Nevin Manimala

J Cancer Res Clin Oncol. 2025 Sep 10;151(9):253. doi: 10.1007/s00432-025-06295-7.

ABSTRACT

PURPOSE: Next-generation sequencing (NGS) has revolutionized cancer treatment by enabling comprehensive cancer genomic profiling (CGP) to guide genotype-directed therapies. While several prospective trials have demonstrated varying outcomes with CGP in patients with advanced solid tumors, its clinical utility in colorectal cancer (CRC) remains to be evaluated.

METHODS: We conducted a prospective observational study of CGP in our hospital between September 2019 and March 2024. Overall survival (OS) of the patients who received CGP-based therapy and those did not was compared, and genomic variables associated with OS were evaluated.

RESULTS: A total of 100 patients with CRC underwent CGP using four platforms. The median patient age was 67 years, and most had a good performance status. The most frequent genomic alterations were TP53 (82%), APC (82%), and KRAS (55%). Actionable mutations such as ERBB2 amplification and BRAF V600E were identified in some patients, and 9% received CGP-based therapy, including immune checkpoint inhibitors for tumor mutational burden-high or microsatellite instability-high tumors. Patients receiving CGP-based therapy had longer OS from expert panel discussion (16.0 vs. 10.8 months) compared to those who did not. Alterations in TP53, SMAD4, and NF1 were associated with worse OS. Interestingly, PTEN mutations were linked to improved survival. TP53 alterations were more common in left-sided CRC.

CONCLUSION: Although some patients with CRC received CGP-guided therapy, a statistically significant survival benefit was not observed. However, TP53 and SMAD4 mutations were identified as negative prognostic markers, indicating their potential as targets for future drug development.

PMID:40931253 | DOI:10.1007/s00432-025-06295-7

J Relig Health. 2025 Sep 10. doi: 10.1007/s10943-025-02445-w. Online ahead of print.

ABSTRACT

The study was conducted to investigate the religious coping and psychological resilience levels of women survivors of the earthquake living in temporary shelters after the devastating earthquakes that struck southern and eastern Turkey in 2023. In this cross-sectional study conducted between July 24, 2024, and September 24, 2024, 386 women living in a temporary shelter in a province in the eastern part of Turkey were included. Data were collected using the Personal Information Form, Religious Coping Scale, and Brief Resilience Scale. In the analysis of the data, descriptive statistics, independent samples t test, Mann-Whitney U test, ANOVA test, Kruskal-Wallis test, and Pearson correlation test were used. The findings indicated that statistically significant differences were determined between the scores the participating women obtained from the overall Positive Religious Coping Subscale of the Religious Coping Scale in terms of the variables such as age, education level, marital status, perceived income level, having living children, presence of a chronic disease, their views on the disaster they were struck by, and their perspectives on the future after the earthquake (p < .05). Statistically significant differences were determined between the scores the participating women obtained from the overall Brief Resilience Scale in terms of the variables such as post-earthquake changes in their sleep pattern and future perspectives (p < .05). There was a statistically significant weak negative relationship between the mean scores the participating women obtained from the Negative Religious Coping subscale of the Religious Coping Scale and the mean scores they obtained from the Brief Resilience Scale (p < .05). The participating women’s psychological resilience levels decreased as their negative religious coping levels increased.

PMID:40931237 | DOI:10.1007/s10943-025-02445-w

AAPS PharmSciTech. 2025 Sep 10;26(7):226. doi: 10.1208/s12249-025-03220-6.

ABSTRACT

The chimpanzee adenovirus-vectored vaccine developed by the University of Oxford (ChAdOx1 nCoV-19) showed good stability when stored in refrigerator. However, the vaccine manufacturer prefers its transportation in frozen condition. Data regarding the stability of the vaccine after exposure to repeated freezing processes have not been explored yet. In the present study, different batches were exposed to 3 repeated freezing/thawing cycles. An orthogonal testing using various techniques was employed to assess any induced changes in the properties of the vaccine in comparison with control samples. Physicochemical properties, including appearance, pH, and molecular size distribution by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) were evaluated. Anion-exchange chromatography (AEC) was used for the determination of virus particles, and DNA to-protein ratio to study the biochemical attributes of the vaccine. Furthermore, the immunological properties were evaluated employing in-vivo test to compare the results obtained by the testing protocol to the vaccine efficiency in animals. Results revealed that the physicochemical attributes of the vaccine were not affected by the applied freeze-thaw cycles. Although the virus particles measured for thawed samples by AEC were below the specified limits of 0.7 – 1.3 × 10¹¹ VP/mL, the values of DNA to protein ratio remained unaffected (1.1 – 1.5), and there was no reduction in the in vivo potency of the tested samples. Statistical analysis of the results of the quantitative tests implied that the vaccine could withstand up to three successive freezing and thawing cycles during transportation without significant loss in its structural integrity and biological potency.

PMID:40931216 | DOI:10.1208/s12249-025-03220-6

Cancer Immunol Immunother. 2025 Sep 11;74(10):303. doi: 10.1007/s00262-025-04168-z.

ABSTRACT

BACKGROUND: Previous studies indicated that over-dissection of lymph nodes might impair the efficacy of immunotherapy. This study aims to explore the prognostic value of ypN + status and the impact of lymph node dissection (LND) on survival after neoadjuvant immunochemotherapy (NICT) for esophageal squamous cell cancer (ESCC).

METHODS: This double-center retrospective study enrolled 206 consecutive ESCC patients who underwent NICT followed by esophagectomy between 2018 and 2024. Overall survival (OS) and disease-free survival (DFS) were compared based on ypN/ypT status and LND count. Cutoff values for LND were determined by restricted cubic spline (RCS) analysis based on Cox regression models.

RESULTS: ypN + status was significantly associated with worse OS (3-year OS: 69.3% vs. 92.8%, p = 0.0063) and DFS (3-year DFS: 52.4% vs. 85.3%, p < 0.001) compared to ypN0. Multivariate Cox analysis confirmed ypN status (ypN2: OS HR = 8.510, p < 0.001; DFS HR = 8.162, p < 0.001. ypN3 DFS HR = 18.82, p = 0.001) as a stronger independent prognostic factor than ypT status. RCS curves identified the cutoff values of 32 and 48 for LND. Patients with 32 < LND ≤ 48 had the best OS and DFS. LND > 48 was associated with significantly worse OS (p = 0.033) and DFS (p = 0.025) compared to 32 < LND ≤ 48. Although not statistically significant, the LND > 48 group had higher rates of total complications (52.3% vs. 42.6%; p = 0.330).

CONCLUSIONS: ypN status is a more powerful prognostic factor than ypT status in ESCC patients treated with NICT and surgery. LND exceeding 48 nodes is associated with diminished survival. An optimal LND range of 32 to 48 nodes is recommended to balance accurate staging, therapeutic benefit, and preservation of immune function.

PMID:40931207 | DOI:10.1007/s00262-025-04168-z

J Math Biol. 2025 Sep 10;91(4):35. doi: 10.1007/s00285-025-02275-0.

ABSTRACT

It has been noticed that when the waiting time distribution exhibits a transition from an intermediate time power-law decay to a long-time exponential decay in the continuous time random walk model, a transition from anomalous diffusion to normal diffusion can be observed at the population level. However, the mechanism behind the transition of waiting time distribution is rarely studied. In this paper, we provide one possible mechanism to explain the origin of such a transition. A stochastic model terminated by a state-dependent Poisson clock is studied by a formal asymptotic analysis for the time evolutionary equation of its probability density function (PDF). The waiting time behavior under a more relaxed setting can be rigorously characterized by probability tools. Both approaches show the transition phenomenon of the waiting time T, which is complemented by particle simulations to shed light on the transition time scale. Our results indicate that small drift relative to noise in the state equation and a stiff response in the Poisson rate are crucial to the transitional phenomena.

PMID:40931200 | DOI:10.1007/s00285-025-02275-0

Nature. 2025 Sep;645(8080):341-347. doi: 10.1038/s41586-025-09475-0. Epub 2025 Sep 10.

ABSTRACT

Quantum simulations of many-body systems are among the most promising applications of quantum computers¹. In particular, models based on strongly correlated fermions are central to our understanding of quantum chemistry and materials problems², and can lead to exotic, topological phases of matter^3,4. However, owing to the non-local nature of fermions, such models are challenging to simulate with qubit devices⁵. Here we realize a digital quantum simulation architecture for two-dimensional fermionic systems based on reconfigurable atom arrays⁶. We utilize a fermion-to-qubit mapping based on Kitaev’s model on a honeycomb lattice³, in which fermionic statistics are encoded using long-range entangled states⁷. We prepare these states efficiently using measurement⁸ and feedforward⁹, realize subsequent fermionic evolution through Floquet engineering^10,11 with tunable entangling gates¹² interspersed with atom rearrangement, and improve results with built-in error detection. Leveraging this fermion description of the Kitaev spin model, we efficiently prepare topological states across its complex phase diagram¹³ and verify the non-Abelian spin-liquid phase³ by evaluating an odd Chern number^14,15. We further explore this two-dimensional fermion system by realizing tunable dynamics and directly probing fermion exchange statistics. Finally, we simulate strong interactions and study the dynamics of the Fermi-Hubbard model on a square lattice. These results pave the way for digital quantum simulations of complex fermionic systems for materials science, chemistry¹⁶ and high-energy physics¹⁷.

PMID:40931156 | DOI:10.1038/s41586-025-09475-0

Aesthetic Plast Surg. 2025 Sep 10. doi: 10.1007/s00266-025-05205-z. Online ahead of print.

ABSTRACT

BACKGROUND: Microfocused ultrasound (MFU) is a non-invasive technique used for facial rejuvenation, yet there is limited quantitative data on its long-term effects. This study aimed to evaluate the long-term efficacy and safety of MFU for facial rejuvenation. We utilized standardized photography along with advanced skin assessment technologies to analyze the impact of MFU on facial morphology, skin function, and patient satisfaction over a 12-month period.

METHODS: A prospective clinical study was conducted on 28 healthy female subjects (age range: 33-55 years) who underwent a single MFU treatment. Comprehensive assessments were performed at baseline and at seven follow-up time points (30 minutes, 1 week, 1 month, 3 months, 6 months, 9 months, and 12 months). Objective measurements included facial volumetric changes nasolabial fold morphology, skin physical parameters, and clinical aesthetic scores. Patient satisfaction and safety data were also collected.

STATISTICAL ANALYSIS: Longitudinal data were analyzed using linear mixed-effects models with subject-specific random intercepts to account for repeated measurements.

RESULTS: Facial volume showed significant immediate increase (5.65 ± 2.15 ml, 95% CI: 4.821-6.486, CV=37.98%, P < 0.001, Cohen’s d = 2.633) post-treatment, followed by progressive tightening, with maximum volume reduction at 3 months (- 3.37 ± 4.79 ml, 95% CI: – 5.227 to – 1.511, CV=142.26%, P < 0.001, Cohen’s d = – 0.703). Both facial and submental regions maintained statistically significant volume reduction through 12 months: Facial region: – 1.86 ± 4.72 ml (P = 0.048, Cohen’s d = – 0.39); Submental region: – 1.26±2.22 ml (95% CI: – 2.118 to – 0.394, P < 0.05, Cohen’s d = – 0.565),with the submental region demonstrating superior durability. The nasolabial fold region, volume, and maximum depth demonstrated the greatest improvement at 3 months (depth reduction: 0.28 ± 0.08 mm, p < 0.001), with ‘wide-short’ morphological subtypes exhibiting superior efficacy compared to ‘narrow-long’ subtypes (P < 0.05). Skin ultrasound collagen intensity showed progressive improvements, peaking at 9 months ( + 10.08 a.u., 95% CI: 7.73-12.44, P < 0.001, Cohen’s d = 1.54) and remained significantly elevated at 12 months with a 9.03 a.u. increase (95% CI: 6.49 to 11.58, P < 0.001, Cohen’s d = 1.38). Treatment induced significant, sustained increases in skin hydration (mean + 50.5-55.8 μS; p < 0.05; Cohen’s d 0.79-1.06) from 30 minutes through 6 months, with effects becoming non-significant at 9 months (+ 36.4 μS) and returning to baseline by 12 months. Transepidermal water loss (TEWL) decreased significantly from 1 month through 9 months, with peak improvement at 6 months (- 3.05 g/m²/h, 95% CI: – 5.39 to – 0.71, P < 0.05, Cohen’s d = – 0.54). GAIS scores peaked at 3 months (physician rating: 3.48 ± 0.48; patient rating: 3.75 ± 0.44) with strong inter-rater correlation (r = 0.728, P < 0.001) and 89.2% of patients willing to undergo retreatment. Adverse events were mild and transient, limited to erythema (67.9%) and edema (28.6%) resolving within one week.

CONCLUSION: MFU facial rejuvenation demonstrated a time-dependent efficacy profile, with peak improvements observed at 3 months and substantial benefits maintained at 9-12 months. Treatment response varied anatomically, showing most durable submental improvement. Nasolabial fold morphological subtypes significantly influenced efficacy, with ‘wide-short’ morphology correlating with superior outcomes. The procedure provided significant rejuvenation with minimal downtime, high patient satisfaction and an excellent safety profile. Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Trial Registrations This trial is registered with ChiCTR2400093439 (China) and NCT06286384 (ClinicalTrials.gov).

PMID:40931143 | DOI:10.1007/s00266-025-05205-z

Eur Spine J. 2025 Sep 11. doi: 10.1007/s00586-025-09347-1. Online ahead of print.

NO ABSTRACT

PMID:40931134 | DOI:10.1007/s00586-025-09347-1

Eur Spine J. 2025 Sep 11. doi: 10.1007/s00586-025-09358-y. Online ahead of print.

ABSTRACT

PURPOSE: This study aims to assess the outcomes of combining oblique lumbar interbody fusion (OLIF) with anterolateral screw fixation (ASF) and stress endplate augmentation (SEA) in comparison to OLIF combined with pedicle screw fixation (PSF) for the treatment of degenerative lumbar spinal stenosis (DLSS) in patients with osteoporosis (OP).

METHODS: We performed a retrospective analysis of patients diagnosed with DLSS who underwent OLIF in conjunction with either SEA and ASF (SEA-ASF group) or PSF (PSF group). Clinical outcomes, including the visual analog scale (VAS) scores for lumbar and leg pain, as well as the Oswestry Disability Index (ODI), were assessed at various postoperative intervals and compared to preoperative values. Additionally, radiographic outcomes such as disc height (DH), lumbar lordosis (LL), segmental lordosis (SL), cage subsidence (CS), and fusion rate were evaluated at different postoperative intervals and compared to their preoperative measurements.

RESULTS: A total of 65 patients were enrolled in the study, comprising 30 individuals in the SEA-ASF group and 35 in the PSF group. No statistically significant differences were observed in surgery-related complications between the groups. While VAS and ODI scores did not differ significantly at the 24-month follow-up, the SEA-ASF group exhibited superior scores at both 1 day and 1 month post-surgery (P < 0.05). Significant differences were observed in DH, LL, and SL at both 12 and 24 months postoperatively between the two groups (P < 0.05). At the 24-month postoperative follow-up, the incidence of CS was observed to be 16.67% (5 out of 30) in the SEA-ASF cohort and 11.43% (4 out of 35) in the PSF cohort. Statistical analysis revealed no significant difference between the two groups (P = 0.542). Fusion rates at the 24-month postoperative follow-up were 83.33% (25/30) in the SEA-ASF group and 85.71% (30/35) in the PSF group, also showing no significant difference (P = 0.791).

CONCLUSION: For the management of DLSS patients with osteoporosis, we propose that the integration of OLIF with SEA and ASF constitutes a viable therapeutic option. This approach demonstrates comparable clinical and radiological outcomes to OLIF-PSF, while offering benefits such as reduce operative duration, decrease blood loss, and minimize tissue trauma.

PMID:40931132 | DOI:10.1007/s00586-025-09358-y

Eur J Nutr. 2025 Sep 11;64(6):274. doi: 10.1007/s00394-025-03791-x.

ABSTRACT

PURPOSE: To investigate how a group-based lifestyle intervention affects food choices and if the dietary patterns at the end of the intervention are associated with incidence type 2 diabetes (T2D). We also investigated if the possible associations between diet and T2D risk were modified by the genetic risk for T2D.

METHODS: Participants in the T2D-GENE study were men with prediabetes aged 50-75 years, body mass index ≥ 25 kg/m², belonging in either low or high genetic risk score (GRS) tertile for T2D. They participated in a 3 year, group-based T2D-GENE lifestyle study (either an intervention or a control arm). Food consumption was measured with a food frequency questionnaire (FFQ) at baseline and at year 3. We included in our study all the T2D-GENE participants who had FFQ available at year 3 (n = 883). To diagnose T2D we used the following criteria, fasting plasma glucose ≥ 7.0 mmol/l, 2 h plasma glucose ≥ 11.1 mmol/l, or HbA1C ≥ 48 mmol/mol ( ≥ 6.5%). The GRS was based on 76 genetic variants associated with T2D.

RESULTS: There were statistically significant changes towards more recommended food consumption (higher frequency of whole-grain products, vegetables, and non-tropical vegetable oils) in the participants receiving lifestyle counselling as compared to their baseline and to the population controls. The intervention group reported increased consumption of healthy dietary pattern (high in e.g. vegetables, whole-grain products, and fish) and decreased consumption of unhealthy (high in e.g. meat, sausages and low-fibre products) at year three as compared to baseline. End-of-intervention healthy dietary pattern was associated with a decrease in the risk of T2D (OR 0.67, 95% CI 0.46; 0.97 in multivariable model) and end-of-intervention unhealthy pattern with increased risk (OR 1.82, 95% CI 1.26; 2.62 in multivariable model). When stratified by the GRS, the associations remained significant for the high genetic risk group.

CONCLUSION: A group-based lifestyle intervention improved diet quality. Healthy dietary pattern associated with lower risk for T2D whereas unhealthy pattern associated with higher risk. After stratification by the GRS, associations were evident in participants with a high genetic risk for T2D.

PMID:40931124 | DOI:10.1007/s00394-025-03791-x