Category: Nevin Manimala

Pol J Pathol. 2025;76(1):54-58. doi: 10.5114/pjp.2025.148390.

ABSTRACT

Determining the status of DNA mismatch repair (MMR) proteins is crucial for patients because they may respond differently to specific treatments and have a better prognosis. We proposed a panel with only 2 antibodies to determine the status of the MMR proteins, improving costs, workload, and delivery of results. Patients with adenocarcinoma and MMR determination were reclassified using only the evaluation of PMS2 and MSH6. The diagnostic performance of the 2-antibody test (proposed panel) and 4-antibody (traditional panel) test was compared against the polymerase chain reaction study (reference standard). A total of 202 cases were identified. The predominant histological type was adenocarcinoma not otherwise specified, the predominant histological grade was 2, and 60.9% of the cases were found in clinical stage II. When comparing the diagnostic performance of the traditional panel of 4 antibodies against a panel of 2 antibodies, no statistically significant differences were found (sensitivity 95.35% vs. 90.7%; specificity 98.74% vs. 98.11%; positive predictive value 95.35% vs. 92.86%; negative predictive value 98.74% vs. 97.50%; area under the curve 0.970 vs. 0.944; p = 0.419).Analysis of MMR status determination with only 2 antibodies demonstrates that it is as effective as using 4 antibodies.

PMID:40755331 | DOI:10.5114/pjp.2025.148390

Pol J Pathol. 2025;76(1):16-24. doi: 10.5114/pjp.2025.149408.

ABSTRACT

The presented work focuses on hypoxia-inducible factor 1a (HIF-1a) and carbonic anhydrase IX (CA IX) in colorectal cancer (CRC). The HIF-1a protein shows increased expression due to hypoxia, resulting in up-regulation of CA IX, which is involved in the survival of hypoxic cancer cells in the tumour microenvironment, with overexpression in various types of carcinomas. HIF-1a and CA IX immunohistochemical analysis was performed on 111 CRC samples. The primary goal was to determine the correlation of expression of proteins with clinical-morphological parameters and mutual correlation of the proteins in question. The HIF-1a expression was detected in 72.1% of CRC samples with exclusive nuclear localisation. The immunoreaction intensity was predominantly strong. Carbonic anhydrase IX protein was expressed in 75.7% of cases. The membrane positivity and strong immunoreaction intensity were mainly noticed. No statistically significant correlation between the expression of studied proteins and clinical-morphological parameters was confirmed. However, the results proved a statistically significant correlation in mutual co-localisation of given proteins. Despite contradictory scientific data, our findings suggest a mutual correlation between HIF-1a and CA IX in CRC. The presented hypothesis that their overexpression may represent a potential new therapeutic target in colorectal carcinogenesis might unveil novel strategies in disease development.

PMID:40755327 | DOI:10.5114/pjp.2025.149408

Pol J Pathol. 2025;76(1):10-15. doi: 10.5114/pjp.2025.149282.

ABSTRACT

C-terminal tensin-like (Cten) is a marker for poorly differentiated breast cancer. We evaluated the immunohistochemical expression of Cten in invasive breast carcinoma in our population and correlated it with known histopathologic prognostic variables. Fifty-seven specimens of modified radical mastectomy diagnosed as invasive ductal carcinoma were collected. The histopathologic findings were noted independent of the result of Cten. According to the results of Cten immunohistochemistry, the tumors were categorized as negative/mild, moderate, or high expression and were statistically corelated with histologic findings. In our study, 47 (82.5%) cases showed negative/mild expression, 2 (3.5%) cases showed moderate staining, and 8 (14%) cases showed strong expression of Cten. Positive Cten was present in pT4 stage tumors. Similarly, grade III tumor showed moderate expression in 2 (3.5%) cases and strong staining in 8 (14%) cases. Posi-tive expression of Cten was observed in cases with lymphovascular invasion (LVI) and high axillary lymph nodal involvement (N3). All these poor prognostic factors were significantly associated with moderate to high expression of Cten. We found that tumor size and extent, histologic grade, LVI, and lymph node status were significantly associated with Cten expression. C-terminal tensin-like can be used as marker of poor prognosis in breast carcinoma.

PMID:40755326 | DOI:10.5114/pjp.2025.149282

Pol J Pathol. 2025;76(1):1-9. doi: 10.5114/pjp.2025.149426.

ABSTRACT

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. At the cell of origin level, cancer stem cells (CSC) are the tumour initiators in breast cancer. SRY-box transcription factor 2 (SOX-2) is a CSC marker that plays a role in tumourigenesis. The objective of this study was to evaluate the association of SOX-2 expression with histopathological parameters and clinical outcomes in TNBC patients. The study included 95 TNBC cases. An in vitro diagnostic SOX-2 antibody was applied to the tumoural slides in a validated automated stainer. The expression of SOX-2 was defined as a SOX-2 H-score ≥ 1. The expression of SOX-2 was observed in 29 cases (30.5%). At a median follow-up of 76 months, SOX-2 expression was not associated with overall or disease-free survival. R-based statistical analysis determined a SOX-2 H-score cut-off of 2. Although the overall and disease-free survival rates of cases with an H-score ≥ 3 were lower than the others, the differences were not statistically significant. The percentage of SOX-2 staining is typically low, as only 1% of tumour cells exhibit CSC characteristics. In conclusion, the prognostic significance of SOX-2 could become clear in a larger group of TNBC patients using standardized methodologies.

PMID:40755325 | DOI:10.5114/pjp.2025.149426

Subst Use Addctn J. 2025 Aug 4:29767342251357089. doi: 10.1177/29767342251357089. Online ahead of print.

ABSTRACT

BACKGROUND: Substance use disorder (SUD) is a chronic and recurrent condition posing a significant health burden. The integration of out-on-pass (OOP) or day leave privileges during inpatient rehabilitation has been theorized to support recovery by enhancing social reintegration and preparing patients for discharge. However, evidence on the impact of inpatient OOP on post-discharge relapse rates is scant. This study investigates the effect of OOP during inpatient treatment and relapse outcomes.

METHODS: A retrospective cohort design was used to analyze data from 72 patients discharged from the Umm Salal Treatment and Rehabilitation Center in 2023, focusing on OOP during rehabilitation and urine drug test results during aftercare. Key variables included OOP frequency, comorbid personality disorders, forensic history, and relapse indicators. Statistical evaluation utilized logistic regression, chi-squared tests (Fisher’s exact test where appropriate), and survival analysis to identify predictors of relapse, adjusted for potential confounders.

RESULTS: Of the participants, 28 (38.9%) were granted OOP during inpatient treatment, while 44 (61.1%) were not. Relapse, defined by a positive urine drug screening post-discharge, occurred in 29 patients (40.3%). The median time-to-relapse was 28 days, with a longer duration observed among those granted OOP. Specifically, during the 26-week study period, 25% of patients with OOP relapsed compared to 50% of those without OOP (statistically significant difference; P = .04892). Survival analysis revealed that time-to-relapse was substantially longer for patients who were granted OOP compared to those who were not (P = .034). Furthermore, the granting of OOP during inpatient treatment of SUD was associated with a 73.2% reduction in relapse hazards ratio (P = .00876).

CONCLUSION: This study highlights the potential of OOP as a therapeutic strategy and tool to support sustained recovery in patients with SUD. While relapse remains a significant challenge, OOP may contribute to extended abstinence periods and reduced relapse rates.

PMID:40755318 | DOI:10.1177/29767342251357089

CNS Neurosci Ther. 2025 Aug;31(8):e70529. doi: 10.1111/cns.70529.

ABSTRACT

AIMS: Postoperative sleep disturbance (PSD) is a common complication following surgical procedures. We aimed to evaluate the effect of prefrontal transcranial alternating current stimulation (tACS) in preventing PSD among patients undergoing gynecological laparoscopic surgery.

METHODS: A total of 176 eligible patients, aged 18-65 years, with ASA Class I to III, and scheduled for gynecological laparoscopic surgery, were randomly allocated to receive either a single 20-min session of prefrontal tACS (2 mA, 7 Hz) or sham stimulation immediately after extubation. The primary outcome was the occurrence of PSD on postoperative day (POD) 1.

RESULTS: The intention-to-treat analysis showed a statistically significant reduction in PSD incidence on POD 1 in the active tACS group (23.9%) compared to the sham group (43.2%), with an odds ratio of 0.41 (95% CI, 0.22-0.79; p = 0.007). Additionally, patients in the active tACS group reported significantly lower anxiety scores on POD 1 (p < 0.001), while depression scores were comparable between the groups. The active tACS group also reported significantly lower pain scores, both on PODs 1 (movement: p = 0.002; rest: p < 0.001) and 3 (movement: p = 0.028; rest: p < 0.001).

CONCLUSIONS: A single session of prefrontal tACS significantly reduces the incidence of PSD on POD 1 and may offer additional benefits in reducing early postoperative anxiety and pain, with a favorable safety and tolerability profile.

TRIAL REGISTRATION: China Clinical Trial Registration Center: ChiCTR2300078658.

PMID:40755300 | DOI:10.1111/cns.70529

Brief Bioinform. 2025 Jul 2;26(4):bbaf384. doi: 10.1093/bib/bbaf384.

ABSTRACT

BACKGROUND: The COVID-19 pandemic has caused over 776 million infections and 7 million deaths globally between December 2019 and November 2024. Since the emergence of the original Wuhan strain, SARS-CoV-2 has evolved into multiple variants-including Alpha, Delta, and Omicron-primarily through mutations in the Spike glycoprotein. The S1 subunit, which binds the human angiotensin-converting enzyme 2 (ACE2) receptor, mutates frequently and plays a key role in infectivity and immune escape, while the more conserved S2 subunit mediates membrane fusion. Anticipating future mutations is essential for guiding vaccine design and therapeutic strategies. Generative Large Language Models (LLMs) have shown promise in protein sequence modeling due to their capacity to produce realistic and functional synthetic sequences. Here, we introduce SARITA, a GPT-3-based LLM with up to 1.2 billion parameters, fine-tuned via continual learning on the protein model RITA trained on 107 017 high-quality SARS-CoV-2 Spike sequences (up to March 1st 2021) to generate high-quality synthetic SARS-CoV-2 Spike S1 subunits.

RESULTS: SARITA is able to generate realistic, full-length synthetic S1 subunits starting from a 14-amino-acid prompt. When evaluated on unseen sequences collected between March 2021 and November 2023-including major Variants of Concern (VOCs) such as Delta and Omicron, and Variants of Interest such as Iota-SARITA outperforms baseline and state-of-the-art LLMs in terms of sequence quality, biological plausibility, and similarity to real-world viral evolution. SARITA generates high-quality sequences in over 97% of cases, with markedly lower False Mutation Rate and higher similarity scores (PAM30, Levenshtein distance) compared to alternative approaches. It also accurately reproduces key mutations characteristic of future variants-such as L212I, R158L, T95P, and E406K-which were not present in the training data but emerged later in VOCs like Omicron and Delta. Structure-based analysis confirms the functional plausibility of these substitutions, with ΔΔG values within experimentally supported thresholds for ACE2 and antibody binding. Furthermore, SARITA anticipates immune-evasive mutations and accurately captures the positional and statistical distribution of mutations found in post- March 1st 2021 variants, highlighting its potential as a predictive tool for viral evolution.

CONCLUSION: These results indicate the potential of SARITA to predict future SARS-CoV-2 S1 evolution, potentially aiding in the development of adaptable vaccines and treatments.

PMID:40755284 | DOI:10.1093/bib/bbaf384

Nurs Open. 2025 Aug;12(8):e70288. doi: 10.1002/nop2.70288.

ABSTRACT

AIMS: The aim of this study is to determine the psychological resilience and self-efficacy levels of caregivers of individuals with Alzheimer’s disease and to examine the effects of these variables on the caregiver burden.

DESIGN: A cross-sectional, quantitative design was used.

METHODS: The study was conducted in the neurology outpatient clinic of a university hospital between March and July 2022. The sample of the study consisted of caregivers of 105 individuals diagnosed with Alzheimer’s disease. Data were collected using the “Zarit Burden Interview,” the “Revised Scale for Caregiving Self-Efficacy,” and the “Resilience Scale Short Form.” In the study, descriptive statistics and Pearson correlation analysis were employed, and the stepwise multiple regression model was applied.

RESULTS: It was determined that caregivers had a moderate to severe caregiving burden (43.57 ± 16.58) and a moderate level of psychological resilience (20.24 ± 5.96) and self-efficacy (62.84 ± 15.96). The stepwise regression analysis results showed that a lower mini mental state score (β = -0.821; p < 0.001), low caregiver income status (β = -0.201; p < 0.008), inadequate social support (β = -0.155; p < 0.030), shorter duration of Alzheimer’s disease diagnosis (β = -0.323; p < 0.001), advanced age (β = -0.299; p < 0.001), and prolonged caregiving (β = -0.216; p < 0.005) were the main predictors of caregiver burden. In addition, the levels of caregiver’s self-efficacy in obtaining respite (β = -0.340; p < 0.001), psychological resilience (β = -0.293; p < 0.001), and self-efficacy in controlling upsetting thoughts (β = -0.240; p < 0.001) about caregiving predicted caregiver burden significantly.

CONCLUSION: The resilience and self-efficacy levels of caregivers predicted caregiver burden significantly. As the psychological resilience and self-efficacy levels of caregivers increase, caregiver burden may decrease significantly.

PATIENT OR PUBLIC CONTRIBUTION: PATIENT OR PUBLIC CONTRIBUTION: Interviews were conducted with the research participants to collect data. Our findings can be used to develop interventions and coping strategies to reduce the care burden of caregivers of individuals with Alzheimer’s disease and to improve their resilience and self-efficacy.

REPORTING METHOD: The results were reported in accordance with STROBE guidelines.

PMID:40755264 | DOI:10.1002/nop2.70288

Disaster Med Public Health Prep. 2025 Aug 4;19:e215. doi: 10.1017/dmp.2025.10084.

ABSTRACT

OBJECTIVES: The aim was to characterize reported food- and waterborne outbreaks in Finland, 2010-2020, and to test local investigation teams’ preparedness to investigate outbreaks.

METHODS: The outbreaks reported to the Finnish registry for food and waterborne outbreaks were characterized by the number of outbreaks and people fallen ill, and the causative agent. Local investigation teams’ measures and their timeliness in a simulated time-constrained case study were scored and analyzed descriptively.

RESULTS: In 537 outbreaks, 12 399 fell ill and 19 (0.15%) died. The causative agent remained unknown in 218 outbreaks. The local investigation teams’ median preparedness score was 15/29 (range 9-23) and the score differed markedly within regions. Differences in the speed of communication and the number of channels used were observed between the teams.

CONCLUSIONS: Differences between environmental health units’ scores indicated inconsistency in outbreak investigations between areas in Finland. The variability in preparedness scores was high in both the highest and lowest outbreak incidence regions. Because outbreaks occur rarely in most EHU areas, preparedness exercises are necessary to maintain investigation skills. Measures to enhance sampling would be needed because the causative agent was unknown in over 1/3 of the outbreaks. Many local investigation teams lack experience in public communication and training on communicating about outbreaks is needed.

PMID:40755261 | DOI:10.1017/dmp.2025.10084

Thorac Cancer. 2025 Aug;16(15):e70144. doi: 10.1111/1759-7714.70144.

ABSTRACT

BACKGROUND: While established biomarkers predict immunotherapy response in advanced nonsmall cell lung cancer (NSCLC), additional noninvasive imaging biomarkers may enhance treatment selection. Pretreatment computed tomography (CT) texture analysis may provide tumor characterization to predict survival outcomes.

METHODS: We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and Cochrane Library databases were searched. Study quality was assessed using the quality in prognosis studies (QUIPS) tool. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effects models.

RESULTS: Ten retrospective studies involving 2400 patients were included. Patients stratified as low-risk based on CT texture features demonstrated significantly improved survival outcomes compared to high-risk patients. The included studies used diverse radiomic features for risk stratification, including texture features from gray-level co-occurrence matrix (GLCM) such as entropy and dissimilarity, first-order statistical parameters including skewness and kurtosis, gray-level run-length matrix (GLRLM) features, and deep learning-derived features. Meta-analysis of five studies (n = 1102) revealed that patients stratified as low-risk based on these quantitative CT texture signatures had substantially better overall survival (OS) (p < 0.0001) with minimal heterogeneity (I² = 0.0%). Similarly, progression-free survival (PFS) analysis of five studies (n = 1799) showed significant benefit for low-risk patients (p < 0.0001), though with moderate heterogeneity (I² = 71.7%).

CONCLUSIONS: Pretreatment quantitative CT texture analysis effectively predicts survival outcomes in advanced NSCLC patients receiving immunotherapy, providing clinically meaningful risk stratification. This noninvasive imaging approach may serve as an additional tool to complement established pathological and molecular biomarkers, including liquid biopsy, for enhanced personalized treatment selection.

PMID:40755255 | DOI:10.1111/1759-7714.70144