Nevin Manimala

Fam Cancer. 2025 Sep 5;24(4):70. doi: 10.1007/s10689-025-00494-4.

ABSTRACT

This study compares three hereditary colorectal cancer (CRC) registries-the Iranian Hereditary Colorectal Cancer Registry (IHCCR), the Singapore Polyposis Registry (SPR), and the University of Cape Town Familial CRC Registry-to illuminate diverse approaches to identification, management, and research across different healthcare systems. Each registry, while emphasizing patient diversity, employed unique strategies reflecting available resources and epidemiological contexts. The IHCCR, leveraging WES, revealed considerable genetic heterogeneity, including novel mutations. The SPR, a nationalized service, focused on structured surveillance and management of FAP and other polyposis syndromes, highlighting the challenges of cultural conservatism and limited public awareness. The UCT registry, initially concentrating on Lynch syndrome, expanded to encompass other hereditary CRC syndromes, revealing a high prevalence of these conditions within the South African population. All three registries encountered challenges related to access to genetic testing and early diagnosis. The registries’ combined experiences underscore the critical need for integrated, culturally sensitive strategies combining genetic testing, enhanced surveillance, and family-based management to improve outcomes for individuals and families affected by hereditary CRC. Future efforts should focus on addressing disparities in access to care and expanding research to improve understanding and management of this complex disease.

PMID:40911264 | DOI:10.1007/s10689-025-00494-4

Pharmacol Rep. 2025 Sep 5. doi: 10.1007/s43440-025-00784-9. Online ahead of print.

ABSTRACT

BACKGROUND: The isobolographic analysis is a gold standard in the assessment of interactions between drugs in experimental studies. Although some isobolographic approaches are available, the most popular methods to characterize drug-drug interactions are the log-probit method accompanied with statistical analysis of interactions (by Tallarida) and the method based on mass-action law using CompuSyn software (elaborated by Chou-Talalay-Martin). The aim of this study was to compare the results from these two isobolographic approaches.

METHODS: Two isobolographic methods (log-probit associated with Tallarida statistics and Chou-Talalay-Martin) were applied to analyze the interaction between two antiseizure medications – clonazepam and lamotrigine in the mouse maximal electroshock-induced seizure model.

RESULTS: Both isobolographic approaches confirmed that the combination of clonazepam with lamotrigine produced synergistic interaction and allowed for detailed characteristics of the interaction at various effect levels for the two-drug mixture. Calculation of the combination index values (at various effect levels) confirmed that synergy slightly decreased when the antiseizure effect increased (combination index values increased from 0.44 for 16% to 0.65 for 84%).

CONCLUSIONS: The log-probit method with statistical analysis of data (by Tallarida) was more subtle and precise in the assessment of the synergistic interaction, whereas the isobolographic analysis by Chou-Talalay-Martin offered more automatic options facilitating visualization of the interaction.

PMID:40911251 | DOI:10.1007/s43440-025-00784-9

J Mol Model. 2025 Sep 5;31(10):264. doi: 10.1007/s00894-025-06486-6.

ABSTRACT

CONTEXT: This study systematically investigates the growth mechanism of nitrogen-doped graphene in a plasma environment, with a particular focus on the effects of temperature and hydrogen radicals on its structural evolution. The results reveal that, at 3000 K, the formation of nitrogen-doped graphene proceeds through three stages: carbon chain elongation, cyclization, and subsequent condensation into planar structures. During this process, nitrogen atoms are gradually incorporated into the carbon network, forming various doping configurations such as pyridinic-N, pyrrolic-N, and graphitic-N. An increase in temperature accelerates the reaction kinetics and cluster growth, but concurrently reduces the stability of nitrogen incorporation. Hydrogen radicals play a dual role: they help maintain the planar structure and suppress the curling of carbon clusters; however, excessive hydrogen radicals compete for edge-active sites, thereby inhibiting nitrogen doping efficiency. This work provides deeper insight into the growth mechanism of nitrogen-doped graphene and offers theoretical guidance for its efficient and controllable synthesis.

METHODS: In this study, we employed molecular dynamics (MD) simulations using the LAMMPS software package combined with the ReaxFF reactive force field to systematically investigate the growth mechanism of nitrogen-doped graphene in a plasma environment, as well as the effects of temperature and hydrogen radicals on its structural evolution. All simulations were performed in the NVT ensemble with a time step of 0.1 fs and a total simulation duration of 15,000 ps. To reduce variability and enhance the reliability of the results, each simulation was carefully repeated three times under identical conditions for subsequent statistical analysis.

PMID:40911219 | DOI:10.1007/s00894-025-06486-6

Bull Math Biol. 2025 Sep 5;87(10):145. doi: 10.1007/s11538-025-01522-1.

ABSTRACT

Tree balance plays an important role in various research areas in phylogenetics and computer science. Typically, it is measured with the help of a balance index or imbalance index. There are more than 25 such indices available, recently surveyed in a book by Fischer et al. They are used to rank rooted binary trees on a scale from the most balanced to the least balanced. We show that a wide range of subtree-size based measures satisfying concavity and monotonicity conditions are minimized by the complete or greedy from the bottom (GFB) tree and maximized by the caterpillar tree, yielding an infinitely large family of distinct new imbalance indices. Answering an open question from the literature, we show that one such established measure, the $\hat{s}$ -shape statistic, has the GFB tree as its unique minimizer. We also provide an alternative characterization of GFB trees, showing that they are equivalent to complete trees, which arise in different contexts. We give asymptotic bounds on the expected $\hat{s}$ -shape statistic under the uniform and Yule-Harding distributions of trees, and answer questions for the related Q-shape statistic as well.

PMID:40911217 | DOI:10.1007/s11538-025-01522-1

J Math Biol. 2025 Sep 5;91(3):33. doi: 10.1007/s00285-025-02254-5.

ABSTRACT

Human movement plays a key role in spreading vector-borne diseases globally. Various spatial models of vector-borne diseases have been proposed and analyzed, mainly focusing on disease dynamics. In this paper, based on a multi-patch Ross-Macdonald model, we study the impact of host migration on the local and global host disease prevalences. Specifically, we find that the local disease prevalence of any patch is bounded by the minimum and maximum disease prevalences of all disconnected patches and establish a weak order-preserving property. For global disease prevalence, we derive its formula at both zero and infinite dispersal rates and compare them under certain conditions, and calculate the right derivative at no dispersal. In the case of two patches, we give two complete classifications of the model parameter space: one is to compare the host disease prevalences with and without host dispersal, and the other is to determine the monotonicity of host disease prevalence with respect to host dispersal rate. Numerical simulations confirm inconsistence between disease persistence and host disease prevalence, as well as between host prevalence and vector prevalence in response to host movement. In general, a more uneven distribution of hosts and vectors in a homogeneous environment leads to lower host prevalence but higher vector prevalence and stronger disease persistence.

PMID:40911201 | DOI:10.1007/s00285-025-02254-5

Equine Vet J. 2025 Sep 5. doi: 10.1111/evj.70091. Online ahead of print.

ABSTRACT

BACKGROUND: Superficial digital flexor tendon (SDFT) injuries cause progressive loss of its mechanical properties. Two-dimensional shear wave elastography (2D-SWE) provides information about tissue stiffness.

OBJECTIVE: To determine the feasibility, repeatability, and reproducibility of 2D-SWE of healthy and pathological forelimb SDFT.

STUDY DESIGN: Prospective observational cohort study.

METHODS: Horses were divided into a noninjured Group (H) and a Group with tendinopathy of the SDFT (P). 2D-SWE of both fore SDFTs was performed at three metacarpal levels (A, B, and C, from proximal to distal). Qualitative and quantitative assessments were performed by two operators, and interobserver agreement was calculated. Differences between Group H and P, and between the affected and unaffected limbs of Group P and with Group H were analysed. Statistical analysis was performed with SPSS IBM. Statistical significance was set for p < 0.05.

RESULTS: Thirty horses were enrolled (13 in Group H, 17 in Group P). Interobserver agreement was excellent to good. Qualitatively, in Group H, SDFT was from light to marked blue; in Group P, it appeared marked blue. Quantitatively, Group H had lower median mean shear wave velocity (SWV, m/s) and Young’s modulus (kPa) at levels B and C (SWV: 8.19 and 8.27 m/s vs. 8.47 and 8.48 m/s; Young’s modulus: 299.21 and 204 kPa vs. 216.03 and 214.44 kPa). In longitudinal scans, the unaffected limbs of Group P were different from the affected limb and from Group H at level B and in the transverse scan. The affected limbs of Group P were different from Group H in the transverse scan at levels B and C.

MAIN LIMITATIONS: Low sample size, examination of naturally occurring lesions, observational nature.

CONCLUSIONS: 2D-SWE is feasible as a supplementary diagnostic method for detecting SDFT tendinopathies. Clinically healthy SDFTs exhibit lower SWV and Young’s modulus values, suggesting less stiffness.

PMID:40910344 | DOI:10.1111/evj.70091

J Biol Dyn. 2025 Dec;19(1):2552730. doi: 10.1080/17513758.2025.2552730. Epub 2025 Sep 5.

ABSTRACT

The fear preoften leads to changes in the physiological characteristics of the prey. Different stages of prey exhibit different physiological behaviours, such as susceptibility to predator risk, which often leads to Allee effect. Taking into account the influence of these factors, a modified Leslie-Gower predator-prey model with Allee effect and stage structure is constructed in this paper. By use of variational technique and normal form theory, the criteria assuring the appearance of transcritical bifurcation, saddle-node bifurcation, Hopf bifurcation and its direction are all established. Specially, such codimension 2 bifurcations as Bautin bifurcation and Bogdanov-Takens bifurcation are presented. The bubble phenomenon and bistability are detected. All theoretical findings are verified by numerical examples. The biological effects of fear level, Allee effect and stage structure on system stability are analysed.

PMID:40910340 | DOI:10.1080/17513758.2025.2552730

Can J Urol. 2025 Aug 29;32(4):359-366. doi: 10.32604/cju.2025.066470.

ABSTRACT

BACKGROUND: The COVID-19 pandemic disrupted healthcare systems globally, raising concerns about delayed cancer diagnosis and treatment. In France, transurethral resection of bladder tumors (TURBT) was prioritized in national urology guidelines to ensure the timely management of urothelial carcinoma. This study aimed to assess the impact of care reorganization on tumor staging, recurrence, palliative care, and mortality in bladder cancer patients from the pre-pandemic through late-pandemic periods.

METHODS: We conducted a retrospective multicenter study including all patients who underwent TURBT with histologically confirmed urothelial carcinoma between April and December of 2019 (pre-pandemic), 2020 (early pandemic), 2021 (mid-pandemic), and 2022 (late pandemic) in two French institutions. TURBT indications were categorized as diagnostic, palliative, or staging. Clinical and pathological data were compared across the four periods. Statistical analyses included Chi-square tests, Estimated Annual Percentage Change (EAPC), and multivariable logistic regression adjusted for age, sex, ASA score, and center.

RESULTS: A total of 790 TURBT procedures were analyzed. The proportion of muscle-invasive bladder cancer (pT ≥ 2) declined over time (18.7% in 2019 to 13.2% in 2022; p = 0.63), while superficial tumors (pTa) increased (57.2% to 65.5%). All-cause mortality significantly decreased from 38.0% in 2019 to 22.0% in 2020, 20.5% in 2021, and 19.5% in 2022 (p = 0.006). EAPC showed a significant annual decline in mortality (-24.3%, p = 0.004). In multivariable analysis, 2020, 2021, and 2022 were each associated with significantly lower odds of mortality compared to 2019. Recurrence rates remained stable across all periods (p = 0.93). Inter-hospital variation persisted in mortality and recurrence.

CONCLUSIONS: Despite the pandemic, urothelial bladder cancer outcomes did not worsen through 2022. On the contrary, timely reorganization, prioritization of TURBT, and triage strategies were associated with reduced mortality and palliative care needs, highlighting the resilience of cancer care when guided by adaptive health policies.

PMID:40910335 | DOI:10.32604/cju.2025.066470

Can J Urol. 2025 Aug 29;32(4):309-315. doi: 10.32604/cju.2025.063408.

ABSTRACT

BACKGROUND: Radical prostatectomy has long been the treatment of choice for men with clinically significant prostate cancer (PCa) in those with concurrent significant lower urinary tract symptoms (LUTS). For men who meet this description with marked prostatomegaly, we present a multi-institutional proof of concept study describing an alternative pathway of robotic simple prostatectomy (RASP) followed by external beam radiation therapy (EBRT) for the treatment of clinically significant prostate cancer.

METHODS: A retrospective study was performed of 17 patients with PCa who underwent RASP followed by EBRT at two institutions from 2015-2023. Demographic, peri-operative, and post-radiation treatment functional outcomes are reported.

RESULTS: No postoperative or post-EBRT complications were reported for any of the 17 patients who underwent RASP followed by EBRT during a median follow-up time of 12 months. The median time from RASP to EBRT was 9 months. Median prostate size was 135 g (IQR 110-165). 13 (76.5%) patients received a pre-EBRT rectal spacer. Median IPSS score preoperatively improved at 90 days post-RASP (13.5 vs. 2.5; IQR 10.8-15.2), and this benefit was sustained post-EBRT with a median IPSS at 3 vs. 12 months (4 vs. 0; IQR 0-5). There was no statistically significant difference between postoperative IPSS and post-EBRT IPSS at 3 (p = 0.677) or 12 (p = 0.627) months. In all 14 patients with localized disease and PSA data, none had recurrence during the study period.

CONCLUSIONS: A subset of patients with clinically significant prostate cancer have marked prostatomegaly and LUTS. We report an alternative treatment approach for patients unwilling to undergo radical prostatectomy. We found robotic simple prostatectomy followed by definitive radiation to be feasible and safe.

PMID:40910328 | DOI:10.32604/cju.2025.063408

Can J Urol. 2025 Aug 29;32(4):299-308. doi: 10.32604/cju.2025.064827.

ABSTRACT

OBJECTIVES: Benign prostatic hyperplasia (BPH) is a common benign tumor in men, with an age-related prevalence of multifactorial etiology. The present study aimed to accurately assess and predict the effect of co-existing metabolic syndrome (MtS) upon treatment outcomes of combination medical therapy in select patients of lower urinary tract symptoms (LUTS) due to BPH.

METHODS: After obtaining informed consent from the patients, 70 eligible patients with LUTS due to BPH with and without MtS were enrolled in this study from September 2022 to January 2024 from the outpatient clinic at the University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi and were treated with a combination of Tamsulosin and Dutasteride, for two months, as per the protocol. The outcomes measured were a change in the International Prostate Symptom Score (IPSS), mean flow rate (MFR), and peak urine flow (Qmax) rates. Data was analysed using SPSS version 23.

RESULTS: The reduction in IPSS was higher in the control group than in the case group (p < 0.001), and the difference in MFR between the groups was also statistically significant (p < 0.001). Although there was a significant change in Qmax in both groups, the difference in the improvement in Qmax between the two groups was not significant (p < 0.829). The control group appeared to have achieved better symptomatic relief after treatment than did the case group.

CONCLUSION: Metabolic syndrome had a negative adverse impact on medical treatment outcomes in selected patients of LUTS due to BPH. The study suggests that urologists should actively consider and appropriately counsel patients with LUTS-BPH and co-existing metabolic syndrome before selecting such patients for combination medical therapy.

PMID:40910327 | DOI:10.32604/cju.2025.064827