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Blood Reviews Jun 2024Despite recent therapeutic advancements in the general field of non-Hodgkin lymphoma, effective treatment of relapsed or refractory (R/R) mantle cell lymphoma (MCL)... (Review)
Review
Despite recent therapeutic advancements in the general field of non-Hodgkin lymphoma, effective treatment of relapsed or refractory (R/R) mantle cell lymphoma (MCL) remains a challenge. The development of Bruton tyrosine kinase (BTK) inhibitors has revolutionized the field and these agents are now the mainstay of R/R MCL management. However, BTK inhibitors are not curative, and as they are increasingly being incorporated into frontline regimens, the shifting treatment landscape for R/R disease presents new challenges. Here we review data for commonly employed treatment strategies including BTK inhibitors, the BCL2-inhibitor venetoclax, lenalidomide-based regimens, and chimeric antigen receptor T-cell therapy. We additionally review data for promising novel agents including antibody-drug conjugates and bispecific antibodies before highlighting some emerging targeted agents that continue to bring promise for improved outcomes in R/R MCL.
PubMed: 38906740
DOI: 10.1016/j.blre.2024.101221 -
Nature Communications Jun 2024Abundant carbon was identified on Mercury by MESSENGER, which is interpreted as the remnant of a primordial graphite flotation crust, suggesting that the magma ocean and...
Abundant carbon was identified on Mercury by MESSENGER, which is interpreted as the remnant of a primordial graphite flotation crust, suggesting that the magma ocean and core were saturated in carbon. We re-evaluate carbon speciation in Mercury's interior in light of the high pressure-temperature experiments, thermodynamic models and the most recent geophysical models of the internal structure of the planet. Although a sulfur-free melt would have been in the stability field of graphite, sulfur dissolution in the melt under the unique reduced conditions depressed the sulfur-rich liquidus to temperatures spanning the graphite-diamond transition. Here we show it is possible, though statistically unlikely, that diamond was stable in the magma ocean. However, the formation of a solid inner core caused diamond to crystallize from the cooling molten core and formation of a diamond layer becoming thicker with time.
PubMed: 38877015
DOI: 10.1038/s41467-024-49305-x -
Nature Jun 2024The solid inner core, suspended within the liquid outer core and anchored by gravity, has been inferred to rotate relative to the surface of Earth or change over years...
The solid inner core, suspended within the liquid outer core and anchored by gravity, has been inferred to rotate relative to the surface of Earth or change over years to decades based on changes in seismograms from repeating earthquakes and explosions. It has a rich inner structure and influences the pattern of outer core convection and therefore Earth's magnetic field. Here we compile 143 distinct pairs of repeating earthquakes, many within 16 multiplets, built from 121 earthquakes between 1991 and 2023 in the South Sandwich Islands. We analyse their inner-core-penetrating PKIKP waves recorded on the medium-aperture arrays in northern North America. We document that many multiplets exhibit waveforms that change and then revert at later times to match earlier events. The matching waveforms reveal times at which the inner core re-occupies the same position, relative to the mantle, as it did at some time in the past. The pattern of matches, together with previous studies, demonstrates that the inner core gradually super-rotated from 2003 to 2008, and then from 2008 to 2023 sub-rotated two to three times more slowly back through the same path. These matches enable precise and unambiguous tracking of inner core progression and regression. The resolved different rates of forward and backward motion suggest that new models will be necessary for the dynamics between the inner core, outer core and mantle.
PubMed: 38867052
DOI: 10.1038/s41586-024-07536-4 -
PeerJ 2024Unionoid freshwater mussels (Bivalvia: Unionidae) are free-living apart from a brief, obligately parasitic, larval stage that infects fish hosts, and gravid female...
Unionoid freshwater mussels (Bivalvia: Unionidae) are free-living apart from a brief, obligately parasitic, larval stage that infects fish hosts, and gravid female mussels have evolved a spectrum of strategies to infect fish hosts with their larvae. In many North American species, this involves displaying a mantle lure: a pigmented fleshy extension that acts as an aggressive mimic of a host fish prey, thereby eliciting a feeding response that results in host infection. The mantle lure of is of particular interest because it is apparently polymorphic, with two distinct primary lure phenotypes. One, described as "darter-like", has "eyespots", a mottled body coloration, prominent marginal extensions, and a distinct "tail". The other, described as "worm-like", lacks those features and has an orange and black coloration. We investigated this phenomenon using genomics, captive rearing, biogeographic, and behavioral analyses. Within-brood lure variation and within-population phylogenomic (ddRAD-seq) analyses of individuals bearing different lures confirmed that this phenomenon is a true polymorphism. The relative abundance of the two morphs appears stable over ecological timeframes: the ratio of the two lure phenotypes in a River Raisin (MI) population in 2017 was consistent with that of museum samples collected at the same site six decades earlier. Within the River Raisin, four main "darter-like" lure motifs visually approximated four co-occurring darter species (, and ), and the "worm-like" lure resembled a widespread common leech, . Darters and leeches are typical prey of (smallmouth bass), the primary fish host of . field recordings of the "darter" and "leech" lure display behaviors, and the lure display of co-occurring congener , were captured. Despite having putative models in distinct phyla, both lure morphs have largely similar display behaviors that differ significantly from that of sympatric individuals. Some minor differences in the behavior between the two morphs were observed, but we found no clear evidence for a behavioral component of the polymorphism given the criteria measured. Discovery of discrete within-brood inheritance of the lure polymorphism implies potential control by a single genetic locus and identifies as a promising study system to identify regulatory genes controlling a key adaptive trait of freshwater mussels.
Topics: Animals; Female; Biological Mimicry; Unionidae; Fresh Water; Polymorphism, Genetic; Phenotype; Host-Parasite Interactions; Phylogeny; Pigmentation
PubMed: 38803583
DOI: 10.7717/peerj.17359 -
Scientific Reports May 2024The subcontinental lithospheric mantle (SCLM) beneath Phanerozoic regions is mostly constituted by fertile lherzolites, which sharply contrast with cratonic mantle made...
The subcontinental lithospheric mantle (SCLM) beneath Phanerozoic regions is mostly constituted by fertile lherzolites, which sharply contrast with cratonic mantle made of highly-depleted peridotites. The question of whether this chemical difference results from lower degrees of melting associated with the formation of Phanerozoic SCLM or from the refertilization of ancient depleted SCLM remains a subject of debate. Additionally, the timing and geodynamic environment of accretion of the fertile SCLM in many Phanerozoic regions are poorly constrained. We here document new geochemical and Nd-Hf isotopic data for orogenic lherzolite massifs from the Ivrea-Verbano Zone (IVZ), Southern Alps. Even though a few Proterozoic Re depletion ages are locally preserved in these mantle bodies, our data reveal that the IVZ lherzolitic massifs were "recently" accreted to the SCLM in the Upper Devonian (ca. 370 Ma) during Pangea amalgamation, with a petrochemical evolution characterized by low-degree (~ 5-12%) depletion and nearly contemporaneous pervasive to focused melt migration. The lithospheric accretion putatively took place through asthenospheric upwelling triggered by Variscan intra-continental extension in a back-arc setting related to the subduction of the Rheic Ocean. We thus conclude that the fertile sections of Phanerozoic SCLM can be accreted during "recent" events of back-arc continental extension, even where Os isotopes preserve memories of melting events in much older times.
PubMed: 38783050
DOI: 10.1038/s41598-024-61763-3 -
ACS Environmental Au May 2024The highly excessive uptake of cadmium (Cd) by rice plants is well known, but the transfer pathway and mechanism of Cd in the paddy system remain poorly understood....
The highly excessive uptake of cadmium (Cd) by rice plants is well known, but the transfer pathway and mechanism of Cd in the paddy system remain poorly understood. Herein, pot experiments and field investigation were systematically carried out for the first time to assess the phytoavailability of Cd and fingerprint its transfer pathway in the paddy system under different treatments (slaked lime and biochar amendments), with the aid of a pioneering Cd isotopic technique. Results unveiled that no obvious differences were displayed in the δCd of Ca(NO)-extractable and acid-soluble fractions among different treatments in pot experiments, while the δCd of the water-soluble fraction varied considerably from -0.88 to -0.27%, similar to those observed in whole rice plant [ΔCd ≈ 0 (-0.06 to -0.03%)]. It indicates that the water-soluble fraction is likely the main source of phytoavailable Cd, which further contributes to its bioaccumulation in paddy systems. However, ΔCd found in field conditions (-0.39 ± 0.05%) was quite different from those observed in pot experiments, mostly owing to additional contribution derived from atmospheric deposition. All these findings demonstrate that the precise Cd isotopic compositions can provide robust and reliable evidence to reveal different transfer pathways of Cd and its phytoavailability in paddy systems.
PubMed: 38765061
DOI: 10.1021/acsenvironau.3c00067 -
Lancet (London, England) May 2024Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the...
Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021.
BACKGROUND
Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021.
METHODS
The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk-outcome pairs. Pairs were included on the basis of data-driven determination of a risk-outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk-outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk-outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws.
FINDINGS
Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7-9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4-9·2]), smoking (5·7% [4·7-6·8]), low birthweight and short gestation (5·6% [4·8-6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8-6·0]). For younger demographics (ie, those aged 0-4 years and 5-14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9-27·7]) and environmental and occupational risks (decrease of 22·0% [15·5-28·8]), coupled with a 49·4% (42·3-56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9-21·7] for high BMI and 7·9% [3·3-12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6-1·9) for high BMI and 1·3% (1·1-1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4-78·8) for child growth failure and 66·3% (60·2-72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP).
INTERPRETATION
Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Humans; Global Burden of Disease; Risk Factors; Global Health; Female; Male; Risk Assessment; Adult; Middle Aged; Aged; Disability-Adjusted Life Years; Adolescent; Young Adult; Quality-Adjusted Life Years
PubMed: 38762324
DOI: 10.1016/S0140-6736(24)00933-4 -
Contributions To Mineralogy and... 2024Quaternary rocks from the East and West Eifel volcanic fields in western Germany are a key suite of intraplate volcanic rocks that can provide insights into volcanism of...
UNLABELLED
Quaternary rocks from the East and West Eifel volcanic fields in western Germany are a key suite of intraplate volcanic rocks that can provide insights into volcanism of the Central European Volcanic Province (CEVP) and into continental intraplate volcanism in general. We present a comprehensive dataset for Eifel lavas including isotope as well as major and trace element data for 59 samples covering representative compositions of the different volcanic fields. In line with previous studies, the lavas are all SiO-undersaturated, alkaline-rich and mainly comprise primitive basanites, melilitites, and nephelinites (Mg# ≥ 57). Geochemical compositions of samples from both volcanic subfields display distinct differences in their trace-element as well as radiogenic isotope compositions, largely confirming previous subdivisions. Coupled trace-element and radiogenic Sr-Nd-Hf-Pb-Os isotope compositions can now provide firm evidence for spatially heterogeneous mantle sources and compositionally distinct magmatic pulses. Within the West Eifel Field, Sr-Nd-Pb isotope compositions of the younger (≤80 ka), ONB-suite (olivine-nephelinite-basanite) are similar to FOZO (FOcal ZOne) or the EAR (European Asthenospheric Reservoir) and resemble compositions that have been previously reported from plume-sourced ocean island basalts (OIB). In marked difference, older (700 Ma to 80 ka) volcanic rocks from the F-suite (Foidite) in the West Eifel field and from the entire east Eifel Field tap a more enriched mantle component, as illustrated by more radiogenic Sr isotope (Sr/Sr up to 0.705408) and variable Pb isotope compositions (Pb/Pb = 18.61-19.70, Pb/Pb = 15.62-15.67 and Pb/Pb = 38.89-39.76). Combined trace-element compositions of ONB-suite samples are in good agreement with results from batch melting models suggesting a hybrid composition of Eifel magmas formed through mixing 10% of a FOZO-like melt with 90% of a DMM-like melt, similar to melts from the Tertiary HEVF. However, radiogenic Sr-Nd-Pb isotope compositions of F-suite and EEVF and some ONB lavas require the admixture of melts from lithospheric mantle sources. Elevated Nb/Ta and Lu/Hf ratios in combination with variable Os/Os ratios can now demonstrate the presence of residual carbonated eclogite components, either in the lithosphere or in the asthenospheric mantle. Finally, by combining geochemical and temporal constraints of Tertiary and Quaternary volcanism it becomes evident that CEVP volcanism in central and western Germany has resulted from compositionally distinct magmatic pulses that tap separate mantle sources. Although the presence of a mantle plume can neither be fully confirmed nor excluded, plume-like melt pulses which partially tap carbonated eclogite domains that interact to variable extents with the lithosphere provide a viable explanation for the temporal and compositional cyclicity of CEVP volcanism.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s00410-024-02137-w.
PubMed: 38736869
DOI: 10.1007/s00410-024-02137-w -
Contributions To Mineralogy and... 2024The aluminous calcium-ferrite type phase (CF) and new aluminous phase (NAL) are thought to hold the excess alumina produced by the decomposition of garnet in MORB...
UNLABELLED
The aluminous calcium-ferrite type phase (CF) and new aluminous phase (NAL) are thought to hold the excess alumina produced by the decomposition of garnet in MORB compositions in the lower mantle. The respective stabilities of CF and NAL in the nepheline-spinel binary (NaAlSiO-MgAlO) are well established. However with the addition of further components the phase relations at lower mantle conditions remain unclear. Here we investigate a range of compositions around the nepheline apex of the nepheline-kalsilite-spinel compositional join (NaAlSiO-KAlSiO-MgAlO) at 28-78 GPa and 2000 K. Our experiments indicate that even small amounts of a kalsilite (KAlSiO) component dramatically impact phase relations. We find NAL to be stable up to at least 71 GPa in potassium-bearing compositions. This demonstrates the stabilizing effect of potassium on NAL, because NAL is not observed at pressures above 48 GPa on the nepheline-spinel binary. We also observe a broadening of the CF stability field to incorporate larger amounts of potassium with increasing pressure. For pressures below 50 GPa only minor amounts () of potassium are soluble in CF, whereas at 68 GPa, we find a solubility in CF of at least . This indicates that CF and NAL are suitable hosts of the alkali content of MORB compositions at lower mantle conditions. For sedimentary compositions at lower mantle pressures, we expect K-Hollandite to be stable in addition to CF and NAL for pressures of 28-48 GPa, based on our simplified compositions.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s00410-024-02129-w.
PubMed: 38686218
DOI: 10.1007/s00410-024-02129-w -
Pesticide Biochemistry and Physiology May 2024Amprolium (AMP) is an organic compound used as a poultry anticoccidiostat. The aim of this work is to repurpose AMP to control the land snail, Eobania vermiculata in the...
Amprolium (AMP) is an organic compound used as a poultry anticoccidiostat. The aim of this work is to repurpose AMP to control the land snail, Eobania vermiculata in the laboratory and in the field. When snails treated with ½ LC₅₀ of AMP, the levels of alkaline phosphatase (ALP), total lipids (TL), urea, creatinine, malondialdehyde (MDA), catalase (CAT), and nitric oxide (NO) were significantly increased, whereas the levels of acetylcholinesterase (AChE), total protein (TP), and glutathione (GSH) decreased. It also induced histopathological and ultrastructural changes in the digestive gland, hermaphrodite gland, kidney, mucus gland, and cerebral ganglion. Furthermore, scanning electron micrographs revealed various damages in the tegumental structures of the mantle-foot region of E. vermiculata snails. The field application demonstrated that the AMP spray caused reduced percentages in snail population of 75 and 84% after 7 and 14 days of treatment. In conclusion, because AMP disrupts the biology and physiology of the land snail, E. vermiculata, it can be used as an effective molluscicide.
Topics: Animals; Molluscacides; Snails; Acetylcholinesterase; Malondialdehyde; Drug Repositioning; Nitric Oxide; Catalase; Alkaline Phosphatase; Glutathione
PubMed: 38685220
DOI: 10.1016/j.pestbp.2024.105889