Nevin Manimala

Circ Genom Precis Med. 2025 Oct 6:e005198. doi: 10.1161/CIRCGEN.125.005198. Online ahead of print.

ABSTRACT

Coronary artery disease remains the leading cause of death worldwide. One of the greatest developments in preventive cardiology has been the identification and treatment of standard modifiable risk factors associated with coronary artery disease. However, despite advances in the management of standard modifiable risk factors, there is an escalating number of patients who continue to present with acute coronary syndromes, a trend that is particularly concerning given the decreasing age-adjusted incidence rates of these conditions. This persistent clinical challenge underscores the urgency to explore alternative approaches for early detection and improved risk stratification. In recent years, the emergence of proteomics technologies has brought forth promising avenues for the discovery of novel biomarkers that hold the potential to revolutionize the timely detection and management of coronary artery disease. Proteomics enables the high throughput and often unbiased analysis of protein abundance, modifications, and interactions within pathways relevant to cardiovascular disease pathogenesis. Of particular importance is the capability to detect low-abundance proteins including those with currently unknown functions. While the functional assessment of these proteins aligns more with mechanistic studies, their role in biomarker discovery is equally important. Such detection may provide new insights into cardiac pathophysiology, including potential new markers for early disease detection and risk assessment. Although the latest proteomics technology and bioinformatic approaches do provide the opportunity for novel discoveries, understanding the limitations of each technology platform is important. This review provides an updated overview of major proteomic platforms and discusses their methodological strengths, constraints, and applications, using recent coronary artery disease studies as illustrative examples. By integrating proteomics data with clinical information, including advanced noninvasive imaging techniques and other omics disciplines, such as genomics and metabolomics, we can deepen our understanding of disease mechanisms and improve risk stratification. Although the discovery of novel biomarkers represents a significant step forward in the field, their true clinical value is contingent upon their rigorous validation in clinical trials and implementation studies. With our current capabilities and emerging advancements, we are well-positioned to advance proteomics-guided precision medicine in cardiovascular care over the coming decade.

PMID:41048024 | DOI:10.1161/CIRCGEN.125.005198

Am J Clin Pathol. 2025 Oct 6:aqaf107. doi: 10.1093/ajcp/aqaf107. Online ahead of print.

ABSTRACT

OBJECTIVE: Targeted therapy in non-small cell lung cancer (NSCLC) is now often included as first-line treatment in the neoadjuvant and adjuvant settings. Delays in optimizing treatments based on biomarker status can affect outcomes. Therefore, we assessed the turnaround time (TAT) of reflex biomarker testing for all NSCLCs clinical stage 1B and greater.

METHODS: A next-generation sequencing (NGS) and PD-L1 immunohistochemistry reflex protocol for NSCLC clinical stage 1B and greater was implemented. Turnaround time intervals between procedure date, pathology sign-out, date received in the molecular laboratory, and date of NGS sign-out were calculated. Median and IQR of each interval before and after implementation of the reflex protocol were calculated and compared using the Mann-Whitney U test.

RESULTS: In total, 492 lung cancer NGS cases were identified, 351 before and 141 after implementation of the reflex protocol. The prereflex cases, after exclusion of biomarker testing ordered on older blocks and outside consults (n = 165), demonstrated a 22-day median time from procedure to NGS sign-out (range, 11-70 days; IQR, 9; mean, 24 days), compared to a 20-day median time (range, 13-54 days; IQR, 4.5; mean, 21 days) postimplementation (n = 120) (P < .000103).

CONCLUSIONS: Reduction in median TAT from procedure to NGS sign-out was statistically significant after implementation of reflex biomarker testing in NSCLC samples.

PMID:41048009 | DOI:10.1093/ajcp/aqaf107

Aliment Pharmacol Ther. 2025 Oct 6. doi: 10.1111/apt.70395. Online ahead of print.

ABSTRACT

BACKGROUND: Faecal microbiota transplantation (FMT) is effective for Clostridioides difficile infection (CDI), but real-world effectiveness data are warranted to refine treatment algorithms. We previously found that FMT effectiveness varied with donors, and the effect of a single capsule FMT administration was lower than expected.

AIMS: To improve FMT outcomes through empirical donor exclusion and application of an optimised capsule FMT dosing regimen.

METHODS: In this multi-site Danish quality improvement study, we included patients with CDI treated with capsule-based FMT from 24 June 2019 to 30 September 2024. The primary outcome was cure of C. difficile-associated diarrhoea (CDAD) 8 weeks after FMT. We assessed this using statistical process control charts monitored separately for the primary FMT centre and the external FMT sites. We used multivariable, mixed-effect logistic regression analysis to evaluate the impact of FMT dosing while adjusting for patient, donor and CDI-related factors.

RESULTS: We included 1176 patients (1707 FMT treatments). At external FMT sites, the cure rate from one FMT treatment changed from 50% (95% confidence interval (CI): 45%-56%) to 59% (55%-63%) following the exclusion of three low-performing donors in November 2022. After implementing a two-dose capsule FMT dosing regimen in February 2024, the cure rate increased to 72% (65%-77%). The impact of the two-dose capsule FMT dosing regimen remained statistically significant after adjustment (odds ratio 1.22; 95% CI 1.16-1.28; p < 0.001).

CONCLUSION: Empirical donor selection and a two-dose capsule FMT regimen improved clinical outcomes in a large-scale system treating patients with CDI.

PMID:41047993 | DOI:10.1111/apt.70395

Acta Chim Slov. 2025 Jul 23;72(3):441-449. doi: 10.17344/acsi.2025.9163.

ABSTRACT

Modelling and data fitting for the prediction of permeate flux during ultrafiltration (UF) of a model feed solution of sodium lignosulfonate was carried out following resistance in series, gel polarization and Kedem Katchalsky equations. The experiments were conducted in a laboratory UF unit equipped with PES/HFUF asymmetric membrane under specific operating conditions by altering some parameters including solute concentration, transmembrane pressure (TMP), and cross flow velocity (CFV). The maximum experimental permeate flux was observed at TMP of 3.92 bar and CFV 0.527 ms-1 was 19.6 × 10-6 m3m-2s-1. The theoretical and experimental volumetric flux was plotted, and their extent of resemblance was compared and validated statistically. The study sheds light on the effective upcycling of sodium lignosulfonate from spent liquor via ultrafiltration.

PMID:41047983 | DOI:10.17344/acsi.2025.9163

Acta Chim Slov. 2025 Jul 23;72(3):450-462. doi: 10.17344/acsi.2025.9199.

ABSTRACT

In the context of pharmacological intervention for pain, Transient Receptor Potential Vanilloid, member 1 (TRPV1), as a non-selective cation channel belonging to the transient receptor potential (TRP) family of ion channels, has emerged as a promising target. However, the availability of selective TRPV1 antagonists and their associated pharmacological properties remains limited. This research paper explores various QSAR modeling techniques applied to a range of piperazinyl-aryl compounds acting as TRPV1 antagonists. The descriptors utilized in the creation of conformation-independent QSAR models included local molecular graph invariants and the SMILES notation, along with the incorporation of the Monte Carlo optimization method as a model development technique. Several statistical methods were employed to evaluate the quality, robustness, and predictive capacity of the developed models, yielding positive results. For the best developed QSAR model following statistical parameters were obtained for training set R2 = 0.7155, CCC = 0.8134, IIC = 0.7430, Q2 = 0.6970, RMSE = 0.645, MAE = 0.489 and F = 157; and for test set R2 = 0.9271, CCC = 0.9469, IIC = 0.9635, Q2 = 0.9241, RMSE = 0.367, MAE = 0.329 and F = 328. Additionally, molecular fragments derived from SMILES notation descriptors, which explain observed changes in the evaluated activity, were identified, leading to the design of four new antagonists. The final validation of the QSAR model and the designed antagonists was conducted through molecular docking, which demonstrated strong correlation with the QSAR modeling results.

PMID:41047980 | DOI:10.17344/acsi.2025.9199

Cancer Biother Radiopharm. 2025 Oct 6. doi: 10.1177/10849785251379696. Online ahead of print.

ABSTRACT

Colorectal cancer (CRC) remains a significant factor contributing to the morbidity and mortality rates linked with cancer throughout the world, especially in its stages of progression. Increasingly attractive therapeutic options include immune modulation combined with preoperative chemotherapy and radiation therapy (CRT). Recent studies have revealed that the protein serine peptidase inhibitor Kazal type 4 (SPINK4), which is abundantly expressed in gastrointestinal tract tissues, plays a role in immune evasion and treatment resistance in cancers. This meta-analysis aims to assess the relationship between SPINK4 expression levels and the therapeutic effectiveness of radiolabeled immune modulators in patients with advanced CRC who are undergoing preoperative chemotherapy and radiation treatment. The degree of SPINK4 expression and a lower objective response to radiolabeled immune modulators showed a statistically significant link. Conversely, patients with low SPINK4 expression have more favorable treatment responses and ongoing clinical improvement following CRT. High SpINK4 expression can act as a negative prognostic biomarker for radiolabeled immune control in advanced CRC.

PMID:41047949 | DOI:10.1177/10849785251379696

Br J Clin Pharmacol. 2025 Oct 6. doi: 10.1002/bcp.70308. Online ahead of print.

ABSTRACT

AIMS: The Medicines and Healthcare products Regulatory Agency (MHRA) introduced a risk-proportionate approach to assess clinical trial applications for authorisation in August 2023. This study evaluates the impact of this approach on the timelines for reviewing proposals.

METHODS: Data on new clinical trial initial submissions and substantial amendments were extracted from the MHRA’s clinical trials unit database. The primary endpoint was the number of days for the MHRA’s first review of initial applications. The secondary endpoints were the days taken by the sponsor’s replies to grounds for nonacceptance, the MHRA’s days to issue the final decision and the percentage of reviews within statutory timelines. For substantial amendments, the days for the final decision and the percentage of statutory timelines met were the endpoints.

RESULTS: Between September 2023 and August 2024, 4617 applications were received, 615 relating to initial clinical trial submissions, while 4002 were substantial amendments. The first review was completed within the statutory timelines for 99% of submissions, with a median of 28 days (interquartile range [IQR] 27-30); 48.5% of sponsors’ replies to grounds for nonacceptance met the statutory timelines with no statistically significant difference between the commercial and noncommercial sponsors (median 15 days, IQR 9-22). The final decision from the MHRA was within the nonstatutory timelines (median 15 days, IQR 13-27); 99.9% of the substantial amendments were completed within the statutory timelines (median 31 days, IQR 24-34).

CONCLUSION: The MHRA’s risk-proportionate approach enabled the Clinical Trials Unit to consistently meet its timelines, confirming its reliability, consistency and predictability while maintaining its priority to protect patient safety.

PMID:41047928 | DOI:10.1002/bcp.70308

Disaster Med Public Health Prep. 2025 Oct 6;19:e289. doi: 10.1017/dmp.2025.10199.

ABSTRACT

OBJECTIVE: Earthquakes cause significant mortality and morbidity, particularly through crush injuries and their complications. This study aimed to evaluate whether systemic immune inflammation index (SII) and Pan-immune inflammatory values (PIV) obtained from complete blood count parameters can predict intensive care needs, dialysis requirements, and mortality in patients with crush injuries following earthquake.

METHODS: We retrospectively analyzed data from 76 patients with crush injuries admitted to a university hospital following the earthquake. Blood samples were collected upon admission. SII and PIV were calculated and compared with conventional laboratory markers for their ability to predict clinical outcomes.

RESULTS: Intensive care unit (ICU) admission was required in 40.8% of patients, and 21.1% required dialysis. In ROC analysis, an SII value above 1372 predicted ICU admission with 67.7% sensitivity and 66.7% specificity (P < .001), while an SII value above 1735 predicted dialysis requirement with 75.0% sensitivity and 73.3% specificity (P < .001). Similarly, a PIV value above 1345 predicted ICU admission with 74.2% sensitivity and 73.3% specificity (P < .001), and a value above 1906 predicted dialysis requirement with 81.3% sensitivity and 78.3% specificity (P < .001).

CONCLUSIONS: Complete blood count-derived inflammatory markers may serve as accessible, early indicators to complement clinical assessment for resource allocation following earthquake-related crush injuries, particularly in resource-limited disaster settings. These tools may aid in patient triage and care planning when comprehensive laboratory testing is limited.

PMID:41047911 | DOI:10.1017/dmp.2025.10199

J Matern Fetal Neonatal Med. 2025 Dec;38(1):2566235. doi: 10.1080/14767058.2025.2566235. Epub 2025 Oct 6.

ABSTRACT

OBJECTIVE: To evaluate neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and other related indices measured at the time of admission for threatened preterm labor and their association with the risk of preterm birth.

METHODS: A prospective observational cohort study was conducted between January 2021 and December 2023 at two regional maternity hospitals. Blood samples were collected from all patients upon hospitalization, prior to the administration of any medical treatment. Patients were categorized into two groups based on delivery time: preterm birth and term delivery. The preterm birth group was further subdivided into early preterm birth (<34 weeks) and late preterm birth (34-36.6 weeks). Demographic characteristics, complete blood count parameters, and systemic inflammatory indices were compared across these groups. To identify independent predictors of preterm birth and early preterm birth, multivariate logistic regression analysis was performed.

RESULTS: The final analysis included 311 pregnant women admitted for threatened preterm labor. The preterm birth group had a higher maternal age and a lower gestational age at admission compared to the term delivery group (p = 0.04, p = 0.02, respectively). The preterm group was statistically associated with higher WBC, neutrophil count, monocyte count, and platelet count. Furthermore, the median NLR, SII, and SIRI values were significantly higher in the preterm group. After adjusting for confounders multivariate regression analysis showed that higher levels of NLR and SII were independently associated with an increased risk of preterm birth.

CONCLUSION: We found that NLR and SII are independent prognostic markers for preterm birth in patients with TPTL, and they demonstrate superior prognostic ability compared to single hemogram parameters.

PMID:41047899 | DOI:10.1080/14767058.2025.2566235

Jpn J Nurs Sci. 2025 Oct;22(4):e70026. doi: 10.1111/jjns.70026.

ABSTRACT

AIM: To evaluate the feasibility of a breast stimulation program using a breast pump shortly after cesarean section (CS) to enhance the onset of lactogenesis II.

METHODS: We used a convergent mixed-methods design. It provided an overall picture through quantitative results, which were complemented by qualitative findings. The results were presented using a joint display. Participants were full-term women who underwent CS at a regional perinatal hospital and nurse-midwives from January to March 2025. The program included: (1) providing information about breastfeeding after CS; and (2) providing breast pump-mediated nipple stimulation, starting within 6 h postpartum and continuing until day 2, at least four times daily under researcher supervision. Main outcomes focused on the feasibility of the program, including acceptability, practicality, and implementation. An eight-item questionnaire and open-ended questions were administered. Quantitative data were analyzed using descriptive statistics; qualitative data were analyzed using content analysis.

RESULTS: Seven full-term women with planned CS and 29 nurse-midwives. Most used a breast pump four times within the first 24 h after CS. Women were satisfied with painless nipple stimulation and early milk expression. Both designs complemented each other, and the program was deemed acceptable based on early postpartum breast milk volume data. Identified challenges included pump operability, individual adaptation, and preparation time.

CONCLUSION: The breast stimulation program initiated shortly after CS was feasible, well accepted, and aspects of breast milk volume. A future randomized controlled trial should consider individual differences and adjustments in the frequency of breast pump usage.

PMID:41047890 | DOI:10.1111/jjns.70026