bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Intrinsic Differences Between Immune Checkpoint Inhibitor Induced Myocarditis: A Retrospective Analysis of Real-World Data
Authors: Lei Yanna , Zheng Xiufeng , Huang Qian , Li Xiaoying , Qiu Meng , Liu Ming 
Published: January 2022

Abstract
Immune-related myocarditis is a severe and even life-threatening immune-related adverse event (irAE) which may also be under-estimated due to the challenge in diagnosis. There have been few reports about the intrinsic difference between patients with immune-associated myocarditis. A retrospective analysis was conducted between March 2019 to June 2020 in West China Hospital and 18 patients with immune-related myocarditis were studied. Cases were classified as mild (n=12) or severe myocarditis (n=6) according to the clinical manifestations and haemodynamic complications. Covariates extracted from medical records were compared in different groups, and factors associated with severe myocarditis were identified. In this retrospective analysis, the median age of the 18 patients was 60 years old. Most cases occur early and approximately after the first or second ICI infusion. The severity of myocarditis may be correlated with lactate dehydrogenase (LDH) (P=0.04) and troponin (P=0.0057). The relationship between troponin and myocarditis was further confirmed in another cohort which including 30 patients. In addition, patients are more likely to develop multi-irAEs, and myositis was the most common second irAE. Those who experience multi-irAEs had significantly higher LDH (P=0.02) as well as myoglobin levels (P=0.02) than did not experience. All patients were treated with steroids timely and the mortality rate was 5.6% in our study. In this study, we explore risk factors for severe myocarditis and we emphasized the importance of a multidisciplinary team in assisting diagnosis and treatment options. It is critical to initiate corticosteroid therapy, regardless of the severity of the myocarditis.
Analysis of Factors Affecting the Length of Stay in the Emergency Department for Critically Ill Patients Transferred to Regional Emergency Medical Centers
Authors: Lee Hyungbok , Lee Sangrim , Kim Hyeoneui 
Published: January 2022

Abstract
BackgroundTransferring an emergency patient to another emergency department (ED) is necessary when she/he is unable to receive necessary treatment from the first visited ED, although the transfer poses potential risks for adverse clinical outcomes and lowering the quality of emergency medical services by overcrowding the transferred ED. This study aimed to understand the factors affecting the ED length of stay (LOS) of critically ill patients and to investigate whether they are receiving prompt treatment through Interhospital Transfer (IHT).MethodsThis study analyzed 968 critically ill patients transferred to the ED of the study site in 2019. Machine learning based prediction models were built to predict the ED LOS dichotomized as greater than 6 hours or less. Explanatory variables in patient characteristics, clinical characteristics, transfer-related characteristics, and ED characteristics were selected through univariate analyses.ResultsAmong the prediction models, the Logistic Regression (AUC 0.85) model showed the highest prediction performance, followed by Random Forest (AUC 0.83) and Naïve Bayes (AUC 0.83). The Logistic Regression model suggested that the need for emergency operation or angiography (OR 3.91, 95% CI=1.65–9.21), the need for Intensive Care Unit (ICU) admission (OR 3.84, 95% CI=2.53–5.83), fewer consultations (OR 3.57, 95% CI=2.84–4.49), a high triage level (OR 2.27, 95% CI=1.43–3.59), and fewer diagnoses (OR 1.32, 95% CI=1.09–1.61) coincided with a higher likelihood of 6-hour-or-less stays in the ED. Furthermore, an interhospital transfer handoff led to significantly shorter ED LOS among the patients who needed emergency operation or angiography, or ICU admission, or had a high triage level.ConclusionsThe results of this study suggest that patients prioritized in emergency treatment receive prompt intervention and leave the ED in time. Also, having a proper interhospital transfer handoff before IHT is crucial to provide efficient care and avoid unnecessarily longer stay in ED.
Modulation of Cortical Inhibition by Lovastatin in Neurofibromatosis Type 1: A Randomized, Triple-Blind, Placebo-Controlled Clinical Trial
Authors: Bernardino Ines , Dionísio Ana , Castelo-Branco Miguel 
Published: January 2022

Abstract
Neurofibromatosis type 1 (NF1) is associated with GABAergic dysfunction which has been suggested as the underlying cause of cognitive impairments. Previous intervention trials investigated the statins’ effects using cognitive outcome measures. However, available outcome measures have led to inconclusive results and there is a need to identify other options. Here, we aimed at investigating alternative outcome measures in a feasibility trial targeting cortical inhibition mechanisms known to be altered in NF1. We explored the neurochemical and physiological changes elicited by lovastatin, with magnetic resonance spectroscopy and transcranial magnetic stimulation (TMS). Fifteen NF1 adults participated in this randomized, triple-blind, placebo-controlled crossover trial (Clinicaltrials.gov NCT03826940) composed by one baseline and two reassessment visits after lovastatin/placebo intake (60mg/day, 3-days). Motor cortex GABA+ and Glx concentrations were measured using HERMES and PRESS sequences, respectively. Cortical inhibition was investigated by paired-pulse, input-output curve and cortical silent period (CSP) TMS protocols. CSP ratios were significantly increased by lovastatin (relative: p=0.027; absolute: p=0.034) but not by placebo. CSP durations showed a negative correlation with LICI 50ms amplitude ratio. Lovastatin was able to modulate cortical inhibition in NF1, as assessed by TMS CSP ratios, highlighting the potential of this outcome measure to be considered in future large-scale studies.
Gene Function Prediction in Five Model Eukaryotes Exclusively Based on Gene Relative Location Through Machine Learning
Authors: Obregón Flavio Pazos , Silvera Diego , Soto Pablo , Yankilevich Patricio , Guerberoff Gustavo , Cantera Rafael 
Published: January 2022

Abstract
The function of most genes is unknown. The best results in automated function prediction are obtained with machine learning-based methods that combine multiple data sources, typically sequence derived features, protein structure and interaction data. Even though there is ample evidence showing that a gene’s function is not independent of its location, the few available examples of gene function prediction based on gene location rely on sequence identity between genes of different organisms and are thus subjected to the limitations of the relationship between sequence and function. Here we predict thousands of gene functions in five model eukaryotes (Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus and Homo sapiens) using machine learning models exclusively trained with features derived from the location of genes in the genomes to which they belong. Our aim was not to obtain the best performing method to automated function prediction but to explore the extent to which a gene's location can predict its function in eukaryotes. We found that our models outperform BLAST when predicting terms from Biological Process and Cellular Component Ontologies, showing that, at least in some cases, gene location alone can be more useful than sequence to infer gene function.
Postmastectomy radiotherapy after neoadjuvant chemotherapy in cT1-2N+ breast cancer patients: a single center experience and review of current literature
Authors: Luo Meng , Chen Huihui , Deng Hao , Jin Yao , Wang Gui , Zhang Kun , Ma Hong , Chen Yiding , Zhang Suzhan , Zhou Jiaojiao 
Published: January 2022

Abstract
PurposePostmastectomy radiotherapy (PMRT) after NAC in breast cancer patients with initial clinical stage cT1−2N+, especially for those who achieved ypT1−2N0, is still controversial. This study was to evaluate the survival prognosis of cT1−2N+ patients after NAC with or without PMRT, and to discuss the selection of patients who may omit PMRT.Patients and MethodsFrom January 2005 to December 2017, 3055 female breast cancer patients underwent mastectomy in our medical center, among whom 215 patients of cT1−2N+ stage, receiving neoadjuvant chemotherapy (NAC) with or without PMRT were finally analyzed. The median follow-up duration was 72.6 months. The primary endpoint was overall survival, and the secondary endpoint was disease-free survival. Comparison was conducted between PMRT and non-PMRT subgroups.ResultsOf the 215 eligible patients, 35.8% (77/215) cT1−2N+ patients achieved ypT0−2N0 after NAC while 64.2% (138/215) of the patients remained nodal positive (ypT0−2N+). The 5-year DFS of ypT0−2N0 non-PMRT was 79.5% (95% confidence interval [CI] 63.4-95.6%). No statistically significant difference was observed between the ypT0−2N0 PMRT and non-PMRT subgroups for the 5-year DFS (78.5% vs 79.5%, p = 0.673) and OS (88.8% vs 90.8%, p = 0.721). The 5-years DFS didn’t obviously differ between the ypT0−2N0 non-PMRT subgroup and cT1−2N0 subgroup (79.5% vs 93.3%, p = 0.070). By using Cox regression model in multivariate analyses of prognosis in ypT0−2N+ PMRT subgroup, HER2 overexpression and triple-negative breast cancer were significantly poor predictors of DFS and OS, while ypN stage was significant independent predictors of OS.ConclusionAn excellent response to NAC (ypT0−2N0) indicates a sufficiently favorable prognosis, and PMRT might be omitted for cT1−2N+ breast cancer patients with ypT0−2N0 after NAC.
Rostral Hypothalamic Differentiation With Minimal Exogenous Signals in Human Naive Induced Pluripotent Stem Cells
Authors: Ozaki Hajime , Suga Hidetaka , Sakakibara Mayu , Soen Mika , Miyake Natsuki , Miwata Tsutomu , Taga Shiori , Nagai Takashi , Kano Mayuko , Mitsumoto Kazuki , Miyata Takashi , Kobayashi Tomoko , Sugiyama Mariko , Onoue Takeshi , Takagi Hiroshi , Hagiwara Daisuke , Iwama Shintaro , Banno Ryoichi , Iguchi Genzo , Takahashi Yutaka , Muguruma Keiko , Inoue Haruhisa , Arima Hiroshi 
Published: January 2022

Abstract
Familial neurohypophyseal diabetes insipidus (FNDI) is a degenerative disease of vasopressin (AVP) neurons. Studies in mouse in vivo models indicate that accumulation of mutant AVP prehormone is associated with FNDI pathology. However, studying human FNDI pathology in vivo is technically challenging. Therefore, an in vitro human model needs to be developed. When exogenous signals are minimized in the early phase of differentiation in vitro, mouse embryonic stem cells (ESCs) differentiate into AVP neurons, whereas human ESCs/induced pluripotent stem cells (iPSCs) die. Human ES/iPSCs are generally more similar to mouse epiblast stem cells compared to mouse ESCs, which are termed as primed and naive, respectively. In this study, we converted human FNDI-specific iPSCs from primed to naive cells, and found improved cell survival under minimal exogenous signals and differentiation into rostral hypothalamic organoids. Overall, this method provides a simple and straightforward differentiation direction, which may improve the efficiency of hypothalamic differentiation.
Evaluation of Ocular Surface Epithelial and Stromal Thicknesses in Psoriasis Using Anterior Segment Optical Coherence Tomography
Authors: Ersan Ismail , Kılıc Sevilay , Isık Selda 
Published: January 2022

Abstract
Purpose: To evaluate the epithelial and stromal thicknesses of conjunctiva and cornea in psoriatic patients with anterior segment optical coherence tomography (AS-OCT),Methods: In this cross-sectional study, 61 patients with psoriasis and 42 age-matched, healthy individuals were enrolled. The epithelial and stromal thicknesses of both inferotemporal bulbar conjunctiva and central cornea were measured using AS-OCT. Results: Both the Tear break-up time and Schirmer-1 test values were significantly lower in the psoriasis group compared with the controls (p<0.05). The epithelial thickness of conjunctiva and cornea did not differ between psoriasis and control groups. (p>0.05) The central corneal stroma was significantly thicker in the psoriasis group (p=0.04). PASI was positively correlated with the thickness of central cornea stroma (r=0.442, p=0.006) in the nail psoriasis group. Conclusions: Psoriasis is not associated with altered epithelial thicknesses of the cornea and conjunctiva. It is accompanied by the stromal thickening of the cornea without conjunctival stromal involvement.
circ_0035277 Promotes Gastric Cancer Proliferation and Metastasis via miR-576-3p/LIN28B Axis
Authors: Wang Xiaoyan , He Rong , Wang Yan , Liu Yunyun , Wang Yuxin , Chen Dandan , Fan Yu 
Published: January 2022

Abstract
Circular RNAs (circRNAs) regulate biological processes of human tumours. Gastric cancer is a prevalent disease that presents tumours with high metastasis. This study aimed to understand regulatory function and mechanism of circ_0035277 in gastric cancer development. circ_0035277 level in tissues and cells was assessed using RT-qPCR assay. Function of circ_0035277 was evaluated via CCK-8, colony formation and Transwell assays. Location of circ_0035277 was verified with FISH assay. Potential mechanism of circ_0035277 was examined using bioinformatics and luciferase reporter assays. BALB/c nude mice were utilised to construct the gastric cancer metastasis model with subcutaneous injection. Haematoxylin–eosin staining was performed to measure visible tumour nodules in lung tissues. Results showed that circ_0035277 is significantly up-regulated in tissues and cell lines of gastric cancer, accelerates the deterioration of gastric cancer, is significantly located in the cytoplasm and serves as a sponge to participate in gastric cancer by targeting miR-576-3p. Furthermore, lin-28 homolog B (LIN28B) was a direct target of miR-576-3p and reversed the role of circ_0035277/miR-576-3p on gastric cancer metastasis. In vivo studies have shown that knockdown of circ_0035277 suppresses gastric cancer metastasis. Overall, circ_0035277 accelerated gastric cancer progression and metastasis by regulating miR-576-3p/LIN28B axis. These findings can provide a potential target for the treatment of gastric cancer.
Comparative Life Cycle Assessment of Safety Shoes Toe Caps Manufacturing Processes
Authors: Bianchi Iacopo , Forcellese Archimede , Simoncini Michela , Vita Alessio , Castorani Vincenzo , Cafagna Damiana , Buccoliero Giuseppe 
Published: January 2022

Abstract
Toe caps are fundamental components of safety footwear used to prevent injuries which can be caused by falling objects. They can be realized by exploiting different materials (metal, composites and plastics) and manufacturing processes (stamping, injection molding, compression molding, etc.). However, they have always to fulfill the stringent requirements of safety regulations. In addition, in order to guarantee an ergonomic use, they must be as light as possible. It is estimated that at least 300 million pairs of safety footwear, with 600 million of toe caps, end up in landfill or are incinerated every year. This huge amount of wastes generates a relevant environmental impact, mainly attributable to toe caps manufacturing. In this context, it is important to develop new solutions which minimize the environmental impacts of toe caps manufacturing. Among others, the reuse of carbon fiber prepreg scraps has been recognized as a valid method to produce effective toe caps. In this paper, a detailed analysis of the environmental impacts associated to toe caps realized with reclaimed prepreg scraps has been conducted exploiting the Life Cycle Assessment methodology. The results have been compared to those obtained by analyzing toe caps realized in steel, aluminum, polycarbonate and glass fiber composite. Results demonstrate that the reclaim process for carbon fiber prepreg scraps can be a valid circular economy model to produce more sustainable toe caps for safety footwear.
Tracing the Origins of Glioblastoma by Investigating the Role of Gliogenic and Related Neurogenic Genes/Signaling Pathways in GBM Development: A Systematic Review
Authors: Shafi Ovais , Siddiqui Ghazia 
Published: January 2022

Abstract
Background: Glioblastoma is one of the most aggressive tumors. The etiology and the factors determining its onset are not yet entirely known. This study investigates the origins of GBM and for this purpose it focuses primarily on developmental gliogenic processes. It also focuses on impact of the related neurogenic developmental processes in glioblastoma oncogenesis. It also addresses why glial cells are at more risk of tumor development compared to neurons.Methods:Databases including PubMed, MEDLINE and Google Scholar were searched for published articles without any date restrictions, involving glioblastoma, gliogenesis, neurogenesis, stemness, neural stem cells, gliogenic signaling and pathways, neurogenic signaling and pathways, astrocytogenic genes.Results:The origin of GBM is dependent on dysregulation in multiple genes and pathways that accumulatively converge the cells towards oncogenesis. There are multiple layers of steps in glioblastoma oncogenesis including the failure of cell fate specific genes to keep the cells differentiated in their specific cell type such as p300, BMP, HOPX, NRSF/REST and others. There are genes and signaling pathways that are involved in differentiation and also contribute to GBM such as FGFR3, JAK-STAT, hey1 and others. The genes that contribute to differentiation processes but also contribute to stemness in GBM include notch, Sox9, Sox4, c-myc gene overrides p300 and then GFAP, leading to upregulation of nestin, SHH, NF-κB and others. GBM mutations pathologically impact the cell circuitry such as the interaction between Sox2 and JAK-STAT pathway, resulting in GBM development and progression. Conclusion: Glioblastoma originates when the gene expression of key gliogenic genes and signaling pathways become dysregulated. This study identifies key gliogenic genes having the ability to control oncogenesis in glioblastoma cells, including p300, BMP, PAX6, HOPX, NRSF/REST, LIF, TGF beta. It also identifies key neurogenic genes having the ability to control oncogenesis including PAX6, neurogenins including Ngn1, NeuroD1, NeuroD4, Numb, NKX6-1 Ebf, Myt1, ASCL1 and others. This study also postulates how aging contributes to the onset of glioblastoma by dysregulating the gene expression of NF-κB, REST/NRSF, ERK, AKT, EGFR and others.
A Green Strategy to Produce Potential Substitute Resource for Bear Bile Using Engineered Saccharomyces Cerevisiae
Authors: Jin Lina , Yang Li , Zhao Shujuan , Wang Zhengtao 
Published: January 2022

Abstract
BackgroundBear bile powder is a precious natural material characterized by high content of tauroursodeoxycholic acid (TUDCA) at a ratio of 1.00–1.50 to taurochenodeoxycholic acid (TCDCA).ResultsIn this study, we use the crude enzymes from engineered Saccharomyces cerevisiae to directional convert TCDCA from chicken bile powder to TUDCA at the committed ratio in vitro. This S. cerevisiae strain was modified with heterologous 7α-hydroxysteroid dehydrogenase (7α-HSDH) and 7β-hydroxysteroid dehydrogenase (7β-HSDH) genes. S. cerevisiae host and HSDH gene combinatorial optimization and response surface methodology was applied to get the best engineered strain and the optimal biotransformation condition, respectively, under which 10.99 ± 0.16 g/L of powder products containing 36.73±6.68 % of TUDCA and 28.22±6.05 % of TCDCA were obtained using 12.00 g/L of chicken bile powder as substrate.Conclusion﻿This study provides a healthy and environmentally friendly way to produce potential alternative resource for bear bile powder from cheap and readily available chicken bile powder, and also gives a reference for the green manufacturing of other rare and endangered animal-derived valuable resource.
Strategies for Prevention of COVID-19 Transmission in Hospitals: a Nationwide Survey of Controversial Issues Related to Infection Control and Prevention in Korea
Authors: Jang Wooyoung , Kim Bongyoung , Kim Eu Suk , Song Kyoung-Ho , Moon Song Mi , Lee Myung Jin , Park Ji Young , Kim Ji-Yeon , Shin Myoung Jin , Lee Hyunju , Kim Hong Bin 
Published: January 2022

Abstract
Background: Infection-control measures against the coronavirus disease 2019 (COVID-19) within a hospital are often based on expert experience and intuition due to the lack of clear guidelines. This study aimed to survey the current strategies for the prevention of the spread of COVID-19 in medical institutions.Methods: In a systematic review of national-level guidelines, 13 key topics were selected. Six hospitals were provided an open survey between August 11 and 25, 2020, to assess their responses to these topics. Using these data, an online questionnaire was developed and sent to the infection-control teams of 46 hospitals in South Korea. The survey was conducted between January 31, 2021, and February 20, 2021.Results: All 46 hospitals responded to the survey. All hospitals operated screening clinics, while 89.1% (41/46) allowed symptomatic patients without COVID-19-associated symptoms to visit the general outpatient clinics. Most hospitals (87.2%; 34/39) conducted polymerase chain reaction (PCR) tests for all hospitalised patients. Moreover, 35 (76.1%) hospitals had preemptive isolation policies for hospitalised patients, of which 97.1% (34/35) released patients from isolation after a single negative PCR test. Most hospitals (76.9%; 20/26) allowed shared-room accommodation for patients who met the national criteria for release from isolation but showed positive PCR results with cycle threshold values above a certain threshold (34.6%; 9/26) or after a certain period that satisfied the national criteria (26.9%; 7/26). Conclusions: Various guidelines were being applied by each medical institution, but an explicit set of national guidelines to support these guidelines was unavailable.
Deep Water Pathways In The North Pacific Ocean Revealed By Lagrangian Particle Tracking
Authors: Kawasaki Takao , Matsumura Yoshimasa , Hasumi Hiroyasu 
Published: January 2022

Abstract
Lagrangian particle tracking experiments are conducted to investigate the pathways of deep water in the North Pacific Ocean. The flow field is taken from a state-of-the-art deep circulation simulation. An unprecedented number of particles are tracked to quantify the volume transport and residence time. Half of the North Pacific deep water returns to the Southern Ocean, and its principal pathway is along the western boundary current in the Southwest Pacific Basin in the deep layer. About 30 % is exported to the Indian Ocean after upwelling to the shallow layer in the western North Pacific Ocean. The rest is transported to the Arctic Ocean through the Bering Strait or evaporates within the Pacific Ocean. Upwelling of deep water is confined in the western North Pacific Ocean owing to the strong vertical mixing. The mean residence time of deep water in the North Pacific Ocean is estimated to be several hundred years, which is considerably shorter than the conventional understandings of the deep Pacific Ocean circulation.