bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2− Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial
Authors: Lu Yen-Shen , Im Seock-Ah , Colleoni Marco , Franke Fabio , Bardia Aditya , Cardoso Fatima , Harbeck Nadia , Hurvitz Sara , Chow Louis , Sohn Joohyuk , Lee Keun Seok , Campos-Gomez Saul , Villanueva Vazquez Rafael , Jung Kyung Hae , Babu K. Govind , Wheatley-Price Paul , De Laurentiis Michelino , Im Young-Hyuck , Kuemmel Sherko , El-Saghir Nagi , O'Regan Ruth , Gasch Claudia , Solovieff Nadia , Wang Craig , Wang Yongyu , Chakravartty Arunava , Ji Yan , Tripathy Debu 
Published: December 2021

Abstract

Purpose:
Ribociclib plus endocrine therapy (ET) demonstrated a statistically significant progression-free survival and overall survival (OS) benefit in the phase III MONALEESA-7 trial of pre-/perimenopausal patients with hormone receptor (HR)-positive (HR+), HER2-negative (HER2−) advanced breast cancer (ABC). The median OS was not reached in the ribociclib arm in the protocol-specified final analysis; we hence performed an exploratory OS and additional outcomes analysis with an extended follow-up (median, 53.5 months).

Patients and Methods:
Patients were randomized to receive ET [goserelin plus nonsteroidal aromatase inhibitor (NSAI) or tamoxifen] with ribociclib or placebo. OS was evaluated with a stratified Cox proportional hazard model and summarized with Kaplan–Meier methods.

Results:
The intent-to-treat population included 672 patients. Median OS was 58.7 months with ribociclib versus 48.0 months with placebo [hazard ratio = 0.76; 95% confidence interval (CI), 0.61–0.96]. Kaplan–Meier estimated OS at 48 months was 60% and 50% with ribociclib and placebo, respectively. Subgroup analyses were generally consistent with the OS benefit, including patients who received NSAI and patients aged less than 40 years. Subsequent antineoplastic therapies following discontinuation were balanced between the ribociclib (77%) and placebo (78%) groups. Use of cyclin-dependent kinase 4/6 inhibitors after discontinuation was higher with placebo (26%) versus ribociclib (13%). Time to first chemotherapy was significantly delayed with ribociclib versus placebo. No drug–drug interactions were observed between ribociclib and either NSAI.

Conclusions:
Ribociclib plus ET continued to show significantly longer OS than ET alone in pre-/perimenopausal patients, including patients aged less than 40 years, with HR+/HER2− ABC with 53.5 months of median follow-up (ClinicalTrials.gov, NCT02278120).
Long-term Follow-up and Patterns of Response, Progression, and Hyperprogression in Patients after PD-1 Blockade in Advanced Sarcoma
Authors: Klemen Nicholas D. , Hwang Sinchun , Bradic Martina , Rosenbaum Evan , Dickson Mark A. , Gounder Mrinal M. , Kelly Ciara M. , Keohan Mary L. , Movva Sujana , Thornton Katherine A. , Chi Ping , Nacev Benjamin A. , Chan Jason E. , Bartlett Edmund K. , Richards Allison L. , Singer Samuel , Donoghue Mark T.A. , Tap William D. , D'Angelo Sandra P. 
Published: December 2021

Abstract

Purpose:
Programmed cell death protein 1 (PD-1) blockade can mediate objective responses in advanced sarcomas, but their durability has not been established and it is unclear if hyperprogressive disease (HPD) occurs in sarcomas treated with PD-1 inhibitors.

Experimental Design:
We pooled patients who were treated prospectively with nivolumab or pembrolizumab as monotherapy or with bempegaldesleukin, epacadostat, ipilimumab, or talimogene laherparepvec. We did a new independent assessment for HPD and analyzed clinical, pathologic, and genomic data from baseline tumor biopsies. Our primary endpoint was the incidence of HPD; secondary endpoints were clinical or genomic correlates of response or HPD.

Results:
We treated 134 patients with advanced sarcoma from 2015 to 2019. Twenty-one patients (16%) had a complete or partial response (CR/PR), and 30% of responses were durable for over 2 years. Forty-eight (36%) patients had stable disease (SD), 45 (34%) had progressive disease without HPD (PD), and 15 (11%) had HPD. Five patients (4%) were not evaluable for HPD. The sarcoma subtypes, sites of metastasis, clinical course, and genomic alterations in patients with PD and HPD were similar, except HPD tumors were smaller at baseline.

Conclusions:
In patients with advanced sarcoma, PD-1 blockade can mediate durable responses. HPD occurs in sarcoma at an incidence that is similar to what has been reported in other solid tumors, but patients with HPD were clinically and biologically similar to those who had PD. Further research is required to establish whether HPD is a biologically distinct phenomenon and whether a theoretical risk of HPD should influence patient management.
Local Treatment of a Pediatric Osteosarcoma Model with a 4-1BBL Armed Oncolytic Adenovirus Results in an Antitumor Effect and Leads to Immune Memory
Authors: Martinez-Velez Naiara , Laspidea Virginia , Zalacain Marta , Labiano Sara , García-Moure Marc , Puigdelloses Montse , Marrodan Lucía , Gonzalez-Huarriz Marisol , Herrador Guillermo , de la Nava Daniel , Ausejo-Mauleon Iker , Fueyo Juan , Gomez-Manzano Candelaria , Patiño-García Ana , Alonso Marta M. 
Published: December 2021

Abstract
Osteosarcoma is an aggressive bone tumor occurring primarily in pediatric patients. Despite years of intensive research, the outcomes of patients with metastatic disease or those who do not respond to therapy have remained poor and have not changed in the last 30 years. Oncolytic virotherapy is becoming a reality to treat local and metastatic tumors while maintaining a favorable safety profile. Delta-24-ACT is a replicative oncolytic adenovirus engineered to selectively target cancer cells and to potentiate immune responses through expression of the immune costimulatory ligand 4-1BB. This work aimed to assess the antisarcoma effect of Delta-24-ACT. MTS and replication assays were used to quantify the antitumor effects of Delta-24-ACT in vitro in osteosarcoma human and murine cell lines. Evaluation of the in vivo antitumor effect and immune response to Delta-24-ACT was performed in immunocompetent mice bearing the orthotopic K7M2 cell line. Immunophenotyping of the tumor microenvironment was characterized by immunohistochemistry and flow cytometry. In vitro, Delta-24-ACT killed osteosarcoma cells and triggered the production of danger signals. In vivo, local treatment with Delta-24-ACT led to antitumor effects against both the primary tumor and spontaneous metastases in a murine osteosarcoma model. Viral treatment was safe, with no noted toxicity. Delta-24-ACT significantly increased the median survival time of treated mice. Collectively, our data identify Delta-24-ACT administration as an effective and safe therapeutic strategy for patients with local and metastatic osteosarcoma. These results support clinical translation of this viral immunotherapy approach.
Deciphering the Polygenic Basis of Racial Disparities in Prostate Cancer By an Integrative Analysis of Genomic and Transcriptomic Data
Authors: Zhang Wensheng , Nicholson Thea , Zhang Kun 
Published: December 2021

Abstract

Prostate cancer prevalence in African Americans (AA) is over 1.5 times the prevalence in European Americans (EA). Among over a hundred index risk SNPs for prostate cancer, only a few can be verified using the available AAs' data. Their relevance to the prevalence inequality and other racial disparities has not been fully determined. We investigated this issue by an integrative analysis of five public datasets. We categorized the datasets into two classes. The training class consisted of the datasets generated by three genome-wide association studies. The test class contained the prostate adenocarcinoma data of The Cancer Genome Atlas and the data of African and European super-populations in the 1000-Genome project. The polygenic risk scores (PRS) of test samples for cancer occurrence were calculated according to the effects of genetic variants estimated from the training samples. We obtained the following findings. Africans' PRSs are higher than Europeans' scores (P &lt; 1 × 10−6). AA patients' PRSs are higher than EA patients' scores (P &lt; 3×10−9). The patients with tumors presenting fusion or abnormal expression in ERG and other E26 transformation-specific (ETS) family genes have lower PRSs than the patients without such aberrations (P &lt; 7×10−5). Five tumor progression-related genes have the expression levels being significantly correlated with PRS (FDR &lt; 0.01). Additional simulation analysis shows that the high prostate cancer prevalence in African populations makes it challenging to identify individual risk variants using African men's data. These results implicate that the index risk SNP-based PRS is compatible with the observed racial disparity in prostate cancer prevalence and ETS abnormal cancers may be less heritable compared with other subtypes.

Prevention Relevance:
This study reveals the relevance of index risk SNP markers with racial disparities in prostate cancer. The findings also indicate that PRS can be used in prostate cancer subtype prediction.
First-in-Human Experience and Acute Procedural Outcomes Using a Novel Pulsed Field Ablation System: The PULSED AF Pilot Trial
Authors: Verma Atul , Boersma Lucas , Haines David E. , Natale Andrea , Marchlinski Francis E. , Sanders Prashanthan , Calkins Hugh , Packer Douglas L. , Hummel John , Onal Birce , Rosen Sofi , Kuck Karl-Heinz , Hindricks Gerhard , Wilsmore Bradley 
Published: December 2021

Background:
Pulsed field ablation (PFA) is a novel form of ablation using electrical fields to ablate cardiac tissue. There are only limited data assessing the feasibility and safety of this type of ablation in humans.

Methods:

PULSED AF (Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF;
https://www.clinicaltrials.gov
; unique identifier: NCT04198701) is a nonrandomized, prospective, multicenter, global, premarket clinical study. The first-in-human pilot phase evaluated the feasibility and efficacy of pulmonary vein isolation using a novel PFA system delivering bipolar, biphasic electrical fields through a circular multielectrode array catheter (PulseSelect; Medtronic, Inc). Thirty-eight patients with paroxysmal or persistent atrial fibrillation were treated in 6 centers in Australia, Canada, the United States, and the Netherlands. The primary outcomes were ability to achieve acute pulmonary vein isolation intraprocedurally and safety at 30 days.

Results:
Acute electrical isolation was achieved in 100% of pulmonary veins (n=152) in the 38 patients. Skin-to-skin procedure time was 160±91 minutes, left atrial dwell time was 82±35 minutes, and fluoroscopy time was 28±9 minutes. No serious adverse events related to the PFA system occurred in the 30-day follow-up including phrenic nerve injury, esophageal injury, stroke, or death.

Conclusions:
In this first-in-human clinical study, 100% pulmonary vein isolation was achieved using only PFA with no PFA system–related serious adverse events.

Graphic Abstract:
A graphic abstract is available for this article.
Early Pregnancy Blood Pressure Patterns Identify Risk of Hypertensive Disorders of Pregnancy Among Racial and Ethnic Groups
Authors: Gunderson Erica P. , Greenberg Mara , Nguyen-Huynh Mai N. , Tierney Cassidy , Roberts James M. , Go Alan S. , Tao Wei , Alexeeff Stacey E. 
Published: December 2021

Background:
Hypertensive disorders of pregnancy are a leading cause of severe maternal morbidity and mortality and confer 4-fold higher perinatal mortality in Black women. Early pregnancy blood pressure patterns may differentiate risk of hypertensive disorders of pregnancy.

Methods:
This study identified distinct blood pressure trajectories from 0 to 20 weeks’ gestation to evaluate subsequent pregnancy-related hypertension in a retrospective cohort of 174 925 women with no prior hypertension or history of preeclampsia, prenatal care entry ≤14 weeks, and a stillborn or live singleton birth delivered at Kaiser Permanente Northern California hospitals in 2009 to 2019. We used electronic health records to obtain clinical outcomes, covariables, and longitudinal outpatient blood pressure measurements ≤20 weeks’ gestation (mean 4.1 measurements). Latent class trajectory modeling identified 6 blood pressure groups: ultra-low-declining(referent), low-declining, moderate-fast-decline, low-increasing, moderate-stable, and elevated-stable. Multivariable logistic regression evaluated trajectory group-associations with the odds of preeclampsia/eclampsia and gestational hypertension‚ and effect modification by race-ethnicity and prepregnancy body size.

Results:

Compared with ultra-low-declining, adjusted odds ratios (95% confidence intervals [CIs]) for low-increasing, moderate-stable, and elevated-stable groups were 3.25 (2.7–3.9), 5.3 (4.5–6.3), and 9.2 (7.7–11.1) for preeclampsia/eclampsia‚ and 6.4 (4.9–8.3), 13.6 (10.5–17.7), and 30.2 (23.2–39.4) for gestational hypertension. Race/ethnicity, and prepregnancy obesity modified the trajectory-group associations with preeclampsia/eclampsia (interaction
P
<0.01), with highest risks for Black, then Hispanic and Asian women for all blood pressure trajectories, and with increasing obesity class.

Conclusions:
Early pregnancy blood pressure patterns revealed racial and ethnic differences in associations with preeclampsia/eclampsia risk within equivalent levels and patterns. These blood pressure patterns may improve individual risk stratification permitting targeted surveillance and early mitigation strategies.
Outcome of Aneurysmal Subarachnoid Hemorrhage in a Population‐Based Cohort: Retrospective Registry Study
Authors: Iversen Mathilde V. , Ingebrigtsen Tor , Totland Jon A. , Kloster Roar , Isaksen Jørgen G. 
Published: December 2021

Background
Studies of aneurysmal subarachnoid hemorrhage report an association between higher patient volumes and better outcomes. In regions with dispersed settlement, this must be balanced against the advantages with shorter prehospital transport times and timely access. The aim of this study is to report outcome for unselected aneurysmal subarachnoid hemorrhage cases from a well‐defined rural population treated in a low‐volume neurosurgical center.

Methods
This is a retrospective, population‐based, observational cohort study from northern Norway (population 486 450). The University Hospital of North Norway provides the only neurosurgical service. We retrieved data for all aneurysmal subarachnoid hemorrhage cases (n=332) admitted during 2007 through 2019 from an institution‐specific register. The outcome measures were mortality rates and functional status assessed with the modified Rankin scale.

Results
The mean annual number of cases was 26 (range, 16–38) and the mean crude incidence rate 5.4 per 100 000 person‐years. Two hundred seventy‐nine of 332 (84%) cases underwent aneurysm repair, 158 (47.5%) with endovascular techniques and 121 (36.4%) with microsurgical clipping, while 53 (15.9%) did not. The overall mortality rate was 16.0% at discharge and 23.8% at 12 months. The proportion with a favorable outcome (modified Rankin scale scores 0–2) was 36.1% at discharge and 51.5% at 12 months. In subgroup analysis of cases who underwent aneurysm repair, the mortality rate was 4.7% at discharge and 11.8% at 12 months, and the proportion with a favorable outcome 42.3% at discharge and 59.9% at 12 months.

Conclusions
We report satisfactory outcomes after treatment of aneurysmal subarachnoid hemorrhage in a low‐volume neurosurgical department serving a rural population. This indicates a reasonable balance between timely access to treatment and hospital case volume
Exploring the Unmet Need in Acute Ischemic Stroke Patients Not Treated With Intravenous Alteplase: The Get With The Guidelines‐Stroke Registry
Authors: Mac Grory Brian , Xian Ying , Solomon Nicole C. , Matsouaka Roland A. , Decker‐Palmer Marquita R. , Fonarow Gregg C. , Smith Eric E. , Schwamm Lee H. 
Published: December 2021

Background
Early administration of intravenous tissue plasminogen activator (IV alteplase) improves functional outcomes in patients with acute ischemic stroke, yet many patients are not treated with IV alteplase. There is a need to understand the reasons for nontreatment and the short‐ and long‐term outcomes in this patient population.

Methods
We analyzed patients ≥65 years old with a primary diagnosis of acute ischemic stroke presenting within 24 hours of time last known well (LKW) but not treated with IV alteplase from 1630 Get With The Guidelines‐Stroke hospitals in the United States between January 2016 and December 2016. We report clinical characteristics, reasons for withholding treatment, in‐hospital mortality, and 90‐day and 1‐year outcomes including costs, stratified by time from LKW to presentation (≤4.5, >4.5–6, and >6–24 hours).

Results
Of 39 760 patients (median age 80 [25th–75th quartiles: 73–87], 56.7% female), 19 391 (48.8%) presented within 4.5 hours of LKW. In those with documented reasons for withholding IV alteplase, the most common reasons were rapid improvement of symptoms (3985/14 782, 27.0%) and mild symptoms (3791/14 782, 25.6%). In 1100 out of 1174 (93.7%) patients presenting in the >3.0‐ to 4.5‐hour time window, the most common reason for not treating was a delay in patient arrival. The most common discharge location for those presenting ≤4.5 hours since LKW was home (8660/19 391, 44.7%). The 90‐day mortality and readmission rates were 18.9% and 23.0% in those presenting ≤4.5 hours since LKW, 19.0% and 22.2% in those presenting between 4.5 and 6 hours, and 19.1% and 23.2% in those presenting between 6 and 24 hours. Median 90‐day total in‐hospital costs remained relatively high at $9471 (Q25–Q75: $5622–$21 356) in patients presenting ≤4.5 hours since LKW.

Conclusions
Patients within the Get With The Guidelines‐Stroke registry not treated with IV alteplase have a high risk of readmission and mortality and have high total in‐hospital and postdischarge costs. This study may inform future efforts to address the unmet need to improve the scope of IV alteplase delivery along with other aspects of acute ischemic stroke care and, consequently, outcomes in this patient population.
Developmental & Ecological Perspective on the Intergenerational
Transmission of Trauma & Violence
Authors: Keels Micere 
Published: December 2021

Abstract
The focus of this essay is on understanding the development and maintenance of patterns of violent behavior for the purpose of identifying points of prevention and intervention. Close attention is paid to using person-centered language that does not conflate exhibiting violent behaviors with being a violent person. There is a meaningful perceptual difference between discussing the behaviors of a violent person versus discussing a person who engaged in violent behaviors: the former is more likely to be associated with immutable characteristics of a person and the latter is more likely to be associated with attempts at understanding social and contextual causes of the behavior.
Lu Märten: An Introduction to Four Texts
Authors: Nachtigall Jenny , Stakemeier Kerstin 
Published: December 2021

Abstract
This article presents an introduction to four texts that the German feminist-materialist art historian Lu Märten (1879–1970) published between 1903 and 1928. It outlines some of the major concepts of and contexts for this unduly neglected thinker. Her writings covered a wide terrain that spanned studies on the labor conditions of female artists, polemics against “proletarian art,” and a monist, rather than dialectical, view on film, art, and what she called the “full life-work of a human.” At the core of her multiple endeavors was the demand for remaking the history of art as a history of form that is more capacious than art's institutionalized Western field. Situating Märten's work in historical debates (e.g., on Marxist aesthetics in the 1930s), the introduction also points to the new legibility that her nonaligned materialism gains with the material turn in the humanities.
The Four Books of Shiʿi Hadith: From Inception to Consolidation
Authors: Ehteshami Amin 
Published: December 2021

Abstract
Since their compilations in the tenth and eleventh centuries ce, the four hadith books, al-Kāfī, al-Faqīh, al-Tahdhīb, and al-Istibṣār, have left an indelible mark on Shiʿi religiosity. The present study takes as its starting point the earliest instance in which these four compilations were collectively referred to as the Four Books (al-kutub al-arbaʿa). I investigate the major developments in the period between the inception of this phrase in the fifteenth century and its consolidation as the demarcator of a unique Imami hadith corpus in the seventeenth century. Following the introduction, each section of the article focuses on a figure whose ideas contributed to this consolidation process. In the conclusion I summarize the findings of the previous sections and reflect on the notion of hadith canonicity within the context of Imami jurisprudence during the period under study.
Understanding and Incorporating the Contradictions around the Book
Authors: Johnson Miriam 
Published: December 2021

Abstract
This article sets out to critically examine how the idea of what a book can be is changing in relation to the growth of digitally social communities and the writers and readers who congregate in these spaces, and to identify how this connectivity is altering the balance of power between the traditional industry and those who choose to write and share their work in a global village. By offering a succinct consideration of the role of social media, citizen authors, communities, gender, and genre, it can potentially help publishers determine if they need to alter the way they provide access to the industry, conventionally through the hierarchical author–agent–publisher gatekeeping system, in order to take advantage of new authors who are writing in digital communities and building a following there.
Publishers and Others Who Publish
Authors: Ungure Elza 
Published: December 2021

Abstract
The objective of the article is to deconstruct the notion of publisher through the lens of the episteme of professionalism and provide a statistical overview of mainstream and marginal book publishers in Latvia. The statistical overview is based on an alternative, experimental approach, in which publishers are grouped by the legal register they are registered in as juridical persons and the output of each group is analysed. This approach is selected to profile publishers in a context where economic indicators or other means by which to analyse publishers are not available. The results provide an insight into the diversity of those who publish books in Latvia as well as give an overview of the characteristics and patterns of their publishing practices.
Writing Africa, Righting America: An Experience of Otherness in J. P. Clark’s America, Their America
Authors: Ayodeji Adewuyi Aremu 
Published: December 2021

Abstract
In this article, I examine one of the finest first-generation Nigerian writers, John Pepper Clark-Bekederemo, who passed away on 13 October 2020, and who has been categorised as a Eurocentric writer. By critiquing his America, Their America, this work investigates the authenticity of this perception of J. P. Clark as a Eurocentric Nigerian writer. By analysing his autobiography vis-à-vis the notion of the Self and the Other, a theoretical concern in contemporary travel writing, the researcher establishes that every culture has its positive and negative aspects. It must not feel too proud to change as time and situation demand. It is clear that Clark vehemently rejects the US claim of the sophistication and superiority of their culture over African culture. The paper concludes that contemporary travel writing should be a rightful site for negotiating cultural compromises between the Self and the Other, since the gap may be difficult to close altogether.