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FEBS Open Bio

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Preprints posted in the last 7 days, ranked by how well they match FEBS Open Bio's content profile, based on 31 papers previously published here. The average preprint has a 0.03% match score for this journal, so anything above that is already an above-average fit.

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Prognostic significance of the C-reactive protein-albumin-lymphocyte (CALLY) index in primary lung malignancies: a systematic review and meta-analysis with GRADE assessment

Shamohammadi, M.; Yarahmadi, D.; Naseri Rad, F.; Patel, I.; Yarahmadi, M.; Rashidi, A.; Yarahmadi, A.; Kordestani Moghadam, P.; Naghavi, N.

2026-10-20 oncology 10.64898/2026.10.18.26365819 medRxiv
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Background: The C-reactive protein-albumin-lymphocyte (CALLY) index integrates systemic inflammation, nutritional status, and immune function. We evaluated its association with survival in primary lung malignancies. Methods: Embase, PubMed, Scopus, and Web of Science were searched from inception to 18 September 2026. Risk of bias was assessed using the Quality In Prognosis Studies tool. Hazard ratios (HRs) were synthesized using random-effects models with restricted maximum likelihood estimation and Hartung-Knapp adjustment. Sensitivity analyses, subgroup analyses, and meta-regression examined robustness and heterogeneity. Results: Eleven studies contributed 13 cohorts to the overall survival (OS) analysis and 8 cohorts from seven studies to a combined recurrence/progression-free survival (RFS/PFS) analysis. Lower CALLY was associated with poorer OS (HR 1.78, 95% CI 1.49-2.12; I2=71.6%) and poorer RFS/PFS (HR 1.60, 95% CI 1.40-1.84; I2=0%). Associations persisted in leave-one-out analyses. No statistically significant subgroup differences were detected. Funnel-plot asymmetry suggested small-study effects for OS and RFS/PFS. Seven studies had moderate and four had high overall risk of bias. The certainty of evidence was rated as low for both OS and RFS/PFS, primarily due to risk of bias, heterogeneity, and endpoint indirectness. Conclusion: Lower CALLY was associated with adverse survival outcomes in the current synthesis. Methodological limitations and variation in biomarker measurement and endpoint definitions restrict interpretation. Prospective validation using standardized measurements and clinically coherent outcomes is needed to establish incremental prognostic value and clinical utility. Keywords: CALLY index; lung cancer; prognosis; overall survival; systematic review; meta-analysis

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Peripheral Biomarkers and Determinants of Survival for Patients with Melanoma Brain Metastasis Treated with Immune Checkpoint Blockade

Hassan, J.; Little, M.; Farkas, A.; Mackay, S.; Coupe, N.; Middleton, M.; Payne, M. J.; Fairfax, B.

2026-10-21 oncology 10.64898/2026.10.19.26365947 medRxiv
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Background Immune checkpoint blockade (ICB) has become the standard of treatment for metastatic melanoma (MM). However, patients with melanoma brain metastases (MBM) are often excluded from clinical trials. Here we analyse patients within the real-world OxCITE cohort receiving ICB treatment for metastatic melanoma, with a focus on MBM, aiming to discern outcomes, prognostic factors and peripheral biomarkers. Methods Patients eligible for ICB treatment were recruited prospectively. Demographic, clinical and radiological data were collected from electronic patient records. Plasma samples were collected prior to the first cycle of treatment for plasma proteomic analysis. Results 307 patients were included, 81 of whom had MBM on commencing ICB. No difference in overall survival between patients with and without brain metastases was noted on multivariable analysis (HR=1.1, 95% CI 0.73-1.6, p=0.68), whereas hepatic metastases were associated with increased risk of death (HR 1.7, 95% CI 1.2-2.4, p=0.0019). Within the MBM group, steroid treatment (HR=2.5, 95% CI 1.3-5.0, p=0.006) was associated with poor OS, whilst treatment with single agent ICB (HR=1.9, 95% CI 0.86-3.9, p=0.11), symptomatic first presentation of MBM (HR=1.5, 95% CI 0.76-2.8, p=0.25) and anti-seizure drug treatment (HR=1.74, 95% CI 0.89-3.4, p=0.10) were not. Amongst all patients carriage of a BRAF mutation was associated with increased risk of MBM (OR 2.49, 95% CI 1.4-4.4, p=0.0007), and increased propensity to new brain metastases on ICB treatment (OR 2.5, 95% CI 1.1-5.9, p=0.036). Analysis of blood and plasma samples demonstrated that patients with MBM have altered haematological profiles, with raised NLR and increased plasma glial fibrillary acidic protein levels, reinforcing the distinct systemic features of MBM. Conclusions In this real-world cohort of patients receiving ICB for metastatic melanoma, the presence of MBM did not associate with worse OS. Conversely, baseline corticosteroid use was adversely prognostic. Intriguingly, plasma GFAP was significantly elevated in patients with MBM and correlated with the burden of intracranial disease, highlighting a potential role for GFAP as a candidate biomarker for MBM in high-risk surveillance. Our observations indicate the adversely prognostic weight historically attached to M1d disease is no longer applicable in the ICB era.

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No decline in functional status or cognitive function during the first year after treatment initiation for early-stage breast cancer in women aged 75 years and older: a prospective observational matched cohort study

van der Plas-Krijgsman, W. G.; Blom, J. W.; Derks, M. G. M.; van Dalen, T.; van Gerven, L.; Guicherit, O. R.; Lans, T. E.; Linthorst-Niers, E. M. H.; Merkus, J. W. S.; Vulink, A. J. E.; Mooijaart, S. P.; de Glas, N. A.; Gussekloo, J.; Liefers, G.-J.; Portielje, J. E. A.

2026-10-15 oncology 10.64898/2026.10.14.26365509 medRxiv
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Background: This study compared functional and cognitive trajectories in older women treated for early breast cancer with matched women without cancer. Methods: Data were derived from two Dutch cohorts: the CLIMB study (women aged 75 years and older with operable breast cancer) and the ISCOPE study (community-dwelling women aged 75 years and older without cancer). Breast cancer patients were matched 1:2 to controls on age and baseline functional or cognitive status. Functional status was assessed using the Groningen Activity Restriction Scale (GARS), and cognitive function using the Mini-Mental State Examination (MMSE). Longitudinal changes over 12 months were analyzed using both unadjusted and confounder-adjusted linear mixed models. Results: 168 breast cancer patients and 336 matched breast cancer-free controls were included with a mean age of 80 years. Most breast cancer patients had stage 0-I or II disease and received surgery and/or radiotherapy; 48% received adjuvant endocrine therapy, chemotherapy was rare (<1%). At baseline, both cohorts were comparable in age and functional or cognitive status, although there was a higher comorbidity burden in the control cohort. No significant differences in functional or cognitive decline were observed between the cohorts over 12 months. Conclusions: In older women, early breast cancer and its treatment did not lead to accelerated decline in functional status or cognitive function within the first year compared to matched older women without cancer. These findings suggest that, for relatively fit older patients, breast cancer treatment may not accelerate functional decline in the short term.

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Near infrared spectroscopy during non-ischaemic handgrip exercise reveals divergent muscle oxygenation signatures in mitochondrial disease and sarcopenia

Devine, H.; Brito da Silva, A.; Hillman, S.; Brownstein, C.; Smith, S.; Rao, K.; Pickett, S.; Turnbull, D.; Whittaker, R.; Hurst, C.; Witham, M. D.; Sayer, A. A.; Bulea, T.; Cooper, R.; Suetterlin, K.

2026-10-21 neurology 10.64898/2026.10.21.26364901 medRxiv
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Background: Mitochondrial dysfunction is a hallmark of ageing and is implicated in the pathogenesis of sarcopenia. Genetically confirmed mitochondrial disease provides a biologically definitive model of impaired oxidative phosphorylation against which novel functional assessments can be validated. We investigated whether a brief, submaximal, non-ischaemic intermittent isometric handgrip exercise protocol combined with Near Infra-Red Spectroscopy (NIRS) could detect distinct muscle oxygenation signatures in mitochondrial disease and sarcopenia. Methods: Adults with genetically confirmed mitochondrial disease (n=10, 7 female) and group-matched controls (n=19, 11 female), underwent assessment of maximal grip force, handgrip relaxation kinetics and a 3-minute intermittent submaximal isometric handgrip test (40% maximal voluntary contraction, 1Hz contraction/relaxation) with continuous force recording at 2000Hz and simultaneous NIRS. Findings were compared with 23 community-dwelling older adults from the Muscle Ageing and Sarcopenia Study (MASS) Lifecourse cohort (n=23, 13 female) including seven with probable or confirmed sarcopenia according to European Working Group on Sarcopenia in Older People (EWGSOP2) criteria. Results: Participants with mitochondrial disease demonstrated an attenuated reduction in tissue saturation index (TSI) during exercise compared with controls (TSI % {middle dot} s150-180s: -59.9 {+/-} 94.5 vs -175.1 {+/-} 128.4; p=0.02). Total haemoglobin (THb) responses did not differ between groups (p=0.10). In contrast, participants with probable or confirmed sarcopenia showed exaggerated reduction in TSI compared with non-sarcopenic participants (TSI % {middle dot} s150-180s: -256.5 {+/-} 146.0 vs -121.2 {+/-} 95.2; p=0.05), while THb responses remained similar. The association between sarcopenia and TSI differed by sex (interaction coefficient -240, p=0.016), with greater TSI reductions observed in males with sarcopenia. Differences in TSI between mitochondrial disease and control groups were independent of age and sex. No statistically significant associations were observed between THb responses and age, sex or force production. Conclusions: A brief, non-ischaemic handgrip exercise protocol combined with NIRS identified divergent muscle oxygenation responses in mitochondrial disease and sarcopenia. The attenuated TSI response observed in genetically confirmed mitochondrial disease is consistent with impaired oxygen utilisation secondary to defective oxidative phosphorylation, whereas the exaggerated TSI reduction observed in sarcopenia suggests a distinct physiological mechanism, potentially involving impaired oxygen delivery, reduced muscle efficiency, or both. This portable and non-invasive approach has significant potential as a physiological biomarker for mechanistic studies and clinical trials in ageing and neuromuscular disease. More broadly, our findings demonstrate how biologically defined rare diseases can provide a powerful framework for interpreting mechanisms in common heterogeneous age-related conditions.

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Host Determinants of Adjuvant Chemotherapy Initiation and Survival in Upper Gastrointestinal Adenocarcinoma

Jiao, B.; Alotaibi, S.; Abumelha, K.; Tankel, J.; Ferri, L.; Asselah, J.; Alcindor, T.; Mueller, C.; Rousseau, M.; Soldera, S.; Lee, L.; Bertos, N.; Dehghani, M.; Ma, K. A.; Cools-Lartigue, J.

2026-10-15 oncology 10.64898/2026.10.13.26365477 medRxiv
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Introduction: Perioperative systemic therapy improves outcomes in gastroesophageal adenocarcinoma, but many patients do not receive postoperative treatment. We examined whether host characteristics and perioperative inflammatory and albumin changes provided information about adjuvant initiation beyond tumour pathology, and whether initiation was associated with survival and disease control. Method: This retrospective cohort included patients undergoing curative-intent resection for gastroesophageal adenocarcinoma at the McGill University Health Centre between 2006 and 2025. Sequential logistic models evaluated pathological characteristics, pre-treatment host variables and perioperative changes in CBC-derived neutrophil-to-lymphocyte ratio (cNLR) and albumin. Postoperative measurements preceded adjuvant initiation. Nested comparisons used matched complete cases. Day-90 landmark and time-varying Cox models assessed associations between adjuvant initiation and survival. Results: Among 243 patients, 78 (32.1%) did not initiate adjuvant therapy. Adding host variables improved apparent discrimination for initiation beyond pathology (AUC 0.672 to 0.763; P=0.002). Greater perioperative cNLR increase was associated with lower odds of initiation (adjusted OR 0.67 per unit increase in {Delta}log2; cNLR, 95% CI 0.47-0.95), whereas more favourable albumin change was associated with higher odds (OR 1.07 per g/L, 95% CI 1.01-1.13). Neither marker retained a clear independent association when modelled together. Adjuvant initiation by day 90 was associated with longer overall survival (adjusted HR 0.53, 95% CI 0.36-0.78) and disease-free survival (HR 0.57, 95% CI 0.39-0.84), with similar time-varying findings. Conclusion: Host inflammatory and albumin changes added information about adjuvant initiation beyond tumour pathology, and initiation was associated with longer survival. Prospective evaluation should determine whether host-directed perioperative strategies can improve postoperative treatment delivery.

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Real-world perioperative FLOT delivery in gastric and gastro-oesophageal junction adenocarcinoma: a single-centre service evaluation in a District General Hospital in the UK

Sabharwal, R.; Bhaskaran, D.

2026-10-21 oncology 10.64898/2026.10.19.26365836 medRxiv
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Background: Although perioperative fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) is the standard neoadjuvant regimen for resectable gastric and gastro-oesophageal junction adenocarcinoma, evidence describing treatment delivery in routine clinical practice remains limited, particularly regarding relative dose intensity (RDI) and treatment completion. Objectives: To evaluate real-world delivery of preoperative FLOT chemotherapy, including treatment completion, progression to surgery, RDI, toxicity and exploratory changes in estimated lean body mass (LBM). Methods: A retrospective single-centre service evaluation included consecutive patients receiving neoadjuvant FLOT during 2024. Outcomes included treatment completion, surgery, RDI, toxicity, pathological response and estimated LBM. Descriptive statistics were used. Results: Twelve patients were included (median age 68.6 years; 91.7% male). Eleven (91.6%) completed all four preoperative cycles and proceeded to surgery. Mean RDI was 76.7%. Pre-emptive dose capping was the predominant dose modification strategy, with only one reactive dose reduction. Two grade 3 adverse events occurred. Major pathological response (Mandard grade 1-2) was observed in 2/12 patients (16.7%). Mean estimated LBM declined from 54.3 to 53.4 kg. Greater LBM loss appeared to coincide with poorer clinical outcomes. Conclusions: High treatment completion and progression to surgery were achieved despite reduced RDI. These findings support prospective evaluation of strategies to optimise chemotherapy delivery while maintaining tolerability in routine clinical practice.

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Plasma Neurofilament Light Chain is Markedly Elevated in General Hospital Inpatients with Delirium

Kang, M. J.; Eratne, D.; Borchard, T.; Patel, K.; Malpas, C. B.; Dang, C.; Storer, M.; Bhalala, O. G.; Yu, J. J.; Santillo, A. F.; Forbes, M.; Zetterberg, H.; Farrand, S.; Loi, S. M.; Mitchell, P. B.; Hopwood, M.; Smith, J.; Chiang, C.; Velakoulis, D.

2026-10-20 geriatric medicine 10.64898/2026.10.18.26365854 medRxiv
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Objective: To determine whether plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are elevated in hospitalised patients with delirium relative to patients with dementia and primary psychiatric disorders (PPD). Methods and analysis: This was a cross-sectional observational study conducted at the Royal Melbourne Hospital, Melbourne, Australia, between April and October 2024, with comparator samples from a research biobank. In Phase 1 (Delirium Discovery Cohort), we measured plasma NfL and GFAP using the Single molecule array (Simoa) platform in hospitalised patients with delirium and compared them with dementia and PPD groups. Biomarker concentrations were the primary outcome and were compared using general linear models adjusted for age, sex, and estimated glomerular filtration rate, with bootstrapped confidence intervals. Discriminative performance was assessed as a secondary outcome using receiver operating characteristic (ROC) curve analysis. In Phase 2, we applied this threshold to independent dementia and PPD groups. Results: In Phase 1 (n =176), inpatients with delirium showed higher concentrations of both NfL and GFAP than patients with dementia ({beta} = 0.78; 95% CI [0.37, 1.20] and {beta} = 0.39 [0.07, 0.73] respectively) or PPD groups ({beta} = 1.17; [0.69, 1.66] and {beta} = 0.83 [0.51, 1.24] respectively). ROC curve analysis for differentiating delirium from dementia and PPD groups yielded an optimal NfL threshold of 24.1 pg/mL (AUC = 0.89, 96% sensitivity, 70% specificity). In comparison, GFAP showed lower accuracy (AUC = 0.85), and combining NfL with GFAP (AUC = 0.90) did not significantly improve performance. In Phase 2 (n = 154), the NfL threshold of > 24 pg/ml maintained strong performance (AUC = 0.95, 96% sensitivity, and 77% specificity). Conclusions: Plasma NfL shows promise as a biomarker for delirium in hospitalised patients, distinguishing it with high sensitivity from patients with dementia and PPD. Larger multicentre studies are needed to refine cut-offs, evaluate temporal dynamics, and determine integration into acute hospital delirium pathways.

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Diagnostic accuracy of deep learning for microsatellite instability prediction in gastric cancer: A systematic review and meta-analysis

Du, Y.; Liao, H.; Li, J.; He, Y.; Di, J.

2026-10-15 oncology 10.64898/2026.10.12.26365351 medRxiv
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Deep learning (DL) applied to haematoxylin and eosin (H&E)-stained pathology images can predict microsatellite instability (MSI) in gastric cancer (GC). We evaluated its diagnostic accuracy and discriminative performance. PubMed, Embase, Cochrane Library and Web of Science were searched for studies applying DL to H&E images for MSI prediction in GC. The protocol was prospectively registered in PROSPERO (CRD420261503140). Risk of bias was assessed with QUADAS-2. Pooled sensitivity and specificity were estimated with a bivariate random-effects model, with subgroup analyses by validation strategy and data source; slide-level areas under the curve (AUCs) were pooled after logit transformation. Prespecified scenario analyses assessed robustness. Ten studies were included; seven independent datasets from six studies entered the primary synthesis. Pooled sensitivity, specificity and summary receiver operating characteristic AUC were 0.78 (95% CI 0.63-0.88), 0.85 (95% CI 0.77-0.90) and 0.89 (95% CI 0.86-0.91); nine studies contributed to the secondary AUC synthesis (pooled AUC 0.85, 95% CI 0.80-0.89). Hospital-derived cohorts showed numerically higher sensitivity (0.86) and diagnostic odds ratio (39.8) than TCGA-derived cohorts (0.71 and 11.5), but subgroup differences were limited by the small number of studies and substantial heterogeneity. DL models show good diagnostic accuracy for MSI prediction in GC, but clinical utility still requires confirmation in standardised multicentre, independent external and prospective studies.

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Genomic correlates with survival after treatment of oesophageal adenocarcinoma by surgery alone

Trinh, A.; Udumanne, T. P.; Lord, S. J.; Falkenback, D.; Levert-Mignon, A. J.; Liew, Y. J.; Pascovici, D.; Bourke, M. J.; Grady, J. P.; McCabe, M.; Naeini, M. M.; Joshua, A.; Barnet, M.; Goldstein, L. D.; Ross, J.; Johansson, J.; Lord, R. V.

2026-10-16 oncology 10.64898/2026.10.14.26365576 medRxiv
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New prognostic biomarkers for oesophageal adenocarcinoma (OAC) may help treatment planning as current staging does not accurately predict survival for many patients. We used a 451 cancer-associated gene panel to assess genomic alterations associated with survival for a cohort of 65 OAC patients who underwent surgical resection without perioperative treatment, reflecting institutional practice at the time. Median age at operation was 72 years, 88% were male, median 32 lymph nodes were removed per patient, and minimum follow-up exceeded 11 years. TNM stages (pTNM, 8th ed.) were 14% stage 1, 14% stage 2, 45% stage 3, and 6% stage 4 (non-locoregional nodal metastases). Copy number changes were common, and somatic mutations were similar to those reported previously. Genetic associations with worse survival included amplification of CCND1 (HR=3.08, p=0.02), EGFR (HR=2.98, p=0.01), loss of ARID2 (HR=2.12, p=0.05), KMT2D (HR=1.99, p=0.07) and missense mutation within RYR1 (HR=2.68, p=0.01). This study identifies candidate genomic prognostic biomarkers in OAC using a cohort treated by surgery alone, enabling assessment of tumour biology independent of the confounding effects of peri-operative systemic therapy and radiotherapy. Several of the identified alterations are potentially targetable, supporting further investigation of genomic profiling to refine prognostication and guide treatment selection.

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Association between Resilience and Financial Toxicity: The Moderating Role of Age, Race and Socioeconomic Factors

Zhan, Y.; Wells, R.; Knobf, T.; Shan, L.; Lustberg, M. B.; Wang, H.-L.

2026-10-21 nursing 10.64898/2026.10.19.26365649 medRxiv
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PURPOSE: Women with metastatic breast cancer (MBC) are at risk of developing financial toxicity due to prolonged treatment. Resilience has been identified as a key protective factor associated with better quality of life among cancer populations. However, it is unknown if resilience is associated with financial toxicity. We sought to examine the relationship between resilience and financial toxicity among women with MBC and explore whether socioeconomic factors moderate this association. PATIENTS AND METHODS: Our sample included 209 women with MBC who completed self-reported questionnaires of the Resilience Scale Specific to Cancer (RS-SC) and the Comprehensive Score for Financial Toxicity (COST). Participants (n=2) with missing data were excluded from analysis. We conducted multiple linear regression to examine the association of resilience with financial toxicity. Interaction terms were used to test moderating effects of age (18-39, 40-64 and > =65 years), race, education, health insurance, household income and employment status. RESULTS: Of the sample, 56.5% were aged 40-64 years, 76.6% were White, and 79.9% had a college or master degree or above. Women reported moderately high resilience with mean RS-SC score of 34.49 (SD = 6.67), and moderate financial toxicity (mean COST score =21.01 [SD = 10.51]). Adjusting for covariates, higher resilience was linked to better financial well-being (b = 0.37, SE= 0.11, 95% CI [0.14, 0.59], P < 0.01). Age, education and health insurance moderated this relationship, with resilience more strongly associated with better financial well-being among those aged 40-64 years, with college/master degree or above and private insurance. Race, household income, and employment status did not moderate the association between resilience and financial toxicity. CONCLUSION: Women with MBC who reported higher resilience are more likely to experience better financial well-being, but the strength of this association varied by socioeconomic factors. Further research is needed to confirm these findings. Our results have important implications for incorporating resilience into financial toxicity interventions and tailoring such interventions based on individual socioeconomic characteristics.

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Does the Disease-free Survival Benefit of Adding Belzutifan to Adjuvant Pembrolizumab Persist Beyond the Planned Treatment Period? A Reconstructed Individual Patient Data Analysis of Phase 3 Renal Cell Carcinoma Trials

Chang, H.-H.; Chang, C.-K.; Tang, T.-Y.; Jhan, J.-H.; Dong, S.-W.; Juan, Y.-S.; Geng, J.-H.; Ou, H.-C.; Lee, H.-Y.; Li, C.-Y.; Yeh, H.-C.; Leong, M.-K.; Liu, C.-H.; Lee, Y.-C.; Huang, S.-P.

2026-10-16 oncology 10.64898/2026.10.14.26365591 medRxiv
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Background and Objective: Adding belzutifan to adjuvant pembrolizumab improved disease-free survival (DFS) in LITESPARK-022, but its durability beyond the 1-year treatment is unknown. Methods: Following a registered plan, we reconstructed individual patient data from published Kaplan-Meier curves of ten phase 3 adjuvant renal cell carcinoma trials. Within each trial, we estimated restricted mean survival time differences ({Delta}RMST), hazard ratios (HRs) before and after planned treatment ended, and DFS differences. Key Findings and Limitations: In LITESPARK-022 (central review), the 24-month {Delta}RMST was 1.34 months (95% confidence interval 0.73-1.95), and the belzutifan arm remained ahead after month 12 ({Delta}RMST increment 0.74 months/yr, 0.32-1.19). The HR was 0.55 (0.43-0.71) before month 12 and 1.16 (0.87-1.54) afterwards (post/pre ratio 2.10); investigator assessment showed similar attenuation. Similar ratios occurred in KEYNOTE-564 at its first interim analysis (2.02), whose benefit persisted, and in SORCE and PROTECT (2.09, 2.59), whose benefit faded. From months 12 to 30 (post hoc), the DFS difference changed by -3.7 percentage points (-8.1 to 0.8) with central review and 0.6 (-4.0 to 5.0) with investigator assessment. Data were reconstructed, and follow-up was short. Conclusions and Clinical Implications: Relative hazard reductions with belzutifan were greater before month 12; durability of the absolute DFS advantage is uncertain and assessment-dependent, so single-HR projections should be avoided.

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Longitudinal associations between neuropsychiatric symptoms, structural and perfusion MRI changes in older adults with Mild Cognitive Impairment

Lombardi, G.; Leung, C. C.-Y.; Burge, R.; Zelaya, F.; Bhattacharyya, S.; Velayudhan, L.

2026-10-19 geriatric medicine 10.64898/2026.10.15.26364284 medRxiv
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Neuropsychiatric symptoms (NPS) are highly prevalent in Mild Cognitive Impairment (MCI), conceptualized as an intermediate clinical state between normal aging and dementia. Although neuroimaging studies have reported associations between NPS and brain alterations in MCI, longitudinal evidence on NPS and their relationship with multimodal MRI measures remains limited. We aimed to investigate (1) longitudinal changes in NPS, volumetric assessment and measurement of regional cerebral blood flow (CBF) within the medial temporal lobe (MTL); (2) associations between longitudinal changes in MRI measures and NPS; (3) whether baseline MRI measures predicted longitudinal changes in NPS. Thirty individuals with MCI aged over 65 years were recruited, of whom eighteen followed up for a mean period of 29 {+/-} 8.9 months. There were significant reductions in total grey matter and white matter volumes, together with volume loss in the bilateral hippocampus, bilateral parahippocampal gyrus and right entorhinal cortex (pFDR[&le;]0.05) over the follow up period. Volume loss in the right parahippocampal gyrus was associated with increase in aggression (pFDR<0.01), and CBF increase in the right hippocampus and parahippocampal gyrus was associated with worsening in agitation (pFDR<0.01). Furthermore, lower baseline volume of the right entorhinal cortex was associated with increase in aggression, and lower baseline CBF in the right hippocampus and parahippocampal gyrus was associated with worsening of agitation (pFDR<0.05). Our findings highlight the importance of identifying NPS in individuals with MCI and the role of structural and perfusion MRI measures as promising biomarkers for monitoring disease progression and improving risk prediction of conversion to dementia.

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Blood-based PhenoAge may reflect disease burden rather than biological aging in cancer

Simhal, A. K.; Lee, J.; Tan, K. S.; McCormick, P. J.; Fischer, G. W.; Scarpa, J. R.; Sapiro, G.; Mincer, J. S.

2026-10-19 oncology 10.64898/2026.10.15.26365671 medRxiv
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PhenoAge, a blood-based biological aging clock, is associated with cancer outcomes, a finding taken as evidence that biological aging shapes prognosis. In 3,067 patients undergoing primary tumor resection, PhenoAge acceleration rose with tumor stage. One or two of its eight blood components, differing by cancer type, carried the prognostic signal, and replacing its general-population weights with equal weights did not weaken it. In cancer, PhenoAge may reflect disease burden rather than biological aging.

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Clinicopathologic Predictors of PSMA-PET Detection, Recurrence Pattern, and Biochemical Outcome Following Salvage Radiotherapy After Radical Prostatectomy

Jubril, R.; Prabhu, A. V.; Ishaq, O.; Ocana, J. A.; Tann, M.; Njeh, C.; Bahler, C. D.; Holmes, J.; Oderinde, O.

2026-10-19 oncology 10.64898/2026.10.16.26365643 medRxiv
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Purpose: Biochemical recurrence (BCR) after radical prostatectomy (RP) presents heterogeneous recurrence patterns and variable outcomes following salvage radiotherapy (sRT). We evaluated clinicopathologic determinants of PSMA-PET/CT detection, anatomical recurrence distribution, and biochemical disease-free survival (bDFS) following PSMA-PET-guided sRT. Methods: This retrospective single-institution study included 140 patients with BCR after RP who underwent Ga-PSMA-PET/CT prior to sRT with or without androgen deprivation therapy. PSMA-PET-positive findings were categorized as prostate bed only (PBO) or pelvic nodal involvement with or without the prostate bed (PLNI). Receiver operating characteristic (ROC) analysis, logistic regression, and Cox proportional hazards models were employed. Results: PSMA-PET detected locoregional recurrence in 77/140 patients (55%). On multivariable analysis, PSA at recurrence (OR=2.07; p=0.003) and age (OR=1.07; p=0.016) were the sole independent predictors of PSMA-PET positivity. ROC analysis yielded AUC=0.74 (optimal threshold of 0.58 ng/mL). Among PSMA-positive patients, PBO was associated with a longer time to BCR (tBCR) (37.5 versus 15 months; p=0.006). Seminal vesicle invasion (SVI) and pT-stage predicted PLNI on univariable analysis. Among 124 of 140 evaluable patients (median follow-up 31 months), estimated bDFS at 24, 36, and 60 months was 89.7%, 80.2%, and 54.1%, respectively. SVI (HR=2.39; p=0.031), EPE (HR=2.82; p=0.012), pT-stage (HR=1.64; p=0.021), and pN-stage (HR=1.83; p=0.045) were associated with increased failure on univariable Cox regression, though none retained independent significance. Conclusion: PSA burden and age independently predicted PSMA-PET detection. Recurrence patterns reflected disease behavior, as PBO was associated with longer tBCR. Adverse pathologic features were associated with pelvic nodal disease and reduced biochemical control; none remained independently predictive.

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Development and Feasibility of a Communication Accommodation Training Module for Health Profession Students

Rothermich, K.; Clark-Stallkamp, R.; Baker-Iyore, R. P.; Cuatico, C.; Lee, J. G. L.; Bobb, S. C.

2026-10-19 medical education 10.64898/2026.10.16.26365768 medRxiv
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Objectives: Health professions students often receive limited training on how to adjust their communication for patients whose first language is not English (LX), despite the risks for diagnosis, treatment, and patient trust. Based on Communication Accommodation Theory, we developed a brief module to improve students' awareness and knowledge of strategic communication adjustments for LX patients. Methods: We tested feasibility in a single-group, pre-post pilot study guided by the Kirkpatrick framework with undergraduate (n=22) and graduate (n=41) speech-language pathology and psychology students in Massachusetts and North Carolina. The module included instructional content, video and audio examples, interactive activities, and a podcast. Learning was assessed with knowledge checks, and self-reported facilitative and resistant accommodation with the Communication Accommodation Behavior Scale (CABS). After training, students rated their confidence and likelihood of using accommodation strategies. Results: At both sites, facilitative accommodation increased and resistant accommodation decreased significantly, with a larger decrease at the undergraduate site. Knowledge-check accuracy was high at both time points, suggesting a ceiling effect. Students reported moderate- to-high confidence in adapting their speech and high likelihood of using a learned strategy in future clinical encounters. Conclusions: A brief module can be feasibly delivered across institutions and is associated with short-term improvements in self-reported communication accommodation. Practice implications: We recommend future work evaluate whether these changes translate into clinical behavior long-term and refine knowledge-check items to better capture learning gains.

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What are the experiences, perceptions and training needs of inpatient general nursing staff on Continuous Glucose Monitoring?

Donat Ergin, B.; Mattishent, K.; Holder, D.; Minihane, A. M.; Kelly, B.; Holt, R.; Murphy, H.; Dhatariya, K.; Hornberger, M.

2026-10-15 nursing 10.64898/2026.10.14.26365417 medRxiv
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Background: Although point-of-care testing is the standard method for inpatient glucose monitoring; it is associated with patient discomfort and late detection of dysglycaemic events. Continuous glucose monitoring (CGM) may improve glycaemic management; however, limited staff education and experience among may hinder its implementation. Aim: To investigate experience, perceptions and training needs on CGM use among inpatient nursing staff across diverse hospital wards. Methods: This is a single-centre, 38-item online survey recruited inpatient nurses in a hospital in the UK. Participants were invited via the e-newsletter and posters; the survey remained open for five months. Results: Nineteen nurses reported positive perceptions of inpatient CGM. Most considered CGM reliable (77.8%) and preferred CGM combined with POCT (66.7%). Views on its impact on workload and patient-room entries were mixed (30% agreed, 30% disagreed). Training needs included sensor placement (92.9%) and alarm management (78.6%). Conclusion: Nurses viewed CGM favourably but highlighted important training needs for inpatient use.

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Discrepancies in Interpretation of Japanese Radiology Report Expressions Between Radiologists and Referring Physicians

Yamaguchi, T.; Matsuo, H.; Nishio, M.; Inukai, J. I.; Matsunaga, T.; Kojita, Y.; Sofue, K.; Murakami, T.

2026-10-21 radiology and imaging 10.64898/2026.10.19.26364709 medRxiv
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Objectives To evaluate discrepancies between radiologists and referring physicians in the interpretation of diagnostic probabilities conveyed by common Japanese expressions used in radiology reports. Materials and Methods Fifteen expressions commonly used to convey diagnostic probabilities in radiology reports were selected by five attending radiologists. An anonymous online survey was distributed to 26 radiologists and 33 referring physicians at a single institution. Participants assigned a diagnostic probability (from 0% to 100% in 10% increments) to each expression. Differences in median probabilities between radiologists and referring physicians were analyzed using the Mann-Whitney U test. Variability in interpretation was assessed using interquartile range (IQR), with IQR [&ge;] 30% defined as substantial variability. Results All radiologists (26/26) and 97% of referring physicians (32/33) completed the survey. Seven of the 15 expressions showed statistically significant differences in interpretation between radiologists and referring physicians: "c/w" (80% vs. 60%; p = 0.031), the Japanese equivalents of "present" (100% vs. 100%; p = 0.024), "suspect of" (80% vs. 70%; p = 0.007), "possibly" (50% vs. 70%; p < 0.001), "unlikely" (10% vs. 10%; p = 0.022), "cannot be ruled out" (25% vs. 40%; p < 0.001), and "not inconsistent with" (80% vs. 90%; p = 0.008). Substantial variability in interpretation (IQR [&ge;] 30%) was observed for four expressions: "cannot be ruled out" (IQR, 10%-40%), "s/o" (IQR, 60%-90%), "c/w" (IQR, 50%-90%), and "not inconsistent with" (IQR, 70%-100%). Conclusion This study revealed that nearly half of the Japanese expressions commonly used to convey diagnostic probabilities were interpreted differently by radiologists and referring physicians. These discrepancies highlight the need for a standardized lexicon to improve clarity and consistency in radiology reporting.

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Professional Identity and Its Influencing Factors Among Nursing Interns: The Mediating Role of Career Adaptability Between Social Support and Professional Identity

Zhao, Y.; Liu, F.; Chen, L.; Li, X.; Wu, B.

2026-10-16 occupational and environmental health 10.64898/2026.10.14.26365571 medRxiv
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Purpose: The internship period is a critical stage for nursing students to develop professional values. This study aimed to investigate the current status of professional identity among nursing interns, analyze the effects of social support, perceived stress, psychological resilience, and career adaptability on professional identity, and explore the mediating role of career adaptability between social support and professional identity, so as to provide empirical evidence for enhancing professional identity and optimizing nursing talent training systems. Methods: Using convenience sampling, 407 nursing interns from a tertiary hospital in Quanzhou were selected as participants from May to July 2025. Data were collected using a general information questionnaire, the Social Support Scale, the Perceived Stress Scale, the Psychological Resilience Scale, the Professional Identity Questionnaire for Nursing Students, the Career Adaptability Scale, and the Questionnaire for Nurse Intention to Retention Employed. SPSS 26.0 was used for reliability analysis, descriptive analysis, independent samples t-test, one-way ANOVA, Pearson correlation analysis, and multiple linear regression analysis. The PROCESS macro was employed to test the mediating effect. Results: The total score of professional identity among nursing interns was (61.74{+/-}11.08), with 73.5% showing moderate professional identity. Parents' attitude toward nursing, reasons for choosing the profession, personal attitude toward the major, and employment intention showed statistically significant differences in professional identity scores (p<0.05). Pearson correlation analysis revealed that professional identity was significantly positively correlated with social support (r=0.474), psychological resilience (r=0.389), and career adaptability (r=0.609) (p<0.01), and significantly negatively correlated with perceived stress (r=-0.378) (p<0.01). Multiple linear regression analysis indicated that career adaptability ({beta}=0.309, p<0.001) and social support ({beta}=0.383, p<0.001) were significant positive predictors of professional identity, whereas reasons for choosing the profession ({beta}=-3.603, p=0.001) and employment intention ({beta}=-7.116, p<0.001) were significant negative predictors. The model explained 49.2% of the variance in professional identity. Mediation effect analysis showed that career adaptability played a partial mediating role between social support and professional identity, with a mediation effect value of 0.288 (95% CI: 0.221-0.363), accounting for 40.2% of the total effect. Conclusions: Nursing interns' professional identity is at a moderately high level. Social support and career adaptability are positive influencing factors. Career adaptability plays a partial mediating role between social support and professional identity; social support indirectly enhances professional identity by strengthening career adaptability.

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Correlation of Axillary Nodal with Breast Response Following Neoadjuvant Chemotherapy in Early Breast Cancer

Agrawal, A.; Soliman, M.; Ahmed, B.; Barmpounakis, P.; Provenzano, E.

2026-10-15 oncology 10.64898/2026.10.14.26365456 medRxiv
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Background: Neoadjuvant chemotherapy (NACT) facilitates de-escalation of breast and axillary treatment in breast cancer, but pathological responses may differ between the primary tumour and axillary lymph nodes. Understanding differential response is crucial for de-escalation strategies. Methods: This single university hospital retrospective study analysed operable breast cancers (cT1-cT3, cN0-cN3) treated with NACT (January 2013-November 2020). Two-tailed Fishers exact test or the Chi-squared test (for 2x2 comparisons) analysed concordance between breast and axillary pathological responses; Cox proportional hazards regression ascertained predictors of distant recurrence and survival; and logistic regression ascertained predictors of complete axillary response. Results: Among 413 patients (cN0=229; cN+=184) with a median age of 51, pathological response concordance between the breast and axilla was 81% (both pCR, 22.2%; concurrent residual disease, 58.8%). The cN0 group had a significantly higher ypN0 rate in breast pCR versus non-pCR (97.1% vs 80.8%, p<0.001). cN+ had axillary pCR concordant with breast pCR, compared to only 16.5% with residual breast disease. Breast pCR was the most significant predictor of axillary pCR (OR=11.6, p<0.001). Axillary pCR was highest in ER-/HER2+(66.7%) and triple-negative(46.9%) subtypes. Residual axillary disease was independently associated with the worst breast cancer-specific (HR=7.13, p=0.006) and overall Survival (HR=3.32, p=0.029). Kaplan-Meier analyses showed a trend towards worse survival outcomes with axillary residual disease, even with a breast pCR. Conclusions: In this limited series, breast pCR predicts axillary pCR in cN0 and cN+, particularly in HER2-positives and triple-negatives, supporting axillary de-escalation strategies in selected patients stratified by careful assessment of disease at the end of NACT.

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Part 2 of a 2-part open-label clinical trial evaluating repeated nicotinamide riboside parenteral administration: 90 days of at-home subcutaneous injections

Russ, A.; Nkrumah-Elie, Y.; Hailu, F.; Kwon, J.; Allen, T.; Shao, A.; Chen, H.

2026-10-15 pharmacology and therapeutics 10.64898/2026.10.13.26365470 medRxiv
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Nicotinamide riboside (NR), a precursor to the essential coenzyme nicotinamide adenine dinucleotide (NAD+), has been extensively studied following oral administration, while the longer-term safety and physiological effects of injectable NR remain less characterized. Following an initial in-clinic phase evaluating repeat intramuscular (IM) and subcutaneous (SC) administration of pharmaceutical-grade NR, participants transitioned to an at-home phase designed to assess the safety, feasibility, and exploratory physiological effects of repeated self-administered SC administration. Participants continued their assigned 50 or 100 mg dose group and self-administered NR subcutaneously 3 times weekly for approximately 90 days. Safety was assessed through adverse event (AE) monitoring, vital signs, and clinical laboratory health measures. Exploratory assessments included markers of mitochondrial bioenergetics, urinary biomarkers of oxidative stress, and participant-reported outcomes related to fatigue, sleep, pain, and quality of life. At-home administration of NR was generally well-tolerated, with no clear dose-dependent safety concerns identified over the study period. Further, participants were able to successfully self-administer repeated SC injections over the study period, demonstrating positive feasibility. Whole-blood NAD+ concentrations remained largely stable over time in both dose groups. MeScreen analysis demonstrated a reduction in GlycoATP at Day 30 and increases in the MitoATP/GlycoATP ratio at Day 30 and Day 90, signifying a preferential shift toward oxidative metabolism. These findings may be indicative of positive metabolic health shifts. Urinary oxidative stress profiling demonstrated heterogeneous temporal responses. Several lipid oxidation markers significantly declined at Day 30 but returned toward baseline at Day 90. Select markers of nucleic acid, nitrative stress, and advanced glycation end-product oxidation demonstrated more sustained reductions. These results for which the majority of measured oxidative stress markers improved suggest that NR injections may exhibit anti-oxidative characteristics. Validated participant-reported sleep and fatigue measures showed improvements. Self-reported facial skin improvement increased descriptively from 11.4% at baseline to 27.8% at Day 30 and 36.8% at Day 90; improvements noticed by others increased from 9.1% to 23.7%, while reported body-skin improvement increased more modestly, from 8.8% to 16.7%. As these outcomes were not designed or powered to establish efficacy or definitive clinical claims, the findings should be considered hypothesis generating and provide preliminary data to inform the selection of outcomes and design considerations for future randomized, placebo-controlled, adequately powered trials of SC NR administration.