bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico-guided metabolic engineering of Bacillus subtilis for efficient biosynthesis of purine nucleosides by blocking the key backflow nodes
Authors: Deng Aihua , Qiu Qidi , Sun Qinyun , Chen Zhenxiang , Wang Junyue , Zhang Yu , Liu Shuwen , Wen Tingyi 
Published: August 2022

Abstract
Background
Purine nucleosides play essential roles in cellular physiological processes and have a wide range of applications in the fields of antitumor/antiviral drugs and food. However, microbial overproduction of purine nucleosides by de novo metabolic engineering remains a great challenge due to their strict and complex regulatory machinery involved in biosynthetic pathways.

Results
In this study, we designed an in silico-guided strategy for overproducing purine nucleosides based on a genome-scale metabolic network model in Bacillus subtilis. The metabolic flux was analyzed to predict two key backflow nodes, Drm (purine nucleotides toward PPP) and YwjH (PPP–EMP), to resolve the competitive relationship between biomass and purine nucleotide synthesis. In terms of the purine synthesis pathway, the first backflow node Drm was inactivated to block the degradation of purine nucleotides, which greatly increased the inosine production to 13.98–14.47 g/L without affecting cell growth. Furthermore, releasing feedback inhibition of the purine operon by promoter replacement enhanced the accumulation of purine nucleotides. In terms of the central carbon metabolic pathways, the deletion of the second backflow node YwjH and overexpression of Zwf were combined to increase inosine production to 22.01 ± 1.18 g/L by enhancing the metabolic flow of PPP. By switching on the flux node of the glucose-6-phosphate to PPP or EMP, the final inosine engineered strain produced up to 25.81 ± 1.23 g/L inosine by a pgi-based metabolic switch with a yield of 0.126 mol/mol glucose, a productivity of 0.358 g/L/h and a synthesis rate of 0.088 mmol/gDW/h, representing the highest yield in de novo engineered inosine bacteria. Under the guidance of this in silico-designed strategy, a general chassis bacterium was generated, for the first time, to efficiently synthesize inosine, adenosine, guanosine, IMP and GMP, which provides sufficient precursors for the synthesis of various purine intermediates.

Conclusions
Our study reveals that in silico-guided metabolic engineering successfully optimized the purine synthesis pathway by exploring efficient targets, which could be applied as a superior strategy for efficient biosynthesis of biotechnological products.
The telomere maintenance mechanism spectrum and its dynamics in gliomas
Authors: Kim Sojin , Chowdhury Tamrin , Yu Hyeon Jong , Kahng Jee Ye , Lee Chae Eun , Choi Seung Ah. , Kim Kyung-Min , Kang Ho , Lee Joo Ho , Lee Soon-Tae , Won Jae-Kyung , Kim Kyung Hyun , Kim Min-Sung , Lee Ji Yeoun , Kim Jin Wook , Kim Yong-Hwy , Kim Tae Min , Choi Seung Hong , Phi Ji Hoon , Shin Young-Kyoung , Ku Ja-Lok , Lee Sungyoung , Yun Hongseok , Lee Hwajin , Kim Dokyoung , Kim Kyoungmi , Hur Junho K. , Park Sung-Hye , Kim Seung-Ki , Park Chul-Kee 
Published: August 2022

Abstract
Background
The activation of the telomere maintenance mechanism (TMM) is one of the critical drivers of cancer cell immortality. In gliomas, TERT expression and TERT promoter mutation are considered to reliably indicate telomerase activation, while ATRX mutation and/or loss indicates an alternative lengthening of telomeres (ALT). However, these relationships have not been extensively validated in tumor tissues.

Methods
Telomerase repeated amplification protocol (TRAP) and C-circle assays were used to profile and characterize the TMM cross-sectionally (n = 412) and temporally (n = 133) across glioma samples. WES, RNA-seq, and NanoString analyses were performed to identify and validate the genetic characteristics of the TMM groups.

Results
We show through the direct measurement of telomerase activity and ALT in a large set of glioma samples that the TMM in glioma cannot be defined solely by the combination of telomerase activity and ALT, regardless of TERT expression, TERT promoter mutation, and ATRX loss. Moreover, we observed that a considerable proportion of gliomas lacked both telomerase activity and ALT. This telomerase activation-negative and ALT negative group exhibited evidence of slow growth potential. By analyzing a set of longitudinal samples from a separate cohort of glioma patients, we discovered that the TMM is not fixed and can change with glioma progression.

Conclusions
This study suggests that the TMM is dynamic and reflects the plasticity and oncogenicity of tumor cells. Direct measurement of telomerase enzyme activity and evidence of ALT should be considered when defining TMM. An accurate understanding of the TMM in glioma is expected to provide important information for establishing cancer management strategies.
Opportunities for a population-based cohort in Belgium
Authors: Schutte Nienke , Saelaert Marlies , Bogaert Petronille , De Ridder Karin , Van Oyen Herman , Van der Heyden Johan , Devleesschauwer Brecht 
Published: August 2022

AbstractPopulation-based cohorts allow providing answers to a wide range of policy-relevant research questions. In Belgium, existing cohort-like initiatives are limited by their focus on specific population groups or specific topics, or they lack a true longitudinal design. Since 2016, consultations and deliberative processes have been set up to explore the opportunities for a population-based cohort in Belgium. Through these processes, several recommendations emerged to pave the way forward – i.e., to facilitate the establishment of administrative linkages, increase digitalisation, secure long-term financial and organisational efforts, establish a consortium of the willing, and identify and tackle ethical and legal bottlenecks. This comment summarizes these recommendations, as these opportunities should be explored in depth to consolidate the existing collaborations between different stakeholders, and refers to current initiatives that can further facilitate the establishment of a Belgian population-based cohort and, more generally, administrative and health data linkage and reuse for research and policy-making.
Risk of transmission of respiratory viruses during aerosol-generating medical procedures (AGMPs) revisited in the COVID-19 pandemic: a systematic review
Authors: Leal Jenine , Farkas Brenlea , Mastikhina Liza , Flanagan Jordyn , Skidmore Becky , Salmon Charleen , Dixit Devika , Smith Stephanie , Tsekrekos Stephen , Lee Bonita , Vayalumkal Joseph , Dunn Jessica , Harrison Robyn , Cordoviz Melody , Dubois Roberta , Chandran Uma , Clement Fiona , Bush Kathryn , Conly John , Larios Oscar 
Published: August 2022

Abstract
Background
In many jurisdictions healthcare workers (HCWs) are using respirators for aerosol-generating medical procedures (AGMPs) performed on adult and pediatric populations with all suspect/confirmed viral respiratory infections (VRIs). This systematic review assessed the risk of VRIs to HCWs in the presence of AGMPs, the role respirators versus medical/surgical masks have on reducing that risk, and if the risk to HCWs during AGMPs differed when caring for adult or pediatric patient populations.

Main text
We searched MEDLINE, EMBASE, Cochrane Central, Cochrane SR, CINAHL, COVID-19 specific resources, and MedRxiv for English and French articles from database inception to September 9, 2021. Independent reviewers screened abstracts using pre-defined criteria, reviewed full-text articles, selected relevant studies, abstracted data, and conducted quality assessments of all studies using the ROBINS-I risk of bias tool. Disagreements were resolved by consensus. Thirty-eight studies were included; 23 studies on COVID-19, 10 on SARS, and 5 on MERS/ influenza/other respiratory viruses. Two of the 16 studies which assessed associations found that HCWs were 1.7 to 2.5 times more likely to contract COVID-19 after exposure to AGMPs vs. not exposed to AGMPs. Eight studies reported statistically significant associations for nine specific AGMPs and transmission of SARS to HCWS. Intubation was consistently associated with an increased risk of SARS. HCWs were more likely (OR 2.05, 95% CI 1.2–3.4) to contract human coronaviruses when exposed to an AGMP in one study. There were no reported associations between AGMP exposure and transmission of influenza or in a single study on MERS. There was limited evidence supporting the use of a respirator over a medical/surgical mask during an AGMP to reduce the risk of viral transmission. One study described outcomes of HCWs exposed to a pediatric patient during intubation.

Conclusion
Exposure to an AGMP may increase the risk of transmission of COVID-19, SARS, and human coronaviruses to HCWs, however the evidence base is heterogenous and prone to confounding, particularly related to COVID-19. There continues to be a significant research gap in the epidemiology of the risk of VRIs among HCWs during AGMPs, particularly for pediatric patients. Further evidence is needed regarding what constitutes an AGMP.
IgG subclass deposition in diabetic nephropathy
Authors: Tang Xuanli , Wan Feng , Zhu Qin , Ye Tian , Jiang Xue , Yang Haichun 
Published: August 2022

Abstract
Purpose
This study aimed to analyze the distribution of IgG subclass in diabetic nephropathy (DN) and its association with clinicopathological features.

Methods
This is a single-center retrospective study enrolling 108 patients with biopsy-proven DN. Immunofluorescence and immunohistochemistry staining were applied, and clinicopathological features and renal outcomes were compared between patients with different patterns or categories of IgG subclass deposition.

Results
Both IgG and its subclasses colocalized with collagen IV α5 on glomerular basement membrane (GBM) and some of tubular basement membrane (TBM). IgG1 and the Mixed type were two predominant types of deposition, no matter on GBM or TBM, and IgG1 showed a much higher deposition rate on GBM than that on TBM (P = 0.004). IgG subclass deposit on multi-location was more associated with a shorter duration of nephropathy and severer tubular interstitial injury (P < 0.05). The mixed type of IgG subclass deposit on GBM was merely associated with higher levels of proteinuria, whereas the deposition on TBM was more associated with higher levels of proteinuria, lower levels of albumin, more KIM-1 positive area, and thicker TBM (P < 0.05). Survival analysis revealed that none of the pattern or the category of IgG subclass deposit was a risk factor or a renal outcome indicator.

Conclusions
IgG subclass was selectively deposited along GBM and/or TBM in DN, and the mixed type of IgG subclass deposition on TBM had more clinical significance than the isotype and that on GBM. IgG subclass deposition is merely a manifestation or a consequence rather than a cause in DN.
A universal approach for multi-model schema inference
Authors: Koupil Pavel , Hricko Sebastián , Holubová Irena 
Published: August 2022

AbstractThe variety feature of Big Data, represented by multi-model data, has brought a new dimension of complexity to all aspects of data management. The need to process a set of distinct but interlinked data models is a challenging task. In this paper, we focus on the problem of inference of a schema, i.e., the description of the structure of data. While several verified approaches exist in the single-model world, their application for multi-model data is not straightforward. We introduce an approach that ensures inference of a common schema of multi-model data capturing their specifics. It can infer local integrity constraints as well as intra- and inter-model references. Following the standard features of Big Data, it can cope with overlapping models, i.e., data redundancy, and it is designed to process efficiently significant amounts of data.To the best of our knowledge, ours is the first approach addressing schema inference in the world of multi-model databases.
Toward a long-term atmospheric CO2 inversion for elucidating natural carbon fluxes: technical notes of NISMON-CO2 v2021.1
Authors: Niwa Yosuke , Ishijima Kentaro , Ito Akihiko , Iida Yosuke 
Published: August 2022

AbstractAccurate estimates of the carbon dioxide (CO2) fluxes at the earth’s surface are imperative for comprehending the carbon cycle mechanisms and providing reliable global warming predictions. Furthermore, they can also provide valuable science-based information that will be helpful in reducing human-induced CO2 emissions. Inverse analysis is a prominent method of quantitatively estimating spatiotemporal variations in CO2 fluxes; however, it involves a certain level of uncertainty and requires technical refinement, specifically to improve the horizontal resolution so that local fluxes can be compared with other estimates made at the regional or national level. In this study, a novel set of inversion schemes was incorporated into a state-of-the-art inverse analysis system named NISMON-CO2. The introduced schemes include a grid conversion, observational weighting, and anisotropic prior error covariance, the details of which are described. Moreover, pseudo-observation experiments were performed to examine the effect of the new schemes and to assess the reliability of NISMON-CO2 for long-term analysis with practical inhomogeneous observations. The experiment results evidently demonstrate the advantages of the grid conversion scheme for high-resolution flux estimates (1° × 1°), with notable improvements being achieved through the observational weighting and anisotropic prior error covariance. Furthermore, the estimated seasonal and interannual variations in regional CO2 fluxes were confirmed to be reliable, although some potential bias in terms of global land–ocean partitioning was observed. Thus, these results are useful for interpreting the flux variations that result from real-observation inverse analysis by NISMON-CO2 ver. 2021.1.
Hemothorax due to a ruptured esophageal gastrointestinal stromal tumor: case report
Authors: Ohki Shohei , Enomoto Naoki , Kato Daiki , Yagi Shusuke , Wake Hitomi , Nohara Kyoko , Miyazaki Hideki , Igari Toru , Kokudo Norihiro , Yamada Kazuhiko 
Published: August 2022

AbstractBackgroundEsophageal gastrointestinal stromal tumors (GISTs) are rare tumors of the gastrointestinal interstitium, and comprise less than 0.7% of all GISTs. The presentation of esophageal GIST is relatively benign, commonly characterized by symptoms of dysphagia and gastrointestinal bleed. On the contrary, it is highly unusual for these tumors to present as surgical emergencies.Case presentationHere, we describe a case of hemothorax secondary to the rupture of a massive (19 cm) esophageal GIST in a 79-year-old male. The patient presented with mild back pain, vomiting, and hypotension. A CT scan revealed significant mediastinal enlargement and left hemothorax. We conducted an emergency thoracotomy which revealed a 19 × 15 × 7 cm ruptured esophageal tumor that was bleeding profusely into the left thoracic cavity. Piecemeal resection without esophagectomy was performed to achieve hemostasis. Pathological evaluation of resected tissue confirmed the diagnosis of GIST. The patient was provided adjuvant imatinib therapy and remains progression-free at the 10-month follow-up.ConclusionsTo the best of our knowledge, this is the first reported case of life-threatening hemothorax caused by a ruptured esophageal GIST. Findings from this case may aid in the diagnosis and management of these rare tumors.
Spatial distribution of vitamin A rich foods intake and associated factors among children aged 6–23 months in Ethiopia: spatial and multilevel analysis of 2019 Ethiopian mini demographic and health survey
Authors: Demsash Addisalem Workie , Chereka Alex Ayenew , Kassie Sisay Yitayih , Donacho Dereje Oljira , Ngusie Habtamu Setegn , Tegegne Masresha Derese , Melaku Mequannent Sharew , Wubante Sisay Maru , Hunde Mekonnen Kenate 
Published: August 2022

AbstractBackgroundInadequate micronutrients in the diet and vitamin A deficiency are worldwide public health problems. In developing regions, many preschool children are undernourished, become blind every year and died before the age of 23 months. This study was aimed to explore the spatial distribution of vitamin A rich foods intake among children aged 6–23 months and identify associated factors in Ethiopia.MethodsEthiopian Mini Demographic and Health Survey 2019 dataset with a total 1407 children aged 6–23 months was used. Data management and processing were done using STATA version 15 software and Microsoft Office Excel. ArcMap version 10.7 software was used for mapping and spatial visualization of the distribution. Spatial scan statistics was performed using SaTScan version 9.5 software for Bernoulli-based model. Multilevel mixed effect logistic regression model was employed to identify associated factors.ResultsOverall, 38.99% (95% CI: 36.46–41.62) of children aged 6– 23 months took vitamin A rich foods. Poor intake of vitamin A rich foods was significantly clustered Dire Dawa city, Somali and Harari regions of Ethiopia. Children aged 6–23 months lived in the primary cluster were 70% (RR = 1.70,P-value < 0.001) more likely to intake vitamin A rich foods than children lived outside the window. In the multilevel mixed effect logistic regression analysis, Primary educational status (AOR:1.42, 95% CI: 1.05, 1.93) and higher educational status (AOR:3.0, 95% CI: 1.59, 5.65) of mother, Dire Dawa (AOR:0.49, 95% CI: 0.22, 1.12) city, Afar (AOR: 0.16, 95% CI: 0.07, 0.36), Amhara (AOR: 0.37, 95% CI: 0.19, 0.71) and Somali (AOR: 0.02, 95% CI: 0.003, 0.08) regions of Ethiopia, children aged 13–23 months (AOR: 1.80, 95% CI: 1.28, 2.36), Mothers’ exposure to media (AOR: 1.41, 95% CI: 1.04, 1.92) were statistically significant factors for vitamin A rich foods intake among children aged 6–23 months.ConclusionsOnly 4 out of ten children took vitamin A rich foods which is too low compared to the national target and significantly clustered in Ethiopia. Mother’s educational status, Region, Child age and Mother’s media exposure are significant factors vitamin A rich foods intake. Stakeholders should strengthen mothers’ education status, creating awareness for mothers on child feeding and using locally available natural resource to produce vitamin A rich foods.
Frequency control of a wind-diesel system based on hybrid energy storage
Authors: Mi Yang , Chen Boyang , Cai Pengcheng , He Xingtang , Liu Ronghui , Yang Xingwu 
Published: August 2022

AbstractTo improve the stability of a wind-diesel hybrid microgrid, a frequency control strategy is designed by using the hybrid energy storage system and the adjustable diesel generator with load frequency control (LFC). The objective of frequency control is to quickly respond to the disturbed system to reduce system frequency deviation and restore stability. By evaluating the area control error, the disturbance state of the system can be divided into four different areas by a corresponding control strategy for precise adjustments. For the diesel generator, an adaptive sliding mode (SM) algorithm is used to design LFC that can participate in frequency modulation. The frequency coordination control strategy proposed in this paper can realize the partition adjustment according to different resources, and ensure frequency stability. The proposed control strategy is verified by RTDS simulations in multiple scenarios.
A model for prognosis of influence of radiation dose on value of charge carrier mobility: an analytical approach for analysis of the introduced model
Authors: Pankratov Evgeny L. 
Published: August 2022

AbstractIn this paper, we analyzed the dependence of charge carriers mobility on value of radiation dose during ion implantation. Based on the considered model, we determine conditions to decrease radiation damage in the irradiated materials. Also we introduce an analytical approach to analyze mass transfer in the irradiated materials. The approach gives a possibility to take into account nonlinearity of the considered process, as well as changes of parameters of the considered process in space and time at one time.
Changes in Circulating Tumor DNA Reflect Clinical Benefit Across Multiple Studies of Patients With Non–Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors
Authors: Vega Diana Merino , Nishimura Katherine K. , Zariffa Névine , Thompson Jeffrey C. , Hoering Antje , Cilento Vanessa , Rosenthal Adam , Anagnostou Valsamo , Baden Jonathan , Beaver Julia A. , Chaudhuri Aadel A. , Chudova Darya , Fine Alexander D. , Fiore Joseph , Hodge Rachel , Hodgson Darren , Hunkapiller Nathan , Klass Daniel M. , Kobie Julie , Peña Carol , Pennello Gene , Peterman Neil , Philip Reena , Quinn Katie J. , Raben David , Rosner Gary L. , Sausen Mark , Tezcan Ayse , Xia Qi , Yi Jing , Young Amanda G. , Stewart Mark D. , Carpenter Erica L. , Aggarwal Charu , Allen Jeff 
Published: August 2022

PURPOSE As immune checkpoint inhibitors (ICI) become increasingly used in frontline settings, identifying early indicators of response is needed. Recent studies suggest a role for circulating tumor DNA (ctDNA) in monitoring response to ICI, but uncertainty exists in the generalizability of these studies. Here, the role of ctDNA for monitoring response to ICI is assessed through a standardized approach by assessing clinical trial data from five independent studies. PATIENTS AND METHODS Patient-level clinical and ctDNA data were pooled and harmonized from 200 patients across five independent clinical trials investigating the treatment of patients with non–small-cell lung cancer with programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1)–directed monotherapy or in combination with chemotherapy. CtDNA levels were measured using different ctDNA assays across the studies. Maximum variant allele frequencies were calculated using all somatic tumor-derived variants in each unique patient sample to correlate ctDNA changes with overall survival (OS) and progression-free survival (PFS). RESULTS We observed strong associations between reductions in ctDNA levels from on-treatment liquid biopsies with improved OS (OS; hazard ratio, 2.28; 95% CI, 1.62 to 3.20; P < .001) and PFS (PFS; hazard ratio 1.76; 95% CI, 1.31 to 2.36; P < .001). Changes in the maximum variant allele frequencies ctDNA values showed strong association across different outcomes. CONCLUSION In this pooled analysis of five independent clinical trials, consistent and robust associations between reductions in ctDNA and outcomes were found across multiple end points assessed in patients with non–small-cell lung cancer treated with an ICI. Additional tumor types, stages, and drug classes should be included in future analyses to further validate this. CtDNA may serve as an important tool in clinical development and an early indicator of treatment benefit.