bluuebunny/crossref_metadata_2025_split huggingface dataset:
A combined clinical and genetic model for predicting risk of ovarian cancer
Authors: Dite Gillian S. , Spaeth Erika , Murphy Nicholas M. , Allman Richard 
Published: December 2022

Objective
Women with a family history of ovarian cancer or a pathogenic or likely pathogenic gene variant are at high risk of the disease, but very few women have these risk factors. We assessed whether a combined polygenic and clinical risk score could predict risk of ovarian cancer in population-based women who would otherwise be considered as being at average risk.

Methods
We used the UK Biobank to conduct a prospective cohort study assessing the performance of 10-year ovarian cancer risks based on a polygenic risk score, a clinical risk score and a combined risk score. We used Cox regression to assess association, Harrell’s C-index to assess discrimination and Poisson regression to assess calibration.

Results
The combined risk model performed best and problems with calibration were overcome by recalibrating the model, which then had a hazard ratio per quintile of risk of 1.338 [95% confidence interval (CI), 1.152–1.553], a Harrell’s C-index of 0.663 (95% CI, 0.629–0.698) and overall calibration of 1.000 (95% CI, 0.874–1.145). In the refined model with estimates based on the entire dataset, women in the top quintile of 10-year risk were at 1.387 (95% CI, 1.086–1.688) times increased risk, while women in the top quintile of full-lifetime risk were at 1.527 (95% CI, 1.187–1.866) times increased risk compared with the population.

Conclusion
Identification of women who are at high risk of ovarian cancer can allow healthcare providers and patients to engage in joint decision-making discussions around the risks and benefits of screening options or risk-reducing surgery.
Huntington-associated protein 1 inhibition contributes to neuropathic pain by suppressing Cav1.2 activity and attenuating inflammation
Authors: Pan JingYing , Zhao YaYu , Sang Rui , Yang RiYun , Bao JingYin , Wu YongJiang , Fei Ying , Wu Jian , Chen Gang 
Published: December 2022

Abstract
Although pain dysfunction is increasingly observed in Huntington disease, the underlying mechanisms still unknown. As a crucial Huntington-associated protein, Huntington-associated protein 1 (HAP1) is enriched in normal spinal dorsal horn and dorsal root ganglia (DRG) which are regarded as “primary sensory center,” indicating its potential functions in pain process. Here, we discovered that HAP1 level was greatly increased in the dorsal horn and DRG under acute and chronic pain conditions. Lack of HAP1 obviously suppressed mechanical allodynia and hyperalgesia in spared nerve injury (SNI)-induced and chronic constriction injury-induced pain. Its deficiency also greatly inhibited the excitability of nociceptive neurons. Interestingly, we found that suppressing HAP1 level diminished the membrane expression of the L-type calcium channel (Cav1.2), which can regulate Ca2+ influx and then influence brain-derived neurotrophic factor (BDNF) synthesis and release. Furthermore, SNI-induced activation of astrocytes and microglia notably decreased in HAP1-deficient mice. These results indicate that HAP1 deficiency might attenuate pain responses. Collectively, our results suggest that HAP1 in dorsal horn and DRG neurons regulates Cav1.2 surface expression, which in turn reduces neuronal excitability, BDNF secretion, and inflammatory responses and ultimately influences neuropathic pain progression.
Effect of Premedication With Pronase Before Upper Gastrointestinal Endoscopy
Authors: Li Jun , Wang Lan , Hu Weiling , Wu Jiaguo , Chen Hongtan , Wang Liangjing , Lv Bin , Zhang Xiaofeng , Dai Yiyang , Huang Zhiming , Cai Zhenzhai , Ding Xiaoyun , Ye Liping , Ding Jin , Xiang Lijuan , Ye Bin , Chen Shujie , Si Jianmin 
Published: December 2022

Objectives:
This study aimed to confirm whether premedication with pronase before endoscopy improves mucosal visualization and increases precancerous lesion and cancer lesion detection rates.

Materials and Methods:
From June 2018 to April 2019, out-patients scheduled for endoscopy from 13 hospitals were screened to be randomly allocated in a 2:1 ratio to premedication with pronase (group A) and water (group B). The primary endpoint was mucosal visibility scores, and the secondary endpoint was precancerous and cancer lesion detection rates. This trial was registered at Chinese Clinical Trial Registry, and the registration number was ChiCTR1800016853.

Results:
Group A showed significantly lower mucosal visibility scores (better mucosal visibility) of esophagus, stomach, and duodenum than group B, with all P-values <0.001. The overall cancer detection rates between group A and group B were 0.83 and 1.08%, and overall detection rates of precancerous and cancer lesion were 4.4 and 4.9%, both without significant difference (P=1.000 and 0.824). In addition, the flushing volume (milliliter) of group A (10.52±23.41) was less than group B (36.30±52.11) (P<0.001), and the flushing frequency of group A (0.46±1.01) was fewer than group B (1.62±2.12) (P<0.001).

Conclusions:
Premedication with pronase could achieve better mucosal visibility and decrease flushing frequency and volume, but may not increase lesion detection rates.
Hepatocellular Adenoma: A Case Report, Current Updates on Subtyping, and Diagnostic Pitfalls
Authors: Jung Geunyoung , Liu Yongjun 
Published: December 2022

Abstract
Hepatocellular adenoma (HCA) is a benign liver neoplasm that typically arises in the noncirrhotic liver. Based on molecular findings, HCA can be subclassified into the following subtypes: hepatocyte nuclear factor 1α–inactivated HCA, inflammatory HCA, β-catenin–activated HCA, sonic hedgehog-activated HCA, and unclassified HCA. Mixed β-catenin–activated inflammatory HCA may rarely occur. We report a case of HCA that was initially diagnosed as inflammatory HCA on a biopsy but finally was confirmed to be β-catenin–activated inflammatory HCA on the resection specimen. Most recent updates on molecular classification, key histologic features of each subtype, and common diagnostic pitfalls are discussed.
Histomorphological Subtypes of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: Review and Update
Authors: Hwang Yoon Jung , Kim Haeryoung 
Published: December 2022

Abstract
Primary liver cancers comprise a heterogeneous group of neoplasms, with the 2 main entities being hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Over the past decades, HCC and iCCA have been recognized to be heterogeneous in morphology, molecular features, and biological behavior, and the most recent World Health Organization classification of digestive system tumors describes various histomorphological subtypes of HCC and iCCA, some of which also have characteristic molecular features, clinical correlates, and prognostic implications. In this review, we discuss 4 recently described subtypes of HCC and iCCA—macrotrabecular HCC, steatohepatitic HCC, scirrhous HCC, and small duct iCCA—based on a series of cases.
A Case Review on Combined Hepatocellular Cholangiocarcinoma
Authors: Kondo Reiichiro , Akiba Jun , Yano Hirohisa 
Published: December 2022

Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver tumor with neoplastic components of both hepatocytic and cholangiocytic differentiation within the same tumor, such as the case reported herein. There is a need to standardize the pathological diagnosis of cHCC-CCA and to improve the concordance of diagnosis among pathologists based on consensus paper because of its histological and phenotypic diversity that leads to confusion in terminology and classification. This case review addresses the terminology, classification, and clinical and pathological characteristics of cHCC-CCA and its differential diagnosis.
SNHG1 alleviates the oxidative stress and inflammatory response in traumatic brain injury through regulating miR-377-3p/DUSP1 axis
Authors: Jiao Wei , Jiang Lili , Zhang Yulei 
Published: December 2022

Objectives
To investigate the role of short nucleolar RNA host gene 1 (SNHG1) in regulating inflammation and brain injury in traumatic brain injury (TBI).

Methods
The Feeney’s free-falling method was used to induce moderate TBI model in mice. Lipopolysaccharide (LPS) was employed to construct the microglia in vitro. Reverse transcription-PCR (RT-PCR) was conducted to monitor expression of SNHG1, microRNAs (miR)-377-3p, oxidative and inflammatory factors. TdT-mediated dUTP nick end labeling and immunohistochemistry were adopted to determine neuronal cell apoptosis. Flow cytometry was conducted to measure apoptosis. Moreover, Bax, Bcl2, Caspase3, dual-specific phosphatase-1 (DUSP1)/mitogen-activated protein kinase/NF-KB were tested by western blot. Furthermore, bioinformatics, dual-luciferase assay and RNA-binding protein immunoprecipitation experiment were implemented to verify the targeting relationship among SNHG1, miR-377-3p and DUSP1.

Results
SNHG1 was knocked down, while miR-377-3p was overexpressed in TBI mice and lipopolysaccharide-induced microglia. Meanwhile, overexpressing SNHG1 reduced neuronal damage and weakened the oxidative stress and inflammation in TBI on matter in vivo or in vitro. Additionally, overexpressing SNHG1 attenuated miR-377-3p-mediated inflammatory factors, oxidative stress and neuronal damage. Moreover, miR-377-3p was the target of SNHG1 and DUSP1.

Conclusions
This study provides a better understanding of the SNHG1/miR-377-3p/DUSP1 axis in regulating the development of TBI, which is helpful to formulate a treatment plan for TBI.
Effects of the genetic knockout of the β-1,3-galactosyltransferase 2 on spatial learning and neurons in the adult mouse hippocampus and somatosensory cortex
Authors: Chen Xiaojie , Wang Pan , Ren Lili , Deng Xinyang , Yin Xuechen , Zhang Luyun , Li Qingyu , Bai Lina , Li Xiaojia , Wang Peng , Bi Jing 
Published: December 2022

Objective
Glycosyltransferases contribute to the biosynthesis of glycoproteins, proteoglycans and glycolipids and play essential roles in various processes in the brain, such as learning and memory, brain development, neuronal survival and neurodegeneration. β-1,3-galactosyltransferase 2 (B3galt2) belongs to the β-1,3-galactosyltransferase gene family and is highly expressed in the brain. Recent studies have indicated that B3galt2 plays a vital role in ischemic stroke through several signaling pathways in a mouse model. However, the function of B3galt2 in the brain remains poorly understood.

Methods
The genotypes of mice were determined by PCR. To verify B3galt2 expression in an adult mouse brain, X-gal staining was performed in 6-month-old B3galt2 heterozygous (B3galt2+/−
) mice. Using adult B3galt2 homozygous (B3galt2−/−
), heterozygous and wild-type (WT) littermates, spatial learning and memory were determined by the Morris Water Maze test, and neurotoxicity and synaptic plasticity were examined by immunofluorescence.

Results
B3galt2 was highly expressed in the adult mouse hippocampus and cortex, especially in the hippocampal dentate gyrus. Compared to that of WT mice, the spatial learning ability of adult B3galt2−/−
mice was impaired. B3galt2 mutations also caused neuronal loss and synaptic dysfunction in the hippocampus and somatosensory cortex, and these changes were more obvious in B3galt2−/−
mice than in B3galt2+/−
mice.

Conclusions
The findings indicate that B3galt2 plays an important role in cognitive function, neuronal maintenance and synaptic plasticity in the adult mouse brain. This study suggests that genetic and/or pharmacological manipulation of glycosyltransferases may be a novel strategy for elucidating the mechanism of and managing various brain disorders.
Exploring B and T-cell epitopes for constructing a Novel Multiepitope vaccine to combat emerging Monkeypox infection: A Reverse Vaccinology approach
Authors: Yousaf Hassan , Naz Anam 
Published: December 2022

AbstractBackgroundWhile the whole mankind is resurrecting from the recent Covid-19 pandemic, new cases of the monkeypox virus have been reported inflicting serious threats to the public health. Monkeypox is a newly emerging, zoonotic orthopoxvirus having similar symptoms as that of the smallpox. So far, no approved treatment and therapeutics are in line to fight the infection.MethodologyTherefore, in the present study, we have deployed a computational pipeline. We have retrieved the helper T-cell lymphocytes, cytotoxic T-cell and B-cell inducing epitopes by targeting the cell surface binding protein of the virus and further filtered the high-quality peptides based on their immunogenicity, antigenicity and allergenicity. After subsequent steps, we constructed and validated the tertiary structure of vaccine and analyzed its molecular interactions with toll like receptor-2 (TLR-2) and toll like receptor-4 (TLR-4) through molecular docking and the atomic movements and stability through molecular dynamics simulation approach. Moreover, C-IMMSIM server was used to evaluate the immune response triggering capacity of the chimeric vaccine through the immunoglobin profile.ConclusionThe conductedin silicostudy concludes that the surface protein of monkeypox virus is one of the major culprit antigens in mediating the disease. Hence, our study will aid in the better formulation of vaccines in future by targeting the suitable drug or vaccine candidates.
Missense variant interaction scanning reveals a critical role of the FERM-F3 domain for tumor suppressor protein NF2 conformation and function
Authors: Moesslacher Christina S. , Woodsmith Jonathan , Auernig Elisabeth , Feichtner Andreas , Jany-Luig Evelyne , Jehle Stefanie , Worseck Josephine M. , Heine Christian L. , Stefan Eduard , Stelzl Ulrich 
Published: December 2022

AbstractNF2 (Neurofibromine 2, merlin) is frequently inactivated in cancer, where its NF2 tumor suppressor functionality is tightly coupled to protein conformation. How NF2 conformation is regulated and how NF2 conformation influences tumor suppressor activity is a largely open question. Here we systematically characterized three NF2 conformation-dependent protein interactions utilizing deep mutational scanning interaction perturbation analyses. We identified two regions in NF2 with clustered mutations which affected conformation dependent protein interactions. NF2 variants in the F3 subdomain and the α3H helix region substantially modulated NF2 conformation and homomerization. Mutations in the F3 subdomain altered proliferation in three cell lines and matched patterns of disease mutations in neurofibromatosis. This study highlights the power of systematic mutational interaction perturbation analysis to identify missense variants impacting NF2 conformation and provides insight into NF2 tumor suppressor function.
Directed evolution of generalist biosensors for single ring aromatics
Authors: Cole Hannah O. , Kosonocky Clayton W. , Schechter Mason , Gollihar Jimmy , Ellington Andrew D. , d’Oelsnitz Simon 
Published: December 2022

AbstractBiosensors can accelerate the engineering of new biosynthetic pathways. Phloroglucinol is a platform chemical of wide utility that can be produced at limited titers inEscherichia coli. Starting from the TetR family repressor RolR that is responsive to the related compound resorcinol, we were able to employ a combined selection and screen to identify variants that had greatly improved activities with phloroglucinol (EC50 for phloroglucinol of 131 uM, relative to an estimated 42 mM for wild-type RolR). The variants obtained were further screened with a panel of similar single ring aromatics, and several were found to be generalists, consistent with the hypothesis that both natural and directed evolution tend to first create semi-specific pockets prior to further optimization for new function
A deep active learning-based and crowdsourcing-assisted solution for named entity recognition in Chinese historical corpora
Authors: Yan Chengxi , Tang Xuemei , Yang Hao , Wang Jun 
Published: December 2022

PurposeThe majority of existing studies about named entity recognition (NER) concentrate on the prediction enhancement of deep neural network (DNN)-based models themselves, but the issues about the scarcity of training corpus and the difficulty of annotation quality control are not fully solved, especially for Chinese ancient corpora. Therefore, designing a new integrated solution for Chinese historical NER, including automatic entity extraction and man-machine cooperative annotation, is quite valuable for improving the effectiveness of Chinese historical NER and fostering the development of low-resource information extraction.Design/methodology/approachThe research provides a systematic approach for Chinese historical NER with a three-stage framework. In addition to the stage of basic preprocessing, the authors create, retrain and yield a high-performance NER model only using limited labeled resources during the stage of augmented deep active learning (ADAL), which entails three steps—DNN-based NER modeling, hybrid pool-based sampling (HPS) based on the active learning (AL), and NER-oriented data augmentation (DA). ADAL is thought to have the capacity to maintain the performance of DNN as high as possible under the few-shot constraint. Then, to realize machine-aided quality control in crowdsourcing settings, the authors design a stage of globally-optimized automatic label consolidation (GALC). The core of GALC is a newly-designed label consolidation model called simulated annealing-based automatic label aggregation (“SA-ALC”), which incorporates the factors of worker reliability and global label estimation. The model can assure the annotation quality of those data from a crowdsourcing annotation system.FindingsExtensive experiments on two types of Chinese classical historical datasets show that the authors’ solution can effectively reduce the corpus dependency of a DNN-based NER model and alleviate the problem of label quality. Moreover, the results also show the superior performance of the authors’ pipeline approaches (i.e. HPS + DA and SA-ALC) compared to equivalent baselines in each stage.Originality/valueThe study sheds new light on the automatic extraction of Chinese historical entities in an all-technological-process integration. The solution is helpful to effectively reducing the annotation cost and controlling the labeling quality for the NER task. It can be further applied to similar tasks of information extraction and other low-resource fields in theoretical and practical ways.
Exploring the perspectives of engineering undergraduates on employability and employability building activities
Authors: Howell Simon , Hall Wayne , Geelan David 
Published: December 2022

PurposeThis study was conducted to gain a better understanding of engineering students' perceptions of the meaning of employability and the activities that contribute to employability development.Design/methodology/approachA survey was used to take a cross-section of student perspectives at key stages in the degree, and was followed by a series of focus groups to further explore student opinions on employability. Responses to selected open-ended questions and relevant sections of focus group transcripts were analysed using a thematic analysis approach.FindingsIt was found that students have different perspectives on the meaning of employability, with the majority describing employability as having the right skills, attributes or competencies. Employability development activities were integrated into three broad categories: developing engineering knowledge, skills and industry experience; career building and industry awareness; and degree progression and completion. Participants also identified barriers to employability development and suggested areas for improvement.Practical implicationsThe study recommends university staff ensure there is a shared understanding of employability within the student cohort by explicitly reframing employability as being about becoming a professional and that students are repeatedly exposed to the relevant set of industry competencies or standards. The study also outlines a range of activities that students connect to their employability development.Originality/valueThe findings of this study will assist university staff across the sector to make decisions about how they can best support employability development in their undergraduate students.
Ties that bind: leveraging horizontal and vertical ties within an entrepreneurial community in cross-promotional social media marketing
Authors: Dowin Kennedy Elena , Horky Alisha Blakeney , Kaufmann Ethan 
Published: December 2022

Purpose
The purpose of this paper is to examine how small and medium enterprises (SMEs) within an entrepreneurial community engage in cross-promotion on social media via Facebook. This paper specifically examines how SME community members leverage their horizontal and vertical ties to generate publicity, improve brand perceptions and drive traffic to themselves or community events.

Design/methodology/approach
This paper uses a qualitative approach, examining 1,025 Facebook posts from 27 members of an entrepreneurial community in the southeast USA to develop typologies of posting strategies, post purposes and post functions.

Findings
This paper finds that in the entrepreneurial community of interest, many members engage in cross-promotion via social media at various frequencies and with distinctive purposes. This paper identifies five distinct patterns of cross-promotion – quality signaling, traffic driving, community amplifying, hybrid cross-promotion and infrequent engagement. This paper also notes differences between cross-promotional strategies of vertical and horizontal partners.

Originality/value
This paper advances understanding of social media marketing and identifies key patterns of SME social media behavior. Although previous research has noted the importance of social media for SMEs, there has been little research regarding posting strategies being used by these firms. Further, to this point, there has not been a framework to understand how firms can use social media to cross-promote one another. This paper seeks to begin filling these gaps by providing a useful framework that can be used by SMEs in coordinating their social media posting strategies as well as by researchers studying SME cross-promotion.
An architecture for a net zero world: Global climate governance beyond the epoch of failure
Authors: Burke Anthony 
Published: December 2022

AbstractIn the wake of the 2021 Glasgow meeting of the Paris Agreement, where states embedded a 2050 pathway to net zero that will overshoot the Earth's remaining carbon budget for 1.5°C, attention is turning to the flaws of the UN Framework Convention on Climate Change. This article highlights ways in which it blocks effective climate action, which has been acknowledged by states who are now pursuing voluntary and nonbinding initiatives on coal, forests, and oil and gas. The article assesses new proposals for treaties on deforestation, the elimination of coal, and a fossil fuel nonproliferation treaty. It argues that states should take these proposals to the UN General Assembly and adopt them as binding treaties consistent with holding global heating at 1.5°C. Following the model of the Nuclear Weapons Convention it further argues that these treaties should be folded into a full Greenhouse Convention, supported by a powerful International Climate Agency, to secure a net zero world. Drawing upon new proposals for an Earth‐centric law that takes in the totality of social‐natural processes at the planetary scale, these proposals could form part of a reformed international legal architecture that could be equal to the diabolical governance challenges of the Anthropocene.