bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Outcomes and Treatment Strategies in Patients With Non-Carbapenemase-producing Carbapenem-Resistant Versus Carbapenem-Susceptible Enterobacterales Infections
Authors: Debnath Ashita , Pillinger Kelly E. , Martin Alysa J. , Dobrzynski David , Cameron Andrew , Shulder Stephanie 
Published: October 2022

Background: Carbapenem-resistant Enterobacterales (CRE) are difficult to treat and can cause significant morbidity and mortality, however most data reflect carbapenemase-producing infections. Objective: Our objective was to evaluate clinical outcomes of non-carbapenemase-producing CRE (nCP-CRE) compared with carbapenem-susceptible Enterobacterales (CSE) infections. Methods: This was a retrospective, multicenter, observational study (January 1, 2018 to December 31, 2020). The primary outcome was clinical success at 30 days with secondary outcomes, including clinical success at 90 days, clinical success based on treatment for nCP-CRE, persistent bacteremia, intensive care unit (ICU) admission, length of stay, and rate of Clostridioides difficile or multidrug resistant infections. Results: The final analysis included 211 patients: 142 (67%) with CSE and 69 (33%) with nCP-CRE infections. Prior carbapenem exposure was more common with nCP-CRE (15% vs 4%, P = 0.01). Clinical success at 30 days was similar between groups (77% vs 74%, P = 0.73). There were no differences in secondary outcomes. There was an overall low use of carbapenems (empiric 6%, definitive 7%). Most nCP-CRE infections were treated with a monotherapy carbapenem-sparing regimen (empiric 88%, definitive 90%). Limitations include the retrospective design and the high rate of urinary infections. Conclusion and Relevance: Our study found no difference in clinical outcomes between nCP-CRE and CSE infections. Application of this study with future studies would help in determining optimal regimens for these infections.
Pathophysiology, prognosis and treatment of tardive dyskinesia
Authors: Takeuchi Hiroyoshi , Mori Yasuhiro , Tsutsumi Yuichiro 
Published: October 2022

Tardive dyskinesia (TD), a movement disorder associated with antipsychotics, most frequently affects the lower face and jaw muscles, but can also affect walking, breathing and use of the hands and limbs. Knowledge of TD among physicians may be limited, and the pathophysiology of TD is poorly understood. We conducted this review to summarise the current knowledge surrounding the pathophysiology of TD and present recommendations for prevention and treatment based on a literature search and roundtable discussion attended by psychiatrists in Japan. It has been suggested that dopamine hypersensitivity, damaged gamma-aminobutyric acidergic neurons and/or increased production of reactive oxygen species may contribute to development of TD. Symptoms can profoundly affect everyday life; patients who develop TD have poorer prognoses, worse health-related quality of life, greater social withdrawal and higher mortality than patients without TD. Traditional treatment options include dietary supplements, although evidence for their effectiveness is low. Among pharmaceutical interventions, there is moderate evidence that switching to the second-generation antipsychotic clozapine, which has a lower affinity for dopamine D2 receptors than other antipsychotics, may improve symptoms. Vesicular monoamine transporter 2 (VMAT-2) inhibitors, which oppose the increased dopaminergic activity associated with prolonged antipsychotic use by interfering with dopamine uptake and storage, have the strongest evidence for efficacy. VMAT-2 inhibitors are approved in the United States for the treatment of TD, and the first VMAT-2 inhibitor was approved in Japan for this indication in March 2022. Most guidelines recommend treating TD by first reducing the dose of antipsychotics or switching to clozapine or other second-generation antipsychotics, which have a lower association with TD than first-generation antipsychotics. We recommend focusing on prevention and monitoring for TD when prescribing antipsychotics, given that TD is often irreversible. Physicians should treat with antipsychotics only when necessary and at the lowest effective dose, and frequently monitor for TD symptoms. Plain Language Summary [Figure: see text] Plain Language Summary ( In Japanese ) Visual Summary [Figure: see text] Visual Summary ( In Japanese )
A smart healthcare-based system for classification of dementia using deep learning
Authors: Lim Jihye 
Published: October 2022

Objectives This study aims to develop a deep learning-based classification model for early detection of dementia using a wearable device that can measure the electrical conductivity of the skin, temperature, and movement as factors related to dementia, interlocking them with an application, and analyzing the collected data. Methods This study was conducted on 18 elderly individuals (5 males, 13 females) aged 65 years or older who consented to the study. The Korean Mini-Mental State Examination survey for cognitive function tests was conducted by well-trained researchers. The subjects were first grouped into high- or low-risk group for dementia based on their Korean Mini-Mental State Examination score. Data obtained by wearable devices of each subject were then used for the classification of the high- and low-risk groups of dementia through a smart healthcare-based system implementing a deep neural network with scaled principal component analysis. The correlation coefficients between the Korean Mini-Mental State Examination score and the featured data were also investigated. Results Our study showed that the proposed system using a deep neural network with scaled principal component analysis was effective in detecting individuals at high risk for dementia with up to 99% accuracy and which performance was better compared with commonly used classification algorithms. In addition, it was found that the electrical conductivity of skin had the closest correlation with the results of the Korean Mini-Mental State Examination score among data collected through wearable devices in this study. Conclusions Our proposed system can contribute to effective early detection of dementia for the elderly, using a non-invasive and easy-to-wear wearable device and classification algorithms with a simple cognitive function test. In the future, we intend to have more subjects participate in the experiment, to include more relevant variables in the wearable device, and to analyze the effectiveness of the smart healthcare-based dementia classification system over the long term.
La adquisición de la notación musical desde la perspectiva del sujeto que aprende. Un estudio en jóvenes sin estudios musicales específicos
Authors: Burcet María Inés , Beltramone Camila María , Uzal Sofía Belén , Rigotti Sofía Melina 
Published: October 2022

Este trabajo trata acerca del rol que se le asigna al sujeto que aprende en el proceso de adquisición de la notación musical. Con el fin de conocer las hipótesis de lectura que proponen quienes no conocen la notación musical, se desarrollaron una serie de entrevistas individuales a 40 jóvenes de entre 18 y 25 años. Los entrevistados debían señalar entre 4 partituras la que consideraban más adecuada para representar diferentes canciones del repertorio infantil tradicional, justificando en cada caso su elección. Se analizaron las justificaciones y, de acuerdo con los elementos y relaciones mencionados, se definieron cinco tipos de respuestas. Todos los sujetos lograron establecer asociaciones entre las canciones y las partituras proponiendo hipótesis acerca de los principios que sustentan la notación musical. Esto evidenciaría que los jóvenes, al encontrarse con un sistema de representación altamente normalizado no esperan obtener conocimiento específico para poder interactuar con la partitura Este estudio tendría importantes derivaciones para la educación musical, especialmente para el desarrollo de un enfoque que permita pensar el proceso de adquisición y apropiación de la notación musical desde la perspectiva del sujeto que aprende.
EVI1 exerts distinct roles in AML via ERG and cyclin D1 promoting a chemoresistant and immune-suppressive environment
Authors: Masamoto Yosuke , Chiba Akira , Mizuno Hideaki , Hino Toshiya , Hayashida Hiroki , Sato Tomohiko , Bando Masashige , Shirahige Katsuhiko , Kurokawa Mineo 
Published: October 2022

Abstract
Aberrant expression of ecotropic viral integration site-1 (EVI1+) is associated with very poor outcomes in acute myeloid leukemia (AML), mechanisms of which are only partially understood. Using the green fluorescent protein reporter system to monitor EVI1 promoter activity, we demonstrated that Evi1high KMT2A-MLLT1–transformed AML cells possess distinct features from Evi1low cells: the potential for aggressive disease independent of stem cell activity and resistance to cytotoxic chemotherapy, along with the consistent gene expression profiles. RNA sequencing and chromatin immunoprecipitation sequencing in EVI1-transformed AML cells and normal hematopoietic cells combined with functional screening by cell proliferation–related short hairpin RNAs revealed that the erythroblast transformation–specific transcription factor ERG (E26 transformation-specific [ETS]-related gene) and cyclin D1 were downstream targets and therapeutic vulnerabilities of EVI1+ AML. Silencing Erg in murine EVI1+ AML models severely impaired cell proliferation, chemoresistance, and leukemogenic capacity. Cyclin D1 is also requisite for efficient EVI1-AML development, associated with gene expression profiles related to chemokine production and interferon signature, and T- and natural killer–cell exhaustion phenotype, depending on the interferon gamma (IFN-γ)/STAT1 pathway but not on CDK4/CDK6. Inhibiting the IFN-γ/STAT1 pathway alleviated immune exhaustion and impaired EVI1-AML development. Overexpression of EVI1 and cyclin D1 was associated with IFN-γ signature and increased expression of chemokines, with increased exhaustion molecules in T cells also in human AML data sets. These data collectively suggest that ERG and cyclin D1 play pivotal roles in the biology of EVI1+ AML, where ERG contributes to aggressive disease nature and chemoresistance, and cyclin D1 leads to IFN-γ signature and exhausted T-cell phenotypes, which could potentially be targeted.
Successful treatment with repeated dexamethasone implant injections for recurrent macular edema after acute retinal necrosis
Authors: Sørland Ragnhild Øvstebø , Erichsen Anne Kjersti , Jonsdottir Thora Elisabet , Bromnes Marius Nordberg , Lauritzen Peter Mæhre , Eidet Jon Roger 
Published: October 2022

Abstract
Background
The treatment of recurrent cystoid macular edema associated with acute retinal necrosis is challenging due to the concern that treatment with intravitreal steroids may reactivate the retinitis.

Case report
An immunocompetent patient diagnosed with acute retinal necrosis was treated with oral valacyclovir and intravitreal injections of foscarnet. Giant tears in her retina necessitated a vitrectomy with silicone oil. She developed cystoid macular edema after the removal of the silicone oil. The edema responded to high-dose prednisolone but recurred when the dose was tapered to 20 mg daily. Under close surveillance and increased antiviral medication, she was treated with a dexamethasone implant with complete resolution of the edema. Unfortunately, the edema recurred, and the treatment had to be repeated. Over 18 months, she received five dexamethasone implants without recurrence of the viral retinitis.

Conclusions
This case shows successful treatment of recurring cystoid macular edema following acute retinal necrosis with repeated intravitreal dexamethasone implants in a patient receiving valacyclovir maintenance treatment.
Phylogenetic divergences in brown rot fungal pathogens of Monilinia species from a worldwide collection: inferences based on the nuclear versus mitochondrial genes
Authors: Silan Ece , Ozkilinc Hilal 
Published: October 2022

AbstractBackgroundPhylogenetic analyses for plant pathogenic fungi explore many questions on diversities, relationships, origins, and divergences of populations from different sources such as species, host, and geography. This information is highly valuable, especially from a large global sampling, to understand the evolutionary paths of the pathogens worldwide.Monilinia fructicolaandM. laxaare two important fungal pathogens of stone fruits that cause the widespread disease commonly known as brown rot. Three nuclear genes (Calmodulin,SDHA,TEF1α) and three mitochondrial genes (Cytochrome_b,NAD2, andNAD5) of the two pathogen species from a worldwide collection including five different countries from four different continents were studied in this work.ResultsBoth Maximum Likelihood and Bayesian approaches were applied to the data sets, and in addition, Maximum Parsimony based approaches were used for the regions having indel polymorphisms.Calmodulin,SDHA,NAD2,andNAD5regions were found phylogenetically informative and utilized for phylogenetics ofMoniliniaspecies for the first time. Each gene region presented a set of haplotypes exceptCytochrome_b, which was monomorphic. According to this large collection of twoMoniliniaspecies around the world,M. fructicolashowed more diversity thanM. laxa, a result that should be carefully considered, asM. fructicolais known to be a quarantine pathogen. Moreover, the other two mitochondrial genes (NAD2andNAD5) did not have any substitution type mutations but presented an intron indel polymorphism indicating the contribution of introns as well as mobile introns to the fungal diversity and evolution. Based on the concatenated gene sets, nuclear DNA carries higher mutations and uncovers more phylogenetic clusters in comparison to the mitochondrial DNA-based data for these fungal species.ConclusionsThis study provides the most comprehensive knowledge on the phylogenetics of both nuclear and mitochondrial genes of two prominent brown rot pathogens,M. fructicolaandM. laxa. Based on the regions used in this study, the nuclear genes resolved phylogenetic branching better than the mitochondrial genes and discovered new phylogenetic lineages for these species.
Association of mTORC1‑dependent circulating protein levels with cataract formation: a mendelian randomization study
Authors: Cai Yingjun , Liu Kangcheng , Wu Pengfei , Yuan Ruolan , He Fei , Zou Jing 
Published: October 2022

Abstract
Background
The mechanistic target of rapamycin (mTOR) signal pathway plays a critical regulating role in the occurrence and development of cataract. However, the role of mTORC1 downstream proteins, including ribosomal protein S6K (RP-S6K), eukaryotic initiation factor 4E-binding protein (EIF4EBP), eukaryotic initiation factor 4G (EIF-4G), eukaryotic initiation factor 4E (EIF-4E), and eukaryotic initiation factor 4A (EIF-4A), in regulating cataract development is still unknown. Herein, we conducted a mendelian randomization (MR) study to understand the function of mTORC1 signaling in the process of cataract development.

Results
The causal estimate was evaluated with inverse-variance weighted (IVW) estimate, weighted median estimator, MR-Egger and MR robust adjusted profile score (MR. RAPS). The single-nucleotide polymorphisms (SNPs), P<5 × 10− 6 and r2<0.05, were selected to genetically predict the RP-S6K, EIF4EBP, EIF-4E, EIF-4A, and EIF-4G. We included a total of 26,758 cases and 189,604 controls in this MR study. The study revealed causal association between circulating EIF4EBP (OR 1.09, 95% confidence interval 1.03,1.16, P = 0.004), RP-S6K (OR 1.04, 95% confidence interval 1.01, 1.08, P = 0.02) and cataract formation with IVW estimate. Whereas after correcting outliers, MR robust adjusted profile score (MR. RAPS) shows consistent result with IVW for EIF4EBP (OR = 1.08, 95%CI:1.05–1.11, P = 0.007). The observation strengthened the confidence in the true causal associations. However, no association was found for circulating EIF-4E (OR 1.03, 95% confidence interval 0.97, 1.09, P = 0.31), EIF-4A (OR 1.02, 95% confidence interval 0.98, 1.07, P = 0.34), and EIF-4G (OR 1.02, 95% confidence interval 0.94, 1.01, P = 0.64) levels with cataract formation. No evidence of heterogeneity and unbalanced horizontal pleiotropy was detected.

Conclusion
The MR study suggests that EIF4EBP is a high-risk factor for cataract development. There may be a potential causal association between the mTORC1/EIF4EBP axis and cataract. This research highlights the potential mechanism for cataract development and a genetic target to prevent as well as treat cataracts.
Species diversity analysis of commercial Mantidis Ootheca samples contaminated by store pests based on DNA metabarcoding
Authors: Xu Liuwei , Zhang Xiaoying , Guo Hua , Yang Xia , Xing Zhimei , Yang Wenzhi , Zhang Jian , Tian Xiaoxuan 
Published: October 2022

AbstractMantidis Ootheca (Sangpiaoxiao, mantis egg case) is a typical multi-origin Chinese medicinal material. The Chinese Pharmacopoeia stipulates that the Mantidis Ootheca originates from three species of Mantis: Tenodera sinensis, Statilia maculate, and Hierodula patellifera. However, Mantidis Ootheca mainly relies on field collection, which leads to confusion of its actual origin in the market. As the clinical use of Mantidis Ootheca with unknown original mantis species will pose potential risks to drug safety, it is necessary to survey the commercially available Mantidis Ootheca origin species. However, as the egg case of Mantis, the morphological characters of Mantidis Ootheca are limited and usually cannot serve as accurate identification tool. DNA barcoding, which is widely used in taxonomic studies of animals, is severely affected by the impact of storage pests and DNA degradation. Thus, this study collected a total of 4580 Mantidis Ootheca and pooled separately Mantidis Ootheca samples according to 18 different sources as DNA samples to analyze the origin diversity of Mantidis Ootheca individuals contaminated by common store pests collected in in the market using DNA metabarcoding, and to provide a basis for quality control of Mantidis Ootheca. 37 Mantis ASVs and 9 Mantis MOTUs were identified through species delimitation, and the high-level intraspecific diversity was depicted as haplotype network plot. Besides Tenodera sinensis and Hierodula patellifera as genuine original mantis species defined in the Chinese Pharmacopoeia, Tenodera angustipennis was also the origin species of these Mantidis Ootheca samples.
Molecular characteristics of global β-lactamase-producing Enterobacter cloacae by genomic analysis
Authors: Hu Jincao , Li Jia , Liu Chang , Zhang Yan , Xie Hui , Li Chuchu , Shen Han , Cao Xiaoli 
Published: October 2022

Abstract
Objective
To analyze the characteristics of global β-lactamase-producing Enterobacter cloacae including the distribution of β-lactamase, sequence types (STs) as well as plasmid replicons.

Methods
All the genomes of the E. cloacae were downloaded from GenBank. The distribution of β-lactamase encoding genes were investigated by genome annotation after the genome quality was checked. The STs of these strains were analyzed by multi-locus sequence typing (MLST). The distribution of plasmid replicons was further explored by submitting these genomes to the genome epidemiology center. The isolation information of these strains was extracted by Per program from GenBank.

Results
A total of 272 out of 276 strains were found to carry β-lactamase encoding genes. Among them, 23 varieties of β-lactamase were identified, blaCMH (n = 130, 47.8%) and blaACT (n = 126, 46.3%) were the most predominant ones, 9 genotypes of carbapenem-hydrolyzing β-lactamase (CHβLs) were identified with blaVIM (n = 29, 10.7%) and blaKPC (n = 24, 8.9%) being the most dominant ones. In addition, 115 distinct STs for the 272 ß-lactamase-carrying E. cloacae and 48 different STs for 106 CHβLs-producing E. cloacae were detected. ST873 (n = 27, 9.9%) was the most common ST. Furthermore, 25 different plasmid replicons were identified, IncHI2 (n = 65, 23.9%), IncHI2A (n = 64, 23.5%) and IncFII (n = 62, 22.8%) were the most common ones. Notably, the distribution of plasmid replicons IncHI2 and IncHI2A among CHβLs-producing strains were significantly higher than theat among non-CHβLs-producing strains (p < 0.05).

Conclusion
Almost all the E. cloacae contained β-lactamase encoding gene. Among the global E. cloacae, blaCMH and blaACT were main blaAmpC genes. BlaTEM and blaCTX-M were the predominant ESBLs. BlaKPC, blaVIM and blaNDM were the major CHβLs. Additionally, diversely distinct STs and different replicons were identified.
An extended 36-week oral esomeprazole improved long-term recurrent peptic ulcer bleeding in patients at high risk of rebleeding
Authors: Chiang Hsueh-Chien , Yang Er-Hsiang , Hu Huang-Ming , Chen Wei-Ying , Chang Wei-Lun , Wu Chung-Tai , Wu Deng-Chyang , Sheu Bor-Shyang , Cheng Hsiu-Chi 
Published: October 2022

Abstract
Background
Patients with Rockall scores ≥6 have an increased risk of long-term peptic ulcer rebleeding. This study was aimed toward investigating whether an extended course of oral esomeprazole up to 1 year decreased ulcer rebleeding in such patients.

Methods
We prospectively enrolled 120 patients with peptic ulcer bleeding and Rockall scores ≥6. After an initial 16-week oral proton pump inhibitor (PPI) treatment, patients were randomized to receive a 36-week course of oral twice-daily esomeprazole 20 mg (Group D, n = 60) or once-daily (Group S, n = 60). Thereafter, they were divided into the PPI-on-demand (n = 32) and PPI-discontinued (n = 77) subgroups. Our previous cohort with Rockall scores ≥6 served as the controls (Group C, n = 135); they received only an initial 8- to 16-week oral PPI. The primary and secondary outcomes were peptic ulcer rebleeding during the first year and the second year-and-thereafter, respectively.

Results
For the primary outcome, groups D and S comprised a higher proportion of rebleeding-free than Group C (P = 0.008 and 0.03, log-rank test). The competing-risks regression analysis confirmed that extended PPI use and American Society of Anesthesiologists classification were independent factors contributing to the primary outcome. For the secondary outcome, PPI-on-demand had a borderline higher proportion of rebleeding-free than Group C (P = 0.07, log-rank test); however, only the Rockall score was the independent factor.

Conclusions
An extended 36-week course of oral esomeprazole 20 mg, twice- or once-daily for patients with Rockall scores ≥6 reduced ulcer rebleeding during the first year, but the effect needed to be further validated when PPIs were shifted to on-demand or discontinued thereafter (NCT02456012, 28/05/2015).