Bone turnover, areal BMD, and bone microarchitecture by second-generation high-resolution peripheral quantitative computed tomography in transfusion-dependent thalassemia.

Thalassemic osteopathy includes low bone mass and impaired bone microarchitecture. We aimed to evaluate the prevalence and determinants of bone quantity (osteoporosis) and quality (microarchitecture) in a cohort of adult patients with transfusion-dependent thalassemia (TDT). Patients with TDT (n = 63) and age- and BMI-matched controls (n = 63) were recruited in the study. Areal bone mineral density (BMD) was measured using DXA Hologic scanner. P1NP and ß-CTX were estimated by electrochemiluminescence assay. Bone geometry and volumetric BMD (vBMD) were estimated by second-generation high-resolution peripheral quantitative computed tomography. Bone turnover marker ß-CTX was significantly lower in the TDT group, but there was no difference in P1NP levels. Low bone mass (Z ≤ -2) was present in greater proportion of patients both at lumbar spine (LS) (54 vs 0%; p = .001) and femoral neck (FN) (33 vs 8%; p = .001). Hypogonadism was associated with low BMD at FN (OR 10.0; 95% CI, 1.2-86; p = .01) and low hemoglobin with low BMD at LS (OR 1.58; 95% CI, 0.96-2.60; p = .07). The mean trabecular bone score was also significantly lower in patients compared with controls (1.261 ± 0.072 vs 1.389 ± 0.058). Total, cortical and trabecular vBMD were significantly lower in cases than controls. The trabecular number and cortical thickness were significantly lower and trabecular separation higher in cases than controls. Adults with TDT have significantly lower areal, cortical and trabecular vBMD. The bone microarchitecture is also significantly impaired in terms of lower number and wider spacing of trabeculae as well as lower cortical thickness and area at both radius and tibia.

Comparative assessment of Brassica cultivars for genotypic variability in phytoremediation of soil exposed to lead (Pb) contamination.

The soil pollution caused with accretion of pollutant elements like lead (Pb) is the major environmental concern nowadays. Phytoremediation of contaminated soils using Brassica cultivars that act as hyperaccumulator plants for Pb emerges as an important technique for decontamination of Pb spiked soils. Therefore, pot study was carried out to compare the efficiency of three Brassica cultivars and select the most efficient cultivar for phytoremediation of Pb spiked soils. The experimental soil was contaminated with Pb applied @ 0, 125, 250, 500, 750, and 1,000 mg kg-1 soil. Our outcomes reflected that increased rates of Pb pollution in soil from 125 to 1,000 mg kg-1 soil resulted in decline of yield but enhanced the Pb acquisition of all Brassica cultivars. Comparison of cultivars indicated the highest biomass production (16.7 g pot-1), Pb acquisition (4,011.7 µg pot-1), contamination indices i.e., tolerance index (70.6), and bioaccumulation coefficient (17.03) by Brassica juncea produced thereby proving it as the most efficient cultivar for phytoremediation of Pb spiked soil.

Consumption of crops raised in Pb spiked soil resulted in impaired health of human beings through its entrance into the food chain. Choice of techniques for decontamination of Pb polluted soils poses a great challenge worldwide. Among different techniques phytoremediation i.e., use of hyper accumulator crops is the most economical and ecological approach for the decontamination of Pb spiked soils. Therefore, this study was conducted for evaluating the comparative efficacy of three Brassica cultivars for their Pb accumulation potential and pollution indices and select the most efficient cultivar for phytoremediation of Pb spiked soils.

The bubbly life and death of animal and plant milk foams.

Milk foams are fragile objects, readily prepared for frothy cappuccinos and lattes using bovine milk. However, evolving consumer preferences driven by health, climate change, veganism, and sustainability have created a substantial demand for creating frothy beverages using plant-based milk alternatives or plant milks. In this contribution, we characterize maximum foam volume and half-lifetime as metrics for foamability and foam stability and drainage kinetics of two animal milks (cow and goat) and compared them to those of the six most popular, commercially available plant milks: almond, oat, soy, pea, coconut, and rice. We used three set-ups: an electric frother with cold (10 °C) and hot (65 °C) settings to emulate the real-life application of creating foam for cappuccinos, a commercial device called a dynamic foam analyzer or DFA and fizzics-scope, a bespoke device we built. Fizzics-scope visualizes foam creation, evolution, and destruction using an extended prism-based imaging system facilitating the capture of spatiotemporal variation in foam microstructure over a broader range of heights and liquid fractions. Among the chosen eight milks, oat produces the longest-lasting foams, and rice has the lowest amount and stability of foam. Using the hot settings, animal milks produce more foam volume using an electric frother than the top three plant milks in terms of foamability (oat, pea, and soy). Using the cold settings, oat, soy, and almond outperform cow milk in terms of foam volume and lifetime for foams made with the frother and sparging. Most plant milks have higher viscosity due to added polysaccharide thickeners, and in some, lecithin and saponin can supplement globular proteins as emulsifiers. Our studies combining foam creation by frothing or sparging with imaging protocols to track global foam volume and local bubble size changes present opportunities for contrasting the physicochemical properties and functional attributes of animal and plant-based milk and ingredients for engineering better alternatives.

Effects of an 8-week intervention of anulom vilom pranayama combined with heartfulness meditation on psychological stress, autonomic function, inflammatory biomarkers, and oxidative stress in healthcare workers during COVID-19 pandemic: a randomized controlled trial.

OBJECTIVES: Health care workers were exposed to huge stress during COVID-19 pandemic affecting their physical and mental health. Practice of anulom vilom pranayama and heartfulness meditation (AVPHFN) can improve mental and physical health and counter stress. The present study explored the effect of 8-week AVPHFN intervention on autonomic functions, emotional stress, oxidative stress, and inflammation markers in the nurse group of health-care givers. METHODS: This was a randomized controlled trial where 50 nurses underwent AVPHFN and 50 participated as controls. At baseline and after 8 week intervention of AVPHFN anthropometric parameters, cardiovascular parameters, autonomic function including time and frequency domain parameters, biochemical parameters, and psychological stress using the questionnaire were assessed. RESULTS: Forty nurses in AVPHFN group and 46 in control group completed the study. AVPHFN intervention resulted in a significant reduction in cardiovascular parameters heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure and rate pressure product (p<0.001, p<0.001, p<0.001, p<0.001, and p<0.001, respectively), perceived stress score and depression, anxiety, and stress scale psychological variables of depression, and stress compared to the control group. Total power, ratio of low frequency to high frequency and change in successive normal sinus (NN) intervals exceeds 50 ms (p<0.01, p=0.05, and p<0.01 respectively) suggesting parasympathodominance due to higher vagal efferent activity. Serum cortisol, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha, interleukin (IL)-1, IL-6 and telomerase significantly decreased in AVPHFN group post intervention. CONCLUSIONS: Eighty-week intervention of AVPHFN improved psychophysiological, autonomic and biochemistry profile of nurse group of health-care workers. AVPHFN module may be beneficial for curtailing stress and improving well-being.

Assessment of amino acid charge states based on cryo-electron microscopy and molecular dynamics simulations of respiratory complex I.

The charge states of titratable amino acid residues play a key role in the function of membrane-bound bioenergetic proteins. However, determination of these charge states both through experimental and computational approaches is extremely challenging. Cryo-EM density maps can provide insights on the charge states of titratable amino acid residues. By performing classical atomistic molecular dynamics simulations on the high resolution cryo-EM structures of respiratory complex I from Yarrowia lipolytica, we analyze the conformational and charge states of a key acidic residue in its ND1 subunit, aspartic acid D203, which is also a mitochondrial disease mutation locus. We suggest that in the native state of respiratory complex I, D203 is negatively charged and maintains a stable hydrogen bond to a conserved arginine residue. Alternatively, upon conformational change in the turnover state of the enzyme, its sidechain attains a charge-neutral status. We discuss the implications of this analysis on the molecular mechanism of respiratory complex I.

Isolated tuberculosis of the patella mimicking as prepatellar bursitis.

Patellar tuberculosis (TB) is a rare manifestation of musculoskeletal tuberculosis, accounting for a small proportion of cases. This case report presents a detailed analysis of a female patient in her early 30s who presented with isolated TB of the patella without concurrent pulmonary involvement. The patient received antitubercular chemotherapy, consisting of a 4-month intensive phase followed by an 8-month continuation phase. This case report underscores the rarity and diagnostic complexities associated with patellar TB. The condition often presents with non-specific symptoms, often mimicking prepatellar bursitis, necessitating a high level of clinical suspicion, particularly in patients from the endemic areas. Radiographic imaging and histopathological examination play crucial roles in establishing an accurate diagnosis. Antitubercular chemotherapy forms the cornerstone of treatment while surgical intervention is reserved for cases of extensive bone destruction or treatment failure.

Radioactive elements in wastewater and potable water: Sources, effects, and methods of analysis and removal.

Radioactive effluents, originating from nuclear power plants, medical-nuclear applications, and various extraction industries worldwide, present a significant and dangerous contamination challenge. The concentrations of radioactive substances in wastewater, surface water, and potable water vary widely depending on the source and location. For example, cesium-137 levels in wastewater from nuclear facilities can range from 0.1 to 10 Bq/L, while tritium concentrations in surface water near nuclear plants can reach up to 100 Bq/L. Regulatory guidelines, like the maximum contaminant level of 0.185 Bq/L for combined radium-226 and radium-228 in drinking water, are critical for ensuring safety and environmental protection. Specifically, in Fukushima, Japan, cesium-137 levels in surface water range from 0.1 to 10 Bq/L due to the nuclear accident. In contrast, regions with natural uranium deposits, like parts of the United States, have reported radium-226 concentrations in potable water up to 1 Bq/L. These variations highlight the necessity for focused monitoring and evaluation to protect water quality and community health. Among various methods, Gamma spectrometry and inductively coupled plasma mass spectrometry are precise for radionuclide quantification, scintillation detectors, and ion exchange, and adsorption techniques efficiently remove radioactive substances from water. This critical review examines the sources, adverse effects, and analysis and remediation strategies for various radioactive elements in wastewater. By thoroughly evaluating the origins and potential dangers associated with radioactive effluents, this report emphasizes the urgent need for rigorous monitoring and effective treatment practices to maintain the integrity of water resources and ecosystems. PRACTITIONER POINTS: Comprehensive analysis of the radioactive elements frequently found in wastewater and drinking water. Assess the negative effects of radioactive elements in water systems. Examine the treatment methods used to eliminate radioactive pollutants from water sources. Outline effective methods and tactics for addressing and controlling radioactive contamination occurrences. Analyze the latest advancements in technology, regulatory enhancements, and optimal methods to guarantee the safety of drinking water and the sustainable handling of radioactive substances in wastewater.

Review on design of real-time posture monitoring system for the cervical region.

In cervical health, the Posture Monitoring System (PMS) employs sensors to capture and transmit posture data to the cloud via Wi-Fi. This systematic review examines wearable PMS devices for cervical posture, analysing their attributes, findings, and limitations. Using systematic literature analysis, related studies were collected from diverse databases concentrating on wearable cervical posture devices. The review analysed the outcomes of each neck posture and each monitor type on the CVA ratio based on PMS. However, limitations, such as small sample sizes, limited functions, and privacy concerns were noted across the devices. The findings underscore the importance of considering user comfort and data accuracy in designing and implementing wearable posture monitors. Future studies should also explore the integration of advanced technologies and user-centred design principles to develop more accurate and user-friendly devices.

For accurate diagnosis and prevention of cervical spondylosis, the review focuses on a survey of PMS in the cervical region. Here, research related to wearable monitoring devices regarding the cervical region is investigated. The major finding is the necessity for designing the PMS device with limited sensors, which effectively monitor the cervical region.

Surviving the stress: Understanding the molecular basis of plant adaptations and uncovering the role of mycorrhizal association in plant abiotic stresses.

Environmental stresses severely impair plant growth, resulting in significant crop yield and quality loss. Among various abiotic factors, salt and drought stresses are one of the major factors that affect the nutrients and water uptake by the plants, hence ultimately various physiological aspects of the plants that compromises crop yield. Continuous efforts have been made to investigate, dissect and improve plant adaptations at the molecular level in response to drought and salinity stresses. In this context, the plant beneficial microbiome presents in the rhizosphere, endosphere, and phyllosphere, also referred as second genomes of the plant is well known for its roles in plant adaptations. Exploration of beneficial interaction of fungi with host plants known as mycorrhizal association is one such special interaction that can facilitates the host plants adaptations. Mycorrhiza assist in alleviating the salinity and drought stresses of plants via redistributing the ion imbalance through translocation to different parts of the plants, as well as triggering oxidative machinery. Mycorrhiza association also regulates the level of various plant growth regulators, osmolytes and assists in acquiring minerals that are helpful in plant's adaptation against extreme environmental stresses. The current review examines the role of various plant growth regulators and plants' antioxidative systems, followed by mycorrhizal association during drought and salt stresses.

Innovative strategies for managing hallucinations by exploring effects of tDCS on source monitoring abilities.

This randomised, crossover, sham-controlled study explored the neural basis of source-monitoring, a crucial cognitive process implicated in schizophrenia. Left superior temporal gyrus (STG) and dorsolateral prefrontal cortex (DLPFC) were the key focus areas. Thirty participants without neurological or psychological disorders underwent offline sham and active tDCS sessions with specific electrode montage targeting the left STG and DLPFC. Source-monitoring tasks, reality monitoring (Hear-Imagine), internal source-monitoring (Say-Imagine), and external source monitoring (Virtual-Real) were administered. Paired t-test and estimation statistics was performed with Graphpad version 10.1.0. The Benjamini-Hochberg procedure was employed to control the false discovery rate in multiple hypothesis testing. A significant improvement in internal source monitoring tasks (p = 0.001, Cohen's d = 0.97) was observed, but reality monitoring tasks demonstrated moderate improvement (p = 0.02, Cohen's d = 0.44). The study provides insights into the neural mechanisms of source monitoring in healthy individuals and proposes tDCS as a therapeutic intervention, laying the foundation for future studies to refine tDCS protocols and develop individualized approaches to address source monitoring deficits in schizophrenia.

Effects of Wearing Personal Protective Equipment on Serum Cortisol Levels and Physiological Variables in Healthcare Workers: A Randomised Controlled Trial in a Simulated Pandemic Environment.

INTRODUCTION: The COVID-19 pandemic has necessitated the widespread use of personal protective equipment (PPE), particularly in high-risk environments. Full-body PPE is favoured for its comprehensive protection against the virus but poses challenges to the body's thermoregulatory system as it inhibits air exchange. This randomised trial was undertaken to investigate the effects of wearing a commonly used gown-type full-body PPE kit in a simulated environment. METHODS: Initially, 65 healthy males were recruited and randomly divided into two groups: a study group wearing a full-body PPE kit (gown-type, full-body PPE kit with trousers, a gown-type shirt with a hood, a shoe cover, an N95 face mask, and an optional face shield) and a control group without PPE. They remained seated for three hours while wearing the PPE kit. Room conditions mimicked non-air-conditioned hospital scenarios, with temperature and humidity recorded and ventilation provided through open doors and windows, along with ceiling fan cooling. Activities with minimal physical exertion were allowed, and access to the toilet was kept to a minimum. Subjects underwent assessments of heart rate, respiratory rate, temperature, blood pressure, heart rate variability (HRV), and blood samples for serum cortisol before donning the PPE kit and entering a simulated ICU/WARD environment and after doffing. RESULTS: A total of 60 participants completed the study (30 in each group). Compared to the controls, serum cortisol levels significantly increased in the PPE groups, and HRV data indicated increased sympathetic activity in the PPE group. CONCLUSION:  Wearing a full-body PPE kit (gown-type upper garment with trousers) was found to have a significant impact on cortisol levels and physiological variables in a simulated environment. This suggests that in situations like the COVID-19 pandemic that warrant the use of such PPE kits, appropriate measures should be taken to provide better thermal stability for maintaining the well-being of healthcare workers.

Dynamic duos: the building blocks of dimensional mechanics.

Mechanics studies the relationships between space, time, and matter. These relationships can be expressed in terms of the dimensions of length , time , and mass . Each dimension broadens the scope of mechanics. Historically, mechanics emerged from geometry, which considers quantities like lengths or areas, with dimensions of the form . With the Renaissance, quantities combining space and time were considered, like speed, acceleration and later diffusivity, all of the form . Eventually, mechanics reached its full potential by including "mass-carrying" quantities such as mass, force, momentum, energy, action, power, viscosity, etc. These standard mechanical quantities have dimensions of the form where x and y are integers. In this contribution, we show that, thanks to this dimensional structure, these mass-carrying quantities can be readily arranged into a table such that x and y increase along the row and column, respectively. Ratios of quantities in the same rows provide characteristic lengths, while those in the same columns yield characteristic times, encompassing a great variety of physical phenomena from atomic to astronomical scales. Most generally, we show that selecting duos of mechanical quantities that are neither on the same row nor column of the table yields dynamics, where one mechanical quantity is understood as impelling motion, while the other impedes it. The force and the mass are the prototypes of impelling and impeding factors, but many other duos are possible. We present examples from the physical and biological realms, including planetary motion, sedimentation, explosions, fluid flows, turbulence, diffusion, cell mechanics, capillary and gravity waves, and spreading, pinching, and coalescence of drops and bubbles. This review provides a novel synthesis revealing the power of scaling or dimensional analysis, to understand processes governed by the interplay of two mechanical quantities. This elementary decomposition of space, time and motion into pairs of mechanical factors is the foundation of "dimensional mechanics", a method that this review wishes to promote and advance. Pairs are the fundamental building blocks, but they are only a starting point. Beyond this simple world of mechanical duos, we envision a richer universe that beckons with an interplay of three, four, or more quantities, yielding multiple characteristic lengths, times, and kinematics. This review is complemented by online video lectures, which initiate a discussion on the elaborate interplay of two or more mechanical quantities.

Reduction of maillard browning in spray dried low-lactose milk powders due to protein polysaccharide interactions.

Lactose hydrolysed concentrated milk was prepared using ß-galactosidase enzyme (4.76U/mL) with a reaction period of 12 h at 4 °C. Addition of polysaccharides (5 % maltodextrin/ß-cyclodextrin) to concentrated milk either before or after lactose hydrolysis did not result in significant differences (p > 0.05) in degree of hydrolysis (% DH) of lactose and residual lactose content (%). Three different inlet temperatures (165 °C, 175 °C and 185 °C) were used for the preparation of powders which were later characterised based on physico-chemical and maillard browning characteristics. Moisture content, solubility and available lysine content of the powders decreased significantly, whereas, browning parameters i.e., browning index, 5-hydroxymethylfurfural, furosine content increased significantly (p < 0.05) with an increase in inlet air temperature. The powder was finally prepared with 5 % polysaccharide and an inlet air temperature of 185 °C which reduced maillard browning. Protein-polysaccharide interactions were identified using Fourier Transform infrared spectroscopy, fluorescence spectroscopy and determination of free amino groups in the powder samples. Maltodextrin and ß-cyclodextrin containing powder samples exhibited lower free amino groups and higher degree of graft value as compared to control sample which indicated protein-polysaccharide interactions. Results obtained from Fourier Transform infrared spectroscopy also confirmed strong protein-polysaccharide interactions, moreover a significant decrease in fluorescence intensity was also observed in the powder samples. These interactions between the proteins and polysaccharides reduced the maillard browning in powders.

Occurrence of Depression and its Association with Oral Health in Elderly People Living in Old Age Homes of Mathura.

Introduction: Depression can affect oral health as a result of neglecting oral hygiene procedures which leads to an increased risk of dental caries and periodontal disease. Aim: To determine relationship between oral health and depression among elder people residing in old age homes of Mathura city. Materials and Methods: The study was conducted among 500 subjects aged ≥60 years where dental condition, number of missing teeth, removable denture wearing, teeth mobility, periodontal condition, pocket depth, loss of attachment, and depression according to the Patient Health Questionnaire-9 scale were assessed. Results: Regression analysis showed a positive relationship of the PHQ-9 value with DMFT and MT. Conclusion: Among people aged 60 years and over, severity of depression increased with higher number of MT and DT.

Long-range electron proton coupling in respiratory complex I - insights from molecular simulations of the quinone chamber and antiporter-like subunits.

Respiratory complex I is a redox-driven proton pump. Several high-resolution structures of complex I have been determined providing important information about the putative proton transfer paths and conformational transitions that may occur during catalysis. However, how redox energy is coupled to the pumping of protons remains unclear. In this article, we review biochemical, structural and molecular simulation data on complex I and discuss several coupling models, including the key unresolved mechanistic questions. Focusing both on the quinone-reductase domain as well as the proton-pumping membrane-bound domain of complex I, we discuss a molecular mechanism of proton pumping that satisfies most experimental and theoretical constraints. We suggest that protonation reactions play an important role not only in catalysis, but also in the physiologically-relevant active/deactive transition of complex I.

Spatiotemporal mapping of nanotopography and thickness transitions of ultrathin foam films.

Freshly formed soap films, soap bubbles, or foam films display iridescent colors due to thin film interference that changes as squeeze flow drives drainage and a progressive decrease in film thickness. Ultrathin (thickness <100 nm) freestanding films of soft matter containing micelles, particles, polyelectrolyte-surfactant complexes, or other supramolecular structures or liquid crystalline phases display drainage via stratification. A fascinating array of thickness variations and transitions, including stepwise thinning and coexistence of thick-thin flat regions, arise in micellar foam films that undergo drainage via stratification. In this tutorial, we describe the IDIOM (interferometry digital imaging optical microscopy) protocols that combine the conventional interferometry principle with digital filtration and image analysis to obtain nanometer accuracy for thickness determination while having high spatial and temporal resolution. We provide fully executable image analysis codes and algorithms for the analysis of nanotopography and summarize some of the unique insights obtained for stratified micellar foam films.

Hole transport layer engineering in high performance quasi-2D perovskite blue light emitting diodes.

Quasi-2D perovskites have emerged as highly promising materials for application in perovskite light-emitting diodes (PeLEDs), garnering significant attention due to their outstanding semiconductor properties. These materials boast an inherent multi-quantum well structure that imparts a robust confinement effect, particularly advantageous for blue emission. However, the development of blue emitters utilizing quasi-2D perovskites encounters challenges, notably colour instability, multipeak emission, and suboptimal fluorescence yield. The hole transfer layer (HTL) on which the perovskite layer is deposited in PeLEDs further affects the performance and efficiency. In this review, we delve into the evolution of blue PeLEDs and elucidate the optical properties of quasi-2D perovskites with the primary focus on HTL materials. We explore different HTL materials like PEDOT:PSS, metal oxides, and conjugated polyelectrolytes as well as ionic liquids, and their role in enhancing the colour stability, minimizing interfacial defects and increasing the fluorescence yield. This review endeavours to provide a holistic perspective of the different HTLs and serve as a valuable reference for researchers navigating the realm of HTL engineering towards the realization of high-performance blue quasi-2D PeLEDs.

Development of a thin layer chromatography-based method to detect sorbitol presence in milk and its applicability in formalin preserved milk samples.

Sorbitol has been the new and emerging adulterant in dairy industry. The main aim of the study was to develop a method to detect sorbitol in milk, which is not affected by other sugars, polyols and formalin. Hence, a thin layer chromatographic (TLC) method was standardized to detect the sorbitol in milk. In the study 90 s duration for the impregnation of Silica gel 60F TLC plates with Cu- ions was found suitable to resolve sorbitol as a distinct spot. The standardized conditions were (1) developing solvent system consisting of n-propanol: ethyl acetate: water (7:1:2), (2) 0.5% of potassium permanganate in 0.1 M NaOH as color developing reagent. (3) Drying temperature (65°C/ 10 min.) after spraying the color developing reagent. The limit of detection was 0.2% of added sorbitol in milk. The standardized method could also detect the sorbitol in the presence of sucrose, glucose and polyols like mannitol and maltitol. In both cow and buffalo milk samples the standardized methodology performed well in detection of sorbitol. The method also performed well in sorbitol spiked formalin preserved milk samples. This method can be an alternative to the other methods involving costly equipment in detecting adulteration of milk with sorbitol.

Molecular basis of JAK2 activation in erythropoietin receptor and pathogenic JAK2 signaling.

Janus kinase 2 (JAK2) mediates type I/II cytokine receptor signaling, but JAK2 is also activated by somatic mutations that cause hematological malignancies by mechanisms that are still incompletely understood. Quantitative superresolution microscopy (qSMLM) showed that erythropoietin receptor (EpoR) exists as monomers and dimerizes upon Epo stimulation or through the predominant JAK2 pseudokinase domain mutations (V617F, K539L, and R683S). Crystallographic analysis complemented by kinase activity analysis and atomic-level simulations revealed distinct pseudokinase dimer interfaces and activation mechanisms for the mutants: JAK V617F activity is driven by dimerization, K539L involves both increased receptor dimerization and kinase activity, and R683S prevents autoinhibition and increases catalytic activity and drives JAK2 equilibrium toward activation state through a wild-type dimer interface. Artificial intelligence-guided modeling and simulations revealed that the pseudokinase mutations cause differences in the pathogenic full-length JAK2 dimers, particularly in the FERM-SH2 domains. A detailed molecular understanding of mutation-driven JAK2 hyperactivation may enable novel therapeutic approaches to selectively target pathogenic JAK2 signaling.