bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct transcriptional programs stratify ovarian cancer cell lines into the five major histological subtypes
Authors: Barnes Bethany M. , Nelson Louisa , Tighe Anthony , Burghel George J. , Lin I-Hsuan , Desai Sudha , McGrail Joanne C. , Morgan Robert D. , Taylor Stephen S. 
Published: September 2021

Abstract
Background
Epithelial ovarian cancer (OC) is a heterogenous disease consisting of five major histologically distinct subtypes: high-grade serous (HGSOC), low-grade serous (LGSOC), endometrioid (ENOC), clear cell (CCOC) and mucinous (MOC). Although HGSOC is the most prevalent subtype, representing 70–80% of cases, a 2013 landmark study by Domcke et al. found that the most frequently used OC cell lines are not molecularly representative of this subtype. This raises the question, if not HGSOC, from which subtype do these cell lines derive? Indeed, non-HGSOC subtypes often respond poorly to chemotherapy; therefore, representative models are imperative for developing new targeted therapeutics.

Methods
Non-negative matrix factorisation (NMF) was applied to transcriptomic data from 44 OC cell lines in the Cancer Cell Line Encyclopedia, assessing the quality of clustering into 2–10 groups. Epithelial OC subtypes were assigned to cell lines optimally clustered into five transcriptionally distinct classes, confirmed by integration with subtype-specific mutations. A transcriptional subtype classifier was then developed by trialling three machine learning algorithms using subtype-specific metagenes defined by NMF. The ability of classifiers to predict subtype was tested using RNA sequencing of a living biobank of patient-derived OC models.

Results
Application of NMF optimally clustered the 44 cell lines into five transcriptionally distinct groups. Close inspection of orthogonal datasets revealed this five-cluster delineation corresponds to the five major OC subtypes. This NMF-based classification validates the Domcke et al. analysis, in identifying lines most representative of HGSOC, and additionally identifies models representing the four other subtypes. However, NMF of the cell lines into two clusters did not align with the dualistic model of OC and suggests this classification is an oversimplification. Subtype designation of patient-derived models by a random forest transcriptional classifier aligned with prior diagnosis in 76% of unambiguous cases. In cases where there was disagreement, this often indicated potential alternative diagnosis, supported by a review of histological, molecular and clinical features.

Conclusions
This robust classification informs the selection of the most appropriate models for all five histotypes. Following further refinement on larger training cohorts, the transcriptional classification may represent a useful tool to support the classification of new model systems of OC subtypes.
Factors associated with medical complications after body art among Israeli adults: a retrospective study
Authors: Korn Liat , Bonny-Noach Hagit , Koren Gideon , Nissanholtz-Gannot Rachel 
Published: September 2021

Abstract
Introduction
Body-art, including tattoos and piercings, is steadily increasing world-wide but with relatively limited reporting of adverse outcomes. The objective of the present study was to identify correlates that would facilitate a preventative strategy to minimize adverse effects of body-art.

Methods
We examined patterns of body-art, health risk and perceptions among 921 participants (54% female, mean age of 35; SD = 10.8) through in-person questionnaire.

Results
A significantly lower frequency of those with body-art acknowledged that not all venues (parlors, clinics, etc.) are safe in terms of health and hygiene (84.7%t vs. 96.6%, p < .001) as compared to those without body-art. Similarly, knowledge of the need for a Ministry of Health certification was reported with lower frequency (77.2% vs. 94.5%, p < .001) among those with body-art. Those who experienced medical complications reported higher frequencies of smoking cigarettes and hookah as well as using ecstasy (MDMA). The risk of medical complication after body-art was 4 times higher in those who used ecstasy (OR = 3.97; CI 1.0–14.4; p < 0.05). In addition, it was more than 3 times higher for street or home tattooing as compared to studio or a licensed medical center (OR = 3.59; CI 1.32–9.76; p < .01), as well as almost 3 times higher among those who did not receive information before performing body-art (OR = 2.70; CI 1.05–6.92; p < .05) and who had somebody other than themselves decide on the body-art design (OR = 2.68; CI 1.00–7.19; p < .05).

Conclusions
A targeted informational-preventative program should be developed, informed by the risks highlighted in this study. In addition, it would be necessary to draft policies related to regulation and enforcement in order to more effectively manage body-art service provision. The Ministry of Health should supervise and guide tattooists and practitioners regarding the health risks of body-art and offer training and raise awareness among potential clients.
Valproic acid autoinduction: a case-based review
Authors: Bennett Sean , Shad Mujeeb U. 
Published: September 2021

AbstractAlthough valproic acid (VPA) induces the metabolism of multiple other drugs, the clinical reports of VPA autoinduction are rare. A comprehensive literature search yielded only one published case series, which provided the rationale to conduct a review of the published cases along with a new case of VPA autoinduction. Although there may be myriad of reasons for lack of published cases of VPA autoinduction, potential underreporting may be one of the core reasons. Lack of understanding into the highly complex metabolism of VPA may also make it difficult to recognize and report VPA autoinduction. However, it is important to mention that in addition to autoinduction increased elimination of VPA may be mediated by several pharmacokinetic (PK) factors, such as drug interactions, genetic polymorphisms of metabolic enzymes, and protein displacement reactions. As VPA is metabolized by multiple metabolic pathways, the risk for drug interactions is relatively high. There is also a growing evidence for high genetic inducibility of some enzymes involved in VPA metabolism. Protein displacement reactions with VPA increase the biologically active and readily metabolizable free fraction and pose a diagnostic challenge as they are usually not requested by most clinicians. Thus, monitoring of free fraction with total VPA levels may prevent clinically serious outcomes and optimize VPA treatment in clinically challenging patients. This case-based review compares the clinical data from three published cases and a new case of VPA autoinduction to enhance clinicians' awareness of this relatively rare but clinically relevant phenomenon along with a discussion of potential underlying mechanisms.
Exploring tertiary EFL practitioners’ knowledge base component of assessment literacy: implications for teacher professional development
Authors: Latif Muhammad Wasim 
Published: September 2021

AbstractLanguage teachers’ assessment literacy has been a much debated subject in the educational arena recently. Teachers’ assessment knowledge base and skills, important aspects of their assessment literacy, have been extensively investigated at the school level; however, the research on this subject in the tertiary EFL context remains underdeveloped. This study reports findings of tertiary EFL teachers’ assessment literacy in terms of their assessment knowledge base in the context of Saudi Arabia. The study is informed by sociocultural theoretical background, with pragmatism as the philosophical underpinning. It uses an adapted instrument called Classroom Assessment Literacy Questionnaire, and the data are obtained from 80 questionnaire respondents. The statistical analysis of the data revealed that tertiary EFL teachers’ current assessment knowledge base is very limited and not consistent with the contemporary trends and approaches to educational assessment in terms of their preparation and readiness for the continuously mounting challenges posed by classroom-based assessments. These results indicating gaps and inadequacies in tertiary EFL practitioners’ assessment literacy have strong implications for teacher development in the area of assessment and testing at the level of policy, practice and professional development programmes.
A facile synthesis of GO/CuO-blended nanofiber sensor electrode for efficient enzyme-free amperometric determination of glucose
Authors: Gijare Medha , Chaudhari Sharmila , Ekar Satish , Garje Anil 
Published: September 2021

AbstractThe development of biosensors with innovative nanomaterials is crucial to enhance the sensing performance of as-prepared biosensors. In the present research work, we prepared copper (II) oxide (CuO) and graphene oxide (GO) composite nanofibers using the hydrothermal synthesis route. The structural and morphological properties of as-prepared GO/CuO nanofibers were analyzed using an X-ray diffractometer, field-emission scanning, energy dispersive X-ray analysis, Fourier transmission infrared spectroscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy. The results indicated GO/CuO nanofibers exhibit nanosized diameters and lengths in the order of micrometers. These GO/CuO nanofibers were employed to prepare non-enzymatic biosensors (GO/CuO nanofibers/FTO (fluorine-doped tin oxide)) modified electrodes for enhanced glucose detection. The sensing performance of the biosensors was evaluated using linear sweep voltammetry (LSV) and chronoamperometry in phosphate buffer solution (PBS). GO/CuO/FTO biosensor achieved high sensitivity of 1274.8 μA mM−1cm−2having a linear detection range from 0.1 to 10 mM with the lower detection limit (0.13 μM). Further, the prepared biosensor showed good reproducibility repeatability, excellent selectivity, and long-time stability. Moreover, the technique used for the preparation of the GO/CuO composite is simple, rapid, cost-effective, and eco-friendly. These electrodes are employed for the detection of glucose in blood serum with RSD ~ 1.58%.
Structural characteristics of the bone surrounding dental implants placed into the tail-suspended mice
Authors: Otsu Yuto , Matsunaga Satoru , Furukawa Takehiro , Kitamura Kei , Kasahara Masaaki , Abe Shinichi , Nakano Takayoshi , Ishimoto Takuya , Yajima Yasutomo 
Published: September 2021

Abstract
Background
There are many unclear points regarding local structural characteristics of the bone surrounding the implant reflecting the mechanical environment.

Purpose
The purpose of this study is to quantitatively evaluate bone quality surrounding implants placed into the femurs of mice in an unloading model, and to determine the influence of the mechanical environment on bone quality.

Methods
Twenty 12-week-old male C57BL6/NcL mice (n = 5/group) were used as experimental animals. The mice were divided into two groups: the experimental group (n = 10) which were reared by tail suspension, and the control group (n = 10) which were reared normally. An implant was placed into the femur of a tail-suspended mouse, and after the healing period, they were sacrificed and the femur was removed. After micro-CT imaging, Villanueva osteochrome bone stain was performed. It was embedded in unsaturated polyester resin. The polymerized block was sliced passing through the center of the implant body. Next, 100-μm-thick polished specimens were prepared with water-resistant abrasive paper. In addition to histological observation, morphometric evaluation of cancellous bone was performed, and the anisotropy of collagen fibers and biological apatite (BAp) crystals was analyzed.

Results
As a result, the femoral cortical bone thickness and new peri-implant bone mass showed low values in the tail suspension group. The uniaxial preferential orientation of BAp c-axis in the femoral long axis direction in the non-implant groups, but biaxial preferential orientation of BAp c-axis along the long axis of implant and femoral long axis direction were confirmed in new bone reconstructed by implant placement. Collagen fiber running anisotropy and orientation of BAp c-axis in the bone surrounding the implant were not significantly different due to tail suspension.

Conclusions
From the above results, it was clarified that bone formation occurs surrounding the implant even under extremely low load conditions, and bone microstructure and bone quality adapted to the new mechanical environment are acquired.
A meta-analysis of observational studies on anticholinergic burden and fracture risk: evaluation of conventional burden scales
Authors: Ogawa Yukari , Hirai Toshinori , Mihara Kiyoshi 
Published: September 2021

Abstract
Background
Anticholinergic burden potentially increases the risk of fracture. Although there are various anticholinergic burden scales, little is known about the inter-scale compatibility regarding the relationship of anticholinergic burden with fracture risk. We performed meta-analysis to examine the association of fracture risk with anticholinergic burden measured using various scales.

Methods
Primary literature was retrieved from PubMed (1966 to March, 2021), the Cochrane Library (1974 to March, 2021), Scopus (1970 to March, 2021), and Ichushi-web (1983 to March, 2021). Cohort and case-control studies that evaluated the association between any fracture and anticholinergic drugs were included. Additionally, we included studies in which patients were administered anticholinergic drugs included on the anticholinergic risk scale (ARS), anticholinergic cognitive burden (ACB), anticholinergic drug scale, or drug burden index-anticholinergic component. Random effects models were used to calculate pooled relative risk (RR) and 95% confidence interval (CI) due to heterogeneity among the studies. Publication bias was examined by funnel plots and the Begg’s test.

Results
A total of 49 datasets from 10 studies were included in the meta-analysis. Six of the 10 studies included only patients aged over 65 years, who accounted for 93% of the total study population (453,186/487,247). Meta-analysis indicated a positive relationship between use of anticholinergic drugs and fracture risk, regardless of the anticholinergic burden scale used. However, the relationship between anticholinergic burden and fracture risk varied depending on the scale used. Fracture risk increased linearly with increasing anticholinergic burden measured using ARS. ARS 1 point was associated with 28% increase in fracture risk, ARS 1–2 point(s) with 39%, ARS 2 points with 54%, ARS 3 points with 66%, and ARS ≥ 4 points with 77%. On the other hand, ACB 1 point and ACB 2 points were associated with similar fracture risk (pooled RR [95% CI]: overall; 1.28 [1.18–1.39], 1 point; 1.12 [1.06–1.18], 2 points; 1.15 [1.08–1.23]).

Conclusions
This result suggests that the relationship between anticholinergic drug burden and fracture risk may differ depending on the anticholinergic burden scale used.
Stability of clonidine hydrochloride in an oral powder form compounded for pediatric patients in Japan
Authors: Saito Jumpei , Hanawa Takehisa , Matsumoto Takahiro , Yoshikawa Nozomi , Harada Tsutomu , Iwahashi Kana , Nakamura Hidefumi , Yamatani Akimasa 
Published: September 2021

Abstract
Background
Clonidine hydrochloride is used to treat sedative agent withdrawals, malignant hypertension, and anesthesia complications. Clonidine is also prescribed off-label to pediatric patients at a dose of 1 μg/kg. The commercially available enteral form of clonidine, Catapres® tablets, is often compounded into a powder form by pharmacists to achieve dosage adjustments for administration to pediatric patients. However, the stability and quality of compounded clonidine powder have not been verified. The objectives of this study were to formulate a 0.2 mg/g oral clonidine hydrochloride powder and assess the stability and physical properties of this compounded product in storage.

Methods
A 0.2 mg/g clonidine powder was prepared by adding lactose monohydrate to crushed and filtrated clonidine tablets. The powder was stored in polycarbonate amber bottles or coated paper packages laminated with cellophane and polyethylene. The stability of clonidine at 25 °C ± 2 °C and 60% ± 5% relative humidity was examined over a 120-d period in “bottle (closed),” “bottle (in use),” and “laminated paper” storage conditions. Drug dissolution and powder X-ray diffraction analysis were conducted to assess physicochemical stabilities. Validated liquid chromatography-diode array detection was used to detect and quantify clonidine and its degradation product, 2,6-dichloroaniline (2,6-DCA).

Results
Clonidine content was maintained between 90.0 and 110.0% of the initial contents in all packaging and storage conditions. After 120 d of storage, 2,6-DCA was not detected, and no crystallographic and dissolution changes were observed.

Conclusions
Compounded clonidine powder stability was maintained for 120 d at 25 °C ± 2 °C and 60% ± 5% relative humidity. This information may contribute to the management of clonidine compounded powder in community and hospital pharmacies in Japan.
The time-varying causal relationship between the Bitcoin market and internet attention
Authors: Zhang Xun , Lu Fengbin , Tao Rui , Wang Shouyang 
Published: September 2021

AbstractThe increasing attention on Bitcoin since 2013 prompts the issue of possible evidence for a causal relationship between the Bitcoin market and internet attention. Taking the Google search volume index as the measure of internet attention, time-varying Granger causality between the global Bitcoin market and internet attention is examined. Empirical results show a strong Granger causal relationship between internet attention and trading volume. Moreover, they indicate, beginning in early 2018, an even stronger impact of trading volume on internet attention, which is consistent with the rapid increase in Bitcoin users following the 2017 Bitcoin bubble. Although Bitcoin returns are found to strongly affect internet attention, internet attention only occasionally affects Bitcoin returns. Further investigation reveals that interactions between internet attention and returns can be amplified by extreme changes in prices, and internet attention is more likely to lead to returns during Bitcoin bubbles. These empirical findings shed light on cryptocurrency investor attention theory and imply trading strategy in Bitcoin markets.
Optimizing auditory input for foreign language learners through a verbotonal-based dichotic listening approach
Authors: Cai Xirui , Lian Andrew , Puakpong Nattaya , Shi Yaoping , Chen Haoqiang , Zeng Yizhen , Ou Jibing , Zheng Wei , Mo Yin 
Published: September 2021

AbstractThe quality of the physical language signals to which learners are exposed and which result in neurobiological activity leading to perception constitutes a variable that is rarely, if ever, considered in the context of language learning. It deserves some attention. The current study identifies an optimal audio language input signal for Chinese EFL/ESL learners generated by modifying the physical features of language-bearing audio signals. This is achieved by applying the principles of verbotonalism in a dichotic listening context. Low-pass filtered (320 Hz cut-off) and unfiltered speech signals were dichotically and diotically directed to each hemisphere of the brain through the contralateral ear. Temporal and spatial neural signatures for the processing of the signals were detected in a combined event-related potential (ERP) and functional magnetic resonance imaging (fMRI) experiment. Results showed that the filtered stimuli in the left ear and unfiltered in the right ear (FL-R) configuration provided optimal auditory language input by actively exploiting left-hemispheric dominance for language processing and right-hemispheric dominance for melodic processing, i.e., each hemisphere was fed the signals that it should be best equipped to process—and it actually did so effectively. In addition, the filtered stimuli in the right ear and unfiltered in the left ear (L-FR) configuration was identified as entirely non-optimal for language learners. Other outcomes included significant load reduction through exposure to both-ear-filtered FL-FR signals as well as the confirmation that non-language signals were recognized by the brain as irrelevant to language and did not trigger any language processing. These various outcomes will necessarily entail further research.
Experience of patients diagnosed as asymptomatic COVID-19 after dental treatment
Authors: Seo Ju-Yeon , Lee Sung-Tak , Choi So-Young , Kim Jin-Wook , Kwon Tae-Geon 
Published: September 2021

Abstract
Background
The potential risk of coronavirus disease 2019 (COVID-19) transmission from asymptomatic COVID-19 patients is a concern in dental practice. However, the impact of this risk is not well documented to date. This report describes our dental clinical experience with patients who did not exhibit symptoms of COVID-19 but were later confirmed as positive for COVID-19.

Case presentation
Of the 149,149 patients who visited the outpatient clinic of KNUDH and the 3291 patients who visited the Oral and Maxillofacial Surgery Clinic of KNUH, 3 were later confirmed as having COVID-1 between 1 February 2020 and 28 February 2021. Owing to close contact with these patients during their treatments, 46 dental and medical staff had to undergo quarantine from the date of the patients’ confirmation of COVID-19 infection.

Conclusion
The presented cases showed the potential existence of asymptomatic COVID-19 patients after dental treatment with aerosol-generating procedures. Clinicians should be aware of the infection prevention measures and try to protect healthcare personnel from secondary infection of COVID-19 during dental treatments.
Perspectives in modeling and model validation during analytical quality by design chromatographic method evaluation: a case study
Authors: Dong Yongzhi , Liu Zhimin , Li Charles , Pinter Emily , Potts Alan , Tadey Tanya , Weiser William 
Published: September 2021

AbstractDesign of experiments (DOE)-based analytical quality by design (AQbD) method evaluation, development, and validation is gaining momentum and has the potential to create robust chromatographic methods through deeper understanding and control of variability. In this paper, a case study is used to explore the pros, cons, and pitfalls of using various chromatographic responses as modeling targets during a DOE-based AQbD approach. The case study involves evaluation of a reverse phase gradient HPLC method by a modified circumscribed central composite (CCC) response surface DOE.Solid models were produced for most responses and their validation was assessed with graphical and numeric statistics as well as chromatographic mechanistic understanding. The five most relevant responses with valid models were selected for multiple responses method optimization and the final optimized method was chosen based on the Method Operable Design Region (MODR). The final method has a much larger MODR than the original method and is thus more robust.This study showcases how to use AQbD to gain deep method understanding and make informed decisions on method suitability. Discoveries and discussions in this case study may contribute to continuous improvement of AQbD chromatography practices in the pharmaceutical industry.