bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Benefit of Metronomic Chemotherapy Among Triple-Negative Breast Cancer Subtypes Treated in the IBCSG Trial 22–00
Authors: Joaquin Garcia Andrea , Rediti Mattia , Venet David , Majjaj Samira , Kammler Roswitha , Munzone Elisabetta , Gianni Lorenzo , Thürlimann Beat , Laáng István , Colleoni Marco , Loi Sherene , Viale Giuseppe , Regan Meredith M. , Buisseret Laurence , Rothé Françoise , Sotiriou Christos 
Published: September 2023

Abstract

Purpose:
To explore whether specific triple-negative breast cancer (TNBC) molecular subtypes are predictive for a benefit from maintenance low-dose cyclophosphamide and methotrexate (CM) in the adjuvant IBCSG 22–00 phase III clinical trial.

Experimental Design:
RNA sequencing was performed on a selection of 347 TNBC formalin-fixed paraffin-embedded (FFPE) tumor samples following a case–cohort-like sampling. TNBC subtypes were computed on gene expression data. The association between TNBC subtypes and treatment outcome was assessed using a Cox proportional-hazards interaction test.

Results:
Immunomodulatory (IM) and basal-like/immune activated (BLIA) molecular subtypes showed a significant survival benefit when treated with low-dose CM [disease-free survival (DFS): HR, 0.5; 95% confidence interval (CI), 0.28–0.89; Pinteraction = 0.018 and HR, 0.49; 95% CI, 0.27–0.9; Pinteraction = 0.021]. Moreover, a high expression of regulatory T-cell immune signature was associated with a better prognosis in the CM arm, in line with a potential immunomodulating role of cyclophosphamide. In contrast, a worse outcome was observed in tumors with a mesenchymal (M) subtype treated with low-dose CM (DFS: HR, 1.9; 95% CI, 1.2–3; Pinteraction = 0.0044).

Conclusions:
Our results show a differential benefit of low-dose CM therapy across different TNBC subtypes. Low-dose CM therapy could be considered as a potential strategy for TNBC tumors with IM subtype in the early-disease setting.
Near-Infrared Spectral Tomography for Predicting Residual Cancer Burden during Early-Stage Neoadjuvant Chemotherapy for Breast Cancer
Authors: Cao Xu , Muller Kristen E. , Chamberlin Mary D. , Gui Jiang , Kaufman Peter A. , Schwartz Gary N. , diFlorio-Alexander Roberta M. , Pogue Brian W. , Paulsen Keith D. , Jiang Shudong 
Published: September 2023

Abstract

Purpose:
The aim of this study is to investigate whether near-infrared spectral tomography (NIRST) might serve as a reliable prognostic tool to predict residual cancer burden (RCB) in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC) based upon early treatment response measurements.

Experimental Design:
A total of thirty-five patients with breast cancer receiving NAC were included in this study. NIRST imaging was performed at multiple time points, including: before treatment, at end of the first cycle, at the mid-point, and post-NAC treatments. From reconstructed NIRST images, average values of total hemoglobin (HbT) were obtained for both the tumor region and contralateral breast at each time point. RCB scores/classes were assessed by a pathologist using histologic slides of the surgical specimen obtained after completing NAC. Logistic regression of the normalized early percentage change of HbT in the tumor region (ΔHbT%) was used to predict RCB and determine its significance as an indicator for differentiating cases within each RCB class.

Results:
The ΔHbT% at the end of the first cycle, as compared with pretreatment levels, showed excellent prognostic capability in differentiating RCB-0 from RCB-I/II/III or RCB-II from RCB-0/I/III (P &lt; 0.001). Corresponding area under the curve (AUC) values for these comparisons were 0.97 and 0.94, and accuracy values were 0.90 and 0.83, respectively.

Conclusions:
NIRST holds promise as a potential clinical tool that can be seamlessly integrated into existing clinical workflow within the infusion suite. By providing early assessment of RCB, NIRST has potential to improve breast cancer patient management strategies.
Deuterium Magnetic Resonance Imaging Using Deuterated Water-Induced 2H-Tissue Labeling Allows Monitoring Cancer Treatment at Clinical Field Strength
Authors: Asano Hirofumi , Elhelaly Abdelazim Elsayed , Hyodo Fuminori , Iwasaki Ryota , Noda Yoshifumi , Kato Hiroki , Ichihashi Koki , Tomita Hiroyuki , Murata Masaharu , Mori Takashi , Matsuo Masayuki 
Published: September 2023

Abstract

Purpose:
An accurate and noninvasive assessment of tumor response following treatment other than traditional anatomical imaging techniques is essential. Deuterium magnetic resonance spectroscopic (MRS) imaging has been demonstrated as an alternative for cancer metabolic imaging by high-field MRI using deuterium-labeled molecules. The study aim was to use 2H tissue labeling and deuterium MRI at clinical field strength for tumor visualization and assessment of three anticancer therapies in pancreatic cancer model mice.

Experimental Design:
MIA PaCa-2 pancreatic carcinoma and C26 colorectal carcinoma models of BALB/c-nu mice was prepared, and repeated deuterium MRI was performed during the first 10 days of free drinking of 30% D2O to track 2H distribution in tissues. 2H accumulation in the tumor after irradiation, bevacizumab administration, or gemcitabine administration was also measured in MIA PaCa-2–bearing mice. Confirmatory proton MRI, ex vivo metabolic hyperpolarization 13C-MRS, and histopathology were performed.

Results:
The mouse's whole-body distribution of 2H was visible 1 day after drinking, and the signal intensity increased daily. Although the tumor size did not change 1 and 3 days after irradiation, the amount of 2H decreased significantly. The 2H image intensity of the tumor also significantly decreased after the administration of bevacizumab or gemcitabine. Metabolic hyperpolarization 13C-MRS, proton MRI, and 2H-NMR spectroscopy confirmed the efficacy of the anticancer treatments.

Conclusions:
Deuterium MRI at 1.5T proved feasible to track 2H distribution throughout mouse tissues during D2O administration and revealed a higher 2H accumulation in the tumor xenografts. This research demonstrated a promising successful method for preliminary assessment of radiotherapy and chemotherapy of cancer.
Personalized Medicine's Coming of Age: One Drug, One Patient
Authors: Qazilbash Muzaffar H. , Kwak Larry W. 
Published: September 2023

SummaryA dendritic cell/myeloma fusion vaccine, given with lenalidomide and GM-CSF, did not result in a statistically significant increase in CR rates at 1 year posttransplant but was associated with a significant increase in circulating multiple myeloma–reactive lymphocytes indicative of tumor-specific immunity.See related article by Chung et al., p. 4784
Aging Is Associated With Organ-Specific Alterations in the Level and Expression Pattern of von Willebrand Factor
Authors: Alavi Parnian , Yousef Abdualla Radya , Brown Douglas , Mojiri Anahita , Nagendran Jayan , Lewis John , Bourque Stephane L. , Jahroudi Nadia 
Published: September 2023

BACKGROUND:
VWF (von Willebrand factor) is an endothelial-specific procoagulant protein with a major role in thrombosis. Aging is associated with increased circulating levels of VWF, which presents a risk factor for thrombus formation.

METHODS:
Circulating plasma, cellular protein, and mRNA levels of VWF were determined and compared in young and aged mice. Major organs were subjected to immunofluorescence analyses to determine the vascular pattern of VWF expression and the presence of platelet aggregates. An in vitro model of aging, using extended culture time of endothelial cells, was used to explore the mechanism of age-associated increased VWF levels.

RESULTS:
Increased circulating plasma levels of VWF with elevated levels of larger multimers, indicative of VWF functional activity, were observed in aged mice. VWF mRNA and cellular protein levels were significantly increased in the brains, lungs, and livers but not in the kidneys and hearts of aged mice. Higher proportion of small vessels in brains, lungs, and livers of aged mice exhibited VWF expression compared with young, and this was concomitant with increased platelet aggregate formation. Prolonged culture of endothelial cells resulted in increased cell senescence that correlated with increased VWF expression; VWF expression was specifically detected in senescent cultured endothelial cells and abolished in response to p53 knockdown. A significantly higher proportion of VWF expressing endothelial cells in vivo exhibited senescence markers SA-β-Gal (senescence-associated β-galactosidase) and p53 in aged mouse brains compared with that of the young.

CONCLUSIONS:
Aging elicits a heterogenic response in endothelial cells with regard to VWF expression, leading to organ-specific increase in VWF levels and alterations in vascular tree pattern of expression. This is concomitant with increased platelet aggregate formation. The age-associated increase in VWF expression may be modulated through the process of cell senescence, and p53 transcription factor contributes to its regulation.
Effect of Individualized Versus Standardized Blood Pressure Management During Endovascular Stroke Treatment on Clinical Outcome: A Randomized Clinical Trial
Authors: Chen Min , Meis Jan , Potreck Arne , Sauer Lukas D. , Kieser Meinhard , Bendszus Martin , Wick Wolfgang , Ringleb Peter A. , Möhlenbruch Markus A. , Schönenberger Silvia 
Published: September 2023

BACKGROUND:
Optimal blood pressure (BP) management during endovascular stroke treatment is not well established. We studied whether an individualized approach for managing BP during endovascular stroke treatment gives a better clinical outcome than an approach with standardized systolic BP targets.

METHODS:
The INDIVIDUATE study (Individualized Blood Pressure Management During Endovascular Treatment of Acute Ischemic Stroke Under Procedural Sedation) is a randomized clinical trial with a prospective randomized open blinded end point (PROBE) design. Patients were recruited between October 1, 2020 and July 7, 2022 at a single center at a tertiary care university hospital. Patients were eligible, when they were suffering from acute ischemic stroke of the anterior circulation with occlusions of the internal carotid artery and middle cerebral artery and a National Institutes of Health Stroke Scale score of ≥8 receiving endovascular stroke treatment in procedural sedation. The intervention consists of an individualized BP management strategy, where preinterventional baseline systolic BP (SBP) values are used as intraprocedural BP targets. As a control, the standard treatment aims to maintain the intraprocedural SBP between 140 and 180 mm Hg. The main prespecified outcome is the proportion of favorable functional outcomes 90 days after stroke, defined as a modified Rankin Scale score of 0 to 2.

RESULTS:

Two hundred fifty patients were enrolled and included in the analysis, mean (SD) age was 77 (12) years, 142 (57%) patients were women, and mean (SD) National Institutes of Health Stroke Scale score on admission was 17 (5.2). In all, 123 (49%) patients were treated with individualized and 127 (51%) with standard BP management. Mean (SD) intraprocedural SBP was similar in the individualized versus standard BP management group (157 [19] versus 154 [18] mm Hg;
P
=0.16). The rate of favorable functional outcome after 3 months was not significantly different between the individualized versus the standard BP management group (25% versus 24%; adjusted odds ratio, 0.81 [95% CI, 0.41–1.61];
P
=0.56).

CONCLUSIONS:
Among patients treated with endovascular stroke treatment due to an acute ischemic stroke of the anterior circulation, no significant difference was seen between the individualized BP management strategy, where intraprocedural SBP was targeted to baseline values, and the standardized regimen of targeting SBP between 140 and 180 mm Hg.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04578288.
Roman Civil Jurisdiction, Nezikin, and Rabbinic Professionalization in the Second Century: A Response to Yair Furstenberg
Authors: Dohrmann Natalie B. 
Published: September 2023

Abstract
Yair Furstenberg’s article in this issue, “The Rabbinic Movement from Pharisees to Provincial Jurists” (DOI: 10.1163/15700631-bja10070), ties what he sees as the changing boundaries of torah law at the hands of the Tannaim to changes in the legal landscape of the eastern provinces of the Roman empire in the second century. This brief essay is a response to the article, musing on its implications and raising questions for future research.
Higher pelvic incidence values are a risk factor for trans-iliac trans-sacral screw malposition in sacroiliac complex fracture treatment
Authors: Luo An-Jhih , Wang Angela , Lai Chih-Yang , Yu Yi-Hsun , Hsu Yung-Heng , Chou Ying-Chao , Chen I.-Jung 
Published: September 2023

Abstract
Background
Percutaneous iliosacral (IS) screw fixation and trans-iliac trans-sacral (TITS) screw fixation are clinically effective treatments of posterior pelvic sacroiliac fractures. In order to accurately assess the sacrum position relative to the pelvis, pelvic incidence (PI) is a commonly utilized radiographic parameter in sagittal view. This study aimed to investigate and compare the surgical outcomes and radiographic parameters of IS or TITS screw fixations for the treatment of posterior sacroiliac complex fractures with different PI values.

Materials and methods
The data on patients with posterior pelvic sacroiliac fractures who underwent percutaneous IS or TITS screw fixations, or both, at a single level I trauma center between January 2017 and June 2020 were reviewed. We documented the patient characteristics and fracture types, reviewed surgical records, and measured the radiographic parameters via plain films and multi-planar computed tomography (mpCT) images. Radiographic variations in PI, sacral slope, pelvic tilt, sacral dysmorphism, pelvic ring reduction quality, screw deviation angles, screw malposition grading, and iatrogenic complications were documented and analyzed.

Results
A total of 85 patients were included, and 65 IS and 70 TITS screws were accounted for. Patients were divided into two groups according to screw fixation method and further divided into four sub-groups based on baseline PI values. The PI cutoff values were 49.85° and 48.05° in the IS and TITS screw groups, respectively, according to receiver operating characteristic analysis and Youden's J statistic. Smaller PI values were significantly correlated with sacral dysmorphism (p = 0.027 and 0.003 in the IS and TITS screw groups, respectively). Patients with larger PI values were at a significantly increased risk of screw malposition in the TITS screw group (p = 0.049), with no association in the IS screw group. Logistic regression confirmed that a larger PI value was a significant risk factor for screw malposition in the TITS screw group (p = 0.010). The post-operative outcomes improved from poor/fair (at 6 months) to good/average (at 12 months) based on the Postel Merle d'Aubigné and Majeed scores, with no significant differences between subgroups.

Conclusions
Both percutaneous IS and TITS screw fixations are safe and effective treatments for posterior pelvic sacroiliac fractures. Due to the higher risk of screw malposition in patients with larger PI values, it is crucial to identify potential patients at risk when performing TITS screw fixation surgery.

Level of evidence:

Level III.
Systematic review of type 1 diabetes biomarkers reveals regulation in circulating proteins related to complement, lipid metabolism, and immune response
Authors: Sarkar Soumyadeep , Elliott Emily C. , Henry Hayden R. , Ludovico Ivo Díaz , Melchior John T. , Frazer-Abel Ashley , Webb-Robertson Bobbie-Jo , Davidson W. Sean , Holers V. Michael , Rewers Marian J. , Metz Thomas O. , Nakayasu Ernesto S. 
Published: September 2023

Abstract
Background
Type 1 diabetes (T1D) results from an autoimmune attack of the pancreatic β cells that progresses to dysglycemia and symptomatic hyperglycemia. Current biomarkers to track this evolution are limited, with development of islet autoantibodies marking the onset of autoimmunity and metabolic tests used to detect dysglycemia. Therefore, additional biomarkers are needed to better track disease initiation and progression. Multiple clinical studies have used proteomics to identify biomarker candidates. However, most of the studies were limited to the initial candidate identification, which needs to be further validated and have assays developed for clinical use. Here we curate these studies to help prioritize biomarker candidates for validation studies and to obtain a broader view of processes regulated during disease development.

Methods
This systematic review was registered with Open Science Framework (https://doi.org/10.17605/OSF.IO/N8TSA). Using PRISMA guidelines, we conducted a systematic search of proteomics studies of T1D in the PubMed to identify putative protein biomarkers of the disease. Studies that performed mass spectrometry-based untargeted/targeted proteomic analysis of human serum/plasma of control, pre-seroconversion, post-seroconversion, and/or T1D-diagnosed subjects were included. For unbiased screening, 3 reviewers screened all the articles independently using the pre-determined criteria.

Results
A total of 13 studies met our inclusion criteria, resulting in the identification of 266 unique proteins, with 31 (11.6%) being identified across 3 or more studies. The circulating protein biomarkers were found to be enriched in complement, lipid metabolism, and immune response pathways, all of which are found to be dysregulated in different phases of T1D development. We found 2 subsets: 17 proteins (C3, C1R, C8G, C4B, IBP2, IBP3, ITIH1, ITIH2, BTD, APOE, TETN, C1S, C6A3, SAA4, ALS, SEPP1 and PI16) and 3 proteins (C3, CLUS and C4A) have consistent regulation in at least 2 independent studies at post-seroconversion and post-diagnosis compared to controls, respectively, making them strong candidates for clinical assay development.

Conclusions
Biomarkers analyzed in this systematic review highlight alterations in specific biological processes in T1D, including complement, lipid metabolism, and immune response pathways, and may have potential for further use in the clinic as prognostic or diagnostic assays.
An improved transmissibility model to detect transgenerational transmitted environmental effects
Authors: David Ingrid , Ricard Anne 
Published: September 2023

Abstract
Background
Evolutionary studies have reported that non-genetic information can be inherited across generations (epigenetic marks, microbiota, cultural inheritance). Non-genetic information is considered to be a key element to explain the adaptation of wild species to environmental constraints because it lies at the root of the transgenerational transmission of environmental effects. The “transmissibility model” was proposed several years ago to better predict the transmissible potential of each animal by taking these diverse sources of inheritance into account in a global transmissible potential. We propose to improve this model to account for the influence of the environment on the global transmissible potential as well. This extension of the transmissibility model is the “transmissibility model with environment” that considers a covariance between transmissibility samplings of animals sharing the same environment. The null hypothesis of “no transmitted environmental effect” can be tested by comparing the two models using a likelihood ratio test (LRT).

Results
We performed simulations that mimicked an experimental design consisting of two lines of animals with one exposed to a particular environment at a given generation. This enabled us to evaluate the performances of the transmissibility model with environment so as to detect and quantify transgenerational transmitted environmental effects. The power and the realized type I error of the LRT were compared to those of a T-test comparing the phenotype of the two lines, three generations after the environmental exposure for different sets of parameters. The power of the LRT ranged from 45 to 94%, whereas that of the T-test was always lower than 26%. In addition, the realized type I error of the T-test was 15% and that of the LRT was 5%, as expected. Variances, the covariance between transmissibility samplings, and path coefficients of transmission estimated with the transmissibility model with environment were close to their true values for all sets of parameters.

Conclusions
The transmissibility model with environment is effective in modeling vertical transmission of environmental effects.
A bioinformatics screen reveals hox and chromatin remodeling factors at the Drosophila histone locus
Authors: Hodkinson Lauren J. , Smith Connor , Comstra H. Skye , Ajani Bukola A. , Albanese Eric H. , Arsalan Kawsar , Daisson Alvaro Perez , Forrest Katherine B. , Fox Elijah H. , Guerette Matthew R. , Khan Samia , Koenig Madeleine P. , Lam Shivani , Lewandowski Ava S. , Mahoney Lauren J. , Manai Nasserallah , Miglay JonCarlo , Miller Blake A. , Milloway Olivia , Ngo Nhi , Ngo Vu D. , Oey Nicole F. , Punjani Tanya A. , SiMa HaoMin , Zeng Hollis , Schmidt Casey A. , Rieder Leila E. 
Published: September 2023

Abstract
Background
Cells orchestrate histone biogenesis with strict temporal and quantitative control. To efficiently regulate histone biogenesis, the repetitive Drosophila melanogaster replication-dependent histone genes are arrayed and clustered at a single locus. Regulatory factors concentrate in a nuclear body known as the histone locus body (HLB), which forms around the locus. Historically, HLB factors are largely discovered by chance, and few are known to interact directly with DNA. It is therefore unclear how the histone genes are specifically targeted for unique and coordinated regulation.

Results
To expand the list of known HLB factors, we performed a candidate-based screen by mapping 30 publicly available ChIP datasets of 27 unique factors to the Drosophila histone gene array. We identified novel transcription factor candidates, including the Drosophila Hox proteins Ultrabithorax (Ubx), Abdominal-A (Abd-A), and Abdominal-B (Abd-B), suggesting a new pathway for these factors in influencing body plan morphogenesis. Additionally, we identified six other factors that target the histone gene array: JIL-1, hormone-like receptor 78 (Hr78), the long isoform of female sterile homeotic (1) (fs(1)h) as well as the general transcription factors TBP associated factor 1 (TAF-1), Transcription Factor IIB (TFIIB), and Transcription Factor IIF (TFIIF).

Conclusions
Our foundational screen provides several candidates for future studies into factors that may influence histone biogenesis. Further, our study emphasizes the powerful reservoir of publicly available datasets, which can be mined as a primary screening technique.