bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole-exome sequencing of 14 389 individuals from the ESP and CHARGE consortia identifies novel rare variation associated with hemostatic factors
Authors: Pankratz Nathan , Wei Peng , Brody Jennifer A , Chen Ming-Huei , de Vries Paul S , Huffman Jennifer E , Stimson Mary Rachel , Auer Paul L , Boerwinkle Eric , Cushman Mary , de Maat Moniek P M , Folsom Aaron R , Franco Oscar H , Gibbs Richard A , Haagenson Kelly K , Hofman Albert , Johnsen Jill M , Kovar Christie L , Kraaij Robert , McKnight Barbara , Metcalf Ginger A , Muzny Donna , Psaty Bruce M , Tang Weihong , Uitterlinden André G , van Rooij Jeroen G J , Dehghan Abbas , O'Donnell Christopher J , Reiner Alex P , Morrison Alanna C , Smith Nicholas L 
Published: May 2022

Abstract
Plasma levels of fibrinogen, coagulation factors VII and VIII and von Willebrand factor (vWF) are four intermediate phenotypes that are heritable and have been associated with the risk of clinical thrombotic events. To identify rare and low-frequency variants associated with these hemostatic factors, we conducted whole-exome sequencing in 10 860 individuals of European ancestry (EA) and 3529 African Americans (AAs) from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and the National Heart, Lung and Blood Institute’s Exome Sequencing Project. Gene-based tests demonstrated significant associations with rare variation (minor allele frequency &lt; 5%) in fibrinogen gamma chain (FGG) (with fibrinogen, P = 9.1 × 10−13), coagulation factor VII (F7) (with factor VII, P = 1.3 × 10−72; seven novel variants) and VWF (with factor VIII and vWF; P = 3.2 × 10−14; one novel variant). These eight novel rare variant associations were independent of the known common variants at these loci and tended to have much larger effect sizes. In addition, one of the rare novel variants in F7 was significantly associated with an increased risk of venous thromboembolism in AAs (Ile200Ser; rs141219108; P = 4.2 × 10−5). After restricting gene-based analyses to only loss-of-function variants, a novel significant association was detected and replicated between factor VIII levels and a stop-gain mutation exclusive to AAs (rs3211938) in CD36 molecule (CD36). This variant has previously been linked to dyslipidemia but not with the levels of a hemostatic factor. These efforts represent the largest integration of whole-exome sequence data from two national projects to identify genetic variation associated with plasma hemostatic factors.
Mice lacking MBNL1 and MBNL2 exhibit sudden cardiac death and molecular signatures recapitulating myotonic dystrophy
Authors: Lee Kuang-Yung , Seah Carol , Li Ching , Chen Yu-Fu , Chen Chwen-Yu , Wu Ching-I , Liao Po-Cheng , Shyu Yu-Chiau , Olafson Hailey R , McKee Kendra K , Wang Eric T , Yeh Chi-Hsiao , Wang Chao-Hung 
Published: May 2022

Abstract
Myotonic dystrophy (DM) is caused by expansions of C(C)TG repeats in the non-coding regions of the DMPK and CNBP genes, and DM patients often suffer from sudden cardiac death due to lethal conduction block or arrhythmia. Specific molecular changes that underlie DM cardiac pathology have been linked to repeat-associated depletion of Muscleblind-like (MBNL) 1 and 2 proteins and upregulation of CUGBP, Elav-like family member 1 (CELF1). Hypothesis solely targeting MBNL1 or CELF1 pathways that could address all the consequences of repeat expansion in heart remained inconclusive, particularly when the direct cause of mortality and results of transcriptome analyses remained undetermined in Mbnl compound knockout (KO) mice with cardiac phenotypes. Here, we develop Myh6-Cre double KO (DKO) (Mbnl1−/−; Mbnl2cond/cond; Myh6-Cre+/−) mice to eliminate Mbnl1/2 in cardiomyocytes and observe spontaneous lethal cardiac events under no anesthesia. RNA sequencing recapitulates DM heart spliceopathy and shows gene expression changes that were previously undescribed in DM heart studies. Notably, immunoblotting reveals a nearly 6-fold increase of Calsequestrin 1 and 50% reduction of epidermal growth factor proteins. Our findings demonstrate that complete ablation of MBNL1/2 in cardiomyocytes is essential for generating sudden death due to lethal cardiac rhythms and reveal potential mechanisms for DM heart pathogenesis.
Early home discharge after robot-assisted coronary artery bypass grafting
Authors: Spanjersberg Alexander , Hoek Leendert , Ottervanger Jan Paul , Nguyen Thi-Yen , Kaplan Emel , Laurens Roland , Singh Sandeep 
Published: May 2022

Abstract

OBJECTIVES
Robot-assisted coronary artery bypass grafting (CABG) has been developed as a less invasive alternative for conventional CABG to enhance postoperative recovery, patient satisfaction and early discharge to home. Furthermore, it may provide a basis for hybrid coronary revascularization. To determine the feasibility of this procedure, we compared robot-assisted with conventional off-pump CABG.

METHODS
All consecutive patients undergoing a robot-assisted left internal mammary artery-to-left anterior descending coronary artery procedure were compared to consecutive patients undergoing conventional off-pump CABG for single-vessel disease from October 2016 to July 2019. The primary outcome was discharge to home within 5 days after the operation. Secondary outcomes were total hospital stay, reoperations within 48 h, transfusions, atrial fibrillation, 30-day mortality and quality of life 1 month postoperatively. A propensity matched cohort was assembled to correct for possible confounders.

RESULTS
A total of 107 patients who had robot-assisted CABG were compared to 194 patients who had conventional off-pump CABG. The primary outcome was reached in 51% of the robot-assisted group versus 19% of the conventional off-pump group (P &lt; 0.01). The median postoperative hospital stay was 5 days for the robot-assisted group versus 7 days in the conventional off-pump group (P &lt; 0.01). Other secondary outcomes did not differ significantly between the groups, and the quality of life 1 month after the operation was equal. The results after propensity matching were similar.

CONCLUSIONS
Early discharge to home is more frequent for patients who have robot-assisted CABG than in those who have conventional off-pump CABG, with no difference in health-related quality of life. Therefore, this approach may reduce healthcare resources and provide a solid basis for hybrid coronary revascularization.
Pharmacists’ use of social media as aiding tools for reading and interpreting illegible prescriptions
Authors: Mathibe Lehlohonolo John , Haffejee Azraa , Mahlaba Nompumelelo , Mnqatu Zipho , Mtshali Zethembe , Noormohamed Salmaan , Sikhakhane Xolani Michael 
Published: May 2022

Abstract

Background
The ability to read and interpret a prescription is a crucial and rate-determining step for the provision of correct medicine(s), appropriate instructions to patients and for good practice of pharmacy in general. However, both in public and private healthcare settings, pharmacists continue to receive numerous illegible handwritten prescriptions. This is time consuming, and it poses serious legal and health consequences if prescriptions are read incorrectly, resulting in wrong medicines being dispensed.

Objectives
This study investigated the impact of using a WhatsApp Group to request assistance to read and interpret illegible prescriptions by pharmacists in South Africa.

Method
Communication records that span between June 2018 and October 2020 were included in this study. Two registered and practising pharmacists, who were not members of WhatsApp Group, verified the correctness of the responses to enquiries.

Key findings
The WhatsApp Group had 189 participants during the period of this study, and 136 enquiries were made. Only 10 enquiries did not receive responses, while 62, 32 and 32 enquiries received one, two and ≥3 responses, respectively. None of the responses to 29 images, or prescriptions that had received three or more responses, were deemed incorrect. The medians for the period of the first and subsequent responses were two minutes (with interquartile range of 1–4 min) and six minutes (with interquartile range of 3–14 min), respectively; and the difference (i.e., four minutes) was statistically significant (P &lt;0.0001).

Conclusion
The findings of this study suggest that social media platforms such as WhatsApp Groups can be used effectively as tools for aiding in the interpretation of illegible prescriptions.
The South African competition agency response to COVID19
Authors: Bonakele Tembinkosi 
Published: May 2022

Abstract
South Africa, as with the rest of the world, faced an unexpected crisis on many levels with the onslaught of the Covid-19 virus. In addition to the human casualties, South Africa experienced a sharp rise in prices for essential goods, such as masks and sanitisers, threatening an economic crisis for South Africa's poor and unemployed. The South African Competition Commission chose to intervene using the regulatory tools available in competition law to tackle excessive pricing. This resulted in the investigation and prosecution of several companies for charging excessive prices for a range of goods and services such as masks, sanitisers and Covid-19 testing services.
Evaluation of real-world referential and probabilistic patient matching to advance patient identification strategy
Authors: Grannis Shaun J , Williams Jennifer L , Kasthuri Suranga , Murray Molly , Xu Huiping 
Published: May 2022

Abstract

Objective
This study sought both to support evidence-based patient identity policy development by illustrating an approach for formally evaluating operational matching methods, and also to characterize the performance of both referential and probabilistic patient matching algorithms using real-world demographic data.

Materials and Methods
We assessed matching accuracy for referential and probabilistic matching algorithms using a manually reviewed 30 000 record gold standard reference dataset derived from a large health information exchange containing over 47 million patient registrations. We applied referential and probabilistic algorithms to this dataset and compared the outputs to the gold standard. We computed performance metrics including sensitivity (recall), positive predictive value (precision), and F-score for each algorithm.

Results
The probabilistic algorithm exhibited sensitivity, positive predictive value (PPV), and F-score of .6366, 0.9995, and 0.7778, respectively. The referential algorithm exhibited corresponding sensitivity, PPV, and F-score values of 0.9351, 0.9996, and 0.9663, respectively. Treating discordant and limited-data records as nonmatches increased referential match sensitivity to 0.9578. Compared to the more traditional probabilistic approach, referential matching exhibits greater accuracy.

Conclusions
Referential patient matching, an increasingly popular method among health IT vendors, demonstrated notably greater accuracy than a more traditional probabilistic approach without the adaptation of the algorithm to the data that the traditional probabilistic approach usually requires. Health IT policymakers, including the Office of the National Coordinator for Health Information Technology (ONC), should explore strategies to expand the evidence base for real-world matching system performance, given the need for an evidence-based patient identity strategy.
Endoscopic surgery of a cavernous hemangioma in the external auditory canal
Authors: Jin Myung Ho , Kwak Min Young 
Published: May 2022

Abstract
Cavernous hemangioma of the external auditory canal (EAC) is a rare clinical finding. Endoscopic ear surgery has been successfully applied for various ear pathologies with a wider surgical sight, minimal canal cuts and precise manipulation of soft tissues. We report a case of a 60-year-old woman with hemangioma of EAC which increased in size without treatment for several years. She underwent excision of the hemangioma using transcanal endoscopic approach. The endoscopic transcanal approach allowed surgical resection of EAC cavernous hemangioma with wider views and minimally invasive techniques.
A case of an intramesenteric GIST accurately diagnosed and completely resected by PET-CT and laparoscopy after gastrectomy for gastric cancer
Authors: Sato Manabu , Sato Masayuki , Yokoyama Tadaaki , Kusaka Akiko , Suzuki Yukie , Fukuhara Kenji 
Published: May 2022

Abstract
We performed the accurate diagnosis and complete surgical resection of a gastrointestinal stromal tumor at the mesentery of the small bowel. Computed tomography (CT) in a 62-year-old man at 2 years after gastrectomy for gastric cancer showed a mesenteric tumor, with no other tumors noted. Positron emission tomography-computed tomography (PET-CT) showed a maximum standardized uptake value (SUV max) of 2.9 at the tumor. The presence of a single and low SUV max tumor allowed us to perform laparoscopic surgery. Partial resection of the tumor with an adequate margin was performed. The pathological findings showed c-kit positivity and a low Ki-67 proliferation index (&lt;5%). In the present case, PET-CT and laparoscopic assessments were useful for accurately evaluating the surgical resectability of the mesenteric tumor after distal gastrectomy for gastric cancer. The low SUV max and laparoscopic findings led to complete surgical resection of a mesenteric tumor.
The transcription factor TaMYB31 regulates the benzoxazinoid biosynthetic pathway in wheat
Authors: Batyrshina Zhaniya S , Shavit Reut , Yaakov Beery , Bocobza Samuel , Tzin Vered 
Published: May 2022

Abstract
Benzoxazinoids are specialized metabolites that are highly abundant in staple crops, such as maize and wheat. Although their biosynthesis has been studied for several decades, the regulatory mechanisms of the benzoxazinoid pathway remain unknown. Here, we report that the wheat transcription factor MYB31 functions as a regulator of benzoxazinoid biosynthesis genes. A transcriptomic analysis of tetraploid wheat (Triticum turgidum) tissue revealed the up-regulation of two TtMYB31 homoeologous genes upon aphid and caterpillar feeding. TaMYB31 gene silencing in the hexaploid wheat Triticum aestivum significantly reduced benzoxazinoid metabolite levels and led to susceptibility to herbivores. Thus, aphid progeny production, caterpillar body weight gain, and spider mite oviposition significantly increased in TaMYB31-silenced plants. A comprehensive transcriptomic analysis of hexaploid wheat revealed that the TaMYB31 gene is co-expressed with the target benzoxazinoid-encoded Bx genes under several biotic and environmental conditions. Therefore, we analyzed the effect of abiotic stresses on benzoxazinoid levels and discovered a strong accumulation of these compounds in the leaves. The results of a dual fluorescence assay indicated that TaMYB31 binds to the Bx1 and Bx4 gene promoters, thereby activating the transcription of genes involved in the benzoxazinoid pathway. Our finding is the first report of the transcriptional regulation mechanism of the benzoxazinoid pathway in wheat.
Blood Donors with Thalassemic Trait, Glucose-6-Phosphate Dehydrogenase Deficiency Trait, and Sickle Cell Trait and Their Blood Products: Current Status and Future Perspective
Authors: Noulsri Egarit , Lerdwana Surada 
Published: May 2022

Abstract
The use of blood products for different medical purposes has increased in recent years. To meet increasing demand, some blood centers allow volunteer donors with thalassemic trait, glucose-6-phosphate dehydrogenase deficiency (G6PD) trait, and sickle cell trait (SCT) to donate blood if their hemoglobin values fall within acceptable ranges and show no signs of hemolysis. Currently, there are no standard guidelines or policies regarding the use or management of blood products obtained from these donors. However, in recent years, there has been advanced research on eligible donors who have these underlying conditions. In this review, we summarize the current knowledge from in vitro and in vivo studies regarding donor characteristics, changes in physical and biochemical parameters in blood products during processing and storage, and posttransfusion efficacy of blood products. In addition, we discuss some unresolved issues concerning blood products from thalassemic trait, G6PD-deficiency trait, and SCT donors.
The changing-look AGN NGC 1566 in quiescence with XMM-Newton: a nuclear starburst and an AGN competing in power?
Authors: Tomás L , Matzeu G A , Jiménez Bailón E , Kalfountzou E , Santos-Lleó M , Parker M L , Ballo L , Loiseau N , Ehle M , Rodríguez-Pascual P , González-Riestra R 
Published: May 2022

ABSTRACT
Star formation accretion on to the super massive black holes (SMBHs) and feedback processes link the evolution of galaxies with their SMBHs. X-ray observations in the imaging and spectral regime have revealed to be an important tool to study the connection between nuclear activity and circumnuclear star formation in nearby active galactic nuclei (AGN). X-ray spectral diagnostics can lead to disentangle, which is the ionization mechanism in the central kiloparsecs of nearby AGN. In this paper, we investigate, by means of XMM-Newton observations, the nuclear X-ray emission of the changing-look AGN NGC 1566 during its quiescent state. European Photon Imaging Camera (EPIC) soft X-ray images show an extended arm-like morphology. A detailed analysis of the high-resolution Reflection Grating Spectrometer (RGS) and medium resolution EPIC spectra shows that the material concentrated in the central kiloparsecs region is not in the photoionization-dominated regime while the presence of collisionally ionized plasma is needed to explain the observed spectral features. In the inner region (∼1.5 kpc), the brightness of the collisionally ionized gas is comparable to the brightness of the photoionized gas: the inner region hosts a luminous starburst whose ionized gas shows up bright in the X-rays when the AGN is in quiescence.
Exceptional among the exceptional: a new species of Stenogyropsis Möllendorff, 1899 (Eupulmonata: Camaenidae), with a review of the free last whorl in terrestrial gastropods
Authors: Chen Zhe-Yu , Huang Bo , Páll-Gergely Barna 
Published: May 2022

ABSTRACT
Stenogyropsis is one of the few genera of Helicoidea having a high-spired shell. Here, we describe a new species (Stenogyropsis chorismenostoma n. sp.) that has a further remarkable trait: its last quarter whorl is detached from the penultimate whorl. We also show that a partly detached last whorl has evolved much more frequently in terrestrial Caenogastropoda than in Stylommatophora relative to the number of species within those groups. This may be due to the more superficial contact of the neighbouring whorls in the former group.
Exon junction complex-associated multi-adapter RNPS1 nucleates splicing regulatory complexes to maintain transcriptome surveillance
Authors: Schlautmann Lena P , Lackmann Jan-Wilm , Altmüller Janine , Dieterich Christoph , Boehm Volker , Gehring Niels H 
Published: May 2022

Abstract
The exon junction complex (EJC) is an RNA-binding multi-protein complex with critical functions in post-transcriptional gene regulation. It is deposited on the mRNA during splicing and regulates diverse processes including pre-mRNA splicing and nonsense-mediated mRNA decay (NMD) via various interacting proteins. The peripheral EJC-binding protein RNPS1 was reported to serve two insufficiently characterized functions: suppressing mis-splicing of cryptic splice sites and activating NMD in the cytoplasm. The analysis of transcriptome-wide effects of EJC and RNPS1 knockdowns in different human cell lines supports the conclusion that RNPS1 can moderately influence NMD activity, but is not a globally essential NMD factor. However, numerous aberrant splicing events strongly suggest that the main function of RNPS1 is splicing regulation. Rescue analyses revealed that the RRM and C-terminal domain of RNPS1 both contribute partially to regulate RNPS1-dependent splicing events. We defined the RNPS1 core interactome using complementary immunoprecipitations and proximity labeling, which identified interactions with splicing-regulatory factors that are dependent on the C-terminus or the RRM domain of RNPS1. Thus, RNPS1 emerges as a multifunctional splicing regulator that promotes correct and efficient splicing of different vulnerable splicing events via the formation of diverse splicing-promoting complexes.
Enzymatic Synthesis of Chemical Nuclease Triplex-Forming Oligonucleotides with Gene-Silencing Applications
Authors: McGorman Bríonna , Fantoni Nicolò Zuin , O’Carroll Sinéad , Ziemele Anna , El-Sagheer Afaf H , Brown Tom , Kellett Andrew 
Published: May 2022

Abstract
Triplex-forming oligonucleotides (TFOs) are short, single-stranded oligomers that hybridise to a specific sequence of duplex DNA. TFOs can block transcription and thereby inhibit protein production, making them highly appealing in the field of antigene therapeutics. In this work, a primer extension protocol was developed to enzymatically prepare chemical nuclease TFO hybrid constructs, with gene-silencing applications. Click chemistry was employed to generate novel artificial metallo-nuclease (AMN)-dNTPs, which were selectively incorporated into the TFO strand by a DNA polymerase. This purely enzymatic protocol was then extended to facilitate the construction of 5-methylcytosine (5mC) modified TFOs that displayed increased thermal stability. The utility of the enzymatically synthesised di-(2-picolyl)amine (DPA)-TFOs was assessed and compared to a specifically prepared solid-phase synthesis counterpart through gel electrophoresis, quantitative PCR, and Sanger sequencing, which revealed similar recognition and damage properties to target genes. The specificity was then enhanced through coordinated designer intercalators—DPQ and DPPZ—and high-precision DNA cleavage was achieved. To our knowledge, this is the first example of the enzymatic production of an AMN-TFO hybrid and is the largest base modification incorporated using this method. These results indicate how chemical nuclease-TFOs may overcome limitations associated with non-molecularly targeted metallodrugs and open new avenues for artificial gene-editing technology.
Identification of genome edited cells using CRISPRnano
Authors: Nguyen Thach , Ramachandran Haribaskar , Martins Soraia , Krutmann Jean , Rossi Andrea 
Published: May 2022

Abstract
Genome engineering-induced cleavage sites can be resolved by non-homologous end joining (NHEJ) or homology-directed repair (HDR). Identifying genetically modified clones at the target locus remains an intensive and laborious task. Different workflows and software that rely on deep sequencing data have been developed to detect and quantify targeted mutagenesis. Nevertheless, these pipelines require high-quality reads generated by Next Generation Sequencing (NGS) platforms. Here, we have developed a robust, versatile, and easy-to-use computational webserver named CRISPRnano (www.CRISPRnano.de) that enables the analysis of low-quality reads generated by affordable and portable sequencers including Oxford Nanopore Technologies (ONT) devices. CRISPRnano allows fast and accurate identification, quantification, and visualization of genetically modified cell lines, it is compatible with NGS and ONT sequencing reads, and it can be used without an internet connection.