Nevin Manimala

Mol Syst Biol. 2025 Oct 10. doi: 10.1038/s44320-025-00160-y. Online ahead of print.

ABSTRACT

Deciphering patient-specific mechanisms of cancer cell reprogramming remains a crucial challenge in systems oncology, as it is key to improving patient diagnosis and treatment. For this reason, comprehensive and patient-specific multi-omic characterization of tumor specimens has become increasingly common in clinical practice. Here, we developed PatientProfiler, a computational workflow that integrates proteogenomic data with curated causal interaction networks to generate mechanistic models of signal transduction for individual patients. PatientProfiler allows multi-omic data analysis and standardization, generation of patient-specific mechanistic models of signal transduction, and extraction of network-based prognostic biomarkers. We successfully benchmarked the tool on proteogenomic and clinical data derived from 122 biopsies of treatment-naïve breast cancer, available through the CPTAC portal. We identified patient-specific mechanistic models that recapitulate oncogenic signaling pathways. In-depth topological exploration of these networks revealed seven subgroups of patients, associated with unique transcriptomic signatures and distinct prognostic values. We identified well-known Basal-like 1 and 2 subtypes, while also highlighting distinct mechanistic drivers such as the MYC-CDK4/6 axis or NF-kappaB-mediated inflammatory programs. Beyond breast cancer, PatientProfiler offers a generalizable framework to transform cohort-level multi-omic data into interpretable mechanistic models, making it applicable across diverse cancer types and other complex diseases.

PMID:41073799 | DOI:10.1038/s44320-025-00160-y

Oral Maxillofac Surg. 2025 Oct 11;29(1):171. doi: 10.1007/s10006-025-01470-z.

ABSTRACT

PURPOSE: To assess postoperative fracture reduction and visualization of titanium-based and bioresorbable osteosynthesis materials in maxillofacial trauma surgery using ultra-high-resolution photon-counting detector computed tomography (PCD-CT) compared with cone-beam computed tomography (CBCT).

METHODS: Fractures were induced in six cadaveric pig mandibles at the angle, body, and parasymphysis and were stabilized using various titanium and bioresorbable plate systems. Specimens were scanned with CBCT and dose-matched PCD-CT in the ultra-high resolution mode, applying standard and low-dose protocols. Two observers assessed fracture reduction and implant delineation using a 5-point visual analog scale. Fracture gap and osteosynthesis materials were quantitatively measured and compared to ground-truth values. Descriptive statistics and inter-reader agreement (weighted κ) were calculated.

RESULTS: PCD-CT enabled excellent assessment of fracture reduction and visualization of osteosynthesis materials, with perfect inter-observer agreement (Median = 5, IQR, 5-5; κ = 1.0, p < 0.001), whereas low-dose CBCT showed reduced image quality and lower reproducibility (Median = 4, IQR, 4-4; κ = 0.92; p < 0.001). Bioresorbable plates were not directly visible using either scanner, but the associated screw drill holes were reliably delineated. PCD-CT achieved the smallest measurement deviations of fracture gap and osteosynthesis materials compared with ground truth, and with superior reproducibility (κ = 0.74-0.84; ICC = 0.95-0.99; all p < 0.001), outperforming CBCT across most parameters.

CONCLUSIONS: Ultra-high resolution PCD-CT combines superior visualization and precise measurements compared with CBCT even at low radiation dose. With further clinical validation, these findings highlight PCD-CT’s strong potential for perioperative imaging in maxillofacial trauma, particularly benefiting younger patients who require repeated scans.

PMID:41073793 | DOI:10.1007/s10006-025-01470-z

Nat Genet. 2025 Oct 10. doi: 10.1038/s41588-025-02399-5. Online ahead of print.

NO ABSTRACT

PMID:41073789 | DOI:10.1038/s41588-025-02399-5

Lasers Med Sci. 2025 Oct 11;40(1):425. doi: 10.1007/s10103-025-04696-1.

ABSTRACT

Rosacea is a common, chronic inflammatory skin condition lacking specific treatment. This study investigates the efficacy of various photoelectric therapies in treating rosacea. 90 rosacea patients who visited the dermatology outpatient clinic of the hospital from August 2022 to November 2023 were analyzed (retrospective registration 20240425). The patients were categorized into three groups based on different treatment methods: the control group received oral hydroxychloroquine sulfate and topical recombinant bovine basic fibroblast growth factor; observation group 1 underwent intense pulsed light therapy in addition to the control group’s treatment; observation group 2 received light-emitting diode therapy on top of the control group’s regimen. The therapeutic effect was evaluated by physicians’ subjective evaluation and patients’ pruritus symptoms. The effective rates of observation group 1, observation group 2, and the control group were 73.3%, 66.7%, and 40%, respectively, with statistical significance (P < 0.05). There was no significant difference between observation group 1 and observation group 2 (P < 0.05). Additionally, there were no significant adverse reactions in any of the three groups. The comparison between observation group 1 and observation group 2 revealed that the two combined treatment methods achieved similar and positive therapeutic effects across various clinical manifestations. The effectiveness of both observation groups was found to be superior to that of drug therapy alone.

PMID:41073773 | DOI:10.1007/s10103-025-04696-1

Sci Rep. 2025 Oct 10;15(1):35508. doi: 10.1038/s41598-025-19518-1.

ABSTRACT

High turnover rates can hinder hospitals and the healthcare system from achieving their goals of providing high-quality medical services. Consequently, turnover intention (TI) has emerged as a critical issue within healthcare environments, adversely affecting the quality of care delivered to patients. This study investigates the relationship between career plateau (CP) and TI among nurses, with job burnout (JB) serving as a mediating factor. This cross-sectional study was conducted from February to November 2021. The population comprised 1,289 nurses from Qazvin University of Medical Sciences (QUMS) teaching hospitals. According to Morgan’s sample size table, the required sample size was determined to be 297 nurses. A stratified sampling method was employed to ensure a representative sample. We utilized standardized questionnaires, including Milliman’s CP Scale, Maslach’s JB Inventory, and Kim-Leong’s TI Scale. Statistical analyses were performed using Structural Equation Modeling (SEM), t-tests, ANOVA, Pearson correlation tests, and regression analyses to explore the relationships among the variables. The results were analyzed using R software version 4.1.1. The means and standard deviations for the study variables were as follows: CP (M = 38.08, SD = 5.75), JB (M = 65.99, SD = 16.68), and TI (M = 8.20, SD = 3.31). The results indicated that CP has an indirect relationship with TI, mediated by job burnout. Significant positive correlations were observed among the variables: JB with TI, JB with CP, and CP with TI (p < 0.05), both content plateau and hierarchical plateau scores were higher in female nurses. Additionally, mean scores for job burnout, emotional exhaustion, depersonalization, and TI were also higher among female nurses. Our findings demonstrate that CP significantly influences JB and TI among nurses. The implications of TI are substantial, as they incur high costs related to recruitment, training, and employee retention. Therefore, healthcare managers should adopt human resource management strategies aimed at alleviating workload and working hours, promoting physical and mental health, reducing stress levels, and enhancing communication skills. Implementing these strategies can improve job satisfaction among nurses and ultimately reduce burnout and TI.

PMID:41073760 | DOI:10.1038/s41598-025-19518-1

Pediatr Radiol. 2025 Oct 11. doi: 10.1007/s00247-025-06416-x. Online ahead of print.

ABSTRACT

BACKGROUND: Pediatric rotator cuff (RTC) injuries are uncommon, yet supraspinatus tendon (SST) signal alterations on T2-weighted imaging are frequently observed.

OBJECTIVE: To compare rates of SST signal alterations on shoulder MRIs of adolescents who are considered low- and high-risk for RTC injury.

MATERIALS AND METHODS: We retrospectively reviewed non-arthrogram shoulder MRI reports in 12-17-year-old patients at a large tertiary children’s hospital (01/2010-09/2024). We identified a low-risk patient cohort who lacked (a) clinical concern for RTC pathology, (b) athletic history associated with RTC injuries, (c) recent trauma, or (d) prior shoulder intervention. We also identified an age- and sex-matched high-risk patient cohort who had clinical concern for RTC pathology. Two experienced pediatric radiologists independently and blindly reviewed the shoulder MRIs in a random order from these cohorts. SST was evaluated using coronal oblique fat-suppressed T2-weighted sequences. Logistic regression models were developed to investigate differences between cohorts.

RESULTS: Both low- and high-risk cohorts included 26 patients (14 males). Their median (inter-quartile range) ages were 14.0 (2.0) years and 14.5 (3.0) years, respectively. In the low-risk cohort, SST signal alterations were identified in 23 (88.5%) and 22 (84.6%) patients by readers 1 and 2, respectively. In the high-risk group, SST signal alterations were identified in 24 (92.3%) and 23 (88.5%) patients by readers 1 and 2, respectively. Overall inter-reader agreement was substantial (Cohen’s kappa=0.63). There was no statistical difference in the SST signal alteration grades between the low- and high-risk cohorts (P≥0.07).

CONCLUSION: SST signal alterations are common in adolescent shoulder MRIs regardless of the clinical concern for RTC injury.

PMID:41073751 | DOI:10.1007/s00247-025-06416-x

J Expo Sci Environ Epidemiol. 2025 Oct 10. doi: 10.1038/s41370-025-00804-z. Online ahead of print.

ABSTRACT

BACKGROUND: U.S. military personnel deployed to Afghanistan and Iraq were stationed on bases impacted by airborne hazards including emissions from combustion sources. Due to limited environmental monitoring during military operations, exposure levels remain poorly characterized.

OBJECTIVE: We used satellite observations to identify the locations and persistence of combustion sources on and near military bases in Afghanistan and Iraq from 2002 to 2012, the peak period of open-air combustion.

METHODS: Daily fire detections from the Moderate Resolution Imaging Spectroradiometer (MODIS) were clustered using density-based methods to identify persistent burning within 5 km of bases. Validation was conducted using military imagery and Google Earth. A sensitivity analysis compared MODIS fire detections to those from the newer Visible Infrared Imaging Spectroradiometer (VIIRS) at a civilian burn pit in Djibouti.

RESULTS: MODIS detected 285,810 fires in Iraq and 3702 in Afghanistan. Clustering identified 398 bases in Iraq and 122 in Afghanistan with burning nearby. In Iraq, persistent clusters were linked to oil and gas flares, while smaller clusters on bases in both countries were consistent with burn pits. MODIS and VIIRS both detected the Djibouti burn pit, but VIIRS recorded three times more fire detections, highlighting its sensitivity in detecting biomass and waste burning.

IMPACT: This study is the first to use satellite fire detections to objectively map and quantify combustion sources at U.S. military bases in Iraq and Afghanistan during 2002-2012. By applying density-based clustering to MODIS data and validating with high-resolution imagery, we identified persistent burning patterns near and on bases. This approach overcomes the limitations of self-reported exposure data and provides a reproducible framework for assessing deployment-related combustion exposures. The findings highlight both the utility and limitations of MODIS and demonstrate the potential of satellite observations for Veteran health research.

PMID:41073689 | DOI:10.1038/s41370-025-00804-z

CNS Drugs. 2025 Oct 10. doi: 10.1007/s40263-025-01235-y. Online ahead of print.

ABSTRACT

BACKGROUND: Migraine is often associated with impaired sleep quality, including insomnia, fragmented sleep, and circadian rhythm disturbances. These factors can exacerbate migraine severity and chronification. Calcitonin gene-related peptide (CGRP), a key player in migraine pathophysiology, also influences sleep regulation. While CGRP monoclonal antibodies have shown mixed effects on sleep, no study to date has evaluated the impact of gepants on sleep quality. This study assessed whether atogepant, recently approved for migraine prevention, affects sleep quality and sleep-related adverse events in real-world settings.

METHODS: We conducted a prospective, observational, open-label, single-center study. All received atogepant 60 mg/day up to 12 weeks. Adults (≥ 18 years) with migraine (with/without aura or chronic migraine) experiencing ≥ 4 monthly migraine days were enrolled. Inclusion required ≥ 1 month of headache diaries and stable preventive or sleep treatments for ≥ 3 months. Patients were accepted regardless of prior preventive failures. Exclusion criteria were unstable treatments, recent sleep-impacting disease, and pregnancy. Sleep quality was assessed using five validated questionnaires (Pittsburgh Sleep Quality Index [PSQI], Athens Insomnia Scale [AIS], Bergen, Epworth Sleepiness Scale [ESS], Insomnia Severity Index [ISI]) at baseline and at follow-up. Migraine frequency, disability (Migraine Disability Assessment [MIDAS], Headache Impact Test [HIT-6]), allodynia (Allodynia Symptom Checklist [ASC-12]), acute medication use, and adverse events (AEs) were also recorded. Pre-post differences were assessed with Wilcoxon and McNemar’s tests, while linear mixed-effects models were applied to evaluate the impact of clinical factors (response status, psychiatric comorbidities, prior anti-CGRP failures) on PSQI outcomes, with model fit estimated via REML and pseudo-R².

RESULTS: The study population included 43 participants (93.0% female, mean age of 51.6 [IQR 48.4-54.8] years, mean age at disease onset of 18.9 [16.0-21.7] years); 30 (69.8%) participants had chronic migraine, and among them, 23 (76.7%) had a concomitant diagnosis of medication overuse headache. Atogepant significantly improved sleep quality with PSQI scores decreased from 9.6 to 8.2 (p = 0.002) and improvements in AIS (p = 0.014) and Bergen scores (p = 0.046). Sleep duration was the only PSQI subdomain with a statistically significant change. No differences were found in ESS or ISI scores. Notably, no patients reported sleep-related AEs such as somnolence, nightmares, or vivid dreams. Psychiatric comorbidities were associated with poorer baseline sleep but did not influence the magnitude of improvement. Prior anti-CGRP failure predicted a lesser sleep benefit. Finally, migraine burden improved across all evaluated migraine-related variables. Only two patients discontinued treatment.

CONCLUSIONS: Atogepant improved subjective sleep quality without causing sleep-related adverse events, supporting its role in comprehensive migraine management, particularly in patients with disrupted sleep.

PMID:41073685 | DOI:10.1007/s40263-025-01235-y

Biol Trace Elem Res. 2025 Oct 10. doi: 10.1007/s12011-025-04837-1. Online ahead of print.

ABSTRACT

Endometriosis is a non-malignant, estrogen-dependent chronic inflammatory disorder that affects 10-15% of women during their reproductive years. Emerging evidence highlights the undeniable role of oxidative stress in the etiopathogenesis of endometriosis. Selenium, a potent antioxidant, is vital for intracellular redox reactions. Recent research has highlighted the potential of antioxidants as therapeutic agents to mitigate oxidative stress and alleviate endometriosis symptoms. Selenium plays a key role in regulating the enzyme glutathione peroxidase (GPx). This study aimed to evaluate the therapeutic efficacy of a yeast-based organic selenium in disease progression and alleviating painful symptoms. This triple-blind randomized controlled clinical trial was executed within 66 women diagnosed with endometriosis in Tabriz, Iran. Participants were required to possess diagnostically verified endometriosis with endometrioma and a dysmenorrhea score of ≥ 16 on the Menstrual Distress Questionnaire (Moos). Using block randomization with block sizes of 4 or 6, participants were assigned (1:1 ratio) to receive either one 200-mcg capsule of organic selenium or an identical placebo along with routine treatment (2 mg of verojest (dienogest) daily for 3 months). Data were collected using socio-demographic and menstrual-obstetric questionnaires, the Moos, and the visual analogue scale (VAS) for pain. After 3 months, participants completed follow-up questionnaires and underwent ultrasonography. Statistical analyses included descriptive and inferential tests (chi-square, independent t-test, ANCOVA, and repeated-measures ANOVA). A p-value of < 0.05 was considered statistically significant. Three months after the intervention, a statistically significant reduction in endometrioma size was observed in the selenium group (from 4.82 to 3.78 cm) compared to placebo (from 4.07 to 5.31 cm) (adjusted mean difference [aMD]: -1.95 cm; 95% CI -2.6 to -1.3; Cohen’s d = -0.86, large effect). Additionally, the selenium group experienced significantly greater reductions in dysmenorrhea scores (aMD -10.94; 95% CI -15.16 to -6.71; Cohen’s d = -1.14, large effect), dyspareunia (aMD -3.21; 95% CI -4.34 to -2.07), dysuria (aMD -1.41; 95% CI -2.12 to -0.69), dyschezia (aMD -2.11; 95% CI -3.22 to -0.99), and non-cyclic pain (aMD -2.73; 95% CI -3.77 to -1.68) over time (at 1, 2, and 3 months post-intervention), compared to placebo. No serious or health-threatening adverse events were reported in either group. Our findings support the hypothesis that organic selenium supplementation may present a promising adjuvant therapy to reduce the size of endometriomas and alleviate various painful symptoms associated with endometriosis, including dysmenorrhea, dyspareunia, dysuria, non-cyclic pain, and dyschezia. ClinicalTrial.gov Identifier: IRCT20110606006709N26.

PMID:41073678 | DOI:10.1007/s12011-025-04837-1

Res Vet Sci. 2025 Sep 23;196:105913. doi: 10.1016/j.rvsc.2025.105913. Online ahead of print.

ABSTRACT

This study evaluated the effect of a stepwise alveolar recruitment manoeuvre (ARM) at the end of anaesthesia on arterial oxygenation and shunt fraction (F-shunt) during the early postoperative period in sheep. Twenty-four healthy, non-pregnant female Merino sheep underwent either laparoscopic or orthopaedic surgery under isoflurane anaesthesia. At the conclusion of surgery, and under isoflurane anaesthesia, oxygenation parameters and F-shunt values were analysed (Baseline). Animals were then randomly allocated to either the ARM group (ARMstepwise: laparoscopic n = 6, orthopaedic n = 6) or Control group (laparoscopic n = 6; orthopaedic n = 6). In the ARMstepwise group, animals received a stepwise, pressure-controlled ARM in sternal recumbency, with parameters re-evaluated 10 min post-application (PostARM). The control animals remained in sternal recumbency for 10 min following the completion of surgery without undergoing a stepwise ARM. Subsequently, isoflurane was discontinued in both groups. Oxygenation parameters and F-shunt values were recorded 10, 30, and 60 min after extubation. A linear mixed model was used for the statistical analysis. The implementation of a stepwise ARM at the end of isoflurane anaesthesia in healthy sheep enhanced oxygenation across both types of surgical procedures and significantly reduced F-shunt during orthopaedic surgery (Baseline: 26.31 ± 7.93 % vs PostARM: 6.47 ± 4.01 %; p = 0.001). These benefits were not sustained throughout the first postoperative hour, most likely because no PEEP was applied and oxygen was delivered with a high FiO₂ via facemask after extubation. Further research should clarify whether repeated intraoperative ARMs with PEEP and ∼ 60 % FiO₂ reduce atelectasis during anaesthetic recovery in sheep.

PMID:41072080 | DOI:10.1016/j.rvsc.2025.105913