Category: Nevin Manimala

Proc Natl Acad Sci U S A. 2025 Jan 28;122(4):e2410227122. doi: 10.1073/pnas.2410227122. Epub 2025 Jan 23.

ABSTRACT

Social media is profoundly changing our society with its unprecedented spreading power. Due to the complexity of human behaviors and the diversity of massive messages, the information-spreading dynamics are complicated, and the reported mechanisms are different and even controversial. Based on data from mainstream social media platforms, including WeChat, Weibo, and Twitter, cumulatively encompassing a total of 7.45 billion users, we uncover a ubiquitous mechanism that the information-spreading dynamics are basically driven by the interplay of social reinforcement and social weakening effects. Accordingly, we propose a concise equation, which, surprisingly, can well describe all the empirical large-scale spreading trajectories. Our theory resolves a number of controversial claims and satisfactorily explains many phenomena previously observed. It also reveals that the highly clustered nature of social networks can lead to rapid and high-frequency information bursts with relatively small coverage per burst. This vital feature enables social media to have a high capacity and diversity for information dissemination, beneficial for its ecological development.

PMID:39847317 | DOI:10.1073/pnas.2410227122

Adv Ther. 2025 Jan 23. doi: 10.1007/s12325-024-03095-2. Online ahead of print.

ABSTRACT

INTRODUCTION: Fabry disease (FD) is a rare lysosomal storage disorder that is associated with pain and progressive damage to the renal, cardiac, and cerebrovascular systems. Enzyme replacement therapy (ERT) is one of the treatment options for FD and the most recently approved ERT agent, pegunigalsidase alfa, has shown clinical efficacy in three phase 3 clinical trials of adults with FD: BALANCE, BRIDGE, and BRIGHT. Recent published guidelines support the mapping of health utility state data to the EuroQol-5 Dimension-3 Level (EQ-5D-3L) index to align with the preferred methodology used by the National Institute for Health and Care Excellence (NICE). Therefore, the primary objective of this study was to estimate EQ-5D-3L values in clinical trials of pegunigalsidase alfa for FD for future cost-utility analyses.

METHODS: A mixed effects model was developed to predict values derived from EQ-5D-3L for the following health states used in cost-utility analyses: no Fabry clinical event (FCE)/no pain-related adverse event (AE), pain-related AE, cardiac FCE, cerebrovascular FCE, and renal FCE.

RESULTS: The baseline EQ-5D-3L utility value had a statistically significant (p < 0.0001) impact on utility values, whereas study, age, sex, disease type, treatment arm, kidney function, and serious AE were not statistically significant. Health state utility values with 95% confidence intervals (CI) for the final model were as follows: no FCE/no pain-related AE, 0.8005 (0.7675, 0.8334); pain-related AE, 0.7737 (0.7262, 0.8211); cardiac FCE, 0.7189 (0.6274, 0.8103); cerebrovascular FCE, 0.7923 (0.6633, 0.9212); and renal FCE, 0.6881 (0.3887, 0.9874).

CONCLUSIONS: The utility values generated by the present study are generally in line with EQ-5D values in the FD literature and can be used to inform both economic evaluations and our understanding of the impact that FD has on quality of life.

TRIAL REGISTRATION: NCT03018730, NCT02795676, NCT03180840.

PMID:39847314 | DOI:10.1007/s12325-024-03095-2

Bull Math Biol. 2025 Jan 23;87(2):32. doi: 10.1007/s11538-024-01403-z.

ABSTRACT

Using genetic data to infer evolutionary distances between molecular sequence pairs based on a Markov substitution model is a common procedure in phylogenetics, in particular for selecting a good starting tree to improve upon. Many evolutionary patterns can be accurately modelled using substitution models that are available in closed form, including the popular general time reversible model (GTR) for DNA data. For more complex biological phenomena, such as variations in lineage-specific evolutionary rates over time (heterotachy), other approaches such as the GTR with rate variation (GTR $+\Gamma$ ) are required, but do not admit analytical solutions and do not automatically allow for likelihood calculations crucial for Bayesian analysis. In this paper, we derive a hybrid approach between these two methods, incorporating $\Gamma (\alpha ,\alpha )$ -distributed rate variation and heterotachy into a hierarchical Bayesian GTR-style framework. Our approach is differentiable and amenable to both stochastic gradient descent for optimisation and Hamiltonian Markov chain Monte Carlo for Bayesian inference. We show the utility of our approach by studying hypotheses regarding the origins of the eukaryotic cell within the context of a universal tree of life and find evidence for a two-domain theory.

PMID:39847307 | DOI:10.1007/s11538-024-01403-z

Dokl Biochem Biophys. 2025 Jan 22. doi: 10.1134/S1607672924701230. Online ahead of print.

ABSTRACT

Creation and long-term in vitro maintenance of valuable genotype collection is one of the modern approach to conservation of valuable gene pool of woody plants. However, during prolonged cultivation, genetic variability of cells and tissues may accumulate and lead to the loss of valuable characteristics of parental plants. It is therefore important to assess the genetic (including cytogenetic) stability of collection clones. The purpose of this work was to study the karyotype features (number, ploidy level and chromosome size) of various willow clones (S. dasyclados Wimm., S. viminalis L., S. purpurea L., S. caspica Pall., х S. palustris Host.) under conditions of long-term in vitro storage. No such research has been conducted on willow so far. Nevertheless, there is evidence of significant influence of ploidy level on growth, productivity, and composition of wood for willow plants. Our study was based on the plants of five micropropagated willow clones rated as promising for plantation forestry. The plants used in the study were maintained in vitro for a long period (14 years) by rare subculturing (once in 5 months) on a hormone-free 1/2 WPM nutrient medium under standard cultivation conditions (25 ± 2°C, 16 h light/8 h dark, 2.0 klx). Throughout the entire in vitro cultivation period, the plants showed proper growth and development, high regeneration activity, and no visible signs of somaclonal variation. Willow is one of the rather difficult objects for karyotype analysis. The authors improved the method of preparation and analysis of specimens. During the long-term cultivation, the clones showed cytogenetic stability, maintaining the ploidy (2n = 2х = 38 or 2n = 4х = 76) and the mixoploid nature of the original plants. Data obtained gives an update on the sizes of chromosomes of clones with different ploidy. The absolute chromosome length for diploid clones varies from 0.8 to 2.1 μm; tetraploid, from 0.9 to 2.5 μm. There were no statistically significant differences in the average chromosome length between diploid and tetraploid clones. All studied willow clones during long-term (for 14 years) in vitro cultivation on a hormone-free nutrient media retain the karyotype of the respective species.

PMID:39847303 | DOI:10.1134/S1607672924701230

Dokl Biochem Biophys. 2025 Jan 22. doi: 10.1134/S1607672924701242. Online ahead of print.

ABSTRACT

The association of the pathogenesis of neurodegenerative diseases, depression, anxiety, and cognitive disorders with neurotrophin-3 deficiency determines the prospect of creating drugs with a similar mechanism of action. Since the use of full-length NT-3 is limited by unsatisfactory pharmacokinetic properties, the creation of low-molecular mimetics of neurotrophin-3 that are active when administered systemically is relevant. The Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies has created a dimeric dipeptide mimetic of the 4th loop of NT-3, hexamethylenediamide bis-(N-γ-oxybutyryl-L-glutamyl-L-asparagine) with the laboratory code GTS-302, which activates TrkC and TrkB receptors.

PURPOSE: The purpose of the work was to study the range of pharmacological activity of GTS-302.

MATERIALS AND METHODS: The pharmacological effects of GTS-302 were revealed by its intraperitoneal administration. The antidepressant-like activity of GTS-302 was studied in the forced swimming test on mice after its acute and 7-day administration. The anxiolytic and memory-enhancing activities of the dipeptide were studied, respectively, in the elevated plus maze on mice and in the novel object recognition test on rats after acute administration. The effect of GTS-302 on pain sensitivity was studied in the hot plate test on mice after acute administration.

RESULTS: It was found that GTS-302 exhibits antidepressant-like activity upon acute administration at doses of 0.5, 1.0, 5.0, and 10 mg/kg. At 7-day administration, the antidepressant-like activity of GTS-302 was more pronounced in terms of the effect expression and statistical significance. Dipeptide GTS-302 at doses of 1.0, 5.0, and 10.0 mg/kg exhibited anxiolytic and memory-enhancing activity and did not affect pain sensitivity.

CONCLUSIONS: The pharmacological spectrum of the low-molecular NT-3 mimetic dipeptide GTS-302, revealed during systemic administration, includes a number of neuropsychotropic effects characteristic of a full-size neurotrophin. This allows GTS-302 to be considered as a potential neuropsychotropic drug.

PMID:39847301 | DOI:10.1134/S1607672924701242

Neurogastroenterol Motil. 2025 Jan 23:e15002. doi: 10.1111/nmo.15002. Online ahead of print.

ABSTRACT

BACKGROUND: Proton pump inhibitors (PPI) for gastroesophageal reflux disease (GERD) are associated with a high failure rate. Our uncontrolled feasibility study aimed determining the effect of a transcutaneous electrical stimulation system (TESS) on GERD symptoms and acid exposure time (AET).

METHODS: Recruited patients with heartburn and regurgitation. During the first phase (one-week, run-in period, off-PPI’s), patients completed symptom diaries and demographic questionnaires. Thereafter, all patients underwent gastroscopy with subsequent placement of a wireless esophageal pH capsule, off-PPI. Based on pH analysis in the first 24 h, only those with increased AET (percent total time pH < 4 above 6%) continued to the next phase. During that phase, patients were treated for up to 3 weeks with TESS and documented their symptoms. The Primary endpoint was the magnitude of reduction in GERD-related symptoms. The secondary endpoints were the magnitude of reduction of AET and DeMeester score, as compared with their baseline values.

RESULTS: Included 31 patients and of those, 26 patients (42% females, aged 49 ± 15 years, mean BMI 25 ± 3 kg/m²) completed the first two phases of the study. At baseline, mean number of daily heartburn and regurgitation episodes was 2.55 ± 1.79 and 1.40 ± 1.73, respectively. Following TESS, mean number of daily heartburn and regurgitation episodes dropped to 0.77 ± 0.75 and 0.36 ± 0.8, respectively (p < 0.001). At base line, mean AET and DeMeester score were 12.4 ± 5.6 and 32.1 ± 12.7, respectively. Following TESS mean AET dropped to 6.0 ± 3.5 and DeMeester score dropped to 16.2 ± 8.2 (p < 0.001).

CONCLUSIONS: TESS is effective in reducing both symptoms and esophageal AET in GERD patients.

PMID:39846242 | DOI:10.1111/nmo.15002

ACR Open Rheumatol. 2025 Jan;7(1):e11778. doi: 10.1002/acr2.11778.

ABSTRACT

OBJECTIVE: Systemic lupus erythematosus (SLE) and Sjögren disease (SjD) are autoimmune diseases with significant female predominance. The prevalence of SLE is increased in Klinefelter syndrome (KS) compared with the general male population. Our study investigates the dose effects of extra X chromosomes on the development of SLE and SjD in KS and triple X syndrome compared with the general population.

METHODS: This multicenter, retrospective cohort study used TriNetX, a global federated research database. Using International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes, patients with a diagnosis of SLE or SjD in the general population, as well as those with SLE and SjD in KS (karyotype 47,XXY) and triple X syndrome (karyotype 47,XXX) from January 1, 2010, to January 1, 2024, were identified. Fisher’s exact test was used to calculate the relative risk of SLE and SjD in males with KS and females with triple X syndrome compared with the general population. The 95% confidence intervals (95% CI) were obtained with STATA statistical software.

RESULTS: A total of 113,748,373 patients were identified. The prevalence of SLE and SjD was 0.59% and 0.077%, respectively, in men, and 0.381% and 0.388% for SLE and SjD, respectively, in women. The male-to-female ratios for all ages were 1:6.4 for SLE and 1:5 for SjD. The prevalence of KS and triple X syndrome in the general population was 0.0017% and 0.0010%, respectively. Among patients with KS, the prevalence of SLE and SjD was both 0.5%. Among patients with triple X syndrome, the prevalence of SLE and SjD was 1.3% and 0.8%, respectively. SLE was 8.5-fold (95% CI 4.6-15.8) and SjD was 6.6-fold (95% CI 3.56-12.26) more common in KS compared with the general male population (P < 0.001 by Fisher’s exact test). SLE was 3.5-fold (95% CI 2.09-5.72) and SjD was 2.3-fold (95% CI 1.22-4.20) more common in triple X syndrome compared with the general female population (P < 0.001 and P < 0.05, respectively).

CONCLUSION: The extra X chromosome in KS and triple X syndrome appears to confer a nonproportional, synergistic dose effect on the development of SLE and SjD when compared with the general population.

PMID:39846238 | DOI:10.1002/acr2.11778

JMIR Form Res. 2025 Jan 10;9:e59937. doi: 10.2196/59937.

ABSTRACT

BACKGROUND: Verbal autopsy (VA) has been a crucial tool in ascertaining population-level cause of death (COD) estimates, specifically in countries where medical certification of COD is relatively limited. The World Health Organization has released an updated instrument (Verbal Autopsy Instrument 2022) that supports electronic data collection methods along with analytical software for assigning COD. This questionnaire encompasses the primary signs and symptoms associated with prevalent diseases across all age groups. Traditional methods have primarily involved paper-based questionnaires and physician-coded approaches for COD assignment, which is time-consuming and resource-intensive. Although computer-coded algorithms have advanced the COD assignment process, data collection in densely populated countries like India remains a logistical challenge.

OBJECTIVE: This study aimed to develop an Android-based mobile app specifically tailored for streamlining VA data collection by leveraging the existing Indian public health workforce. The app has been designed to integrate real-time data collection by frontline health workers and seamless data transmission and digital reporting of COD by physicians. This process aimed to enhance the efficiency and accuracy of COD assignment through VA.

METHODS: The app was developed using Android Studio, the primary integrated development environment for developing Android apps using Java. The front-end interface was developed using XML, while SQLite and MySQL were employed to streamline complete data storage on the local and server databases, respectively. The communication between the app and the server was facilitated through a PHP application programming interface to synchronize data from the local to the server database. The complete prototype was specifically built to reduce manual intervention and automate VA data collection.

RESULTS: The app was developed to align with the current Indian public health system for district-level COD estimation. By leveraging this mobile app, the average duration required for VA data collection to ascertainment of COD, which typically ranges from 6 to 8 months, is expected to decrease by approximately 80%, reducing it to about 1-2 months. Based on annual caseload projections, the smallest administrative public health unit, health and wellness centers, is anticipated to handle 35-40 VA cases annually, while medical officers at primary health centers are projected to manage 150-200 physician-certified VAs each year. The app’s data collection and transmission efficiency were further improved based on feedback from user and subject area experts.

CONCLUSIONS: The development of a unified mobile app could streamline the VA process, enabling the generation of accurate national and subnational COD estimates. This mobile app can be further piloted and scaled to different regions to integrate the automated VA model into the existing public health system for generating comprehensive mortality statistics in India.

PMID:39846203 | DOI:10.2196/59937

J Cereb Blood Flow Metab. 2025 Jan 23:271678X251314682. doi: 10.1177/0271678X251314682. Online ahead of print.

ABSTRACT

Zero echo time (zero-TE) pulse sequences provide a quiet and artifact-free alternative to conventional functional magnetic resonance imaging (fMRI) pulse sequences. The fast readouts (<1 ms) utilized in zero-TE fMRI produce an image contrast with negligible contributions from blood oxygenation level-dependent (BOLD) mechanisms, yet the zero-TE contrast is highly sensitive to brain function. However, the precise relationship between the zero-TE contrast and neuronal activity has not been determined. Therefore, we aimed to derive a function to model the temporal dynamics of the zero-TE fMRI signal in response to neuronal activity. Furthermore, we examined the correlation of zero-TE fMRI with neuronal activity across stimulation frequencies. To these ends, we performed simultaneous electrophysiological recordings and zero-TE fMRI in rats subjected to whisker stimulation. The presented impulse response function provides a basis for the statistical modeling of neuronal activity-induced changes in the zero-TE fMRI signal. The temporal characteristics of the zero-TE fMRI response were found to be consistent with the previously postulated non-BOLD hemodynamic origin of the functional contrast. The zero-TE fMRI signal was well predicted by electrophysiological recordings, although systematic stimulation-dependent residuals were also observed, suggesting nonlinearities in neurovascular coupling. We conclude that zero-TE fMRI provides a robust proxy for neuronal activity.

PMID:39846159 | DOI:10.1177/0271678X251314682

Circ Genom Precis Med. 2025 Jan 23:e004629. doi: 10.1161/CIRCGEN.124.004629. Online ahead of print.

ABSTRACT

BACKGROUND: Established risk models may not be applicable to patients at higher cardiovascular risk with a measured Lp(a) (lipoprotein[a]) level, a causal risk factor for atherosclerotic cardiovascular disease.

METHODS: This was a model development study. The data source was the Nashville Biosciences Lp(a) data set, which includes clinical data from the Vanderbilt University Health System. We included patients with an Lp(a) measured between 1989 and 2022 and who had at least 1 year of electronic health record data before measurement of an Lp(a) level. The end point of interest was time to first myocardial infarction, stroke/TIA, or coronary revascularization. A random survival forest model was derived and compared with a Cox proportional hazards model derived from traditional cardiovascular risk factors (ie, the variables used to estimate the Pooled Cohort Equations for the primary prevention population and the variables used to estimate the Second Manifestations of Arterial Disease and Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention scores for the secondary prevention population). Model discrimination was evaluated using Harrell C-index.

RESULTS: A total of 4369 patients were included in the study (49.5% were female, mean age was 51 [SD, 18] years, and mean Lp(a) level was 33.6 [38.6] mg/dL, of whom 23.7% had a prior cardiovascular event). The random survival forest model outperformed the traditional risk factor models in the test set (c-index, 0.82 [random forest] versus 0.69 [primary prevention] versus 0.80 [secondary prevention]). These results were similar when restricted to a primary prevention population and under various strategies to handle competing risk. A Cox proportional hazard model based on the top 25 variables from the random forest model had a c-index of 0.80.

CONCLUSIONS: A random survival forest model outperformed a model using traditional risk factors for predicting cardiovascular events in patients with a measured Lp(a) level.

PMID:39846157 | DOI:10.1161/CIRCGEN.124.004629