bluuebunny/crossref_metadata_2025_split huggingface dataset:
High levels of Tryptophan reduce cell wall or membrane stress tolerance in Saccharomyces cerevisiae
Authors: Ohashi Kazuto , Chaleckis Romanas 
Published: August 2021

ABSTRACT
Tryptophan (Trp) is a proteinogenic aromatic amino acid; however, high levels of Trp are toxic in animals and yeast with unknown mechanisms. Previously, we suggested that aromatic aminotransferase Aro9 is important for excess Trp degradation. Besides, Schroeder and Ikui showed that aro9Δ is sensitive to membrane stress by sodium dodecyl sulfate. Therefore, Trp accumulation may reduce the cell wall or membrane (CW/M) stress tolerance through participation of cell wall integrity (CWI) pathway, which detects and responds to CW/M perturbations. In this study, we found that yeast mutants of the CWI mitogen-activated protein kinase cascade were susceptible to excess Trp. Also, the Trp degradation deficient mutant aro8Δ aro9Δ cells, in which Trp accumulation was confirmed, were sensitive to several CW/M stresses. These results indicated that accumulation of Trp is adverse for the CW/M stress resistance and may disturb appropriate signal transduction responding to the stress.
Construction of recombinant Escherichia coli producing nitrogenase-related proteins from Azotobacter vinelandii
Authors: Tatemichi Yuki , Nakahara Takeharu , Ueda Mitsuyoshi , Kuroda Kouichi 
Published: August 2021

ABSTRACT
Biological nitrogen fixation by nitrogenase has attracted attention as an alternative method to chemical nitrogen fixation, which requires large amounts of fossil fuels. Azotobacter vinelandii, which produces an oxygen-sensitive nitrogenase, can fix nitrogen even under aerobic conditions; therefore, the heterologous expression of nif-related genes from A. vinelandii is a promising strategy for developing a biological nitrogen fixation method. We assembled 17 nif-related genes, which are scattered throughout the genome of A. vinelandii, into synthetic gene clusters by overlap-extension-PCR and seamless cloning and expressed them in Escherichia coli. The transcription and translation of the 17 nif-related genes were evaluated by RT-qPCR and LC-MS/MS, respectively. The constructed E. coli showed nitrogenase activity under anaerobic and microaerobic conditions. This strain would be a useful model for examining the effect of other genes from A. vinelandii on nitrogen fixation by expressing them in addition to the minimal set of nif-related genes.
Characterization and proposed spontaneous deletion mechanism of AVR-Pik locus in Pyricularia oryzae
Authors: Thwin Phyo Han , Funabiki Mai , Tomita Yuki , Yamazaki Takehiko , Abe Ayumi , Sone Teruo 
Published: August 2021

ABSTRACT
In phytopathogenic fungi, a mutation in the avirulence gene can lead to the breakdown of resistance in the host plant. The nucleotide sequences of the AVR-Pik locus in the strain Ina168 and its spontaneous mutant Ina168m95-5 of Pyricularia oryzae were determined. An AVR-Pik spontaneous deletion mechanism of Ina168m95-5, including multiple homologous recombination events involving repetitive transposable elements, is proposed.
DeepSec: a deep learning framework for secreted protein discovery in human body fluids
Authors: Shao Dan , Huang Lan , Wang Yan , He Kai , Cui Xueteng , Wang Yao , Ma Qin , Cui Juan 
Published: August 2021

Abstract

Motivation
Human proteins that are secreted into different body fluids from various cells and tissues can be promising disease indicators. Modern proteomics research empowered by both qualitative and quantitative profiling techniques has made great progress in protein discovery in various human fluids. However, due to the large number of proteins and diverse modifications present in the fluids, as well as the existing technical limits of major proteomics platforms (e.g. mass spectrometry), large discrepancies are often generated from different experimental studies. As a result, a comprehensive proteomics landscape across major human fluids are not well determined.

Results
To bridge this gap, we have developed a deep learning framework, named DeepSec, to identify secreted proteins in 12 types of human body fluids. DeepSec adopts an end-to-end sequence-based approach, where a Convolutional Neural Network is built to learn the abstract sequence features followed by a Bidirectional Gated Recurrent Unit with fully connected layer for protein classification. DeepSec has demonstrated promising performances with average area under the ROC curves of 0.85–0.94 on testing datasets in each type of fluids, which outperforms existing state-of-the-art methods available mostly on blood proteins. As an illustration of how to apply DeepSec in biomarker discovery research, we conducted a case study on kidney cancer by using genomics data from the cancer genome atlas and have identified 104 possible marker proteins.

Availability
DeepSec is available at https://bmbl.bmi.osumc.edu/deepsec/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Satb2 Regulates EphA7 to Control Soma Spacing and Self-Avoidance of Cortical Pyramidal Neurons
Authors: He Chun-Hui , Zhang Lei , Song Ning-Ning , Mei Wan-Ying , Chen Jia-Yin , Hu Ling , Zhang Qiong , Wang Yu-Bing , Ding Yu-Qiang 
Published: August 2021

Abstract
Soma spacing and dendritic arborization during brain development are key events for the establishment of proper neural circuitry and function. Transcription factor Satb2 is a molecular node in regulating the development of the cerebral cortex, as shown by the facts that Satb2 is required for the regionalization of retrosplenial cortex, the determination of callosal neuron fate, and the regulation of soma spacing and dendritic self-avoidance of cortical pyramidal neurons. In this study, we explored downstream effectors that mediate the Satb2-implicated soma spacing and dendritic self-avoidance. First, RNA-seq analysis of the cortex revealed differentially expressed genes between control and Satb2 CKO mice. Among them, EphA7 transcription was dramatically increased in layers II/III of Satb2 CKO cortex. Overexpression of EphA7 in the late-born cortical neurons of wild-type mice via in utero electroporation resulted in soma clumping and impaired self-avoidance of affected pyramidal neurons, which resembles the phenotypes caused by knockdown of Satb2 expression. Importantly, the phenotypes by Satb2 knockdown was rescued by reducing EphA7 expression in the cortex. Finally, ChIP and luciferase reporter assays indicated a direct suppression of EphA7 expression by Satb2. These findings provide new insights into the complexity of transcriptional regulation of the morphogenesis of cerebral cortex.
Proposed Linezolid Dosing Strategies to Minimize Adverse Events for Treatment of Extensively Drug-Resistant Tuberculosis
Authors: Imperial Marjorie Z , Nedelman Jerry R , Conradie Francesca , Savic R M 
Published: August 2021

Abstract

Background
We evaluated Nix-TB trial data (NCT02333799, N = 109) to provide dosing recommendations to potentially minimize linezolid toxicity in patients with extensively drug-resistant tuberculosis. .

Methods
A pharmacokinetic model and toxicodynamic models for peripheral neuropathy, hemoglobin, and platelets were developed. Simulations compared safety outcomes for daily linezolid of 1200 and 600 mg, with and without dose adjustments for toxicity. Severe neuropathy was based on symptom scores from the Brief Peripheral Neuropathy Screen. Severe anemia and thrombocytopenia were defined as ≥ grade 3 adverse events according to the NIAID Division of Microbiology and Infectious Disease Adult Toxicity table.

Results
Predicted concentration-time profiles were a major predictor in all toxicodynamic models. Simulations showed higher percentages of patients with severe neuropathy (median, 19%; 90% confidence interval [CI], 17%–22% vs 5%, 4%–7%) and severe anemia (15%, 12%–17% vs 1%, 0%–2%) between 1200 and 600 mg daily linezolid. No differences in severe thrombocytopenia were observed (median, &lt;1% for both daily doses). Generally, neuropathy occurred after 3 to 6 months of treatment and, with protocol-specified management, reversed within 15 months after onset. Simulations indicated that a &gt;10% decrease in hemoglobin level after 4 weeks of treatment would have maximum sensitivity (82%) and specificity (84%) for predicting severe anemia. Reducing the dose from 1200 to 600 mg triggered by this marker may prevent 60% (90% CI, 45%–72%) of severe anemia.

Conclusions
Simple neuropathy symptom and hemoglobin monitoring may guide linezolid dosing to avoid toxicities, but prospective testing is needed to confirm the benefit-to-risk ratio.
Direct Water-Assisted Laser Desorption/Ionization Mass Spectrometry Lipidomic Analysis and Classification of Formalin-Fixed Paraffin-Embedded Sarcoma Tissues without Dewaxing
Authors: Ogrinc Nina , Caux Pierre-Damien , Robin Yves-Marie , Bouchaert Emmanuel , Fatou Benoit , Ziskind Michael , Focsa Cristian , Bertin Delphine , Tierny Dominique , Takats Zoltan , Salzet Michel , Fournier Isabelle 
Published: August 2021

Abstract

Background
Formalin-fixed paraffin-embedded (FFPE) tissue has been the gold standard for routine pathology for general and cancer postoperative diagnostics. Despite robust histopathology, immunohistochemistry, and molecular methods, accurate diagnosis remains difficult for certain cases. Overall, the entire process can be time consuming, labor intensive, and does not reach over 90% diagnostic sensitivity and specificity. There is a growing need in onco-pathology for adjunct novel rapid, accurate, reliable, diagnostically sensitive, and specific methods for high-throughput biomolecular identification. Lipids have long been considered only as building blocks of cell membranes or signaling molecules, but have recently been introduced as central players in cancer. Due to sample processing, which limits their detection, lipid analysis directly from unprocessed FFPE tissues has never been reported.

Methods
We present a proof-of-concept with direct analysis of tissue-lipidomic signatures from FFPE tissues without dewaxing and minimal sample preparation using water-assisted laser desorption ionization mass spectrometry and deep-learning.

Results
On a cohort of difficult canine and human sarcoma cases, classification for canine sarcoma subtyping was possible with 99.1% accuracy using “5-fold” and 98.5% using “leave-one-patient out,” and 91.2% accuracy for human sarcoma using 5-fold and 73.8% using leave-one-patient out. The developed classification model enabled stratification of blind samples in &lt;5 min and showed &gt;95% probability for discriminating 2 human sarcoma blind samples.

Conclusion
It is possible to create a rapid diagnostic platform to screen clinical FFPE tissues with minimal sample preparation for molecular pathology.
The governance of 5G infrastructure: between path dependency and risk-based approaches
Authors: Radu Roxana , Amon Cedric 
Published: August 2021

Abstract
The fifth generation (5G) wireless technology promises a powerful, reliable and fast infrastructure to match artificial intelligence and Internet of Things developments. But its rollout has stirred strong political tensions around the prominent role that Chinese providers might be allowed to play in building the new networks. Between 2018 and 2020, a few countries have banned—partially or totally—the use of networking equipment produced by Huawei and ZTE, while others have mandated technical and security reviews to mitigate the risks associated with Chinese-origin components in the national 5G infrastructure. This article provides a thematic analysis of the security arguments and policy options emerging in the early days of the 5G debates. Based on key high-level statements, parliamentary debates and legislative acts published from mid-2018 to 2020, we examine perceived risks and threats surfacing in the public discourse, as well as the main regulatory directions emerging in seven countries. Our analysis shows policy alignment across multilateral commitments such as the European Union (EU) or the Five Eyes intelligence alliance. While selected EU member states lean towards risk-based governance and adaptive policies, Five Eyes nations opt for pre-emptive bans of 5G Chinese vendors, revealing path-dependent strategies for the sector. We conclude by discussing the policy reversal experienced by the UK in 2020 and the consolidation of new governance approaches for 5G infrastructure.
Ten-year all-cause death after percutaneous or surgical revascularization in diabetic patients with complex coronary artery disease
Authors: Wang Rutao , Serruys Patrick W , Gao Chao , Hara Hironori , Takahashi Kuniaki , Ono Masafumi , Kawashima Hideyuki , O’leary Neil , Holmes David R , Witkowski Adam , Curzen Nick , Burzotta Francesco , James Stefan , van Geuns Robert-Jan , Kappetein Arie Pieter , Morel Marie-angele , Head Stuart J , Thuijs Daniel J F M , Davierwala Piroze M , O’Brien Timothy , Fuster Valentin , Garg Scot , Onuma Yoshinobu 
Published: August 2021

Abstract

Aims
The aim of this article was to compare rates of all-cause death at 10 years following coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in patients with or without diabetes.

Methods and results
The SYNTAXES study evaluated up to 10-year survival of 1800 patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) randomized to receive either PCI or CABG in the SYNTAX trial. Ten-year all-cause death according to diabetic status and revascularization strategy was examined. In diabetics (n = 452), the risk of mortality was numerically higher with PCI compared with CABG at 5 years [19.6% vs. 13.3%, hazard ratio (HR): 1.53, 95% confidence interval (CI): 0.96, 2.43, P = 0.075], with the opposite seen between 5 and 10 years (PCI vs. CABG: 20.8% vs. 24.4%, HR: 0.82, 95% CI: 0.52, 1.27, P = 0.366). Irrespective of diabetic status, there was no significant difference in all-cause death at 10 years between patients receiving PCI or CABG, the absolute treatment difference was 1.9% in diabetics (PCI vs. CABG: 36.4% vs. 34.5%, difference: 1.9%, 95% CI: −7.6%, 11.1%, P = 0.551). Among insulin-treated patients (n = 182), all-cause death at 10 years was numerically higher with PCI (47.9% vs. 39.6%, difference: 8.2%, 95% CI: −6.5%, 22.5%, P = 0.227).

Conclusions
The treatment effects of PCI vs. CABG on all-cause death at 10 years in patients with 3VD and/or LMCAD were similar irrespective of the presence of diabetes. There may, however, be a survival benefit with CABG in patients with insulin-treated diabetes. The association between revascularization strategy and very long-term ischaemic and safety outcomes for patients with diabetes needs further investigation in dedicated trials.

Trial registration
SYNTAX: ClinicalTrials.gov reference: NCT00114972 and SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050.
Combining Knowledge- and Data-Driven Fuzzy Approach to Evaluate Shelf-Life of Various Seafood Products
Authors: Moosavi-Nasab Marzieh , Khoshnoudi-Nia Sara 
Published: August 2021

AbstractDue to the complexity of the deterioration process of seafood products, relying on one indicator is not adequate to determine the quality of such products. Usually, shelf-life was estimated based on various indicators complicating the decision-making process. Decision Support Systems are considered as a good solution. The current study aims to establish a simple and novel fuzzy model based on a combination of knowledge- and data-driven approaches to define a fuzzy quality deterioration index (FQDI) in various seafood products (rainbow trout, threadfin bream, and white shrimp samples) during cold storage. Total volatile basic nitrogen (TVB-N) and psychrotrophic microorganisms counts (PMCs) were determined based on traditional methods. The sensory analysis was performed by a data-driven fuzzy approach. Overall, the shelf-life of the rainbow trout fillet was estimated to be 8 days, based on all the freshness parameters. However, the shelf-life of the Japanese threadfin bream fillet was 5–7 days according to the microbial and chemical parameters, respectively. This time for shrimp samples was 6–8 days using sensory score and TVB-N contents. The results of data-driven fuzzy approach showed all of the quality properties were considered as the ‘Important’–‘Very Important’ (defuzzification score &gt;75). The TVB-N and PMCs were the most and weakest freshness quality properties (defuzzified-values: 84.64 and 78.75, respectively). Based on FQDI, the shelf-life of the rainbow trout, Japanese threadfin bream, and shrimp samples were estimated to be 8, 5, and 7 days, respectively. This method was able to successfully provide a comprehensive deterioration index for evaluating the seafood shelf-life. Such a total index can be considered as a comprehensive output (y variable) to predict seafood freshness by rapid and nondestructive method.
Exercise Therapy Is Effective at Improving Short- and Long-Term Mobility, Activities of Daily Living, and Balance in Older Patients Following Hip Fracture: A Systematic Review and Meta-Analysis
Authors: Hulsbæk Signe , Juhl Carsten , Røpke Alice , Bandholm Thomas , Kristensen Morten Tange 
Published: August 2021

Abstract

Background
A systematic review and meta-analysis was performed to evaluate the short- and long-term effects of exercise therapy on physical function, independence, and well-being in older patients following hip fracture and, secondly, whether the effect was modified by trial-level characteristics such as intervention modality, duration, and initiation timepoint.

Method
Medline, CENTRAL, Embase, CINAHL, and PEDro were searched up to November 2020. Eligibility criteria were randomized controlled trials investigating the effect of exercise therapy on physical function, independence, and well-being in older patients following hip fracture, initiated from time of surgery up to 1 year.

Results
Forty-nine studies involving 3 905 participants showed a small-to-moderate effect of exercise therapy at short term (end of intervention) on mobility (standardized mean difference [SMD] 0.49, 95% confidence interval [CI]: 0.22–0.76); activities of daily living (ADL) (SMD 0.31, 95% CI: 0.16–0.46); lower limb muscle strength (SMD 0.36, 95% CI: 0.13–0.60); and balance (SMD 0.34, 95% CI: 0.14–0.54). At long term (closest to 1 year), small-to-moderate effects were found for mobility (SMD 0.74, 95% CI: 0.15–1.34), ADL (SMD 0.42, 95% CI: 0.23–0.61), balance (SMD 0.50, 95% CI: 0.07–0.94), and health-related quality of life (SMD 0.31, 95% CI: 0.03–0.59). Certainty of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation ranging from moderate to very low, due to study limitation and inconsistency.

Conclusion
We found low certainty of evidence for a moderate effect of exercise therapy on mobility in older patients following hip fracture at end of treatment and follow-up. Further, low evidence was found for small-to-moderate short-term effect on ADL, lower limb muscle strength and balance.

Clinical Trials Registration Number
CRD42020161131
Presence of birth companion—a deterrent to disrespectful behaviours towards women during delivery: an exploratory mixed-method study in 18 public hospitals of India
Authors: Singh Shalini , Goel Richa , Gogoi Aparajita , Caleb-Varkey Leila , Manoranjini Mercy , Ravi Tina , Rawat Deewanshi 
Published: August 2021

Abstract
Birthing women require support, particularly emotional support, during the process of labour and delivery. Traditionally, across cultures, this support was made available by the continuous presence of a companion during labour, childbirth and the immediate post-partum period. However, this practice is not universal, especially in health facilities in low- and middle-income countries. This cross-sectional study was conducted in 18 tertiary health care facilities of India using a mixed-method approach. The quantitative data were collected to document the number of birthing women, birth companions and healthcare providers in the labour rooms, and the typology of disrespect and abuse (D&A) faced by women. This was followed by in-depth interviews with 55 providers to understand their perspective on the various dimensions of D&A and the challenges they face to provide respectful care. This article explores the status of birth companionship in India and its plausible associations with D&A faced by birthing women in public facilities. Our study reveals that birth companionship is still not a common practice in Indian public hospitals. Birth companions were present during less than half of the observational period, also less than half of the birthing women were accompanied by a birth companion. Lack of hospital policy, space constraints, overcrowding and privacy concerns for other patients were cited as reasons for not allowing birth companions in the labour rooms, whose supportive roles, both for women and providers, were otherwise widely acknowledged during the qualitative interviews. Also, the presence of birth companions was found to be critically negatively associated with occurrences of D&A of birthing women. We contend that owing to the high pressure on the public hospitals in India, birth companions can be a low-cost intervention model for promoting respectful maternity care. However, adequate infrastructure is a critical aspect to be taken care of.
COVID-19 response in South-East Asia: promoting healthcare quality through political engagement
Authors: Rana Bhupendra Kumar 
Published: August 2021

AbstractCoronavirus disease-2019 (COVID-19), a disease caused by coronavirus severe acute respiratory syndrome coronavirus 2, led to a pandemic that affected every region of the world. The World Health Organization South-East Asia Region (SEARO) is composed of 11 countries: Bangladesh, Bhutan, Democratic People’s Republic of Korea, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand, and Timor-Leste. Each of these countries faced different challenges in tackling COVID-19 depending upon their resources and health system. However, in general it was evidenced that no country was prepared to handle such a pandemic. Two strategies were adopted globally: closing the international borders and restricting movement within countries. These measures were adopted throughout the SEARO.