bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ki67 and breast cancer mortality in women with invasive breast cancer
Authors: Probert Jake , Dodwell David , Broggio John , Charman Jackie , Dowsett Mitch , Kerr Amanda , McGale Paul , Taylor Carolyn , Darby Sarah C , Mannu Gurdeep S 
Published: August 2023

Abstract

Background
The percentage of cells staining positive for Ki67 is sometimes used for decision-making in patients with early invasive breast cancer (IBC). However, there is uncertainty regarding the most appropriate Ki67 cut points and the influence of interlaboratory measurement variability. We examined the relationship between breast cancer mortality and Ki67 both before and after accounting for interlaboratory variability and 8 patient and tumor characteristics.

Methods
A multicenter cohort study of women with early IBC diagnosed during 2009-2016 in more than 20 NHS hospitals in England and followed until December 31, 2020.

Results
Ki67 was strongly prognostic of breast cancer mortality in 8212 women with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative early IBC (Ptrend &lt; .001). This relationship remained strong after adjustment for patient and tumor characteristics (Ptrend &lt; .001). Standardization for interlaboratory variability did little to alter these results. For women with Ki67 scores of 0%-5%, 6%-10%, 11%-19%, and 20%-29% the corresponding 8-year adjusted cumulative breast cancer mortality risks were 3.3% (95% confidence interval [CI] = 2.8% to 4.0%), 3.7% (95% CI = 3.0% to 4.4%), 3.4% (95% CI = 2.8% to 4.1%), and 3.4% (95% CI = 2.8% to 4.1%), whereas for women with Ki67 scores of 30%-39% and 40%-100%, these risks were higher, at 5.1% (95% CI = 4.3% to 6.2%) and 7.7% (95% CI = 6.6% to 9.1) (Ptrend &lt; .001). Similar results were obtained when the adjusted analysis was repeated with omission of pathological information about tumor size and nodal involvement, which would not be available preoperatively for patients being considered for neoadjuvant therapy.

Conclusion
Our findings confirm the prognostic value of Ki67 scores of 30% or more in women with ER-positive, HER2-negative early IBC, irrespective of interlaboratory variability. These results also suggest that Ki67 may be useful to aid decision-making in the neoadjuvant setting.
Exploring temporal and topical dynamics of research on climate/environment–migration nexus: A critical comparative perspective
Authors: İçduygu Ahmet , Gören Hacer 
Published: August 2023

Abstract
Research on climate/environmental change and human migration have undergone significant transformations since the early 1990s. Attention by migration-related journals and environment/climate-oriented journals has been uneven. What is absent is a critical comparative approach to this unevenness and the evolving dynamics of the nexus in a continuum. We conducted a critical comparative analysis of six scholarly journals to fill this gap. Based on multi-stage mixed methods, our findings suggest: (1) scholarly research has disproportionately focused on the impacts of X (climate/environmental change effects) on Y (human migration), vulnerabilities, and agency of moving people and broader social and political processes receiving less attention; (2) Compared with migration-related journals, climate/environment-oriented journals have contributed more to research on the climate/environment–migration nexus, with significant differences in their approach and topical selections; (3) ‘Migration as an adaptation strategy to climate change’ as a theme has shown an unprecedented rise since 2010, with most articles having a skewed emphasis on migration as an individual and unplanned form of adaptation rather than that of planned adaptation; (4) Research on the climate/environment–migration nexus has recently entered the early maturation period, which approximates research into mainstream migration studies. Consequently, we divide the research’s last three decades into three stages: prognostic period (early 1990s to early 2000s), transitionary period (early 2000s to 2010), and growth period (2010-present). We suggest that both journal groups embrace more inclusive and diverse foci on different scales.
Expanding Behavioral and Occupational Health Research in Military Police
Authors: Horan Kristin A , Schlenk Michael A , Collette Tyler L , Channer Bianca C , Sanchez-Cardona Israel , Moore Brian A 
Published: August 2023

ABSTRACT

Introduction
It is important to understand the behavioral and occupational health needs of military police personnel, a high-risk and understudied population.

Materials and Methods
The incidence rates of behavioral and occupational conditions were examined from the years of 2005 to 2021 from the Defense Medical Epidemiology Database. Single-sample chi-square analyses were performed to analyze the differences in the incidence rates across demographic groups relative to population density.

Results
There were moderate-to-large increases in sleep-related disorders and mood or stress-related disorders. There were also patterns of overrepresentation or underrepresentation in diagnoses of various conditions by sex, age group, marital status, race, service branch, and pay grade.

Conclusions
It is important to provide tailored resources and programming to employees in high-stress settings to help prevent or manage behavioral and occupational health conditions and reduce the stigma surrounding the utilization of such resources and programs.
Physical parameters of stellar population in star formation regions of galaxies
Authors: Gusev A S , Sakhibov F , Egorov O V , Kostiuk V S , Shimanovskaya E V 
Published: August 2023

ABSTRACT
We present the results of a study of young unresolved stellar groupings (clusters, OB associations, and their complexes) associated with H ii regions, based on the coupling of spectroscopic, photometric and H α spectrophotometric observations of star formation regions. Along with our own observations, we use a part of the spectroscopic and H α data from the literature and open data bases. The study is based on the catalogue of 1510 star formation regions with ages ∼10–20 Myr in 19 spiral galaxies, compiled by us earlier. We study the morphology of stellar groupings and their relation with the associated H α emission region. Extinctions, gas chemical abundances, and sizes of star formation regions are measured. Using numerical simple stellar population models computed for metallicities fixed from observations to intrinsic colours of the studied star formation regions, we estimated ages and masses of stellar population of 400 young stellar groupings. Different relations between observational and physical parameters of the young stellar population in star formation regions are discussed.
Variables for differential diagnosis of familial Mediterranean fever: Multiple correspondence analysis of a large Japanese cohort
Authors: Kishida Dai , Nakamura Akinori , Yazaki Masahide , Tsuchiya-Suzuki Ayako , Ichikawa Takanori , Shimojima Yasuhiro , Sekijima Yoshiki 
Published: August 2023

ABSTRACT

Objectives
We investigated differential diagnoses that should be noted with familial Mediterranean fever (FMF) and useful variables for differentiation in a large Japanese cohort.

Methods
Patients aged ≥13 years who were clinically suspected of having FMF by Livneh criteria were studied 1 year after MEFV genetic testing. Patients ultimately diagnosed with other diseases were studied, and the association among each disease, patient characteristics, and clinical variables were analysed using multiple correspondence analysis.

Results
In total, 504 patients were included in this study; 34 (6.7%) were diagnosed with a disease other than FMF. The most common diagnosis was Behçet’s disease, followed by periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, inflammatory bowel disease, myelodysplastic syndromes (MDS), and infectious diseases. Although none of the non-FMF patients had exon 10 variants, some responded to colchicine treatment. Multiple correspondence analysis suggested that atypical symptoms such as stomatitis were associated with Behçet’s disease and PFAPA syndrome, whereas characteristic situations such as disease onset ≥40 years were associated with MDS and infectious diseases.

Conclusion
Careful follow-ups and reanalysis of the diagnosis should be performed for patients with atypical findings and no exon 10 variants, even if their symptoms meet the clinical criteria for FMF.
CRI-SPA: a high-throughput method for systematic genetic editing of yeast libraries
Authors: Cachera Paul , Olsson Helén , Coumou Hilde , Jensen Mads L , Sánchez Benjamín J , Strucko Tomas , van den Broek Marcel , Daran Jean-Marc , Jensen Michael K , Sonnenschein Nikolaus , Lisby Michael , Mortensen Uffe H 
Published: August 2023

Abstract
Biological functions are orchestrated by intricate networks of interacting genetic elements. Predicting the interaction landscape remains a challenge for systems biology and new research tools allowing simple and rapid mapping of sequence to function are desirable. Here, we describe CRI-SPA, a method allowing the transfer of chromosomal genetic features from a CRI-SPA Donor strain to arrayed strains in large libraries of Saccharomyces cerevisiae. CRI-SPA is based on mating, CRISPR-Cas9-induced gene conversion, and Selective Ploidy Ablation. CRI-SPA can be massively parallelized with automation and can be executed within a week. We demonstrate the power of CRI-SPA by transferring four genes that enable betaxanthin production into each strain of the yeast knockout collection (≈4800 strains). Using this setup, we show that CRI-SPA is highly efficient and reproducible, and even allows marker-free transfer of genetic features. Moreover, we validate a set of CRI-SPA hits by showing that their phenotypes correlate strongly with the phenotypes of the corresponding mutant strains recreated by reverse genetic engineering. Hence, our results provide a genome-wide overview of the genetic requirements for betaxanthin production. We envision that the simplicity, speed, and reliability offered by CRI-SPA will make it a versatile tool to forward systems-level understanding of biological processes.
STING agonist-boosted mRNA immunization via intelligent design of nanovaccines for enhancing cancer immunotherapy
Authors: Zhou Lei , Yi Wenzhe , Zhang Zehong , Shan Xiaoting , Zhao Zitong , Sun Xiangshi , Wang Jue , Wang Hao , Jiang Hualiang , Zheng Mingyue , Wang Dangge , Li Yaping 
Published: August 2023

ABSTRACT
Messenger RNA (mRNA) vaccine is revolutionizing the methodology of immunization in cancer. However, mRNA immunization is drastically limited by multistage biological barriers including poor lymphatic transport, rapid clearance, catalytic hydrolysis, insufficient cellular entry and endosome entrapment. Herein, we design a mRNA nanovaccine based on intelligent design to overcome these obstacles. Highly efficient nanovaccines are carried out with machine learning techniques from datasets of various nanocarriers, ensuring successful delivery of mRNA antigen and cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) to targets. It activates stimulator of interferon genes (STING), promotes mRNA-encoded antigen presentation and boosts antitumour immunity in vivo, thus inhibiting tumour growth and ensuring long-term survival of tumour-bearing mice. This work provides a feasible and safe strategy to facilitate STING agonist-synergized mRNA immunization, with great translational potential for enhancing cancer immunotherapy.
Overexpression of a Plant-Specific Gγ Protein, AGG3, in the Model Monocot Setaria viridis Confers Tolerance to Heat Stress
Authors: Torres Rodríguez María Daniela , Bhatnagar Nikita , Pandey Sona 
Published: August 2023

Abstract
The vascular plant-specific, cysteine-rich type III Gγ proteins, which are integral components of the heterotrimeric G-protein complex, play crucial roles in regulating a multitude of plant processes, including those related to crop yield and responses to abiotic stresses. The presence of multiple copies of type III Gγ proteins in most plants and a propensity of the presence of specific truncated alleles in many cultivated crops present an ambiguous picture of their roles in modulating specific responses. AGG3 is a canonical type III Gγ protein of Arabidopsis, and its overexpression in additional model crops offers the opportunity to directly evaluate the effects of protein expression levels on plant phenotypes. We have shown that AGG3 overexpression in the monocot model Setaria viridis leads to an increase in seed yield. In this study, we have investigated the response of the S. viridis plants overexpressing AGG3 to heat stress (HS), one of the most important abiotic stresses affecting crops worldwide. We show that a short span of HS at a crucial developmental time point has a significant effect on plant yield in the later stages. We also show that plants with higher levels of AGG3 are more tolerant to HS. This is attributed to an altered regulation of stress-responsive genes and improved modulation of the photosynthetic efficiency during the stress. Overall, our results confirm that AGG3 plays a crucial role in regulating plant responses to unfavorable environmental conditions and may contribute positively to avoiding crop yield losses.
Machine learning a time-local fluctuation theorem for nonequilibrium steady states
Authors: Sanderson Stephen , Petersen Charlotte F , Searles Debra J 
Published: August 2023

Abstract
Fluctuation theorems (FTs) quantify the thermodynamic reversibility of a system, and for deterministic systems they are defined in terms of the dissipation function. However, in a nonequilibrium steady state of deterministic dynamics, the phase space distribution is unknown, making the dissipation function difficult to evaluate without extra information. As such, steady state FTs for deterministic systems to date have required either that the trajectory segment of interest is relatively long, or that information is available about the entire trajectory surrounding that segment. In this work, it is shown that a simple machine learning model trained to predict whether a given steady state trajectory segment is being played forward or backward in time calculates a function which satisfies an FT and relies solely on information within the segment of interest. The FT is satisfied even for very short trajectory segments where the approximate relation derived from theory breaks down, for systems far from equilibrium, and for various nonequilibrium dynamics. It is further demonstrated that any function which is a well-calibrated predictor of time’s arrow must satisfy an FT, and that a local FT can be derived which depends only on local dissipation and its correlations with the surrounding nonlocal dissipation.
Construction of 3D bioprinting of HAP/collagen scaffold in gelation bath for bone tissue engineering
Authors: Guo Chuang , Wu Jiacheng , Zeng Yiming , Li Hong 
Published: August 2023

Abstract
Reconstruction of bone defects remains a clinical challenge, and 3D bioprinting is a fabrication technology to treat it via tissue engineering. Collagen is currently the most popular cell scaffold for tissue engineering; however, a shortage of printability and low mechanical strength limited its application via 3D bioprinting. In the study, aiding with a gelatin support bath, a collagen-based scaffold was fabricated via 3D printing, where hydroxyapatite (HAP) and bone marrow mesenchymal stem cells (BMSCs) were added to mimic the composition of bone. The results showed that the blend of HAP and collagen showed suitable rheological performance for 3D extrusion printing and enhanced the composite scaffold’s strength. The gelatin support bath could effectively support the HAP/collagen scaffold’s dimension with designed patterns at room temperature. BMSCs in/on the scaffold kept living and proliferating, and there was a high alkaline phosphate expression. The printed collagen-based scaffold with biocompatibility, mechanical properties and bioactivity provides a new way for bone tissue engineering via 3D bioprinting.
Nature-inspired nanocarriers for improving drug therapy of atherosclerosis
Authors: Ji Weihong , Zhang Yuanxing , Deng Yuanru , Li Changyong , Kankala Ranjith Kumar , Chen Aizheng 
Published: August 2023

Abstract
Atherosclerosis (AS) has emerged as one of the prevalent arterial vascular diseases characterized by plaque and inflammation, primarily causing disability and mortality globally. Drug therapy remains the main treatment for AS. However, a series of obstacles hinder effective drug delivery. Nature, from natural micro-/nano-structural biological particles like natural cells and extracellular vesicles to the distinctions between the normal and pathological microenvironment, offers compelling solutions for efficient drug delivery. Nature-inspired nanocarriers of synthetic stimulus-responsive materials and natural components, such as lipids, proteins and membrane structures, have emerged as promising candidates for fulfilling drug delivery needs. These nanocarriers offer several advantages, including prolonged blood circulation, targeted plaque delivery, targeted specific cells delivery and controlled drug release at the action site. In this review, we discuss the nature-inspired nanocarriers which leverage the natural properties of cells or the microenvironment to improve atherosclerotic drug therapy. Finally, we provide an overview of the challenges and opportunities of applying these innovative nature-inspired nanocarriers.
Banking Integration and Capital Misallocation: Evidence from China
Authors: Ye Naide , Kong Dongmin 
Published: August 2023

Abstract
Using the staggered intercity but within-province deregulation of local banks in China as exogenous variations, we evaluate the effect of banking integration across geographical segmentation on capital misallocation. Based on an administrative data set comprehensively covering Chinese manufacturing firms, we find that for firms with initially high marginal revenue products of capital (MRPK), the integration increases physical capital by 19.3%, and reduces MRPK by 33.1% relative to low MRPK firms. Our findings are more pronounced for non-state-owned firms and firms with higher exposure to integrated banks. Integration also significantly increases the responsiveness of firms’ investments to deposit shock on other cities within the same province. (JEL G21, G32, D24)
Received October 12, 2022; editorial decision July 11, 2023 by Editor Isil Erel
Transcriptomic network analysis reveals key drivers of response to anti-TNF biologics in patients with rheumatoid arthritis
Authors: Yu Chae-Yeon , Lee Hye-Soon , Joo Young Bin , Cho Soo-Kyung , Choi Chan-Bum , Sung Yoon-Kyoung , Kim Tae-Hwan , Jun Jae-Bum , Yoo Dae Hyun , Bae Sang-Cheol , Kim Kwangwoo , Bang So-Young 
Published: August 2023

Abstract

Objective
Anti-TNF biologics have been widely used to ameliorate disease activity in patients with RA. However, a large fraction of patients show a poor response to these agents. Moreover, no clinically applicable predictive biomarkers have been established. This study aimed to identify response-associated biomarkers using longitudinal transcriptomic data in two independent RA cohorts.

Methods
RNA sequencing data from peripheral blood cell samples of Korean and Caucasian RA cohorts before and after initial treatment with anti-TNF biologics were analysed to assess treatment-induced expression changes that differed between highly reliable excellent responders and null responders. Weighted correlation network, immune cell composition, and key driver analyses were performed to understand response-associated transcriptomic networks and cell types and their correlation with disease activity indices.

Results
In total, 305 response-associated genes showed significantly different treatment-induced expression changes between excellent and null responders. Co-expression network construction and subsequent key driver analysis revealed that 41 response-associated genes played a crucial role as key drivers of transcriptomic alteration in four response-associated networks involved in various immune pathways: type I IFN signalling, myeloid leucocyte activation, B cell activation, and NK cell/lymphocyte–mediated cytotoxicity. Transcriptomic response scores that we developed to estimate the individual-level degree of expression changes in the response-associated key driver genes were significantly correlated with the changes in clinical indices in independent patients with moderate or ambiguous response outcomes.

Conclusion
This study provides response-specific treatment-induced transcriptomic signatures by comparing the transcriptomic landscape between patients with excellent and null responses to anti-TNF drugs at both gene and network levels.
Doctors’ Commons: the Civilians’ Influence on Equity and Trusts
Authors: Brown Lloyd 
Published: August 2023

Abstract
The core of this article lies in its broad examination of the influence that civil law and the now defunct Doctors’ Commons may have had on equity and trusts. Doctors’ Commons was like an Inn of Court for civil lawyers based in England. Historically, these civilian practitioners had a monopoly over certain legal jurisdictions, including wills and probate. To show the civilians’ influence, this article examines Doctors’ Commons’ dominion over the proving of wills. It further looks at the civil law’s possible development of equity’s core concepts, with a specific focus on the Graeco-Roman concept of “conscience”.
Seroprevalence and risk factors for Toxoplasma gondii infection among pregnant women at Debre Markos Referral Hospital, northwest Ethiopia
Authors: Kassie Enirsie , Kebede Nigatu , Kassa Tesfu , Garoma Abebe , Girma Musse , Asnake Yewbnesh , Alemu Ayinalem , Degu Sileshi , Tsigie Meshesha 
Published: August 2023

ABSTRACT

Background
To assess the seroprevalence and risk factors of Toxoplasma gondii infection in pregnant women at the Debre Markos Referral Hospital, northwest Ethiopia.

Methods
A facility-based cross-sectional study was undertaken among pregnant women from March 2020 to May 2021. Sociodemographic and clinical data were collected from randomly selected participants. Five millilitres of blood was collected and an enzyme-linked immunosorbent assay kit was used to test for T. gondii immunoglobulin G (IgG) antibodies. A logistic regression model was computed to identify the risk factors. The adjusted odds ratio (aOR) was estimated along with the 95% confidence interval (CI). A statistically significant association was defined as p&lt;0.05.

Results
T. gondii IgG antibody positivity was found in 38.8% (n=132) of 340 pregnant women. Contact with cats (AOR 2.5 [95% CI 1.5 to 4.2]), eating raw/undercooked meat (AOR 5.7 [95% CI 3.2 to 10.3]), consuming unwashed vegetables (AOR 4.1 [95% CI 2.1 to 8.0]), a history of abortion (AOR 1.9 [95% CI 1.1 to 3.3]) and drinking water sources (AOR 2.5 [95% CI 1.2 to 5.2]) demonstrated a statistically significant association with T. gondii infection.

Conclusions
Toxoplasmosis was found to be fairly common in pregnant mothers. Proper cat excreta disposal, not eating raw/undercooked meat, maintaining hand cleanliness and following environmental sanitation protocols could be important to decrease T. gondii infection.