bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA–MONO/GOG-3020/ENGOT-ov45)
Authors: Monk Bradley J. , Parkinson Christine , Lim Myong Cheol , O'Malley David M. , Oaknin Ana , Wilson Michelle K. , Coleman Robert L. , Lorusso Domenica , Bessette Paul , Ghamande Sharad , Christopoulou Athina , Provencher Diane , Prendergast Emily , Demirkiran Fuat , Mikheeva Olga , Yeku Oladapo , Chudecka-Glaz Anita , Schenker Michael , Littell Ramey D. , Safra Tamar , Chou Hung-Hsueh , Morgan Mark A. , Drochýtek Vít , Barlin Joyce N. , Van Gorp Toon , Ueland Fred , Lindahl Gabriel , Anderson Charles , Collins Dearbhaile C. , Moore Kathleen , Marme Frederik , Westin Shannon N. , McNeish Iain A. , Shih Danny , Lin Kevin K. , Goble Sandra , Hume Stephanie , Fujiwara Keiichi , Kristeleit Rebecca S. 
Published: June 2022

PURPOSE ATHENA (ClinicalTrials.gov identifier: NCT03522246 ) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or BRCA2 (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA–MONO comparison of rucaparib versus placebo. METHODS Patients with stage III-IV high-grade ovarian cancer undergoing surgical cytoreduction (R0/complete resection permitted) and responding to first-line platinum-doublet chemotherapy were randomly assigned 4:1 to oral rucaparib 600 mg twice a day or placebo. Stratification factors were HRD test status, residual disease after chemotherapy, and timing of surgery. The primary end point of investigator-assessed progression-free survival was assessed in a step-down procedure, first in the HRD population (BRCA-mutant or BRCA wild-type/loss of heterozygosity high tumor), and then in the intent-to-treat population. RESULTS As of March 23, 2022 (data cutoff), 427 and 111 patients were randomly assigned to rucaparib or placebo, respectively (HRD population: 185 v 49). Median progression-free survival (95% CI) was 28.7 months (23.0 to not reached) with rucaparib versus 11.3 months (9.1 to 22.1) with placebo in the HRD population (log-rank P = .0004; hazard ratio [HR], 0.47; 95% CI, 0.31 to 0.72); 20.2 months (15.2 to 24.7) versus 9.2 months (8.3 to 12.2) in the intent-to-treat population (log-rank P < .0001; HR, 0.52; 95% CI, 0.40 to 0.68); and 12.1 months (11.1 to 17.7) versus 9.1 months (4.0 to 12.2) in the HRD-negative population (HR, 0.65; 95% CI, 0.45 to 0.95). The most common grade ≥ 3 treatment-emergent adverse events were anemia (rucaparib, 28.7% v placebo, 0%) and neutropenia (14.6% v 0.9%). CONCLUSION Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD.
Financial Toxicity, Symptom Burden, Illness Perceptions, and Communication Confidence in Cancer Clinical Trial Participants
Authors: Perni Subha , Azoba Chukwuma , Gorton Emily , Park Elyse R. , Chabner Bruce A. , Moy Beverly , Nipp Ryan D. 
Published: June 2022

PURPOSE: Cancer clinical trial (CCT) participants are at risk for experiencing adverse associations from financial toxicity, but these remain understudied. METHODS: From July 2015 to July 2017, we prospectively enrolled CCT participants referred for financial assistance and a group of patients matched by age, sex, cancer type, trial, and trial phase. We assessed financial burden of cancer care, cost concerns about CCTs, physical (Edmonton Symptom Assessment Scale [ESAS]) and psychologic (Patient Health Questionnaire-4 [PHQ-4]) symptoms, illness perceptions (Brief Illness Perception Questionnaire), and communication confidence (Perceived Efficacy in Patient-Physician Interactions). Adjusting for age, sex, race, performance status, marital status, income, insurance, and disease status, we examined associations of financial burden and cost concerns with patients' symptoms, illness perceptions, and communication confidence. RESULTS: Of 198 patients, 112 (56.6%) reported financial burden and 82 (41.4%) reported cost concerns. Higher ESAS-total (odds ratio [OR] = 1.03; 95% CI, 1.01 to 1.06; P = .001), PHQ-4 depression (OR = 1.58; 95% CI, 1.20 to 2.08; P < .001), PHQ-4 anxiety (OR = 1.26; 95% CI, 1.02 to 1.55; P = .025), and more negative illness perceptions (OR = 1.04; 95% CI, 1.00 to 1.07; P = .029) were associated with financial burden, but not communication confidence (OR = 0.98; 95% CI, 0.02 to 1.05; P = .587). Higher ESAS-total (OR = 1.03; 95% CI, 1.01 to 1.05; P = .004), PHQ-4 depression (OR = 1.36; 95% CI, 1.08 to 1.71; P = .03), PHQ-4 anxiety (OR = 1.26; 95% CI, 1.03 to 1.53; P = .018), more negative illness perceptions (OR = 1.06; 95% CI, 1.02 to 1.10; P = .001), and decreased communication confidence (OR = 0.93; 95% CI, 0.86 to 1.00; P = .029) were associated with cost concerns. CONCLUSION: In this study of CCT participants, greater symptom burden, more negative illness perceptions, and lower communication confidence were associated with financial toxicity, underscoring the importance of addressing these issues when seeking to alleviate adverse associations of financial toxicity.
Longitudinal Shifts of Solid Tumor and Liquid Biopsy Sequencing Concordance in Metastatic Breast Cancer
Authors: Liu Minetta C. , MacKay Matthew , Kase Matthew , Piwowarczyk Aneta , Lo Christine , Schaeffer Jeff , Finkle Justin D. , Mason Christopher E. , Beaubier Nike , Blackwell Kimberly L. , Park Ben Ho 
Published: June 2022

PURPOSETissue-based next-generation sequencing (NGS) in metastatic breast cancer (mBC) is limited by the inability to noninvasively track tumor evolution. Cell-free DNA (cfDNA) NGS has made sequential testing feasible; however, the relationship between cfDNA and tissue-based testing in mBC is not well understood. Here, we evaluate concordance between tissue and cfDNA NGS relative to cfDNA sampling frequency in a large, clinically annotated mBC data set.METHODSTempus LENS was used to analyze deidentified records of mBC cases with Tempus xT (tissue) and xF (cfDNA) sequencing results. Then, various metrics of concordance were assessed within overlapping probe regions of the tissue and cfDNA assays (104 genes), focusing on pathogenic variants. Variant allele frequencies of discordant and concordant pathogenic variants were also compared. Analyses were stratified by mBC subtype and time between tests.RESULTSRecords from 300 paired tissue and liquid biopsies were analyzed. Median time between tissue and blood collection was 78.5 days (standard deviation = 642.99). The median number of pathogenic variants/patient was one for cfDNA and two for tissue. Across the cohort, 77.8% of pathogenic tissue variants were found in cfDNA and 75.7% of pathogenic cfDNA variants were found in tissue when tests were ≤ 7 days apart, which decreased to 50.3% and 51.8%, respectively, for > 365 days. Furthermore, the median patient-level variant concordance was 67% when tests were ≤7 days apart and 30%-37% when > 30 days. The median variant allele frequencies of discordant variants were generally lower than those of concordant variants within the same time frame.CONCLUSIONWe observed high concordances between tissue and cfDNA results that generally decreased with longer durations between tests. Thus, cfDNA NGS reliably measures tissue genomics and is likely beneficial for longitudinal monitoring of molecular changes in mBC.
Intralymphatic GAD-Alum (Diamyd®) Improves Glycemic Control in Type 1 Diabetes With HLA DR3-DQ2
Authors: Nowak Christoph , Lind Marcus , Sumnik Zdenek , Pelikanova Terezie , Nattero-Chavez Lía , Lundberg Elena , Rica Itxaso , Martínez-Brocca Maria A , Ruiz de Adana MariSol , Wahlberg Jeanette , Hanas Ragnar , Hernandez Cristina , Clemente-León Maria , Gómez-Gila Ana , Ferrer Lozano Marta , Sas Theo , Pruhova Stepanka , Dietrich Fabricia , Puente-Marin Sara , Hannelius Ulf , Casas Rosaura , Ludvigsson Johnny 
Published: June 2022

Abstract

Aims
Residual beta cell function in type 1 diabetes (T1D) is associated with lower risk of complications. Autoantigen therapy with GAD-alum (Diamyd) given in 3 intralymphatic injections with oral vitamin D has shown promising results in persons with T1D carrying the human leukocyte antigen (HLA) DR3-DQ2 haplotype in the phase 2b trial DIAGNODE-2. We aimed to explore the efficacy of intralymphatic GAD-alum on blood glucose recorded by continuous glucose monitoring (CGM).

Methods
DIAGNODE-2 (NCT03345004) was a multicenter, randomized, placebo-controlled, double-blind trial of 109 recent-onset T1D patients aged 12 to 24 years with GAD65 antibodies and fasting C-peptide &gt; 0.12 nmol/L, which randomized patients to 3 intralymphatic injections of 4 μg GAD-alum and oral vitamin D, or placebo. We report results for exploratory endpoints assessed by 14-day CGM at months 0, 6, and 15. Treatment arms were compared by mixed-effects models for repeated measures adjusting for baseline values.

Results
We included 98 patients with CGM recordings of sufficient quality (DR3-DQ2-positive patients: 27 GAD-alum-treated and 15 placebo-treated). In DR3-DQ2-positive patients, percent of time in range (TIR, 3.9-10 mmol/L) declined less between baseline and month 15 in GAD-alum-treated compared with placebo-treated patients (-5.1% and -16.7%, respectively; P = 0.0075), with reduced time &gt; 13.9 mmol/L (P = 0.0036), and significant benefits on the glucose management indicator (P = 0.0025). No differences were detected for hypoglycemia. GAD-alum compared to placebo lowered the increase in glycemic variability (standard deviation) observed in both groups (P = 0.0219). Change in C-peptide was correlated with the change in TIR.

Conclusions
Intralymphatic GAD-alum improves glycemic control in recently diagnosed T1D patients carrying HLA DR3-DQ2.
Generation of a homozygous mutant drug transporter (ABCB1) knockout line in the sea urchinLytechinus pictus
Authors: Vyas Himanshu , Schrankel Catherine S. , Espinoza Jose A. , Mitchell Kasey L. , Nesbit Katherine T. , Jackson Elliot , Chang Nathan , Lee Yoon , Warner Jacob , Reitzel Adam , Lyons Deirdre C. , Hamdoun Amro 
Published: June 2022

ABSTRACTSea urchins are premier model organisms for the study of early development. However, the lengthy generation times of commonly used species have precluded application of stable genetic approaches. Here, we use the painted sea urchin Lytechinus pictus to address this limitation and to generate a homozygous mutant sea urchin line. L. pictus has one of the shortest generation times of any currently used sea urchin. We leveraged this advantage to generate a knockout mutant of the sea urchin homolog of the drug transporter ABCB1, a major player in xenobiotic disposition for all animals. Using CRISPR/Cas9, we generated large fragment deletions of ABCB1 and used these readily detected deletions to rapidly genotype and breed mutant animals to homozygosity in the F2 generation. The knockout larvae are produced according to expected Mendelian distribution, exhibit reduced xenobiotic efflux activity and can be grown to maturity. This study represents a major step towards more sophisticated genetic manipulation of the sea urchin and the establishment of reproducible sea urchin animal resources.
Humanized yeast to model human biology, disease and evolution
Authors: Kachroo Aashiq H. , Vandeloo Michelle , Greco Brittany M. , Abdullah Mudabir 
Published: June 2022

ABSTRACT
For decades, budding yeast, a single-cellular eukaryote, has provided remarkable insights into human biology. Yeast and humans share several thousand genes despite morphological and cellular differences and over a billion years of separate evolution. These genes encode critical cellular processes, the failure of which in humans results in disease. Although recent developments in genome engineering of mammalian cells permit genetic assays in human cell lines, there is still a need to develop biological reagents to study human disease variants in a high-throughput manner. Many protein-coding human genes can successfully substitute for their yeast equivalents and sustain yeast growth, thus opening up doors for developing direct assays of human gene function in a tractable system referred to as ‘humanized yeast’. Humanized yeast permits the discovery of new human biology by measuring human protein activity in a simplified organismal context. This Review summarizes recent developments showing how humanized yeast can directly assay human gene function and explore variant effects at scale. Thus, by extending the ‘awesome power of yeast genetics’ to study human biology, humanizing yeast reinforces the high relevance of evolutionarily distant model organisms to explore human gene evolution, function and disease.
How inclusive are cell lines in preclinical engineered cancer models?
Authors: Raghavan Shreya 
Published: June 2022

ABSTRACT
Diverse factors contribute to significant and dire disparities in cancer risk and treatment outcomes. To address this, there was a call for inclusion of sex as a biological variable, which resulted in more instances of careful inclusion of sex in preclinical studies of cancer. Another variable in cancer treatment is genetic ancestry. Although this is considered explicitly in clinical research, it is considerably neglected in preclinical studies. Preclinical research can use several 3D in vitro model systems, such as spheroids/organoids, xenografts, or other bioengineered systems that combine biomaterials and cellular material. Ultimately, the cellular base for all of these in vitro model systems is derived from human cell lines or patient samples, to investigate mechanisms of cancer and screen novel therapeutics, all of which aim to maximize successful outcomes in clinical trials. This in itself offers an opportunity to potentiate effective treatments for many groups of people, when diverse variables like genetic ancestry are consciously included into study design. This Perspective highlights the need for conscious inclusion of genetic ancestry in preclinical cancer tissue engineering, especially when it pertains to determining therapeutic outcomes.
Analysis of monocyte cell tractions in 2.5D reveals mesoscale mechanics of podosomes during substrate-indenting cell protrusion
Authors: Schürmann Hendrik , Abbasi Fatemeh , Russo Antonella , Hofemeier Arne D. , Brandt Matthias , Roth Johannes , Vogl Thomas , Betz Timo 
Published: June 2022

ABSTRACT
Podosomes are mechanosensitive protrusive actin structures that are prominent in myeloid cells, and they have been linked to vascular extravasation. Recent studies have suggested that podosomes are hierarchically organized and have coordinated dynamics on the cell scale, which implies that the local force generation by single podosomes can be different from their global combined action. Complementary to previous studies focusing on individual podosomes, here we investigated the cell-wide force generation of podosome-bearing ER-Hoxb8 monocytes. We found that the occurrence of focal tractions accompanied by a cell-wide substrate indentation cannot be explained by summing the forces of single podosomes. Instead, our findings suggest that superimposed contraction on the cell scale gives rise to a buckling mechanism that can explain the measured cell-scale indentation. Specifically, the actomyosin network contraction causes peripheral in-plane substrate tractions, while the accumulated internal stress results in out-of-plane deformation in the central cell region via a buckling instability, producing the cell-scale indentation. Hence, we propose that contraction of the actomyosin network, which connects the podosomes, leads to a substrate indentation that acts in addition to the protrusion forces of individual podosomes.
This article has an associated First Person interview with the first author of the paper.
Fluorescence exclusion – a rapid, accurate and powerful method for measuring yeast cell volume
Authors: García-Ruano Daniel , Venkova Larisa , Jain Akanksha , Ryan Joseph C. , Radhakrishnan Balasubramaniam Vasanthakrishnan , Piel Matthieu , Coudreuse Damien 
Published: June 2022

ABSTRACT
Cells exist in an astonishing range of volumes across and within species. However, our understanding of cell size control remains limited, owing in large part to the challenges associated with accurate determination of cell volume. Much of our comprehension of size regulation derives from yeast models, but even for these morphologically stereotypical cells, assessment of cell volume has mostly relied on proxies and extrapolations from two-dimensional measurements. Recently, the fluorescence exclusion method (FXm) was developed to evaluate the size of mammalian cells, but whether it could be applied to smaller cells remained unknown. Using specifically designed microfluidic chips and an improved data analysis pipeline, we show here that FXm reliably detects subtle differences in the volume of fission yeast cells, even for those with altered shapes. Moreover, it allows for the monitoring of dynamic volume changes at the single-cell level with high time resolution. Collectively, our work highlights how the coupling of FXm with yeast genetics will bring new insights into the complex biology of cell growth.
Association of Cardiovascular Risk Markers and Fitness with Task-Related Neural Activity during Animacy Perception
Authors: ISHIHARA TORU , MIYAZAKI ATSUSHI , TANAKA HIROKI , MATSUDA TETSUYA 
Published: June 2022

ABSTRACT

Purpose
Numerous studies have demonstrated the association between cardiovascular risk markers and fitness, and broad aspects of cognition; however, the possible association of cardiovascular risk markers and fitness with social cognition, which plays a significant role in the development and maintenance of social relationships, has largely been ignored. Herein, we investigated the relationship of cardiovascular risk markers and fitness with task-related neural activity during animacy perception.

Methods
We analyzed data from the Human Connectome Project derived from 1027 adults age 22–37 yr. Canonical correlation analysis (CCA) was conducted to evaluate the association between participants’ body mass index, systolic and diastolic blood pressure, submaximal endurance, gait speed, hand dexterity, and muscular strength with task-related neural activity during animacy perception.

Results
We observed a single significant CCA mode. Body mass index and blood pressure demonstrated negative cross-loadings with task-related neural activity in the temporoparietal, superior and anterior temporal, posterior cingulate, and inferior frontal regions, whereas submaximal endurance, hand dexterity, and muscular strength demonstrated positive cross-loadings. The observed CCA variates did not seem highly heritable, as the absolute differences in CCA variates in monozygotic twins, dizygotic twins, and nontwin siblings were not statistically different. Furthermore, the cardiovascular risk markers and fitness CCA variates were positively associated with animacy perception and emotion recognition accuracy, which was mediated by the task-related neural activity.

Conclusions
The present findings can provide new insights into the role of markers for cardiovascular health and fitness, specifically their association with social cognition and the underlying neural basis. The intervention for cardiovascular risk and fitness could be a potentially cost-effective method of targeting social cognition.
The effect of the challenge with Newcastle disease virus on the gastrointestinal bacterial population in Japanese quail (Coturnix japonica)
Authors: Talazadeh Forough 
Published: June 2022

Newcastle disease (ND), caused by virulent strains of Newcastle disease virus (NDV), is a devastating disease of poultry worldwide. The effect of a challenge with Newcastle disease virus on bacterial population in quail is poorly documented, so for this purpose, a total of 100 day-old Japanese quail were purchased and divided into 2 equal groups randomly. Each group was divided into 2 subgroups of 25 quails. The birds in group A challenged with a velogenic chicken isolate of Newcastle disease virus. The birds in group B did not challenge with Newcastle disease virus as the control group. For the determination of lactobacillus counts in the intestine and crop of Japanese quail, at the end of the period, 10 birds of each subgroup (20 birds of each treatment) were chosen randomly. One gram of the crop and ileocecal content were taken and cultured on MRS for determination of lactobacillus counts. The colony-forming units of Escherichia coli in digesta of ileocecal on Mac Conkey agar were investigated. Also, crop and ileocecal content of dead birds were taken and cultured on MRS and Mac Conkey agar. The results of this study showed that challenge with a velogenic chicken isolate of Newcastle disease virus could increase colony-forming units of Escherichia coli in group A compared to the control group. Also, it reduced lactobacillus counts of intestine and crop compared to the control group. So it concluded that velogenic chicken isolate of Newcastle disease virus influences microflora of intestine and crop of Japanese quail.
Prevalence of oral manifestations in patients with lupus erythematosus in a sample of the Egyptian population: a hospital based cross-sectional study
Authors: Saeed Hager Moustafa , Mohammad Amr Eman , Rezk Lotfy Rezk Alshaimaa , Abd Elmoneim Wesam 
Published: June 2022

Background: Several systemic diseases manifest themselves in the oral cavity. Dentists who are unaware of these lesions will possibly miss them. This cross-sectional study aimed to assess the prevalence of oral manifestations in patients with LE in a sample of the Egyptian population. Methods: The present cross-sectional study was performed on 189 patients attending the Internal Medicine Department, Rheumatology Clinic in EL Qasr El Ainy Hospital, Cairo University. Every patient was examined clinically after completing a questionnaire. Patients’ medical records were evaluated. The oral manifestations were assessed according to the WHO guide to physical examination of the oral cavity and classified according to their morphologic aspects and localization. Results: Out of 189 patients, there were 182 females (96.3%) and seven males (3.7%). The prevalence of oral lesions in SLE patients was 55.6%. The most affected site was the tongue 25.7%. The most common clinical aspect was patches, 53%. About 77.1% of the lesions were asymptomatic. Conclusions: The present study emphasizes the importance of early diagnosis of oral lesions to recognize patients with SLE as the WHO considers oral manifestations of SLE a widespread state. Also, the implementation of oral hygiene measures to improve patients’ nutritional state and health-related quality of life is recommended.