Geographic origin, ancestry, and death circumstances at the Cornaux/Les Sauges Iron Age bridge, Switzerland.

Cornaux/Les Sauges (Switzerland, Late Iron Age) revealed remnants of a wooden bridge, artifacts, and human and animal skeletal remains. The relationship between the collapsed structure and the skeletal material, whether it indicates a potential accident or cultural practices, remains elusive. We evaluate the most plausible scenario for Cornaux based on osteological, taphonomic, isotopic, and paleogenomic analysis of the recovered individuals. The latter amount to at least 20 individuals, mostly adult males. Perimortem lesions include only blunt force traumas. Radiocarbon data fall between the 3rd and 1st c. BCE, although in some cases predating available dendrochronological estimates from the bridge. Isotopic data highlight five to eight nonlocals. No close genetic relatedness links the analyzed skeletons. Paleogenomic results, the first for Iron Age Switzerland, point to a genetic affinity with other Central and Western European Iron Age groups. The type of skeletal lesions supports an accidental event as the more plausible explanation. Radiocarbon data and the demographic structure of the sample may suggest a sequence of different events possibly including executions and/or sacrifices. Isotopic and paleogenomic data, while not favoring one scenario over the other, do support earlier interpretations of the last centuries BCE in Europe as a dynamic period from a biocultural perspective.

Prevalence, T2 Biomarkers, and Cost of Severe Asthma in the Era of Biologics: The BRAVO-1 Study

Background: The last decade has seen new classifications of the pathophysiology of asthma that have changed the treatment options available. Objectives: To update data on the prevalence of T2 asthma, comorbidities, biomarker characterization, and costs of severe asthma in patients aged ≥12 years, taking into account new classifications and treatment options. Methods: Retrospective, observational, nationwide study using a top-down approach. Data were obtained from BIG-PAC®, an electronic medical record database of 1.7 million patients in Spain. The study population comprised patients aged ≥12 years who had received medical care during the period 2016-2017 and been diagnosed with asthma at least 1 year prior to the index date. Patients were followed for 1 year. Results: The prevalence of asthma was 5.5%. Asthma was severe in 3031 of these patients (7.7%), 81.2% of whom presented T2 asthma. Among patients with severe asthma, 64.1% had uncontrolled disease, 31.2% were oral corticosteroid–dependent (37% in the uncontrolled severe asthma group), and only 3.8% were receiving biologics. The most common T2 comorbidities were allergic rhinitis (66.1%), atopic dermatitis (29.1%), and chronic rhinosinusitis with nasal polyps (14.6%). Mortality rates in the total population and uncontrolled severe asthma groups were 4.2% and 5.5%, respectively. The total annual costs per patient with severe asthma were €5890 (uncontrolled) and €2841 (controlled). Conclusions: In the era of biologics, most severe asthma patients present T2 asthma. Despite the availability of new treatments, rates of oral corticosteroid–dependent patients with uncontrolled severe asthma remain high, although biologics continue to be underused. The costs of uncontrolled severe asthma are twice as high as those of controlled severe asthma. (AU)

Introducción: En la última década se han concadenado una serie de clasificaciones de la fisiopatología del asma que han cambiado las opciones de tratamientos disponibles. Objetivos: Actualizar los datos de prevalencia del asma T2, comorbilidades, caracterización de biomarcadores y costes del asma grave en pacientes ≥12 años en esta nueva situación. Métodos: Estudio retrospectivo, observacional y de ámbito nacional con un enfoque descendente. Los datos se obtuvieron de BIG-PAC®, una base de datos de historias clínicas electrónicas de 1,7 millones de pacientes en España. Se incluyeron pacientes ≥12 años que habían recibido atención médica durante el periodo 2016-2017 y que habían sido diagnosticados de asma al menos un año antes de la fecha índice y fueron seguidos durante un año. Resultados: La prevalencia del asma fue del 5,5%. De estos pacientes, 3.031 presentaban asma grave (7,7%), de los cuales el 81,2% presentaba asma T2. Entre los pacientes con asma grave, el 64,1% no estaban controlados, el 31,2% eran dependientes de corticosteroides orales (37% en el grupo de asma grave no controlada) y solo el 3,8% estaban en tratamiento con biológicos. Las comorbilidades T2 más frecuentes fueron la rinitis alérgica (66,1%), la dermatitis atópica (29,1%) y la rinosinusitis crónica con poliposis nasal (14,6%). Las tasas de mortalidad en los grupos de asma grave total y no controlada fueron del 4,2% y del 5,5%, respectivamente. Los costes totales anuales por paciente con asma grave fueron de 5.890 euros (no controlado) y 2.841 euros (controlado). Conclusiones: En la era de los biológicos, la mayoría de los pacientes con asma grave presentan asma T2. A pesar de la disponibilidad de nuevos tratamientos, las tasas de pacientes con asma grave no controlados y dependientes de corticosteroides orales siguen siendo altas, y los biológicos siguen estando infrautilizados. Los costes del asma grave no controlada duplican los del asma grave controlada. (AU)

Genomic history of coastal societies from eastern South America.

Sambaqui (shellmound) societies are among the most intriguing archaeological phenomena in pre-colonial South America, extending from approximately 8,000 to 1,000 years before present (yr BP) across 3,000 km on the Atlantic coast. However, little is known about their connection to early Holocene hunter-gatherers, how this may have contributed to different historical pathways and the processes through which late Holocene ceramists came to rule the coast shortly before European contact. To contribute to our understanding of the population history of indigenous societies on the eastern coast of South America, we produced genome-wide data from 34 ancient individuals as early as 10,000 yr BP from four different regions in Brazil. Early Holocene hunter-gatherers were found to lack shared genetic drift among themselves and with later populations from eastern South America, suggesting that they derived from a common radiation and did not contribute substantially to later coastal groups. Our analyses show genetic heterogeneity among contemporaneous Sambaqui groups from the southeastern and southern Brazilian coast, contrary to the similarity expressed in the archaeological record. The complex history of intercultural contact between inland horticulturists and coastal populations becomes genetically evident during the final horizon of Sambaqui societies, from around 2,200 yr BP, corroborating evidence of cultural change.

Fecal Fungal Microbiota (Mycobiome) Study as a Potential Tool for Precision Medicine in Inflammatory Bowel Disease.

There is growing evidence of the role of fungal microbiota in the pathogenesis of inflammatory bowel disease (IBD). Fungi can exert direct pro-inflammatory effects or modify the bacterial composition via interkingdom interactions. Although several studies have demonstrated alterations in the fecal fungal microbiota composition in IBD, there is a wide variation in the mycobiome in different populations, with no definite pattern that can define the mycobiome in IBD having yet been identified. Recent work has suggested that characterizing the fecal fungal composition may influence therapeutic decisions and help to predict outcomes in a subset of IBD patients. In this study, we review the current literature on the emerging role of the fecal mycobiome as a potential tool for precision medicine in IBD.

Small-scale mobility fostering the interaction networks of Patagonian (Argentina) hunter-gatherers during the Late Holocene: Perspectives from strontium isotopes and exotic items.

During the Late Holocene, hunter-gatherer interaction networks significantly grew in intensity and extension across Patagonia. Although this growth is evidenced by the increased flow of exotic items across the region, the mechanisms behind these strengthening social networks remain unclear. Since evidence suggests that some individuals might have performed long-distance trips, this article aims to address the potential relationship between these individuals and the flows of exotic items in North Patagonia. We analyzed 54 enamel teeth for strontium isotopes and reconstructed their probable mobility using mixed-effect models and isotope-based geographic assignments. We inferred population and individual mobility trends and compared them against the flow of exotic items built from a standardized compilation. Our results indicate that most individuals have isotopic composition compatible with residence within their burial and surrounding areas. However, a few individuals show isotopic composition incompatible with their burial areas, which suggests axes -from the burial location to the most likely isotope integration area- of extraordinary mobility. At the same time, the flows of exotic items overlap with these axes around the eastern sector of the study area suggesting that this location could have been a central point of convergence for people and items. We argue that small-scale socially driven mobility could have played a relevant role as a general mechanism of interaction that fostered and materialized Patagonian interaction networks during the Late Holocene.

Fecal Fungal Microbiota (Mycobiome) Study as a Potential Tool for Precision Medicine in Inflammatory Bowel Disease

There is growing evidence of the role of fungal microbiota in the pathogenesis of inflammatory bowel disease (IBD). Fungi can exert direct pro-inflammatory effects or modify the bacterial composition via interkingdom interactions. Although several studies have demonstrated alterations in the fecal fungal microbiota composition in IBD, there is a wide variation in the mycobiome in different populations, with no definite pattern that can define the mycobiome in IBD having yet been identified. Recent work has suggested that characterizing the fecal fungal composition may influence therapeutic decisions and help to predict outcomes in a subset of IBD patients. In this study, we review the current literature on the emerging role of the fecal mycobiome as a potential tool for precision medicine in IBD.

Prevalence, T2-biomarkers and cost of severe asthma in the era of biologics: The BRAVO-1 study.

BACKGROUND AND OBJECTIVES: The last decade has seen a new era of classifications of asthma pathophysiology which have changed the treatment options available. To update the figures of prevalence of T2 asthma, comorbidities, biomarker characterization and costs of severe asthma in patients≥12-years-old adapted to this new situation. METHODS: Retroprospective, observational, nationwide study using a top-down approach. Data were obtained from the BIG-PAC®, an electronic medical record database of 1.7 million patients in Spain. Patients≥12-years-old who had received medical care during the period 2016-2017 and diagnosed with asthma at least one year prior to the index date were included and followed for one year. RESULTS: Prevalence of asthma was 5.5%. Of these patients, asthma was severe in 3.031 (7.7%), 81.2% of whom presented T2 asthma. Among severe asthma patients, 64·1% were uncontrolled, 31.2% were Oral corticosteroids-dependent (37% in the uncontrolled severe asthma group) and only 3.8% were on biologics. The most common T2 comorbidities were allergic rhinitis (66·1%), atopic dermatitis (29·1%) and chronic rhinositis with nasal polyps (14.6%). Mortality rates in the total and the uncontrolled severe asthma groups were 4.2% and 5.5% respectively. The total annual costs per patient with severe asthma were 5.890€ (uncontrolled) and 2.841€ (controlled). CONCLUSIONS: In the era of biologics, most severe asthma patients present T2 asthma. Despite the availability of new treatments, the rates of uncontrolled and oral corticosteroids-dependent patients with severe asthma remain high, but biologics still underused. The costs of uncontrolled severe asthma are twice as high as those of controlled severe asthma.

A Neandertal dietary conundrum: Insights provided by tooth enamel Zn isotopes from Gabasa, Spain.

The characterization of Neandertals' diets has mostly relied on nitrogen isotope analyses of bone and tooth collagen. However, few nitrogen isotope data have been recovered from bones or teeth from Iberia due to poor collagen preservation at Paleolithic sites in the region. Zinc isotopes have been shown to be a reliable method for reconstructing trophic levels in the absence of organic matter preservation. Here, we present the results of zinc (Zn), strontium (Sr), carbon (C), and oxygen (O) isotope and trace element ratio analysis measured in dental enamel on a Pleistocene food web in Gabasa, Spain, to characterize the diet and ecology of a Middle Paleolithic Neandertal individual. Based on the extremely low δ66Zn value observed in the Neandertal's tooth enamel, our results support the interpretation of Neandertals as carnivores as already suggested by δ15N isotope values of specimens from other regions. Further work could help identify if such isotopic peculiarities (lowest δ66Zn and highest δ15N of the food web) are due to a metabolic and/or dietary specificity of the Neandertals.

Deep-Learning Model Based on Convolutional Neural Networks to Classify Apnea-Hypopnea Events from the Oximetry Signal.

Automated analysis of the blood oxygen saturation (SpO2) signal from nocturnal oximetry has shown usefulness to simplify the diagnosis of obstructive sleep apnea (OSA), including the detection of respiratory events. However, the few preceding studies using SpO2 recordings have focused on the automated detection of respiratory events versus normal respiration, without making any distinction between apneas and hypopneas. In this sense, the characteristics of oxygen desaturations differ between obstructive apnea and hypopnea episodes. In this chapter, we use the SpO2 signal along with a convolutional neural network (CNN)-based deep-learning architecture for the automatic identification of apnea and hypopnea events. A total of 398 SpO2 signals from adult OSA patients were used for this purpose. A CNN architecture was trained using 30-s epochs from the SpO2 signal for the automatic classification of three classes: normal respiration, apnea, and hypopnea. Then, the apnea index (AI), the hypopnea index (HI), and the apnea-hypopnea index (AHI) were obtained by aggregating the outputs of the CNN for each subject (AICNN, HICNN, and AHICNN). This model showed a promising diagnostic performance in an independent test set, with 80.3% 3-class accuracy and 0.539 3-class Cohen's kappa for the classification of respiratory events. Furthermore, AICNN, HICNN, and AHICNN showed a high agreement with the values obtained from the standard PSG: 0.8023, 0.6774, and 0.8466 intra-class correlation coefficients (ICCs), respectively. This suggests that CNN can be used to analyze SpO2 recordings for the automated diagnosis of OSA in at-home oximetry tests.

Food for the soul and food for the body. Studying dietary patterns and funerary meals in the Western Roman Empire: An anthropological and archaeozoological approach.

Ancient written sources show that Roman funerary rituals were relevant along the entire Roman Republic and Empire, as they ensured the protection of deities and the memory of the deceased. Part of these rituals consisted of funerary offerings and banquets that were held on the day of the burial, in festivities and other stipulated days. The faunal remains recovered inside the graves and around them are evidence of these rituals. Therefore, their study can allow us to know if the funerary meals and rituals developed in the Roman necropolis were special and implied food that differed from everyday dietary habits, according to the importance of these rituals. To test this, we analysed the archaeozoological and anthropological material from the necropolis of Vila de Madrid (Barcelona, Catalonia), which was in use between the first half of the 2nd century AD and mid 3rd century AD. The archaeozoological analysis of the faunal remains recovered in the necropolis and inside the graves, as well as carbon and nitrogen stable isotope ratios results on bone collagen from 50 faunal specimens and 41 humans, suggest that, overall, funerary meals in Vila de Madrid necropolis did not imply different food than that consumed during life. Regarding age, sex, offerings and diet, some differences are observed, suggesting that inequalities present in life could have been also present in the funerary rituals.

Ancient dental calculus preserves signatures of biofilm succession and interindividual variation independent of dental pathology.

Dental calculus preserves oral microbes, enabling comparative studies of the oral microbiome and health through time. However, small sample sizes and limited dental health metadata have hindered health-focused investigations to date. Here, we investigate the relationship between tobacco pipe smoking and dental calculus microbiomes. Dental calculus from 75 individuals from the 19th century Middenbeemster skeletal collection (Netherlands) were analyzed by metagenomics. Demographic and dental health parameters were systematically recorded, including the presence/number of pipe notches. Comparative data sets from European populations before and after the introduction of tobacco were also analyzed. Calculus species profiles were compared with oral pathology to examine associations between microbiome community, smoking behavior, and oral health status. The Middenbeemster individuals exhibited relatively poor oral health, with a high prevalence of periodontal disease, caries, heavy calculus deposits, and antemortem tooth loss. No associations between pipe notches and dental pathologies, or microbial species composition, were found. Calculus samples before and after the introduction of tobacco showed highly similar species profiles. Observed interindividual microbiome differences were consistent with previously described variation in human populations from the Upper Paleolithic to the present. Dental calculus may not preserve microbial indicators of health and disease status as distinctly as dental plaque.

Understanding the microbial biogeography of ancient human dentitions to guide study design and interpretation.

The oral cavity is a heterogeneous environment, varying in factors such as pH, oxygen levels, and salivary flow. These factors affect the microbial community composition and distribution of species in dental plaque, but it is not known how well these patterns are reflected in archaeological dental calculus. In most archaeological studies, a single sample of dental calculus is studied per individual and is assumed to represent the entire oral cavity. However, it is not known if this sampling strategy introduces biases into studies of the ancient oral microbiome. Here, we present the results of a shotgun metagenomic study of a dense sampling of dental calculus from four Chalcolithic individuals from the southeast Iberian peninsula (ca. 4500-5000 BP). Interindividual differences in microbial composition are found to be much larger than intraindividual differences, indicating that a single sample can indeed represent an individual in most cases. However, there are minor spatial patterns in species distribution within the oral cavity that should be taken into account when designing a study or interpreting results. Finally, we show that plant DNA identified in the samples is likely of postmortem origin, demonstrating the importance of including environmental controls or additional lines of biomolecular evidence in dietary interpretations.

Archaeometric evidence for the earliest exploitation of lignite from the bronze age Eastern Mediterranean.

This paper presents the earliest evidence for the exploitation of lignite (brown coal) in Europe and sheds new light on the use of combustion fuel sources in the 2nd millennium BCE Eastern Mediterranean. We applied Thermal Desorption/Pyrolysis-Gas Chromatography-Mass Spectrometry and Polarizing Microscopy to the dental calculus of 67 individuals and we identified clear evidence for combustion markers embedded within this calculus. In contrast to the scant evidence for combustion markers within the calculus samples from Egypt, all other individuals show the inhalation of smoke from fires burning wood identified as Pinaceae, in addition to hardwood, such as oak and olive, and/or dung. Importantly, individuals from the Palatial Period at the Mycenaean citadel of Tiryns and the Cretan harbour site of Chania also show the inhalation of fire-smoke from lignite, consistent with the chemical signature of sources in the northwestern Peloponnese and Western Crete respectively. This first evidence for lignite exploitation was likely connected to and at the same time enabled Late Bronze Age Aegean metal and pottery production, significantly by both male and female individuals.

Genomic transformation and social organization during the Copper Age-Bronze Age transition in southern Iberia.

The emerging Bronze Age (BA) of southeastern Iberia saw marked social changes. Late Copper Age (CA) settlements were abandoned in favor of hilltop sites, and collective graves were largely replaced by single or double burials with often distinctive grave goods indirectly reflecting a hierarchical social organization, as exemplified by the BA El Argar group. We explored this transition from a genomic viewpoint by tripling the amount of data available for this period. Concomitant with the rise of El Argar starting ~2200 cal BCE, we observe a complete turnover of Y-chromosome lineages along with the arrival of steppe-related ancestry. This pattern is consistent with a founder effect in male lineages, supported by our finding that males shared more relatives at sites than females. However, simple two-source models do not find support in some El Argar groups, suggesting additional genetic contributions from the Mediterranean that could predate the BA.

Current impact of viral hepatitis on liver cancer development: The challenge remains.

Chronic infections due to hepatitis B and hepatitis C viruses are responsible for most cases of hepatocellular carcinoma (HCC) worldwide, and this association is likely to remain during the next decade. Moreover, viral hepatitis-related HCC imposes an important burden on public health in terms of disability-adjusted life years. In order to reduce such a burden, some major challenges must be faced. Universal vaccination against hepatitis B virus, especially in the neonatal period, is probably the most relevant primary preventive measure against the development of HCC. Moreover, considering the large adult population already infected with hepatitis B and C viruses, it is also imperative to identify these individuals to ensure their access to treatment. Both hepatitis B and C currently have highly effective therapies, which are able to diminish the risk of development of liver cancer. Finally, it is essential for individuals at high-risk of HCC to be included in surveillance programs, so that tumors are detected at an early stage. Patients with hepatitis B or C and advanced liver fibrosis or cirrhosis benefit from being followed in a surveillance program. As hepatitis B virus is oncogenic and capable of leading to liver cancer even in individuals with early stages of liver fibrosis, other high-risk groups of patients with hepatitis B are also candidates for surveillance. Considerable effort is required concerning these strategies in order to decrease the incidence and the mortality of viral hepatitis-related HCC.

Next-Generation Biomarkers for Cholangiocarcinoma.

The increasing mortality rates of cholangiocarcinoma (CCA) registered during the last decades are, at least in part, a result of the lack of accurate non-invasive biomarkers for early disease diagnosis, making the identification of patients who might benefit from potentially curative approaches (i.e., surgery) extremely challenging. The obscure CCA pathogenesis and associated etiological factors, as well as the lack of symptoms in patients with early tumor stages, highly compromises CCA identification and to predict tumor development in at-risk populations. Currently, CCA diagnosis is accomplished by the combination of clinical/biochemical features, radiological imaging and non-specific serum tumor biomarkers, although a tumor biopsy is still needed to confirm disease diagnosis. Furthermore, prognostic and predictive biomarkers are still lacking and urgently needed. During the recent years, high-throughput omics-based approaches have identified novel circulating biomarkers (diagnostic and prognostic) that might be included in large, international validation studies in the near future. In this review, we summarize and discuss the most recent advances in the field of biomarker discovery in CCA, providing new insights and future research directions.

The evolution and changing ecology of the African hominid oral microbiome.

The oral microbiome plays key roles in human biology, health, and disease, but little is known about the global diversity, variation, or evolution of this microbial community. To better understand the evolution and changing ecology of the human oral microbiome, we analyzed 124 dental biofilm metagenomes from humans, including Neanderthals and Late Pleistocene to present-day modern humans, chimpanzees, and gorillas, as well as New World howler monkeys for comparison. We find that a core microbiome of primarily biofilm structural taxa has been maintained throughout African hominid evolution, and these microbial groups are also shared with howler monkeys, suggesting that they have been important oral members since before the catarrhine-platyrrhine split ca. 40 Mya. However, community structure and individual microbial phylogenies do not closely reflect host relationships, and the dental biofilms of Homo and chimpanzees are distinguished by major taxonomic and functional differences. Reconstructing oral metagenomes from up to 100 thousand years ago, we show that the microbial profiles of both Neanderthals and modern humans are highly similar, sharing functional adaptations in nutrient metabolism. These include an apparent Homo-specific acquisition of salivary amylase-binding capability by oral streptococci, suggesting microbial coadaptation with host diet. We additionally find evidence of shared genetic diversity in the oral bacteria of Neanderthal and Upper Paleolithic modern humans that is not observed in later modern human populations. Differences in the oral microbiomes of African hominids provide insights into human evolution, the ancestral state of the human microbiome, and a temporal framework for understanding microbial health and disease.

Dietary evidence from Central Asian Neanderthals: A combined isotope and plant microremains approach at Chagyrskaya Cave (Altai, Russia).

Neanderthals are known primarily from their habitation of Western Eurasia, but they also populated large expanses of Northern Asia for thousands of years. Owing to a sparse archaeological record, relatively little is known about these eastern Neanderthal populations. Unlike in their western range, there are limited zooarchaeological and paleobotanical studies that inform us about the nature of their subsistence. Here, we perform a combined analysis of carbon and nitrogen stable isotopes on bone collagen and microbotanical remains in dental calculus to reconstruct the diet of eastern Neanderthals at Chagyrskaya Cave in the Altai Mountains of Southern Siberia, Russia. Stable isotopes identify one individual as possessing a high trophic level due to the hunting of large- and medium-sized ungulates, while the analysis of dental calculus also indicates the presence of plants in the diet of this individual and others from the site. These findings indicate eastern Neanderthals may have had broadly similar subsistence patterns to those elsewhere in their range.

Quality assurance for the use of computational methods in dosimetry: activities of EURADOS Working Group 6 'Computational Dosimetry'.

Working Group (WG) 6 'Computational Dosimetry' of the European Radiation Dosimetry Group promotes good practice in the application of computational methods for radiation dosimetry in radiation protection and the medical use of ionising radiation. Its cross-sectional activities within the association cover a large range of current topics in radiation dosimetry, including more fundamental studies of radiation effects in complex systems. In addition, WG 6 also performs scientific research and development as well as knowledge transfer activities, such as training courses. Monte Carlo techniques, including the use of anthropomorphic and other numerical phantoms based on voxelised geometrical models, play a strong part in the activities pursued in WG 6. However, other aspects and techniques, such as neutron spectra unfolding, have an important role as well. A number of intercomparison exercises have been carried out in the past to provide information on the accuracy with which computational methods are applied and whether best practice is being followed. Within the exercises that are still ongoing, the focus has changed towards assessing the uncertainty that can be achieved with these computational methods. Furthermore, the future strategy of WG 6 also includes an extension of the scope toward experimental benchmark activities and evaluation of cross-sections and algorithms, with the vision of establishing a gold standard for Monte Carlo methods used in medical and radiobiological applications.