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PubMed2026

Lactylation-related immune-metabolic dysregulation defines prognostic and therapeutic stratification in lung adenocarcinoma.

BACKGROUND: Lactylation links lactate metabolism with inflammatory signaling and immune regulation in tumors. However, its cellular distribution and translational value in lung adenocarcinoma (LUAD) remain unclear. METHODS: Single-cell RNA-sequencing datasets GSE189357 and GSE171145 were integrated to characterize lactylation-related activity, intercellular communication, and malignant epithelial cell states in LUAD. Single-cell-derived lactylation-related differentially expressed genes were mapped to TCGA-LUAD and multiple GEO cohorts. Univariate Cox regression and machine learning algorithms were used to construct a lactylation-related prognostic signature (LRPS). The associations of LRPS with prognosis, immunotherapy response, drug sensitivity, genomic alterations, immune infiltration, and inflammation- and metabolism-related pathways were evaluated. KRT7 was further validated using virtual knockout analysis, spatial transcriptomics, and in vitro and in vivo experiments. RESULTS: lactylation-related transcriptional activity showed heterogeneous distribution across LUAD cell populations and was associated with altered cell-cell communication. In malignant epithelial cells, LRTS-high and LRTS-low states exhibited distinct metabolic, inflammatory, and tumor-related pathway activities. LRPS showed stable prognostic performance in TCGA-LUAD and multiple GEO cohorts and remained an independent prognostic factor. Low LRPS was associated with greater potential benefit from immunotherapy, whereas different LRPS groups displayed distinct drug sensitivity, genomic alteration, and immune microenvironment patterns. KRT7 was highly expressed in LUAD and associated with poor prognosis. KRT7 knockdown suppressed LUAD cell proliferation, migration, invasion, colony formation, and tumor growth in vivo. CONCLUSIONS: This study identifies lactylation-related immune-metabolic dysregulation as a clinically relevant feature of LUAD and develops a single-cell-guided LRPS for prognosis and therapeutic stratification. KRT7 emerged as an LRPS-related functional candidate with experimentally supported roles in malignant LUAD phenotypes.

Immunotherapy↗

PubMed2026

Comparative safety and operative efficiency of surgical approaches for open reduction and internal fixation of mandibular condylar fractures: a systematic review and network meta-analysis.

BACKGROUND: The optimal surgical approach for mandibular condyle fractures remains controversial, particularly regarding the trade-off between facial nerve safety and surgical efficiency. METHODS: Our systematic review and frequentist NMA analyzed studies evaluating open reduction and internal fixation (ORIF) for mandibular condyle fractures. The primary safety outcome was transient or persistent (≥6 months) facial nerve weakness. The efficiency outcome was operative exposure time. Surgical approaches were categorized, and random-effects NMAs estimated odds ratios (ORs) and mean differences (MDs). Treatments were ranked using P-scores, and clustered rankings explored safety-efficiency relationships. RESULTS: Overall, 121 studies (n = 6659 patients) were included. For facial nerve safety, endoscope-assisted (EA), preauricular transmasseteric anteroparotid (PATMA), and high submandibular (HSMA) approaches ranked highest, while the retromandibular transparotid (RMTA) approach carried a higher risk. Analyses restricted to persistent weakness yielded consistent results. For exposure time, submandibular (SM), HSMA, and retromandibular transmasseteric anteroparotid (RMTMA) approaches were most efficient. Clustered ranking analysis identified HSMA and RMTMA as achieving the best overall balance between safety and efficiency. Subgroup analyses confirmed the overall hierarchy, though evidence for high-level and intracapsular fractures remains limited. CONCLUSIONS: HSMA and RMTMA offer an optimal compromise between safety and efficiency for extracapsular condylar fractures, while EA may minimize nerve injury risk where technical expertise allows. High-quality comparative trials - particularly for intracapsular fractures - are warranted.

Humans↗

PubMed2026

Single antiplatelet therapy and tirofiban bridged with surface modified flow diverters for ruptured blood blister-like aneurysms: single center experience and systematic review.

BACKGROUND: Blood blister-like aneurysms (BBAs) of the internal carotid artery are rare but high risk lesions that frequently re-rupture due to their fragile structure and dissecting pathology. Treatment is particularly challenging in ruptured cases, given the risks associated with dual antiplatelet therapy. Recent advancements in flow diverter stents (FDSs) with surface modifications, and the use of single antiplatelet therapy (SAPT), offer a potential alternative strategy. METHODS: We conducted a retrospective review of 17 patients with ruptured internal carotid artery BBAs treated with surface modified FDS under SAPT (ticagrelor or prasugrel) bridged periprocedurally with intravenous tirofiban. All procedures were performed within the acute phase of subarachnoid hemorrhage. Clinical, radiographic outcomes, and procedure related complications were evaluated. RESULTS: Among 17 patients, 94.1% achieved complete angiographic occlusion, and 76.5% attained favorable clinical outcomes (modified Rankin Scale score ≤2). No aneurysm rebleeding or device related ischemic events occurred. A total of 11 patients underwent external ventricular drainage or ventriculoperitoneal shunting without discontinuing SAPT, and no hemorrhagic complications were observed. A literature review incorporating seven additional series identified a total of 42 FDS plus SAPT treated BBA cases, with similar safety and efficacy profiles. CONCLUSIONS: Surface modified FDS with SAPT and tirofiban bridging appears to be a promising treatment option for ruptured BBAs, offering high occlusion rates with minimal thromboembolic and hemorrhagic complications. Larger prospective studies are needed to validate these findings.

Humans↗

PubMed2026

Towards microplastic bioremediation: Fungal degradation of pristine and pretreated high-density polyethylene and polystyrene.

Microplastic (MP) contamination has become a significant ecological issue because of its enduring existence in the ecosystem and its possible negative impacts. Therefore, using degrading strategies to eliminate these stubborn polymers has been a subject of scientific research. However, the currently used degradation methods are relatively inefficient. Given the pervasiveness of High-Density Polyethylene (HDPE) and Polystyrene (PS) and their resistance to biodegradability, disposal strategies are critical and must be addressed. This manuscript examines the biodegradation of pristine and UV-treated HDPE and PS MPs by Aspergillus flavus species in minimal growth media over 70 days. The maximum weight loss observed at 70 days for pristine HDPE and PS in sole carbon source (SCS) media was (29.33 ± 0.28) % and (17.67 ± 0.35) %, respectively. Whereas, for UV-treated HDPE and PS MPs, the % weight reduction was (33 ± 0.21) % and (25 ± 0.19) %, respectively. UV-treated MPs exhibited greater weight reduction, as UV induced oxygenated functional groups enhance polymer susceptibility to enzymes, thereby promoting biodegradation. HDPE MPs typically show a higher proportion of particles in the lower size range compared to PS MPs. This assertion was based on the weight loss, particle size distribution, and SEM analysis. Furthermore, chemical changes were evaluated using Fourier transform Infrared Spectroscopy (FTIR) analysis, which also displayed chemical oxidation occurring during biodegradation. Liquid Chromatography-Mass Spectrometry (LC-MS) results indicate that UV pretreatment enhances biodegradability by promoting chain scission. These findings further suggest that this fungus's natural and ubiquitous occurrence in terrestrial and marine environments may actively contribute to MP biodegradation while requiring few nutrients.

Microplastics↗

PubMed2026

The effect of olfactory training and odor exposure on visual selective attention.

Olfactory training (OT) is a well-established, non-invasive intervention that improves olfactory function by repeated, structured exposure to odorants. Beyond sensory outcomes, it also influences multiple aspects of cognition. Yet, its influence on attention, a fundamental process underlying many cognitive domains, remains unclear. This study examined the impact of a 12-week OT program on visual selective attentional performance and the effect of on-task odor exposure. Ninety-four healthy participants were initially included, and randomized into OT or placebo groups. Participants completed the d2 Test of Attention simultaneously with and without odor exposure in a randomized sequence at baseline, post-training, and a follow-up four weeks after stopping the training. The d2 test measures commission errors, omission errors, and concentration performance. Ninety-three participants (OT=51, placebo=42) completed baseline measurement, 74 (OT=39, placebo=35) returned for post-training session, and 57 participants (OT=29, placebo=28) returned for the follow-up appointment. Results showed that OT did not significantly improve d2 test performance. In the primary model, on-task PEA exposure reduced commission errors compared to the odorless condition, suggesting a possible transient effect of olfactory input on the inhibitory control in the context of the d2 attentional test. This effect, however, was no longer significant once the follow-up data were included and should be regarded as preliminary. Overall, these findings raise the possibility of a distinction between relatively long-term OT and short-term odor exposure: while OT did not improve visual selective attention, brief on-task odor exposure may transiently enhance inhibitory control during attentional tasks, a possibility that remains to be confirmed.

Humans↗

PubMed2026

Understanding psychosocial adjustment in military-to-civilian transition: A latent profile analysis of ex-serving Australian Defence Force members.

Military-to-civilian transition is a critical life stage that can expose veterans to elevated risks of psychological distress, social difficulties, and reduced wellbeing. Although psychosocial factors are central to successful reintegration, little is known about distinct patterns of needs among ex-serving Australian Defence Force (ADF) members. This study used latent profile analysis (LPA) to identify psychosocial needs profiles across five domains of the Military-Civilian Adjustment and Reintegration Measure (M-CARM) in a sample of 725 ex-serving ADF members. The optimal three-class solution identified: a Low Adjustment Need (LAN) group (20.7%) reporting minimal reintegration challenges; a Cultural Adjustment Need (CAN) group (42.9%) characterized by cultural adaptation difficulties, particularly beliefs about civilians and regimentation; and a Cultural and Psychological Need (CPN) group (36.4%) showing broader challenges across beliefs about civilians, purpose and connection, regimentation, and resentment and regret. The CAN group was more likely to be male, have lower educational attainment, and have no combat deployment history. The CPN group was similarly male dominated with lower education, and was additionally characterized by Navy service, unemployment or not being in the labor force, and medical discharge. Compared with the LAN group, both CAN and CPN groups reported higher levels of depression, anxiety, posttraumatic stress, and nightmare distress, as well as poorer quality of life and greater functional impairment. These findings highlight persistent reintegration challenges among veterans and support the need for stratified support models, ranging from psychoeducation to intensive multidisciplinary care, to better address diverse psychosocial needs of ex-serving ADF members.

Australian defense force↗

PubMed2026

Redox Rewiring in Nicotine-Driven Gastric Carcinogenesis: Uncovering ROS-Dependent Oncogenic Circuits.

SIGNIFICANCE: Nicotine from tobacco products, secondhand smoke, and emerging delivery systems remains a major but underappreciated driver of gastric carcinogenesis (GC). Although reactive oxygen species (ROS) have long been implicated in tumor biology, current models incompletely explain how chronic nicotine selectively reprograms gastric epithelial signaling. This review advances the concept of redox rewiring, whereby nicotine establishes a persistent oxidative state that orchestrates multiple oncogenic programs via spatially compartmentalized NOX signaling. RECENT ADVANCES: We synthesize evidence for a unified model wherein nicotine activates nAChR/β-AR signaling, Ca2+ influx, PKC, and compartmentalized NOX-derived ROS to generate distinct oncogenic outputs. Beyond the established NOX/ROS/NF-κB/MAPK-driven IL-8 and MMP-9 axes, we integrate emerging evidence into three interconnected modules governing EMT/metastasis (ABL1/STAT3/COX-2/periostin), survival/chemoresistance (ERK/GLI1/Bcl-2), and invasion/immune evasion (miR-21/PDCD4). Collectively, these circuits suggest that ROS function not merely as damaging byproducts but as spatially organized signaling mediators dictating tumor behavior. CRITICAL ISSUES: A major challenge is distinguishing established mechanisms from incompletely validated models. The three proposed axes are testable hypotheses requiring experimental validation. Most data derive from in vitro studies with nonphysiologic nicotine concentrations, and artifacts from nonspecific ROS probes are common. Compensatory pathway activation and multi-target effects of natural products remain underexplored. FUTURE DIRECTIONS: We outline a precision-redox oncology roadmap linking pathway-specific biomarkers, mechanistically matched natural products, and biomarker-enriched trials. Priorities include genetic validation of the three axes, time-resolved ROS imaging, and pulsed natural product regimens. By reframing nicotine-driven GC as adaptive redox network remodeling, this review provides a framework for prevention, stratification, and next-generation therapy. Antioxid. Redox Signal. 00, 000-000.

gastric cancer↗

PubMed2026

Pelvic lymph node dissection in prostate cancer: current evidence, controversies, and future directions.

BACKGROUND: Pelvic lymph node dissection (PLND) remains controversial in the management of prostate cancer. Although it provides the most accurate pathological staging, its therapeutic value beyond staging has long been debated due to conflicting evidence and concerns regarding procedure-related morbidity. OBJECTIVE: To critically evaluate the contemporary role of PLND, particularly extended pelvic lymph node dissection (ePLND), in prostate cancer management in the context of modern imaging, risk stratification tools, and evolving oncologic endpoints. EVIDENCE ACQUISITION: A narrative review of recent literature was conducted, focusing on high-level evidence including randomized trials, observational studies, and contemporary guideline recommendations addressing the indications, extent, oncologic outcomes, and complications of PLND. EVIDENCE SYNTHESIS: Recent randomized and observational studies suggest that ePLND improves nodal staging accuracy and may be associated with modest improvements in metastasis-free survival (MFS) in selected patients with intermediate- and high-risk prostate cancer, although the absolute benefit remains limited and causality is not definitively established. Advances in molecular imaging, particularly prostate-specific membrane antigen (PSMA) PET/CT, together with multiparametric MRI, validated nomograms, and emerging genomic classifiers, now allow more precise identification of patients most likely to benefit from ePLND. The integration of these tools supports a more individualized surgical strategy, including image-guided and sentinel lymph node approaches designed to maximize staging accuracy while minimizing unnecessary dissection. CONCLUSIONS: In the contemporary PSMA imaging era, ePLND continues to play an important role in nodal staging and may contribute to improved oncologic outcomes in carefully selected patients.

Humans↗

PubMed2026

Misalignment between ultra-processed status and 'better for you' claims on premix alcohol products.

BACKGROUND: Premix alcohol products (also known as ready-to-drink beverages) are a rapidly expanding alcohol category and frequently marketed using 'better for you' claims (e.g., 'Low sugar', 'Natural'). Little is known about the extent to which these products are ultra-processed or whether marketing claims align with ultra-processed status. This study aimed to address this evidence gap by auditing ingredient disclosure on premix products, assessing the ultra-processed status of these products, and determining the prevalence of 'better for you' claims with a particular focus on claims relating to ultra-processed status. METHODS: 534 premix alcohol products sold in major Australian retail outlets were assessed. Products were evaluated for compliance with mandatory ingredient disclosure, classified according to ultra-processed status based on the presence of indicators of ultra-processing (additives and other industrial ingredients), and analysed to determine the prevalence and types of 'better for you' marketing claims. RESULTS: Only 79% of assessed products displayed an ingredients list. Among compliant products, 98% contained at least one additive or ingredient indicative of ultra-processing, most commonly flavours, carbonating agents, colours, and sweeteners. One-third (33%) of products containing an ultra-processing indicator displayed a claim suggesting naturalness or minimal processing. Substantially higher proportions of ultra-processed products than non-ultra-processed products carried health-related claims. DISCUSSION AND CONCLUSIONS: Premix beverages available in Australia are overwhelmingly ultra-processed, yet many are marketed in ways that may mislead consumers about their composition and healthfulness. Stronger regulatory oversight of ingredient disclosure and marketing claims in this sector is urgently needed to support informed consumer decision-making.

Alcoholic Beverages↗

PubMed2026

The Impact of Oncological Treatments on Return to Work, Work Ability, and Sickness Absence in Breast Cancer Survivors: A Systematic Review.

PURPOSE: Returning to work and maintaining an adequate ability to work serve as key indicators of quality of life, psychological well-being and psychosocial adjustment. Therefore, this study aims to analyze the impact of breast cancer treatments on return to work (RTW), work ability (WA), and sick leave (SL) among breast cancer survivors. METHODS: A systematic review was conducted according to the PRISMA guidelines. The sample consisted of 26 studies published between 2016 and 2025, including prospective multicenter cohorts and national registries from fifteen countries across four continents, with more than 25,000 participants. A methodological quality assessment and a narrative synthesis were performed to synthesize the results. RESULTS: Chemotherapy is the most consistent predictor of prolonged SL, delayed RTW, and significantly reduced WA. Radical surgery and axillary lymph node dissection (ALND) are associated with a significantly delayed RTW due to physical sequelae. While outcomes showed strong relationship with clinical factors, certain psychosocial variables such as depression, anxiety, and low self-efficacy seemed to act as important secondary factors that can further complicate the process. CONCLUSION: The findings suggest that more invasive or aggressive treatments (chemotherapy, ALND, and radical surgery) were associated with poorer outcomes on RTW, WA, and SL. Furthermore, the clinical recovery associated with treatment completion did not necessarily equate to a functional recovery in WA that facilitated a successful RTW. Thus, it is necessary to explore in depth the impact of cancer treatments on WA, alongside psychosocial variables, to design multidisciplinary interventions that enable sustainable occupational reintegration. REGISTRATION: PROSPERO 2026 (CRD420261322638).

Breast cancer survivors↗

PubMed2026

Navigated repetitive transcranial magnetic stimulation for post-stroke recovery: A systematic review and meta-analysis of randomized controlled trials.

Repetitive transcranial magnetic stimulation (rTMS) is a subcategory of non-invasive brain stimulation (NIBS), used to modulate brain plasticity and improve post-stroke recovery. Neuronavigation is used to improve the accuracy of stimulation with the aim of achieving a superior clinical outcome than with conventional targeting. The objective of this review is to evaluate the efficacy of navigated rTMS in subacute and chronic stroke patients in comparison to sham stimulation. We conducted a systematic-review and meta-analysis of randomized controlled trials (RCTs) identified from Pubmed, Scopus and Cochrane CENTRAL. Trials employing neuronavigated rTMS were included of these five types; high and low frequency rTMS, intermittent and continuous theta-burst stimulation (TBS) and Hebbian-type stimulation. 13 RCTs were included after a screening of 1900 studies. 606 patients receiving either active (n = 360) or sham stimulation (n = 246) were assessed. The pooled standardized mean difference (SMD) favored rTMS over sham SMD = 0.4 (95 %CI: 0.11-0.69), with moderate heterogeneity I2 = 55 %. Among stimulation modalities, continuous TBS showed the largest pooled effect. rTMS was also associated with significant improvements in disability-related outcomes, SMD = 0.61 (95 % CI 0.14-1.08). Navigated rTMS is associated with modest but significant improvements in motor and disability outcomes in subacute and chronic stroke. Large comparative trials are required to clarify the potential added value over conventional targeting approaches.

Humans↗

PubMed2026

Evolution of Candidaemia and azole resistance in Italy: A multicentre retrospective study.

PURPOSE: Candidaemia is the most common healthcare-associated invasive fungal infection. The evolution of the epidemiology of candidaemia in Italy has not been assessed, except at the local level. The primary objective of this study is monitoring changes in the epidemiology of candidaemia and in the susceptibility profiles of Candida isolates between 2015 and 2023. METHODS: This retrospective multicentre study (2015-2023), involved 11 tertiary-care hospital microbiology laboratories across the Italian country. The confirmed candidaemia episodes were included and demographic data, hospital ward, species identification, and antifungal susceptibility profiles (Sensititre Yeast One) were collected. RESULTS: 6,927 candidaemia cases were identified; incidence increased from 1.1/1000 hospitalisations in 2017 to 2.3/1000 in 2020-2021, peaking during the COVID-19 pandemic, and declined in 2023 while remaining above prepandemic levels. Patients older than 65 years accounted for most infections. Medical wards represented the main setting of occurrence, followed by intensive care units, especially during pandemic years. C. albicans remained the most common species (45.4%), followed by C. parapsilosis (24.7%), C. glabrata (11.8%), and C. tropicalis (11.4%). Echinocandin resistance remained low (< 2% for C. albicans and C. glabrata), whereas azole resistance increased markedly, particularly in C. parapsilosis, reaching fluconazole resistance rates of 25.6% in 2022. CONCLUSIONS: Candidaemia increased during the 9-year study period in Italy, particularly in the COVID-19 pandemic, in medical wards and ICU. Emerged a growing azole resistance, underscoring the need for enhanced surveillance and informed empirical treatment strategies.

Candida species etiology↗

PubMed2026

Influence of built environment on occupational health of women workers in tea plantations of India: a systematic review.

The built environment, comprising homes, buildings, roads, public spaces, infrastructure, land use, civic design, and amenities, has a considerable influence on occupational health. In India's tea plantations, where women comprise majority of the workforce, the built environment plays a crucial role in determining occupational health. The aforementioned point can be explained by the co-occurrence of living and working conditions, which often coexist in tea plantations, further resulting in vulnerabilities to the health of women workers. Therefore, to understand the influence of built environment on the occupational health of women workers in tea plantations of India, the present paper employs a systematic review using the PRISMA 2020 framework. In the first search, 421 studies were identified, of which 21 studies met all the inclusion criteria. A quality appraisal and risk of bias of the included studies have been undertaken. The results identified that musculoskeletal disorders (MSDs) are the most prevalent occupational health consequence, affecting over 80 % of the women workers in Indian tea plantations, substantiated by a range of estimates in the studies reviewed. Gendered disparities in wage earning, self-autonomy, and dual responsibilities often lead to emotional distress, as delineated in minimal of the reviewed studies, grounded on self-disclosed or qualitative analysis. Further, deprived housing conditions and other facilities across the reviewed studies reflect institutional negligence. Therefore, by conducting a systematic synthesis of occupational health of women workers in the Indian tea plantation sector through the lens of the built environment, prior accounts have been extended. Addressing these issues is essential for safeguarding women workers, which will ensure the longevity of the Indian tea industry.

Female↗

PubMed2026

To Treat or Not to Treat: Navigating Early-Stage CLL in the Era of Targeted Therapy.

Chronic lymphocytic leukemia (CLL) is most frequently diagnosed at early, asymptomatic stages (Rai 0/Binet A), in which a watch-and-wait strategy remains the standard of care, based on historical trials demonstrating no overall survival benefit from early treatment. Over the past two decades, however, substantial advances in genomic profiling-including immunoglobulin heavy-chain variable region (IGHV) mutational status, TP53 disruption, recurrent gene mutations, and complex karyotype-have uncovered marked biological heterogeneity among early-stage patients and substantially improved prediction of disease progression. In parallel, targeted therapies such as Bruton tyrosine kinase (BTK) inhibitors and venetoclax-based combinations have transformed the management of symptomatic CLL, raising renewed interest in whether early intervention might favorably alter the natural history of biologically high-risk disease. In this review, we critically examine the evolution of prognostication in early-stage CLL, integrate contemporary molecular and clinical risk models, and summarize evidence from both historical chemotherapy-era studies and modern early-intervention trials. We discuss key unresolved controversies, including reliance on surrogate endpoints, the risks of overtreatment, and the persistent absence of an overall survival benefit across all early-treatment strategies. Finally, we outline future research priorities, including refined genomic stratification, minimal residual disease-driven (MRD)-driven approaches, and combination targeted therapies currently under investigation. Despite renewed interest in preemptive treatment, available evidence supports continued observation for asymptomatic patients outside clinical trials.

Humans↗

PubMed2026

Integration of single-cell transcriptomics and genomic mutation analysis identifies an immunotherapy-resistant tumor subcluster and validates ARNTL2 as a malignant driver in lung adenocarcinoma.

BACKGROUND: Immunotherapy resistance in lung adenocarcinoma (LUAD) remains a critical clinical challenge, and the mechanisms underlying resistance-associated intratumoral heterogeneity are poorly characterized. METHODS: We performed single-cell RNA sequencing of LUAD patients receiving neoadjuvant immunotherapy (responders vs. non-responders), integrating inferCNV, GSVA, and differential expression analyses. Cluster-specific genes were validated across seven independent cohorts (TCGA-LUAD, GSE13213, GSE26939, GSE29016, GSE30219, GSE31210, GSE42127). A multi-algorithm machine learning framework was used to construct a prognostic model, and the immune microenvironment was characterized using TCIA scoring, seven infiltration algorithms, and ESTIMATE. ARNTL2 function was assessed by CCK-8 and Transwell assays in A549 and H1299 cells. RESULTS: Non-responders showed significant enrichment of epithelial cells, depletion of cytotoxic T/NK cells, and elevated copy number variation burden versus responders (p < 0.0001). A resistance-enriched malignant subcluster (Cluster 2) exhibited hyperproliferative and metabolic reprogramming signatures with upregulated KRT17, S100A2, and CST6, which showed tumor-specific overexpression, adverse prognostic value, and genomic amplification across cohorts. CoxBoost combined with survivalSVM achieved optimal predictive performance (C-index = 0.686), yielding robust risk stratification (HR: 2.54-10.51, all p < 0.05). Low-risk patients showed greater immune infiltration and higher TCIA immunophenoscores. ARNTL2 was an independent prognostic factor (HR: 2.07-4.64) strongly correlated with risk score (r = 0.69), and its knockdown suppressed proliferation and invasion in both LUAD cell lines (all p < 0.05). CONCLUSION: This study identifies a resistance-associated malignant subcluster in LUAD, constructs a validated CoxBoost + survivalSVM prognostic model with robust immune stratification, and establishes ARNTL2 as a core oncogenic driver and therapeutic target.

ARNTL2↗

PubMed2026

Accurate quantification of canine mitochondrial DNA copy number from canine blood and brain samples.

Acute brain injury is difficult to evaluate in veterinary medicine and tools to investigate the potential involvement of mitochondrial involvement are limited. The brain is highly enriched in mitochondria and contains thousands of copies of mitochondrial DNA (mtDNA) per cell, but robust methods for quantifying mitochondrial DNA copy number (mtDNA-CN) in canine tissues are lacking. We describe the development of a quantitative real-time PCR assay for absolute measurement of mtDNA-CN which was validated in canine blood and brain tissue. To minimize amplification of nuclear mitochondrial insertion sequences (NumtS) and repetitive regions, species-specific oligonucleotide primers were designed following in silico genomic filtering. The assay was applied to a small pilot cohort comprising blood samples from dogs with and without acute brain injury (n = 4-6 per group) and cerebral cortex samples (n = 1 per group) to assess feasibility and biological plausibility. In non-brain injury dogs, blood mtDNA-CN ranged from 98 to 288 copies per nuclear genome (mean 193 ± 72), while values in brain-injured cases ranged from 163 to 228 copies per genome (mean 200 ± 33). Cerebral cortex samples exhibited higher mtDNA-CN than blood, consistent with known tissue-specific mitochondrial enrichment. In a single brain-injured case with serial sampling, mtDNA-CN increased over five days. This study presents a validated assay and pilot data for mtDNA-CN quantification in canine samples. While not powered for biomarker evaluation, this method may enable future studies of mitochondrial dynamics in canine brain injury and metabolic disease.

Animals↗

PubMed2026

Hypothalamic-Pituitary Axis Involvement in Primary Central Nervous System Lymphoma.

CONTEXT: Primary central nervous system lymphoma (PCNSL) is a rare malignancy that may involve the hypothalamic-pituitary axis (HPA), leading to underrecognized but clinically significant endocrine dysfunction. OBJECTIVE: This work aims to characterize the spectrum and patterns of HPA-related endocrine disturbances in patients with PCNSL. DATA SOURCES: A systematic search was conducted in PubMed, EMBASE, Scopus, and Web of Science, supplemented by gray literature. The search concluded in February 2025. STUDY SELECTION: We included studies reporting adult PCNSL cases with documented dysfunction of at least one hormonal axis. Exclusion criteria were preexisting hypopituitarism or lack of endocrine data. DATA EXTRACTION: Data on demographics, tumor localization, hormonal axes affected, radiological findings, treatment, and outcomes were extracted. Risk of bias was assessed using JBI tools. RESULTS: Ninety-nine cases met the inclusion criteria. Diffuse large B-cell lymphoma accounted for 84% of cases. Endocrine dysfunction included isolated adenohypophyseal involvement (46%), neurohypophyseal (8%), and combined (45%). The most affected pituitary axes were the gonadal and thyroid axes, with 89.7% and 89.2% involvement, respectively. Hypothalamic tumors were strongly associated with combined dysfunction (odds ratio = 9.47; 95% CI, 3.76-23.86; P < .001). Persistent endocrinopathy was more frequent in progressive disease. No direct association was found between endocrine dysfunction and mortality. CONCLUSION: HPA dysfunction in PCNSL is frequent and often underdiagnosed. Hypothalamic involvement is associated broader hormonal impairment. Routine hormonal screening and multidisciplinary management should be standard in PCNSL care to minimize complications and improve outcomes.

Humans↗

PubMed2026

Adjuvant CDK4/6 inhibitors in early-stage breast cancer: Clinical evidence and considerations for risk stratification and treatment selection.

Hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer is the most common biologic subtype and carries a persistent risk of recurrence, particularly in patients with high-risk, early-stage disease. Cyclin-dependent kinase 4 and 6 inhibitors, initially established as a standard component of first-line therapy in the metastatic setting based on improvements in progression-free and overall survival, have since been evaluated in the adjuvant setting. While adjuvant palbociclib did not improve invasive disease-free survival, the monarchE and NATALEE trials demonstrated that abemaciclib and ribociclib, respectively, reduce recurrence risk in patients with high-risk, early-stage disease, with emerging overall survival data further supporting their use. However, the absolute magnitude of benefit varies substantially with baseline risk, and treatment-related toxicity and adherence challenges must be considered, as approximately 20% to 25% of patients discontinue therapy before completion. The integration of these agents into clinical practice also intersects with ongoing efforts to deescalate axillary surgery, as treatment eligibility has been largely defined by anatomic staging, particularly nodal status. Available data suggest that the incremental impact of axillary surgery on identifying candidates for cyclin-dependent kinase 4 and 6 inhibition is modest, especially among the favorable-risk populations now eligible for surgical deescalation. As the field evolves, advances in molecular risk stratification, genomic profiling, and dynamic biomarkers are poised to shift treatment selection from anatomic staging toward biologically driven approaches. Multidisciplinary decision-making that integrates tumor biology, anticipated absolute benefit, toxicity, patient preferences, and surgical considerations will be essential to ensure individualized care.

Humans↗