bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction and characterization of BsGDH-CatIB variants and application as robust and highly active redox cofactor regeneration module for biocatalysis
Authors: Küsters Kira , Saborowski Ronja , Wagner Christian , Hamel Rebecca , Spöring Jan-Dirk , Wiechert Wolfgang , Oldiges Marco 
Published: June 2022

Abstract
Background
Catalytically active inclusion bodies (CatIBs) are known for their easy and cost efficient production, recyclability as well as high stability and provide an alternative purely biological technology for enzyme immobilization. Due to their ability to self-aggregate in a carrier-free, biodegradable form, no further laborious immobilization steps or additional reagents are needed. These advantages put CatIBs in a beneficial position in comparison to traditional immobilization techniques. Recent studies outlined the impact of cooperative effects of the linker and aggregation inducing tag on the activity level of CatIBs, requiring to test many combinations to find the best performing CatIB variant.

Results
Here, we present the formation of 14 glucose dehydrogenase CatIB variants of Bacillus subtilis, a well-known enzyme in biocatalysis due to its capability for substrate coupled regeneration of reduced cofactors with cheap substrate glucose. Nine variants revealed activity, with highest productivity levels for the more rigid PT-Linker combinations. The best performing CatIB, BsGDH-PT-CBDCell, was characterized in more detail including long-term storage at −20 °C as well as NADH cofactor regeneration performance in repetitive batch experiments with CatIB recycling. After freezing, BsGDH-PT-CBDCell CatIB only lost approx. 10% activity after 8 weeks of storage. Moreover, after 11 CatIB recycling cycles in repetitive batch operation 80% of the activity was still present.

Conclusions
This work presents a method for the effective formation of a highly active and long-term stable BsGDH-CatIB as an immobilized enzyme for robust and convenient NADH regeneration.
Association between hypertriglyceridemic-waist phenotype and non-alcoholic fatty liver disease: a general population-based study
Authors: Yang Ming , Xu Yaqin , Hu Chong , Zhang Shuhua , Kuang Maobin , Zou Yang 
Published: June 2022

Abstract
Background
Hypertriglyceridemic-waist (HTGW) phenotype has been proposed as a practical tool for screening the risk of cardiovascular diseases and glycemic metabolic disease. This study sought to investigate the relationship between HTGW phenotype and non-alcoholic fatty liver disease (NAFLD).

Methods
A total of 14,251 subjects who took part in health screening were enrolled in the study and NAFLD was diagnosed by abdominal ultrasound. According to triglyceride (TG) and waist circumference, the study population was divided into four phenotypes, in which HTGW phenotype was defined as TG ≥ 1.7 mmol/L and male waist circumference ≥ 90 cm or female waist circumference ≥ 80 cm. Multivariate logistic regression analysis was used to evaluate the relationship between HTGW phenotype and NAFLD.

Results
In the current study, 2.43% of the subjects had HTGW phenotype, while the prevalence of NAFLD in subjects with HTGW phenotype was 77.81%. After full adjustment for covariates, compared with people with normal waist circumference and TG levels, the risk of NAFLD in people with normal TG levels but enlarged waist circumference increased by 39% [OR:1.39, 95%CI: 1.15, 1.68], in people with normal waist circumference but elevated TG levels increased by 96% [OR:1.96, 95%CI: 1.65, 2.33], and in subjects with HTGW phenotype increased by 160% [OR:2.60, 95%CI: 1.88, 3.58]. Additionally, further analysis suggested that there were significant interactions between age, height, BMI and NAFLD risk associated with TGW phenotypes. Receiver operating characteristic curves analysis suggested that the combination of TG and waist circumference further improved the diagnostic value for NAFLD.

Conclusions
HTGW phenotype is associated with NAFLD risk in the general population, which may be a novel and accessible indicator for NAFLD screening.
A comprehensive review about immune responses and exhaustion during coronavirus disease (COVID-19)
Authors: Mohammed Rebar N. , Tamjidifar Rozita , Rahman Heshu Sulaiman , Adili Ali , Ghoreishizadeh Shadi , Saeedi Hossein , Thangavelu Lakshmi , Shomali Navid , Aslaminabad Ramin , Marofi Faroogh , Tahavvori Mina , Danshina Svetlana , Akbari Morteza , Ercan Gülinnaz 
Published: June 2022

AbstractCoronavirus disease (COVID-19) is a viral infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The infection was reported in Wuhan, China, in late December 2019 and has become a major global concern due to severe respiratory infections and high transmission rates. Evidence suggests that the strong interaction between SARS-CoV-2 and patients' immune systems leads to various clinical symptoms of COVID-19. Although the adaptive immune responses are essential for eliminating SARS-CoV-2, the innate immune system may, in some cases, cause the infection to progress. The cytotoxic CD8+ T cells in adaptive immune responses demonstrated functional exhaustion through upregulation of exhaustion markers. In this regard, humoral immune responses play an essential role in combat SARS-CoV-2 because SARS-CoV-2 restricts antigen presentation through downregulation of MHC class I and II molecules that lead to the inhibition of T cell-mediated immune response responses. This review summarizes the exact pathogenesis of SARS-CoV-2 and the alteration of the immune response during SARS-CoV-2 infection. In addition, we’ve explained the exhaustion of the immune system during SARS-CoV-2 and the potential immunomodulation approach to overcome this phenomenon.
Feasibility of establishing a core set of sexual, reproductive, maternal, newborn, child, and adolescent health indicators in humanitarian settings: results from a multi-methods assessment in the Democratic Republic of Congo
Authors: Emina Jacques , Etinkum Rinelle , Aissaoui Anya , Gbomosa Cady Nyombe , Elamurugan Kaeshan , Rajendra Kanya Lakshmi , El Mowafi Ieman Mona , Kobeissi Loulou 
Published: June 2022

Abstract
Background
Reliable and rigorously collected sexual, reproductive, maternal, newborn, child, and adolescent health (SRMNCAH) data in humanitarian settings are often sparse and variable in quality across different humanitarian settings, and there is a lack of consensus about a core set of indicators that humanitarian actors including national health systems should report on. To address this gap in quality data, the World Health Organization (WHO) developed a core set of indicators for monitoring and evaluating SRMNCAH services and outcomes and assessed their feasibility in four countries, including the Democratic Republic of Congo (DRC) with the goal of aggregating information from global consultations and field-level assessments to reach consensus on a set of core SRMNCAH indicators among WHO partners.

Methods
The feasibility assessment in the DRC focused on the following constructs: relevance/usefulness, feasibility of measurement, systems and resources, and ethical issues. The multi-methods assessment included five components; a desk review, key informant interviews, focus group discussions, facility assessments, and observational sessions.

Results
The findings suggest that there is widespread support among stakeholders for developing a standardized core list of SRMNCAH indicators to be collected among all humanitarian actors in the DRC. There are numerous resources and data collection systems that could be leveraged, built upon, and improved to ensure the feasibility of collecting this proposed set of indicators. However, the data collection load requested from donors, the national government, international and UN agencies, and coordination/cluster systems must be better harmonized, standardized, and less burdensome.

Conclusions
Despite stakeholder support in developing a core set of indicators, this would only be useful if it has the buy-in from the international community. Greater harmonization and coordination, alongside increased resource allocation, would improve data collection efforts and allow stakeholders to meet indicators’ reporting requirements.
Genome-wide DNA methylation reveals potential epigenetic mechanism of age-dependent viral susceptibility in grass carp
Authors: He Libo , Liang Xinyu , Wang Qian , Yang Cheng , Li Yongming , Liao Lanjie , Zhu Zuoyan , Wang Yaping 
Published: June 2022

Abstract
Background
Grass carp are an important farmed fish in China that are infected by many pathogens, especially grass carp reovirus (GCRV). Notably, grass carp showed age-dependent susceptibility to GCRV; that is, grass carp not older than one year were sensitive to GCRV, while those over three years old were resistant to this virus. However, the underlying mechanism remains unclear. Herein, whole genome-wide DNA methylation and gene expression variations between susceptible five-month-old (FMO) and resistant three-year-old (TYO) grass carp were investigated aiming to uncover potential epigenetic mechanisms.

Results
Colorimetric quantification revealed that the global methylation level in TYO fish was higher than that in FMO fish. Whole-genome bisulfite sequencing (WGBS) of the two groups revealed 6214 differentially methylated regions (DMRs) and 4052 differentially methylated genes (DMGs), with most DMRs and DMGs showing hypermethylation patterns in TYO fish. Correlation analysis revealed that DNA hypomethylation in promoter regions and DNA hypermethylation in gene body regions were associated with gene expression. Enrichment analysis revealed that promoter hypo-DMGs in TYO fish were significantly enriched in typical immune response pathways, whereas gene body hyper-DMGs in TYO fish were significantly enriched in terms related to RNA transcription, biosynthesis, and energy production. RNA-seq analysis of the corresponding samples indicated that most of the genes in the above terms were upregulated in TYO fish. Moreover, gene function analysis revealed that the two genes involved in energy metabolism displayed antiviral effects.

Conclusions
Collectively, these results revealed genome-wide variations in DNA methylation between grass carp of different ages. DNA methylation and gene expression variations in genes involved in immune response, biosynthesis, and energy production may contribute to age-dependent susceptibility to GCRV in grass carp. Our results provide important information for disease-resistant breeding programs for grass carp and may also benefit research on age-dependent diseases in humans.
5’isomiR-183-5p|+2 elicits tumor suppressor activity in a negative feedback loop with E2F1
Authors: Li Xiaoya , Michels Birgitta Elisabeth , Tosun Oyku Ece , Jung Janine , Kappes Jolane , Ibing Susanne , Nataraj Nishanth Belugali , Sahay Shashwat , Schneider Martin , Wörner Angelika , Becki Corinna , Ishaque Naveed , Feuerbach Lars , Heßling Bernd , Helm Dominic , Will Rainer , Yarden Yosef , Müller-Decker Karin , Wiemann Stefan , Körner Cindy 
Published: June 2022

Abstract
Background
MicroRNAs (miRNAs) and isomiRs play important roles in tumorigenesis as essential regulators of gene expression. 5’isomiRs exhibit a shifted seed sequence compared to the canonical miRNA, resulting in different target spectra and thereby extending the phenotypic impact of the respective common pre-miRNA. However, for most miRNAs, expression and function of 5’isomiRs have not been studied in detail yet. Therefore, this study aims to investigate the functions of miRNAs and their 5’isomiRs.

Methods
The expression of 5’isomiRs was assessed in The Cancer Genome Atlas (TCGA) breast cancer patient dataset. Phenotypic effects of miR-183 overexpression in triple-negative breast cancer (TNBC) cell lines were investigated in vitro and in vivo by quantifying migration, proliferation, tumor growth and metastasis. Direct targeting of E2F1 by miR-183-5p|+2 was validated with a 3’UTR luciferase assay and linked to the phenotypes of isomiR overexpression.

Results
TCGA breast cancer patient data indicated that three variants of miR-183-5p are highly expressed and upregulated, namely miR-183-5p|0, miR-183-5p|+1 and miR-183-5p|+2. However, TNBC cell lines displayed reduced proliferation and invasion upon overexpression of pre-miR-183. While invasion was reduced individually by all three isomiRs, proliferation and cell cycle progression were specifically inhibited by overexpression of miR-183-5p|+2. Proteomic analysis revealed reduced expression of E2F target genes upon overexpression of this isomiR, which could be attributed to direct targeting of E2F1, specifically by miR-183-5p|+2. Knockdown of E2F1 partially phenocopied the effect of miR-183-5p|+2 overexpression on cell proliferation and cell cycle. Gene set enrichment analysis of TCGA and METABRIC patient data indicated that the activity of E2F strongly correlated with the expression of miR-183-5p, suggesting transcriptional regulation of the miRNA by a factor of the E2F family. Indeed, in vitro, expression of miR-183-5p was regulated by E2F1. Hence, miR-183-5p|+2 directly targeting E2F1 appears to be part of a negative feedback loop potentially fine-tuning its activity.

Conclusions
This study demonstrates that 5’isomiRs originating from the same arm of the same pre-miRNA (i.e. pre-miR-183-5p) may exhibit different functions and thereby collectively contribute to the same phenotype. Here, one of three isomiRs was shown to counteract expression of the pre-miRNA by negatively regulating a transcriptional activator (i.e. E2F1). We speculate that this might be part of a regulatory mechanism to prevent uncontrolled cell proliferation, which is disabled during cancer progression.

Graphical Abstract
CircCEMIP promotes anoikis-resistance by enhancing protective autophagy in prostate cancer cells
Authors: Yu Ying , Song Yarong , Cheng Lulin , Chen Liang , Liu Bing , Lu Dingheng , Li Xuexiang , Li Yunxue , Lv Fang , Xing Yifei 
Published: June 2022

Abstract
Background
Circular RNAs (circRNAs) are essential participants in the development and progression of various malignant tumors. Previous studies have shown that cell migration-inducing protein (CEMIP) accelerates prostate cancer (PCa) anoikis resistance (AR) by activating autophagy. This study focused on the effect of circCEMIP on PCa metastasis.

Methods
This study gradually revealed the role of circ_0004585 in PCa anoikis resistance via quantitative real-time PCR (qRT-PCR) analysis, western blotting, pull-down assays, and dual fluorescence reporter assays.

Results
Functionally, circ_0004585 promoted PCa cells invasion and metastasis both in vitro and in vivo. Mechanistically, circ_0004585 directly interacted with miR-1248 to upregulate target gene expression. Furthermore, target prediction and dual-luciferase reporter assays identified transmembrane 9 superfamily member 4 (TM9SF4) as a potential miR-1248 target. Pathway analysis revealed that TM9SF4 activated autophagy to promote PCa cells anoikis resistance via mTOR phosphorylation.

Conclusions
These results demonstrated that circ_0004585 played an oncogenic role during PCa invasion and metastasis by targeting the miR-1248/TM9SF4 axis while providing new insight into therapeutic strategy development for metastatic PCa.
Neonatal resuscitation practices in Italy: a survey of the Italian Society of Neonatology (SIN) and the Union of European Neonatal and Perinatal Societies (UENPS)
Authors: Gizzi Camilla , Trevisanuto Daniele , Gagliardi Luigi , Vertecchi Giulia , Ghirardello Stefano , Di Fabio Sandra , Moretti Corrado , Mosca Fabio 
Published: June 2022

Abstract
Background
Providing appropriate care at birth remains a crucial strategy for reducing neonatal mortality and morbidity. We aimed to evaluate the consistency of practice and the adherence to the international guidelines on neonatal resuscitation in level-I and level-II Italian birth hospitals.

Methods
This was a cross-sectional electronic survey. A 91-item questionnaire focusing on current delivery room practices in neonatal resuscitation was sent to the directors of 418 Italian neonatal facilities.

Results
The response rate was 61.7% (258/418), comprising 95.6% (110/115) from level-II and 49.0% (148/303) from level-I centres. In 2018, approximately 300,000 births occurred at the participating hospitals, with a median of 1664 births/centre in level-II and 737 births/centre in level-I hospitals. Participating level-II hospitals provided nasal-CPAP and/or high-flow nasal cannulae (100%), mechanical ventilation (99.1%), HFOV (71.0%), inhaled nitric oxide (80.0%), therapeutic hypothermia (76.4%), and extracorporeal membrane oxygenation ECMO (8.2%). Nasal-CPAP and/or high-flow nasal cannulae and mechanical ventilation were available in 77.7 and 21.6% of the level-I centres, respectively. Multidisciplinary antenatal counselling was routinely offered to parents at 90.0% (90) of level-II hospitals, and 57.4% (85) of level-I hospitals (p < 0.001). Laryngeal masks were available in more than 90% of participating hospitals while an end-tidal CO2 detector was available in only 20%. Significant differences between level-II and level-I centres were found in the composition of resuscitation teams for high-risk deliveries, team briefings before resuscitation, providers qualified with full resuscitation skills, self-confidence, and use of sodium bicarbonate.

Conclusions
This survey provides insight into neonatal resuscitation practices in a large sample of Italian hospitals. Overall, adherence to international guidelines on neonatal resuscitation was high, but differences in practice between the participating centres and the guidelines exist. Clinicians and stakeholders should consider this information when allocating resources and planning perinatal programs in Italy.
PragmaTic, prospEctive, randomized, controlled, double-blind, mulTi-centre, multinational study on the safety and efficacy of a 6% HydroxYethyl Starch (HES) solution versus an electrolyte solution in trauma patients: study protocol for the TETHYS study
Authors: Palma Clementina Duran , Mamba Musawenkosi , Geldenhuys Johan , Fadahun Oluwafolajimi , Rossaint Rolf , Zacharowski Kai , Brand Martin , Díaz-Cambronero Óscar , Belda Javier , Westphal Martin , Brauer Ute , Dormann Dirk , Dehnhardt Tamara , Hernandez-Gonzalez Martin , Schmier Sonja , de Korte Dianne , Plani Frank , Buhre Wolfgang 
Published: June 2022

Abstract
Background
Trauma may be associated with significant to life-threatening blood loss, which in turn may increase the risk of complications and death, particularly in the absence of adequate treatment. Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss to maintain or re-establish hemodynamic stability with the ultimate goal to avoid organ hypoperfusion and cardiovascular collapse. The current study compares a 6% HES 130 solution (Volulyte 6%) versus an electrolyte solution (Ionolyte) for volume replacement therapy in adult patients with traumatic injuries, as requested by the European Medicines Agency to gain more insights into the safety and efficacy of HES in the setting of trauma care.

Methods
TETHYS is a pragmatic, prospective, randomized, controlled, double-blind, multicenter, multinational trial performed in two parallel groups. Eligible consenting adults ≥ 18 years, with an estimated blood loss of ≥ 500 ml, and in whom initial surgery is deemed necessary within 24 h after blunt or penetrating trauma, will be randomized to receive intravenous treatment at an individualized dose with either a 6% HES 130, or an electrolyte solution, for a maximum of 24 h or until reaching the maximum daily dose of 30 ml/kg body weight, whatever occurs first. Sample size is estimated as 175 patients per group, 350 patients total (α = 0.025 one-tailed, power 1–β = 0.8). Composite primary endpoint evaluated in an exploratory manner will be 90-day mortality and 90-day renal failure, defined as AKIN stage ≥ 2, RIFLE injury/failure stage, or use of renal replacement therapy (RRT) during the first 3 months. Secondary efficacy and safety endpoints are fluid administration and balance, changes in vital signs and hemodynamic status, changes in laboratory parameters including renal function, coagulation, and inflammation biomarkers, incidence of adverse events during treatment period, hospital, and intensive care unit (ICU) length of stay, fitness for ICU or hospital discharge, and duration of mechanical ventilation and/or RRT.

Discussion
This pragmatic study will increase the evidence on safety and efficacy of 6% HES 130 for treatment of hypovolemia secondary to acute blood loss in trauma patients.

Trial registration
Registered in EudraCT, No.: 2016-002176-27 (21 April 2017) and ClinicalTrials.gov, ID: NCT03338218 (09 November 2017).
Zhizhu Kuanzhong Capsule in treating patients with functional dyspepsia postprandial distress syndrome: study protocol for a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial
Authors: Xiao Mengli , Zhong Linda L. D. , Lam Wai Ching , Zhao Yingpan , Gwee Kok-Ann , Holtmann Gerald , Tack Jan , Suzuki Hidekazu , Chen Min-Hu , Xiao Yinglian , Hou Xiaohua , Liu Jinsong , Li Yang , Tang Xu-Dong , Lu Fang 
Published: June 2022

Abstract
Background
Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders. Based on the various symptoms present in patients with functional dyspepsia postprandial distress syndrome (FD-PDS), routine agents such as acid suppressants, prokinetic drugs, and centrally acting drugs, offer limited treatment choices with potential side effects. As a preliminary clinical trial showed that the marketed product Zhizhu Kuanzhong Capsule (ZZKZ) can improve symptoms in FD-PDS patients, our study aims to provide further evidence on the clinical efficacy and safety of ZZKZ in the treatment of patients with FD-PDS.

Methods
In this multicenter, randomized, patient- and investigator-blinded, placebo-controlled, parallel-group clinical trial, we will recruit patients with FD-PDS from 18 hospitals in China and Australia. The trial will enroll patients with FD-PDS based on the Rome IV diagnostic criteria. A total of 480 eligible patients will be randomized 1:1 into either ZZKZ or placebo group with 8 weeks of treatment and 4 weeks of follow-up. The primary endpoint will be measured by a self-rated Visual Analogue Score (VAS) for the degree of discomfort with both symptoms of postprandial fullness and early satiation, recorded once a day and 7 days a week. The primary analysis will aim to compare the response rate for FD-PDS VAS score between the groups before and after 8 weeks of treatment with an alpha level of 0.05 (2-sided).

Discussion
This trial aims to strengthen the evidence for the efficacy and safety of ZZKZ, a marketed product, in treating FD-PDS. Compared to the previous clinical trial that targeted FD-PDS, this trial will have an 8-week double-blind treatment period to investigate the effect of long-term mediation through comparison with the placebo group.

Trial registration
ClinicalTrials.gov NCT03825692. Registered on 28 January 2019