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Improving Proteomic Dynamic Range with Multiple Accumulation Precursor Mass Spectrometry
Phlairaharn, Teeradon , Shannon, Ariana E. , Zeng, Xinlei, Truong, Dong‐Jiunn Jeffery , Schoof, Erwin M. , Searle, Brian C. , Searle, Brian C , Zeng, Xinlei, Ye, Zilu

Journal of Proteome Research | September 13, 2025 | Volume: 24 | Issue: 10 | Pages: 5116-5126

10.1021/acs.jproteome.5c00469 | PMID 40940309 Get It

AAPM TG report 330: EPID‐based quality assurance of linear accelerators
Sun, Baozhou, Yaddanapudi, Sridhar, Mutic, Sasa, Shi, Chengyu, McCurdy, Boyd M. C., Popple, Richard A., Lu, Minghui, Kim, Taeho, Clark, Jennifer R, Greer, Peter B, Yaddanapudi, Sridhar , Yaddanapudi, Sridhar , Sun, Baozhou, Mutic, Sasa, Shi, Chengyu, McCurdy, Boyd M. C., Popple, Richard A., Lu, Minghui, Kim, Taeho, Clark, Jennifer R, Greer, Peter B.

Medical Physics | September 13, 2025 | Volume: 52 | Issue: 9 | Pages: No page available

10.1002/mp.18114 Get It

Abstract Electronic portal imaging devices (EPIDs) have been in widespread clinical use for almost two decades due to favorable measurement characteristics such as fast image acquisition, high sensitivity and resolution, digital data format, long‐term stability, linear dose response, and large detection area. On‐board EPIDs are widely used as a quality assurance (QA) tool to monitor nearly every aspect of linear accelerator (linac) performance. In both the commercial QA equipment market and in clinical practice, there is a trend toward replacing conventional QA approaches with fully automated, EPID‐based QA tools. Despite widespread use, EPIDs are complex devices, and there has yet to be consensus or formal recommendations published by the AAPM for their use in routine linac QA. Task Group 330 (TG‐330) was, therefore, formed to provide guidelines and recommendations for physicists on the safe and appropriate use of EPIDs for linac QA. In particular, the report: (a) provides a comprehensive review of the characteristics and limitations of EPIDs as time‐resolved measurement devices and dosimeters; (b) summarizes the application of EPIDs for linac QA; (c) provides recommendations on efficient and effective implementations of EPID‐based QA techniques; (d) describes risks associated with the use of EPIDs for linac QA and provides examples of how risk analysis can be used to ensure the safe use of EPIDs for linac QA. Many of the guidelines in this report are drawn from the literature that is included in the references and from the collective experience of the task group members. This report does not provide recommendations on the implementation of EPID‐based patient‐specific IMRT or VMAT QA, which is the topic of AAPM's report from AAPM TG‐307.
Lung Disease in Children With Laryngotracheoesophageal Clefts
Hosfield, Emily A., Patten, Hannah C, Hopson, Puanani , Cofer, Shelagh A. , Wiedermann, Joshua P. , Boesch, R. Paul , Hopson, Puanani E, HC, Patten

Pediatric Pulmonology | September 12, 2025 | Volume: 60 | Issue: 9 | Pages: No page available

10.1002/ppul.71285 | PMID 40939098 Get It

ABSTRACT Introduction Laryngotracheoesophageal clefts (LTEC) are aspiration‐related lesions often assessed using swallow studies and symptoms like respiratory or feeding difficulties. However, these indicators are unreliable predictors of disease severity. Lung inflammation and injury, though significant concerns, are rarely and inconsistently evaluated or reported. As a result, the correlation between swallow study findings and actual pulmonary disease remains unclear. Methods A retrospective cohort of children with LTEC seen in our Aerodigestive Program between October 1, 2012, and September 30, 2023, who underwent videofluoroscopic swallow study (VFSS) or flexible endoscopic evaluation of swallowing (FEES) were included. Data collected included clinical history, risk factors, BAL, chest CT, impedance probe, VFSS/FEES findings, and FOIS‐P/I scores at baseline and follow‐up. Results Eight‐two subjects identified. Lung inflammation and bronchiectasis were common and correlated. Clinical factors, impedance probe, and the presence/severity of swallowing abnormalities on VFSS/FEES were not predictive of lung disease. Fifty‐seven patients underwent LTEC repair for a range of indications, only 49% based on CT and/or BAL findings. Of 57 children who had LTEC repair, only 49% were based on CT or BAL findings. LTEC repair was associated with modest improvement feeding and swallowing. Discussion Children with LTEC have a high prevalence of inflammatory lung disease and injury and undergo repair for a variety of reasons. Swallow studies detect functional swallowing issues but do not reliably identify lung disease. Despite this limitation, LTEC repair is linked to improved feeding and swallowing in some patients, though not all benefit.
The Broken Wing Sign: A New Clinical Test to Detect Gluteus Medius Pathology with and without Fatty Infiltration
Sierra, Rafael J. , Perez, Sergio F. Guarin , Restrepo, Diego J., Howe, Benjamin M. , Tai, Ta-Wei, Restrepo, Diego J. , Guarin Perez, Sergio F , Restrepo, Diego J. , Sierra, Rafael J , Tai, Ta-Wei

Journal of Bone and Joint Surgery | September 12, 2025 | Volume: 107 | Issue: 21 | Pages: 2359-2364

10.2106/jbjs.25.00427 | PMID 40938961 Get It

Background: Gluteus medius tears and atrophy cause lateral hip pain, limp, and functional impairment. We developed the “broken wing sign,” a novel physical examination test for detecting gluteus medius tendon tears and muscle degeneration. This study evaluated its diagnostic accuracy and clinical utility against magnetic resonance imaging (MRI) and intraoperative findings. Methods: We prospectively examined 59 patients (75 hips; mean age, 69.5 ± 10.8 years; 48 women) with suspected hip abductor insufficiency. The broken wing sign was tested with patients prone, the knee flexed at 90°, and the hip actively extended. A positive sign involved ≥10° of compensatory external hip rotation, visible as an inward drift of the foot, indicating gluteus medius (and resulting internal rotation) weakness. MRI served as the reference standard for classifying gluteus medius integrity as no tear, partial, full-thickness, or massive. Fatty infiltration was graded (Goutallier grades 0 to 4), quantified, and analyzed for a correlation with the examination findings. Diagnostic accuracy metrics were calculated. Results: The broken wing sign demonstrated high accuracy (sensitivity, 81.8%; specificity, 80.0%; positive predictive value [PPV], 91.8%; negative predictive value, 61.5%; diagnostic odds ratio, 17.8). An external rotation threshold of ≥30° yielded 100% specificity and 100% PPV for a tear. The sign detected acute tears with no or minimal fatty infiltration (100% sensitivity for massive tears). The degree of the external rotation angle was strongly correlated with muscle atrophy with fatty infiltration, showing 88.0% sensitivity for Goutallier grade ≥3 and 100% sensitivity for grade 4. Conclusions: The broken wing sign is clinically useful for diagnosing gluteus medius tendon tears and muscle atrophy, particularly massive tears and advanced fatty degeneration. It effectively guides MRI utilization and surgical planning, serving as a valuable initial diagnostic tool in the clinical setting. Level of Evidence: Diagnostic Level II . See Instructions for Authors for a complete description of levels of evidence.
Circulating Tumor DNA and Tissue Testing for Pancreatobiliary Tumors
Majeed, Umair , Patel, Jaydeepbhai, Ahmed, Ahmed , Elhariri, Ahmed , Albelal, Douaa , Rao, Nakka Naga Malleswara, Rachamala, Hari Krishnareddy, Mahadevan, Daruka , Ahn, Daniel H. , Halfdanarson, Thor R, Fonkoua, Lionel Aurelien Kankeu , Bekaii-Saab, Tanios S , Mody, Kabir , Babiker, Hani, Nakka, Naga Malleswara Rao , Ahmed, Ahmed K , Mosalem, Osama , Sonbol, Mohamad Bassam , Tran, Nguyen , Kankeu Fonkoua, Lionel A, Majeed, Umair , Mahadevia, Himil , Rao, Nakka Naga Malleswara, Rachamala, Hari Krishnareddy, Mukhopadhyay, Debabrata , Jones, Jeremy C , Borad, Mitesh J. , Tran, Nguyen, Mahipal, Amit , Wee, Wen , McWilliams, Robert R. , Bekaii‐Saab, Tanios

JAMA Network Open | September 12, 2025 | Volume: 8 | Issue: 9 | Pages: e2531373

10.1001/jamanetworkopen.2025.31373 | PMID 40938601 Get It

Importance The prognosis of advanced pancreaticobiliary tumors is poor. Next-generation sequencing (NGS) of tissue samples is utilized to identify actionable alterations, but there are occasional limitations due to inadequate tissue acquisition. Circulating tumor DNA (ctDNA) is an alternative method, but its correlation with tissue-based NGS remains unexplored. Objectives To assess the mutation concordance (mCR) rates between ctDNA and tissue testing for patients with pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CC) and to evaluate how ctDNA performs as a treatment response biomarker. Design, Setting, and Participants This retrospective cohort study was conducted among patients with PDAC and CC treated at academic institutions from January 2014 to January 2025. Patients underwent ctDNA testing using 1 platform and tissue NGS testing using 2 platforms. Main Outcomes and Measures mCR, which measures the shared gene alterations observed by both ctDNA and tissue-based NGS testing, was calculated using the Spearman correlation for PDAC and CC. The performance of ctDNA as a treatment response biomarker was assessed by comparing serial ctDNA data with restaging scans and cancer antigen 19-9 levels in patients with PDAC. Results Our cohort included 790 patients: 570 with advanced PDAC (265 [46.5%] female; median [IQR] age, 64 [33-84] years) and 220 with advanced CC (95 [43.2%] female; median [IQR] age, 66 [42-88] years). Overall, 461 patients with PDAC (80.9%) and 192 patients with CC (87.2%) underwent ctDNA testing, while 239 patients with PDAC (41.9%) and 70 patients with CC (31.8%) had tissue NGS testing. Among patients with PDAC, 85 of 130 patients (65.4%) showed shared specific gene alterations between ctDNA and tissue testing; there was a significant mCR, with a Spearman correlation of 0.47 (95% CI, 0.28-0.62; P < .001). For patients with CC, 32 of 48 (66.7%) had shared alterations between ctDNA and tissue testing; there was a significant mCR, with a Spearman correlation of 0.56 (95% CI, 0.35-0.70; P < .001). A subgroup analysis of patients with PDAC who underwent serial ctDNA testing suggested that new TP53 subclones and increased ctDNA variant allele frequency levels of TP53 and KRAS were associated with higher odds of progressive disease (eg, increased TP53 frequency: odds ratio, 7.28; 95% CI, 2.15-24.66; P = .001). Conclusions and Relevance In this cohort study of patients with pancreaticobiliary tumors, there was a significant mCR between ctDNA and tissue NGS testing. Additionally, results suggest that ctDNA might detect resistant clones and enable assessment of treatment response.
MPN Transformation Is Characterized By Heterogeneous Shifts In Lineage Character Resulting In Both HSC-Like And More Differentiated Lineage Signatures
Rampal, Raajit K. , Menghrajani, Kamal , Dilip, Deepika , Farnoud, Noushin , Famulare, Chris, Mascarenhas, John , Mauro, Michael J. , Glass, Jacob L. , Mascarenhas, John , McGovern, Erin , Sirenko, Maria , Kosiorek, Heidi , Hoffman, Ronald , Levine, Ross L. , Koche, Richard P

No container title available | September 12, 2025 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.21203/rs.3.rs-7539321/v1 Get It

Abstract Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) have a propensity to transform to an accelerated or blast phase (MPN-AP/BP). The resulting disease has clinically similar manifestations to Acute Myeloid Leukemia (AML) but worse clinical outcomes. Here we present the first comprehensive description of the transcriptomic characteristics of MPN-AP/BP. Our analysis incorporates data from 261 patients of the BeatAML cohort and 56 MPN-AP/BP patients, 11 of whom had paired samples from before and after transformation. We establish that transformed MPN is a transcriptionally distinct entity from de novo AML and chronic phase MPNs. Genomic pathways traditionally associated with MPN pathogenesis, such as IL2/STAT5 signaling and IL6/JAK/STAT3 signaling were enriched in chronic-phase MPNs but are absent in transformed disease, suggesting JAK2 directed therapy may be less effective in this disease phase. We also discovered that gene expression signatures associated with doxorubicin resistance are highly enriched in transformed MPNs, which may explain the lack of efficacy of standard AML therapies. In addition, we identify that lineage composition at the time of transformation may define distinct subsets of MPN-AP/BP patients, which may assist in the future development of novel treatment strategies.
The Effect of Knee Flexion Contracture on Patient Reported Outcome Measures after Distal Femur Fractures (OTA/AO Type 33):A Multi-Center Prospective Evaluation
Dunbar, Robert P. , Cooke, Margaret E., Born, Christopher T. , Collinge, Cory A. , Egol, Kenneth A., Ertl, William J., Friess, Darin , Gardner, Michael J. , Humphrey, Catherine A. , Jones, Clifford B. , Krieg, James C. , Ostrum, Robert F. , Perez, Edward A., Phieffer, Laura S. , Ricci, William M. , Sems, Andrew, Siegel, Judith A., Teague, David , Zonno, Alan J., Tornetta, Paul , Egol, Kenneth A. , Gardner, Michael J. , Mullis, Brian , Sagi, H. Claude , Schmidt, Andrew H.

No container title available | September 12, 2025 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.21203/rs.3.rs-7223366/v1 Get It

Abstract OBJECTIVES: · To determine if patients with knee flexion contracture after distal femur fracture have poorer outcomes than patients who regain full knee extension. · To determine if factors such as patient age, gender, open fracture or implant used favors knee flexion contracture. METHODS: Design: Prospective, multicenter trial Setting: Twenty academic level I trauma centers Patient Selection Criteria: Patients with a distal femur fracture. Patients were evaluated for knee flexion contracture at 3, 6 and 12 months post-operatively. Outcome Measures and Comparisons: SMFA, Bother Index and EQ Health Index scores were recorded. Walking and stair climbing ability were assessed. RESULTS: · 126 patients had radiographic follow up for 12 months. There was clinical follow-up for 99 patients at 3 months, 90 patients at 6 months and 74 pts at 12 months. · Patients with full knee extension had better SMFA scores at 12 months than patients with knee flexion contracture (p = 0.308). · Bother Index (p = 0.29) and EQ Health State (p = 0.12) scores did not demonstrate a difference between patients with or without knee flexion contracture at any time point. · Patients with full knee extension had improved walking ability compared to patients with flexion contracture (p = 0.008). Patients with full knee extension had better stair climbing ability than patients with flexion contracture (p = 0.02). · Only older patient age showed a difference in likelihood of flexion contracture (p = 0.01) The rates of flexion contracture in women versus men (p = 0.51), RIMN versus LLP (p = 0.74) and open versus closed fracture (p = 0.24) were not statistically different. CONCLUSIONS: · Patients with knee flexion contractures after distal femur fracture do worse than patients who regain full extension. · Older patients with distal femur fractures are at greater risk for knee flexion contracture. LEVEL OF EVIDENCE: Level I
From the Editor-in-Chief’s Desk: Challenges and Opportunities for the Assessment of Complex Neurodevelopmental Phenotypes
Croarkin, Paul E. , Croarkin, Paul E

Journal of Child and Adolescent Psychopharmacology | September 12, 2025 | Volume: 35 | Issue: 7 | Pages: 373-374

10.1177/10445463251376278 | PMID 40880341 Get It

Randomized controlled trials comparing cervical disc arthroplasty and anterior cervical discectomy and fusion outcomes in degenerative spine disease: a systematic review and meta-analysis
Yakdan, Salim, Benedict, Braeden , Botterbush, Kathleen , Lagisetty, Adhya, Kaleem, M. , Alessio, Rachel, Javeed, Saad , Ruiz-Cardozo, Miguel A. , Wang, Jing , Bydon, Mohamad, Ray, Wilson Z. , Yakdan, Salim M. , Alessio, Rachel, Hardi, Angela , Yahanda, Alexander T. , Bydon, Mohamad , Greenberg, Jacob K

Journal of Neurosurgery: Spine | September 12, 2025 | Volume: 43 | Issue: 6 | Pages: 703-716

10.3171/2025.4.spine241277 | PMID 40882232 Get It

OBJECTIVE Anterior cervical discectomy and fusion (ACDF) is an established treatment for cervical degenerative disc disease; however, the procedure can cause loss of cervical spine range of motion and potentially accelerate adjacent segment degeneration. Cervical disc arthroplasty (CDA) seeks to preserve native motion of the cervical spine, which can theoretically reduce the incidence of adjacent level degeneration. The literature regarding the relative efficacy of ACDF versus CDA remains inconsistent. In this study, the authors investigate the difference in outcomes between ACDF and CDA and identify factors contributing to the heterogeneity in the literature. METHODS The Ovid, Embase, Scopus, Cochrane, and ClinicalTrials.gov databases were systematically searched from inception to September 5, 2023, for randomized controlled trials (RCTs) comparing ACDF and CDA for degenerative disc disease. Studies were extracted by two authors and verified by a third. Random-effects meta-analysis was performed. The primary outcome was the difference in clinical outcomes between the two surgical groups. The secondary outcomes were the differences in radiological outcomes, surgical characteristics, complication rates, and hospital lengths of stay. The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO; registration no. CRD42023469204) and adhered to the PRISMA guidelines. RESULTS From 584 articles uploaded to the Covidence platform for screening, 35 studies derived from 25 RCTs were included in this systematic review and meta-analysis. A total of 4530 patients were treated with ACDF (2081) and CDA (2449). Forty-six percent of the patients (2063) were male, and the mean age of the study cohort was 45 ± 3 years. In terms of the primary outcome, CDA showed higher rates of neurological and overall success. Regarding the secondary outcomes, CDA demonstrated a significantly lower rate of adjacent level disease, higher rate of heterotopic ossification, and greater range of motion at the operated level. Additionally, CDA had lower rates of reoperation but significantly longer operative times than ACDF. The inclusion of myelopathic patients and variations in follow-up between the surgical groups contributed to the observed effect heterogeneity among studies. CONCLUSIONS In this study, CDA showed comparable or potentially greater success in overall and neurological outcomes, along with a lower incidence of adjacent level degeneration and reoperation rates but longer operative times.
Cervical deformity correction: comparison of neurological, radiographic, and patient-reported outcome measures by three-column osteotomy level
Mikula, Anthony L. , Mazur-Hart, David J. , Pennington, Zach , Semonche, Alexa , Choy, Winward , Nguyen, Terry H., Deviren, Vedat , Pennington, Zach , Wozny, Thomas A. , Kim, Jaemin, Scheer, Justin K. , Clark, Allan , Ames, Christopher Pearson

Journal of Neurosurgery: Spine | September 12, 2025 | Volume: 43 | Issue: 4 | Pages: 433-442

10.3171/2025.4.spine241538 | PMID 40680312 Get It

OBJECTIVE The purpose of this study was to evaluate whether level selection for a three-column osteotomy (3CO) impacts cervical deformity correction outcomes, including neurological, radiographic, and patient-reported outcomes. METHODS A retrospective review was performed of patients who underwent a cervical or upper thoracic 3CO for cervical deformity correction by the senior author from 2008 to 2024. Collected outcome measures included neurological outcomes, mechanical complication rates, spinopelvic alignment, and patient-reported outcomes. The minimum follow-up was 1 year. RESULTS One hundred fifteen patients were identified who underwent a cervical or upper thoracic 3CO for cervical deformity correction, of whom 77 met inclusion criteria for this study with a minimum follow-up of 1 year. The median age was 66 years, the median BMI was 27, and 43% of patients were male. Sixteen patients underwent a 3CO at the C7–T1 levels and 61 patients at T2–6 levels. Patients who underwent C7–T1 3CO were more likely to experience a new postoperative neurological deficit compared with those who underwent T2–6 3CO (56% vs 18%, p = 0.004), had less correction in their T1 slope (6° vs 18°, p = 0.027), had less correction in C2–T4 sagittal vertical axis (2.8 cm vs 4.9 cm, p = 0.043), and had a worse Neck Disability Index (NDI) score at 1 year compared with baseline (an increase of 7 vs a decrease of 12, p = 0.033). CONCLUSIONS Cervical deformity patients who underwent a 3CO at C7–T1 had a higher rate of postoperative neurological deficits, less radiographic correction, and worse NDI scores at 1 year compared with patients who underwent a 3CO from T2 to T6. Although 3CO level selection is multifactorial and patient specific, surgeons should consider a 3CO level caudal to T1 when feasible.