bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of prenatal and lactational exposure to iodoacetic acid on the F1 generation of mice
Authors: Gonsioroski Andressa , Plewa Michael J , Flaws Jodi A 
Published: April 2022

Abstract
Water disinfection can generate water disinfection byproducts (DBPs). Iodoacetic acid (IAA) is one DBP, and it has been shown to be an ovarian toxicant in vitro and in vivo. However, it is unknown if prenatal and lactational exposure to IAA affects reproductive outcomes in female offspring. This study tested the hypothesis that prenatal and lactational exposure to IAA adversely affects reproductive parameters in F1 female offspring. Adult female CD-1 mice were dosed with water (control) or IAA (10, 100, and 500 mg/L) in the drinking water for 35 days and then mated with unexposed males. IAA exposure continued throughout gestation. Dams delivered naturally, and pups were continuously exposed to IAA through lactation until postnatal day (PND) 21. Female pups were euthanized on PND 21 and subjected to measurements of anogenital distance, ovarian weight, and vaginal opening. Ovaries were subjected to histological analysis. In addition, sera were collected to measure reproductive hormone levels. IAA exposure decreased vaginal opening rate, increased the absolute weight of the ovaries, increased anogenital index, and decreased the percentage of atretic follicles in female pups compared to control. IAA exposure caused a borderline decrease in the levels of progesterone and follicle-stimulating hormone (FSH) and increased levels of testosterone in female pups compared to control. Collectively, these data show that prenatal and lactational exposure to IAA in drinking water affects vaginal opening, anogenital index, the weight of the ovaries, the percentage of atretic follicles, and hormone levels in the F1 generation in mice.
Downregulating HK2 inhibits proliferation of endometrial stromal cells through a noncanonical pathway involving phosphorylation of signal transducer and activator of transcription 1 in endometriosis
Authors: Hou Shuhui , Lei Shating , Peng Haiyan , Weng Lichun , Lv Siji , Li Mingqing , Zhao Dong 
Published: April 2022

Abstract

Background
Endometriosis is a benign gynecologic disease that causes chronic pelvic pain, dysmenorrhea and infertility and shares several characteristics with malignant tumors, afflicting women of reproductive age. Hexokinase 2 plays an essential role as the first rate-limiting enzyme in the metabolic glycolysis pathway, and its abnormal elevation in tumors is associated with tumor genesis and metastasis. However, the expression and role of hexokinase 2 in endometriosis remain unclear.

Methods
We sequenced the primary endometrial stromal cells from patients with endometrioma and utilized immunohistochemistry, quantitative real-time PCR, and western blot to determine the expression of hexokinase 2. Then wound healing assays, cell invasion assays, and cell proliferation assays were performed to explore the functions of hexokinase 2 in endometrial stromal cells. Furthermore, mice models of endometriosis were used to observe the effects of hexokinase 2 inhibitors in vivo. Lastly, glycolysis metabolism detection and transcriptome sequencing were carried out in hexokinase 2-knockdown endometrial stromal cells to analyze the mechanism of hexokinase 2 affecting cell function.

Results
Endometrial stromal cells of endometrioma displayed active glycolysis metabolism and elevated expression of hexokinase 2. Downregulating hexokinase 2 reduced the migration, invasion, and proliferation capacity of endometrial stromal cells. Knockdown of hexokinase 2 induced upregulation of signal transducer and activator of transcription 1 and their phosphorylation to attenuate the proliferation of endometrial stromal cells.

Conclusions
Hexokinase 2 is associated with the migration, invasion, and proliferation of endometrial stromal cells, which might provide new insights into the pathogenesis and treatment of endometriosis.

Summary Sentence
HK2 is upregulated in ovarian endometrioma and knockdown of HK2 induced upregulation of signal transducer and activator of transcription 1 (STAT1) and their phosphorylation to attenuate the proliferation of endometrial stromal cells.
Habitat Protection, Ideology and the British Nature State: The Politics of the Wildlife and Countryside Act 1981
Authors: Kelly Matthew 
Published: April 2022

Abstract
The Wildlife and Countryside Act 1981 was the most important piece of environmental legislation passed by a British government since the National Parks and Access to the Countryside Act 1949. It sought to enhance the protection of listed flora and fauna, prevent further damage to existing habitat and resolve issues that had arisen with respect to rights of public access to the countryside. Although the bill was long and complex, many of its provisions sought to rationalise existing statutes or extend existing provision rather than create new powers. Provisions seeking to protect habitat proved highly contentious. The proprietary interest resented what it saw as an unjustified interference in private property rights; statutory bodies were alarmed that the centralising aspects of the Act would empower ministers at the expense of their ‘scientific’ independence; and the emergent environmental lobby, increasingly frustrated by the cautious approach of the statutory bodies, was determined that the bill’s habitat protection provisions be strengthened. This article examines the lengthy and disputatious consultation and parliamentary process in terms of longer-term frustration with the apparent weakness of statutory protections and how it brought the environmental effect of agricultural intensification into mainstream political debate. This article contextualises the growing insistence that there was a public interest in the health of the natural environment and situates the argument with respect to what environmental historians have started to analyse as the history of the ‘nature state’, a distinct realm of state activity comparable to the welfare state, warfare state or security state.
Exome sequencing of hepatocellular carcinoma in lemurs identifies potential cancer drivers
Authors: Gunady Ella F , Ware Kathryn E , Hoskinson Plumlee Sarah , Devos Nicolas , Corcoran David , Prinz Joseph , Misetic Hrvoje , Ciccarelli Francesca D , Harrison Tara M , Thorne Jeffrey L , Schopler Robert , Everitt Jeffrey I , Eward William C , Somarelli Jason A 
Published: April 2022

Abstract

Background and objectives
Hepatocellular carcinoma occurs frequently in prosimians, but the cause of these liver cancers in this group is unknown. Characterizing the genetic changes associated with hepatocellular carcinoma in prosimians may point to possible causes, treatments and methods of prevention, aiding conservation efforts that are particularly crucial to the survival of endangered lemurs. Although genomic studies of cancer in non-human primates have been hampered by a lack of tools, recent studies have demonstrated the efficacy of using human exome capture reagents across primates.

Methodology
In this proof-of-principle study, we applied human exome capture reagents to tumor–normal pairs from five lemurs with hepatocellular carcinoma to characterize the mutational landscape of this disease in lemurs.

Results
Several genes implicated in human hepatocellular carcinoma, including ARID1A, TP53 and CTNNB1, were mutated in multiple lemurs, and analysis of cancer driver genes mutated in these samples identified enrichment of genes involved with TP53 degradation and regulation. In addition to these similarities with human hepatocellular carcinoma, we also noted unique features, including six genes that contain mutations in all five lemurs. Interestingly, these genes are infrequently mutated in human hepatocellular carcinoma, suggesting potential differences in the etiology and/or progression of this cancer in lemurs and humans.

Conclusions and implications
Collectively, this pilot study suggests that human exome capture reagents are a promising tool for genomic studies of cancer in lemurs and other non-human primates.

Lay Summary
Hepatocellular carcinoma occurs frequently in prosimians, but the cause of these liver cancers is unknown. In this proof-of-principle study, we applied human DNA sequencing tools to tumor–normal pairs from five lemurs with hepatocellular carcinoma and compared the lemur mutation profiles to those of human hepatocellular carcinomas.
Efficacy and safety of same-day discharge after atrial fibrillation ablation compared with post-procedural overnight stay: a systematic review and meta-analysis
Authors: Tang Pok Tin , Davies Mark , Bashir Yaver , Betts Timothy R , Pedersen Michala , Rajappan Kim , Ginks Matthew R , Wijesurendra Rohan S 
Published: April 2022

Abstract

Aims
Catheter ablation for atrial fibrillation (AF) has historically required inpatient admission post-procedure, but same-day discharge (SDD) has recently been reported. We aimed to assess the efficacy and safety of SDD compared with overnight stay (OS) post-ablation.

Methods and results
We performed a systematic search of the PubMed database. Random-effects meta-analysis was performed to assess the efficacy (successful SDD) and safety (24 h complications, 30-day complications, 30-day re-admissions, and 30-day mortality) of a SDD AF ablation strategy. Fourteen non-randomized observational studies met criteria for inclusion, encompassing 26488 patients undergoing AF ablation, of whom 9766 were SDD. The mean age of participants was 61.9 years, and 67.9% were male. Around 61.7% underwent ablation for paroxysmal AF. The pooled success rate of SDD was 83.2% [95% confidence intervals (CIs): 61.5–97.0%, I2 100%]. The risk of bias was severe for all effect estimates due to confounding, as most cohorts were retrospectively identified without appropriately matched comparators. There was no significant difference in 30-day complications [odds ratio (OR): 0.95, 95% CI: 0.65–1.40, I2 53%] or 30-day re-admission (OR 0.96, 95% CI: 0.49–1.89, I2 82%) between groups. There were insufficient data for meta-analysis of 24 h complications and 30-day mortality. Where reported, no re-admissions occurred due to 24 h complications after SDD. Two deaths (0.04%) were reported in both SDD and OS groups.

Conclusion
Same-day discharge after AF ablation appears to be an effective and safe strategy in selected patients. However, the available evidence is of low quality, and more robust prospective studies comparing SDD to OS are needed.
Aftershock distributions, moment tensors and stress evolution of the 2016 Iniskin and 2018 Anchorage Mw 7.1 Alaskan intraslab earthquakes
Authors: Drolet Doriane , Bostock Michael G , Plourde Alexandre P , Sammis Charles G 
Published: April 2022

SUMMARY
We present a detailed study of two Mw 7.1 intraslab earthquakes that occurred in southern Alaska: the Iniskin earthquake of 24 January 2016, and the Anchorage earthquake of 30 November 2018. We have relocated and recovered moment tensors for hundreds of aftershocks following both events, and inverted for stress histories. The aftershock distribution of the Iniskin earthquake suggests that the rupture propagated updip along a fault dipping steeply into the Pacific Plate and terminated at a stratigraphic horizon, inferred to be either the interface or Moho of the subducting slab. In addition, four earthquakes ruptured the main fault in the preceding two years and had similar moment tensors to the mainshock. This evidence suggests that the mainshock likely reactivated a pre-existing, outer-rise fault. The Anchorage earthquake sequence is complex due to its location near the boundary of the subducting Yakutat and Pacific plates, as evidenced by the aftershock distribution. Aftershock hypocentres form two main clusters that appear to correspond to orthogonal, conjugate faults, consistent with the two nodal planes of the dominant focal mechanisms. Both geographic groups display many focal mechanisms similar to the mainshock, which could indicate simultaneous rupture on conjugate planes. The time dependence in stress ratio for the Iniskin sequence can be interpreted in terms of pore-pressure evolution within the mainshock fault zone. In particular, our observations are consistent with a dehydration-assisted transfer mechanism where fluids are produced during rupture through antigorite dehydration and raised to high pore pressures through matrix collapse and/or thermal pressurization. The Anchorage sequence exhibits a more complex stress ratio evolution that may be associated with stress adjustments within a distributed fault network, or reflect a strongly heterogeneous stress field.
Does calculation method matter for targeting vancomycin area under the curve?
Authors: Chang Jack , Patel Dhara , Vega Ana , Claeys Kimberly C , Heil Emily L , Scheetz Marc H 
Published: April 2022

Abstract

Objectives
To assess differences in vancomycin AUC estimates from two common, clinically applied first-order pharmacokinetic equation methods compared with Bayesian estimates.

Methods
A cohort of patients who received vancomycin and therapeutic drug monitoring was studied. First-order population pharmacokinetic equations were used to guide initial empirical dosing. After receipt of the first dose, patients had peak and trough serum levels drawn and steady-state AUC was estimated using first-order pharmacokinetic equations as standard care. We subsequently created a Bayesian model and used individual Empirical Bayes Estimates to precisely calculate vancomycin AUC24–48, AUC48–72 and AUC72–96 in this cohort. AUC at steady state (AUCSS) differences from the first-order methods were compared numerically and categorically (i.e. below, within or above 400–600 mg·h/L) to Bayesian AUCs, which served as the gold standard.

Results
A total of 65 adult inpatients with 409 plasma samples were included in this analysis. A two-compartment intravenous infusion model with first-order elimination fit the data well. The mean of Bayesian AUC24–48 was not significantly different from AUC estimates from the two first-order pharmacokinetic equation methods (P = 0.68); however, Bayesian AUC48–72 and Bayesian AUC72–96 were both significantly different when compared with both first-order pharmacokinetic equation methods (P &lt; 0.01 for each). At the patient level, categorical classifications of AUC estimates from the two first-order pharmacokinetic equation methods differed from categorizations derived from the Bayesian calculations. Categorical agreement was ∼50% between first-order and Bayesian calculations, with declining categorical agreement observed with longer treatment courses. Differences in categorical agreement between calculation methods could potentially result in different dose recommendations for the patient.

Conclusions
Bayesian-calculated AUCs between 48–72 and 72–96 h intervals were significantly different from first-order pharmacokinetic method-estimated AUCs at steady state. The various calculation methods resulted in different categorical classification, which could potentially lead to erroneous dosing adjustments in approximately half of the patients.
The Committee of the Rights of the Child—Does Size Matter?
Authors: Winter Justice Renate 
Published: April 2022

Abstract
The Convention on the Rights of the Child celebrated its 30th birthday in November 2019. All Member States to the United Nations save one have ratified the convention during the 30 years of its existence. Three Optional Protocols were added to the Convention. In order to monitor and check progress, a treaty body was created, the Committee on the Rights of the Child, based in Geneva. This treaty body is regularly evaluating the reports of Member States. Concluding observations have to be drawn to assist Member States in upgrading the level of child protection in their respective countries. Treaty bodies have also to draft General Comments among other duties. Moreover, the Committee has to react to individual communications coming from children or persons acting on their behalf.
Proving properties of binary classification neural networks via Łukasiewicz logic
Authors: Preto Sandro , Finger Marcelo 
Published: April 2022

Abstract
Neural networks are widely used in systems of artificial intelligence, but due to their black box nature, they have so far evaded formal analysis to certify that they satisfy desirable properties, mainly when they perform critical tasks. In this work, we introduce methods for the formal analysis of reachability and robustness of neural networks that are modeled as rational McNaughton functions by, first, stating such properties in the language of Łukasiewicz infinitely-valued logic and, then, using the reasoning techniques of such logical system. We also present a case study where we employ the proposed techniques in an actual neural network that we trained to predict whether it will rain tomorrow in Australia.
Epidermal growth factor receptor as a potential target of momordin Ic to promote apoptosis of cholangiocarcinoma cells
Authors: Senggunprai Laddawan , Kukongviriyapan Veerapol , Prawan Auemduan , Kongpetch Sarinya 
Published: April 2022

Abstract

Objectives
Strategies that induce apoptosis of malignant cells are recognized as effective cancer treatments. This study evaluated the apoptosis-inducing ability of momordin Ic against cholangiocarcinoma (CCA) cells and the respective underlying mechanisms.

Methods
Quantification of apoptotic cells was performed using Annexin V/7-AAD double dye staining followed by flow cytometry. The effect of momordin Ic on the expression of epidermal growth factor receptor (EGFR) and its downstream signalling molecules was determined via Western blot analysis. The RT2 Profiler PCR Array was used to determine the expression of cell death-associated genes. Expression levels of apoptosis-related proteins were examined using an apoptosis antibody array.

Key findings
Momordin Ic potently limited the ability of CCA cells to thrive by promoting apoptotic cell death. This apoptosis-inducing activity was accompanied with suppression of expression of EGFR, p-EGFR, c-Myc and other downstream EGFR signalling-related molecules. Additional molecular analyses demonstrated that momordin Ic modified the expression profile of cell death-associated genes in CCA cells. Moreover, significant upregulation of apoptosis-activating proteins and downregulation of apoptosis-inhibiting protein were also observed after exposure to momordin Ic.

Conclusions
These results suggest that momordin Ic has a potential therapeutic opportunity for CCA treatment by acting as an EGFR suppressant.
Development of a comprehensive method based on quantitative 1H NMR for quality evaluation of Traditional Chinese Medicine injection: a case study of Danshen Injection
Authors: Li Wenzhu , Zhao Fang , Yang Jiayu , Pan Jianyang , Qu Haibin 
Published: April 2022

Abstract

Objectives
This study aimed to establish a rapid and comprehensive method for quantitative determination of complex ingredients in Traditional Chinese Medicine injections.

Methods
A 1H quantitative nuclear magnetic resonance method was developed to simultaneously quantify comprehensive chemical components in Danshen Injection. Multivariate statistical analysis technique was applied to quality evaluation of multiple batches of Danshen injection.

Key findings
A complete signal attribution to the 1H nuclear magnetic resonance spectrum of Danshen injection was developed and performed for the first time. A total of 32 chemical components were identified from Danshen Injection. Among them, 20 were quantified simultaneously, accounting for up to 80% (w/w) of the total solids and 95% (w/w) of total organic matter, representing success compared to the previous studies. The developed method was further applied to analyze 13 batches of Danshen Injection from three manufacturers to make a realistic analysis.

Conclusion
It was found that the comprehensive chemical information provides an adequate characterization for quality profiles among different commercial batches of Danshen Injection. The developed method further offered a guarantee for improving the consistency and safety of Traditional Chinese Medicine injections.
Lianhuaqingwen alleviates p53-mediated apoptosis in alveolar epithelial cells to prevent LPS-induced ALI
Authors: Yang Ruhao , Yang Haizhen , Li Wenqiang , Yue Fang , Chen Hao , Hao Yueying , Hu Ke 
Published: April 2022

Abstract

Background
Our previous study found that Lianhuaqingwen reduces lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice by suppressing p53-mediated apoptosis. To identify the type of lung cells affected by Lianhuaqingwen, we conducted a cell experiment.

Methods
C57/B6 mice and A549 cells were administered Lianhuaqingwen and LPS. A549 cells were transfected with p53 siRNA to inhibit p53. The degree of ALI in mice was validated by haematoxylin and eosin staining as well as measurement of IL-1β and MCP-1 levels. In A549 cells, Cell Counting Kit-8 (CCK-8), DHE and TUNEL assays were used to assess cell viability, reactive oxygen species (ROS) production and apoptosis, respectively. Western blot analysis was used to evaluate the protein expression of p53, Bcl-2, Bax, caspase-9 and caspase-3. Co-immunofluorescence was used to detect cytochrome C distribution.

Key findings
Lianhuaqingwen alleviated LPS-induced ALI in vivo. Lianhuaqingwen at 300 μg/ml increased cell viability, lowered ROS production and reduced apoptotic cells in vitro. Lianhuaqingwen enhanced Bcl-2 expression and reduced Bax, caspase-9 and caspase-3 expression as well as blocked cytochrome C release under LPS stimulation. Treatment with a combination of Lianhuaqingwen and p53 siRNA was more effective than treatment with Lianhuaqingwen alone.

Conclusion
Lianhuaqingwen inhibits p53-mediated apoptosis in alveolar epithelial cells, thereby preventing LPS-induced ALI.
Outbreak: Contagion and Culture in the Victorian Era: Introduction
Authors: Krishnan Lakshmi , Nixon Kari 
Published: April 2022

Abstract
One can hardly read a Victorian text without encountering contagious diseases, those striving against them, or those marked by them: from the tuberculous resonances in Dracula (1897) to Jonathan Hutchinson’s (1828–1913) syphilography, Mary Seacole’s pioneering nursing and treatment of cholera in Panama (Wonderful Adventures of Mrs. Seacole in Many Lands, 1857), and finally Bleak House’s Esther, disfigured by smallpox. This Roundtable asks how the Victorians approached contagion, examining the ways in which it became such a central preoccupation for a society already fixated upon health and illness and the transactions between life and death. Through our analysis of the long nineteenth century, we hope to illuminate our own contagious transformations. As the novel coronavirus pandemic continues to reveal our individual and communal interdependence, complicated navigation of information, panic, sickness, harm, and isolation, and as it underscores tensions between individual liberty and the collective good, Victorian understandings of contagion acquire fresh relevance to us. In Victorian studies, these interpretations remain a critical touchstone for thinking about medicine, history, narrative, and social and public policy.
Sleep Deprivation and Self-Harm Associated With Excessive Gaming: A Case Report
Authors: Hall Amanda M , Glass Stuart D , McDonald William A , Almond Nathaniel B , Doan Andrew P 
Published: April 2022

ABSTRACT
Excessive gaming may be associated with sleep deprivation and self-harm. One active duty member committed self-injurious behavior to avoid work-related consequences. It was discovered that the patient participated in a video-gaming binge throughout an entire 72-hour weekend liberty. The patient experienced severe sleep deprivation to the point where he overslept and failed to report to work. He injured himself and fabricated a robbery and assault to avoid disciplinary consequences. Military health care providers should consider excessive gaming in patients presenting with sleep issues, self-harm, and disciplinary problems. As the prevalence of gaming increases, the military leadership should be aware that excessive gaming can degrade force readiness.