bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polyadenylation-related isoform switching in human evolution revealed by full-length transcript structure
Authors: Li Yumei , Shen Qing Sunny , Peng Qi , Ding Wanqiu , Zhang Jie , Zhong Xiaoming , An Ni A , Ji Mingjun , Zhou Wei-Zhen , Li Chuan-Yun 
Published: April 2021

AbstractRhesus macaque is a unique nonhuman primate model for human evolutionary and translational study, but the error-prone gene models critically limit its applications. Here, we de novo defined full-length macaque gene models based on single molecule, long-read transcriptome sequencing in four macaque tissues (frontal cortex, cerebellum, heart and testis). Overall, 8 588 227 poly(A)-bearing complementary DNA reads with a mean length of 14 106 nt were generated to compile the backbone of macaque transcripts, with the fine-scale structures further refined by RNA sequencing and cap analysis gene expression sequencing data. In total, 51 605 macaque gene models were accurately defined, covering 89.7% of macaque or 75.7% of human orthologous genes. Based on the full-length gene models, we performed a human–macaque comparative analysis on polyadenylation (PA) regulation. Using macaque and mouse as outgroup species, we identified 79 distal PA events newly originated in humans and found that the strengthening of the distal PA sites, rather than the weakening of the proximal sites, predominantly contributes to the origination of these human-specific isoforms. Notably, these isoforms are selectively constrained in general and contribute to the temporospatially specific reduction of gene expression, through the tinkering of previously existed mechanisms of nuclear retention and microRNA (miRNA) regulation. Overall, the protocol and resource highlight the application of bioinformatics in integrating multilayer genomics data to provide an intact reference for model animal studies, and the isoform switching detected may constitute a hitherto underestimated regulatory layer in shaping the human-specific transcriptome and phenotypic changes.
Machine learning builds full-QM precision protein force fields in seconds
Authors: Han Yanqiang , Wang Zhilong , Wei Zhiyun , Liu Jinyun , Li Jinjin 
Published: April 2021

Abstract
Full-quantum mechanics (QM) calculations are extraordinarily precise but difficult to apply to large systems, such as biomolecules. Motivated by the massive demand for efficient calculations for large systems at the full-QM level and by the significant advances in machine learning, we have designed a neural network-based two-body molecular fractionation with conjugate caps (NN-TMFCC) approach to accelerate the energy and atomic force calculations of proteins. The results show very high precision for the proposed NN potential energy surface models of residue-based fragments, with energy root-mean-squared errors (RMSEs) less than 1.0 kcal/mol and force RMSEs less than 1.3 kcal/mol/Å for both training and testing sets. The proposed NN-TMFCC method calculates the energies and atomic forces of 15 representative proteins with full-QM precision in 10–100 s, which is thousands of times faster than the full-QM calculations. The computational complexity of the NN-TMFCC method is independent of the protein size and only depends on the number of residue species, which makes this method particularly suitable for rapid prediction of large systems with tens of thousands or even hundreds of thousands of times acceleration. This highly precise and efficient NN-TMFCC approach exhibits considerable potential for performing energy and force calculations, structure predictions and molecular dynamics simulations of proteins with full-QM precision.
Potential risk factors for caesarean scar pregnancy: a retrospective case–control study
Authors: Gull B , Klerelid V , Jormeus A , Strandell A 
Published: April 2021

AbstractSTUDY QUESTIONWhat are the important risk factors for having a caesarean scar pregnancy (CSP)?SUMMARY ANSWERIndependent risk factors were smoking in the first trimester, higher parity, and previous caesarean section (CS) before the index caesarean delivery.WHAT IS KNOWN ALREADYA spectrum of risk factors for CSP has been suggested but not proven: parity, number of previous caesarean section, elective as opposed to emergency CS, IVF-pregnancy, breech presentation, previous gynaecological surgery as well as suture technique.STUDY DESIGN, SIZE, DURATIONThis retrospective case-control study included 31 women with a CSP during the period 2003–2018 treated at a tertiary care centre for gynaecology and reproduction. A control cohort of 8300 women with a history of a CS and a subsequent delivery during the same time period was formed.PARTICIPANTS/MATERIALS, SETTING, METHODSVariables describing demography, lifestyle factors, and reproductive and obstetric history were retrieved from medical records and the obstetric hospital database. Logistic regression analyses were applied to identify potential risk factors.MAIN RESULTS AND THE ROLE OF CHANCEIn a multivariable analysis, smoking in first trimester (adjusted odds ratio (OR) 3.03, 95% CI 1.01–9.07), higher parity (adjusted OR 1.30, 95% CI 1.03–1.64) and previous CS in addition to the preceding CS (adjusted OR 3.43, 95% CI 1.35–8.66) were independently predictive of a CSP. An elective CS at the index pregnancy was associated with an increased risk of CSP but did not remain significant in the multivariable analysis.LIMITATIONS, REASONS FOR CAUTIONCSP is a very rare phenomenon and several of the risk factor estimates are imprecise. Nevertheless, significant risk factors could be identified. Another limitation is the lack of electronically recorded details on suture techniques.WIDER IMPLICATIONS OF THE FINDINGSThe identified factors, namely higher parity and previous CS before the index caesarean section, are in accordance with previously suggested risk factors. Whether there is a true risk association between elective CS and future CSP needs to be investigated further. Smoking in the first trimester is a new finding, which has a plausible rationale. These factors should be recognised when counselling women after a caesarean delivery, particularly in a subsequent pregnancy with early complications.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by a grant from the Swedish state under the agreement between the Swedish government and the county councils the ALF-agreement (ALFGBG-720291). None of the authors has any conflict of interest to declare.
Semantic Aspects of National Varieties of Spanish in a Dictionary of Neologisms, theAntenario
Authors: Adelstein Andreína , Boschiroli Victoria de los Ángeles 
Published: April 2021

AbstractThe process of including neologisms in dictionaries has usually been studied in Spanish from the point of view of only one specific kind of dictionary, the general language dictionary, in terms of how the headword list and entries are updated. This fails to address a key question: What does the inclusion of new words in a dictiXNnary of neologisms actually involve? The aim of this paper is to explore problems of representation of neological variation by discussing how the tension between neologicity and geolectal variation is dealt with in a non-pan-Hispanic dictionary, the Antenario. Diccionario en línea de neologismos de las variedades del español (http://www.antenario.wordpress.com), designed and written by the Antenas Neológicas Network (https://www.upf.edu/web/antenas), and thus contribute to further the characterization of dictionaries of neologisms. We will focus the analysis on three aspects of lexicographic representation which are clearly linked to geolectal variation: degrees of neologicity, synonymy and polysemy.
The Use of Online Writing Tools by Learners of English: Evidence From a Process Corpus
Authors: Gilquin Gaëtanelle , Laporte Samantha 
Published: April 2021

Abstract
This paper examines the use of online writing tools by French-speaking learners of English based on the analysis of screen recordings of a free composition task that come from the Process Corpus of English in Education, a process corpus of learner writing. The study charts learners’ use of online resources by investigating how often learners resort to tools, which tools they use, and what effect the use of tools has on their texts. Results show considerable individual variation in the extent to which learners use online tools and a general propensity to rely on a limited range of tool types, most often bilingual tools. Overall, the use of tools helps learners improve their texts, but a close examination of their consultation behaviour also reveals shortcomings in learners’ strategies, such as a tendency to carry out single-word searches or a lack of critical thinking about the information that tools provide.
An analysis of hospital pharmacy practice in Namibia, based on FIP’s Basel Statements
Authors: Bare Andrea , Ivey Marianne , Kibuule Dan , Stevenson James G 
Published: April 2021

Abstract

Background
Sub-Saharan Africa, a region faced with a double challenge of infectious and non-communicable diseases requires strengthening of hospital pharmacy practice to improve treatment outcomes and patient safety.

Objectives
The objectives of this study were to assess the current state of pharmacy practice in hospitals in Namibia and to identify opportunities for expanding pharmacists’ role in addressing public health challenges and improving medicines use outcomes.

Methods
A survey utilized FIP’s self-assessment tool to evaluate current hospital pharmacy practice in Namibia against best practices articulated in the Basel Statements. The study was conducted among hospital pharmacists across Namibia. Quantitative and qualitative data were analysed using descriptive statistics and thematic analysis.

Key findings
The study was conducted in 24 hospital pharmacies across Namibia, the majority of which were public facilities (67%). Overall, current hospital pharmacy practice activities are focused on medicine procurement, preparation and distribution. The main barriers to optimal hospital pharmacy services are associated with limited human resources and collaboration across healthcare providers, as well as policy gaps.

Conclusions
There is a strong desire among hospital pharmacists to expand their contributions to improving medicines outcomes and solving public health problems. Namibia’s pharmacy educational system is a strength and should be utilized to continue advancing hospital pharmacy practice and medicines use. Therapeutics committees are usually part of each hospital’s structure and can be very effective for hospital-based policy change. The opportunity exists to optimize pharmacists’ contributions by utilizing the local therapeutics committees in combination with the educational system to advance hospital pharmacy practice in Namibia.
Performance Evaluation of an Automated Fentanyl Immunoassay
Authors: Tang Mei San , Lloyd Matthew , Williams Monette , Farnsworth Christopher W , Budelier Melissa M 
Published: April 2021

Abstract

Background
High-throughput fentanyl immunoassays have recently emerged for clinical use, but early reports have demonstrated relatively high false-positive rates. The purpose of this study was to compare 2 immunoassays, the ARK and ARK II fentanyl immunoassays, and to demonstrate the clinical impact of implementing the ARK II assay.

Methods
The ARK and ARK II fentanyl assays were performed on a Roche c 502 chemistry analyzer. Positive and negative percentage agreement was assessed for each assay with 112 residual patient specimens relative to liquid chromatography–tandem mass spectrometry (LC–MS/MS). Cross-reactivity was assessed with the primary metabolite, norfentanyl, and analogs acetylfentanyl, acrylfentanyl, and furanylfentanyl. The proportion of specimens that did not confirm was assessed retrospectively from the laboratory information system.

Results
The concordance of the ARK assay was 75% (kappa 0.46, 95%CI 0.28–0.63) and the ARK II was 93% (kappa 0.86, 95%CI 0.76–0.95) with LC–MS/MS. 30 ng/mL of norfentanyl was required for a positive result by ARK and 15 ng/mL by ARK II. Similar cross-reactivity was observed when fentanyl and norfentanyl were both present in the specimen and with fentanyl analogs. After implementing the ARK II assay, the proportion of specimens that did not confirm by LC–MS/MS decreased from 11.7% per month to 2.0% per month.

Conclusions
The ARK II fentanyl immunoassay has improved concordance relative to the original ARK fentanyl immunoassay using LC–MS/MS as the comparator method. Improved analyte specificity resulted in a reduced proportion of clinical samples that do not confirm.
How SARS-CoV-2 Transformed the Clinical Laboratory: Challenges and Lessons Learned
Authors: Tsai Jonathan M , Tolan Nicole V , Petrides Athena K , Kanjilal Sanjat , Brigl Manfred , Lindeman Neal I , Li Yen-Der , Tanasijevic Milenko J , Basu Sankha S , Melanson Stacy E F 
Published: April 2021

Abstract
The COVID-19 pandemic has made a devastating impact on global health and continues to challenge healthcare infrastructure and delivery. The clinical laboratories were no exception as they are responsible for diagnostic testing that dictates many clinical, infection control, and public health decisions. Information technology and laboratory management tools are critical assets for maintaining and adapting operations in response to crises. When utilized effectively, they promote the integration between the clinical laboratory specialties (e.g., chemistry, hematology, microbiology, and molecular pathology). During the COVID-19 pandemic, our systems and processes were strained due to high testing volumes, demand for rapid turnaround times, supply chain constraints, and constantly evolving testing algorithms and result interpretations as our knowledge of the virus and of diagnostics increased over time. In this report, we describe those challenges and subsequent adaptations made by each clinical laboratory section. We hope these details help to provide potential solutions and approaches for other hospitals facing COVID-19 surges or other future pandemics.
The Hidden Cost of Hemolyzed Blood Samples in the Emergency Department
Authors: Phelan Michael P , Ramos Christopher , Walker Laura E , Richland Gerald , Reineks Edmunds Z 
Published: April 2021

Abstract

Background
On average, patients with hemolyzed potassium samples spend about 1 h longer in the emergency department (ED), regardless of acuity level or disposition. We aimed to quantify the direct expenses associated with poor-quality preanalytic blood samples collected in the ED.

Methods
We created a simple table with a range of direct expenses (i.e., costs) and rates of hemolyzed sample draws, allowing for identification of potential high-level cost-of-care impact analysis. We included a range of costs informed by review of literature on the topic. Those costs range from $600 to $3000 per bed-hour. This amount was inflation adjusted from 1996 to 2020 (1.68 × [direct cost per visit] × [100 000 visits per year/365 days/24 h]). We provided a range of hemolysis incidence based on previously reported data.

Results
We showed that for an ED with 100 000 annual visits, a 40% draw rate for routine chemistries (including potassium), and a 10% hemolysis incidence, the direct cost impact of hemolysis waste is approximately $4 million/year as a result of the 1 h of added length of stay on average for a patient with a hemolyzed blood sample. This amount represents an annualized estimated cost of caring for a patient in the ED with an avoidable extended length of stay.

Conclusions
The financial burden of poor-quality blood samples can be estimated using cost per bed-hour and rate of sample failure. Similar methodology may identify additional QC issues with previously invisible financial implications.
The role of the pharmacist in contraception and pre-pregnancy management for women with diabetes: a study of patient and pharmacist perspectives
Authors: Garsia Kathryn , MacMillan Freya , Dune Tinashe , Simmons David 
Published: April 2021

Abstract

Objectives
Women with diabetes are at increased risk of adverse pregnancy outcomes compared to women with gestational diabetes (GDM) or no diabetes. Pregnancy outcomes are improved by specialist pre-pregnancy care. We aimed to explore pharmacists’ and women with diabetes’ perceptions of the roles and barriers to pharmacist participation in a diabetes contraception and pre-pregnancy program in South-Western Sydney (SWS).

Methods
The Diabetes Contraception and Pre-pregnancy Program (DCAPP) aims to reduce adverse pregnancy outcomes among women with diabetes. This includes awareness raising among, and through, pharmacists. Surveys to explore pharmacists’ roles in contraception and pre-pregnancy management (CPPM) were completed by SWS pharmacists and women with diabetes from diabetes clinics aged 18–50 years. Survey themes were then discussed in interviews and focus groups with pharmacists across Australia. Thematic analysis of transcripts was undertaken.

Key findings
Pharmacists were seen to have a role in diabetes health promotion, information distribution and referral to pre-pregnancy clinics. Pharmacists and women recognised the need for increased knowledge and educational materials about CPPM and effective awareness and coordination of CPPM services. Some pharmacists recognised deficits in their knowledge regarding diabetes in pregnancy, including CPPM and differences to GDM. Barriers to pharmacists’ involvement in CPPM included difficulty identifying applicable women and reluctance to initiate pregnancy planning and contraception conversations, often due to language and cultural barriers.

Conclusions
Pharmacists and women with diabetes see an important role for pharmacists in CPPM. Co-designed diabetes training for pharmacists and increased communication about DCAPP were seen important for ongoing implementation.
Crystal structures of N-terminally truncated telomerase reverse transcriptase from fungi
Authors: Zhai Liu-Tao , Rety Stephane , Chen Wei-Fei , Song Ze-Yu , Auguin Daniel , Sun Bo , Dou Shuo-Xing , Xi Xu-Guang 
Published: April 2021

Abstract
Telomerase plays critical roles in cellular aging, in the emergence and/or development of cancer, and in the capacity for stem-cell renewal, consists of a catalytic telomerase reverse transcriptase (TERT) and a template-encoding RNA (TER). TERs from diverse organisms contain two conserved structural elements: the template-pseudoknot (T-PK) and a helical three-way junction (TWJ). Species-specific features of the structure and function of telomerase make obtaining a more in-depth understanding of the molecular mechanism of telomerase particularly important. Here, we report the first structural studies of N-terminally truncated TERTs from Candida albicans and Candida tropicalis in apo form and complexed with their respective TWJs in several conformations. We found that Candida TERT proteins perform only one round of telomere addition in the presence or absence of PK/TWJ and display standard reverse transcriptase activity. The C-terminal domain adopts at least two extreme conformations and undergoes conformational interconversion, which regulates the catalytic activity. Most importantly, we identified a conserved tertiary structural motif, called the U-motif, which interacts with the reverse transcriptase domain and is crucial for catalytic activity. Together these results shed new light on the structure and mechanics of fungal TERTs, which show common TERT characteristics, but also display species-specific features.
Detailed analysis of the poorly studied northern open cluster NGC 1348 using multi-color photometry and GAIA EDR3 astrometry
Authors: Bisht Devendra , Zhu Qingfeng , Elsanhoury W H , Sariya Devesh P , Rangwal Geeta , Yadav Ramakant Singh , Durgapal Alok , Jiang Ing-Guey 
Published: April 2021

Abstract
The membership determination for open clusters in noisy environments of the Milky Way is still an open problem. In this paper, our main aim is to provide the membership probability of stars using proper motions and parallax values of stars using Gaia Third Data Release astrometry. Apart from the Gaia astrometry, we have also used other photometric data sets like the UKIRT Infrared Deep Sky Survey, WISE, the American Association of Variable Star Observers (AAVSO) Photometric All-Sky Survey, and Pan-STARRS1 in order to understand cluster properties from optical to mid-infrared regions. We selected 438 likely members with membership probabilities higher than $50\%$ and G ≤ 20 mag. We obtained the mean value of proper motion as μx = 1.27 ± 0.001 and μy = −0.73 ± 0.002 mas yr−1. The cluster’s radius is determined as ${7{^{\prime }_{.}}5}$ (5.67 pc) using radial density profile. Our analysis suggests that NGC 1348 is located at a distance of 2.6 ± 0.05 kpc. The mass function slope is found to be 1.30 ± 0.18 in the mass range 1.0–4.1 M⊙, which is in fair agreement with Salpeter’s value within the 1σ uncertainty. The present study validates that NGC 1348 is a dynamically relaxed cluster. We computed the apex coordinates (A, D) for NGC 1348 as (A°, D°) = (−23.°815 ± 0.°135, −22.°228 ± 0.°105). In addition, calculations of the velocity ellipsoid parameters (VEPs), matrix elements μij, direction cosines (lj, mj, nj), and the galactic longitude of the vertex have been conducted in this analysis.
Origin of Antecrysts in Igneous Rocks from the Salavat Range (NW Iran): an Explanation for the Geochemical Signature of Potassic Alkaline Rocks
Authors: Soltanmohammadi Azam , Grégoire Michel , Ceuleneer Georges , Benoit Mathieu , Bédard L Paul , Gouy Sophie , Rabinowicz Michel 
Published: April 2021

AbstractAbundant silica-undersaturated potassic lavas are found in the centre of the Turkish–Iranian plateau (NW Iran) as flows, pillows and dykes. They display abundant zoned clinopyroxene macrocrysts and xenoliths of igneous cumulates. We determined four types of zoned crystals (Type-I, -II, -III and -IV) on the basis of their composition and zoning patterns. Use of in situ compositional data, together with whole-rock major and trace elements and the isotopic signatures of the host lavas provided evidence for the derivation of the different types of zoned clinopyroxenes from at least two contrasting parental melts. Our findings are consistent with an origin of the ultrapotassic and sodic alkaline melts from the deep-seated compaction pockets inferred from our previous studies of the alkaline magmatism throughout the Turkish–Iranian plateau. The ultrapotassic melt, which accumulated at the top of the compaction pockets, eventually ponded close to the spinel–garnet mantle transition and generated colourless antecrysts (Type-I and Type-II) and clinopyroxenite cumulates. When the compaction pocket impinged on the continental lithosphere, interstitial melts segregated and flowed inside dykes where grass green antecrysts (Type-III) and zoned phenocrysts (Type-IVa) crystallized from a melt having a geochemical signature of sodic alkaline melt. Later, at the crustal level, melt crystallization processes produced Type-IVb zoned phenocrysts. Our results are at odds with the paradigm of potassic magmas in NW Iran being derived strictly from a single mantle source.
How Do We Semantically Individuate Natural Numbers?†
Authors: Buijsman Stefan 
Published: April 2021

ABSTRACTHow do non-experts single out numbers for reference? Linnebo has argued that they do so using a criterion of identity based on the ordinal properties of numerals. Neo-logicists, on the other hand, claim that cardinal properties are the basis of individuation, when they invoke Hume’s Principle. I discuss empirical data from cognitive science and linguistics to answer how non-experts individuate numbers better in practice. I use those findings to develop an alternative account that mixes ordinal and cardinal properties to provide a detailed (though not conclusively proven) answer to the question: how do we in fact semantically individuate numbers?