J Endocr Soc. 2025 Apr 18;9(7):bvaf068. doi: 10.1210/jendso/bvaf068. eCollection 2025 Jul.

ABSTRACT

OBJECTIVE: We evaluated provider sentiments and practices that influence recommendations for insulin pump use.

METHODS: We surveyed US adult endocrinologists and used descriptive statistics to assess guideline adherence and criteria for insulin pump candidacy. Providers were categorized as permissive or selective prescribers based on reliance on criteria outside of clinical guidelines. Adjusted logistic regression identified factors associated with selective prescribing.

RESULTS: In 2023, we emailed surveys to 5684 endocrinologists, and 299 (5%) responded. Criteria for insulin pump use varied across providers: carbohydrate counting (55%), a minimum number of daily glucose checks (51%), a minimum number of clinic visits (48%), continuous glucose monitor use (42%), a minimum duration after diagnosis (20%), and a specific A1c (8%). While 94% reported being aware of diabetes care guidelines, 52% almost never referenced guidelines when determining insulin pump candidacy. The majority reported relying on their own judgment about insulin pump candidacy when it conflicted with clinical guidelines. Selective prescribers were more likely to report using guidelines sometimes or more (vs not often/never), have a low proportion of diabetes in their clinical case mix, and see patients primarily with public insurance.

CONCLUSION: Less than half of endocrinologists referenced national guidelines for pump candidacy, with many relying on nonevidence-based criteria. These findings demonstrate an important disconnect between guideline recommendations and clinical practice that may lead to underutilization of insulin pumps, which can enhance diabetes care and outcomes. Additional work is needed to better align clinical practice with current recommendations.

PMID:40452799 | PMC:PMC12123061 | DOI:10.1210/jendso/bvaf068

Microbiologyopen. 2025 Jun;14(3):e70015. doi: 10.1002/mbo3.70015.

ABSTRACT

SCOPE: Iron deficiency (ID) is the most common nutritional deficiency worldwide, impacting gut bacteria's metabolism and cellular biochemistry, but its effects on the microbiota-gut-brain axis (MGB) are poorly understood. Early-life ID-related dysbiosis is linked to neurodevelopmental impairments like autism and attention deficit hyperactivity disorder. Studying ID's impact on bacterial signaling can guide interventions to target MGB in iron-deficient populations. This study examined the responses of Escherichia coli (E. coli) and Limosilactobacillus reuteri (L. reuteri) to in-vitro ID conditions using the iron chelator 2,2'-Bipyridyl (BP).

METHODS AND RESULTS: We assessed and modeled their growth and cultivability and explored their bioelectric profiles using the voltage-sensitive dye DiBAC4(3). Results showed differential responses: L. reuteri's growth and cultivability were unaffected by BP, while E. coli's growth rate and cultivability decreased under ID. Additionally, we created a deterministic mathematical model that demonstrated a decrease in the population's average reproduction rate in E. coli under ID. Only E. coli exhibited an altered bioelectric profile, marked by increased cell depolarization in ID conditions, which was largely rescued upon the addition of a saturating concentration of iron.

CONCLUSION: These findings highlight specific bioelectrical responses in gut bacteria to ID. Understanding this variability is crucial for deciphering the microbiota's role in health and disease, particularly concerning nutritional iron imbalance and bacterial signaling in the MGB.

PMID:40452591 | DOI:10.1002/mbo3.70015

Mol Biol Evol. 2025 Jun 2:msaf129. doi: 10.1093/molbev/msaf129. Online ahead of print.

ABSTRACT

Shikimate kinase-like 1 (SKL1) plays an essential role in chloroplast biogenesis in Arabidopsis thaliana whereby mutants present a pigment-defective phenotype. The inability to identify SKL1 in organisms pre-dating land plants suggests an important role for this gene coinciding with the emergence of terrestrial plants. A role for SKL1 in chloroplast biogenesis has previously been determined in Arabidopsis, however the biological function for SKL1 has not been established in early land plants. In the present study, we provided functional and evolutionary insights into the diversification of SKL1 in the early land plant Marchantia polymorpha. We identified the SK gene homologues common to all land plants, two of which were shown to have high sequence similarity to SK. We confirmed that one member possessed kinase activity shikimate, whereas the second member is inactive. These findings led us to identify MpSK (Mp3g21830) and infer the identity of MpSKL1 (Mp6g03600). Consistent with previous studies in Arabidopsis, disruption of MpSKL1 in Marchantia resulted in a pigment-defective phenotype with abnormal chloroplast morphology and thylakoid network organization. Given an early origin of SKL1 in land plant evolution, we investigated requisite structural modifications to an ancestral SK that led to the functional diversification of SKL1. We provided evidence that SKL1 displays an open and accessible substrate binding pocket, conferring its biological function for chloroplast biogenesis. Together, our results demonstrate that the acquisition of SKL1 corresponds with the emergence of terrestrial land plants and that this biological function is conserved across distant plant lineages.

PMID:40452216 | DOI:10.1093/molbev/msaf129

Brief Bioinform. 2025 May 1;26(3):bbaf252. doi: 10.1093/bib/bbaf252.

ABSTRACT

CpG island hypermethylation, a hallmark of cancer, exhibits substantial heterogeneity across tumors, presenting both opportunities and challenges for cancer diagnostics and therapeutics. While this heterogeneity offers potential for patient stratification to predict clinical outcomes and personalize treatments, it complicates the development of robust biomarkers for early detection. Understanding the mechanisms driving this heterogeneity is essential for advancing biomarker design. Here, simulation-based analyses demonstrate that tumor purity and the high prevalence of low epi-mutation samples significantly obscure the identification of negative, rather than positive, regulators of CpG island hypermethylation, limiting a comprehensive understanding of heterogeneity sources. By addressing these confounders, we identify impaired DNA methylation maintenance, as indicated by global hypomethylation levels, as the primary contributor to CpG island hypermethylation variability among known regulators. This finding is supported by integrative analyses of datasets from The Cancer Genome Atlas (TCGA) Pan-Cancer Atlas, Genomics of Drug Sensitivity in Cancer (GDSC1000) cancer cell lines, and epi-allele analyses of two independent whole-genome bisulfite sequencing cohorts, using a newly developed method, MeHist (https://github.com/vhang072/MeHist). Furthermore, we assess widely used hypermethylation biomarkers across ten cancer types and find that 65 out of 246 (26.4%) are significantly influenced by impaired methylation maintenance. Incorporating hypomethylation and hypermethylation markers improves the robustness of cancer detection, as validated across multiple plasma cell-free DNA datasets. In summary, our findings highlight the value of simulation-guided integrative analysis in mitigating confounding effects and identify impaired DNA methylation maintenance as a key regulator of CpG island hypermethylation heterogeneity.

PMID:40452146 | DOI:10.1093/bib/bbaf252

Surg Case Rep. 2025;11(1):25-0104. doi: 10.70352/scrj.cr.25-0104. Epub 2025 May 28.

ABSTRACT

INTRODUCTION: The use of immune checkpoint inhibitors (ICIs) as neoadjuvant therapies for locally advanced and resectable non-small cell lung cancer is increasing. As a result, immune-related adverse events (irAEs) may be observed before surgery and may require preoperative intervention. We report the case of a patient with destructive thyroiditis induced by neoadjuvant ICI treatment, in which surgical resection was performed after steroid treatment.

CASE PRESENTATION: A 74-year-old woman was diagnosed with slow-growing squamous cell carcinoma of the right upper lobe during treatment for another disease. Imaging studies revealed a small nodule suggestive of pulmonary metastasis in the right upper lobe and hilar lymph node metastasis. The patient was initially diagnosed with primary lung cancer of the right upper lobe (cT3N1M0, Stage IIIA, TNM Classification, 8th edition), and neoadjuvant nivolumab combined with chemotherapy was planned every 3 weeks for three cycles. After the first cycle, the patient experienced drug-induced kidney injury. Nivolumab and chemotherapy were discontinued, and surgical resection was planned. However, a laboratory analysis on the day before surgery revealed elevated free triiodothyronine and free thyroxine, and decreased thyroid-stimulating hormone. Subsequent examination led to a diagnosis of destructive thyroiditis due to irAEs, and surgery was postponed. Dexamethasone was administered orally for 1 week, and once the thyroid function showed consistent improvement, a thoracoscopic right upper lobectomy was performed. The patient progressed without any other complications after surgery.

CONCLUSIONS: This report highlights a case of preoperative destructive thyroiditis secondary to irAEs. In patients receiving preoperative ICIs therapy, routine blood tests, including thyroid function tests, are recommended as part of preoperative assessment. In this case, the patient underwent lobectomy safely following steroid administration. The optimal timing of surgery in patients with preoperative ICI-induced destructive thyroiditis requires further investigation.

PMID:40454085 | PMC:PMC12127077 | DOI:10.70352/scrj.cr.25-0104

Front Oncol. 2025 May 16;15:1567317. doi: 10.3389/fonc.2025.1567317. eCollection 2025.

ABSTRACT

BACKGROUND: Drug-induced interstitial lung disease (DIILD) is a serious complication of cancer treatment that is primarily treated with corticosteroids. However, effective standardized regimens for corticosteroid-refractory DIILD have not been established. Cyclophosphamide (CPA) is an immunosuppressant that is potentially effective against DIILD, but supporting evidence is limited, particularly for diseases induced by novel chemotherapeutic drugs. In this study, we examined the efficacy and safety of CPA in corticosteroid-refractory DIILD caused by various anticancer drugs.

METHODS: We retrospectively reviewed the medical records of patients who underwent CPA therapy for corticosteroid-refractory DIILD at the National Cancer Center Hospital East between January 2013 and October 2023. Corticosteroid-refractory DIILD was defined as cases of DIILD classified as grade ≥3 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, in which no improvement was observed within 48 hours after initiating corticosteroid therapy. The primary endpoint was 30-day survival post-CPA. The secondary endpoints included radiological improvements and changes in oxygen supplementation.

RESULTS: Fifteen patients (median age 73 years; 80% male) were included in the analysis. Patients were classified into molecular-targeted drugs (MT; 20%, 3/15), MT + cytotoxic drugs (33%, 5/15), immune checkpoint inhibitors (ICI) ± cytotoxic drugs (27%, 4/15), and cytotoxic drugs alone (20%, 3/15) groups. The overall 30-day survival rate was 47% (7/15). Improvement of oxygen demand allowed 20% (3/15) of patients to discontinue oxygen supplementation. CPA demonstrated drug class-dependent efficacy: highest in the MT group (67% survival, 2/3), less benefit in the cytotoxic drugs alone group (0% survival, 0/3). Adverse events included grade 3 anemia (n=2), grade 4 neutropenia (n=1), and grade 2 cytomegalovirus infection (n=1), with no treatment-related deaths.

CONCLUSION: CPA exhibited potential efficacy for corticosteroid-refractory DIILD, particularly in patients with MT-induced DIILD, with manageable toxicity. The differential responses based on drug category suggest tailored approaches to DIILD management may be warranted. These findings may contribute to optimizing the management of severe DIILD during cancer treatment.

PMID:40452849 | PMC:PMC12122744 | DOI:10.3389/fonc.2025.1567317

Cureus. 2025 May 1;17(5):e83302. doi: 10.7759/cureus.83302. eCollection 2025 May.

ABSTRACT

This systematic review and meta-analysis evaluated the efficacy and safety of tegoprazan compared to proton pump inhibitors (PPIs) in the treatment of erosive esophagitis (EE). A comprehensive literature search was conducted across multiple electronic databases from inception to 25 March 2025. Randomized controlled trials comparing tegoprazan with PPIs in patients with endoscopically confirmed EE were included. Primary outcomes were healing rates and safety profiles. Four randomized controlled trials comprising 963 patients were included. Meta-analysis revealed comparable healing rates between tegoprazan and PPIs (RR: 1.03, 95% CI: 0.97-1.10), with no significant differences observed at both four weeks (RR: 1.05, 95% CI: 0.96-1.16) and eight weeks (RR: 1.01, 95% CI: 0.96-1.06). Safety analyses demonstrated similar profiles between treatments, with no significant differences in treatment-emergent adverse events (RR: 0.93, 95% CI: 0.73-1.35), drug-related adverse events (RR: 0.93, 95% CI: 0.51-1.69), or serious adverse events (RR: 1.07, 95% CI: 0.12-9.29). Symptom relief was comparable between groups across all studies, with tegoprazan showing consistent efficacy, regardless of CYP2C19 genotype. Most patients had mild to moderate EE (LA grades A and B), limiting conclusions about efficacy in severe cases. This first meta-analysis directly comparing tegoprazan with PPIs suggests that tegoprazan is an effective and safe alternative to PPIs for EE treatment. Its efficacy independent of CYP2C19 polymorphism represents a potential advantage. However, limitations include the small number of studies, predominantly Asian populations, and relatively short follow-up periods. Further research is needed to assess long-term outcomes and efficacy in diverse populations.

PMID:40452708 | PMC:PMC12126153 | DOI:10.7759/cureus.83302

Can J Psychiatry. 2025 Jun 2:7067437251342279. doi: 10.1177/07067437251342279. Online ahead of print.

ABSTRACT

ObjectivesTo compare the short-term safety and efficacy of centanafadine, an investigational treatment, versus long-acting controlled-release methylphenidate hydrochloride (methylphenidate, Foquest®) among adult patients with attention-deficit/hyperactivity disorder (ADHD), using matching-adjusted indirect comparison (MAIC).MethodsThis anchored MAIC used pooled individual patient data (IPD) from two centanafadine trials (NCT03605680, NCT03605836) and published aggregate data from one methylphenidate trial (NCT02139124). Using propensity scores, IPD from the centanafadine trials were reweighted to match the aggregate baseline characteristics of the methylphenidate trial. Safety and efficacy outcomes were compared at Week 4. Safety outcomes were the rates of adverse events reported by ≥5% of patients in any treatment group in either trial with an incidence twice that of the placebo. The efficacy outcome was the mean change from baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS)/ADHD Rating Scale-5 (ADHD-RS-5) score at Week 4.ResultsAfter matching, no significant differences in baseline characteristics were observed across trials. Relative to methylphenidate, centanafadine exhibited a better safety profile, with a significantly lower risk of insomnia (risk difference in percentage points: -9.46 points) and initial insomnia (-4.68 points). There was no significant difference in efficacy across treatments as measured by the mean change from baseline in AISRS/ADHD-RS-5 score.ConclusionsIn this MAIC, centanafadine was associated with a lower risk of insomnia and comparable (i.e., nondifferent) efficacy compared to methylphenidate at Week 4. Information on the comparative safety and efficacy of ADHD treatments in the adult population will help inform personalized treatment decisions given the range of treatment options with varying attributes.

PMID:40452389 | DOI:10.1177/07067437251342279

Oncologist. 2025 Jun 2:oyaf163. doi: 10.1093/oncolo/oyaf163. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: The prognosis of biliary tract cancers (BTC) after radical resection is still unsatisfactory. However, the clinical value of adjuvant therapy remains controversial. This retrospective study aimed to evaluate the clinical value of adjuvant chemotherapy and adjuvant chemoimmunotherapy in patients with BTC after radical resection.

METHODS: Data from BTC patients who underwent radical resection were retrospectively obtained from Hunan Provincial People's Hospital between January 2020 and July 2024. Patients were divided into observation group, adjuvant chemotherapy group and adjuvant chemoimmunotherapy group according to the treatment received by the patient after surgery. Survival curves were determined by the Kaplan-Meier method. The COX proportional hazards regression model was used to determine independent prognostic risk factors. The adjuvant chemotherapy group and adjuvant chemoimmunotherapy group were analyzed by propensity score matching at 1:1 ratio.

RESULTS: A total of 219 patients with BTC were reenrolled in this study, with 108 cases of iCCA, 39 cases of pCCA, 15 cases of DCCA and 57 cases of GBC. 87 patients (39.73%) received surgery alone, 69 patients (31.51%) received postoperative adjuvant chemotherapy, 63 patients (28.77%) received postoperative adjuvant chemoimmunotherapy. There was no different significance for median recurrence-free survival (RFS) in three groups (13.20 months vs 20.40 months vs 19.68 months) (P =0.195). The median overall survival (OS) was the longest in the chemoimmunotherapy group (29.20 months vs 31.5 months vs 43.27 months) (P=0.003). After PSM, there was no difference in median RFS in two adjuvant groups (22.03 months vs 19.87 months) (P =0.350). The median OS was longer in the chemoimmunotherapy group (45.27 months vs 29.40 months) (P =0.015). In Cox analysis, lymph node metastasis, differentiation, and adjuvant treatment were the independent predictor of OS in patients with BTC. The most common adverse events were of any grade of hematologic toxicity. No drug-related deaths occurred in either group.

CONCLUSIONS: The safety of chemoimmunotherapy was acceptable and could significantly prolong the overall survival of BTC. These data provided a basis for an additional prospective clinical trial to evaluate the efficacy of chemoimmunotherapy in adjuvant therapy for BTC.

PMID:40452387 | DOI:10.1093/oncolo/oyaf163

J Sci Med Sport. 2025 May 20:S1440-2440(25)00155-0. doi: 10.1016/j.jsams.2025.05.009. Online ahead of print.

ABSTRACT

OBJECTIVES: Childhood cancer treatment has long-term health sequelae but there is more controversy for physical fitness. We compared fitness and echocardiographic variables in childhood cancer survivors (CCSs) and controls. A secondary aim was to determine the potential role of previous enrollment in inpatient exercise, and of current physical activity (PA) levels.

DESIGN: Cross-sectional.

METHODS: CCSs (age = 5-18 yrs, ≥4 yrs since diagnosis) and controls (no cancer history) were recruited. Outcomes included anthropometric, cardiorespiratory fitness (CRF)-related variables, upper/lower-body muscle strength (5-repetition maximum), functional mobility (timed up and down stairs [TUDS] test), and echocardiography. We performed sub-analyses attending to previous enrollment in supervised exercise training during intensive treatment and current accelerometer-determined PA.

RESULTS: 126 CCSs (12.8 ± 3.2 yrs, 41 % female) and 497 controls (11.2 ± 3.3 yrs, 40 % female) were studied. CCSs had a higher body mass index (+1.6 kg/m2, p < 0.001). Despite no significant differences in peak oxygen uptake (-0.5 %, p = 0.900), CCSs had lower ventilatory threshold (-9.8 %, p = 0.018), strength (-42.9 to -52.2 % depending on the analyzed exercise, p < 0.001 for most exercises) and TUDS performance (-23 %, p < 0.001) values than controls. CCSs showed a higher prevalence of left-ventricle hypertrophy and concentric cardiac remodeling. These results were independent of inpatient exercise background. CCSs showed lower levels of moderate-to-vigorous PA (MVPA) and vigorous PA (VPA) (p < 0.005). In CCSs, a positive correlation was found between MVPA/VPA levels and CRF or strength-related variables (all r > 0.4, p < 0.05).

CONCLUSIONS: CCSs showed impairments in some physical fitness and cardiac parameters ≥4 yrs posttreatment, which seemed independent of previous inpatient exercise background but not of MVPA/VPA levels after treatment.

PMID:40450428 | DOI:10.1016/j.jsams.2025.05.009

Atherosclerosis. 2025 May 26:120229. doi: 10.1016/j.atherosclerosis.2025.120229. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) have a favourable efficacy and safety profile. Advancing age may pose challenges such as increasing drug toxicity, polypharmacy, and comorbidities. This study aims to assess whether the efficacy and safety of PCSK9 mAbs are comparable between patients ≥70 years versus patients <70 years.

METHODS: In a prospective registry of all consecutive patients who started PCSK9 mAbs as part of routine care in a university medical center-based lipid clinic, data was collected on LDL cholesterol levels, side effects, and discontinuation. Data on efficacy and safety (reported side effects and discontinuation) were stratified for patients ≥70 and < 70 years.

RESULTS: Of the 474 patients (median age 59 [51-66] years, 51 % men) who started a PCSK9 mAb, 70 patients were ≥70 years (15 %). After 6 months, relative and absolute LDL cholesterol reduction was similar across age groups (relative decrease: 58 % [48-70] vs 59 % [44-71], p = 0.99; mean (SD) absolute decrease 2.4 (0.8) vs 2.4 (1.2) mmol/L, p = 0.90). A comparable proportion of patients ≥70 years compared to those <70 years achieved European and Dutch guideline-recommended goals (36 % vs 46 %, p = 0.18, and 54 % vs 62 %, p = 0.26, respectively). Efficacy outcomes were similar after 12 and 24 months follow-up. Reported side effects and discontinuation of PCSK9 mAbs were comparable across age groups.

CONCLUSIONS: Efficacy and safety of PCSK9 mAbs are comparable for patients ≥70 years and patients <70 years in a real-world study.

PMID:40450473 | DOI:10.1016/j.atherosclerosis.2025.120229

Int J Pharm. 2025 May 30:125789. doi: 10.1016/j.ijpharm.2025.125789. Online ahead of print.

ABSTRACT

Integrating artificial intelligence (AI) into drug discovery has revolutionized pharmaceutical innovation, addressing the challenges of traditional methods that are costly, time-consuming, and suffer from high failure rates. By utilizing machine learning (ML), deep learning (DL), and natural language processing (NLP), AI enhances various stages of drug development, including target identification, lead optimization, de novo drug design, and drug repurposing. AI tools, such as AlphaFold for protein structure prediction and AtomNet for structure-based drug design, have significantly accelerated the discovery process, improved efficiency and reduced costs. Success stories like Insilico Medicine's AI-designed molecule for idiopathic pulmonary fibrosis and BenevolentAI's identification of baricitinib for COVID-19 highlight AI's transformative potential. Additionally, AI enables the exploration of vast chemical spaces, optimization of clinical trials, and the identification of novel therapeutic targets, paving the way for precision medicine. However, challenges such as limited data accessibility, integration of diverse datasets, interpretability of AI models, and ethical concerns remain critical hurdles. Overcoming these limitations through enhanced algorithms, standardized databases, and interdisciplinary collaboration is essential. Overall, AI continues to reshape drug discovery, reducing timelines, increasing success rates, and driving the development of innovative and accessible therapies for unmet medical needs.

PMID:40451590 | DOI:10.1016/j.ijpharm.2025.125789

Antiviral Res. 2025 May 30:106205. doi: 10.1016/j.antiviral.2025.106205. Online ahead of print.

ABSTRACT

The incidence of orthoflavivirus infections is on the rise, yet effective antivirals are unavailable for all members of this family. Additionally, new orthoflaviviruses are emerging, highlighting the need for antiviral strategies with a pan-flavivirus activity. In response, the Global Health Priority Box was screened, leading to the identification of a compound with pan-flavivirus activity. This hit compound demonstrated inhibition of viral replication, consistent efficacy across various cell lines, and maintained activity even at high multiplicity of infection. Importantly it has a high barrier to resistance and possibly acts through a novel mechanism of action. Due to these attributes and its favorable in vitro ADMET profile, compound MMV1791425 emerges as a promising candidate for the future development of a pan-flavivirus antiviral.

PMID:40451519 | DOI:10.1016/j.antiviral.2025.106205

Discov Oncol. 2025 Jun 1;16(1):978. doi: 10.1007/s12672-025-02716-8.

ABSTRACT

BACKGROUND: Cancer poses a significant health threat, causing millions of deaths annually. Although chemotherapy-based comprehensive therapies are common, their low accuracy and severe side effects limit effectiveness. Metal-organic frameworks (MOFs), with their superior biocompatibility and stability, show great promise for drug delivery and cancer treatment. This study aims to explore the potential and developmental trajectories of MOFs in cancer research through a bibliometric analysis.

METHODS: The Web of Science Core Collection was searched for documents from its inception in 2009 to December 31, 2023. We analyzed and visualized document types, countries, institutions, authors, journals, references, and keywords using the Bibliometrix package, dplyr, sankeywheel, term extraction, and ggplot2. Additionally, the Latent Dirichlet Allocation (LDA) algorithm was employed for detailed semantic analysis, uncovering latent thematic distributions.

RESULTS: A total of 7106 authors from 1591 institutions across 45 countries contributed 1955 papers on MOFs in cancer research, published in 327 journals. China leads in research output and international collaboration, with the Chinese Academy of Sciences as the top institution. Lin Wenbin from the University of Chicago is the most influential author, and ACS Applied Materials & Interfaces is the most active journal. MOFs are predominantly studied for breast cancer, followed by lung and liver cancers. Drug delivery remains a focal point for future research.

CONCLUSIONS: This study provides a comprehensive overview of the research landscape on MOFs in cancer treatment, offering insights into key trends and future directions, particularly in drug delivery and disease-specific applications.

PMID:40450655 | DOI:10.1007/s12672-025-02716-8

BMC Cancer. 2025 Jun 1;25(1):974. doi: 10.1186/s12885-025-14162-4.

ABSTRACT

AIM: To investigate the impact of tamoxifen dose, CYP2D6 inhibitors, CYP2D6*4 genotype, and non-genetic parameters on the outcomes of tamoxifen treated female breast cancer patients.

METHOD: We retrospectively included 3218 female patients who initiated tamoxifen following a diagnosis of breast cancer with long-term follow-up (median 7.5 years). A subgroup analysis of 303 genotyped patients with a median follow-up of 9.7 years was also conducted. The outcomes of interest were overall survival (OS) and breast-cancer-specific survival (BCS).

RESULTS: In the whole cohort, an additional 20 mg of tamoxifen during six-month duration was associated with a 1.6% reduction in all-cause mortality (HR: 0.984, 95% CI: 0.982-0.985, P < 0.001) and a 1.9% decrease in breast cancer mortality (HR: 0.981, 95% CI: 0.979-0.984, P < 0.001). In the genotyped subgroup, CYP2D6*4 heterozygotes had a 76% greater risk of all-cause mortality than *4 non-carriers (HR: 1.76, 95% CI: 1.07-2.9, P = 0.025). For breast cancer-specific mortality, CYP2D6*4 heterozygotes and homozygotes had increased risk by 3.7-fold (HR: 3.7, 95% CI: 1.32-10.6, P = 0.01) and 11.6-fold (HR: 11.6, 95% CI: 1.3-103.5, P = 0.03), respectively.

CONCLUSION: Our study demonstrates that carriers of CYP2D6*4 have a higher risk of both all-cause and breast cancer-specific mortality and indicates that longer follow-up time may be crucial to determining impact. The shorter follow-up in previous studies may be a key reason for the conflicting results. A large real-world pharmacogenomic study with long-term follow-up is warranted to determine the impact of CYP2D6 genotyping and its implications for clinical decision making.

PMID:40452016 | DOI:10.1186/s12885-025-14162-4

J Toxicol Sci. 2025;50(6):245-261. doi: 10.2131/jts.50.245.

ABSTRACT

Ototoxicity, or hearing loss and damage to the auditory system caused by certain medications, is a significant clinical challenge. Many commonly used drugs, including antimicrobials, cancer therapies, and loop diuretics, have the potential to induce temporary or permanent ototoxicity. The underlying mechanisms are complex, involving both genetic and environmental factors. Pharmacogenomics, the study of how an individual's genetic makeup influences their response to drugs, has emerged as a promising field for understanding and mitigating ototoxicity. Developing personalized approaches to prevent and manage ototoxicity is crucial, and this is where the pharmacogenomic basis of ototoxicity becomes crucial. This review aims to provide healthcare professionals with an updated perspective on the genetics of ototoxicity by summarizing the latest research and insights in this rapidly evolving field. It presents a comprehensive overview of the mechanisms and genetic factors associated with drug-induced ototoxicity, with a particular focus on cisplatin and aminoglycoside antibiotics.

PMID:40451854 | DOI:10.2131/jts.50.245

J Cyst Fibros. 2025 May 31:S1569-1993(25)01497-3. doi: 10.1016/j.jcf.2025.05.008. Online ahead of print.

ABSTRACT

The use of bacteriophage (phage) to treat bacterial infection of airways in persons with cystic fibrosis (CF) is gaining interest. However, phenotypic diversification of bacteria during chronic airway infection presents a potential challenge to this therapy. We recovered and subcultured two or three Burkholderia colonies from each of 12 CF sputum samples. All isolates were tested for their susceptibility to a panel of 65 Burkholderia-targeting phages. We observed that 9 (75%) of the 12 colony sets comprised mixtures of isolates that were sensitive or resistant to one or more of the phages tested. The occurrence of mixed populations of phage-sensitive and phage-resistant Burkholderia in individuals with CF needs to be considered in the development of phage therapy for this patient population.

PMID:40451706 | DOI:10.1016/j.jcf.2025.05.008

Eur J Nucl Med Mol Imaging. 2025 Jun 2. doi: 10.1007/s00259-025-07350-8. Online ahead of print.

ABSTRACT

PURPOSE: To develop and validate a novel nomogram combining multi-organ PET metabolic metrics for major pathological response (MPR) prediction in resectable non-small cell lung cancer (rNSCLC) patients receiving neoadjuvant immunochemotherapy.

METHODS: This retrospective cohort included rNSCLC patients who underwent baseline [18F]F-FDG PET/CT prior to neoadjuvant immunochemotherapy at Xiangya Hospital from April 2020 to April 2024. Patients were randomly stratified into training (70%) and validation (30%) cohorts. Using deep learning-based automated segmentation, we quantified metabolic parameters (SUVmean, SUVmax, SUVpeak, MTV, TLG) and their ratio to liver metabolic parameters for primary tumors and nine key organs. Feature selection employed a tripartite approach: univariate analysis, LASSO regression, and random forest optimization. The final multivariable model was translated into a clinically interpretable nomogram, with validation assessing discrimination, calibration, and clinical utility.

RESULTS: Among 115 patients (MPR rate: 63.5%, n = 73), five metabolic parameters emerged as predictive biomarkers for MPR: Spleen_SUVmean, Colon_SUVpeak, Spine_TLG, Lesion_TLG, and Spleen-to-Liver SUVmax ratio. The nomogram demonstrated consistent performance across cohorts (training AUC = 0.78 [95%CI 0.67-0.88]; validation AUC = 0.78 [95%CI 0.62-0.94]), with robust calibration and enhanced clinical net benefit on decision curve analysis. Compared to tumor-only parameters, the multi-organ model showed higher specificity (100% vs. 92%) and positive predictive value (100% vs. 90%) in the validation set, maintaining 76% overall accuracy.

CONCLUSIONS: This first-reported multi-organ metabolic nomogram noninvasively predicts MPR in rNSCLC patients receiving neoadjuvant immunochemotherapy, outperforming conventional tumor-centric approaches. By quantifying systemic host-tumor metabolic crosstalk, this tool could help guide personalized therapeutic decisions while mitigating treatment-related risks, representing a paradigm shift towards precision immuno-oncology management.

PMID:40451983 | DOI:10.1007/s00259-025-07350-8

Sci Rep. 2025 Jun 1;15(1):19223. doi: 10.1038/s41598-025-03358-0.

ABSTRACT

Brain Tumours are highly complex, particularly when it comes to their initial and accurate diagnosis, as this determines patient prognosis. Conventional methods rely on MRI and CT scans and employ generic machine learning techniques, which are heavily dependent on feature extraction and require human intervention. These methods may fail in complex cases and do not produce human-interpretable results, making it difficult for clinicians to trust the model's predictions. Such limitations prolong the diagnostic process and can negatively impact the quality of treatment. The advent of deep learning has made it a powerful tool for complex image analysis tasks, such as detecting brain Tumours, by learning advanced patterns from images. However, deep learning models are often considered "black box" systems, where the reasoning behind predictions remains unclear. To address this issue, the present study applies Explainable AI (XAI) alongside deep learning for accurate and interpretable brain Tumour prediction. XAI enhances model interpretability by identifying key features such as Tumour size, location, and texture, which are crucial for clinicians. This helps build their confidence in the model and enables them to make better-informed decisions. In this research, a deep learning model integrated with XAI is proposed to develop an interpretable framework for brain Tumour prediction. The model is trained on an extensive dataset comprising imaging and clinical data and demonstrates high AUC while leveraging XAI for model explainability and feature selection. The study findings indicate that this approach improves predictive performance, achieving an accuracy of 92.98% and a miss rate of 7.02%. Additionally, interpretability tools such as LIME and Grad-CAM provide clinicians with a clearer understanding of the decision-making process, supporting diagnosis and treatment. This model represents a significant advancement in brain Tumour prediction, with the potential to enhance patient outcomes and contribute to the field of neuro-oncology.

PMID:40451921 | DOI:10.1038/s41598-025-03358-0

Magn Reson Med Sci. 2025 May 30. doi: 10.2463/mrms.mp.2024-0202. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the effect of model-based deep-learning reconstruction (DLR) compared with that of compressed sensing-sensitivity encoding (CS) on cine cardiac magnetic resonance (CMR).

METHODS: Cine CMR images of 10 healthy volunteers were obtained with reduction factors of 2, 4, 6, and 8 and reconstructed using CS and DLR. The visual image quality scores assessed sharpness, image noise, and artifacts. Left-ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) were manually measured. LV global circumferential strain (GCS) was automatically measured using the software. The precision of EDV, ESV, SV, EF, and GCS measurements was compared between CS and DLR using Bland-Altman analysis with full-sampling data as the gold standard.

RESULTS: Compared with CS, DLR significantly improved image quality with reduction factors of 6 and 8. The precision of EDV and ESV with a reduction factor of 8, and GCS with reduction factors of 6 and 8 measurements improved with DLR compared with CS, whereas those of SV and EF measurements were not different between DLR and CS.

CONCLUSION: The effect of DLR on cine CMR's image quality and precision in evaluating quantitative volume and strain was equal or superior to that of CS. DLR may replace CS for cine CMR.

PMID:40451846 | DOI:10.2463/mrms.mp.2024-0202