bluuebunny/crossref_metadata_2025 huggingface dataset:
CRISPR/Cas9 mediated T7 RNA polymerase gene knock-in in E. coli BW25113 makes T7 expression system work efficiently
Authors: Ye Changchuan , Chen Xi , Yang Mengjie , Zeng Xiangfang , Qiao Shiyan
Published: August 2021

T7 Expression System is a common method of ensuring tight control and high-level induced expression. However, this system can only work in some bacterial strains in which theT7 RNA Polymerasegene resides in the chromosome. In this study, we successfully introduced a chromosomal copy of theT7 RNA Polymerasegene under control of the lacUV5 promoter intoEscherichia coliBW25113. The T7 Expression System worked efficiently in this mutant strain named BW25113-T7. We demonstrated that this mutant strain could satisfactorily produce 5-Aminolevulinic Acid via C5 pathway. A final study was designed to enhance the controllability of T7 Expression System in this mutant strain by constructing a T7 Promoter Variants Library. These efforts advancedE. coliBW25113-T7 to be a practical host for future metabolic engineering efforts.
TPEN attenuates amyloid-β25–35-induced neuronal damage with changes in the electrophysiological properties of voltage-gated sodium and potassium channels
Authors: Chen Wen-bo , Wang Yu-xiang , Wang Hong-gang , An Di , Sun Dan , Li Pan , Zhang Tao , Lu Wan-ge , Liu Yan-qiang
Published: August 2021

To understand the role of intracellular zinc ion (Zn2+) dysregulation in mediating age-related neurodegenerative changes, particularly neurotoxicity resulting from the generation of excessive neurotoxic amyloid-β (Aβ) peptides, this study aimed to investigate whether N, N, N′, N′-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a Zn2+-specific chelator, could attenuate Aβ25–35-induced neurotoxicity and the underlying electrophysiological mechanism. We used the 3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay to measure the viability of hippocampal neurons and performed single-cell confocal imaging to detect the concentration of Zn2+ in these neurons. Furthermore, we used the whole-cell patch-clamp technique to detect the evoked repetitive action potential (APs), the voltage-gated sodium and potassium (K+) channels of primary hippocampal neurons. The analysis showed that TPEN attenuated Aβ25–35-induced neuronal death, reversed the Aβ25–35-induced increase in intracellular Zn2+ concentration and the frequency of APs, inhibited the increase in the maximum current density of voltage-activated sodium channel currents induced by Aβ25–35, relieved the Aβ25–35-induced decrease in the peak amplitude of transient outward K+ currents (IA) and outward-delayed rectifier K+ currents (IDR) at different membrane potentials, and suppressed the steady-state activation and inactivation curves of IA shifted toward the hyperpolarization direction caused by Aβ25–35. These results suggest that Aβ25–35-induced neuronal damage correlated with Zn2+ dysregulation mediated the electrophysiological changes in the voltage-gated sodium and K+ channels. Moreover, Zn2+-specific chelator-TPEN attenuated Aβ25–35-induced neuronal damage by recovering the intracellular Zn2+ concentration.
XPO1/CRM1 is a promising prognostic indicator for neuroblastoma and represented a therapeutic target by selective inhibitor verdinexor
Authors: Pan Lijia , Cheng Cheng , Duan Peiwen , Chen Kai , Wu Yeming , Wu Zhixiang
Published: August 2021

Background

High-risk neuroblastoma patients have a 5-year survival rate of less than 50%. It’s an urgent need to identify new therapeutic targets and the appropriate drugs. Exportin-1 (XPO1), also known as chromosomal region maintenance 1, plays important roles in the progression of tumorigenesis. However, the prognostic and therapeutic values of XPO1 in neuroblastoma have not been reported.

Methods

Correlations between XPO1 expression level and clinical characteristics were analyzed using the Neuroblastoma Research Consortium (NRC) dataset and tissue microarray analysis. Cell proliferation assays, colony formation assays, apoptosis assays, cell cycle analysis were performed to analyze the anti-tumor effects of verdinexor (KPT-335) in vitro. Western blot and mRNA sequencing were performed to explore underlying mechanism. In vivo anti-tumor effects of verdinexor were studied in a neuroblastoma xenograft model.

Results

Higher XPO1 levels were associated with advanced stage and poor prognosis in neuroblastoma patients. The specific inhibitor of XPO1 verdinexor suppressed the neuroblastoma cell growth both in vitro and in vivo. Specifically, inhibition of XPO1 suppressed the neuroblastoma cell proliferation and induced cell apoptosis by nuclear accumulation of FOXO1 and RB1 in the neuroblastoma due to the inhibition of the PI3K/AKT pathway, and induced G0/G1 phase cell cycle arrest by activation of P53 function.

Conclusions

XPO1 is a promising prognostic indicator for neuroblastoma and a novel target for antitumor treatment with selective inhibitor verdinexor.
Effects of moderate-intensity intermittent hypoxic training on health outcomes of patients recovered from COVID-19: the AEROBICOVID study protocol for a randomized controlled trial
Authors: Trapé Átila Alexandre , Camacho-Cardenosa Marta , Camacho-Cardenosa Alba , Merellano-Navarro Eugenio , Rodrigues Jhennyfer Aline Lima , da Silva Lizzi Elisangela Aparecida , Sorgi Carlos Arterio , Papoti Marcelo , Brazo-Sayavera Javier
Published: August 2021

Background

Recent studies point to a lower number and reduced severity of cases in higher altitude cities with decreased oxygen concentration. Specific literature has shown several benefits of physical training, so, in this sense, physical training with hypoxic stimulus appears as an alternative that supports the conventional treatments of the COVID-19 patient’s recovery. Thus, this study’s primary aim is to analyze the effects of moderate-intensity intermittent hypoxic training on health outcomes in COVID-19 recovered patients.

Methods

A clinical trial controlled double-blind study was designed. Participants (30–69 years old) will be recruited among those with moderate to severe COVID-19 symptoms, approximately 30 days after recovery. They will be included in groups according to the training (T) and recovery (R) association with hypoxia (H) or normoxia (N): (a) TH:RH, (b) TN:RH, (c) TN:RN, and last (d) the control group. The 8-week exercise bike intervention will be carried out with a gradual load increase according to the established periods, three times a week in sets of 5 min, 90 to 100% of the anaerobic threshold (AT), and a 2.5-min break. Blood will be collected for genotyping. First, after 4 weeks (partial), after 8 weeks, and later, 4 weeks after the end of the physical training intervention, participants will perform assessments. The primary outcome is the maximum oxygen consumption (VO2peak). The secondary outcomes include lung function, inflammatory mediators, hematological, autonomic parameters, AT, body composition analysis, quality of life, mental health, anthropometric measurements, and physical fitness. The statistical analysis will be executed using the linear regression model with mixed effects at a 5% significance level.

Discussion

This study is designed to provide evidence to support the clinical benefits of moderate-intensity intermittent hypoxic training as a part of the treatment of patients recovered from COVID-19. It may also provide evidence on the efficacy and safety of intermittent hypoxic training in different health conditions. Lastly, this study presents an innovative strategy enabling up to 16 participants in the same training session.

Trial registration

ClinicalTrials.govRBR-5d7hkv. Registered after the start of inclusion on 3 November 2020 with the Brazilian Clinical Trials Registry
Sleeping for two: study protocol for a randomized controlled trial of cognitive behavioral therapy for insomnia in pregnant women
Authors: MacKinnon Anna L. , Madsen Joshua W. , Dhillon Ashley , Keys Elizabeth , Giesbrecht Gerald F. , Williamson Tyler , Metcalfe Amy , Campbell Tavis , Mrklas Kelly J. , Tomfohr-Madsen Lianne
Published: August 2021

Background

Insomnia and sleep disturbances are common in pregnancy and have potentially significant consequences for both maternal and infant health. There is limited research examining the effectiveness of cognitive behavioral therapy for insomnia (CBT-I) during pregnancy. With increased distress and limited access to services during the COVID-19 pandemic, there is also an unprecedented need for telehealth delivery of treatment programs for pregnant women. The aims of this trial are to evaluate the impact of the Sleeping for Two adaptation of CBT-I in pregnancy (in-person or telehealth) versus treatment as usual (TAU) in reducing symptoms of insomnia (primary outcome), as well as increasing gestational length and reducing symptoms of depression (secondary outcomes).

Methods

A two-arm, single-blinded, parallel group randomized controlled trial (RCT) design with repeated measures will be used to evaluate the impact of CBT-I compared to TAU among a sample of 62 pregnant women, enrolled between 12 and 28 weeks of gestation, who self-identify as experiencing insomnia. Five weekly individual sessions of CBT-I will be delivered in person or via telehealth depending on physical distancing guidelines. Assessment of insomnia diagnosis by structured interview, self-reported insomnia symptom severity and sleep problems, and sleep quantity and quality as measured by a daily diary and actigraphy will occur at 12–28 weeks of pregnancy (T1), 1 week post-treatment (T2), and 6 months postpartum (T3).

Discussion

CBT-I delivered in pregnancy has the potential to reduce symptoms of insomnia and depression and could lead to reduced risk of preterm birth, all of which can minimize risk of negative maternal and child health and developmental consequences in the short (e.g., infant death) and long terms (e.g., developmental delays). This RCT builds on a successful open pilot trial conducted by our team and will provide further evaluation of a novel evidence-based treatment for pregnancy-related insomnia, which can be widely disseminated and used to treat individuals that are most in need of intervention. Findings will enhance understanding of pregnancy-related sleep problems, as well as means by which to improve the health and sleep of mothers and their children.

Trial registration

ClinicalTrials.govNCT03918057. Registered on 17 April 2019.
CAZymes from the thermophilic fungus Thermoascus aurantiacus are induced by C5 and C6 sugars
Authors: Gabriel Raphael , Mueller Rebecca , Floerl Lena , Hopson Cynthia , Harth Simon , Schuerg Timo , Fleissner Andre , Singer Steven W.
Published: August 2021

Background

Filamentous fungi are excellent lignocellulose degraders, which they achieve through producing carbohydrate active enzymes (CAZymes). CAZyme production is highly orchestrated and gene expression analysis has greatly expanded understanding of this important biotechnological process. The thermophilic fungus Thermoascus aurantiacus secretes highly active thermostable enzymes that enable saccharifications at higher temperatures; however, the genome-wide measurements of gene expression in response to CAZyme induction are not understood.

Results

A fed-batch system with plant biomass-derived sugars d-xylose, l-arabinose and cellobiose established that these sugars induce CAZyme expression in T. aurantiacus. The C5 sugars induced both cellulases and hemicellulases, while cellobiose specifically induced cellulases. A minimal medium formulation was developed to enable gene expression studies of T. aurantiacus with these inducers. It was found that d-xylose and l-arabinose strongly induced a wide variety of CAZymes, auxiliary activity (AA) enzymes and carbohydrate esterases (CEs), while cellobiose facilitated lower expression of mostly cellulase genes. Furthermore, putative orthologues of different unfolded protein response genes were up-regulated during the C5 sugar feeding together with genes in the C5 sugar assimilation pathways.

Conclusion

This work has identified two additional CAZyme inducers for T. aurantiacus, l-arabinose and cellobiose, along with d-xylose. A combination of biochemical assays and RNA-seq measurements established that C5 sugars induce a suite of cellulases and hemicellulases, providing paths to produce broad spectrum thermotolerant enzymatic mixtures.
Blastocystis in the faeces of children from six distant countries: prevalence, quantity, subtypes and the relation to the gut bacteriome
Authors: Cinek Ondrej , Polackova Katerina , Odeh Rasha , Alassaf Abeer , Kramná Lenka , Ibekwe MaryAnn Ugochi , Majaliwa Edna Siima , Ahmadov Gunduz , Elmahi Bashir Mukhtar Elwasila , Mekki Hanan , Oikarinen Sami , Lebl Jan , Abdullah Mohammed Ahmed
Published: August 2021

Background

Blastocystisis a human gut symbiont of yet undefined clinical significance. In a set of faecal samples collected from asymptomatic children of six distant populations, we first assessed the community profiles of protist 18S rDNA and then characterizedBlastocystissubtypes and testedBlastocystisassociation with the faecal bacteriome community.

Methods

Stool samples were collected from 244 children and young persons (mean age 11.3 years, interquartile range 8.1–13.7) of six countries (Azerbaijan 51 subjects, Czechia 52, Jordan 40, Nigeria 27, Sudan 59 and Tanzania 15). The subjects showed no symptoms of infection. Amplicon profiling of the 18S rDNA was used for verification thatBlastocystiswas the most frequent protist, whereas specific real-time PCR showed its prevalence and quantity, and massive parallel amplicon sequencing defined theBlastocystissubtypes. The relation betweenBlastocystisand the stool bacteriome community was characterized using 16S rDNA profiling.

Results

Blastocystiswas detected by specific PCR in 36% (88/244) stool samples and was the most often observed faecal protist. Children from Czechia and Jordan had significantly lower prevalence than children from the remaining countries. The most frequent subtype was ST3 (49%, 40/81 sequenced samples), followed by ST1 (36%) and ST2 (25%). Co-infection with two different subtypes was noted in 12% samples. The faecal bacteriome had higher richness inBlastocystis-positive samples, andBlastocystiswas associated with significantly different community composition regardless of the country (p < 0.001 in constrained redundancy analysis). Several taxa differed withBlastocystispositivity or quantity: two genera of Ruminococcaceae were more abundant, whileBifidobacterium, Veillonella, Lactobacillusand several other genera were undrerrepresented.

Conclusions

Asymptomatic children frequently carryBlastocystis, and co-infection with multiple distinct subtypes is not exceptional. Prevalence and quantity of the organism clearly differ among populations.Blastocystisis linked to both faecal bacteriome diversity and its composition.

Graphical Abstract
Requirement of Toxoplasma gondii metacaspases for IMC1 maturation, endodyogeny and virulence in mice
Authors: Li Muzi , Liu Jing , Wu Yayun , Wu Yihan , Sun Xiaodong , Fu Yong , Zhang Xiao , Liu Qun
Published: August 2021

Background

Metacaspases are multifunctional proteins found in plants, fungi and protozoa, and are involved in processes such as insoluble protein aggregate clearance and cell proliferation. Our previous study demonstrated that metacaspase-1 (MCA1) contributes to parasite apoptosis inToxoplasma gondii. Deletion of MCA1 fromT. gondiihas no effect on the growth and virulence of the parasites. Three metacaspases were identified in the ToxoDBToxoplasmaInformatics Resource, and the function of metacaspase-2 (MCA2) and metacaspase-3 (MCA3) has not been demonstrated.

Methods

In this study, we constructed MCA1, MCA2 and MCA1/MCA2 transgenic strains from RHΔku80 (Δku80), including overexpressing strains and knockout strains, to clarify the function of MCA1 and MCA2 ofT. gondii.

Results

MCA1 and MCA2 were distributed in the cytoplasm with punctuated aggregation, and part of the punctuated aggregation of MCA1 and MCA2 was localized on the inner membrane complex ofT. gondii. The proliferation of the MCA1/MCA2 double-knockout strain was significantly reduced; however, the two single knockout strains (MCA1 knockout strain and MCA2 knockout strain) exhibited normal growth rates as compared to the parental strain, Δku80. In addition, endodyogeny was impaired in the tachyzoites whose MCA1 and MCA2 were both deleted due to multiple nuclei and abnormal expression of IMC1. We further found that IMC1 of the double-knockout strain was detergent-soluble, indicating that MCA1 and MCA2 are associated with IMC1 maturation. Compared to the parental Δku80 strain, the double-knockout strain was more readily induced from tachyzoites to bradyzoites in vitro. Furthermore, the double-knockout strain was less pathogenic in mice and was able to develop bradyzoites in the brain, which formed cysts and established chronic infection.

Conclusion

MCA1 and MCA2 are important factors which participate in IMC1 maturation and endodyogeny ofT. gondii. The double-knockout strain has slower proliferation and was able to develop bradyzoites both in vitro and in vivo.

Graphic abstract
Surgery for lung cancer: postoperative changes and complications—what the Radiologist needs to know
Authors: Burel Julien , El Ayoubi Mathias , Baste Jean-Marc , Garnier Matthieu , Montagne François , Dacher Jean-Nicolas , Demeyere Matthieu
Published: August 2021

Imaging findings after thoracic surgery can be misleading. Knowledge of the normal post-operative anatomy helps the radiologist to recognise life-threatening complications and conversely not to wrongly evoke a complication in cases of trivial post-operative abnormalities. In this educational article, we reviewed the expected patterns after thoracic surgery including sublobar resection, lobectomy, pneumonectomy and related techniques. Imaging aspects of frequent and less common complications and their typical imaging features are then presented.
The impact of childhood psychological maltreatment on mental health outcomes in adulthood: a protocol for a systematic review and meta-analysis
Authors: Xiao Zhuoni , Baldwin Mina Murat , Meinck Franziska , Obsuth Ingrid , Murray Aja Louise
Published: August 2021

Background

Research suggests that childhood psychological maltreatment (i.e., emotional abuse and emotional neglect) is associated with mental health problems that persist into adulthood, for example anxiety, depression, post-traumatic stress disorder (PTSD), suicidal ideation, and aggression; however, a systematic review and meta-analysis of the existing literature would help clarify the magnitude and moderators of these associations, and the extent to which they may be affected by publication bias, as well as the methodological strengths and weakness of studies in this area.

Method

The reporting of this protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) Statement. Searches will be carried out via several databases, including Web of Science, Medline, PubMed, PsycINFO, Applied Social Science Index and Abstract, ERIC and EMBASE. Empirical peer-reviewed research articles that fit pre-specified eligibility criteria will be included in the review. Studies will be eligible if they include participants age 18 or over at time of mental health assessment, include information on childhood psychological maltreatment (emotional abuse and/or neglect) perpetrated by a primary caregiver or adult in the same household, and provide quantitative information on the association between these factors. Studies using prospective and retrospective designs and written in either English or Chinese will be eligible. Two independent reviewers will screen and assess studies for inclusion in the review as well as extract the data, with consensus reached through discussion in cases of discrepancy. A third reviewer will be consulted to resolve any discrepancies that remain. The relevant Newcastle–Ottawa scales will be used for assessing the quality of studies. If a sufficient number of comparable studies are retrieved, a meta-analysis will be conducted using a random effects model. Study-level moderators (i.e., year of publication, quality of the study and study geographical location) will be examined in the meta-analyses.

Discussion

This systematic review will provide an understanding of the long-term effects of childhood psychological maltreatment on adult mental health, which adds to previous reviews focusing primarily on the effects of physical and sexual abuse. The results of the review will help inform clinical practice in approaches to treating those with a history of psychological maltreatment in childhood. The gaps and weaknesses in the evidence identified will also inform recommendations for future research.
Identification of subgroups along the glycolysis-cholesterol synthesis axis and the development of an associated prognostic risk model
Authors: Zhang Enchong , Chen Yijing , Bao Shurui , Hou Xueying , Hu Jing , Mu Oscar Yong Nan , Song Yongsheng , Shan Liping
Published: August 2021

Background

Skin cutaneous melanoma (SKCM) is one of the most highly prevalent and complicated malignancies. Glycolysis and cholesterogenesis pathways both play important roles in cancer metabolic adaptations. The main aims of this study are to subtype SKCM based on glycolytic and cholesterogenic genes and to build a clinical outcome predictive algorithm based on the subtypes.

Methods

A dataset with 471 SKCM specimens was downloaded from The Cancer Genome Atlas (TCGA) database. We extracted and clustered genes from the Molecular Signatures Database v7.2 and acquired co-expressed glycolytic and cholesterogenic genes. We then subtyped the SKCM samples and validated the efficacy of subtypes with respect to simple nucleotide variations (SNVs), copy number variation (CNV), patients’ survival statuses, tumor microenvironment, and proliferation scores. We also constructed a risk score model based on metabolic subclassification and verified the model using validating datasets. Finally, we explored potential drugs for high-risk SKCM patients.

Results

SKCM patients were divided into four subtype groups: glycolytic, cholesterogenic, mixed, and quiescent subgroups. The glycolytic subtype had the worst prognosis andMGAMSNV extent. Compared with the cholesterogenic subgroup, the glycolytic subgroup had higher rates ofDDR2andTPRCNV and higher proliferation scores and MK167 expression levels, but a lower tumor purity proportion. We constructed a forty-four-gene predictive signature and identified MST-321, SB-743921, Neuronal Differentiation Inducer III, romidepsin, vindesine, and YM-155 as high-sensitive drugs for high-risk SKCM patients.

Conclusions

Subtyping SKCM patients via glycolytic and cholesterogenic genes was effective, and patients in the glycolytic-gene enriched group were found to have the worst outcome. A robust prognostic algorithm was developed to enhance clinical decisions in relation to drug administration.
Applying arterial enhancement fraction (AEF) texture features to predict the tumor response in hepatocellular carcinoma (HCC) treated with Transarterial chemoembolization (TACE)
Authors: Mao Xiaonan , Guo Yan , Wen Feng , Liang Hongyuan , Sun Wei , Lu Zaiming
Published: August 2021

Background

To evaluate the application of Arterial Enhancement Fraction (AEF) texture features in predicting the tumor response in Hepatocellular Carcinoma (HCC) treated with Transarterial Chemoembolization (TACE) by means of texture analysis.

Methods

HCC patients treated with TACE in Shengjing Hospital of China Medical University from June 2018 to December 2019 were retrospectively enrolled in this study. Pre-TACE Contrast Enhanced Computed Tomography (CECT) and imaging follow-up within 6 months were both acquired. The tumor responses were categorized according to the modified RECIST (mRECIST) criteria. Based on the CECT images, Region of Interest (ROI) of HCC lesion was drawn, the AEF calculation and texture analysis upon AEF values in the ROI were performed using CT-Kinetics (C.K., GE Healthcare, China). A total of 32 AEF texture features were extracted and compared between different tumor response groups. Multi-variate logistic regression was performed using certain AEF features to build the differential models to predict the tumor response. The Receiver Operator Characteristic (ROC) analysis was implemented to assess the discriminative performance of these models.

Results

Forty-five patients were finally enrolled in the study. Eight AEF texture features showed significant distinction between Improved and Un-improved patients (p < 0.05). In multi-variate logistic regression, 9 AEF texture features were applied into modeling to predict “Improved” outcome, and 4 AEF texture features were applied into modeling to predict “Un-worsened” outcome. The Area Under Curve (AUC), diagnostic accuracy, sensitivity, and specificity of the two models were 0.941, 0.911, 1.000, 0.826, and 0.824, 0.711, 0.581, 1.000, respectively.

Conclusions

Certain AEF heterogeneous features of HCC could possibly be utilized to predict the tumor response to TACE treatment.
Regulation of DNA methylation on key parasitism genes of Cysticercus cellulosae revealed by integrative epigenomic-transcriptomic analyses
Authors: Wang Xinrui , Song Weiyi , Ji Guanyu , Song Yining , Liu Xiaolei , Luo Xuenong , Liu Mingyuan , Sun Shumin
Published: August 2021

Background

The life cycle of Taenia solium is characterized by different stages of development, requiring various kinds of hosts that can appropriately harbor the eggs (proglottids), the oncospheres, the larvae and the adults. Similar to other metazoan pathogens, T. solium undergoes transcriptional and developmental regulation via epigenetics during its complex lifecycle and host interactions.

Result

In the present study, we integrated whole-genome bisulfite sequencing and RNA-seq technologies to characterize the genome-wide DNA methylation and its effect on transcription of Cysticercus cellulosae of T. solium. We confirm that the T. solium genome in the cysticercus stage is epigenetically modified by DNA methylation in a pattern similar to that of other invertebrate genomes, i.e., sparsely or moderately methylated. We also observed an enrichment of non-CpG methylation in defined genetic elements of the T. solium genome. Furthermore, an integrative analysis of both the transcriptome and the DNA methylome indicated a strong correlation between these two datasets, suggesting that gene expression might be tightly regulated by DNA methylation. Importantly, our data suggested that DNA methylation might play an important role in repressing key parasitism-related genes, including genes encoding excretion-secretion proteins, thereby raising the possibility of targeting DNA methylation processes as a useful strategy in therapeutics of cysticercosis.
Utility of a Cancer Predisposition Screening Tool for Predicting Subsequent Malignant Neoplasms in Childhood Cancer Survivors
Authors: Cullinan Noelle , Schiller Ian , Di Giuseppe Giancarlo , Mamun Mohammed , Reichman Lara , Cacciotti Chantel , Wheaton Laura , Caswell Kimberly , Di Monte Bruna , Gibson Paul , Johnston Donna L. , Fleming Adam , Pole Jason D. , Malkin David , Foulkes William D. , Dendukuri Nandini , Goudie Catherine , Nathan Paul C.
Published: August 2021

PURPOSE

Childhood cancer survivors (CCS) are at risk of developing subsequent malignant neoplasms (SMNs) resulting from exposure to prior therapies. CCS with underlying cancer predisposition syndromes are at additional genetic risk of SMN development. The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) tool identifies children with cancer at increased likelihood of having a cancer predisposition syndrome, guiding clinicians through a series of Yes or No questions that generate a recommendation for or against genetic evaluation. We evaluated MIPOGG's ability to predict SMN development in CCS.

METHODS

Using the provincial cancer registry (Ontario, Canada), and adopting a nested case-control approach, we identified CCS diagnosed and/or treated for a primary malignancy before age 18 years (1986-2015). CCS who developed an SMN (cases) were matched, by primary cancer and year of diagnosis, with CCS who did not develop an SMN (controls) over the same period (1:5 ratio). Potential predictors for SMN development (chemotherapy, radiation, and MIPOGG output) were applied retrospectively using clinical data pertaining to the first malignancy. Conditional logistic regression models estimated hazard ratios and 95% CIs associated with each covariate, alone and in combination, for SMN development.

RESULTS

Of 13,367 children with a primary cancer, 317 (2.4%) developed an SMN and were matched to 1,569 controls. A MIPOGG output recommending evaluation was significantly associated with SMN development (hazard ratio 1.53; 95% CI, 1.06 to 2.19) in a multivariable model that included primary cancer therapy exposures. MIPOGG was predictive of SMN development, showing value in nonhematologic malignancies and in CCS not exposed to radiation.

CONCLUSION

MIPOGG has additional value for SMN prediction beyond treatment exposures and may be beneficial in decision making for enhanced individualized SMN surveillance strategies for CCS.
Procalcitonin as an Alternative Tumor Marker of Medullary Thyroid Carcinoma
Authors: Giovanella Luca , Garo Maria Luisa , Ceriani Luca , Paone Gaetano , Campenni’ Alfredo , D’Aurizio Federica
Published: August 2021

Context

Calcitonin (CT) measurement is pivotal in the management of medullary thyroid carcinoma (MTC), but several pitfalls can affect its reliability. Procalcitonin (ProCT) has been reported as a promising alternative MTC tumor marker.

Objective

This study aimed to determine the ProCT diagnostic accuracy in prediction and treatment monitoring of MTC.

Methods

Electronic databases were searched for observational studies published until May 2021 without language or time restrictions. Studies comparing ProCT and calcitonin accuracy were included. After removing duplicates and exclusion of not-eligible articles, relevant articles were screened independently by 2 reviewers. Eleven studies (4.5% of the identified studies) met the selection criteria. Two reviewers independently extracted data and assessed data quality and validity through QUADAS-2.

Results

A meta-analysis was performed on 11 sufficiently clinically and statistically homogeneous studies (n = 5817 patients, 335 MTC patients). Hierarchical summary receiver operating characteristics and bivariate methods were applied. Serum ProCT was found to be a highly accurate test for MTC diagnosis and monitoring. The pooled sensitivity, specificity, positive and negative likelihood ratios, area under the curve, and positive and negative predictive values for ProCT were 0.90 (95% CI: 0.71-0.97), 1.00 (95% CI: 0.85-1.00), 288 (95% CI: 5.6-14 929.3), 0.10 (95% CI: 0.03-0.33), 0.97 (95% CI: 0.95-0.98), 99%, and 2%, respectively.

Conclusions

The high accuracy, compounded with favorable analytical characteristics, give ProCT great potential to replace calcitonin as a new standard of care in the management of MTC.
In vivo live imaging of postnatal neural stem cells
Authors: Marymonchyk Alina , Malvaut Sarah , Saghatelyan Armen
Published: August 2021

Neural stem cells (NSCs) are maintained in specific regions of the postnatal brain and contribute to its structural and functional plasticity. However, the long-term renewal potential of NSCs and their mode of division remain elusive. The use of advanced in vivo live imaging approaches may expand our knowledge of NSC physiology and provide new information for cell replacement therapies. In this Review, we discuss the in vivo imaging methods used to study NSC dynamics and recent live-imaging results with respect to specific intracellular pathways that allow NSCs to integrate and decode different micro-environmental signals. Lastly, we discuss future directions that may provide answers to unresolved questions regarding NSC physiology.
Cognitive maps in the wild: revealing the use of metric information in black howler monkey route navigation
Authors: de Guinea Miguel , Estrada Alejandro , Nekaris K. Anne-Isola , Van Belle Sarie
Published: August 2021

When navigating, wild animals rely on internal representations of the external world – called ‘cognitive maps’ – to take movement decisions. Generally, flexible navigation is hypothesized to be supported by sophisticated spatial skills (i.e. Euclidean cognitive maps); however, constrained movements along habitual routes are the most commonly reported navigation strategy. Even though incorporating metric information (i.e. distances and angles between locations) in route-based cognitive maps would likely enhance an animal's navigation efficiency, there has been no evidence of this strategy reported for non-human animals to date. Here, we examined the properties of the cognitive map used by a wild population of primates by testing a series of cognitive hypotheses against spatially explicit movement simulations. We collected 3104 h of ranging and behavioural data on five groups of black howler monkeys (Alouatta pigra) at Palenque National Park, Mexico, from September 2016 through August 2017. We simulated correlated random walks mimicking the ranging behaviour of the study subjects and tested for differences between observed and simulated movement patterns. Our results indicated that black howler monkeys engaged in constrained movement patterns characterized by a high path recursion tendency, which limited their capacity to travel in straight lines and approach feeding trees from multiple directions. In addition, we found that the structure of observed route networks was more complex and efficient than simulated route networks, suggesting that black howler monkeys incorporate metric information into their cognitive map. Our findings not only expand the use of metric information during route navigation to non-human animals, but also highlight the importance of considering efficient route-based navigation as a cognitively demanding mechanism.
Thyroglobulin Measurement Through Fine-Needle Aspiration for Optimizing Neck Node Dissection in Papillary Thyroid Cancer
Authors: Jia Xi , Wang Yuanbo , Liu Yan , Wang Xiang , Yao Xiaobao , Tao Runyi , Liu Hui , Yang Aimin , Gao Rui
Published: August 2021

Background

Thyroglobulin measurement in fine-needle aspiration (FNA-Tg) is an additional diagnostic tool of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC). However, its performance as a preoperative indicator of lateral neck LNM in PTC is unclear. We evaluated the use of FNA cytology and FNA-Tg to detect neck LNM presurgery using a simple methodology, and established a cut-off value for diagnosing LNM in PTC.

Methods

We performed a retrospective cohort study based on hospital records, including 299 FNA-Tg measurements from 228 patients with PTC. The cut-off value for FNA-Tg was obtained through a receiver operating characteristic (ROC) curve analysis. The relationships between various parameters and FNA-Tg were analyzed using Spearman’s correlation.

Results

Of 299 lymph nodes (LNs) from 228 patients following surgery, 151 were malignant and 148 were benign. The median FNA-Tg levels were 414.40 ng/mL and 6.36 ng/mL in the metastatic and benign LNs, respectively. An FNA-Tg cut-off value of 28.3 ng/mL had the best diagnostic performance (93.38% sensitivity, 70.27% specificity, area under the ROC curve [AUC] 0.868) in the whole cohort. The diagnostic value performed better in the lateral neck group (level II–V,n = 163) than in the central neck group (level VI,n = 136); in the lateral neck group, the sensitivity and specificity of the FNA-Tg cut-off (16.8 ng/mL) were 96.25% and 96.36%, respectively.

Conclusions

FNA-Tg is a useful technique for the diagnosis of LNM before surgery, especially in lateral neck dissection.

Clinical trial registration number

ChiCTR1900028547.
Informing the Public About a Pandemic
Authors: de Véricourt Francis , Gurkan Huseyin , Wang Shouqiang
Published: August 2021

This paper explores how governments may efficiently inform the public about an epidemic to induce compliance with their confinement measures. Using an information design framework, we find the government has an incentive to either downplay or exaggerate the severity of the epidemic if it heavily prioritizes the economy over population health or vice versa. Importantly, we find that the level of economic inequality in the population has an effect on these distortions. The more unequal the disease’s economic impact on the population, the less the government exaggerates and the more it downplays the severity of the epidemic. When the government weighs the economy and population health sufficiently equally, however, the government should always be fully transparent about the severity of the epidemic.

This paper was accepted by Stefan Scholtes, healthcare management.
Focusing Provider Attention: An Empirical Examination of Incentives and Feedback in Flu Vaccinations
Authors: Niewoehner Robert J. , Staats Bradley R.
Published: August 2021

Background. Influenza imposes heavy societal costs through healthcare expenditures, missed days of work, and numerous hospitalizations each year. Considering these costs, the healthcare and behavioral science literature offers suggestions on increasing demand for flu vaccinations. Yet, the adult flu vaccination rate fluctuated between 37% and 46% between 2010 and 2019. Aim. Although a demand-side approach represents one viable strategy, an operations management approach would also highlight the need to consider a supply-side approach. In this paper, we investigate how to improve clinic vaccination rates by altering provider behavior. Methodology. We implement and study a flu vaccine intervention among 145 clinics from nine different states. This intervention randomly assigned these clinics to a control group or one of two separate treatment arms that received either relative performance feedback or financial incentives. Results. We find clinics that received relative performance feedback outperformed all others: Our intervention led to a 12% increase in flu shots for this group of clinics. Moreover, we also find clinics in this group exhibit rank response behavior, specifically last-place aversion; in particular, clinics near last place outperform the corresponding control clinics by 23% points. Conclusion. Overall, we find that clinic-level performance feedback can effectively drive operational improvement. Even a small increase in the U.S. adult flu vaccination rate might confer hundreds of millions of dollars in societal benefits and prevents thousands of hospitalizations. We discuss the implications of our work for healthcare operations theory, healthcare providers, and healthcare administrators.

This paper was accepted by Charles Corbett, operations management.
Hedge Fund Flows and Performance Streaks: How Investors Weigh Information
Authors: Baquero Guillermo , Verbeek Marno
Published: August 2021

Cash flows to hedge funds are highly sensitive to performance streaks, a streak being defined as subsequent quarters during which a fund performs above or below a benchmark, even after controlling for a wide range of common performance measures. At the same time, streaks have limited predictive power regarding future fund performance. This suggests investors weigh information suboptimally, and their decisions are driven too strongly by a belief in continuation of good performance, consistent with the “hot hand fallacy.” The hedge funds that investors choose to invest in do not perform significantly better than those they divest from. These findings are consistent with overreaction to certain types of information and do not support the notion that sophisticated investors have superior information or superior information processing abilities.

This paper was accepted by David Simchi-Levi, finance.
Formulasi Fruit Bars Berbasis Tepung Pisang Ditinjau dari Karakteristik Fisik, Kimia dan Organoleptik
Authors: Nekstaria Adryananda , Fardhani Zidan Arief , Qulub Ahmad Syifa'ul , Muflihati Iffah
Published: August 2021

Penelitian ini bertujuan untuk mengetahui formulasi serta karakteristik fisik, kimia dan organoleptik fruit bars berbahan dasar tepung buah pisang kepok, raja dan susu dengan penambahan tepung kedelai. Penelitian menggunakan rancangan acak lengkap dengan satu faktor yaitu penggunaan bahan dasar tepung pisang kepok, tepung pisang raja dan tepung pisang susu. Hasil penelitian menunjukkan bahwa fruit bars dari ketiga jenis pisang memiliki kadar air dan kadar serat yang tidak berbeda nyata, sedangkan pada rendemen adonan dan uji organoleptik menunjukkan hasil berbeda nyata. Rendemen adonan tertinggi pada perlakuan fruit bars dengan menggunakan bahan dasar tepung susu yaitu 0,88 g dan uji organoleptik fruit bars yang dapat diterima panelis adalah pada perlakuan fruit bars menggunakan bahan dasar pisang kepok.
Examination of Mother-Child Math Talks’ Content and Process during Shared Book Reading
Authors: Turker-Biber Belma , Akinci-Cosgun Aysegul , Aydin-Bolukbas Feyza
Published: August 2021

The study aims to analyze, in terms of content and process, the math talks between the mother and child during the shared book reading of the illustrated storybooks with math contents. The study group under the research is comprised of nine pairs of mother and child. The process of the study 18 videos which were recorded when two storybooks with math contents were read by the mothers. In the data collection process, each pair of mother and child together read two storybooks given to them in their home environment, and the entire process was video-recorded. Subsequently, interviews were held with mothers for identifying their views about supporting their children’s math skills. It was shown that the content of mother-child math talks in the home environment was mostly about the learning area of numbers and counting skills. It was a remarkable result that math concepts such as sorting/ranking and properties/features of objects were not in the contents of mother-child math talks. The results from interviews with mothers, it was inferred that the mothers viewed themselves as inadequate for talking to their children about math concepts, and performed the math talks mostly on the basic skills such as counting the numbers.
Outcome and complications following revision shoulder arthroplasty
Authors: Ravi Vinayak , Murphy Richard James , Moverley Robert , Derias Mina , Phadnis Joideep
Published: August 2021

Aims

It is important to understand the rate of complications associated with the increasing burden of revision shoulder arthroplasty. Currently, this has not been well quantified. This review aims to address that deficiency with a focus on complication and reoperation rates, shoulder outcome scores, and comparison of anatomical and reverse prostheses when used in revision surgery.

Methods

A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) systematic review was performed to identify clinical data for patients undergoing revision shoulder arthroplasty. Data were extracted from the literature and pooled for analysis. Complication and reoperation rates were analyzed using a meta-analysis of proportion, and continuous variables underwent comparative subgroup analysis.

Results

A total of 112 studies (5,379 shoulders) were eligible for inclusion, although complete clinical data was not ubiquitous. Indications for revision included component loosening 20% (601/3,041), instability 19% (577/3,041), rotator cuff failure 17% (528/3,041), and infection 16% (490/3,041). Intraoperative complication and postoperative complication and reoperation rates were 8% (230/2,915), 22% (825/3,843), and 13% (584/3,843) respectively. Intraoperative and postoperative complications included iatrogenic humeral fractures (91/230, 40%) and instability (215/825, 26%). Revision to reverse total shoulder arthroplasty (TSA), rather than revision to anatomical TSA from any index prosthesis, resulted in lower complication rates and superior Constant scores, although there was no difference in American Shoulder and Elbow Surgeons scores.

Conclusion

Satisfactory improvement in patient-reported outcome measures are reported following revision shoulder arthroplasty; however, revision surgery is associated with high complication rates and better outcomes may be evident following revision to reverse TSA. Cite this article: Bone Jt Open 2021;2(8):618–630.
PEDESTRIAN BRIDGES AS ELEMENTS OF THE NEW URBAN IDENTITY OF CITIES
Authors:   Josip Juraj Strossmayer University of Osijek, Faculty of Civil Engineering and Architecture Osijek, Jurković Željka , Koški Željko ,   Josip Juraj Strossmayer University of Osijek, Faculty of Civil Engineering and Architecture Osijek, Lovoković Danijela ,   Josip Juraj Strossmayer University of Osijek, Faculty of Civil Engineering and Architecture Osijek
Published: August 2021

By the start of the 21st century, the majority of the world’s population was living in cities. Therefore, a top priority has been solving the problem of connecting parts of the city divided by traffic infrastructure in the shortest possible manner by using pedestrian paths. The aim of this study was to analyze, systematize, and typologically define the specific types of structures that make this possible, specifically pedestrian bridges located above roads and railway corridors. The primary and secondary requirements that must be met when designing a pedestrian bridge were identified, and an analysis and comparison of examples of constructed pedestrian bridges in Croatia and the world are herein presented. The results of this study enable the conclusion that, in recent times, in the age of the spectacle society and spectacle architecture, pedestrian bridges are simultaneously deemed architecture, engineering, and infrastructure projects. They are becoming new elements in a city’s image and contribute to the creation of a new urban identity. The original design of pedestrian bridges fosters the use of different construction systems and materials in accordance with technical and technological advancements in construction.
APPLICATION OF PRINCIPAL COMPONENT ANALYSIS TO DROUGHT INDICATORS OF THREE REPRESENTATIVE CROATIAN REGIONS
Authors:   Josip Juraj Strossmayer University of Osijek, Faculty of Civil Engineering and Architecture Osij, Tadić Lidija , Brleković Tamara , Potočki Kristina ,   Josip Juraj Strossmayer University of Osijek, Faculty of Civil Engineering and Architecture Osijek,   University of Zagreb, Faculty of Civil Engineering, Leko-Kos Marija ,   Insitute IGH, Osijek
Published: August 2021

Drought has become a very frequent hydrological event globally, including in Croatia. It can generally be explained by air temperature and precipitation changes on an annual and seasonal basis, owing to climate change. To contribute to the knowledge on drought phenomena in Croatia, the changes in air temperature and precipitation over a relatively long period between 1951 and 2018 were analyzed. The meteorological stations included in the research were Osijek, Zagreb, and Split, which represented the climate of the entire country. Drought was estimated using the standardized precipitation evapotranspiration index, which is one of the most comprehensive drought indices. Furthermore, the drought severity and duration were calculated using run theory. These parameters were tested for homogeneity using the standard normal homogeneity test. Only the air temperature exhibited inhomogeneity, with a break year in 1991 (Zagreb and Split) and 1998 (Osijek). The existence of significant temporal trends was tested using the non-parametric Mann–Kendall trend test. The probability of drought occurrence with a certain duration and severity was calculated using the copula function. Finally, principal component analysis was applied to the computed standardized Mann–Kendall test statistic (ZMK ) to define the relevance of each parameter change and their combination in drought occurrence on a seasonal basis. Drought occurrence was less recognizable from 1951 to 1991 (1998). In the second sub-period, the impact of an increasing air temperature was the most significant variable, particularly in Zagreb.