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The mafic sills intruding into the dolostone in the uppermost part of the Vempalle Formation, Cuddapah Supergroup, have caused extensive metasomatism in the dolostone, resulting in serpentinisation and hydrothermal chrysotile mineralisation in the Pulivendla asbestos belt. Three different coloured varieties of serpentine, namely black, green, and yellow serpentine, have developed successively away from the mafic sill-dolostone contact. These serpentines belong to the lizardite variety and occur in the form of massive bands, irregular replacement patches, and stylolite fills in dolostone. Due to high XH2O activity and lesser silica activity, in some portions of dolostone, brucite has formed in excess of lizardite. This is the first report of brucite mineralisation from this asbestos belt. Major and trace element data indicate a greater contribution from the mafic sill for the formation of black serpentine and a greater role of dolostone in the formation of yellow and green serpentine. A simple mixing model of the 143Nd/144Nd values also supports the contribution of the mafic sill and carbonate in the proportion of 60:40 in the formation of black serpentine. Variation in the concentration of transition metals Fe, V, Cr, Co and Ni is possibly responsible for the development of serpentine having different colours. Serpentinised dolostone commonly shows depletion in δ13C and δ18O values ranging from –1.43 to –0.76‰ and –18.01 to –17.06‰, respectively, compared to those of unaltered dolostone (δ13C: 0.35–0.97‰ and δ18O: –7.11 to –8.75‰). The depletion in δ13C and δ18O values in the serpentinised dolostone is inferred to be caused by decarbonation and interaction with the mafic magma. Serpentinisation of dolostone was accompanied by extensive fracturing and development of stylolites, and followed by hydrothermal fluid flow when some of the early formed serpentines were dissolved in the hydrothermal fluid and re-precipitated as chrysotile filling fractures and stylolites.Research highlightsDolostone in the uppermost part of Vempalle Formation was serpentinised upon emplacement of mafic sill.Chrysotile mineralisation occurred after the serpentinisation of dolostone by dissolution and re-precipitation of previously formed lizardite variety of serpentine.Incidence of brucite mineralisation in serpentinised dolostone of Pulivendla asbestos belt is identified and reported for the first time.

The Vempalle Formation of the Cuddapah Supergroup consists of a carbonate-siliciclastic unit with extensive mafic sills and dykes in the upper part of the formation, which hosts barite and chrysotile mineralization in a 44 km long SE–NW trending zone between Vempalle and Lingala. The barite mineralization occurs mainly in the Vemula–Velpula area as fracture-fill and breccia-fill veins in mafic dykes that intrude the carbonate of the Vempalle Formation. The barite mineralized mafic rock has undergone extensive hydrothermal alteration, with the primary calcic plagioclase and clinopyroxene replaced by albite and clinochlore, respectively, along with the introduction of secondary epidote, quartz, and calcite, while in the surrounding carbonate, no hydrothermal alteration is observed. The extensive hydrothermal alteration of mineralized mafic rock and large variation in its Ba concentration (68 to 3012 ppm), which generally is abnormally high, indicates that Ba has been scavenged from the mafic rock by fluid-rock reaction. The δ 34 S values of the barite range from +16.19 to +23.24‰, which is comparable to the δ 34 S value of Proterozoic seawater. The characteristics of carbonate and mafic rock indicate that barite mineralization has taken place at shallow crustal depths, where seawater could not be directly involved in the hydrothermal process. Hence, it is inferred that the evolved seawater, i.e., basinal brine, is the source of S. Research highlights Large variation and abnormally high Ba concentration in mafic rocks of the Vempalle Formation in the Cuddapah Basin, together with the extensive hydrothermal alteration present in the mafic rock hosting barite deposit, indicate that Ba was scavenged from the mafic rock through fluid-rock reaction. δ 34 S values of Vempalle barite (+16.19 to +23.24‰) fall within the range estimated for Proterozoic seawater (+10 to +30‰), from which we infer that the primary source of S was seawater.

The mafic sills intruding into the dolostone in the uppermost part of the Vempalle Formation, Cuddapah Supergroup, have caused extensive metasomatism in the dolostone, resulting in serpentinisation and hydrothermal chrysotile mineralisation in the Pulivendla asbestos belt. Three different coloured varieties of serpentine, namely black, green, and yellow serpentine, have developed successively away from the mafic sill-dolostone contact. These serpentines belong to the lizardite variety and occur in the form of massive bands, irregular replacement patches, and stylolite fills in dolostone. Due to high X H 2 O activity and lesser silica activity, in some portions of dolostone, brucite has formed in excess of lizardite. This is the first report of brucite mineralisation from this asbestos belt. Major and trace element data indicate a greater contribution from the mafic sill for the formation of black serpentine and a greater role of dolostone in the formation of yellow and green serpentine. A simple mixing model of the 143 Nd/ 144 Nd values also supports the contribution of the mafic sill and carbonate in the proportion of 60:40 in the formation of black serpentine. Variation in the concentration of transition metals Fe, V, Cr, Co and Ni is possibly responsible for the development of serpentine having different colours. Serpentinised dolostone commonly shows depletion in δ 13 C and δ 18 O values ranging from –1.43 to –0.76‰ and –18.01 to –17.06‰, respectively, compared to those of unaltered dolostone ( δ 13 C: 0.35–0.97‰ and δ 18 O: –7.11 to –8.75‰). The depletion in δ 13 C and δ 18 O values in the serpentinised dolostone is inferred to be caused by decarbonation and interaction with the mafic magma. Serpentinisation of dolostone was accompanied by extensive fracturing and development of stylolites, and followed by hydrothermal fluid flow when some of the early formed serpentines were dissolved in the hydrothermal fluid and re-precipitated as chrysotile filling fractures and stylolites. Research highlights Dolostone in the uppermost part of Vempalle Formation was serpentinised upon emplacement of mafic sill. Chrysotile mineralisation occurred after the serpentinisation of dolostone by dissolution and re-precipitation of previously formed lizardite variety of serpentine. Incidence of brucite mineralisation in serpentinised dolostone of Pulivendla asbestos belt is identified and reported for the first time.

In this paper, the performance of three machine-learning methods for predicting short-term evolution and for reproducing the long-term statistics of a multiscale spatiotemporal Lorenz 96 system is examined. The methods are an echo state network (ESN, which is a type of reservoir computing; hereafter RC–ESN), a deep feed-forward artificial neural network (ANN), and a recurrent neural network (RNN) with long short-term memory (LSTM; hereafter RNN–LSTM). This Lorenz 96 system has three tiers of nonlinearly interacting variables representing slow/large-scale (X), intermediate (Y), and fast/small-scale (Z) processes. For training or testing, only X is available; Y and Z are never known or used. We show that RC–ESN substantially outperforms ANN and RNN–LSTM for short-term predictions, e.g., accurately forecasting the chaotic trajectories for hundreds of numerical solver's time steps equivalent to several Lyapunov timescales. The RNN–LSTM outperforms ANN, and both methods show some prediction skills too. Furthermore, even after losing the trajectory, data predicted by RC–ESN and RNN–LSTM have probability density functions (pdf's) that closely match the true pdf – even at the tails. The pdf of the data predicted using ANN, however, deviates from the true pdf. Implications, caveats, and applications to data-driven and data-assisted surrogate modeling of complex nonlinear dynamical systems, such as weather and climate, are discussed.

Radical resection of bone tumors is a clinically effective but costly procedure. Despite the implementation of federal price transparency mandates, little is known about the nationwide variation in negotiated prices for these specialized oncologic surgeries. This study aimed to quantify the variation in negotiated rates for radical resection of the humerus and femur/knee and identify associated hospital, payor, and state-policy drivers. This cross-sectional study analyzed hospital-negotiated payor rates from the Turquoise Health database for current procedural terminology (CPT) codes 24150 (humerus resection) and 27365 (femur/knee resection). Multivariate linear regression was used to determine the associations between hospital size and type, payor class, and state-level policies (Medicaid expansion, Certificate of Need [CoN] laws, All-Payer Claims Database [APCD] mandates, and Nurse Practitioner [NP] scope of practice) on negotiated payor rates. A total of 285,857 negotiated rates were analyzed. Significant price variation was observed across all factors. Large hospitals (>1000 beds) and Critical Access Hospitals (for femur/knee resection only) had significantly higher rates. CoN laws were associated with higher prices for both procedures (+$348.25 and +$667.98, respectively), as were APCD mandates for femur/knee resections (+$1231.24). Medicare Advantage plans paid inconsistently compared to commercial plans, paying more for humerus but substantially less for femur/knee resections. Negotiated prices for radical bone tumor resection are highly variable and influenced by a complex interplay of market dynamics, challenging the assumption that price transparency alone can standardize healthcare costs for specialized care.

Nanomedicine offers powerful opportunities for targeted drug delivery and cancer therapy, yet clinical translation remains limited by the complex and dynamic interactions of nanoparticles within biological systems. This review integrates current evidence on how nanoparticle size, shape, and surface properties govern cellular uptake and processing, systemic biodistribution, immune interactions, and therapeutic performance across in vitro, ex vivo, and in vivo models. By comparatively analyzing findings across two-dimensional, three-dimensional, xenograft, and immunocompetent tumor models, this review identifies model-dependent determinants of nanoparticle performance that influence translational outcomes. Foundational studies in two-dimensional monolayers established relationships between physicochemical attributes, endocytic pathways, vesicular trafficking, and exocytosis. Three-dimensional spheroids introduce extracellular matrix density and cellular packing constraints that limit nanoparticle movement and alter uptake trends observed in monolayers. In vivo, xenograft models emphasize the influence of vascular permeability and stromal architecture but often overestimate delivery due to exaggerated enhanced permeability and retention effects and the lack of adaptive immunity. Immunocompetent tumor models capture complement activation, opsonization, macrophage-mediated clearance, dynamic protein corona evolution, and cytokine-driven vascular changes. These immune-mediated processes reshape biodistribution patterns and often diminish ligand-mediated targeting benefits. They operate alongside systemic factors such as renal and hepatosplenic filtration, biotransformation, and species-specific differences in vascular structure and immune composition, influencing nanoparticle pharmacokinetics and therapeutic response. Together, these findings underscore that successful nanomedicine design requires integrating material engineering with an understanding of immune surveillance, vascular biology, tumor microenvironment heterogeneity, and whole-body transport dynamics. Future progress will depend on developing nanoparticles that maintain functional stability in immune-intact hosts, minimize premature clearance, and achieve sustained intratumoral delivery. These advances must be supported by predictive, physiologically relevant models that bridge gaps between in vitro results, preclinical outcomes, and clinical translation.

To investigate roles for bone marrow adipocyte (BMAd) lipolysis in bone homeostasis, we created a BMAd-specific Cre mouse model in which we knocked out adipose triglyceride lipase (ATGL, Pnpla2 gene). BMAd- Pnpla2 -/- mice have impaired BMAd lipolysis, and increased size and number of BMAds at baseline. Although energy from BMAd lipid stores is largely dispensable when mice are fed ad libitum, BMAd lipolysis is necessary to maintain myelopoiesis and bone mass under caloric restriction. BMAd-specific Pnpla2 deficiency compounds the effects of caloric restriction on loss of trabecular bone in male mice, likely due to impaired osteoblast expression of collagen genes and reduced osteoid synthesis. RNA sequencing analysis of bone marrow adipose tissue reveals that caloric restriction induces dramatic elevations in extracellular matrix organization and skeletal development genes, and energy from BMAd is required for these adaptations. BMAd-derived energy supply is also required for bone regeneration upon injury, and maintenance of bone mass with cold exposure.

BACKGROUNDMirabegron is a β3-adrenergic receptor (β3-AR) agonist approved only for the treatment of overactive bladder. Encouraging preclinical results suggest that β3-AR agonists could also improve obesity-related metabolic disease by increasing brown adipose tissue (BAT) thermogenesis, white adipose tissue (WAT) lipolysis, and insulin sensitivity.METHODSWe treated 14 healthy women of diverse ethnicities (27.5 ± 1.1 years of age, BMI of 25.4 ± 1.2 kg/m2) with 100 mg mirabegron (Myrbetriq extended-release tablet, Astellas Pharma) for 4 weeks in an open-label study. The primary endpoint was the change in BAT metabolic activity as measured by [18F]-2-fluoro-d-2-deoxy-d-glucose (18F-FDG) PET/CT. Secondary endpoints included resting energy expenditure (REE), plasma metabolites, and glucose and insulin metabolism as assessed by a frequently sampled intravenous glucose tolerance test.RESULTSChronic mirabegron therapy increased BAT metabolic activity. Whole-body REE was higher, without changes in body weight or composition. Additionally, there were elevations in plasma levels of the beneficial lipoprotein biomarkers HDL and ApoA1, as well as total bile acids. Adiponectin, a WAT-derived hormone that has antidiabetic and antiinflammatory capabilities, increased with acute treatment and was 35% higher upon completion of the study. Finally, an intravenous glucose tolerance test revealed higher insulin sensitivity, glucose effectiveness, and insulin secretion.CONCLUSIONThese findings indicate that human BAT metabolic activity can be increased after chronic pharmacological stimulation with mirabegron and support the investigation of β3-AR agonists as a treatment for metabolic disease.TRIAL REGISTRATIONClinicaltrials.gov NCT03049462.FUNDINGThis work was supported by grants from the Intramural Research Program of the NIDDK, NIH (DK075112, DK075116, DK071013, and DK071014).

Despite global commitments to achieving gender equality and improving health and wellbeing for all, quantitative data and methods to precisely estimate the effect of gender norms on health inequities are underdeveloped. Nonetheless, existing global, national, and subnational data provide some key opportunities for testing associations between gender norms and health. Using innovative approaches to analysing proxies for gender norms, we generated evidence that gender norms impact the health of women and men across life stages, health sectors, and world regions. Six case studies showed that: (1) gender norms are complex and can intersect with other social factors to impact health over the life course; (2) early gender-normative influences by parents and peers can have multiple and differing health consequences for girls and boys; (3) non-conformity with, and transgression of, gender norms can be harmful to health, particularly when they trigger negative sanctions; and (4) the impact of gender norms on health can be context-specific, demanding care when designing effective gender-transformative health policies and programmes. Limitations of survey-based data are described that resulted in missed opportunities for investigating certain populations and domains. Recommendations for optimising and advancing research on the health impacts of gender norms are made.