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PubMed2026

A systematic approach to standardizing the visual appearance of endometriotic lesions for artificial intelligence recognition.

INTRODUCTION: Numerous studies have shown that the diagnostic performance and reproducibility of visual recognition of endometriosis during laparoscopy are poor. The use of artificial intelligence (AI) seems relevant for exhaustive lesion recognition. Standardization of the visual classification of lesions, in the form of an ontology, is an essential prerequisite to enable medical experts to annotate surgical data consistently and subsequently allow engineers to train and build an artificial intelligence tool for endometriosis recognition. MATERIAL AND METHODS: A systematic search was conducted in the MEDLINE (via PubMed), EMBASE, and the Cochrane Library databases up to May 2022, aiming to identify studies describing the laparoscopic visual appearance of superficial endometriosis, endometriomas, and deep infiltrating endometriosis. The accumulated data in the literature concerning the visual appearance of the different forms of endometriosis were used to create an ontology that could be used for artificial intelligence applications. RESULTS: Out of 932 articles screened, 35 studies were selected based on the inclusion criteria of human subjects with histologically confirmed endometriosis lesions visualized via laparoscopy. The selected studies were reviewed to develop a visual ontology of endometriosis lesions observed via laparoscopy. The lesions were categorized into 4 classes and further subdivided into 11 subclasses: superficial (black, red, white, or subtle), adhesions (dense or filmy), deep (obliteration, retraction, or deformation), and ovarian (endometrioma or chocolate fluid). The positive predictive value (PPV) varied across lesion types: black lesions (PPV 47%-97%), red lesions (PPV 33%-100%), white lesions (PPV 20%-81%), and ovarian endometriosis (PPV 42%-98%). Nonspecific lesions such as adhesions (PPV 16%-50%) and subtle superficial lesions (PPV 0%-67%) presented lower PPVs. Deep endometriosis lesions, often buried within organs, required indirect signs (obliteration, retraction, deformation) for identification. CONCLUSIONS: The visual ontology proposed in this systematic search could facilitate the detection and classification of endometriosis lesions using artificial intelligence. This study highlights the challenges of reaching a consensus on lesion recognition and classification in AI projects due to the diverse visual presentations of endometriosis.

Humans↗

PubMed2026

Integrative quantum and systems biology of cancer: From molecular fluctuations to ecological outcomes.

This review treats cancer as a multiscale adaptive system, asks what the framework must predict to be worth adopting, and separates at each scale what the evidence establishes from what is proposed. It is an expert narrative synthesis, not a systematic review, and states the limits of that design. Proton transfer and tautomeric shifts contribute to spontaneous mispairing but do not license claims of directed or non-random mutation: replication timing, three-dimensional chromatin organization, sequence context and known mutagenic processes explain most mutational heterogeneity, leaving any quantum contribution as a residual against that baseline. The Waddington quasi-potential is bounded: outside detailed balance the dynamics are not gradient-derivable and require a probability-flux term. Hysteresis, rate-limited bimodality and return to state after perturbation distinguish an attractor from a transcriptomic cluster. Single-cell karyotype and live-imaging evidence supports whole-genome doubling as an unstable intermediate of heterogeneous origin and context-dependent consequence, not a uniform adaptive strategy. Systems and synthetic biology, virtual cells and digital twins are assessed against benchmarks, not promise. Tissue-scale ecology is reported with the spatial measurements now quantifying it, including evidence that stromal niche construction is not uniformly tumor-supporting. RNA modification is a layer in its own right, showing that the interpretation of a regulatory signal, not its magnitude, is biologically decisive. A dedicated section states the framework's commitments, the observable and evidence at each scale, and what would falsify them, asking what this adds to somatic mutation theory with clonal evolution and plasticity.

Neoplasms↗

PubMed2026

Lung function after randomization to metformin, lifestyle intervention or placebo in the Diabetes Prevention Program Outcomes Study (DPPOS).

INTRODUCTION: Metformin and physical activity have been suggested as beneficial for chronic lung disease; however, there are no prior randomized trials. METHODS: The Diabetes Prevention Program (DPP) was a 3-year trial that randomized 3234 individuals at risk for diabetes to metformin, lifestyle intervention or placebo. After the DPP, 88% of participants enrolled in the DPP Outcomes Study that offered lifestyle intervention to all and open-label continuation of metformin. Spirometry was performed at approximately 19 and 22 years post-randomization. Lung function measures were compared in an intention-to-treat (ITT) analysis by original randomization group. Models were unadjusted and adjusted for demographics, body size, smoking and sitting/standing at spirometry. Additional analyses tested prevalence of obstruction (FEV1/FVC <70%), restrictive pattern (FVC < LLN and FEV1/FVC ≥70%), preserved ratio impaired spirometry (PRISm: FEV1 <80% predicted, FEV1/FVC ≥70%) and symptoms (COPD Assessment Test [CAT] score ≥10). RESULTS: The 1888 participants with spirometry were a mean (±SD) age of 68.2 ± 9.3 years, 70% female and 6% currently smoked and 33% had previously smoked cigarettes. Mean follow-up time was 19.0 ± 0.8 years. The mean FEV1 was 2.14 ± 0.60 L, FVC 2.74 ± 0.74 L, FEV1/FVC 78.4 ± 6.4%, mean BMI was 32.4 ± 6.7 kg/m2 and 58% had diabetes. In both unadjusted and adjusted ITT analyses, randomization group was not associated with FEV1, FVC or FEV1/FVC. Likewise, rates of obstruction, restrictive pattern, PRISm or symptoms did not differ by randomization group. CONCLUSIONS: In this long-term follow-up after a randomized trial, we found no significant associations between randomization to metformin or lifestyle intervention and lung function or respiratory symptoms.

Humans↗

PubMed2026

Mortality of Individuals With PRNP Variants Associated With Prion Disease in the United States, 1998-2024.

BACKGROUND AND OBJECTIVES: To characterize the survival of individuals with pathogenic PRNP variants-including to estimate annual hazards, to judge the accuracy of previously reported survival data, and to evaluate the utility of public record searches in determining vital status. METHODS: In this single-center cohort study, we gathered data on individuals who received positive antemortem PRNP genetic tests at the US National Prion Disease Pathology Surveillance Center (NPDPSC), including both diagnostic tests in symptomatic individuals, and predictive tests in asymptomatic individuals. Genetic test and autopsy results were queried from the NPDPSC database, and public record searches were conducted using online tools. RESULTS: Four hundred four individuals received positive genetic test results. Of 206 cases symptomatic at the time of genetic testing, 188 are likely now deceased based on typical disease duration for their genetic variants. Combined autopsy and public record searches in combination confirmed 174 of these deaths, for an estimated 92.6% sensitivity. We evaluated the age-dependent penetrance of the reportedly highly penetrance variants D178N and E200K and the reportedly low-penetrance variant V210I. Among 99 initially asymptomatic individuals with the pathogenic E200K variant, more than 936 person-years of follow-up, 18 deaths were observed, significantly fewer than 27.4 expected according to life tables based on retrospective data. The age-dependent penetrance of E200K calculated from these longitudinal data was significantly lower than that from retrospective data, with 69% penetrance by age 80 and a median age at death of 75. For the pathogenic D178N variant, the median age at death was 57, which was numerically later, but not significantly different from, that seen in retrospective data. For V210I, just 2 deaths occurred, both after age 90, consistent with minimal penetrance. DISCUSSION: Our data support high penetrance of PRNP D178N and E200K variants and low penetrance of V210I. For E200K, the age at onset distribution appears to be shifted slightly later, and lifetime risk slightly lower, than previously reported. Autopsy data and public death records in combination were sensitive and concordant for determining long-term outcomes, but additional prospective data should be gathered to support future preventive trials.

Journal Article↗

PubMed2026

Molecular Landscape and Advanced Diagnostic Technologies for BRAF Mutations in Cancer: From Quantitative PCR and ddPCR to CRISPR-Based Platforms.

BRAF mutations are key oncogenic alterations across multiple malignancies, including melanoma, thyroid carcinoma, colorectal cancer, non-small cell lung cancer, glioma, and hairy cell leukemia. The most prevalent variant, BRAF-V600E, induces constitutive activation of the MAPK signaling pathway, promoting tumor progression and influencing therapeutic responsiveness. Accurate detection of BRAF alterations is therefore essential for molecular classification, prognostic assessment, treatment selection, and resistance surveillance. This review summarizes the molecular heterogeneity of BRAF mutations and critically evaluates current diagnostic methodologies. Conventional approaches such as allele-specific PCR and Sanger sequencing are compared with advanced quantitative platforms, including high-resolution melting analysis, droplet digital PCR, and next-generation sequencing, with emphasis on analytical sensitivity, mutation coverage, and clinical applicability. Emerging technologies such as CRISPR-based assays, rolling circle amplification systems, and nanoparticle-based biosensors and point-of-care diagnostic platforms are also discussed for their potential to enhance ultra-sensitive detection, particularly in liquid biopsy settings. These emerging tools are highlighted for their potential to enable ultra-sensitive, rapid, and decentralized mutation detection, particularly in liquid biopsy settings. Key challenges, including intratumoral heterogeneity, low allele-frequency variants, FFPE-associated artifacts, and clonal evolution under therapeutic pressure, are examined within a translational framework. In addition, we examine critical barriers to clinical implementation, including standardization, cost, and global accessibility of molecular diagnostics, and outline potential solutions through scalable technologies and decentralized testing strategies. We propose that optimal BRAF testing requires a mutation subclass-informed and clinically integrated strategy combining comprehensive baseline profiling with longitudinal molecular monitoring. Future diagnostic paradigms will likely integrate multi-omics data and artificial intelligence (AI)-assisted interpretation to refine precision oncology implementation. Looking forward, we propose that optimal BRAF testing will require integration of multi-omics profiling with AI-assisted interpretation, enabling automated variant classification, real-time clinical decision support, and improved prediction of therapeutic response and resistance.

Humans↗

PubMed2026

A polygenic risk score for peripheral artery disease and major adverse limb events.

BACKGROUND AND AIMS: Large-scale genome-wide association studies have identified common genetic variants that predict the risk of peripheral artery disease (PAD). This study assessed whether a polygenic risk score (PRS) is associated with PAD and the incidence of major adverse limb events (MALE) independent of clinical risk factors in patients with established cardiometabolic disease. METHODS: A genetic analysis was performed, pooling individual patient-level data from six TIMI trials. The association of a recently validated PAD PRS with prevalent PAD and the incidence of MALE (acute limb ischaemia, chronic limb-threatening ischaemia, major amputation, or peripheral revascularization) was assessed. RESULTS: A total of 68 816 patients were included in this analysis, with a median follow-up of 2.6 years. Of these, 5986 (8.7%) had known PAD at baseline. After adjusting for clinical risk factors, a higher PAD PRS was independently associated with a 15% greater odds of prevalent PAD (adjusted odds ratio per 1-SD: 1.15 [95% confidence interval 1.12-1.18], P < .0001), a magnitude of risk as strong as established clinical risk factors. A total of 577 patients experienced MALE during follow-up. A higher PAD PRS was associated with a 30% increased risk of MALE (adjusted hazard ratio per 1-SD: 1.30 [1.19-1.42], P < .0001). Adding the PAD PRS to clinical risk factors resulted in a statistically significant but modest improvement in discrimination (area under the curve went from 0.651 to 0.662 P < .0001). CONCLUSIONS: In a broad spectrum of patients with cardiometabolic disease, the PAD PRS is associated with an increased risk of PAD and the incidence of MALE beyond clinical risk factors; however, the improvement in discrimination was statistically significant but clinically modest.

Humans↗

PubMed2026

Exploring precision risk in pediatric vesicoureteral reflux: Innate immune gene variations and reflux outcomes in the RIVUR cohort.

INTRODUCTION: Children with vesicoureteral reflux (VUR) are at increased risk for morbidity from recurrent urinary tract infections (UTIs), yet the factors influencing spontaneous VUR resolution remain poorly defined. This study evaluates whether genetic variations in key urinary innate immune effectors (DEFA1A3, DMBT1, and RNASE7) influences VUR resolution and interacts with prophylaxis to alter clinical response. METHODS: We conducted a secondary analysis of 303 RIVUR participants with available DEFA1A3 and DMBT1 copy number variation (CNV) data and RNASE7 rs1263872 genotype. Primary outcomes were (1) VUR improvement (decrease in grade) and (2) VUR resolution at study exit. Multivariable logistic regression models included genotype, treatment, and their interactions, adjusting for age, sex, baseline grade (high vs low), laterality, bowel/bladder dysfunction, and any UTI. Internal validation used 2000-sample bootstrap with bias-corrected and accelerated confidence intervals and influence diagnostics. RESULTS: Clinical covariates did not significantly predict VUR improvement. Children with DEFA1A3 CNV >5 had higher odds of improvement (OR 2.36, 95% CI 1.12-4.96, p = 0.023), an effect that remained significant in bootstrap analyses. High-grade VUR was associated with lower odds of resolution (OR 0.34, 95% CI 0.12-0.94, p = 0.038). A significant interaction was observed between prophylaxis and high DMBT1 copy number for VUR resolution (interaction OR 2.99, 95% CI 1.11-8.04, p = 0.031); no interaction was seen for improvement. RNASE7 rs1263872 was not associated with either outcome. CONCLUSION: Innate immune gene variation may contribute to heterogeneity in VUR outcomes. High DEFA1A3 copy number was associated with reflux improvement and a DMBT1-prophylaxis interaction was associated with reflux resolution. The results of this study is hypothesis-generating and prompt further evaluation to assess whether a subset of children may experience structural benefit from prophylaxis or have a more favorable natural history based on their innate immune genotype.

Humans↗

PubMed2026

Imaging-based surgical stratification of parasagittal meningiomas involving the superior sagittal sinus: a case analysis of 62 patients.

OBJECTIVE: The objective was to evaluate the Superior Sagittal Sinus Involvement Grading (SSIG) system as an imaging-based surgical stratification framework for parasagittal meningiomas adjacent to the superior sagittal sinus (SSS) and to assess its relationship with established sinus invasion grading, venous sinus patency, and operative strategy. METHODS: In this single-center retrospective cohort study, the authors included 62 consecutive parasagittal meningioma resections performed by a single surgeon. SSIG grade was assigned primarily on contrast-enhanced coronal MRI, with CT/MR venography used when available to evaluate sinus patency and collateral venous drainage. Operative variables, resection strategy, and clinicopathological factors were compared across SSIG and Sindou grades, and postoperative complications were compared between low- and high-involvement SSIG groups. RESULTS: SSIG correlated significantly with Sindou grade (rs = 0.790, τb = 0.702, both p < 0.001), and among patients with available venous imaging, it also correlated with the venous sinus involvement grade (rs = 0.742, τb = 0.665, both p < 0.001). With increasing SSIG grade, operative time, intraoperative blood loss, and intraoperative fluid administration increased (p = 0.012, p = 0.008, and p = 0.007, respectively). Compared with the low-involvement group (SSIG grades 1, 2, and 4a), the high-involvement group (SSIG grades 3, 4b, and 5) was less likely to achieve Simpson grade I resection and more likely to adopt Simpson grades II-III strategies (66.7% vs 13.6%, p < 0.001; OR 12.667). Surgery-related complication rates did not differ significantly between groups. The mean follow-up was 13.3 ± 7.9 months, with no radiographic recurrence or progression at last follow-up. CONCLUSIONS: SSIG characterizes parasagittal meningiomas by integrating sinus invasion, venous patency, falcine extension, and parasagittal convexity involvement on preoperative imaging. This surgically oriented framework may help anticipate operative exposure, sinus handling, and resection strategy. Its predictive value for complications and long-term oncological outcomes requires validation in larger cohorts with longer follow-up.

Humans↗

PubMed2026

A prospective crossover study comparing ICCS-recommended and Palmer-adjusted filling rates in children with spina bifida.

OBJECTIVE: This study aimed to investigate whether the maximal cystometric capacity (MCC) in children with spina bifida (SB) is indeed lower, as predicted by the Palmer formula, and to evaluate the impact of different bladder filling rates on urodynamic parameters. MATERIALS AND METHODS: This prospective, randomized, two-sequence crossover-controlled study included 70 children aged 3-18 years with spina bifida under regular follow-up. In Group 1, the first two bladder fillings were performed at the ICCS-recommended rate, and the third at 75% of that rate (Palmer formula). In Group 2, the sequence was reversed. Urodynamic parameters, including maximal cystometric capacity (MCC), bladder compliance, detrusor activity, filling pressures, and detrusor leak point pressure (DLPP), were analyzed across fillings. RESULTS: Cystometric bladder capacity was lower during fillings performed at the Palmer-adjusted rate compared with those at the ICCS-recommended rate. The proportion of reduced compliance significantly decreased in Group 1 (p = 0.046) but remained unchanged in Group 2. A significant positive correlation was observed between expected bladder capacity (EBC) and measured MCC in both groups (ρ ≈ 0.5-0.6). The highest correlation and agreement were found in Group 1 during the third filling at the Palmer rate (ICC = 0.606). No significant intra- or intergroup differences were observed in detrusor pressure, end-filling pressure, DLPP, or overactive bladder prevalence. CONCLUSION: Bladder filling rate was associated with differences in both cystometric capacity and bladder compliance in children with spina bifida. Fillings performed according to the Palmer formula (approximately 75% of the ICCS-recommended rate) were associated with capacities that more closely approximated age-expected values and with modest differences in bladder compliance. Conversely, faster filling rates did not produce similar benefits. These findings suggest that slower filling strategies may improve measurement consistency and agreement with expected bladder capacity estimates. However, the magnitude and direct clinical impact of these differences should be interpreted cautiously, particularly in light of the potential influence of sequence-related effects.

Humans↗

PubMed2026

Omics in hereditary optic neuropathies: A systematic review of clinical studies with an integrated point of view.

Hereditary optic neuropathies are characterized by bilateral visual loss due to the degeneration of retinal ganglion cells, resulting in optic nerve degeneration and atrophy. Although the genetic origin of the main isolated and syndromic hereditary optic neuropathies has been characterized, the clinical phenotypes exhibit significant and poorly understood variability in both penetrance and expressivity. Additionally, the genetic and environmental factors that influence the onset of these optic neuropathies remain poorly understood, with limited biomarkers to predict disease progression or as readouts for therapeutic trials. Data-driven omics strategies allow deep phenotyping to improve our understanding of pathophysiological mechanisms and to search for new biomarkers and therapeutic targets. We explore whether the omics strategies applied to patients with hereditary optic neuropathies have provided such new insights. MEDLINE, Web of Science and EMBASE databases were screened for studies with terms relating to hereditary optic neuropathies, transcriptomics, epigenomics, proteomics, metabolomics and lipidomics in clinical studies exploring patients' samples. Out of 1244 references identified, 22 articles were included after double-masked data curation. These articles focused only on the 3 main forms of hereditary optic neuropathies, namely, OPA1-related dominant optic atrophy (n = 4), Leber hereditary optic neuropathy (n = 13), and Wolfram syndrome (n = 5). While the methodological designs and results of these studies were highly heterogeneous, they revealed molecular alterations that we have attempted to discuss at the integrated multi-omics level. This data integration highlighted several common pathophysiological mechanisms such as energetic impairment, endoplasmic reticulum stress, proteotoxic and oxidative stresses, lipid remodeling and altered amino acid and purine metabolisms, while suggesting potential new biomarkers and therapeutic targets. These findings underscore the potential of integrated multi-omics approaches to deepen our understanding of the phenotypic complexity of hereditary optic neuropathies and to support the development of innovative diagnostic and therapeutic strategies.

Humans↗

PubMed2026

Targeting cortico-striatal-amygdalar networks via theta-band frontoparietal synchronization in opioid use disorder: a randomized tACS-fMRI Trial.

Theta-band oscillation is integral to fronto-parietal connectivity in the executive control network and its top-down regulation on subcortical areas. External frontoparietal synchronization using theta-frequency transcranial alternating current (tACS) is a technology to potentially engage this network. In this pre-registered, triple-blind, sham-controlled trial (NCT03907644), we tested this intervention targeting the right frontoparietal network in people with opioid use disorder (OUD) to measure network engagement and behavioral outcomes. Sixty male participants with OUD were randomized to receive 20 min of active or sham 6 Hz tACS (HD electrodes over F4 and P4). Structural, resting-state, task-based fMRI drug cue reactivity, and repeated cue-induced craving assessments were collected immediately before and after stimulation. Pre-registered outcome measures were analyzed using time × group interaction models to examine (1) modulation of drug cue-related brain activity, (2) changes in craving, (3) alterations in functional connectivity, and (4) relationship between electric field, neural responses, and craving behavior. (1) A significant Time × Group interaction revealed decreased post-stimulation opioid cue-related activity in the active group relative to sham, involving key nodes in reward processing (ventral striatum, amygdala and ventral tegmental area) (FWE corrected α = 0.05) (2) subjective craving did not differ significantly between groups (3) Group by time generalized psychophysiological interaction analyses showed increased right frontoparietal network engagement (β = 2.63, p= 0.0308) following stimulation, and increased top-down inhibitory regulation of frontoparietal network on right ventral striatum (β = 1.99, p= 0.037) and left medial amygdala (β = 1.97, p= 0.039) (4) Electric field strength in the right frontal/parietal node predicted frontoparietal network engagement in the active group (r = 0.43, p= 0.02). Together, these findings demonstrate that theta-band frontoparietal tACS can modulate activity and task-dependent coupling within cortical-subcortical circuits in OUD, supporting network-targeted neuromodulation as a potential intervention for addiction.

Humans↗

PubMed2026

Effects of a situational interest-based rotational fitness training program on positive affect in university students: A randomized controlled trial.

BACKGROUND: To evaluate whether a 12-week situational interest-based rotational fitness program improved positive emotional states in university students, to compare module-specific effects, and to examine whether the intervention moderated the heart rate-emotion association. METHODS: In this 2-arm randomized controlled trial, 560 freshmen from 10 Chinese universities were assigned to an experimental (n = 280) or control group (n = 280). The experimental group completed weekly 90-minute sessions covering strength, endurance, speed, and agility modules; controls received regular physical education. Positive emotional states were assessed using the positive well-being subscale of the Subjective Exercise Experiences Scale through ecological momentary assessment at 3 points per session, yielding over 14,000 observations. Linear mixed-effects models tested group, time, group × time, heart rate, and heart rate × group effects. Assessors and analysts were blinded. Ethical approval for the trial was granted by the Institutional Review Board of Capital University of Physical Education and Sports (2025A055). RESULTS: Improvement was greater in the experimental group than in controls (EMM change: 1.843 vs 0.505; difference = 1.338, 95% confidence interval [CI]: 1.275-1.400, P < .001). At week 12, the raw between-group difference was 1.85 (d = 2.23), and all group × week interactions from weeks 2 to 12 were significant. Heart rate positively predicted emotional states in controls (B = 0.005, 95% CI: 0.003-0.007), but this association was attenuated in the experimental group (interaction B = -0.008, 95% CI: -0.011 to -0.005). Strength and agility showed significant improvements, while endurance produced consistently higher emotional states across assessment points. Heart rate moderation was significant for strength and endurance, but not speed or agility. CONCLUSION: The rotational program improved positive emotional states more than regular physical education, although effects varied by module. Strength showed the most robust benefit. The program also weakened, but did not eliminate, the heart rate-emotion association during more demanding activities.

Humans↗

PubMed2026

The radiographic effect of cage subsidence on neuroforamina after anterior cervical discectomy and fusion.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: The objective of this study is to investigate the effect of cage subsidence on neuroforaminal area after anterior cervical discectomy and fusion (ACDF) utilizing computed tomography (CT). SUMMARY OF BACKGROUND DATA: Restoration of disc height via implantation of an interbody device provides an indirect decompression of the cervical neuroforamina. Interbody cage subsidence is a potential postoperative occurrence, but the effect of this on neuroforaminal area has yet to be characterized. METHODS: A retrospective review was conducted of patients who underwent one- to four-levels of ACDF utilizing an interbody device with anterior plating. Cage subsidence, neuroforaminal area, height and width were measured on CT scans preoperatively and at least 6 months postoperatively. Levels with a cumulative sum of cranial and caudal subsidence greater than 4 mm were classified as severely subsided, while levels with cumulative subsidence less than 4 mm were classified as non-severely subsided. RESULTS: A total of 83 patients (151 levels) were included in this retrospective analysis. Average endplate subsidence was 3.2 ± 1.9 mm. Non-severely subsided levels demonstrated a greater perioperative increase in neuroforaminal area (7.9 vs 2.1 mm2, p < 0.001), neuroforaminal height (1.1 vs 0.4 mm, p < 0.001) and neuroforaminal width (0.7 vs 0.1 mm, p < 0.001) compared to severely subsided levels. Interbody subsidence significantly predicted a decreased change in neuroforaminal height, width and area (p < 0.001). Severe subsidence was associated with an increased rate of pseudarthrosis, but similar reoperation rates and recurrent neurologic deficits between the two groups. CONCLUSIONS: Severe subsidence of interbody cages after an ACDF was associated with a decreased perioperative change in neuroforaminal dimensions. This decrease in the size of the neuroforamen may reduce the effect of indirect decompression of the nerve root.

Humans↗

PubMed2026

Risk factors associated with urinary tract infection within 4 days of male rectal cancer surgery in the era of enhanced recovery after surgery (ERAS) programs.

BACKGROUND: Bladder drainage is systematically used in rectal cancer surgery in male patients, even in the era of enhanced recovery after surgery (ERAS). However, little data is available on risk factors for urinary tract infection (UTI). Identifying the risk factors associated with UTI within 4 days of male rectal cancer surgery in an ERAS program could support more individualized decision-making. METHODS: We used data from the GRECCAR 10 randomized clinical trial, a comparison of outcomes of transurethral catheterization (TUC) or suprapubic catheterization (SPC). 240 patients were randomized, 209 retained in the study (TUC n = 99; SPC n = 109). Univariate and multivariate logistic regression post-hoc study analyses were performed to assess association between potential predictive factors and UTI within 30 days after surgery. RESULTS: Out of 208 patients (median age 64.5 years), 19 (9.1%) had UTI, 26 (12.5%) had bacteriuria and 145 (69.7%) had pyuria. Univariate analysis identified age ≥ 65 years (OR = 3.08 [1.07-8.89]; p = 0.038), hypertension (OR = 3.65 [1.23-10.84]; p = 0.020) and ASA score ≥ 3 (OR = 4.15 [1.53-11.2]; p = 0.005) as risk factors for UTI until POD4. Multivariate analysis identified ASA score ≥ 3 with a risk of UTI. CONCLUSION: Regarding male rectal cancer surgery, our study shows that nearly 1 in 10 patients had UTI within 4 days. An ASA score ≥ 3 is an independent risk factor linked to UTI. Identifying this risk factor for UTI is necessary to advise patients, support a tailored decision-making process, and prevent these complications.

Humans↗

PubMed2026

PGR expression as a pharmacogenomic companion biomarker to GENE70-derived genomic risk in ER-positive/HER2-negative breast cancer.

BACKGROUND: The biology of the estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancers is heterogeneous even when they are categorized by their risk via genomics. Transcriptomic PGR expression reflects endocrine pathway activity and may provide complementary biological information within established GENE70-derived genomic-risk categories. Whether this molecular marker improves the biological interpretation of genomic-risk stratification beyond conventional clinicopathological assessment remains uncertain. OBJECTIVES: The aim of this study was to determine whether transcriptomic PGR expression provides complementary biological and prognostic information within reconstructed GENE70-derived genomic-risk categories and refines the characterization of endocrine-related tumour biology in ER-positive/HER2-negative breast cancer. METHODS: This study analysed publicly available transcriptomic and clinical data from three cohorts: METABRIC (discovery cohort), GSE96058/SCAN-B cohort (validation cohort) and TCGA-BRCA cohort (molecular validation cohort). The GENE70-derived genomic-risk score was reconstructed for each cohort using matched genes. Cox regression, Kaplan-Meier analysis and subgroup comparisons were used to assess relationships between PGR expression, clinicopathologic variables, molecular features and survival outcomes. RESULTS: Across the three independent cohorts, low transcriptomic PGR expression was consistently associated with higher GENE70-derived genomic risk, increased MKI67 expression, reduced ESR1 expression and enrichment of the Luminal B subtype. Survival findings differed between cohorts. In the discovery METABRIC cohort, transcriptomic PGR expression showed heterogeneous associations with survival, particularly within GENE70-derived high-risk subgroups, whereas the external GSE96058/SCAN-B validation cohort demonstrated consistent associations between low PGR expression and poorer overall survival in both the overall ER-positive/HER2-negative population and GENE70-derived high-risk subgroups. CONCLUSION: These findings suggest that transcriptomic PGR provides complementary biological and prognostic information within GENE70-derived genomic-risk categories. However, because treatment response was not evaluated in the present study, the findings should not be interpreted as evidence of predictive or pharmacogenomic utility and prospective studies incorporating treatment-response analyses are required before such applications can be established.

Humans↗

PubMed2026

Antibody-drug conjugates against multidrug-resistant cancers: Biomarker-guided patient selection, payload engineering, linker chemistry, and bystander effects.

Antibody-drug conjugates (ADCs) are one of the most significant advancements in modern cancer therapeutics. Combining the target selectivity of monoclonal antibodies with the cytotoxic potential of payloads, ADCs effectively kill cancer cells and offer hope to patients with even refractory cancer types. Beyond simply increasing the number of therapeutic options available for cancer patients, ADCs have become a powerful frontline agent in overcoming multidrug resistance (MDR). As one of the most challenging obstacles to effective cancer care, MDR is mediated by ATP-binding cassette (ABC) transporter-mediated drug efflux, target-based mutations, and dysregulated apoptosis. The clinical success of ADCs specifically engineered to overcome MDR, including in heterogeneous tumors and cancer cells that exhibit bypass signaling, is well established. This is especially evident with trastuzumab deruxtecan (T-DXd) in HER2-low, HER2-positive, and HER2-mutant cancers; sacituzumab govitecan (SG) in TROP2-expressing triple-negative breast cancer (TNBC) and urothelial carcinoma; and enfortumab vedotin in Nectin-4-positive bladder cancer. By overcoming MDR, ADCs have enabled more effective treatment algorithms across multiple malignancies. Most importantly, the clinical application of ADCs has become inextricably linked to cancer genomics. HER2 testing has evolved from a two-tiered system to a continuous spectrum including HER2-ultralow, HER2-low, HER2-positive, and ERBB2-mutant categories. Each of these categories exhibits different eligibility guidelines for ADC patient selection. As cancer cells continue to evolve and develop resistance to even ADCs through mutations and variants, researchers and clinicians have used pharmacogenomics to predict ADC response and resistance. To define the genomic architecture of ADC-resistant tumor subpopulations, single-cell transcriptomic studies and liquid biopsy approaches are being used to enable real-time examination of the tumor genome during ADC therapy, thereby optimizing treatment and circumventing resistance driven by emerging mutations and variants. This review provides a comprehensive analysis of the molecular structure of ADCs, the pharmacological principles underlying their potent cytotoxic activity against MDR cancer cells, the genomic and transcriptomic biomarkers that guide ADC patient selection, and the emerging resistance mechanisms that will shape the next generation of promising ADC development.

Humans↗

PubMed2026

Candidate biomarkers for early Giardia duodenalis infection revealed by time-resolved secretome proteomics.

Giardia duodenalis is a zoonotic protozoan parasite that causes giardiasis in humans and other mammals. Early diagnosis remains challenging because current diagnostic methods, including microscopy and enzyme-linked immunosorbent assays (ELISAs), primarily detect established infections. Consequently, a critical diagnostic gap exists during the early stage of infection within the first 2-48 h following exposure. To address this limitation, we characterized the proteins released by in vitro-cultured G. duodenalis trophozoites under serum-free conditions and evaluated their potential as early diagnostic biomarkers. Proteomic analysis of culture supernatants collected during early trophozoite incubation identified 31,773 peptides corresponding to 2504 quantifiable proteins. Temporal profiling showed distinct secretion patterns, including proteins that peaked during the early stage, progressively accumulated over time, or remained persistently abundant throughout the incubation period. Based on their secretion characteristics and predicted immunogenic properties, five candidate biomarkers were selected for further evaluation. Polyclonal antibodies raised against selected candidates successfully detected the corresponding proteins in serum-free culture supernatants, providing preliminary evidence for their potential utility as early-stage diagnostic targets. These findings identify stage-associated candidate proteins that may serve as a resource for future early giardiasis diagnostic development, provide a valuable resource for investigating host-parasite interactions, and establish a foundation for future diagnostic assay development. However, further validation in clinical and biological samples is required to confirm their diagnostic applicability. SIGNIFICANCE: Giardiasis, caused by Giardia duodenalis, is a major diarrheal disease worldwide. Although enzyme-linked immunosorbent assays (ELISAs) provide rapid detection, their diagnostic utility is limited by the lack of biomarkers capable of identifying infection during its earliest stages, creating a critical gap in the detection of active infection within 2-48 h following exposure. Using data-independent acquisition proteomics, this study provides a time-resolved characterization of proteins released by G. duodenalis trophozoites into serum-free culture supernatants. Our findings reveal temporal secretion dynamics of protein secretion and identify candidate biomarkers with potential utility for the development of early-stage diagnostic assays pending rigorous biological and clinical validation. In addition, this proteomic resource provides a foundation for investigating host-parasite interactions and may facilitate the development of future point-of-care diagnostic strategies.

Giardiasis↗

PubMed2026

Blood pressure management after endovascular thrombectomy in acute ischemic stroke: association with symptomatic intracranial hemorrhage and functional outcome at 3 months.

BACKGROUND: No clear consensus exists on ideal systolic blood pressure (SBP) targets after endovascular thrombectomy (EVT) following an acute ischemic stroke (AIS). This study investigated the association between SBP parameters within the first 24 h after EVT and 3-month functional outcomes and the risk of symptomatic intracranial hemorrhage (sICH). METHODS: We retrospectively collected and prospectively followed clinical, and radiological data for patients undergoing EVT for AIS from 2016 to 2024, including 2-hourly BP measurements during the first 24 h and SBP variability assessed by standard deviation (SD) and coefficient of variation (CV). Outcomes included 3-month functional status and sICH, and their associations with post-EVT BP metrics were analyzed. RESULTS: A total of 268 post EVT patients were included with a median age of 61 years (IQR, 51-69). Mean SBP was 129.67 ± 17.17 mm Hg, with SBP variability (SD 12.6 ± 5.4 mm Hg; CV 9.6 ± 3.8 %), while good functional outcome and sICH occurred in 39.7 % and 4.9 % of patients, respectively. Multivariate regression showed that higher admission NIHSS (>15) [0.90 (95 %CI, [0.86, 0.95], p = 0.000)], recanalization status [1.88 (95 %CI, [1.43, 2.48], p = 0.00)], and SBP-CV ≥ 10 [0.44 (95 %CI, [0.2, 0.94], p = 0.036)] was independently associated with poor 3-month functional outcome, while higher admission NIHSS (>15) [0.87 (95 %CI, [0.77,0.98], p = 0.02)] and diabetes [0.12 (95 %CI, [0.03, 0.54], p = 0.006)] predicted increased risk of sICH. CONCLUSIONS: The study showed that reduced BP variability during the first 24 h post-EVT was associated with better 3-month functional outcomes. A clear association between SBP and sICH risk was not demonstrated.

Humans↗