bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospital mortality in patients with rare diseases during pandemics: lessons learnt from the COVID-19 and SARS pandemics
Authors: Chung Claudia Ching Yan , Wong Wilfred Hing Sang , Chung Brian Hon Yin 
Published: August 2021

Abstract
Background
The threat and experience of pandemics occur differently for different groups. The rare disease population is at particular risk of being further marginalised during pandemics. In this study, our objective was to assess the hospital mortality patterns in the rare disease and the general populations during the coronavirus disease of 2019 (COVID-19) and severe acute respiratory syndrome (SARS) pandemics in Hong Kong.

Methods
All admission records during the COVID-19 pandemic (January 23–August 23, 2020) and SARS pandemic (March 11–June 30, 2003) were extracted from the local public healthcare database. Patients with rare diseases were identified using one or more of the 1084 10th version International Classification of Diseases and Related Health Problems (ICD-10) codes cross-referenced with 467 ORPHAcodes. Hospital mortality patterns were compared in patients with and without COVID-19/SARS infection. Admission records during the same period in 2019 and 2002 were retrieved for comparison.

Results
During the COVID-19 pandemic, 407,219 patients were admitted to one or more of the 43 public hospitals in Hong Kong, of which, 13,894 were patients with rare diseases (3.4%). A total of 4381 and 77 patients from the general and rare disease populations were infected with COVID-19. Rare disease patients had an adjusted 3.4 times odds of COVID-19-related hospital mortality compared with that of the general population (95% C.I. 1.24–9.41). COVID-19-related mortality was almost exclusively seen in patients ≥ 60 years. While age-related increase in mortality was also observed for the general population during the SARS pandemic, the pattern observed in the rare disease population was significantly different, with a 12.5 times higher SARS-related mortality observed in rare disease patients ≤ 18 years than those in the general population (12.5% vs 1.0%). Patients admitted during the same pandemic periods without coronavirus infection had a significantly higher hospital mortality compared with those admitted one year before the pandemic (p < 0.001).

Conclusion
This population-based study demonstrated the differential impacts of the COVID-19 and SARS pandemics on the rare disease population. In the era of budget and resource scarcity, this study warrants cautious healthcare planning, with consideration of the rare disease population in healthcare prioritisation.
Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery
Authors: Bai Bing , Vanderwall David , Li Yuxin , Wang Xusheng , Poudel Suresh , Wang Hong , Dey Kaushik Kumar , Chen Ping-Chung , Yang Ka , Peng Junmin 
Published: August 2021

AbstractMass spectrometry-based proteomics empowers deep profiling of proteome and protein posttranslational modifications (PTMs) in Alzheimer’s disease (AD). Here we review the advances and limitations in historic and recent AD proteomic research. Complementary to genetic mapping, proteomic studies not only validate canonical amyloid and tau pathways, but also uncover novel components in broad protein networks, such as RNA splicing, development, immunity, membrane transport, lipid metabolism, synaptic function, and mitochondrial activity. Meta-analysis of seven deep datasets reveals 2,698 differentially expressed (DE) proteins in the landscape of AD brain proteome (n = 12,017 proteins/genes), covering 35 reported AD genes and risk loci. The DE proteins contain cellular markers enriched in neurons, microglia, astrocytes, oligodendrocytes, and epithelial cells, supporting the involvement of diverse cell types in AD pathology. We discuss the hypothesized protective or detrimental roles of selected DE proteins, emphasizing top proteins in “amyloidome” (all biomolecules in amyloid plaques) and disease progression. Comprehensive PTM analysis represents another layer of molecular events in AD. In particular, tau PTMs are correlated with disease stages and indicate the heterogeneity of individual AD patients. Moreover, the unprecedented proteomic coverage of biofluids, such as cerebrospinal fluid and serum, procures novel putative AD biomarkers through meta-analysis. Thus, proteomics-driven systems biology presents a new frontier to link genotype, proteotype, and phenotype, accelerating the development of improved AD models and treatment strategies.
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

AbstractT7 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

AbstractTo 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

Abstract
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

AbstractBackgroundRecent 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.MethodsA 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.DiscussionThis 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 registrationClinicalTrials.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

AbstractBackgroundInsomnia 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).MethodsA 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).DiscussionCBT-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 registrationClinicalTrials.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

Abstract
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

AbstractBackgroundBlastocystisis 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.MethodsStool 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.ResultsBlastocystiswas 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.ConclusionsAsymptomatic 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

AbstractBackgroundMetacaspases 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.MethodsIn 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.ResultsMCA1 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.ConclusionMCA1 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

AbstractImaging 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.