bluuebunny/crossref_metadata_2025_split huggingface dataset:
ST6GAL1-Mediated Sialylation of PECAM-1 Promotes a Transcellular Diapedesis-Like Process that Directs Lung Tropism of Metastatic Breast Cancer
Authors: Chen Shih-Yin , He Pei-Lin , Lu Li-Yu , Lin Meng-Chieh , Chan Shih-Hsuan , Tsai Jia-Shiuan , Luo Wen-Ting , Wang Lu-Hai , Li Hua-Jung 
Published: December 2024

Abstract
Metastasis is the leading cause of mortality in breast cancer, with lung metastasis being particularly detrimental. Identification of the processes determining metastatic organotropism could enable the development of approaches to prevent and treat breast cancer metastasis. Here, we found that lung-tropic and non-lung-tropic breast cancer cells differ in their response to sialic acids, affecting the sialylation of surface proteins. Lung-tropic cells showed higher levels of ST6GAL1, while non-lung-tropic cells had more ST3GAL1. ST6GAL1-mediated α-2,6-sialylation, unlike ST3GAL1-mediated α-2,3-sialylation, increased lung metastasis by promoting cancer cell migration through pulmonary endothelial layers and reducing junction protein levels. α-2,6-sialylated PECAM-1 on breast cancer cells facilitated extravasation through the pulmonary endothelium, a critical step in lung metastasis. Knockdown of ST6GAL1 or PECAM-1 significantly reduced lung metastasis. Human pulmonary endothelium displayed high PECAM-1 levels. Through transhomophilic interaction with pulmonary PECAM-1, α-2,6-sialylated PECAM-1 on ST6GAL1-positive cancer cells increased pulmonary extravasation in a diapedesis-like, cell-autonomous manner. Additionally, lung-tropic cells and their exosomes increased the permeability of pulmonary endothelial cells, promoting metastasis in a non-cell-autonomous manner. Analysis of human breast cancer samples showed a correlation between elevated ST6GAL1/PECAM-1 expression and lung metastasis. These results suggest that targeting ST6GAL1-mediated α-2,6-sialylation could be a potential therapeutic strategy to prevent lung metastasis in breast cancer patients.
Phase II Open-Label Trial of Brentuximab Vedotin with Pembrolizumab in PD-1–Pretreated Metastatic Non–Small Cell Lung Cancer and Metastatic Cutaneous Melanoma
Authors: Lee Sylvia M. , Hamid Omid , Jotte Robert , Zakharia Yousef , Medina Theresa , Gillespie-Twardy Amanda , Mehmi Inderjit , Chandra Sunandana , Watson Graham , Ward Patrick , Chaney Marya , Lu Hailing , Berndt Jason , O’Connor Brian P. , Rathi Kapil , Shaikh Eeman , Cowey Charles Lance 
Published: December 2024

Abstract

Purpose:
Brentuximab vedotin (BV) is hypothesized to selectively deplete T regulatory cells that express CD30 and resensitize tumors to anti–PD-1 therapy. This study evaluated responses to BV + pembrolizumab after PD-1 therapy and explored corresponding biomarkers.

Patients and Methods:
A total of 55 patients with metastatic non–small cell lung cancer and 58 patients with metastatic cutaneous melanoma received ≥1 dose of BV + pembrolizumab. Patients had received a median of 2.0 prior lines of systemic therapies (range, 1–7). The primary endpoint was confirmed objective response rate (ORR). Exploratory endpoints included overall survival (OS) and biomarker analysis in blood and tumor.

Results:
For the secondary refractory metastatic non–small cell lung cancer cohort (RECIST v1.1), the ORR was 14%, median progression-free survival (PFS) was 5.85 months, and median OS was 14.4 months. For the secondary refractory metastatic cutaneous melanoma cohort (immune RECIST), the ORR was 24%, median PFS was 4.44 months, and median OS was 21.9 months. Overall, the median duration of OS follow-up was 17.2 months (95% confidence interval, 14.62–22.87). No new safety signals were identified. No treatment-related grade 5 toxicity was seen. Longitudinal immune phenotyping in peripheral blood demonstrated a transient decrease in T regulatory cells. Paired tumor biopsies from baseline and cycle 3 day 1 showed a trend of increased CD8 T-cell infiltration, especially in responding patients.

Conclusions:
BV + pembrolizumab in solid tumor malignancies resulted in clinically meaningful, durable responses with encouraging OS and PFS rates supportive of the immunomodulatory activity of this combination. Stronger antitumor activity was observed in secondary refractory cohorts. The safety profile of this combination was consistent with the individual drug risk profiles.
Activity and Safety of Avelumab in High-Grade Neuroendocrine Tumors and Poorly Differentiated Neuroendocrine Carcinomas Progressive after Chemotherapy (AveNEC Trial)
Authors: Fottner Christian , Apostolidis Leonidas , Krug Sebastian , Rinke Anja , Grün Barbara , Michl Patrick , Gress Thomas M. , Wagner Daniel-Christoph , Roth Wilfried , Mettler Esther , Topsch Jana , Ruckes Christian , Galle Peter R. , Weber Matthias M. 
Published: December 2024

Abstract

Purpose:
Neuroendocrine neoplasms grade 3 (NEN G3) are rare tumors with poor prognosis and no established second-line therapy. The role of immune checkpoint blockade in these aggressive tumors remains unclear.

Patients and Methods:
The phase II AveNEC study evaluated the effect of avelumab (AVE, 10 mg/kg i.v. every 2 weeks) in 60 patients with well-differentiated high-grade neuroendocrine tumors (N = 22) or poorly differentiated neuroendocrine carcinomas (N = 38) progressing after ≥1 prior chemotherapy (excluding Merkel cell carcinoma and small cell lung cancer).

Results:
The best overall response according to immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) was partial response (PR) in three (5%) and stable disease (SD) in nine (15%) patients, with a disease control rate at 16 weeks of 15% (3 PRs; 6 SDs) and a median duration of response of 4.3 months. Six (10%) patients achieved SD or PR for &gt;6 months and two for &gt;1 year. Response rates were similar regardless of differentiation, Ki-67 expression, or primary localization. The median progression-free survival was 1.9 months, and the overall survival was 6.6 months. After a median follow-up of 3.6 years, only four (7%) patients were still alive; 1- and 2-year survival rates were 33% and 17%, respectively. Responders had a significantly longer overall survival of 30.2 months compared with 4.8 months in nonresponders. AVE was well tolerated, with few treatment-related grade 3/4 adverse events, and the quality of life remained stable during treatment.

Conclusions:
In patients with progressive high-grade NEN G3, AVE was well tolerated and provided disease control with significant clinical benefit in 15% of heavily pretreated patients.
RAD51 Testing in Patients with Early HER2-Negative Breast Cancer and Homologous Recombination Deficiency: A Post Hoc Analysis of the GeparOLA Trial
Authors: Villacampa Guillermo , Llop-Guevara Alba , Filmann Natalie , Herencia-Ropero Andrea , Fasching Peter A. , Karn Thomas , Marmé Frederik , Klare Peter , Müller Volkmar , Stefek Andrea , Schem Christian , Uleer Christoph , Fehm Tanja , Doering Gabriele , Stickeler Elmar , van Mackelenbergh Marion , Felder Bärbel , Nekljudova Valentina , Balmaña Judith , Denkert Carsten , Loibl Sibylle , Serra Violeta 
Published: December 2024

Abstract

Purpose:
The randomized GeparOLA trial reported comparable pathologic complete response (pCR) rates with neoadjuvant treatment containing olaparib versus carboplatin. In this study, we evaluate the association between functional homologous recombination deficiency (HRD) by RAD51 foci and pCR and the potential of improving patient selection by combining RAD51 and stromal tumor-infiltrating lymphocytes.

Patients and Methods:
This is a post hoc blinded biomarker analysis from the randomized GeparOLA trial. Patients with early-stage HER2-negative breast cancer and HRD assessed by Myriad MyChoice or BRCA1/BRCA2 mutations were randomized 1:1 to receive (i) paclitaxel plus olaparib or (ii) paclitaxel plus carboplatin, both followed by epirubicin/cyclophosphamide. Functional HRD was predefined as a RAD51 score ≤10% (RAD51-low).

Results:
Overall, 90 of 97 (92.8%) samples were evaluable for RAD51 testing, and 72 of 90 (80.0%) were RAD51-low. The pCR rate in patients with RAD51-low tumors was 66.7% (48/72), whereas it decreased to 22.2% (4/18) in those with RAD51-high. In the multivariable model including clinicopathologic factors and treatment, the RAD51 score remained significantly associated with pCR (OR = 12.03; 95% confidence interval, 2.60–55.73; P = 0.002). Patients with RAD51-low and high stromal tumor-infiltrating lymphocytes in their tumors achieved a pCR rate of 75.0% (27/36). Similar results were observed for olaparib or carboplatin. In the exploratory disease-free survival analysis, no differences were observed between RAD51 groups (high vs. low: HR = 0.85; 95% confidence interval, 0.25–2.97).

Conclusions:
In a preselected population with HRD, according to a genetic test, RAD51 testing identifies patients with different pCR rates under PARP inhibitor-based or platinum-based therapies. Future biomarker-driven studies should consider this information to refine stratification factors and to improve patient selection.
OBI-992, a Novel TROP2-Targeted Antibody–Drug Conjugate, Demonstrates Antitumor Activity in Multiple Cancer Models
Authors: Li Wan-Fen , Chiang Ming-Feng , Weng Hao-Cheng , Yang Jhih-Jie , Wu Hsin-Shan , Wu Szu-Yu , Chen Yu-Jung , Lu Chi-Huan , Tu Jyy-Shiuan , Hsu Ren-Yu , Shia Chi-Sheng , Huang Teng-Yi , Lai Ming-Tain 
Published: December 2024

Abstract
Trophoblast cell surface antigen 2 (TROP2) is highly expressed in multiple cancers relative to normal tissues, supporting its role as a target for cancer therapy. OBI-992 is an antibody–drug conjugate (ADC) derived from a novel TROP2-targeted antibody linked to the topoisomerase 1 (TOP1) inhibitor exatecan via an enzyme-cleavable hydrophilic linker, with a drug–antibody ratio of 4. This study evaluated and compared the antitumor activity of OBI-992 with that of benchmark TROP2-targeted ADCs datopotamab deruxtecan (Dato-DXd) and sacituzumab govitecan (SG) in cell line–derived xenograft (CDX) and patient-derived xenograft (PDX) models. OBI-992 treatment exhibited statistically significant antitumor activity versus controls at doses of 3 and 10 mg/kg in various CDX and PDX models, demonstrating comparable or better antitumor activity with benchmark ADCs. In a large-tumor model, longer survival times were observed in OBI-992-treated mice compared with Dato-DXd-treated mice. OBI-992 treatment induced marked bystander killing of TROP2-negative cells in the presence of nearby TROP2-positive cells in both in vitro and in vivo studies. In lung adenocarcinoma CDX models with overexpression of either P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) to mimic ATP-binding cassette transporter–mediated multidrug resistance, OBI-992 treatment maintained antitumor activity when Dato-DXd treatment became less effective. The combination of OBI-992 at suboptimal doses with either poly (ADP-ribose) polymerase (PARP) inhibitors or an immune check point inhibitor produced synergistic antitumor effects in mouse models. Taken together, these translational results support further development of OBI-992 as a cancer therapy.
ЕТІОЛОГІЧНІ, ЕПІДЕМІОЛОГІЧНІ ТА КЛІНІЧНІ АСПЕКТИ ГАРЯЧКИ ЗАХІДНОГО НІЛУ
Authors: Копча В. С. 
Published: December 2024

Вірус Західного Нілу (ВЗН) переважно інфікує комарів, птахів, коней і людей. Цей збудник може спричиняти безсимптомне інфікування або захворювання з різноманітними клінічними проявами – від легкої гарячки до смертельно небезпечних нейроінвазивних форм хвороби. Останнім часом в Європейському Союзі та сусідніх країнах зросла частота і тяжкість захворювань, зумовлених ВЗН, особливо в середземноморському регіоні. Ймовірно ця тенденція пов’язана з підвищенням як середньої температури повітря, так і кількості опадів, що є сприятливими для поширення ВЗН. Завдяки помітному та зростаючому географічному розповсюдженню переносника та високому ендемічному потенціалу ВЗН, він викликає дедалі більше побоювань для громадської охорони здоров’я.
Клінічний спектр симптоматичної гарячки Західного Нілу (ГЗН) у людей широкий. У близько 80 % людей інфекція перебігає безсимптомно, у 20 % виявляють неспецифічне гарячкове захворювання, ступінь тяжкості якого може варіювати від легкого до тяжкого, тоді як у невеликої групи пацієнтів (<1 %) розвивається потенційно летальне нейроінвазивне захворювання. Одужання від ГЗН може бути повільним, а рівень смертності досягає 10 %, хоча й залежить від віку та імунного стану пацієнтів.
Особливо непокоїть той факт, що наразі немає вакцини або специфічних противірусних засобів для лікування таких хворих.
Patient engagement in rehabilitation: An evolutionary concept analysis
Authors: Jiang Hu , Lin Beilei , Liu Zhiwei , Mei Yongxia , Li Xin , Ma Ling , Zhang Zhenxiang 
Published: December 2024

Objective The purpose of this study was to clarify the concept of engagement in rehabilitation by analyzing its application in both theoretical and empirical literature. Data sources PubMed, Web of Science, CINAHL, Embase, and Scopus were searched for relevant studies published from January 1, 2003 to July 14, 2024. Review methods A literature-based concept analysis was carried out using Rogers’ six-step evolutionary concept analysis method. Literature screening and data extraction were conducted separately by two researchers according to predetermined inclusion and exclusion criteria. The basic information and the relevant primary data of the included studies were extracted in detail. Results In total, 41 studies were included and analyzed. The antecedents included demographic factors, physical health, psychological and emotional factors, cognitive factors, behavioral factors, socio-cultural factors, environmental factors, and rehabilitation programs. The attributes contained collaborative therapeutic relationships, continual commitment and investment, a dynamic process and state, and goal-oriented. The consequences included multidisciplinary collaborations, communication, functional recovery, future independent exercise, and mental health. Conclusion This study clarified the concept of engagement in rehabilitation and identified antecedents, attributes, and consequences of the concept. Further research is required to investigate and apply this concept to specific populations and settings.
Development of a highly accurate diagnostic model for prostate cancer through the integration of clinical indices with apparent diffusion coefficient values derived from 3.0-T magnetic resonance
Authors: Hao Pan , Xin Ruiqiang , Peng Ruchen , Li Yancui , Na Xu , Zhong Jiali , Lv Xiaoyong , Sun Lixin 
Published: December 2024

Objective We aimed to evaluate the diagnostic utility of 3.0-T magnetic resonance (MR) diffusion-weighted imaging (DWI)-derived apparent diffusion coefficient (ADC) values in conjunction with clinical indices for prostate cancer (PCa). Methods A retrospective analysis was conducted on the clinical data of 181 patients with suspected PCa who underwent MR DWI prior to biopsy at LuHe Hospital, Beijing, between February 2022 and July 2023. Patients were placed into Malignancy and Benign groups according to the biopsy results. Univariate and multivariate analyses were performed on the ADC values and clinical indicators, and then a combination predictive model was developed. The model’s diagnostic accuracy was assessed using receiver operating characteristic (ROC) curve and decision curves analysis (DCA), and a nomogram was constructed for the assessment of individual risk. Results The ADC value and the free prostate-specific antigen and total prostate-specific antigen (tPSA) levels were found to be independent predictors of PCa. tPSA showed the best diagnostic performance, with an area under the curve (AUC) of 0.914. However, the combined model had a higher diagnostic accuracy, with an AUC of 0.959. Conclusion The combined model has superior predictive performance to other diagnostic methods and should help with the avoidance of unnecessary prostate biopsies.
Usefulness of multiparametric MRI for local staging of bladder cancer
Authors: Paudyal Prajwal , Mete Uttam , Gorsi Ujjwal , Kumar Santosh , Kakkar Nandita 
Published: December 2024

Introduction: Under staging and over staging are not uncommon with traditional MRI while staging bladder cancer. Current improvements in MRI technology due to addition of functional MR sequences that is, dynamic contrast-enhanced (DCE) imaging and diffusion-weighted imaging (DWI) have enhanced its clinical utility. The current study was designed to look for staging accuracy of multiparametric MRI (mp-MRI) that is, T2W + DCE + DWI, over conventional MRI. Material and methods: Forty patients with bladder cancer were included were subjected to mp-MRI on a 3T scanner with a phased array body coil. Four MR image sets that is, T2W, T2W + DCE, T2W + DWI, and T2W + DCE + DWI were interpreted. Accuracy of each image set was determined separately and was compared with the gold standard histopathological staging. Result: Staging accuracy of different image set increased from T2W (55%) to DCE (72.5%) to DWI (80%). Maximum accuracy was seen in mp-MRI (T2W + DWI + DCE) (87.5%). While differentiating non muscle invasive from muscle invasive disease (⩽T1 vs ⩾T2 stage) staging accuracy increased from T2W (65%) to DCE (80%) to DWI (85%) with maximum in mp-MRI (90%). Conclusion: mp-MRI offers high staging accuracy for bladder cancer.
Puerarin Promotes Tibial Shaft Fracture Healing in Rats and Its Relationship with BMP-Smad Pathway
Authors: Mao Yini , Li Jun , Zhang Feifei 
Published: December 2024

Background Fracture healing involves multiple growth factors and the interaction between multiple signaling pathways. Pue (puerarin) is a natural compound with multiple biological activities, but its effect on fracture healing and its relationship with the bone morphogenic protein (BMP)-Smad pathway is not yet clear. Purpose This study intends to assess the effect of puerarin on fracture healing. Methods Seventy rats were used for the study to establish a tibial shaft fracture rat model. The experimental rats were divided into a tibial fracture group, Pue dose group (low, medium, and high), BMP-2 group, Noggin group, Pue + SY-LB-35 group, and Pue + Noggin group through the random number method. We observed the fracture healing through micro-CT and histology, observed the tibial stump tissue with hematoxylin and eosin (HE) staining, and detected the expression of genes related to the BMP-Smad pathway through quantitative real-time polymerase chain reaction (qPCR) and Western blot. Results We found that puerarin can promote tibial shaft fracture healing in rats in a dose-dependent manner; through micro-CT and histological analysis, we observed increased trabecular bone formation during fracture healing in rats treated with puerarin. Callus formation is accelerated, and bone density increases. In addition, puerarin also significantly increased the expression of genes related to the BMP-Smad pathway, including BMP2, Smad1, Smad5, and so on. Conclusion Puerarin can promote tibial shaft fracture healing in rats, and its mechanism is related to upregulating the expression of genes related to the BMP-Smad pathway. It further improves the fracture-healing mechanism and provides candidate drugs for the treatment of tibial shaft fracture healing in clinical medicine.
Using a Functional Upper Limb Motor Task to Predict Cognitive and Functional Decline in Mild Cognitive Impairment and Alzheimer’s Disease
Authors: Koppelmans Vincent , Duff Kevin , Schaefer Sydney Y. 
Published: December 2024

Background: Predicting the rate of cognitive and functional decline over the course of Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD) is vital for advancing clinical care and research initiatives. Objectives: The current study examined if a functional upper limb motor task could predict 1-year change in cognition (Mini Mental Status Examination [MMSE]) and daily function (Quick Dementia Rating System [QDRS]) from a sample of 61 cognitively intact, 35 MCI, and 32 AD subjects. Results: Analyses adjusted for age, sex, and education showed that performance speed and variability on the motor task significantly predicted change in performance on the MMSE and QDRS over 1 year, and that these effects were small to medium in size (η2 = 0.04-0.05). Conclusion: These results suggest the potential of a simple motor task to estimate disease progression in MCI and AD, which could be used to provide additional clinical resources for and enrich clinical trials with those most likely to decline.
Is the use of abduction pillows crucial for post-operative rehabilitation following reverse total shoulder arthroplasty?
Authors: Cullen Mark M , Warren Eric , Hurley Eoghan T , Goltz Daniel E , Lorentz Samuel , Crook Bryan S , Adu-Kwarteng Kwabena , Levin Jay M , Klifto Christopher S , Anakwenze Oke A 
Published: December 2024

Background Surgeons often use abduction pillows after reverse total shoulder arthroplasty (rTSA), but evidence for their benefits is limited. This study compares outcomes for patients using a sling with or without an abduction pillow post-operatively. Methods A retrospective review was conducted on patients undergoing primary rTSA. Patients were grouped based on post-operative use of an abduction pillow or not. Data was collected at 6 weeks, 3 months, 6 months, 1 year, and final follow-up. Primary outcomes included rates of post-operative dislocation, range of motion, and patient-reported outcomes. Results Patients using an abduction pillow showed reduced forward flexion at 3 months (120° vs. 139°, p = 0.002) and 6 months (135° vs. 147°, p = 0.049). At 6 weeks, abduction was lower in the pillow group (90° vs. 124°, p = 0.01). There were no significant differences in other range-of-motion metrics or patient-reported outcomes. Using no pillow did not increase dislocation risk (OR: 1.67, p = 0.60), infection, readmission, revision, or repeat surgery rates. Conclusions Post-operative sling use without an abduction pillow after rTSA appears safe, with no increase in complications and similar patient satisfaction and outcomes. Level of Evidence Therapeutic Level III
Mid Term Survivorship of the Infinity Ankle Replacement in the National Joint Registry
Authors: Jennison Toby , Favier Barabara , Goldberg Andrew J. J. 
Published: December 2024

Category: Ankle Arthritis; Ankle Introduction/Purpose: The Infinity ankle replacement is a two component fixed bearing implant. It was introduced to the market in in 2014 is now the most commonly implanted ankle replacement globally. The National Joint Registry of England Wales and Northern Ireland is the largest ankle replacement registry in the world which captures outcomes of ankle replacements in a voluntary but mandated fashion. The primary aim of this study was to determine the failure rates of the Infinity ankle replacement in the UK. Methods: Data was collected prospectively by the NJR with all primary ankle replacements captured on proforma forms known as the NJR A1. All failures of ankle replacements are recorded using an NJR A2 form. Results: Overall 3781 implants have been implanted. The mean age was 68.5 and median BMI of 29, 60.5% male. 82.7% of patients were ASA 1 or 2 and the indication was osteoarthritis in 92.5%. Overall 60 implants have been revised. The most common reason was infection in 33 cases, followed by aseptic loosening of the tibia. Aseptic loosening of the talus only occurred in 2 cases. The failure rate of the Infinity was significantly better (P< 0.001) when compared to the expected number of revisions of 96.03. 20 revisions were exchange of polyethylene, with 15 revisions of both components. The 1 year failure rate is 0.5% (95% CI 0.3-0.7%). The 5 year failure rate is 2.2% (1.7%-2.8%), and 7 year survival in 225 patients is 3.5% (2.3-4.8%). Conclusion: The Infinity ankle replacement has lower failure rates than expected when compared to other contemporary ankle replacements. This data highlights the improvement in outcomes of a new fourth generation fixed bearing ankle replacement