bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant Trebananib plus Paclitaxel-based Chemotherapy for Stage II/III Breast Cancer in the Adaptively Randomized I-SPY2 Trial—Efficacy and Biomarker Discovery
Authors: Albain Kathy S. , Yau Christina , Petricoin Emanuel F. , Wolf Denise M. , Lang Julie E. , Chien A. Jo , Haddad Tufia , Forero-Torres Andres , Wallace Anne M. , Kaplan Henry , Pusztai Lajos , Euhus David , Nanda Rita , Elias Anthony D. , Clark Amy S. , Godellas Constantine , Boughey Judy C. , Isaacs Claudine , Tripathy Debu , Lu Janice , Yung Rachel L. , Gallagher Rosa I. , Wulfkuhle Julia D. , Brown-Swigart Lamorna , Krings Gregor , Chen Yunn Yi , Potter David A. , Stringer-Reasor Erica , Blair Sarah , Asare Smita M. , Wilson Amy , Hirst Gillian L. , Singhrao Ruby , Buxton Meredith , Clennell Julia L. , Sanil Ashish , Berry Scott , Asare Adam L. , Matthews Jeffrey B. , DeMichele Angela M. , Hylton Nola M. , Melisko Michelle , Perlmutter Jane , Rugo Hope S. , Symmans W. Fraser , van't Veer Laura J. , Yee Douglas , Berry Donald A. , Esserman Laura J. 
Published: December 2023

Abstract

Purpose:
The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel±trastuzumab in the I-SPY2 breast cancer trial.

Patients and Methods:
I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone receptor (HR) and HER2 status and MammaPrint risk (MP1, MP2). The primary endpoint is pathologic complete response (pCR). A therapy “graduates” if/when it achieves 85% Bayesian probability of success in a phase III trial within a given subtype. Patients received weekly paclitaxel (plus trastuzumab if HER2-positive) without (control) or with weekly intravenous trebananib, followed by doxorubicin/cyclophosphamide and surgery. Pathway-specific biomarkers were assessed for response prediction.

Results:
There were 134 participants randomized to trebananib and 133 to control. Although trebananib did not graduate in any signature [phase III probabilities: Hazard ratio (HR)-negative (78%), HR-negative/HER2-positive (74%), HR-negative/HER2-negative (77%), and MP2 (79%)], it demonstrated high probability of superior pCR rates over control (92%–99%) among these subtypes. Trebananib improved 3-year event-free survival (HR 0.67), with no significant increase in adverse events. Activation levels of the Tie2 receptor and downstream signaling partners predicted trebananib response in HER2-positive disease; high expression of a CD8 T-cell gene signature predicted response in HR-negative/HER2-negative disease.

Conclusions:
The angiopoietin (Ang)/Tie2 axis inhibitor trebananib combined with standard neoadjuvant therapy increased estimated pCR rates across HR-negative and MP2 subtypes, with probabilities of superiority &gt;90%. Further study of Ang/Tie2 receptor axis inhibitors in validated, biomarker-predicted sensitive subtypes is warranted.
Niraparib plus Dostarlimab in Pleural Mesothelioma or Non–Small Cell Lung Cancer Harboring HRR Mutations: Interim Results of the UNITO-001 Phase II Prospective Trial
Authors: Passiglia Francesco , Righi Luisella , Bironzo Paolo , Listì Angela , Farinea Giovanni , Capelletto Enrica , Novello Silvia , Merlini Alessandra , Scagliotti Giorgio V. 
Published: December 2023

Abstract

Purpose:
Treatment of homologous recombination repair–deficient (HRD)-tumors with PARP inhibitors has the potential to further increase tumor immunogenicity, suggesting a synergistic effect with immunotherapy. Here we present the preliminary results of niraparib in combination with dostarlimab for pleural mesothelioma (PM) or non–small cell lung cancer (NSCLC) harboring HRR mutations.

Patients and Methods:
UNITO-001 is a phase II, prospective, study aiming to investigate the combination of niraparib plus dostarlimab in pretreated patients with HRD and programmed death ligand-1 (PD-L1) ≥1% NSCLC and/or PM. The primary endpoint is progression-free survival (PFS).

Results:
Seventeen of 183 (10%) screened patients (12 PM and 5 NSCLC) were included. The objective response rate (ORR) was 6% [95% confidence interval (CI): 0.1–28.7] and the disease control rate (DCR) was 53% (95% CI: 27.8–77). Median PFS was 3.1 (95% CI: 2.7–N.A) and median overall survival (OS) was 4.2 (95% CI: 1.58–NA) months. The PFS was 14.1 months in one PM patient harboring a germline BAP1 mutation. The treatment duration was 9.8 months in one PM patient harboring a somatic BRCA2 mutation. The most common adverse events (AE) were grade 1–2 lymphopenia (59%), anemia (35%), hyponatremia (29%), and hypokalemia (29%). Grade ≥3 AEs were reported in 23% of the patients.

Conclusions:
This preliminary analysis highlighted the lack of antitumor activity for the combination of niraparib and dostarlimab in patients with PM and/or advanced NSCLC harboring BAP1 somatic mutations. A potential antitumor activity emerged for PM with germline BAP1 and/or BRCA2 somatic mutations along with a good tolerability profile.
Hospital‐Level Variability in Reporting of Ischemic Stroke Subtypes and Supporting Diagnostic Evaluation in GWTG‐Stroke Registry
Authors: Mullen Michael T. , Gurol M. Edip , Prabhakaran Shyam , Messé Steven R. , Kleindorfer Dawn O. , Smith Eric E. , Fonarow Gregg C. , Xu Haolin , Zhao Xin , Cigarroa Joaquin E. , Schwamm Lee H. 
Published: December 2023

Background
Secondary prevention of ischemic stroke (IS) requires adequate diagnostic evaluation to identify the likely etiologic subtype. We describe hospital‐level variability in diagnostic testing and IS subtyping in a large nationwide registry.

Methods and Results
We used the GWTG‐Stroke (Get With The Guidelines–Stroke) registry to identify patients hospitalized with a diagnosis of acute IS at 1906 hospitals between January 1, 2016, and September 30, 2017. We compared the documentation rates and presence of risk factors, diagnostic testing, achievement/quality measures, and outcomes between patients with and without reported IS subtype. Recording of diagnostic evaluation was optional in all IS subtypes except cryptogenic, where it was required. Of 607 563 patients with IS, etiologic IS subtype was documented in 57.4% and missing in 42.6%. Both the rate of missing stroke pathogenesis and the proportion of cryptogenic strokes were highly variable across hospitals. Patients missing stroke pathogenesis less frequently had documentation of risk factors, evidence‐based interventions, or discharge to home. The reported rates of major diagnostic testing, including echocardiography, carotid and intracranial vascular imaging, and short‐term cardiac monitoring were <50% in patients with documented IS pathogenesis, although these variables were missing in >40% of patients. Long‐term cardiac rhythm monitoring was rarely reported, even in cryptogenic stroke.

Conclusions
Reporting of IS etiologic subtype and supporting diagnostic testing was low overall, with high rates of missing optional data. Improvement in the capture of these data elements is needed to identify opportunities for quality improvement in the diagnostic evaluation and secondary prevention of stroke.
The Cross-Shelf Regime of a Wind-Driven Supercritical River Plume
Authors: Yankovsky Elizabeth , Yankovsky Alexander 
Published: December 2023

Abstract
River plumes are a dominant forcing agent in the coastal ocean, transporting tracers and nutrients offshore and interacting with coastal circulation. In this study we characterize the novel “cross-shelf” regime of freshwater river plumes. Rather than remaining coastally trapped (a well-established regime), a wind-driven cross-shelf plume propagates for tens to over 100 km offshore of the river mouth while remaining coherent. We perform a suite of high-resolution idealized numerical experiments that offer insight into how the cross-shelf regime comes about and the parameter space it occupies. The wind-driven shelf flow comprising the geostrophic along-shelf and the Ekman cross-shelf transport advects the plume momentum and precludes geostrophic adjustment within the plume, leading to continuous generation of internal solitons in the offshore and upstream segment of the plume. The solitons propagate into the plume interior, transporting mass within the plume and suppressing plume widening. We examine an additional ultra-high-resolution case that resolves submesoscale dynamics. This case is dynamically consistent with the lower-resolution simulations, but additionally captures vigorous inertial-symmetric instability leading to frontal erosion and lateral mixing. We support these findings with observations of the Winyah Bay plume, where the cross-shelf regime is observed under analogous forcing conditions to the model. The study offers an in-depth introduction to the cross-shelf plume regime and a look into the submesoscale mixing phenomena arising in estuarine plumes.

Significance Statement
In this study, we characterize a novel regime of freshwater river plumes. Rather than spreading near to or along the coast, under certain conditions river plumes may propagate away from the coast and remain coherent for tens to over 100 km offshore. Cross-shelf plumes provide a mechanism by which freshwater and river-borne materials may be transported into the open ocean, especially across wide continental shelves. Such plumes carry nutrients critical for biological productivity offshore and interact with large-scale oceanic features such as the Gulf Stream. We use high-resolution numerical modeling to examine how the cross-shelf regime arises and support our findings with observational evidence. We also study the mixing phenomena and fluid instabilities evolving within such plumes.
Post-operative interventional radiotherapy (brachytherapy) in advanced ocular surface and eyelid tumors as an alternative to surgical retreatment
Authors: Cuffaro Giovanni , Fionda Bruno , Piccinni Fabrizio , Pagliara Monica Maria , Sammarco Maria Grazia , Blasi Maria Antonietta , Molinario Clelia , Castri Federica , Tagliaferri Luca , Massi Daniela , Savino Gustavo 
Published: December 2023

Purpose The main purpose of treatment of advanced ocular surface and periocular malignant tumors is to eradicate the tumor while trying to preserve visual function and aesthetics. Our purpose is to describe the outcome of a retrospective case series of 10 patients with advanced ocular surface and periocular tumors treated surgically in first instance and then with postoperative interventional radiotherapy (IRT/Brachiterapy). Materials and Methods We describe the clinicopathological features, treatments and outcome, in a retrospective case series of 10 patients with advanced tumors involving ocular surface (staging ≥ T2) and eyelids (staging ≥ T3), with involvement of periocular and/or orbit tissues. Patients were first surgically treated, most of them with incomplete excision, and then underwent a post-operative interventional radiotherapy (IRT/Brachytherapy) as an alternative to more invasive and disfiguring surgical retreatment. Tumor location, risk factors, staging, histological features, and follow-up timing were analyzed. Results Three patients had advanced eyelid basal cell carcinomas, 2 patients were diagnosed with eyelid and conjunctival squamous cell carcinomas, 3 as sebaceous carcinomas, and 2 as primary conjunctival melanomas. The mean follow-up time from IRT to last clinical follow-up was 58.6 weeks, range 28.4–168 (median 43.65, IQR 28.9–72.9). Two patients - one with ocular surface SCC, the other with conjunctival melanoma - had a local recurrence 23.4 and 40,9 weeks after IRT, respectively. An overview of the current knowledge on adjuvant or post-operative IRT is also provided. Conclusions IRT can be considered an effective therapeutic option to avoid more invasive surgical retreatment in advanced tumors involving eyelids and ocular surface.
Effectiveness of the preventive administration of vasoactive amines in counterbalancing significant patient blood pressure drops following nimodipine administration during mechanical thrombectomy procedures
Authors: Bernava Gianmarco , Tesoro Rosa , Boto José , Challita Myriam , Rosi Andrea , Hofmeister Jeremy , Yilmaz Hasan , Carrera Emmanuel , Brina Olivier , Reymond Philippe , Muster Michel , Kulcsar Zsolt , Lovblad Karl-Olof , Machi Paolo 
Published: December 2023

Background Focal vasospasm (FV) of the occluded vessel can occur during the endovascular treatment of acute ischemic stroke (AIS). Nimodipine is commonly used to treat vasospasm and can play a role in distinguishing it from artery narrowing due to iatrogenic dissection or residual clot. However, nimodipine administration can result in arterial hypotension and subsequent enlargement of the ischemic core. Objective To assess the efficacy of preventive and continuous vasoactive amine infusion to counterbalance nimodipine-induced hypotension. Methods We reviewed data from a prospective registry of patients treated for AIS between January 2019 and January 2022 who were administered nimodipine. All patients were equipped with an arterial cannula for invasive blood pressure measurement and given vasoactive amines preemptively before general anesthesia and throughout the procedure. Data obtained from invasive monitoring of mean arterial blood pressure (MABP) in a time-lapse of 25 min before and after nimodipine administration were analyzed. Results MABP significantly decreased after nimodipine administration but remained within the recommended range (81.79 ± 0.49 mmHg). Nimodipine was effective in reducing FV caused by stent retriever passage in 76.3% of cases. Furthermore, it proved valuable in diagnosing iatrogenic dissection (9.2%), residual clot (10.5%), or intracranial stenosis (4%). Conclusions Infusion of vasoactive amines effectively counteracted the intraarterial nimodipine effect, thus avoiding frank arterial hypotension during endovascular treatment. Nimodipine has been useful in differentiating the diagnosis of FV resulting from mechanical thrombectomy and other potential causes, such as iatrogenic dissection or residual clot.
Educational Improvement Science: The Art of the Improving Organization
Authors: Li (李军) Jun 
Published: December 2023

Purpose To advocate educational improvement science (EIS) as an emerging transdisciplinary field, I reflect on the three major pathways of educational advancement in human history, discern the misuses and pitfalls of reform, and theorize how education can be improved to better serve its mission. Design/Approach/Methods Employing a multiperspectival approach, I critically re-examine educational reforms and improvements worldwide and conceptualize the emerging transdisciplinary field through an extensive literature review, etymological analysis, international comparisons, and socio-historical, -cultural and -philosophical reflections. Findings In this paper, I advance the concept of neo-improvementalism for EIS by elucidating its philosophical assumptions, disciplinary fundamentals, and theoretical frameworks through historical and comparative lenses. I identify and construct disciplinary knowledge of EIS comprising two categories, namely, subject matter knowledge and profound knowledge, adopted from improvement science. I then highlight three methodological approaches of EIS and the building of professional improvement communities empowering individual and institutional improvement capabilities. I propose that EIS is the art of the improving organization for classes, schools, and/or more broadly defined educational agencies. Originality/Value This study recognizes the significance of EIS and research thereon, especially discipline-building and exploration based on local characteristics in a global vision, and the cultivation of new frontiers of educational research and practices.
Prevalence & Risk Factors for Perinatal Stroke: A Population-Based Study
Authors: Roy Bithi , Webb Annabel , Walker Karen , Morgan Catherine , Badawi Nadia , Nunez Carlos , Eslick Guy , Kent Alison L , Hunt Rod W , Mackay Mark T , Novak Iona 
Published: December 2023

Objectives The study objective was to calculate the birth prevalence of perinatal stroke and examine risk factors in term infants. Some risk factors are present in healthy infants, making it difficult to determine at-risk infants. Study Design Prospective population-based perinatal stroke data were compared to the Australian general population data using chi-squared and Fisher's exact tests and multivariable logistic regression analysis. Results Sixty perinatal stroke cases were reported between 2017 and 2019. Estimated stroke prevalence was 9.6/100,000 live births/year including 5.8 for neonatal arterial ischemic stroke and 2.9 for neonatal hemorrhagic stroke. Eighty seven percent had multiple risk factors. Significant risk factors were cesarean section ( p = 0.04), 5-min Apgar score <7 ( p < 0.01), neonatal resuscitation ( p < 0.01) and nulliparity ( p < 0.01). Conclusions Statistically significant independent risk factors do not fully explain the cause of perinatal stroke, because they are not a direct causal pathway to stroke. These data now require validation in a case-control study.
Prevalence of Cesarean Section Among Nurses: Predictors and Effect on Exclusive Breastfeeding
Authors: Alhassan Abdul Rauf 
Published: December 2023

Introduction The prevalence of cesarean sections (CSs) in both industrialized and developing nations is a significant issue for public health officials, particularly in light of the knowledge of their socioeconomic underlying determinants. Objective To ascertain the prevalence of CS delivery among nurses, their predictors, and the effect it has on exclusive breastfeeding practice in Tamale, Ghana. Methods This study used a quantitative technique and an analytical cross-sectional design. Data analysis was done using Statistical Package for the Social Sciences, and variable associations and predictions were identified using chi-square and logistics regression analysis. Results There were 326 fully completed and returned questionnaires; the majority (40.0%) of respondents were registered general nurses (RGN). The majority of respondents (56.0%) were between the ages of 31 and 40. The prevalence rate of CS delivery was 21.1%. Predictor variables were; Community health nurses/RGN (adjusted odds ratio [AOR] = 3.7, 95% confidence interval [CI] = 1.2–11.0), and second degree/first degree level of educational attainment (AOR = 36.0, 95% CI = 2.4–528.9). The effects of CS delivery on exclusive breastfeeding were; low confidence to exclusively breastfeed, opting to combine both breastfeeding and artificial feeding, and less likely to practice exclusive breastfeeding. Conclusion Even though CSs and exclusive breastfeeding practices are both problems facing nurses, CSs seem to compound the problem of exclusive breastfeeding among nurses.
Career Regret and Health-Related Quality of Life among Medical Students: A Nationwide Cross-Sectional Study in Jordan
Authors: Khanfar Asim N. , Alshrouf Mohammad A. , Albandi Alaa M. , Odeh Qusai B. , Hammad Nouran H. , Abu Jbara Fahed Khaled , AlRyalat Saif Aldeen 
Published: December 2023

OBJECTIVES Medical students have a lower quality of life (QoL) when compared to the general population. This lower QoL is associated with multiple factors such as burnout and depressive symptoms. QoL can be reflected in the degree of career satisfaction and career regret. We aim to study the prevalence of career regret in Jordanian medical students and its association with QoL and other related factors METHODS This national cross-sectional study consisted of an anonymous online survey distributed to medical students enrolled in all six Jordanian medical schools over a period of 6 weeks. A validated tool was used to assess QoL and students were asked a series of questions related to their career satisfaction and career regret. RESULTS A total of 544 medical students completed the survey. The mean age was 21.5 ± 1.63 years (range 17-29), with 45.6% being males. The overall mean physical health score was 45.9 ± 5.17, and the overall mean mental health score (mental component summary (MCS)) was 42.04 ± 5.52. 76.3% of students have regretted studying medicine, citing stress as the main reason. There was a significant relation between the year of study and the percentage of career regret. Additionally, mean MCS was significantly lower in students who were frequently or always thinking about dropping out of medical school. DISCUSSION The high percentage of career regret and the low mental QoL in Jordanian students are alarming findings, highlighting an underlying source of psychological distress in Jordanians. This calls for further investigations into the psychological health of medical students, as well as interventions to prevent the development of consequences that can impact both students and their future patients.
Promotion of nutritional behaviors in the prevention of cardiovascular diseases: application of the health belief model in primary health care centers
Authors: Midjani Nasrin , Hossaini Fatemeh Alsadat , Sharifi Nader 
Published: December 2023

AbstractBackgroundCardiovascular diseases (CVD) are the most important cause of death in many countries of the world, including Iran. This study aimed to investigate the effect of educational intervention based on the Health Belief Model (HBM) on the promotion of nutritional behaviors to prevent CVD among the all people (aged 30–59 years).MethodsThis semi-experimental study was conducted on all people (aged 30–59 years) referring to the primary healthcare centers of Jahorm city, southern Iran, from September 2021 to July 2022. In this study, 100 participants (50 participants for the intervention group and 50 for the control group) were selected using a multistage cluster random sampling method. The data collection tool was a questionnaire with confirmed validity and reliability. Also, the food consumption frequency checklist was used. The educational intervention included holding four sessions, each lasting for 60 min. The methods used for training included lectures, questions and answers, and group discussions. Before the intervention and three months after, the intervention and control groups completed the questionnaire. The obtained data were analyzed by SPSS 17.Resultsafter the educational intervention, the mean score of knowledge (4.84 ± 0.84; 2.76 ± 1.41; p < 0.001), perceived susceptibility (9.52 ± 1.81; 8.76 ± 1.9; p = 0.004), perceived severity (14.78 ± 1.66; 13.80 ± 2.23; p = 0.015), perceived benefits (10.66 ± 1.79; 7.52 ± 1.99; p < 0.001), perceived barriers (5.92 ± 2.81; 12.68 ± 10.24; p < 0.001) and practice (178.78 ± 14.35; 147.36 ± 13.19; p < 0.001) showed a significant difference between the intervention and control groups.ConclusionThe results showed that the educational intervention effectively improved people (aged 30–59 years) knowledge and HBM constructs to prevent CVD. Also, improving people’s performance regarding CVD prevention behaviors will be successful by implementing an educational intervention based on the HBM.