Cardiac Reverse Remodeling Mediated by HeartMate 3 Left Ventricular Assist Device: Comparison to Older Generation Devices.

Currently, the fully magnetically levitated left ventricular assist device (LVAD) HeartMate 3 (HM3) is the only commercially available device for advanced heart failure (HF) patients. However, the left ventricular (LV) functional and structural changes following mechanical unloading and circulatory support (MCS) with the HM3 have not been investigated. We compared the reverse remodeling induced by the HM3 to older generation continuous-flow LVADs. Chronic HF patients (n = 405) undergoing MCS with HeartWare Ventricular Assist Device (HVAD, n = 115), HM3 (n = 186), and HeartMate II (HM2, n = 104) at four programs were included. Echocardiograms were obtained preimplant and at 1, 3, 6, and 12 months following LVAD implantation. There were no differences in the postimplant serial LV ejection fraction (LVEF) between the devices. The postimplant LV internal diastolic diameter (LVIDd) was significantly lower for HM2 at 3 and 6 months compared with HVAD and HM3. The proportion of patients achieving "cardiac reverse remodeling responder" status (defined as LVEF improvement to ≥40% and LVIDD ≤5.9 cm) was 11.9%, and was similar between devices. HeartMate 3 appears to result in similar cardiac reverse remodeling as older generation CF-LVADs, suggesting that the fully magnetically levitated device technology could provide an effective platform to further study and promote cardiac reverse remodeling.

Annual rhythm in immune functions of blood leucocytes in an ophidian, Natrix piscator.

Annual variations in animal's physiological functions are an essential strategy to deal with seasonal challenges which also vary according to the time of year. Information regarding annual adaptations in the immune-competence to cope with seasonal stressors in reptiles is scarce. The present research plan was designed to analyze the presence of circannual immune rhythms in defense responses of the leucocytes in an ophidian, Natrix piscator. Peripheral blood leucocytes were obtained, counted, and superoxide anion production, neutrophil phagocytosis, and nitrite release were tested to assess the innate immune functions. Peripheral blood lymphocytes were separated by centrifugation (utilizing density gradient) and the cell proliferation was measured. The Cosinor rhythmometry disclosed the presence of significant annual rhythms in the number of leucocytes, superoxide anion production, nitric oxide production, and proliferation of stimulated lymphocytes. The authors found that respiratory burst activity and proliferative responses of lymphocytes were crucial immune responses that showed the annual rhythm. It was summarized that the immune function of the N. piscator is a labile attribute that makes the animal competent to cope with the seasonal stressor by adjustment in the potency of response.

System of wheat intensification (SWI): Effects on lodging resistance, photosynthetic efficiency, soil biomes, and water productivity.

Intense cultivation with narrow row spacing in wheat, a common practice in the Indo-Gangetic plains of South Asia, renders the crop more susceptible to lodging during physiological maturity. This susceptibility, compounded by the use of traditional crop cultivars, has led to a substantial decline in overall crop productivity. In response to these challenges, a two-year field study on the system of wheat intensification (SWI) was conducted. The study involved three different cultivation methods in horizontal plots and four wheat genotypes in vertical plots, organized in a strip plot design. Our results exhibited that adoption of SWI at 20 cm × 20 cm resulted in significantly higher intercellular CO2 concentration (5.9-6.3%), transpiration rate (13.2-15.8%), stomatal conductance (55-59%), net photosynthetic rate (126-160%), and photosynthetically active radiation (PAR) interception (1.6-25.2%) over the existing conventional method (plant geometry 22.5 cm × continuous plant to plant spacing) of wheat cultivation. The lodging resistance capacity of both the lower and upper 3rd nodes was significantly higher in the SWI compared to other cultivation methods. Among different genotypes, HD 2967 demonstrated the highest recorded value for lodging resistance capacity, followed by HD 2851, HD 3086, and HD 2894. In addition, adoption of the SWI at 20 cm × 20 cm enhanced crop grain yield by 36.9-41.6%, and biological yield by 27.5-29.8%. Significantly higher soil dehydrogenase activity (12.06 µg TPF g-1 soil hr-1), arylsulfatase activity (82.8 µg p-nitro phenol g-1 soil hr-1), alkaline phosphatase activity (3.11 n moles ethylene g-1 soil hr-1), total polysaccharides, soil microbial biomass carbon, and soil chlorophyll content were also noted under SWI over conventional method of the production. Further, increased root volumes, surface root density and higher NPK uptake were recorded under SWI at 20×20 cm in comparison to rest of the treatments. Among the tested wheat genotypes, HD-2967 and HD-3086 had demonstrated notable increases in grain and biological yields, as well as improvements in the photosynthetically active radiation (PAR) and chlorophyll content. Therefore, adoption of SWI at 20 cm ×20 cm (square planting) with cultivars HD 2967 might be the best strategy for enhancing crop productivity and resource-use efficiency under the similar wheat growing conditions of India and similar agro-ecotypes of the globe.

Ultrasonic-assisted synthesis of CaCu3Ti4O12/reduced graphene oxide composites for enhanced photocatalytic degradation of pharmaceutical products: Ibuprofen and Ciprofloxacin.

The objective of this research is to create a highly effective approach for eliminating pollutants from the environment through the process of photocatalytic degradation. The study centers around the production of composites consisting of CaCu3Ti4O12 (CCTO) and reduced graphene oxide (rGO) using an ultrasonic-assisted method, with a focus on their capacity to degrade ibuprofen (IBF) and ciprofloxacin (CIP) via photodegradation. The impact of rGO on the structure, morphology, and optical properties of CCTO was inspected using XRD, FTIR, Raman, FESEM, XPS, BET, and UV-Vis. Morphology characterization showed that rGO particles were dispersed within the CCTO matrix without any specific chemical interaction between CCTO and C in the rGO. The BET analysis revealed that with increasing the amount of rGO in the composite, the specific surface area significantly increased compared to the CCTO standalone. Besides, increasing rGO resulted in a reduction in the optical bandgap energy to around 2.09 eV, makes it highly promising photocatalyst for environmental applications. The photodegradation of IBF and CIP was monitored using visible light irradiation. The results revealed that both components were degraded above 97% after 60 min. The photocatalyst showed an excellent reusability performance with a slight decrease after five runs to 93% photodegradation efficiency.

Antimicrobial peptide mimetic minimalistic approach leads to very short peptide amphiphiles-gold nanostructures for potent antibacterial activity.

Strategically controlling concentrations of lipid-conjugated L-tryptophan (vsPA) guides the self-assembly of nanostructures, transitioning from nanorods to fibres and culminating in spherical shapes. The resulting Peptide-Au hybrids, exhibiting size-controlled 1D, 2D, and 3D nanostructures, show potential in antibacterial applications. Their high biocompatibility, favourable surface area-to-volume ratio, and plasmonic properties contribute to their effectiveness against clinically relevant bacteria. This controlled approach not only yields diverse nanostructures but also holds promise for applications in antibacterial therapeutics.

Declining groundwater and its impacts along Ganga riverfronts using combined Sentinel-1, GRACE, water levels, and rainfall data.

The Indo-Gangetic Plains (IGP) in northern India are vast alluvial tracts with huge shallow aquifers, densely populated and agriculturally productive regions. In the last few decades, IGP has been facing water scarcity driven by erratic monsoon dynamics, anthropogenic activity, and hydroclimatic variability. In urban centers, continuous groundwater withdrawal leads to high stress, affecting surface deformation and a threat to buildings and infrastructures. An attempt has been made to explore the possible linkage and coupling between groundwater level, hydroclimatic variables, and subsidence in the Central Ganga Plains (CGP), in Varanasi metropolis using the combined multisensory multitemporal data, Sentinel-1 (2017-2023), GRACE (2003-2023), groundwater levels (1998-2023), and precipitation (2002-2023). Long-term hydrological response in the CGP shows continuous depletion (14.6 ± 5.6 mm/yr) in response to precipitation variability. Results show spatiotemporal variations between GWS, and precipitation estimate with nonlinear trend response due to associated inter-annual/inter-seasonal climate variability and anthropogenic water withdrawal, specifically during the observed drought years. The significant storage response in the urban center compared to a regional extent suggests the potential impact of exponentially increasing urbanization and building hydrological stress in the cities. The implications of reducing storage capacity show measured land subsidence (∼2-8 mm/yr) patterns developed along the meandering stretch of the Ganga riverfronts in Varanasi. The groundwater level data from the piezometric supports the hydroclimatic variables and subsidence coupling. Considering the vital link between water storage, food security, and socioeconomic growth, the results of this study require systematic inclusion in water management strategies as climate change seriously impacts water resources in the future.

Structural DNA nanotechnology at the nexus of next-generation bio-applications: challenges and perspectives.

DNA nanotechnology has significantly progressed in the last four decades, creating nucleic acid structures widely used in various biological applications. The structural flexibility, programmability, and multiform customization of DNA-based nanostructures make them ideal for creating structures of all sizes and shapes and multivalent drug delivery systems. Since then, DNA nanotechnology has advanced significantly, and numerous DNA nanostructures have been used in biology and other scientific disciplines. Despite the progress made in DNA nanotechnology, challenges still need to be addressed before DNA nanostructures can be widely used in biological interfaces. We can open the door for upcoming uses of DNA nanoparticles by tackling these issues and looking into new avenues. The historical development of various DNA nanomaterials has been thoroughly examined in this review, along with the underlying theoretical underpinnings, a summary of their applications in various fields, and an examination of the current roadblocks and potential future directions.

CA19-9 and CEA biosensors in pancreatic cancer.

Cancer is a complex pathophysiological condition causing millions of deaths each year. Early diagnosis is essential especially for pancreatic cancer. Existing diagnostic tools rely on circulating biomarkers such as Carbohydrate Antigen 19-9 (CA19-9) and Carcinoembryonic Antigen (CEA). Unfortunately, these markers are nonspecific and may be increased in a variety of disorders. Accordingly, diagnosis of pancreatic cancer generally involves more invasive approaches such as biopsy as well as imaging studies. Recent advances in biosensor technology have allowed the development of precise diagnostic tools having enhanced analytical sensitivity and specificity. Herein we examine these advances in the detection of cancer in general and in pancreatic cancer specifically. Furthermore, we highlight novel technologies in the measurement of CA19-9 and CEA and explore their future application in the early detection of pancreatic cancer.

Dynamics of land, ocean, and atmospheric parameters associated with Tauktae cyclone.

During the pre- and post-monsoon season, the eastern and western coasts are highly vulnerable to cyclones. The tropical cyclone "Tauktae" formed in the Arabian Sea on 14 May 2021 and moved along the west coast of India, and landfall occurred on 17 May 2021. During the cyclone, the maximum wind speed was 220 km/h with a pressure of 935 mb affecting meteorological, atmospheric parameters, and weather conditions of the northern and central parts of India causing devastating damage. Analysis of satellite, Argo, and ground data show pronounced changes in the oceanic, atmospheric, and meteorological parameters associated during the formation and landfall of the cyclone. During cyclone generation (before landfall), the air temperature (AT) was maximum (30.51 °C), and winds (220 km/h) were strong with negative omega values (0.3). The relative humidity (RH) and rainfall (RF) were observed to be higher at the location of the cyclone formation in the ocean and over the landfall location, with an average value of 81.28% and 21.45 mm/day, respectively. The concentration of total column ozone (TCO), CO volume mixing ratio (COVMR), H2O mass mixing ratio (H2O MMR), aerosol parameters (AOD, AE) and air quality parameter (PM) was increased over land and along the cyclone track, leading to a deterioration in the air quality. The strong wind mixes the air mass from the surroundings to the local anthropogenic emissions, and causing strong mixing of the aerosols. The detailed results show a pronounced change in the ocean, land, meteorological, and atmospheric parameters showing a strong land-ocean-atmosphere coupling associated with the cyclone.

Trends in the Use of Recombinant Activated Factor VII and Prothrombin Complex Concentrate in Heart Transplant Patients in Virginia.

OBJECTIVES: To explore trends in intraoperative procoagulant factor concentrate use in patients undergoing heart transplantation (HTx) in Virginia. Secondarily, to evaluate their association with postoperative thrombosis. DESIGN: Patients who underwent HTx were identified using a statewide database. Trends in off-label recombinant activated factor VII (rFVIIa) use and on-label and off-label prothrombin complex concentrate (PCC) use were tested using the Mantel-Haenszel test. Multivariate logistic regression was used to test for an association between procoagulant factor concentrate administration and thrombosis. SETTING: Virginia hospitals performing HTx. PARTICIPANTS: Adults undergoing HTx between 2012 and 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 899 patients who required HTx, 100 (11.1%) received off-label rFVIIa, 69 (7.7%) received on-label PCC, and 80 (8.9%) received off-label PCC. There was a downward trend in the use of rFVIIa over the 10-year period (p = 0.04). There was no trend in on-label PCC use (p = 0.12); however, there was an increase in off-label PCC use (p < 0.001). Patients who received rFVIIa were transfused more and had longer cardiopulmonary bypass time (p < 0.001). Receipt of rFVIIa was associated with increased thrombotic risk (odds ratio [OR] 1.92; 95% CI 1.12-3.29; p = 0.02), whereas on-label and off-label PCC use had no association with thrombosis (OR 0.98, 95% CI 0.49-1.96, p = 0.96 for on-label use; and OR 0.61, 95% CI 0.29-1.30, p = 0.20 for off-label use). CONCLUSIONS: Use of rFVIIa in HTx decreased over the past decade, whereas off-label PCC use increased. Receipt of rFVIIa was associated with thrombosis; however, patients who received rFVIIa were more severely ill, and risk adjustment may have been incomplete.

A Novel Hybrid Approach to Management of KD: Role of Robotic Surgery.

The management of Kommerell's Diverticulum (KD) has been evolving from open repair to a hybrid of open and endovascular repair. While there is no consensus regarding the optimal strategy, the need for less invasive treatment with less morbidity early recovery, and improved quality of life is a common goal for both the patient and the provider.

Hydrogenated TiO2 Carbon Support for PtRu Anode Catalyst in High-Performance Anion-Exchange Membrane Fuel Cells.

The availability of durable, high-performance electrocatalysts for the hydrogen oxidation reaction (HOR) is currently a constraint for anion-exchange membrane fuel cells (AEMFCs). Herein, a rapid microwave-assisted synthesis method is used to develop a core-shell catalyst support based on a hydrogenated TiO2 /carbon for PtRu nanoparticles (NPs). The hydrogenated TiO2 provides a strong metal-support interaction with the PtRu NPs, which improves the catalyst's oxophilicity and HOR activity compared to commercial PtRu/C and enables greater size control of the catalyst NPs. The as-synthesized PtRu/TiO2 /C-400 electrocatalyst exhibits respectable performance in an AEMFC operated at 80 °C, yielding the highest current density (up to 3× higher) within the catalytic region (compared at 0.80-0.90 V) and voltage efficiency (68%@ 0.5 A cm-2 ) values in the compared literature. In addition, the cell demonstrates promising short-term voltage stability with a minor voltage decay of 1.5 mV h-1 . This "first-of-its-kind in alkaline" work may open further research avenues to develop rapid synthesis methods to prepare advanced core-shell metal-oxide/carbon supports for electrocatalysts for use in the next-generation of AEMFCs with potential applicability to the broader electrochemical systems research community.

Spatio-temporal evolution of groundwater quality and its health risk assessment in Punjab (India) during 2000-2020.

The state known as the bread basket of India has now been defamed as the cancer capital of the country. The toxicity of groundwater associated with the declining water level is reported in recent years. However, an extensive temporal and spatial analysis is required to identify hotspots. In this study, spatial tools are utilized to understand the evolution of groundwater in Punjab (> 315 sites) for the last two decades (2000-2020) for drinking purposes using the water quality index (WQI). The data for pH, electric conductivity (EC), bicarbonate (HCO3¯), chloride (Cl¯), sulfate (SO42¯), nitrate (NO3¯), fluoride (F¯), calcium (Ca2+), magnesium (Mg2+), sodium (Na+), and potassium (K+) collected from the Central Groundwater Board (CGWB) were analyzed. The results show that the average cation abundance is in declining order of Na > Mg > Ca > K, and anion abundance is in order of HCO3¯ > SO42¯ > Cl¯ > NO3 > F. The ions are compared with water quality standards defined by BIS and WHO. The study shows that in the year 2000, 69.52% of locations are above the acceptable limit for EC, 68.89% for Mg2, 84.76% for Na+, 51.75% for HCO3¯, 38.41% for NO3¯, and 17.20% for F¯. While in the year 2020, 48.89% exceed the acceptable limit for EC, 57.78% for Mg2+, 68.25% for Na+, 34.92% for HCO3¯, 27.30% for NO3¯, and 8.88% for F¯. WQI shows that in the year 2000, 13.01% of sampling locations are categorized as very poor and 20% as unsuitable for drinking. Meanwhile, in 2020, 6.35% of locations are categorized as very poor and 12.38% as unsuitable for drinking in the study area. In addition to the effect on plant growth, consumption of contaminated water can adversely affect human health. The health hazards for F¯ (HQF) and NO3¯ (HQN) and their total health index (THI) are also evaluated that depicts 244 groundwater sampling sites in the year 2000, and 152 sampling sites in the year 2020 show high non-carcinogenic effects on adults, children, and infants. Southwestern Punjab is found to be the worst affected, while north-eastern regions drained by the Himalayan rivers show better quality water. Shifting in agricultural practices in the last two decades and declining water levels due to excess pumping of water from deeper water tables deteriorated the quality of water in the Southern region as observed from the geospatial analysis.

Sirolimus-Coated Balloon in an All-Comer Population of Coronary Artery Disease Patients: The EASTBOURNE Prospective Registry.

BACKGROUND: Drug-coated balloons (DCB) represent 1 of the most promising innovations in interventional cardiology and may represent a valid alternative to drug-eluting stents. Currently, some sirolimus-coated balloons (SCB) are being investigated for several coronary artery disease applications. OBJECTIVES: This study sought to understand the role of a novel SCB for the treatment of coronary artery disease. METHODS: EASTBOURNE (All-Comers Sirolimus-Coated Balloon European Registry) is a prospective, multicenter, investigator-driven clinical study that enrolled real-world patients treated with SCB. Primary endpoint was target lesion revascularization (TLR) at 12 months. Secondary endpoints were procedural success, myocardial infarction (MI), all-cause death, and major adverse clinical events (a composite of death, MI, and TLR). All adverse events were censored and adjudicated by an independent clinical events committee. RESULTS: A total population of 2,123 patients (2,440 lesions) was enrolled at 38 study centers in Europe and Asia. The average age was 66.6 ± 11.3 years, and diabetic patients were 41.5%. De novo lesions (small vessels) were 56%, in-stent restenosis (ISR) 44%, and bailout stenting occurred in 7.7% of the patients. After 12 months, TLR occurred in 5.9% of the lesions, major adverse clinical events in 9.9%, and spontaneous MI in 2.4% of the patients. The rates of cardiac/all-cause death were 1.5% and 2.5%, respectively. The primary outcome occurred more frequently in the ISR cohort (10.5% vs 2.0%; risk ratio: 1.90; 95% CI: 1.13-3.19). After multivariate Cox regression model, the main determinant for occurrence of the primary endpoint was ISR (OR: 5.5; 95% CI: 3.382-8.881). CONCLUSIONS: EASTBOURNE, the largest DCB study in the coronary field, shows the safety and efficacy of a novel SCB in a broad population of coronary artery disease including small vessels and ISR patients at mid-term follow-up. (The All-Comers Sirolimus-Coated Balloon European Registry [EASTBOURNE]; NCT03085823).

TRAF4-mediated nonproteolytic ubiquitination of androgen receptor promotes castration-resistant prostate cancer.

Castration-resistant prostate cancer (CRPC) poses a major clinical challenge with the androgen receptor (AR) remaining to be a critical oncogenic player. Several lines of evidence indicate that AR induces a distinct transcriptional program after androgen deprivation in CRPCs. However, the mechanism triggering AR binding to a distinct set of genomic loci in CRPC and how it promotes CRPC development remain unclear. We demonstrate here that atypical ubiquitination of AR mediated by an E3 ubiquitin ligase TRAF4 plays an important role in this process. TRAF4 is highly expressed in CRPCs and promotes CRPC development. It mediates K27-linked ubiquitination at the C-terminal tail of AR and increases its association with the pioneer factor FOXA1. Consequently, AR binds to a distinct set of genomic loci enriched with FOXA1- and HOXB13-binding motifs to drive different transcriptional programs including an olfactory transduction pathway. Through the surprising upregulation of olfactory receptor gene transcription, TRAF4 increases intracellular cAMP levels and boosts E2F transcription factor activity to promote cell proliferation under androgen deprivation conditions. Altogether, these findings reveal a posttranslational mechanism driving AR-regulated transcriptional reprogramming to provide survival advantages for prostate cancer cells under castration conditions.

Spatiotemporal dynamics of DNA nanocage uptake in zebrafish embryos for targeted tissue bioimaging applications.

Three-dimensional DNA nanocages have attracted significant attention for various biomedical applications including targeted bioimaging in vivo. Despite the numerous advantages, the use and in vivo exploration of DNA nanocages are limited as the cellular targeting and intracellular fate of these DNA nanocages within various model systems have not been explored well. Herein, using a zebrafish model system, we provide a detailed understanding of time-, tissue- and geometry-dependent DNA nanocage uptake in developing embryos and larvae. Of all the geometries tested, tetrahedrons showed significant internalization in 72 hours post-fertilized larvae upon exposure, without disturbing the expression of genes involved in embryo development. Our study provides a detailed understanding of the time and tissue-specific uptake of DNA nanocages in the zebrafish embryos and larvae. These findings will provide valuable insights into the internalization and biocompatible potential of DNA nanocages and will help to predict their candidature for biomedical applications.

An Isothiazolanthrone-Based Self-Assembling Anticancer Color-Changing Dye for Concurrent Imaging and Monitoring of Cell Viability.

We report the photophysical properties, self-assembly and biological evaluation of an isothiazolanthrone-based dye, 7-amino-6H-anthra[9,1-cd]isothiazol-6-one (AAT), which reveals anticancer properties and can be potentially used as dye for monitoring cell viability. The solvent-dependent photophysical studies suggest that the emission of AAT is sensitive to environment polarity due to which interesting changes in the colored emission may be observed owing to the charge transfer (CT) processes. AAT also self-assembles to tree-like branched morphologies and produce, a greenish emission inside the cells when imaged after short interval (15 mins) of incubation while a red fluorescence could be noted after 24 h. Interestingly, AAT also produce differential emission inside mouse normal cells as compared to its cancer cell lines since it possess anticancer activity. The experimental observations were also validated theoretically via computational modeling.

Primary graft dysfunction following lung transplantation: From pathogenesis to future frontiers.

Lung transplantation is the treatment of choice for patients with end-stage lung disease. Currently, just under 5000 lung transplants are performed worldwide annually. However, a major scourge leading to 90-d and 1-year mortality remains primary graft dysfunction. It is a spectrum of lung injury ranging from mild to severe depending on the level of hypoxaemia and lung injury post-transplant. This review aims to provide an in-depth analysis of the epidemiology, patho physiology, risk factors, outcomes, and future frontiers involved in mitigating primary graft dysfunction. The current diagnostic criteria are examined alongside changes from the previous definition. We also highlight the issues surrounding chronic lung allograft dysfunction and identify the novel therapies available for ex-vivo lung perfusion. Although primary graft dysfunction remains a significant contributor to 90-d and 1-year mortality, ongoing research and development abreast with current technological advancements have shed some light on the issue in pursuit of future diagnostic and therapeutic tools.