bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brca1L63X/+ rat is a novel model of human BRCA1 deficiency displaying susceptibility to radiation‐induced mammary cancer
Authors: Nakamura Yuzuki , Kubota Jo , Nishimura Yukiko , Nagata Kento , Nishimura Mayumi , Daino Kazuhiro , Ishikawa Atsuko , Kaneko Takehito , Mashimo Tomoji , Kokubo Toshiaki , Takabatake Masaru , Inoue Kazumasa , Fukushi Masahiro , Arai Masami , Saito Mitsue , Shimada Yoshiya , Kakinuma Shizuko , Imaoka Tatsuhiko 
Published: July 2022

AbstractWomen who are heterozygous for deleterious BRCA1 germline mutations harbor a high risk of hereditary breast cancer. Previous Brca1‐heterozygous animal models do not recapitulate the breast cancer phenotype, and thus all currently used knockout models adopt conditional, mammary‐specific homozygous Brca1 loss or addition of Trp53 deficiency. Herein, we report the creation and characterization of a novel Brca1 mutant rat model harboring the germline L63X mutation, which mimics a founder mutation in Japan, through CRISPR‐Cas9–based genome editing. Homozygotes (Brca1L63X/L63X) were embryonic lethal, whereas heterozygotes (Brca1L63X/+) showed apparently normal development. Without carcinogen exposure, heterozygotes developed mammary carcinoma at a comparable incidence rate with their wild‐type (WT) littermates during their lifetime. Intraperitoneal injection of 1‐methyl‐1‐nitrosourea (25 or 50 mg/kg) at 7 weeks of age induced mammary carcinogenesis at comparable levels among the heterozygotes and their littermates. After exposure to ionizing radiation (0.1–2 Gy) at 7 weeks of age, the heterozygotes, but not WT littermates, displayed dose‐dependent mammary carcinogenesis with 0.8 Gy−1 excess in hazard ratio during their middle age; the relative susceptibility of the heterozygotes was more prominent when rats were irradiated at 3 weeks of age. The heterozygotes had tumors with a lower estrogen receptor α immunopositivity and no evidence of somatic mutations of the WT allele. The Brca1L63X/+ rats thus offer the first single‐mutation, heterozygous model of BRCA1‐associated breast cancer, especially with exposure to a DNA break‐inducing carcinogen. This implies that such carcinogens are causative and a key to breast cancer prevention in individuals who carry high‐risk BRCA1 mutations.
Reflection and Reasoning in Moral Judgment: Two Preregistered Replications of Paxton, Ungar, and Greene (2012)
Authors: Herec Jonas , Sykora Jaroslav , Brahmi Kamil , Vondracek David , Dobesova Oldriska , Smelik Martin , Vaculik Martin , Prochazka Jakub 
Published: July 2022

AbstractThis study consists of two preregistered systematic replications of an experiment on reflection and reasoning in moral judgment by Paxton, Ungar, and Greene (2012). Czech students read a scenario involving incest between consenting adult siblings and an argument supporting the moral acceptability of the behavior. We manipulated the factors of argument strength (strong vs. weak) and the time that participants had to reflect on the argument (no time vs. 2 min). In the first replication (n= 347), neither the manipulated factors nor their interaction influenced how participants rated the moral acceptability of the incestuous behavior. The only significant predictor in the second replication (n= 717) was argument strength but with a very small effect. The effect of argument strength did not differ across groups either with or without deliberation time. Therefore, neither of the studies replicated the effect that deliberation time moderates the influence of argument strength on moral judgment, even though the samples were considerably larger than in the original study. We thus conclude that the effect of the interaction between the strength of an argument and deliberation time on moral judgment either does not exist or is moderated by certain contextual or sample characteristics.
Perinatal changes of right ventricle‐pulmonary artery coupling and its value in predicting persistent pulmonary hypertension of the newborn
Authors: Zhang Jun , Zheng Xiao‐Zhi , Wu Xu‐Chu 
Published: July 2022

AbstractBackgroundRight ventricle‐pulmonary artery (RV‐PA) coupling is an independent predictor of outcome in pulmonary arterial hypertension in adults. Here, we aimed to investigate the changes in RV‐PA coupling during the perinatal period, and to evaluate its performance on predicting persistent pulmonary hypertension of the newborn (PPHN).MethodsA total of 1196 fetuses underwent a dedicated echocardiography screening for foetal heart defects during second trimester (24–27 weeks' gestation), third trimester (34–37 weeks' gestation) and neonatal period (within 14 days after delivery) with the measurement of tricuspid annular plane systolic excursion (TAPSE) and mean pulmonary artery pressure (MPAP). The RV‐PA coupling (TAPSE/MPAP ratio) was calculated.ResultsSix fetuses were diagnosed as persistent pulmonary hypertension of the newborn (PPHN). In normal fetuses, RV‐PA coupling had been increasing from the second trimester to the third trimester and then to the neonatal period (0.12 ± 0.02 vs. 0.18 ± 0.05 vs. 0.23 ± 0.08 mm/mmHg, p < 0.05), while it had been decreasing during the same period of time in abnormal fetuses (0.18 ± 0.02 vs. 0.17 ± 0.02 vs. 0.17 ± 0.01 mm/mmHg, p < 0.05). There was a strong positive correlation between RV‐PA coupling and gestational age (GA) in normal fetuses (r = 0.71, p < 0.0001). The area under receiver operating characteristic curve (AUC) of 0.989 for RV‐PA coupling during second trimester was superior to that for RV‐PA coupling during third trimester (AUC: 0.536) in predicting PPHN. The optimal cutoff value was 0.16 mm/mmHg, with a sensitivity of 100.00%, a specificity of 96.36% and an accuracy of 97.73%.ConclusionRV‐PA coupling had close relation with GA in normal fetuses. It was a strong predictor of PPHN.
CD33‐targeting extracellular vesicles deliver antisense oligonucleotides against FLT3‐ITD and miR‐125b for specific treatment of acute myeloid leukaemia
Authors: Chen Huan , Jayasinghe Migara Kavishka , Yeo Eric Yew Meng , Wu Zhiyuan , Pirisinu Marco , Usman Waqas Muhammad , Pham Thach Tuan , Lim Kah Wai , Tran Nhan Van , Leung Anskar Y. H. , Du Xin , Zhang Qiaoxia , Phan Anh Tuân , Le Minh T. N. 
Published: July 2022

AbstractIntroductionAcute Myeloid Leukaemia (AML) is the most common blood cancer in adults. Although 2 out of 3 AML patients go into total remission after chemotherapies and targeted therapies, the disease recurs in 60%–65% of younger adult patients within 3 years after diagnosis with a dramatically decreased survival rate. Therapeutic oligonucleotides are promising treatments under development for AML as they can be designed to silence oncogenes with high specificity and flexibility. However, there are not many well validated approaches for safely and efficiently delivering oligonucleotide drugs. This issue could be resolved by utilizing a new generation of delivery vehicles such as extracellular vesicles (EVs).MethodsIn this study, we harness red blood cell‐derived EVs (RBCEVs) and engineer them via exogenous drug loading and surface functionalization to develop an efficient drug delivery system for AML. Particularly, EVs are designed to target CD33, a common surface marker with elevated expression in AML cells via the conjugation of a CD33‐binding monoclonal antibody onto the EV surface.ResultsThe conjugation of RBCEVs with the CD33‐binding antibody significantly increases the uptake of RBCEVs by CD33‐positive AML cells, but not by CD33‐negative cells. We also load CD33‐targeting RBCEVs with antisense oligonucleotides (ASOs) targeting FLT3‐ITD or miR‐125b, 2 common oncogenes in AML, and demonstrate that the engineered EVs improve leukaemia suppression in in vitro and in vivo models of AML.ConclusionTargeted RBCEVs represent an innovative, efficient, and versatile delivery platform for therapeutic ASOs and can expedite the clinical translation of oligonucleotide drugs for AML treatments by overcoming current obstacles in oligonucleotide delivery.
Administrative Division Adjustment and Housing Price Comovement: Evidence from City‐County Mergers in China
Authors: Zhang Sihan , Zhang Ming‐ang , Sun Weizeng 
Published: July 2022

AbstractInterregional housing price comovement is a stylized fact worldwide. This study explores how it is affected by administrative division adjustment. We exploit city‐county mergers in China as a quasi‐natural experiment to construct a difference‐in‐differences strategy for causal identification. Based on monthly housing price data for districts (counties) in China from 2010 to 2019, we find that city‐county mergers significantly improve correlations in housing prices between the merged county and the urban district. This effect is more obvious in cities with a large economic gap between merged counties and urban districts, located in the central and western regions, and with lower administrative hierarchies (non‐provincial‐capital cities). The mechanism test shows that the impact of city‐county mergers on housing price comovement results mainly from integrating housing demand rather than integrating housing supply, like the unified land supply policy that local government implements in the new administrative scope after mergers. The results are helpful in understanding housing price comovement from the view of regional integration and provide clear policy implications for housing market regulation in China.
Assisted reproductive technology: Short‐ and long‐term outcomes
Authors: Graham Mary Elaine , Jelin Angie , Hoon Alexander H. , Wilms Floet Anna Maria , Levey Eric , Graham Ernest M. 
Published: July 2022

AbstractAssisted reproductive technology (ART) includes fertility treatment in which either eggs or embryos are handled outside a female's body to promote successful pregnancies and healthy offspring. Current ART procedures encompass in vitro fertilization with or without intracytoplasmic sperm injection. The most common complication of ART is related to the consequences of multiple pregnancy, which can be prevented or minimized by reducing the number of embryos transferred to the uterus, commonly single embryo transfer. ART has been shown to be variably associated with adverse short‐ and long‐term perinatal outcomes, including cerebral palsy, autism, neurodevelopmental imprinting disorders, and cancer. However, there is uncertainty as to whether reported problems are related to the ART procedure itself, to factors related to infertility, to other medical and environmental factors, or a combination thereof. From a pathophysiological perspective, whether ART alters epigenetic mechanisms of gene expression, leading to later developmental, medical, and behavioral disorders, is an area of active investigation. With the meticulously conducted short‐ and long‐term outcome studies completed so far, overall, and after controlling for multiple gestations and preterm delivery, the results suggest that ART is a safe procedure, offering hope to many parent(s) wishing for a healthy child. This paper highlights ART methods and the risk factors and confounders in the interpretation of short‐ and long‐term outcome data, providing the reader with a means to evaluate findings and conclusions of outcome studies.What this paper adds

Assisted reproductive technology (ART) is a relatively safe procedure.
Single embryo implantation optimizes outcome.
Informed consent, including the risks and benefits of ART, should be required.
Ongoing longitudinal studies are necessary to fully understand ART outcomes.
The effect of a non‐tobacco‐based nicotine pouch on mucosal lesions caused by Swedish smokeless tobacco (snus)
Authors: Alizadehgharib Sara , Lehrkinder Anna , Alshabeeb Ali , Östberg Anna‐Karin , Lingström Peter 
Published: July 2022

AbstractOral mucosal lesions are commonly found in Swedish smokeless tobacco (snus) users where the pouch is placed. These lesions are reversible, that is, clinical and histological tissue changes return to normal following cessation. However, the exact mechanisms behind these changes are unknown. The main aim of this study was to investigate how snus‐like non‐tobacco‐based nicotine pouches affect the oral mucosa and the severity of pre‐existing lesions. Sixty regular users of Swedish smokeless tobacco were encouraged to substitute their snus with non‐tobacco‐based nicotine pouch products during a 6‐week period. Meanwhile, oral mucosal lesions were assessed using a four‐degree scale. Over time, a reduction of pre‐existing mucosal lesions was observed between baseline and the final visit. In a second part, the effect of exposure to regular snus on the production of 48 different cytokines in peripheral blood mononuclear cells was compared in vitro with that resulting from exposure to the non‐tobacco‐based nicotine products. Results showed significantly increased production of proinflammatory cytokines in cells exposed to regular snus compared to untreated or cells exposed to the non‐tobacco‐based nicotine products. This may be related to the improved clinical appearance of the oral mucosa in the participants that used the non‐tobacco‐based nicotine test pouches.
Febrile seizures lead to prolonged epileptiform activity and hyperoxia that when blocked prevents learning deficits
Authors: Harris Sydney A. , George Antis G. , Barrett Karlene T. , Scantlebury Morris H. , Teskey G. Campbell 
Published: July 2022

AbstractObjectiveIn adult brain tissue, oxygen levels typically remain in the normoxic zone, but status epilepticus results in hyperoxia, whereas brief self‐terminating seizures lead to postictal hypoxia. The dynamic changes in oxygen levels and the underlying mechanisms are unknown in juveniles with febrile seizures.MethodsEight‐day‐old female and male rat pups were implanted with an electrode and oxygen‐sensing optode in the hippocampus and then received once daily injections of lipopolysaccharide for 4 days to induce an immune response. Local partial pressure of oxygen (pO2) and local field potentials were recorded before, during, and after a heat‐induced febrile seizure. Separate groups of pups received injections of vehicle or drugs targeting cyclooxygenase (COX)‐1, COX‐2, L‐type calcium channels (LTCCs), and cannabinoid receptor type 1 (CB1) and transient receptor potential vanilloid‐1 (TRPV1) receptors prior to febrile seizure induction to determine pO2 mechanisms. Following febrile seizures, a subset of pups were raised to young adulthood and then tested for learning impairments using the novel object recognition task.ResultsFebrile seizures resulted in predictable oxygen dynamics that were related to behavioral seizures and epileptiform activity. During a behavioral seizure, pO2 rapidly increased, rapidly decreased, and then returned to near baseline. When the behavioral seizure terminated, oxygen levels climbed into the hyperoxic zone during a time of prolonged epileptiform activity. When epileptiform activity terminated, oxygen levels slowly returned to baseline. A COX‐1 antagonist prevented hyperoxia, whereas a COX‐2 antagonist did not. An LTCC antagonist exacerbated hyperoxia. Boosting levels of an endocannabinoid also exacerbated hyperoxia, whereas blocking CB1 receptors and TRPV1 receptors reduced hyperoxia. Inhibiting TRPV1 receptors during a febrile seizure prevented learning deficits in young adult female rats.SignificanceBrain oxygenation during and following a febrile seizure has a distinct pattern and multiple mechanisms. Brain oxygen dynamics may be an important consideration in the development of treatments for febrile seizures.
Malignancy risk ofnon‐biologicimmunosuppressive therapies: A review of the literature withevidence‐basedtreatment recommendations
Authors: Scott Stratman , Shireen Golpanian Rachel , Rachel Fayne , Kirsner Robert S. , Maderal Andrea D. 
Published: July 2022

AbstractNon‐biologic immunosuppressive therapies are a mainstay in the treatment of various dermatologic conditions. However, the use of these therapies has been scrutinized for potentially increasing risk of haematologic or solid‐organ malignancies. Currently, there are no evidence‐based guidelines stratifying the risk of malignancy in patients receiving these immunosuppressive agents for the treatment of dermatologic disease. In our review, we evaluate the risk of solid organ and haematologic malignancies in patients receiving non‐biologic immunosuppressant therapy for dermatologic indications. A literature search was conducted on PubMed/MEDLINE. Search terms included commonly prescribed non‐biologic immunosuppressants and common dermatologic conditions for which non‐biologic immunosuppressants are typically prescribed. Levels of evidence and grades of recommendation were used for guidelines. All immunosuppressants evaluated, with the exception of cyclophosphamide, demonstrated low solid‐organ or haematologic malignancy potential. Co‐morbidities may play a role in malignancy risk in the context of immunosuppressant treatment, including autoimmune disease, which have been associated with increased risk of malignancy and confound overall risk. Duration and/or dosage of treatment may influence this risk as well. Limitations of the review include that the majority of studies were of small sample size, retrospective in nature, and there was lack of direct comparison trials.
San Antonio Water System, Texas Carrizo Aquifer Storage Recovery Program
Authors: Snyder Grant L. , Pyne R. David G. , Morrison Kevin , Nixon Kirk 
Published: July 2022

AbstractSan Antonio Water System (SAWS) developed its Aquifer Storage Recovery (ASR) program in the Carrizo aquifer to provide potable water supply reliability for San Antonio during droughts while protecting natural ecosystems and threatened and endangered species at Comal Springs and San Marcos Springs and augmenting downstream flows in the San Antonio River and estuarine ecosystems. It enables SAWS to completely optimize use of its Edwards Aquifer Withdrawal Permit with no wasted water, leveling out seasonal demand stresses on the Edwards aquifer. The SAWS Carrizo ASR wellfield recovery hydraulic capacity was designed to provide 64 million gallons per day (MGD) (0.24 Mm3/D). However, as built, the briefly tested recovery capacity, in practice, is approximately 80 MGD (Kirk Nixon and Kevin Morrison, verbal communication, 2022). Almost 200,000 acre feet (AF) (247 Mm3) of drinking water have been stored to date. The water recovered from storage requires only re‐disinfection prior to transmission and distribution to customers. During the period 2011 to 2014, a drought of near record intensity required SAWS to recover a total volume exceeding 50,000 AF (61.7 Mm3) over the 4‐year period. The ASR wellfield area and H2Oaks treatment facility serve as a central location for integration of two other long‐term water supply strategies including desalination of brackish groundwater from the underlying Wilcox aquifer and groundwater production from the local Carrizo aquifer. Several lessons have been learned during 18 years of ASR operation, as addressed in this article.
A qualitative evaluation of bystander training: What works?
Authors: Roberts Nicola , Marsh Heaven 
Published: July 2022

AbstractResearch shows that bystander training has the potential to reduce violence and abuse. It is not clear how and why the training works. We evaluated bystander training to find out what works. We found that interactive techniques, such as group discussions, ‘the video’, and the use of real‐world examples were the best ways of delivering the training because they stood out and were remembered by participants. These findings add to the paucity of research on what works in bystander training, and in doing so, raises implications for the design and delivery of future training.
Psychometric properties of the Thai version of the Scale of Oral Health Outcomes for 5‐year‐old children
Authors: Ariyavutikul Wilai , Jirarattanasopha Varangkanar , Duangthip Duangporn , Gao Sherry Shiqian 
Published: July 2022

AbstractBackgroundAs caries prevalence in Thai preschool children is very high and its consequences have scarcely been evaluated, the Scale of Oral Health Outcomes for 5‐year‐old children (SOHO‐5) is considered as an appropriate tool to measure the children's oral health‐related quality of life (OHRQoL).AimTo translate the SOHO‐5 into Thai (Th‐SOHO‐5) and assess its psychometric characteristics.DesignThe cross‐cultural adaptation of the SOHO‐5 into Thai comprised forward–backward translation by experts and face validation by 20 child–parent dyads. To evaluate psychometric properties of the final version, a cross‐sectional study was conducted on 306 child–parent pairs using an interview mode for children and a self‐administered mode for parents. A trained investigator examined children's caries status.ResultsThe Th‐SOHO‐5 showed satisfactory psychometric characteristics. Cronbach's alpha values were above 0.8 for both child and proxy reports. Overall intraclass correlation coefficients were > 0.9. Factor analysis supported a single‐factor structure model of the Th‐SOHO‐5 and showed an excellent fit. Th‐SOHO‐5 scores were correlated with all global rating scales of oral health and well‐being. Children with higher caries experience or caries with pulpal involvement demonstrated significantly higher Th‐SOHO‐5 scores.ConclusionThe Th‐SOHO‐5 possessed good reliability and validity. It can be used to evaluate the OHRQoL of preschool children in Thailand.
On modeling ambiguity through entropy
Authors: Aggarwal Manish , Hanmandlu Madasu 
Published: July 2022

AbstractFirst, a concept of ambiguity function is devised as an analogue of membership function, which directly and intuitively represents the ambiguity as perceived by the agent corresponding to a membership function. The ambiguity function is then deployed to develop an adaptive fuzzy entropy function that gives the overall fuzzy entropy of a fuzzy system as perceived by the agent. The proposed function considers also the agent's specific attitude as well as the given context (e.g., collection of the membership grades with respect to an attribute/criterion or property), both of which inevitably shape our perception of uncertainty. The usefulness of the proposed fuzzy entropy function is shown in multicriteria decision aiding in identifying those criteria that are most effective in distinguishing among the alternatives.