bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization and modulation of endoplasmic reticulum stress response target genes in Kluyveromyces marxianus to improve secretory expressions of heterologous proteins
Authors: Shi Tianfang , Zhou Jungang , Xue Aijuan , Lu Hong , He Yungang , Yu Yao
Published: December 2021

Background

Kluyveromyces marxianus is a promising cell factory for producing bioethanol and that raised a demand for a high yield of heterologous proteins in this species. Expressions of heterologous proteins usually lead to the accumulation of misfolded or unfolded proteins in the lumen of the endoplasmic reticulum (ER) and then cause ER stress. To cope with this problem, a group of ER stress response target genes (ESRTs) are induced, mainly through a signaling network called unfolded protein response (UPR). Characterization and modulation of ESRTs direct the optimization of heterologous expressions. However, ESRTs in K. marxianus have not been identified so far.

Results

In this study, we characterized the ER stress response in K. marxianus for the first time, by using two ER stress-inducing reagents, dithiothreitol (DTT) and tunicamycin (TM). Results showed that the Kar2–Ire1–Hac1 pathway of UPR is well conserved in K. marxianus. About 15% and 6% of genes were upregulated during treatment of DTT and TM, respectively. A total of 115 upregulated genes were characterized as ESRTs, among which 97 genes were identified as UPR target genes and 37 UPR target genes contained UPR elements in their promoters. Genes related to carbohydrate metabolic process and actin filament organization were identified as new types of UPR target genes. A total of 102 ESRTs were overexpressed separately in plasmids and their effects on productions of two different lignocellulolytic enzymes were systematically evaluated. Overexpressing genes involved in carbohydrate metabolism, including PDC1, PGK and VID28, overexpressing a chaperone gene CAJ1 or overexpressing a reductase gene MET13 substantially improved secretion expressions of heterologous proteins. Meanwhile, overexpressing a novel gene, KLMA_50479 (named ESR1), as well as overexpressing genes involved in ER-associated protein degradation (ERAD), including HRD3, USA1 andYET3, reduced the secretory expressions. ESR1 and the aforementioned ERAD genes were deleted from the genome. Resultant mutants, except the yet3Δ mutant, substantially improved secretions of three different heterologous proteins. During the fed-batch fermentation, extracellular activities of an endoxylanase and a glucanase in hrd3Δ cells improved by 43% and 28%, respectively, compared to those in wild-type cells.

Conclusions

Our results unveil the transcriptional scope of the ER stress response in K. marxianus and suggest efficient ways to improve productions of heterologous proteins by manipulating expressions of ESRTs.
Proteomic and biochemical responses to different concentrations of CO2 suggest the existence of multiple carbon metabolism strategies in Phaeodactylum tricornutum
Authors: Wu Songcui , Gu Wenhui , Jia Shuao , Wang Lepu , Wang Lijun , Liu Xuehua , Zhou Lu , Huang Aiyou , Wang Guangce
Published: December 2021

Background

Diatoms are well known for high photosynthetic efficiency and rapid growth rate, which are not only important oceanic primary producer, but also ideal feedstock for microalgae industrialization. Their high success is mainly due to the rapid response of photosynthesis to inorganic carbon fluctuations. Thus, an in-depth understanding of the photosynthetic carbon fixation mechanism of diatoms will be of great help to microalgae-based applications. This work directed toward the analysis of whether C4 photosynthetic pathway functions in the model marine diatom Phaeodactylum tricornutum, which possesses biophysical CO2-concentrating mechanism (CCM) as well as metabolic enzymes potentially involved in C4 photosynthetic pathway.

Results

For P. tricornutum, differential proteome, enzyme activities and transcript abundance of carbon metabolism-related genes especially biophysical and biochemical CCM-related genes in response to different concentrations of CO2 were tracked in this study. The upregulated protein abundance of a carbonic anhydrases and a bicarbonate transporter suggested biophysical CCM activated under low CO2 (LC). The upregulation of a number of key C4-related enzymes in enzymatic activity, transcript and protein abundance under LC indicated the induction of a mitochondria-mediated CCM in P. tricornutum. Moreover, protein abundance of a number of glycolysis, tricarboxylic acid cycle, photorespiration and ornithine–urea cycle related proteins upregulated under LC, while numbers of proteins involved in the Calvin cycle and pentose phosphate pathway were downregulated. Under high CO2 (HC), protein abundance of most central carbon metabolism and photosynthesis-related proteins were upregulated.

Conclusions

The proteomic and biochemical responses to different concentrations of CO2 suggested multiple carbon metabolism strategies exist in P. tricornutum. Namely, LC might induce a mitochondrial-mediated C4-like CCM and the improvement of glycolysis, tricarboxylic acid cycle, photorespiration and ornithine–urea cycle activity contribute to the energy supply and carbon and nitrogen recapture in P. tricornutum to cope with the CO2 limitation, while P. tricornutum responds to the HC environment by improving photosynthesis and central carbon metabolism activity. These findings can not only provide evidences for revealing the global picture of biophysical and biochemical CCM in P. tricornutum, but also provide target genes for further microalgal strain modification to improve carbon fixation and biomass yield in algal-based industry.
Distinct role of histone chaperone Asf1a and Asf1b during fertilization and pre-implantation embryonic development in mice
Authors: Wang Xuemei , Wang Lu , Dou Jie , Yu Tianjiao , Cao Pengbo , Fan Na , Borjigin Uyunbilig , Nashun Buhe
Published: December 2021

Background

Asf1 is a well-conserved histone chaperone that regulates multiple cellular processes in different species. Two paralogous genes, Asf1a and Asf1b exist in mammals, but their role during fertilization and early embryogenesis remains to be investigated further.

Methods

We analyzed the dynamics of histone chaperone Asf1a and Asf1b in oocytes and pre-implantation embryos in mice by immunofluorescence and real-time quantitative PCR, and further investigated the role of Asf1a and Asf1b during fertilization and pre-implantation development by specific Morpholino oligos-mediated knock down approach.

Results

Immunofluorescence with specific antibodies revealed that both Asf1a and Asf1b were deposited in the nuclei of fully grown oocytes, accumulated abundantly in zygote and 2-cell embryonic nuclei, but turned low at 4-cell stage embryos. In contrast to the weak but definite nuclear deposition of Asf1a, Asf1b disappeared from embryonic nuclei at morula and blastocyst stages. The knockdown of Asf1a and Asf1b by specific Morpholino oligos revealed that Asf1a but not Asf1b was required for the histone H3.3 assembly in paternal pronucleus. However, knockdown of either Asf1a or Asf1b expression decreased developmental potential of pre-implantation embryos. Furthermore, while Asf1a KD severely reduced H3K56 acetylation level and the expression of Oct4 in blastocyst stage embryos, Asf1b KD almost eliminated nuclear accumulation of proliferating cell marker-PCNA in morula stage embryos. These results suggested that histone chaperone Asf1a and Asf1b play distinct roles during fertilization and pre-implantation development in mice.

Conclusions

Our data suggested that both Asf1a and Asf1b are required for pre-implantation embryonic development. Asf1a regulates H3K56ac levels and Oct4 expression, while Asf1b safeguards pre-implantation embryo development by regulating cell proliferation. We also showed that Asf1a, but not Asf1b, was necessary for the assembly of histone H3.3 in paternal pronuclei after fertilization.
RNA-seq analysis identified glucose-responsive genes and YqfO as a global regulator in Bacillus subtilis
Authors: Kanesaki Yu , Ogura Mitsuo
Published: December 2021

Objective

We observed that the addition of glucose enhanced the expression of sigX and sigM, encoding extra-cytoplasmic function sigma factors in Bacillus subtilis. Several regulatory factors were identified for this phenomenon, including YqfO, CshA (RNA helicase), and YlxR (nucleoid-associated protein). Subsequently, the relationships among these regulators were analyzed. Among them, YqfO is conserved in many bacterial genomes and may function as a metal ion insertase or metal chaperone, but has been poorly characterized. Thus, to further characterize YqfO, we performed RNA sequencing (RNA-seq) analysis of YqfO in addition to CshA and YlxR.

Results

We first performed comparative RNA-seq to detect the glucose-responsive genes. Next, to determine the regulatory effects of YqfO in addition to CshA and YlxR, three pairs of comparative RNA-seq analyses were performed (yqfO/wt, cshA/wt, and ylxR/wt). We observed relatively large regulons (approximately 420, 780, and 180 for YqfO, CshA, and YlxR, respectively) and significant overlaps, indicating close relationships among the three regulators. This study is the first to reveal that YqfO functions as a global regulator in B. subtilis.
Associations between indicators of socioeconomic position and DNA methylation: a scoping review
Authors: Cerutti Janine , Lussier Alexandre A. , Zhu Yiwen , Liu Jiaxuan , Dunn Erin C.
Published: December 2021

Background

Socioeconomic position (SEP) is a major determinant of health across the life course. Yet, little is known about the biological mechanisms explaining this relationship. One possibility widely pursued in the scientific literature is that SEP becomes biologically embedded through epigenetic processes such as DNA methylation (DNAm), wherein the socioeconomic environment causes no alteration in the DNA sequence but modifies gene activity in ways that shape health.

Methods

To understand the evidence supporting a potential SEP-DNAm link, we performed a scoping review of published empirical findings on the association between SEP assessed from prenatal development to adulthood and DNAm measured across the life course, with an emphasis on exploring how the developmental timing, duration, and type of SEP exposure influenced DNAm.

Results

Across the 37 identified studies, we found that: (1) SEP-related DNAm signatures varied across the timing, duration, and type of SEP indicator; (2) however, longitudinal studies examining repeated SEP and DNAm measures are generally lacking; and (3) prior studies are conceptually and methodologically diverse, limiting the interpretability of findings across studies with respect to these three SEP features.

Conclusions

Given the complex relationship between SEP and DNAm across the lifespan, these findings underscore the importance of analyzing SEP features, including timing, duration, and type. To guide future research, we highlight additional research gaps and propose four recommendations to further unravel the relationship between SEP and DNAm.
Dynamic planar scintigraphy for the rapid kinetic measurement of myocardial 123I-MIBG turnover can identify Lewy body disease
Authors: Kumakura Yoshitaka , Shimizu Yuji , Hariu Masatsugu , Ichikawa Ken-ichi , Yoshida Norihito , Suzuki Masato , Oji Satoru , Narukawa Shinya , Yoshimasu Haruo , Nomura Kyoichi
Published: December 2021

Background

Using two static scans for 123I-meta-iodobenzyl-guanidine (123I-MIBG) myocardial scintigraphy ignores the dynamic response from vesicular trapping in nerve terminals. Moreover, the long pause between scans is impractical for patients with Lewy body diseases (LBDs). Here, we optimized indices that capture norepinephrine kinetics, tested their diagnostic performance, and determined the differences in 123I-MIBG performance among disease groups.

Methods

We developed a new 30-min protocol for 123I-MIBG dynamic planar imaging for suspected LBD patients. Pharmacokinetic modelling of time-activity curves (TACs) was used to calculate three new indices: unidirectional uptake of 123I-MIBG to vesicular trapping (iUp), rate of myocardial 123I-MIBG loss (iLoss), and non-specific fractional distribution of 123I-MIBG in the interstitial space. We compared the performance of the new and existing indices with regard to discrimination of patients with or without LBDs. Subgroup analysis was performed to examine differences in 123I-MIBG turnover between patients in a dementia with Lewy bodies (DLB) group and two Parkinson’s disease (PD) groups, one with and the other without REM sleep behaviour disorder (RBD).

Results

iLoss was highly discriminative, particularly for patients with low myocardial 123I-MIBG trapping, and the new indices outperformed existing ones. ROC analysis revealed that the AUC of iLoss (0.903) was significantly higher than that of early HMR (0.863), while comparable to that of delayed HMR (0.892). The RBD-positive PD group and the DLB group had higher turnover rates than the RBD-negative PD group, indicating a potential association between prognosis and iLoss.

Conclusion

123I-MIBG turnover can be quantified in 30 min using a three-parameter model based on 123I-MIBG TACs. The discriminatory performance of the new model-based indices might help explain the neurotoxicity or neurodegeneration that occurs in LBD patients.
L-type amino acid transporter (LAT) 1 expression in 18F-FET-negative gliomas
Authors: Vettermann Franziska J. , Diekmann Caroline , Weidner Lorraine , Unterrainer Marcus , Suchorska Bogdana , Ruf Viktoria , Dorostkar Mario , Wenter Vera , Herms Jochen , Tonn Jörg-Christian , Bartenstein Peter , Riemenschneider Markus J. , Albert Nathalie L.
Published: December 2021

Background

O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) is a highly sensitive PET tracer for glioma imaging, and its uptake is suggested to be driven by an overexpression of the L-type amino-acid transporter 1 (LAT1). However, 30% of low- and 5% of high-grade gliomas do not present enhanced 18F-FET uptake at primary diagnosis (“18F-FET-negative gliomas”) and the pathophysiologic basis for this phenomenon remains unclear. The aim of this study was to determine the expression of LAT1 in a homogeneous group of newly diagnosed 18F-FET-negative gliomas and to compare them to a matched group of 18F-FET-positive gliomas. Forty newly diagnosed IDH-mutant astrocytomas without 1p/19q codeletion were evaluated (n = 20 18F-FET-negative (tumour-to-background ratio (TBR) < 1.6), n = 20 18F-FET-positive gliomas (TBR > 1.6)). LAT1 immunohistochemistry (IHC) was performed using SLC7A5/LAT1 antibody. The percentage of LAT1-positive tumour cells (%) and the staining intensity (range 0–2) were multiplied to an overall score (H-score; range 0–200) and correlated to PET findings as well as progression-free survival (PFS).

Results

IHC staining of LAT1 expression was positive in both, 18F-FET-positive as well as 18F-FET-negative gliomas. No differences were found between the 18F-FET-negative and 18F-FET-positive group with regard to percentage of LAT1-positive tumour cells, staining intensity or H-score. Interestingly, the LAT1 expression showed a significant negative correlation with the PFS (p = 0.031), whereas no significant correlation was found for TBRmax, neither in the overall group nor in the 18F-FET-positive group only (p = 0.651 and p = 0.140).

Conclusion

Although LAT1 is reported to mediate the uptake of 18F-FET into tumour cells, the levels of LAT1 expression do not correlate with the levels of 18F-FET uptake in IDH-mutant astrocytomas. In particular, the lack of tracer uptake in 18F-FET-negative gliomas cannot be explained by a reduced LAT1 expression. A higher LAT1 expression in IDH-mutant astrocytomas seems to be associated with a short PFS. Further studies regarding mechanisms influencing the uptake of 18F-FET are necessary.
Amyloid PET quantification using low-dose CT-guided anatomic standardization
Authors: Matsuda Hiroshi , Yamao Tensho , Shakado Mitsuru , Shigemoto Yoko , Okita Kyoji , Sato Noriko
Published: December 2021

Background

Centiloid (CL) scaling has become a standardized quantitative measure in amyloid PET because it facilitates the direct comparison of results across institutions, even when different analytical methods or tracers are used. Standard volumes of interest must be used to calculate the CL scale after the anatomic standardization of amyloid PET images using coregistered MRI; if the MRI is unavailable, the CL scale cannot be accurately calculated. This study sought to determine the substitutability of low-dose CT, which is used to correct PET attenuation in PET/CT equipment, by evaluating the measurement accuracy when low-dose CT is used as an alternative to MRI in the calculation of the CL scale. Amyloid PET images obtained using 18F-flutemetamol from 24 patients with possible or probable Alzheimer’s disease were processed to calculate the CL scale using 3D T1-weighted MRI and low-dose CT of PET/CT. CLMRI and CLCT were, respectively, defined as the use of MRI and CT for anatomic standardization and compared. Regional differences in the CT-based and MRI-based standardized anatomic images were also investigated. Trial registration: Japan Registry of Clinical Trials, jRCTs031180321 (registered 18 March 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031180321).

Results

A Bland–Altman plot showed that CLCT was slightly but significantly underestimated (mean ± standard deviation, − 1.7 ± 2.4; p < 0.002) compared with CLMRI. The 95% limits of agreement ranged from − 2.8 to − 0.7. Pearson correlation analysis showed a highly significant correlation of r = 0.998 between CLCT and CLMRI (p < 0.001). The linear regression equation was CLMRI = 1.027 × CLCT + 0.762. In a Bland–Altman plot, Spearman correlation analysis did not identify a significant association between the difference in CLMRI versus CLCT and CL load (ρ =  − 0.389, p = 0.060). This slight underestimation of CLCT may derive from slightly higher uptake when the cerebellum is used as a reference area in CT-based anatomically standardized PET images versus MRI-based images.

Conclusions

Low-dose CT of PET/CT can substitute for MRI in the anatomic standardization used to calculate the CL scale from amyloid PET, although a slight underestimation occurs.
Identification of Gm15441, a Txnip antisense lncRNA, as a critical regulator in liver metabolic homeostasis
Authors: Xin Mingyang , Guo Qian , Lu Qingchun , Lu Juan , Wang Po-shun , Dong Yun , Li Tao , Chen Ye , Gerhard Glenn S. , Yang Xiao-feng , Autieri Michael , Yang Ling
Published: December 2021

Background

The majority of mammalian genome is composed of non-coding regions, where numerous long non-coding RNAs (lncRNAs) are transcribed. Although lncRNAs have been identified to regulate fundamental biological processes, most of their functions remain unknown, especially in metabolic homeostasis. Analysis of our recent genome-wide screen reveals that Gm15441, a thioredoxin-interacting protein (Txnip) antisense lncRNA, is the most robustly induced lncRNA in the fasting mouse liver. Antisense lncRNAs are known to regulate their sense gene expression. Given that Txnip is a critical metabolic regulator of the liver, we aimed to investigate the role of Gm15441 in the regulation of Txnip and liver metabolism.

Methods

We examined the response of Gm15441 and Txnip under in vivo metabolic signals such as fasting and refeeding, and in vitro signals such as insulin and key metabolic transcription factors. We investigated the regulation of Txnip expression by Gm15441 and the underlying mechanism in mouse hepatocytes. Using adenovirus-mediated liver-specific overexpression, we determined whether Gm15441 regulates Txnip in the mouse liver and modulates key aspects of liver metabolism.

Results

We found that the expression levels of Gm15441 and Txnip showed a similar response pattern to metabolic signals in vivo and in vitro, but that their functions were predicted to be opposite. Furthermore, we found that Gm15441 robustly reduced Txnip protein expression in vitro through sequence-specific regulation and translational inhibition. Lastly, we confirmed the Txnip inhibition by Gm15441 in vivo (mice) and found that Gm15441 liver-specific overexpression lowered plasma triglyceride and blood glucose levels and elevated plasma ketone body levels.

Conclusions

Our data demonstrate that Gm15441 is a potent Txnip inhibitor and a critical metabolic regulator in the liver. This study reveals the therapeutic potential of Gm15441 in treating metabolic diseases.
Involvement and skepticism towards the JCI Accreditation process among hospital’s four sectors employees: suggestions for cultural change
Authors: Bord Shiran , Sass Inna , Hayms Gila , Moskowitz Kobi , Baruch Hagar , Basis Fuad
Published: December 2021

Background

Implementing the JCI Accreditation process as an organizational culture may face resistance. However, the skepticism and involvement of different hospital sectors (medical, nursing, paramedical, and administrative/logistic) in the process may vary. Conducting organizational change needs tools to decrease resistance.

Objectives

To investigate the attitudes, cultural norms, and satisfaction of the different sectors regarding the accreditation process, and to suggest ways to integrate the process as part of the organizational culture.

Materials and methods

A cross-sectional survey was conducted among 462 respondents (187 nurses, 95 physicians, 92 administrative, 88 paramedical) at Rambam Health Care Campus, a tertiary hospital in Israel. The hospital employees' attitudes, cultural norms, and satisfaction were assessed. ANOVA tests were used to examine the differences among the different sectors. The association between the satisfaction from the process and the preferred type of training was examined using Pearson's correlation coefficient.

Results

Significant differences were found among the sectors in the scores related to attitude, cultural norms, and satisfaction from the accreditation process (F (3, 456) = 17.95, p < 0.001, η2 = 0.10). Gabriel post-hoc test revealed significantly lower scores between the medical and paramedical sectors. A positive correlation was found between the degree of satisfaction with the process and the satisfaction with the training type. Frontal education and video demonstrations were rated significantly higher among all 10 training types.

Conclusions

More efforts should be made to increase involvement among physicians and paramedical teams in the accreditation process. Each sector leadership involvement is essential for their involvement too. Early involvement of the Israeli Medical Association in the process might have achieved better physicians’ collaboration. Frontal education and video demonstrations may help decrease skepticism and increase positive attitudes.
The efficacy and safety of antimuscarinics for the prevention or treatment of catheter-related bladder discomfort: a systematic review and meta-analysis of randomized controlled trials
Authors: Zhou Zhongbao , Cui Yuanshan , Zhang Xiaoyi , Lu Youyi , Chen Zhipeng , Zhang Yong
Published: December 2021

Objectives

This meta-analysis aimed to evaluate the efficacy and safety of antimuscarinics for the prevention or treatment of catheter related bladder discomfort (CRBD).

Methods

The MEDLINE, EMBASE, and Cochrane Controlled Trials Register (from 1987 to July 2021) were used to search randomized controlled trials. The PRISMA checklists were followed. RevMan5.4.0 was used for statistical analysis.

Results

Eleven studies involving 1165 patients were involved in the analysis. The study reported that the incidence of CRBD observed in the antimuscarinics group was significantly lower than that of the control group at 0-, 1-, 2-, and 6-h after drug therapy (P = 0.001, P < 0.0001, P = 0.0005, and P = 0.001, respectively). For side effects, there were not statistical differences between the antimuscarinics group and the control group, mainly including dry mouth (risk ratio (RR) = 1.31, 95% confidence interval (CI) = 0.95 to 1.80, P = 0.09), postoperative nausea and vomiting (RR = 1.02, 95% CI = 0.55 to 1.90, P = 0.87), facial flushing (RR = 1.06, 95% CI = 0.43 to 2.61, P = 0.90), and blurred vision (RR = 0.95, 95% CI = 0.35 to 2.58, P = 0.91). Besides, rescue analgesics were required less in the antimuscarinics group than in the control group (RR = 0.51, 95% CI = 0.32 to 0.80, P = 0.003).

Conclusions

Compared with the control group, the antimuscarinics group had a significant improvement on CRBD, the patients were well tolerated and the use rate of rescue analgesics was low.
Mortality and associated risk factors in perioperative acute kidney injury treated with continuous renal replacement therapy
Authors: Uusalo Panu , Hellman Tapio , Järvisalo Mikko J.
Published: December 2021

Background

Perioperative acute kidney injury (AKI) is associated with multiple postoperative complications leading to prolonged hospital stay and higher costs. AKI requiring continuous renal replacement therapy (CRRT) after surgery has an incidence of 2–6% and mortality approximates 40–60%. Previous studies examining mortality in perioperative AKI patients managed with CRRT have concentrated on cardiac surgery patients and there are very limited data on broad surgical patient populations requiring CRRT. We examined long-term mortality and factors associated with poor outcome in a broad surgical population requiring CRRT for perioperative AKI during a 10-year period.

Methods

Surgical patients admitted to the intensive care unit (ICU) of academic tertiary hospital requiring CRRT between years 2010–2019 were included. CRRT was performed using regional citrate-calcium-anticoagulation. Extracted data included patient demographics, comorbidities, and clinical parameters at ICU admission and at the initiation of CRRT. Creatinine and estimated glomerular filtration rate (eGFR) were measured at 1 year after ICU admission.

Results

A total of 157 patients were included in the study. ICU mortality was 42.7%, 90-day mortality 58.0% and 1-year mortality 62.4%. Blood lactate at ICU admission and CRRT initiation were independently associated with mortality in the multivariate models. Patients with lactate > 4 mmol/l had higher mortality than patients with normal lactate (77% vs. 21%) (p< 0.001). Creatinine (p= 0.004) and eGFR (p< 0.001) remained significantly altered at 1 year of follow-up compared to baseline.

Conclusions

Patients undergoing surgery and requiring perioperative CRRT in the ICU have a high risk of mortality. Mortality appears to be independently associated with lactate levels.
Comparison of different scales for the evaluation of anxiety and compliance with anesthetic induction in children undergoing scheduled major outpatient surgery
Authors: Vieco-García Alberto , López-Picado Amanda , Fuentes Manuel , Francisco-González Laura , Joyanes Belén , Soto Carmen , Garcia de la Aldea Ana , Gonzalez-Perrino Carlos , Aleo Esther
Published: December 2021

Introduction

Anxiety in children triggered by a scheduled surgical intervention is a major issue due to its frequency and consequences. Preoperative anxiety is associated with increased patient fear and agitation on anesthetic induction. The aim of this study is to compare three preoperative anxiety scales for children undergoing elective outpatient surgery, and to correlate each of these tools with the degree of patient compliance on induction, as assessed by the Induction Compliance Checklist (ICC).

Methods

An observational prospective study was performed on a cohort of children with ages between 2 and 16 years old, scheduled for outpatient surgery. Anxiety was assessed upon arrival to the hospital (M0), during transfer to the surgical unit (M1), and in the operating room during anesthetic induction (M2). Anxiety in the parents (measured with the State-Trait Anxiety Inventory, STAI) and in the children (measured with the Spence Anxiety Scale-Pediatric, SCAS-P, the State-Trait Anxiety Inventory Children, STAIC, and Modified Yale Preoperative Anxiety Scale, m-YPAS) was assessed. Compliance with anesthetic induction was assessed with ICC.

Results

The study included 76 patients (72.4% male, median age 7.9 years). Anxiety scores (m-YPAS) increased as the moment of surgery approached, being greater at the entrance to the surgical unit (M0 = 26.1 ± 9.5; M1 = 31.8 ± 18.1; M2 = 33.5 ± 21.1). A strong correlation was found between ICC scale and m-YPAS at M1 (0.738) and M2 timepoints (0.794), but not with the rest of scales at M0.

Conclusions

Standard anxiety assessment scales do not predict the quality of anesthetic induction. m-YPAS scale can detect increasing anxiety in children as they approach the surgical procedure and this correlates strongly with a worse anesthetic induction, defined by higher score on ICC scale.
Evaluating the implementation of the standard treatment guidelines (STGs) and essential medicines list (EML) at a public South African tertiary institution and its associated primary health care (PHC) facilities
Authors: Govender Tashni , Suleman Fatima , Perumal-Pillay Velisha Ann
Published: December 2021

Background

The standard treatment guidelines (STGs) and essential medicines list (EML) were a policy option recommended in the National Drug Policy for South Africa in 1996 to address the irrational and bloated medicines procurement list. STGs/EML serve as a tool to promote cost-effective use of medicines; rational prescribing; and improve accessibility to medicines for all citizens. The purpose of this study was to evaluate the use and implementation of the STGs/EML by prescribers at a public tertiary institution and its associated Primary Health Care (PHC) facilities in the uMhlathuze subdistrict of KwaZulu Natal. The study aimed to provide feedback and to make recommendations to policy makers to improve the use and implementation of the STGs/EML and to inform National Health Insurance (NHI) policy development.

Method

An observational quantitative descriptive research design was used. A retrospective audit of prescriptions was conducted, and questionnaires were utilized to collect data from prescribers and the facilities to evaluate the utilization of the STGs/EML and the rational use of medicines. All descriptive analyses were presented as counts with percentages, and Fisher’s exact test was used to compare results. The data was summarized, reduced, and analysed using SAS statistics software.

Results

107 medical doctors (97%) responded to the questionnaire at hospital level and 98 nurses (98%) responded to the questionnaire at the PHC level. Results revealed that the majority of doctors, 94.4%, had access to the latest STGs/EML compared with only 41.8% of nurses. 70.3% and 78.3% of doctor’s and nurse’s prescriptions, respectively, adhered to the guidelines. 94.9% of nurses requested training on the use of STGs/EML as most of them had not received formal training on its use.

Conclusion

This study showed suboptimal adherence to STGs/EML by all prescribers, in contrast to previous research amongst nurses when hardcopies were available. Training on the use of the STGs/EML is needed at PHC level and improved monitoring of STGs/EML compliance is necessary. This study may be replicated for a wider population to paint a national picture and to periodically assess the extent of the implementation of the STGs/EML.
Light detection and ranging (LIDAR) laser altimeter for the Martian Moons Exploration (MMX) spacecraft
Authors: Senshu Hiroki , Mizuno Takahide , Umetani Kazuhiro , Nakura Toru , Konishi Akihiro , Ogawa Akihiko , Ikeda Hirokazu , Matsumoto Koji , Noda Hirotomo , Ishihara Yoshiaki , Sasaki Sho , Tateno Naoki , Ikuse Yasuyuki , Mayuzumi Katsunori , Kase Teiji , Kashine Hisayoshi
Published: December 2021

An altimeter is a critical instrument in planetary missions, for both safe operations and science activities. We present required specifications and link budget calculations for light detection and ranging (LIDAR) onboard the Martian Moons Exploration (MMX) spacecraft. During the mission phase, this LIDAR will continuously measure the distance between the spacecraft and its target. The time-series distance provides important diagnostic information for safe spacecraft operations and important information for geomorphological studies. Because MMX is a sample return mission, its LIDAR must accommodate physical disturbances on the Martian satellite surface. This resulted in changes to the optical system design.

Graphical abstract
A population-based method to determine the time-integrated activity in molecular radiotherapy
Authors: Hardiansyah Deni , Riana Ade , Kletting Peter , Zaid Nouran R. R. , Eiber Matthias , Pawiro Supriyanto A. , Beer Ambros J. , Glatting Gerhard
Published: December 2021

Background

The calculation of time-integrated activities (TIAs) for tumours and organs is required for dosimetry in molecular radiotherapy. The accuracy of the calculated TIAs is highly dependent on the chosen fit function. Selection of an adequate function is therefore of high importance. However, model (i.e. function) selection works more accurately when more biokinetic data are available than are usually obtained in a single patient. In this retrospective analysis, we therefore developed a method for population-based model selection that can be used for the determination of individual time-integrated activities (TIAs). The method is demonstrated at an example of [177Lu]Lu-PSMA-I&T kidneys biokinetics. It is based on population fitting and is specifically advantageous for cases with a low number of available biokinetic data per patient.

Methods

Renal biokinetics of [177Lu]Lu-PSMA-I&T from thirteen patients with metastatic castration-resistant prostate cancer acquired by planar imaging were used. Twenty exponential functions were derived from various parameterizations of mono- and bi-exponential functions. The parameters of the functions were fitted (with different combinations of shared and individual parameters) to the biokinetic data of all patients. The goodness of fits were assumed as acceptable based on visual inspection of the fitted curves and coefficients of variation CVs < 50%. The Akaike weight (based on the corrected Akaike Information Criterion) was used to select the fit function most supported by the data from the set of functions with acceptable goodness of fit.

Results

The function $$A_{1} { }\beta { }e^{{ - \left( {\lambda_{1} + \lambda_{{{\text{phys}}}} } \right)t}} + A_{1} { }\left( {1 - \beta } \right){ }e^{{ - \left( {\lambda_{{{\text{phys}}}} } \right)t}}$$

A
1

β

e

-

λ
1

+

λ
phys

t

+

A
1

1
-
β

e

-

λ
phys

t

with shared parameter $$\beta$$
β
was selected as the function most supported by the data with an Akaike weight of 97%. Parameters $$A_{1}$$

A
1

and $$\lambda_{1}$$

λ
1

were fitted individually for every patient while parameter $$\beta { }$$

β

was fitted as a shared parameter in the population yielding a value of 0.9632 ± 0.0037.

Conclusions

The presented population-based model selection allows for a higher number of parameters of investigated fit functions which leads to better fits. It also reduces the uncertainty of the obtained Akaike weights and the selected best fit function based on them. The use of the population-determined shared parameter for future patients allows the fitting of more appropriate functions also for patients for whom only a low number of individual data are available.
The effects of managerial ability on firm performance and the mediating role of capital structure: evidence from Taiwan
Authors: Ting Irene Wei Kiong , Tebourbi Imen , Lu Wen-Min , Kweh Qian Long
Published: December 2021

This study utilizes mediation analysis and bootstrapping to analyze the mediating effect of capital structure on the association between managerial ability and firm performance. The dataset consists of 6384 firm-year observations from the Taiwanese electronics industry during 2005–2018. Our results indicate that (1) low (high) levels of debt are likely observed in firms with CEOs with high (low) ability, (2) managerial ability positively affects firm performance, and (3) capital structure mediates the positive relationship between managerial ability and firm performance. Overall, the findings may have limited generalizability due to the specific sample characteristics and provide convincing support for the importance of capital structure as a mediator in the managerial ability-firm performance nexus. Specifically, this study highlights the need for examining the effect of managerial ability on firm performance through a mediator.
Development and validation of ester impregnated pH strips for locating nasogastric feeding tubes in the stomach—a multicentre prospective diagnostic performance study
Authors: Ni Melody , Adam Mina E. , Akbar Fatima , Huddy Jeremy R. , Borsci Simone , Buckle Peter , Rubulotta Francesca , Carr Reuben , Fotheringham Ian , Wilson Claire , Tsang Matthew , Harding Susan , White Nichola , Hanna George B.
Published: December 2021

Background

NG (nasogastric) tubes are used worldwide as a means to provide enteral nutrition. Testing the pH of tube aspirates prior to feeding is commonly used to verify tube location before feeding or medication. A pH at or lower than 5.5 was taken as evidence for stomach intubation. However, the existing standard pH strips lack sensitivity, especially in patients receiving feeding and antacids medication. We developed and validated a first-generation ester-impregnated pH strip test to improve the accuracy towards gastric placements in adult population receiving routine NG-tube feeding. The sensitivity was improved by its augmentation with the action of human gastric lipase (HGL), an enzyme specific to the stomach.

Methods

We carried out a multi-centred, prospective, two-gate diagnostic accuracy study on patients who require routine NG-tube feeding in 10 NHS hospitals comparing the sensitivity of the novel pH strip to the standard pH test, using either chest X-rays or, in its absence, clinical observation of the absence of adverse events as the reference standard. We also tested the novel pH strips in lung aspirates from patients undergoing oesophageal cancer surgeries using visual inspection as the reference standard. We simulated health economics using a decision analytic model and carried out adoption studies to understand its route to commercialisation. The primary end point is the sensitivity of novel and standard pH tests at the recommended pH cut-off of 5.5.

Results

A total of 6400 ester-impregnated pH strips were prepared based on an ISO13485 quality management system. A total of 376 gastric samples were collected from adult patients in 10 NHS hospitals who were receiving routine NG-tube feeding. The sensitivities of the standard and novel pH tests were respectively 49.2% (95% CI 44.1‑54.3%) and 70.2% (95% CI 65.6‑74.8%) under pH cut-off of 5.5 and the novel test has a lung specificity of 89.5% (95% CI 79.6%, 99.4%). Our simulation showed that using the novel test can potentially save 132 unnecessary chest X-rays per check per every 1000 eligible patients, or direct savings of £4034 to the NHS.

Conclusions

The novel pH test correctly identified significantly more patients with tubes located inside the stomach compared to the standard pH test used widely by the NHS.

Trial registration

http://www.isrctn.com/ISRCTN11170249, Registered 21 June 2017—retrospectively registered
A novel out of step relaying algorithm based on wavelet transform and a deep learning machine model
Authors: Desai Jigneshkumar Pramodbhai , Makwana Vijay Hiralal
Published: December 2021

Out-of-step protection of one or a group of synchronous generators is unreliable in a power system which has significant renewable power penetration. In this work, an innovative out-of-step protection algorithm using wavelet transform and deep learning is presented to protect synchronous generators and transmission lines. The specific patterns are generated from both stable and unstable power swing, and three-phase fault using the wavelet transform technique. Data containing 27,008 continuous samples of 48 different features is used to train a two-layer feed-forward network. The proposed algorithm gives an automatic, setting free and highly accurate classification for the three-phase fault, stable power swing, and unstable power swing through pattern recognition within a half cycle. The proposed algorithm uses the Kundur 2-area system and a 29-bus electric network for testing under different swing center locations and levels of renewable power penetration. Hardware-in-the-loop (HIL) tests show the hardware compatibility of the developed out-of-step algorithm. The proposed algorithm is also compared with recently reported algorithms. The comparison and test results on different large-scale systems show that the proposed algorithm is simple, fast, accurate, and HIL tested, and not affected by changes in power system parameters.
Simultaneous administration of coffee and rasagiline/l-dopa protects against paraquat-induced neurochemical and motor behavior impairments in vivo
Authors: Aboutabl Mona E. , Salman Asmaa M. , Gamal el Din Amina A. , Maklad Yousreya A.
Published: December 2021

Background

Caffeine is a natural alkaloid present in a variety of highly consumed popular drinks such as coffee, tea and soft drinks as well as chocolate. Its consumption elicits beneficiary psychostimulant that has been linked to a reduced risk of developing Parkinson’s disease (PD). The aim of the present study is to investigate the possible synergistic neuroprotective effects of co-administration of caffeine (CAF) or coffee (COF) with rasagiline (R) or l-dopa against paraquat (PQ)-induced neurochemical and motor behavior impairments in mice.

Results

In behavioral tests, R + COF increased the locomotor activity in rotarod test compared to l-dopa + COF. l-Dopa combinations decreased the immobility time in FST compared to rasagiline combinations; l-dopa + CAF provided a similar increase in locomotor activity compared to R + CAF. Combination of CAF or COF with l-dopa or rasagiline resulted in a substantial improvement in brain neurotransmitter and antioxidant levels as they significantly increased dopamine and super oxide dismutase but significantly decreased nitric oxide levels as compared to l-dopa or rasagiline, respectively. Furthermore, they also exerted a protective effect against the neurodegenerative histopathological changes induced by PQ.

Conclusions

Our findings demonstrated co-administration of COF or CAF, adenosine 2A receptor antagonists, along with l-dopa or rasagiline possesses a new therapeutic strategy for the management of PD neurochemical disturbances and motor behavior impairments through preservation of the brain dopamine and serotonin content, antioxidants level and histological features.
Cerebroplacental ratio for prediction of adverse intrapartum and neonatal outcomes in a term uncomplicated pregnancy
Authors: Mohamed Mariam Lotfy , Mohamed Salwa Adel , Elshahat Amal Mohamed
Published: December 2021

Background

Fetal hypoxia is one of the major causes of high perinatal morbidity and mortality rates. Doppler ultrasound tests such as cerebroplacental ratio (CPR) evaluation are commonly used to assess blood flow disturbances in placento-umbilical and feto-cerebral circulations. A low cerebroplacental ratio has been shown to be associated with an increased risk of stillbirth regardless of the gestation or fetal weight. We conducted this study to assess the fetal cerebroplacental ratio in prediction of adverse intrapartum and neonatal outcomes in a term, uncomplicated pregnancy to reduce fetal and neonatal morbidity and mortality.

Results

It was found that neonates with CPR ≤1.1 had significantly higher frequencies of cesarean delivery (CS) for intrapartum fetal compromise compared to those with CPR >1.1 (p=0.043). Neonates with CPR ≤1.1 had significantly lower Apgar score at 1 min and 5 min than those with CPR >1.1 (p=0.004) and (p=0.003), respectively. Neonates with CPR ≤1.1 had significantly higher rates of NICU admission than those with CPR <1.1 (p=0.004).

Conclusion

The cerebroplacental ratio shows the highest sensitivity in the prediction of fetal heart rate abnormalities and adverse neonatal outcome in uncomplicated pregnancies at term. The cerebroplacental ratio index is useful in clinical practice in antenatal monitoring of these women in order to select those at high risk of intra- and postpartum complications.
Gender-related romantic attachment and serum oxytocin level difference in adult patients with obsessive compulsive disorder
Authors: Dessoki Hani H. , Sadek Mohamed N. , Abd Elrassol Hwayda A. , El-Sayed Sayed G. , Soltan Mohamed R.
Published: December 2021

Background

Given the scarcity of data on gender-related romantic attachment changes and the potential role of oxytocin (OT) in the pathophysiology of obsessive-compulsive illness (OCD), the current study aimed to assess gender-related differences in romantic attachment characteristics and their relationship to serum oxytocin in a set of forty OCD cases compared with a similar group of healthy controls .Simultaneously examining the gender differences in serum oxytocin levels in OCD patients, the diagnosis of OCD patients was determined using DSM-5 criteria, and the severity of OCD was determined using the Y-BOCS rating scale. All of the patients were drug-free and not depressed. The romantic attachment was assessed using the “Experiences in Close Relationship” Questionnaire. Standard ELISA kits were used to assess plasma OT levels.

Results

Regarding romantic attachments, patients with obsessive compulsive disorder scored higher on the anxiety and avoidance domains than controls with no significant gender difference. Serum oxytocin was higher in patients with OCD than in healthy controls, indicating a possible underlying pathophysiology of the illness. Also, there was a significant gender difference, with female patients having higher serum oxytocin and symptoms severity being negatively associated.

Conclusions

Taken together, these findings propose that OT may play a role in OCD pathophysiology with gender specificity. Also, OCD associated with insecure romantic attachment.
Emerging techniques of western blotting for purification and analysis of protein
Authors: Singh Krishna Kumar , Gupta Anshika , Bharti Charu , Sharma Himanchal
Published: December 2021

Background

Western blotting is frequently employed in molecular techniques like Proteomics and Biology. Because it is a sequential framework, differences and inaccuracies could even take place at any stage, decreasing this particular method's reproducibility and reliability.

Main text

New approaches, like automated microfluid western blotting, DigiWest, single cell resolution, microchip electrophoresis, and capillary electrophoresis, were all implemented to reduce the future conflicts linked with the western blot analysis approach. Discovery of new in devices and higher susceptibility for western blots gives innovative opportunities to expand Western blot’s clinical relevance. The advancements in various region of west blotting included in this analysis of transfer of protein and validation of antibody are described.

Conclusion

This paper describes another very developed strategy available as well as demonstrated the correlation among Western blotting techniques of the next generation and their clinical implications. In this review, the different techniques of western blotting and their improvement in different stages have been discussed.