 in SAMs increases brown adipose tissue (BAT) content, causes browning of white fat, increases thermogenesis, and leads to substantial and sustained weight loss in obese mice. We further show that this pathway is conserved, as human sympathetic ganglia also contain SAMs expressing the analogous molecular machinery for NE clearance, which thus constitutes a potential target for obesity treatment., Author(s): Roksana M Pirzgalska [1]; Elsa Seixas [1]; Jason S Seidman [2]; Verena M Link [2, 3]; Noelia Martínez Sánchez [1]; Inês Mahú [1]; Raquel Mendes [1]; Vitka Gres [1]; [...]