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Suicidality remains a clear and present danger in society in general, and for mental health patients in particular. Lack of widespread use of objective and/or quantitative information has hampered treatment and prevention efforts. Suicidality is a spectrum of severity from vague thoughts that life is not worth living, to ideation, plans, attempts, and completion. Blood biomarkers that track suicidality risk provide a window into the biology of suicidality, as well as could help with assessment and treatment. Previous studies by us were positive. Here we describe new studies we conducted transdiagnostically in psychiatric patients, starting with the whole genome, to expand the identification, prioritization, validation and testing of blood gene expression biomarkers for suicidality, using a multiple independent cohorts design. We found new as well as previously known biomarkers that were predictive of high suicidality states, and of future psychiatric hospitalizations related to them, using cross-sectional and longitudinal approaches. The overall top increased in expression biomarker was SLC6A4, the serotonin transporter. The top decreased biomarker was TINF2, a gene whose mutations result in very short telomeres. The top biological pathways were related to apoptosis. The top upstream regulator was prednisolone. Taken together, our data supports the possibility that biologically, suicidality is an extreme stress-driven form of active aging/death. Consistent with that, the top subtypes of suicidality identified by us just based on clinical measures had high stress and high anxiety. Top therapeutic matches overall were lithium, clozapine and ketamine, with lithium stronger in females and clozapine stronger in males. Drug repurposing bioinformatic analyses identified the potential of renin-angiotensin system modulators and of cyclooxygenase inhibitors. Additionally, we show how patient reports for doctors would look based on blood biomarkers testing, personalized by gender. We also integrated with the blood biomarker testing social determinants and psychological measures (CFI-S, suicidal ideation), showing synergy. Lastly, we compared that to machine learning approaches, to optimize predictive ability and identify key features. We propose that our findings and comprehensive approach can have transformative clinical utility.

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Natural and human-induced toxic elements can accumulate in the environment, posing significant risks to human health and ecosystems. This study explores cave bat guano, an unconventional and relatively under-researched environmental repository, to reveal historical pollution trends and sources. Through trace elements analysis of a 1.5-m-thick guano deposit from Zidita Cave (Romania), we track changes in mining and metallurgy from 1000 CE-2012. We identified substantial pollution primarily from porphyry copper and Au-Ag-Te mines, but also impacts from usage of leaded gasoline and agricultural practices. Our record shows disruptions caused by the Bubonic plague around 1250 CE and a major surge âˆ¼ 1500 CE. After the decline triggered by the European silver market collapse in 1525 CE, our study reveals a brief mining revival. This resurgence was followed by a continuous decline lasting until the early 1800s, driven by socio-economic upheavals and recurrent outbreaks of the bubonic plagues. The Industrial Revolution sparked prolonged growth that lasted until 1989 CE, only briefly interrupted by the Great Depression and World War II. Consequently, cave bat guano proves to be a critical resource for understanding spatial pollution patterns, both locally and regionally, and for identifying specific pollution sources.

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Lanzarote (Canary Islands, Spain) is one of the best terrestrial analogs to Martian volcanology. Particularly, Lanzarote lava tubes may offer access to recognizably preserved chemical and morphological biosignatures valuable for astrobiology. By combining microbiological, mineralogical, and organic geochemistry tools, an in-depth characterization of speleothems and associated microbial communities in lava tubes of Lanzarote is provided. The aim is to untangle the underlying factors influencing microbial colonization in Earth's subsurface to gain insight into the possibility of similar subsurface microbial habitats on Mars and to identify biosignatures preserved in lava tubes unequivocally. The microbial communities with relevant representativeness comprise chemoorganotrophic, halophiles, and/or halotolerant bacteria that have evolved as a result of the surrounding oceanic environmental conditions. Many of these bacteria have a fundamental role in reshaping cave deposits due to their carbonatogenic ability, leaving behind an organic record that can provide evidence of past or present life. Based on functional profiling, we infer that Crossiella is involved in fluorapatite precipitation via urea hydrolysis and propose its Ca-rich precipitates as compelling biosignatures valuable for astrobiology. In this sense, analytical pyrolysis, stable isotope analysis, and chemometrics were conducted to characterize the complex organic fraction preserved in the speleothems and find relationships among organic families, microbial taxa, and precipitated minerals. We relate organic compounds with subsurface microbial taxa, showing that organic families drive the microbiota of Lanzarote lava tubes. Our data indicate that bacterial communities are important contributors to biomarker records in volcanic-hosted speleothems. Within them, the lipid fraction primarily consists of low molecular weight n-alkanes, α-alkenes, and branched-alkenes, providing further evidence that microorganisms serve as the origin of organic matter in these formations. The ongoing research in Lanzarote's lava tubes will help develop protocols, routines, and predictive models that could provide guidance on choosing locations and methodologies for searching potential biosignatures on Mars.

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Nearly half a century ago, two papers postulated the likelihood of lunar lava tube caves using mathematical models. Today, armed with an array of orbiting and fly-by satellites and survey instrumentation, we have now acquired cave data across our solar system-including the identification of potential cave entrances on the Moon, Mars, and at least nine other planetary bodies. These discoveries gave rise to the study of planetary caves. To help advance this field, we leveraged the expertise of an interdisciplinary group to identify a strategy to explore caves beyond Earth. Focusing primarily on astrobiology, the cave environment, geology, robotics, instrumentation, and human exploration, our goal was to produce a framework to guide this subdiscipline through at least the next decade. To do this, we first assembled a list of 198 science and engineering questions. Then, through a series of social surveys, 114 scientists and engineers winnowed down the list to the top 53 highest priority questions. This exercise resulted in identifying emerging and crucial research areas that require robust development to ultimately support a robotic mission to a planetary cave-principally the Moon and/or Mars. With the necessary financial investment and institutional support, the research and technological development required to achieve these necessary advancements over the next decade are attainable. Subsequently, we will be positioned to robotically examine lunar caves and search for evidence of life within Martian caves; in turn, this will set the stage for human exploration and potential habitation of both the lunar and Martian subsurface.

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Suicides are preventable tragedies, if risk factors are tracked and mitigated. We had previously developed a new quantitative suicidality risk assessment instrument (Convergent Functional Information for Suicidality, CFI-S), which is in essence a simple polyphenic risk score, and deployed it in a busy urban hospital Emergency Department, in a naturalistic cohort of consecutive patients. We report a four years follow-up of that population (n = 482). Overall, the single administration of the CFI-S was significantly predictive of suicidality over the ensuing 4 years (occurrence- ROC AUC 80%, severity- Pearson correlation 0.44, imminence-Cox regression Hazard Ratio 1.33). The best predictive single phenes (phenotypic items) were feeling useless (not needed), a past history of suicidality, and social isolation. We next used machine learning approaches to enhance the predictive ability of CFI-S. We divided the population into a discovery cohort (n = 255) and testing cohort (n = 227), and developed a deep neural network algorithm that showed increased accuracy for predicting risk of future suicidality (increasing the ROC AUC from 80 to 90%), as well as a similarity network classifier for visualizing patient's risk. We propose that the widespread use of CFI-S for screening purposes, with or without machine learning enhancements, can boost suicidality prevention efforts. This study also identified as top risk factors for suicidality addressable social determinants. Supplementary Information: The online version contains supplementary material available at 10.1007/s44192-022-00016-z.

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An accurate record of preindustrial (pre-1900 CE) sea level is necessary to contextualize modern global mean sea level (GMSL) rise with respect to natural variability. Precisely dated phreatic overgrowths on speleothems (POS) provide detailed rates of Late Holocene sea-level rise in Mallorca. Statistical analysis indicates that sea level rose locally by 0.12 to 0.31 m (95% confidence) from 3.26 to 2.84 thousand years (ka) ago (2σ) and remained within 0.08 m (95% confidence) of preindustrial levels from 2.84 ka to 1900 CE. This sea-level history is consistent with glacial isostatic adjustment models adopting relatively weak upper mantle viscosities of ~1020 Pa s. There is virtual certainty (>0.999 probability) that the average GMSL rise since 1900 CE has exceeded even the high average rate of sea-level rise between 3.26 and 2.84 ka inferred from the POS record. We conclude that modern GMSL rise is anomalous relative to any natural variability in ice volumes over the past 4000 years.

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Sea-level reconstructions are important for understanding past ice sheet variability and its response to past and future warming. Here we present Neogene and Quaternary sea-level snapshots using phreatic overgrowths on speleothems (POS) from caves on Mallorca, Spain. POS are excellent sea level index points because of their clear relationship to sea level and precise U-Pb chronology. We find that local sea-level before and at the onset of the Messinian Salinity Crisis was at 33.3 ± 0.25 m (6.54 ± 0.37 Ma) and 31.8 ± 0.25 m (5.86 ± 0.60 Ma) above present levels, respectively. We further present global mean sea level (GMSL) estimates, i.e. local sea level corrected for glacial isostatic adjustment and long-term uplift, for three other POS. The results show that GMSL during the Pliocene-Pleistocene Transition was 6.4 m (- 2.0-8.8 m) at 2.63 ± 0.11 Ma and during the beginning and the end of the Mid-Pleistocene Transition was - 1.1 m (- 5.6-2.4 m) and 5 m (1.5-8.1 m), respectively. These estimates provide important constraints for the past evolution of sea level and show that local sea level prior to the MSC was similar to the highest stand during the Pliocene, with markedly lower position afterwards.

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Water availability for Native Americans in the southwestern United States during periods of prolonged droughts is poorly understood as regional hydroclimate records are scant or contradicting. Here, we show that radiocarbon-dated charcoal recovered from an ice deposit accumulated in Cave 29, western New Mexico, provide unambiguous evidence for five drought events that impacted the Ancestral Puebloan society between ~ AD 150 and 950. The presence of abundant charred material in this cave indicates that they periodically obtained drinking water by using fire to melt cave ice, and sheds light on one of many human-environment interactions in the Southwest in a context when climate change forced growing Ancestral Puebloan populations to exploit water resources in unexpected locations. The melting of cave ice under current climate conditions is both uncovering and threatening a fragile source of paleoenvironmental and archaeological evidence of human adaptations to a seemingly marginal environment.

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Esophageal diverticula are uncommon; however, when present, they can cause symptoms of dysphagia, regurgitation, and chest pain. Based on location and pathophysiological characteristics, they are classified as pulsion- and traction-type diverticula. In the past, the open surgical approach was the only treatment available; however, in the past few decades, transoral incisionless approaches in the form of rigid and flexible endoscopy have gained popularity. Diverticular peroral endoscopic myotomy has emerged as an alternative treatment option. In this paper, we reviewed the role of peroral endoscopic myotomy as a treatment option for different types of esophageal diverticula. Although a safe and effective procedure, this novel submucosal tunneling technique for the treatment of esophageal diverticula requires further validation, and head-to-head comparisons between the different approaches for the treatment of esophageal diverticula are warranted.

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Caves formed by sulfuric acid dissolution have been identified worldwide. These caves can host diverse microbial communities that are responsible for speleogenesis and speleothem formation. It is not well understood how microbial communities change in response to surface water entering caves. Illumina 16S rRNA sequencing and bioinformatic tools were used to determine the impact of surface water on the microbial community diversity and function within a spring pool found deep in the Monte Conca Cave system in Sicily, Italy. Sulfur oxidizers comprised more than 90% of the microbial community during the dry season and were replaced by potential anthropogenic contaminants such as Escherichia and Lysinibacillus species after heavy rains. One sampling date appeared to show a transition between the wet and dry seasons when potential anthropogenic contaminants (67.3%), sulfur-oxidizing bacteria (13.6%), and nitrogen-fixing bacteria (6.5%) were all present within the spring pool.

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Esophageal diverticula are uncommon; however, when present, they can cause symptoms of dysphagia, regurgitation, and chest pain. Based on location and pathophysiological characteristics, they are classified as pulsion- and traction-type diverticula. In the past, the open surgical approach was the only treatment available; however, in the past few decades, transoral incisionless approaches in the form of rigid and flexible endoscopy have gained popularity. Diverticular peroral endoscopic myotomy has emerged as an alternative treatment option. In this paper, we reviewed the role of peroral endoscopic myotomy as a treatment option for different types of esophageal diverticula. Although a safe and effective procedure, this novel submucosal tunneling technique for the treatment of esophageal diverticula requires further validation, and head-to-head comparisons between the different approaches for the treatment of esophageal diverticula are warranted.

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Esophageal diverticula are uncommon; however, when present, they can cause symptoms of dysphagia, regurgitation, and chest pain. Based on location and pathophysiological characteristics, they are classified as pulsion- and traction-type diverticula. In the past, the open surgical approach was the only treatment available; however, in the past few decades, transoral incisionless approaches in the form of rigid and flexible endoscopy have gained popularity. Diverticular peroral endoscopic myotomy has emerged as an alternative treatment option. In this paper, we reviewed the role of peroral endoscopic myotomy as a treatment option for different types of esophageal diverticula. Although a safe and effective procedure, this novel submucosal tunneling technique for the treatment of esophageal diverticula requires further validation, and head-to-head comparisons between the different approaches for the treatment of esophageal diverticula are warranted.

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Reconstructing the evolution of sea level during past warmer epochs such as the Pliocene provides insight into the response of sea level and ice sheets to prolonged warming1. Although estimates of the global mean sea level (GMSL) during this time do exist, they vary by several tens of metres2-4, hindering the assessment of past and future ice-sheet stability. Here we show that during the mid-Piacenzian Warm Period, which was on average two to three degrees Celsius warmer than the pre-industrial period5, the GMSL was about 16.2 metres higher than today owing to global ice-volume changes, and around 17.4 metres when thermal expansion of the oceans is included. During the even warmer Pliocene Climatic Optimum (about four degrees Celsius warmer than pre-industrial levels)6, our results show that the GMSL was 23.5 metres above the present level, with an additional 1.6 metres from thermal expansion. We provide six GMSL data points, ranging from 4.39 to 3.27 million years ago, that are based on phreatic overgrowths on speleothems from the western Mediterranean (Mallorca, Spain). This record is unique owing to its clear relationship to sea level, its reliable U-Pb ages and its long timespan, which allows us to quantify uncertainties on potential uplift. Our data indicate that ice sheets are very sensitive to warming and provide important calibration targets for future ice-sheet models7.

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Background: The purpose of this study was to determine whether plasma levels of the collagen triple helix repeat containing 1 (CTHRC1) protein can serve as a blood-based biomarker for improved diagnosis of rheumatoid arthritis (RA) patients and monitoring of RA disease activity. Methods: We measured levels of CTHRC1 in the plasma of patients diagnosed with RA, osteoarthritis (OA), reactive arthritis (ReA), as well as in healthy individuals. We then assessed the correlation between CTHRC1 protein and a range of indices including the 28-joint disease activity score (DAS28), rheumatoid factor (RF), C-reactive protein (CRP), anti-citrullinated protein antibodies (ACPA), erythrocyte sedimentation rate (ESR), as well as a panel of cytokines, including interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), interleukin 8 (IL-8), and interferon gamma (IFNγ). Receiver operating characteristic (ROC) analysis was further performed to assess the diagnostic value of CTHRC1. Results: CTHRC1 plasma levels were significantly elevated in RA patients compared to healthy individuals, OA and ReA patients. ROC curve and risk score analysis suggested that plasma CTHRC1 can accurately discriminate patients with RA from healthy controls and may have practical value for RA diagnosis. CTHRC1 levels were positively associated with RF, ACPA, CRP, and disease activity based on the combined index of DAS28 with CRP (DAS28-CRP), and also strongly correlated with IL-1ß, IL-6, IL-8, and IFNγ. Conclusion: Our studies show that CTHRC1 is a sensitive and easy-to-measure plasma marker that differentiates between RA and healthy status and also distinguishes between RA and other forms of arthritis, such as OA and ReA. At the current level of understanding, plasma CTHRC1 levels may improve the diagnosis of RA and these findings warrant confirmation in a larger, more comprehensive patient population.

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Two speleothem stable isotope records from East-Central Europe demonstrate that Greenland Stadial 12 (GS12) and GS10-at 44.3-43.3 and 40.8-40.2 ka-were prominent intervals of cold and arid conditions. GS12, GS11, and GS10 are coeval with a regional pattern of culturally (near-)sterile layers within Europe's diachronous archeologic transition from Neanderthals to modern human Aurignacian. Sterile layers coeval with GS12 precede the Aurignacian throughout the middle and upper Danube region. In some records from the northern Iberian Peninsula, such layers are coeval with GS11 and separate the Châtelperronian from the Aurignacian. Sterile layers preceding the Aurignacian in the remaining Châtelperronian domain are coeval with GS10 and the previously reported 40.0- to 40.8-ka cal BP [calendar years before present (1950)] time range of Neanderthals' disappearance from most of Europe. This suggests that ecologic stress during stadial expansion of steppe landscape caused a diachronous pattern of depopulation of Neanderthals, which facilitated repopulation by modern humans who appear to have been better adapted to this environment. Consecutive depopulation-repopulation cycles during severe stadials of the middle pleniglacial may principally explain the repeated replacement of Europe's population and its genetic composition.

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In this review, we present modern aspects of etiology and pathogenesis of atherosclerosis. We describe the roles played by inflammatory cells, components of cellular response in allergic reactions, disturbances of carbohydrate metabolism, cellular aging, and infection at various stages of formation of atherosclerotic plaques. Special attention is given to the specific characteristics of atherosclerosis and calcification of coronary arteries. We show the influence of age and gender on the disease progression. The review includes information on the importance of myocardial bridges for the change of hemodynamics in segments of coronary arteries. The data presented indicate that differences in localization of atherosclerotic lesions between systems of the right and left coronary arteries depends on their hemodynamic, anatomical and physiological characteristics. According to the literature, anterior descending artery is more vulnerable in this respect.

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Currently there is a scarcity of paleo-records related to the North Atlantic Oscillation (NAO), particularly in East-Central Europe (ECE). Here we report δ15N analysis of guano from a cave in NW Romania with the intent of reconstructing past variation in ECE hydroclimate and examine NAO impacts on winter precipitation. We argue that the δ15N values of guano indicate that the nitrogen cycle is hydrologically controlled and the δ15N values likely reflect winter precipitation related to nitrogen mineralization prior to the growing season. Drier conditions indicated by δ15N values at AD 1848-1852 and AD 1880-1930 correspond to the positive phase of the NAO. The increased frequency of negative phases of the NAO between AD 1940-1975 is contemporaneous with higher δ15N values (wetter conditions). A 4‰ decrease in δ15N values at the end of the 1970's corresponds to a strong reduction in precipitation associated with a shift from negative to positive phase of the NAO. Using the relationship between NAO index and δ15N values in guano for the instrumental period, we reconstructed NAO-like phases back to AD 1650. Our results advocate that δ15N values of guano offer a proxy of the NAO conditions in the more distant past, helping assess its predictability.