bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 length of hospital stay: a systematic review and data synthesis
Authors: Rees Eleanor M. , Nightingale Emily S. , Jafari Yalda , Waterlow Naomi R. , Clifford Samuel , B. Pearson Carl A. , Group CMMID Working , Jombart Thibaut , Procter Simon R. , Knight Gwenan M.
Published: September 2020

Background

The COVID-19 pandemic has placed an unprecedented strain on health systems, with rapidly increasing demand for healthcare in hospitals and intensive care units (ICUs) worldwide. As the pandemic escalates, determining the resulting needs for healthcare resources (beds, staff, equipment) has become a key priority for many countries. Projecting future demand requires estimates of how long patients with COVID-19 need different levels of hospital care.

Methods

We performed a systematic review of early evidence on length of stay (LoS) of patients with COVID-19 in hospital and in ICU. We subsequently developed a method to generate LoS distributions which combines summary statistics reported in multiple studies, accounting for differences in sample sizes. Applying this approach, we provide distributions for total hospital and ICU LoS from studies in China and elsewhere, for use by the community.

Results

We identified 52 studies, the majority from China (46/52). Median hospital LoS ranged from 4 to 53 days within China, and 4 to 21 days outside of China, across 45 studies. ICU LoS was reported by eight studies—four each within and outside China—with median values ranging from 6 to 12 and 4 to 19 days, respectively. Our summary distributions have a median hospital LoS of 14 (IQR 10–19) days for China, compared with 5 (IQR 3–9) days outside of China. For ICU, the summary distributions are more similar (median (IQR) of 8 (5–13) days for China and 7 (4–11) days outside of China). There was a visible difference by discharge status, with patients who were discharged alive having longer LoS than those who died during their admission, but no trend associated with study date.

Conclusion

Patients with COVID-19 in China appeared to remain in hospital for longer than elsewhere. This may be explained by differences in criteria for admission and discharge between countries, and different timing within the pandemic. In the absence of local data, the combined summary LoS distributions provided here can be used to model bed demands for contingency planning and then updated, with the novel method presented here, as more studies with aggregated statistics emerge outside China.
Oxidative stress mediates the apoptosis and epigenetic modification of the Bcl-2 promoter via DNMT1 in a cigarette smoke-induced emphysema model
Authors: Zeng Huihui , Li Tiao , He Xue , Cai Shan , Luo Hong , Chen Ping , Chen Yan
Published: September 2020

Background

Emphysema is a crucial pathological characteristic of chronic obstructive pulmonary disease (COPD). Oxidative stress, apoptosis and epigenetic mechanisms contribute to the pathogenesis of emphysema. However, an attempt to accurately identify whether these mechanisms interact with each other and how they are triggered has never been conducted.

Method

The total reactive oxygen species (ROS) level, pulmonary apoptosis and B-cell lymphoma/leukemia-2 (Bcl-2) expression, an apoptosis regulator, were detected in samples from COPD patients. Bisulfite sequencing PCR (BSP) was conducted to observe the alterations in the methylation of the Bcl-2 promoter in specimens. The dysregulation of DNA methyltransferase enzyme 1 (DNMT1), a vital DNA methyltransferase enzyme, in the lungs of patients was confirmed through western blotting. To find out interactions between oxidative stress and DNA methylation in emphysema, mouse models were built with antioxidant treatment and DNMT1 silencing, and were examined with the pulmonary apoptosis, Bcl-2 and DNMT1 levels, and epigenetic alterations of Bcl-2.

Results

Higher ROS levels and pulmonary apoptosis were observed in COPD patients than in healthy controls. Downregulated Bcl-2 expression with increased promoter methylation and DNMT1 protein expression was found in COPD patients. Antioxidant treatment reduced the level of ROS, DNMT1 protein and emphysematous progression in the smoking models. Following DNMT1 blockade, smoking models showed improved lung function, pulmonary apoptosis, emphysematous progression, and increased Bcl-2 protein level with less promoter methylation than emphysema mice.

Conclusion

Cigarette-induced oxidative stress mediates pulmonary apoptosis and hypermethylation of the Bcl-2 promoter in emphysema models through DNMT1.
Application of different types of CRISPR/Cas-based systems in bacteria
Authors: Liu Zhenquan , Dong Huina , Cui Yali , Cong Lina , Zhang Dawei
Published: September 2020

As important genome editing tools, CRISPR/Cas systems, especially those based on type II Cas9 and type V Cas12a, are widely used in genetic and metabolic engineering of bacteria. However, the intrinsic toxicity of Cas9 and Cas12a-mediated CRISPR/Cas tools can lead to cell death in some strains, which led to the development of endogenous type I and III CRISPR/Cas systems. However, these systems are hindered by complicated development and limited applications. Thus, further development and optimization of CRISPR/Cas systems is needed. Here, we briefly summarize the mechanisms of different types of CRISPR/Cas systems as genetic manipulation tools and compare their features to provide a reference for selecting different CRISPR/Cas tools. Then, we show the use of CRISPR/Cas technology for bacterial strain evolution and metabolic engineering, including genome editing, gene expression regulation and the base editor tool. Finally, we offer a view of future directions for bacterial CRISPR/Cas technology.
Utility of ultra-sensitive qPCR to detect Plasmodium falciparum and Plasmodium vivax infections under different transmission intensities
Authors: Gruenberg Maria , Moniz Clara Antunes , Hofmann Natalie E. , Koepfli Cristian , Robinson Leanne J. , Nate Elma , Monteiro Wuelton Marcelo , de Melo Gisely Cardoso , Kuehn Andrea , Siqueira Andre M. , Nguitragool Wang , Bassat Quique , Lacerda Marcus , Sattabongkot Jetsumon , Mueller Ivo , Felger Ingrid
Published: September 2020

Background

The use of molecular diagnostics has revealed an unexpectedly large number of asymptomatic low-density malaria infections in many malaria endemic areas. This study compared the gains in parasite prevalence obtained by the use of ultra-sensitive (us)-qPCR as compared to standard qPCR in cross-sectional surveys conducted in Thailand, Brazil and Papua New Guinea (PNG). The compared assays differed in the copy number of qPCR targets in the parasite genome.

Methods

Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) parasites were quantified by qPCR amplifying the low-copy Pf_ and Pv_18S rRNA genes or the multi-copy targets Pf_varATS and Pv_mtCOX1. Cross-sectional surveys at the three study sites included 2252 participants of all ages and represented different transmission intensities.

Results

In the two low-transmission areas, P. falciparum positivity was 1.3% (10/773) (Thailand) and 0.8% (5/651) (Brazil) using standard Pf_18S rRNA qPCR. In these two countries, P. falciparum positivity by Pf_varATS us-qPCR increased to 1.9% (15/773) and 1.7% (11/651). In PNG, an area with moderate transmission intensity, P. falciparum positivity significantly increased from 8.6% (71/828) by standard qPCR to 12.2% (101/828) by us-qPCR. The proportions of P. falciparum infections not detected by standard qPCR were 33%, 55% and 30% in Thailand, Brazil and PNG. Plasmodium vivax was the predominating species in Thailand and Brazil, with 3.9% (30/773) and 4.9% (32/651) positivity by Pv_18S rRNA qPCR. In PNG, P. vivax positivity was similar to P. falciparum, at 8.0% (66/828). Use of Pv_mtCOX1 us-qPCR led to a significant increase in positivity to 5.1% (39/773), 6.4% (42/651) and 11.5% (95/828) in Thailand, Brazil, and PNG. The proportions of P. vivax infections missed by standard qPCR were similar at all three sites, with 23%, 24% and 31% in Thailand, Brazil and PNG.

Conclusion

The proportional gains in the detection of P. falciparum and P. vivax infections by ultra-sensitive diagnostic assays were substantial at all three study sites. Thus, us-qPCR yields more precise prevalence estimates for both P. falciparum and P. vivax at all studied levels of endemicity and represents a significant diagnostic improvement. Improving sensitivity in P. vivax surveillance by us-qPCR is of particular benefit, because the additionally detected P. vivax infections signal the potential presence of hypnozoites and subsequent risk of relapse and further transmission.
Ultra-sensitive RDT performance and antigen dynamics in a high-transmission Plasmodium falciparum setting in Mali
Authors: Reichert Emily N. , Hume Jen C. C. , Sagara Issaka , Healy Sara A. , Assadou Mahamadoun H. , Guindo Merepen A. , Barney Rebecca , Rashid Andy , Yang Ihn Kyung , Golden Allison , Domingo Gonzalo J. , Duffy Patrick E. , Slater Hannah C.
Published: September 2020

Background

The recent expansion of tools designed to accurately quantify malaria parasite-produced antigens has enabled us to evaluate the performance of rapid diagnostic tests (RDTs) as a function of the antigens they detect—typically histidine rich protein 2 (HRP2) or lactate dehydrogenase (LDH).

Methods

For this analysis, whole blood specimens from a longitudinal study in Bancoumana, Mali were used to evaluate the performance of the ultra-sensitive HRP2-based Alere™ Malaria Ag P.f RDT (uRDT). The samples were collected as part of a transmission-blocking vaccine trial in a high transmission region for Plasmodium falciparum malaria. Furthermore, antigen dynamics after successful anti-malarial drug treatment were evaluated in these samples using the Q-Plex Human Malaria Array (4-Plex) to quantify antigen concentrations.

Results

The uRDT had a 50% probability of a positive result at 207 pg/mL HRP2 [95% credible interval (CrI) 160–268]. Individuals with symptomatic infection remained positive by uRDT for a median of 33 days [95% confidence interval (CI) 28–47] post anti-malarial drug treatment. Biphasic exponential decay models accurately captured the population level post-treatment dynamics of both HRP2 and Plasmodium LDH (pLDH), with the latter decaying more rapidly. Motivated by these differences in rates of decay, a novel algorithm that used HRP2:pLDH ratios to predict if an individual had active versus recently cleared P. falciparum infection was developed. The algorithm had 77.5% accuracy in correctly classifying antigen-positive individuals as those with and without active infection.

Conclusions

These results characterize the performance of the ultra-sensitive RDT and demonstrate the potential for emerging antigen-quantifying technologies in the field of malaria diagnostics to be helpful tools in distinguishing between active versus recently cleared malaria infections.
Multifunctional nanobubbles carrying indocyanine green and paclitaxel for molecular imaging and the treatment of prostate cancer
Authors: Lan Minmin , Zhu Lianhua , Wang Yixuan , Shen Daijia , Fang Kejing , Liu Yu , Peng Yanli , Qiao Bin , Guo Yanli
Published: September 2020

Background

Combining ultrasound imaging with photoacoustic imaging provides tissue imaging with high contrast and resolution, thereby enabling rapid, direct measurements and the tracking of tumour growth and metastasis. Moreover, ultrasound-targeted nanobubble destruction (UTND) provides an effective way to deliver drugs, effectively increasing the content of the drug in the tumour area and reducing potential side effects, thereby successfully contributing to the treatment of tumours.

Results

In this study, we prepared multifunctional nanobubbles (NBs) carrying indocyanine green (ICG) and paclitaxel (PTX) (ICG-PTX NBs) and studied their applications in ultrasound imaging of prostate cancer as well as their therapeutic effects on prostate cancer when combined with UTND. ICG-PTX NBs were prepared by the mechanical oscillation method. The particle size and zeta potential of the ICG-PTX NBs were 469.5 ± 32.87 nm and − 21.70 ± 1.22 mV, respectively. The encapsulation efficiency and drug loading efficiency of ICG were 68% and 2.52%, respectively. In vitro imaging experiments showed that ICG-PTX NBs were highly amenable to multimodal imaging, including ultrasound, photoacoustic and fluorescence imaging, and the imaging effect was positively correlated with their concentration. The imaging effects of tumour xenografts also indicated that ICG-PTX NBs were of good use for multimodal imaging. In experiments testing the growth of PC-3 cells in vitro and tumour xenografts in vivo, the ICG-PTX NBs + US group showed more significant inhibition of cell proliferation and the promotion of cell apoptosis compared to the other groups (P < 0.05). Blood biochemical analysis of the six groups showed that the levels of aspartate aminotransferase (AST), phenylalanine aminotransferase (ALT), serum creatinine (CRE) and blood urea nitrogen (BUN) in the ICG-PTX NBs and the ICG-PTX NBs + US groups were significantly lower than those in the PTX group (P < 0.05). Moreover, H&E staining of tissue sections from vital organs showed no obvious abnormalities in the ICG-PTX NBs and the ICG-PTX NBs + US groups.

Conclusions

ICG-PTX NBs can be used as a non-invasive, pro-apoptotic contrast agent that can achieve multimodal imaging, including ultrasound, fluorescence and photoacoustic imaging, and can succeed in the local treatment of prostate cancer providing a potential novel method for integrated research on prostate cancer diagnosis and treatment.
Radiosensitizing high-Z metal nanoparticles for enhanced radiotherapy of glioblastoma multiforme
Authors: Choi Jinyeong , Kim Gaeun , Cho Su Bin , Im Hyung-Jun
Published: September 2020

Radiotherapy is an essential step during the treatment of glioblastoma multiforme (GBM), one of the most lethal malignancies. The survival in patients with GBM was improved by the current standard of care for GBM established in 2005 but has stagnated since then. Since GBM is a radioresistant malignancy and the most of GBM recurrences occur in the radiotherapy field, increasing the effectiveness of radiotherapy using high-Z metal nanoparticles (NPs) has recently attracted attention. This review summarizes the progress in radiotherapy approaches for the current treatment of GBM, the physical and biological mechanisms of radiosensitization through high-Z metal NPs, and the results of studies on radiosensitization in the in vitro and in vivo GBM models using high-Z metal NPs to date.
Construction of prognostic predictor by comprehensive analyzing alternative splicing events for colon adenocarcinoma
Authors: Qu Yaqi , Chen Yujia , Zhang Le , Tian Lifei
Published: September 2020

Background

Colon adenocarcinoma (COAD) is one of the most common malignant tumors, with high incidence and mortality rates worldwide. Reliable prognostic biomarkers are needed to guide clinical practice.

Methods

Comprehensive gene expression with alternative splicing (AS) profiles for each patient was downloaded using the SpliceSeq database from The Cancer Genome Atlas. Cox regression analysis was conducted to screen for prognostic AS events. The R package limma was used to screen differentially expressed genes (DEGs) between normal and tumor samples in the COAD cohort. A Venn plot analysis was performed between DEGs and prognostic AS events, and the DEGs that co-occurred with prognostic AS events (DEGAS) were identified. The top 30 most-connected DEGAS in protein–protein interaction analysis were identified through Cox proportional hazards regression to establish prognostic models.

Results

In total, 350 patients were included in the study. A total of 22,451 AS events were detected, of which 2004 from 1439 genes were significantly associated with survival time. By overlapping these 1439 genes with 6455 DEGs, 211 DEGs with AS events were identified. After the construction of the protein–protein interaction network, the top 30 hub genes were included in a multivariate analysis. Finally, a risk score based on 12 genes associated with overall survival was established (P < 0.05). The area under the curve was 0.782. The risk score was an independent predictor (P < 0.001).

Conclusions

By exploring survival-associated AS events, a powerful prognostic predictor consisting of 12 DEGAS was built. This study aims to propose a novel method to provide treatment targets for COAD and guide clinical practice in the future.
First detection of African swine fever (ASF) virus genotype X and serogroup 7 in symptomatic pigs in the Democratic Republic of Congo
Authors: Bisimwa Patrick N. , Ongus Juliette R. , Tiambo Christian K. , Machuka Eunice M. , Bisimwa Espoir B. , Steinaa Lucilla , Pelle Roger
Published: September 2020

Background

African swine fever (ASF) is a highly contagious and severe hemorrhagic viral disease of domestic pigs. The analysis of variable regions of African swine fever virus (ASFV) genome led to more genotypic and serotypic information about circulating strains. The present study aimed at investigating the genetic diversity of ASFV strains in symptomatic pigs in South Kivu province of the Democratic Republic of Congo (DRC).

Materials and methods

Blood samples collected from 391 ASF symptomatic domestic pigs in 6 of 8 districts in South Kivu were screened for the presence of ASFV, using a VP73 gene-specific polymerase chain reaction (PCR) with the universal primer set PPA1-PPA2. To genotype the strains, we sequenced and compared the nucleotide sequences of PPA-positive samples at three loci: the C-terminus of B646L gene encoding the p72 protein, the E183L gene encoding the p54 protein, and the central hypervariable region (CVR) of the B602L gene encoding the J9L protein. In addition, to serotype and discriminate between closely related strains, the EP402L (CD2v) gene and the intergenic region between the I73R and I329L genes were analyzed.

Results

ASFV was confirmed in 26 of 391 pigs tested. However, only 19 and 15 PPA-positive samples, respectively, were successfully sequenced and phylogenetically analyzed for p72 (B646L) and p54 (E183L). All the ASFV studied were of genotype X. The CVR tetrameric repeat clustered the ASFV strains in two subgroups: the Uvira subgroup (10 TRS repeats, AAAABNAABA) and another subgroup from all other strains (8 TRS repeats, AABNAABA). The phylogenetic analysis of the EP402L gene clustered all the strains into CD2v serogroup 7. Analyzing the intergenic region between I73R and I329L genes revealed that the strains were identical but contained a deletion of a 33-nucleotide internal repeat sequence compared to ASFV strain Kenya 1950.

Conclusion

ASFV genotype X and serogroup 7 was identified in the ASF disease outbreaks in South Kivu province of DRC in 2018–2019. This represents the first report of ASFV genotype X in DRC. CVR tetrameric repeat sequences clustered the ASFV strains studied in two subgroups. Our finding emphasizes the need for improved coordination of the control of ASF.
Alcohol drinking as a mediator of the influence of smoking prevalence on second-hand smoke exposure in workplaces: a mediation analysis
Authors: Lin Haoxiang , Chang Chun , Liu Zhao
Published: September 2020

Objective

Both alcohol drinking and second-hand smoke (SHS) exposure have shown a strong association with smoking behaviour. This study uses mediation analysis to clarify the process underlying the relationship between smoking prevalence and SHS exposure and the extent to which this relationship is mediated by alcohol use in the workplace.

Method

A total of 14,195 employees from 81 companies in China participated in this survey. Mediation analysis was used to establish the mediation effect of alcohol drinking. Structural equation modelling (SEM) was used to evaluate the role of alcohol drinking when a smoke-free (SF) workplace policy was imposed.

Results

For males, approximately 6.3% of the effects on SHS exposure were mediated through the channel of alcohol use. For females, this channel mediated 14.1% of the total effects. SF policy was negatively associated with smoking prevalence and SHS exposure. The indirect effect of the SF policy on reducing SHS exposure by controlling smoking behaviour was significant. For smokers, worksite smoking bans were negatively associated with the smoking amount and drinking behaviour, and the indirect effect of this policy on promoting smokers’ intention to quit by reducing the smoking amount and controlling drinking behaviour was significant.

Conclusion

This study confirmed that alcohol drinking is among the channels that mediate the association between smoking prevalence and SHS exposure in workplaces. Our results also find a spillover effect of SF workplace policy and call for effective interventions for alcohol use, which may influence the outcomes of SF policy implementation.
Comparison of symptomatic spondylolysis in young soccer and baseball players
Authors: Yokoe Takuji , Tajima Takuya , Sugimura Hiroshi , Kubo Shinichirou , Nozaki Shotarou , Yamaguchi Nami , Morita Yudai , Chosa Etsuo
Published: September 2020

Background

Spondylolysis is the main cause of low back pain (LBP) in young athletes. There are few studies analyzing the difference of spondylolysis among young athletes with different sports activities. The purpose of this study was to compare the clinical factors and distribution of the lesions of spondylolysis on magnetic resonance imaging (MRI) scans in young soccer and baseball players with symptomatic spondylolysis.

Methods

The medical records of 267 young athletes aged 7 to 18 years old who underwent MRI to evaluate the cause of LBP between 2017 and 2020 were retrospectively reviewed to identify patients with spondylolysis. Of the young athletes with symptomatic spondylolysis, clinical factors and MRI findings in soccer and baseball players were retrospectively evaluated. The clinical factors were age, sex, interval from onset of LBP to MRI, and side of the dominant leg in the sports field. MRI findings included number, lumbar level, and side of the lesions.

Results

A total of 33 soccer players (mean age, 15.4 ± 1.4 years) and 49 baseball players (mean age, 15.4 ± 1.6 years) with symptomatic spondylolysis were enrolled. All patients were male. No significant differences were noted in age and the interval from onset of LBP to MRI between the groups. Soccer players had greater numbers of multiple (p< 0.001) and bilateral (p< 0.001) lesions than baseball players. The dominant side of the hand for pitching or batting was correlated with the contralateral-side lesions in baseball players (p= 0.001).

Conclusions

The distribution of the lesions of spondylolysis differed in young soccer and baseball players. Pitching or batting with the dominant-side hand would be associated with contralateral-side lesions in baseball players. Sports-specific movements and the side of the dominant leg should be considered when treating young athletes with symptomatic spondylolysis.
Medicinal plants used in managing diseases of the respiratory system among the Luo community: an appraisal of Kisumu East Sub-County, Kenya
Authors: Mailu James Kiamba , Nguta Joseph Mwanzia , Mbaria James Mucunu , Okumu Mitchel Otieno
Published: September 2020

Background

Poor access to healthcare in rural communities causes many people to seek herbalists who use medicinal plants for the treatment of various disease conditions. Most knowledge of traditional herbal medicine makes use of indigenous remedies which are often undocumented and are at risk of being lost. The preservation of this knowledge may facilitate scientific inquiry into promising new therapeutic molecules.

Methods

Semi-structured questionnaires were used to collect the sociodemographic information of 30 herbalists in Kisumu East Sub County. The local names of medicinal plants used in managing illnesses of the respiratory system, their habit, active parts, indications, methods of preparation, routes of administration, scientific identity, and conservation status were also recorded. Other reported traditional uses, pharmacological activities, and toxicological data were identified via a literature search.

Results

Most herbalists were female (86.7%), aged between 61 and 70 years (43.3%) with no formal education (56.7%), and had 21–30 years of practice (30%). 44 plant species, belonging to 43 genera and 28 families were identified. Leguminosae and Rutaceae plant families were predominant, leaves were frequently used (33%), and trees were the most common habit (44.4%). Most plants were collected in the wild (79.2%), preparation was mainly by decoction (68.8%), and the administration was mainly orally. The main indication was cough and 79.5% of all documented plant species had previously been reported to have a pharmacological activity relevant to the mitigation of respiratory illnesses. Toxicological data was available for 84.1% of the plant species identified.

Conclusions

The predominant use of roots, root barks, and root tubers by herbalists in Kisumu East Sub County threatens to negatively impact the ecological survival of some plant species. The preservation of herbalists’ knowledge of medicinal plants in the study area is a pressing concern considering their advanced age and little formal education. There is a need to conserve some of the medicinal plants documented in this study. The medicinal claims made by herbalists also warrant scientific scrutiny.
Alternating Hemiplegia of Childhood: gastrointestinal manifestations and correlation with neurological impairments
Authors: Pratt Milton , Uchitel Julie , McGreal Nancy , Gordon Kelly , Prange Lyndsey , McLean Melissa , Noel Richard J. , Rikard Blaire , Rogers Boruta Mary K. , Mikati Mohamad A.
Published: September 2020

Background

Alternating Hemiplegia of Childhood (AHC) is caused by mutations of the ATP1A3 gene which is expressed in brain areas that include structures controling autonomic, gastrointestinal, gut motility and GABAergic functions. We aimed to investigate, in a cohort of 44 consecutive AHC patients, two hypotheses: 1) AHC patients frequently manifest gastrointestinal, particularly motility, problems. 2) These problems are often severe and their severity correlates with neurological impairments.

Results

41/44 (93%) exhibited gastrointestinal symptoms requiring medical attention. For these 41 patients, symptoms included constipation (66%), swallowing problems (63%), vomiting (63%), anorexia (46%), diarrhea (44%), nausea (37%), and abdominal pain (22%). Symptoms indicative of dysmotility occurred in 33 (80%). The most common diagnoses were oropharyngeal dysphagia (63%) and gastroesophageal reflux (63%). 16 (39%) required gastrostomy and two fundoplication. Severity of gastrointestinal symptoms correlated with non-paroxysmal neurological disability index, Gross Motor Function Classification System scores, and with the presence/absence of non-gastrointestinal autonomic dysfunction (p = 0.031, 0.043, Spearman correlations and 0.0166 Cramer’s V, respectively) but not with the paroxysmal disability index (p = 0.408).

Conclusions

Most AHC patients have gastrointestinal problems. These are usually severe, most commonly are indicative of dysmotility, often require surgical therapies, and their severity correlates with that of non-paroxysmal CNS manifestations. Our findings should help in management-anticipatory guidance of AHC patients. Furthermore, they are consistent with current understandings of the pathophysiology of AHC and of gastrointestinal dysmotility, both of which involve autonomic and GABAergic dysfunction.
Cell therapy for spinal cord injury by using human iPSC-derived region-specific neural progenitor cells
Authors: Kajikawa Keita , Imaizumi Kent , Shinozaki Munehisa , Shibata Shinsuke , Shindo Tomoko , Kitagawa Takahiro , Shibata Reo , Kamata Yasuhiro , Kojima Kota , Nagoshi Narihito , Matsumoto Morio , Nakamura Masaya , Okano Hideyuki
Published: September 2020

The transplantation of neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) has beneficial effects on spinal cord injury (SCI). However, while there are many subtypes of NPCs with different regional identities, the subtype of iPSC-derived NPCs that is most appropriate for cell therapy for SCI has not been identified. Here, we generated forebrain- and spinal cord-type NPCs from human iPSCs and grafted them onto the injured spinal cord in mice. These two types of NPCs retained their regional identities after transplantation and exhibited different graft-host interconnection properties. NPCs with spinal cord regional identity but not those with forebrain identity resulted in functional improvement in SCI mice, especially in those with mild-to-moderate lesions. This study highlights the importance of the regional identity of human iPSC-derived NPCs used in cell therapy for SCI.
High HbA1c is associated with decreased 6-month survival and poor outcomes after out-of-hospital cardiac arrest: a retrospective cohort study
Authors: Lee Junhaeng , Oh Joo Suk , Zhu Jong Ho , Hong Sungyoup , Park Sang Hyun , Kim Ji Hoon , Kim Hyungsoo , Seo Mingu , Kim Kiwook , Lee Doo Hyo , Jung Hyun Ho , Park Jungtaek , Oh Young Min , Choi Semin , Choi Kyoung Ho
Published: September 2020

Background

To evaluate the associations between glycated hemoglobin (HbA1c) at admission and 6-month mortality and outcomes after out-of-hospital cardiac arrest (OHCA) treated by hypothermic targeted temperature management (TTM).

Methods

This single-center retrospective cohort study included adult OHCA survivors who underwent hypothermic TTM from December 2011 to December 2019. High HbA1c at admission was defined as a level higher than 6%. Poor neurological outcomes were defined as cerebral performance category scores of 3–5. The primary outcome was 6-month mortality. The secondary outcome was the 6-month neurological outcome. Descriptive statistics, log-rank tests, and multivariable regression modeling were used for data analysis.

Results

Of the 302 patients included in the final analysis, 102 patients (33.8%) had HbA1c levels higher than 6%. The high HbA1c group had significantly worse 6-month survival (12.7% vs. 37.5%,p < 0.001) and 6-month outcomes (89.2% vs. 73.0%,p = 0.001) than the non-high HbA1c group. Kaplan-Meier analysis and the log-rank test showed that the survival time was significantly shorter in the patients with HbA1c > 6% than in those with HbA1c ≤6%. In the multivariable logistic regression analysis, HbA1c > 6% was independently associated with 6-month mortality (OR 5.85, 95% CI 2.26–15.12, p < 0.001) and poor outcomes (OR 4.18, 95% CI 1.41–12.40, p < 0.001).

Conclusions

This study showed that HbA1c higher than 6% at admission was associated with increased 6-month mortality and poor outcomes in OHCA survivors treated with hypothermic TTM. Poor long-term glycemic management may have prognostic significance after cardiac arrest.
EPISCORE: cell type deconvolution of bulk tissue DNA methylomes from single-cell RNA-Seq data
Authors: Teschendorff Andrew E. , Zhu Tianyu , Breeze Charles E. , Beck Stephan
Published: September 2020

Cell type heterogeneity presents a challenge to the interpretation of epigenome data, compounded by the difficulty in generating reliable single-cell DNA methylomes for large numbers of cells and samples. We present EPISCORE, a computational algorithm that performs virtual microdissection of bulk tissue DNA methylation data at single cell-type resolution for any solid tissue. EPISCORE applies a probabilistic epigenetic model of gene regulation to a single-cell RNA-seq tissue atlas to generate a tissue-specific DNA methylation reference matrix, allowing quantification of cell-type proportions and cell-type-specific differential methylation signals in bulk tissue data. We validate EPISCORE in multiple epigenome studies and tissue types.
Efficacy and safety of Jia Wei Bushen Yiqi formulas as an adjunct therapy to systemic glucocorticoids on acute exacerbation of COPD: study protocol for a randomized, double-blinded, multi-center, placebo-controlled clinical trial
Authors: Kong Qing , Mo Shuming , Wang Wenqian , Tang Zihui , Wei Ying , Du Yijie , Liu Baojun , Kong Lingwen , Lv Yubao , Dong Jingcheng
Published: September 2020

Background

Systemic glucocorticoids are effective for the management of chronic obstructive pulmonary disease (COPD) exacerbation but have serious adverse effects. Traditional Chinese medicine (TCM) can bring additional benefits to these patients but has few adverse effects. The present study aims to evaluate the efficacy and safety of Jia Wei Bushen Yiqi (JWBY) formulas in patients who suffer from COPD exacerbations and to investigate whether the short-term (5-days) systemic glucocorticoid therapy is non-inferior to the long-term (9-day) regime.

Methods

In this multi-center, randomized, double-blinded trial, eligible inpatients with COPD exacerbation are randomly assigned to four groups (A, B, C, and D). Group A will receive placebo plus 5-day prednisone, group B will receive placebo plus 9-day prednisone, group C will receive JWBY formulas plus 5-day prednisone, and group D will receive JWBY formulas plus 9-day prednisone. The primary outcomes are the time interval to the patient’s next exacerbation during a 180-day following up and the COPD assessment test (CAT) during treatment. Secondary outcomes include lung function, TCM syndrome assessment, laboratory tests, and safety. The changes of the hypothalamic pituitary adrenaline axis (HPA axis) and inflammatory cytokine will be measured as well.

Discussion

By demonstrating the advantages of utilizing TCM and an appropriate duration of systemic glucocorticoids, this effectiveness comparison trial will provide new references to physicians on how to improve the management of COPD exacerbation. The results of HPA axis and inflammation cytokine measurements will shed light on the molecular mechanisms and entail further mechanism studies.

Trial registration

www.chictr.org.cnChiCTR1900023364. Registered on 24 May 2019.
Hydrocortisone to treat early bronchopulmonary dysplasia in very preterm infants: study protocol for a randomized controlled trial
Authors: He Yuan , Zhang Yong , Gao Shuqiang , Wang Xiaoling , He Na , Zhang Deshuang , Dong Wenbin , Wieg Christian , Lei Xiaoping
Published: September 2020

Background

Bronchopulmonary dysplasia (BPD) is still a common complication in very premature infants. At present, there is no effective treatment for BPD. Glucocorticoids are drugs commonly used to prevent or treat BPD before and after birth. In very premature infants with high risk factors for BPD, early use of dexamethasone can reduce the rate of death and/or BPD but may cause long-term adverse neurodevelopmental outcomes. Hydrocortisone (HC), as an alternative drug to dexamethasone, has been increasingly used to prevent BPD. However, no study has reported the efficacy and safety of HC to treat early BPD diagnosed at postnatal day (PND) 28.

Methods

This study protocol is for a multicenter double-blind randomized controlled trial of low-dose HC in the treatment of early BPD. Early BPD infants will be randomly assigned to the HC treatment group or control group. Infants in the HC group will receive 0.5 mg/kg HC twice a day for 7 days and then 0.5 mg/kg HC once a day for 3 days. The control group will be given the same volume of placebo and no intervention on the basis of routine treatment. The primary outcome is survival without moderate or severe BPD at 36 weeks postmenstrual age. Secondary outcomes are the short- and long-term effects on growth, metabolism, neurodevelopment, and other possible complications.

Discussion

This trial will determine the efficacy and safety of low-dose HC administration compared to placebo for the reduction of moderate or severe BPD at 36 weeks postmenstrual age in very preterm infants with early BPD.

Trial registration

China Clinical Trial Registration Center ChiCTR1900021854. Registered on 13 March 2019.
Probiotics ameliorate pioglitazone-associated bone loss in diabetic rats
Authors: Gholami Ahmad , Dabbaghmanesh Mohammad Hossein , Ghasemi Younes , Talezadeh Pedram , Koohpeyma Farhad , Montazeri-Najafabady Nima
Published: September 2020

Background

Pioglitazone, as a PPAR gamma agonist, is used for the management of type 2 diabetes mellitus. Nevertheless, evidence showed that the therapeutic modulation of PPAR gamma activity using pioglitazone might be linked with bone mass reduction and fracture risk in type 2 diabetes mellitus patients. The objective of the current research was to inspect the preventive role of some types of probiotic strains, including (Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei, Bifidobacterium longum, and Bacillus coagulans) against pioglitazone-induced bone loss.

Methods

Streptozotocin (60 mg/kg) was administered for diabetes induction. Diabetic rats were fed orally with pioglitazone (300 mg/kg) and probiotics (1 × 109 CFU/ml/day) alone and in combination for four weeks. Dual-energy X-ray absorptiometry (DXA) was used to assess BMD, BMC, and area of the femur, spine, and tibia at the end of the experiment. Serum glucose, serum calcium (Ca), alkaline phosphatase (ALP), phosphorus (P), Blood urea nitrogen (BUN), creatinine, and urine calcium were also analyzed.

Results

Administration of pioglitazone and probiotics alone and, in combination, significantly reduced elevated blood glucose. Pioglitazone treatment significantly increased urinary calcium and BUN and decreased ALP and creatinine. Co-treatment of probiotics with pioglitazone significantly decreased urinary calcium, creatinine, and ALP. Pioglitazone showed detrimental effects on femur-BMD, whereas treatment with probiotics remarkably ameliorated these effects. Among the tested probiotics, Bifidobacterium longum displayed the best protective effects on pioglitazone-induced bone loss in diabetic rats.

Conclusion

This study suggests probiotic supplementation in diabetic patients on pioglitazone regime could be considering as an excellent strategy to ameliorate bone loss induced by pioglitazone.
MRI of rectal cancer—relevant anatomy and staging key points
Authors: Santiago Inês , Figueiredo Nuno , Parés Oriol , Matos Celso
Published: September 2020

Rectal cancer has the eighth highest cancer incidence worldwide, and it is increasing in young individuals. However, in countries with a high human development index, mortality is decreasing, which may reflect better patient management, imaging being key. We rely on imaging to establish the great majority of clinical tumour features for therapeutic decision-making, namely tumour location, depth of invasion, lymph node involvement, circumferential resection margin status and extramural venous invasion. Despite major improvements in technique resulting in better image quality, and notwithstanding the dissemination of guidelines and examples of standardised reports, rectal cancer staging is still challenging on the day-to-day practice, and we believe there are three reasons. First, the normal posterior pelvic compartment anatomy and variants are not common knowledge to radiologists; second, not all rectal cancers fit in review paper models, namely the very early, the very low and the mucinous; and third, the key clinical tumour features may be tricky to analyse. In this review, we discuss the normal anatomy of the rectum and posterior compartment of the pelvis, systematise all rectal cancer staging key points and elaborate on the particularities of early, low and mucinous tumours. We also include our suggested reporting templates and a discussion of its comparison to the reporting templates provided by ESGAR and SAR.
Correction to: LncRNA-NEAT1 from the competing endogenous RNA network promotes cardioprotective efficacy of mesenchymal stem cell-derived exosomes induced by macrophage migration inhibitory factor via the miR-142-3p/FOXO1 signaling pathway
Authors: Chen Hanbin , Xia Wenzheng , Hou Meng
Published: September 2020

An amendment to this paper has been published and can be accessed via the original article.
Acute kidney injury in patients with SARS-CoV-2 infection
Authors: Joseph Adrien , Zafrani Lara , Mabrouki Asma , Azoulay Elie , Darmon Michael
Published: September 2020

Background

Acute Kidney Injury (AKI) is a frequent complication of severe SARS-CoV-2 infection. Multiple mechanisms are involved in COVID-19-associated AKI, from direct viral infection and secondary inflammation to complement activation and microthrombosis. However, data are limited in critically-ill patients. In this study, we sought to describe the prevalence, risk factors and prognostic impact of AKI in this setting.

Methods

Retrospective monocenter study including adult patients with laboratory confirmed SARS-CoV-2 infection admitted to the ICU of our university Hospital. AKI was defined according to both urinary output and creatinine KDIGO criteria.

Results

Overall, 100 COVID-19 patients were admitted. AKI occurred in 81 patients (81%), including 44, 10 and 27 patients with AKI stage 1, 2 and 3 respectively. The severity of AKI was associated with mortality at day 28 (p = 0.013). Before adjustment, the third fraction of complement (C3), interleukin-6 (IL-6) and ferritin levels were higher in AKI patients. After adjustment for confounders, both severity (modified SOFA score per point) and AKI were associated with outcome. When forced in the final model, C3 (OR per log 0.25; 95% CI 0.01–4.66), IL-6 (OR per log 0.83; 95% CI 0.51–1.34), or ferritin (OR per log 1.63; 95% CI 0.84–3.32) were not associated with AKI and did not change the model.

Conclusion

In conclusion, we did not find any association between complement activation or inflammatory markers and AKI. Proportion of patients with AKI during severe SARS-CoV-2 infection is higher than previously reported and associated with outcome.
Coverless information hiding based on the generation of anime characters
Authors: Cao Yi , Zhou Zhili , Wu Q. M. Jonathan , Yuan Chengsheng , Sun Xingming
Published: September 2020

To fundamentally resist the steganalysis, coverless information hiding has been proposed, and it has become a research hotspot in the field of covert communication. However, the current methods not only require a huge image database, but also have a very low hidden capacity, making it difficult to apply practically. In order to solve the above problems, we propose a coverless information hiding method based on the generation of anime characters, which first converts the secret information into an attribute label set of the anime characters, and then uses the label set as a driver to directly generate anime characters by using the generative adversarial networks (GANs). The experimental results show that compared with the current methods, the hidden capacity of the proposed method is improved by nearly 60 times, and it also has good performance in image quality and robustness.
Regularization of the fractional Rayleigh–Stokes equation using a fractional Landweber method
Authors: Luc Nguyen Hoang , Huynh Le Nhat , O’Regan Donal , Can Nguyen Huu
Published: September 2020

In this paper, we consider a time-fractional backward problem for the fractional Rayleigh–Stokes equation in a general bounded domain. We propose a fractional Landweber regularization method for solving this problem. Error estimates between the regularized solution and the sought solution are also obtained under some choice rules for both a-priori and a-posterior regularization parameters.
On a new fixed point theorem with an application on a coupled system of fractional differential equations
Authors: Afshari Hojjat , Jarad Fahd , Abdeljawad Thabet
Published: September 2020

In this work, new theorems and results related to fixed point theory are presented. The results obtained are used for the sake of proving the existence and uniqueness of a positive solution of a coupled system of equations that involves fractional derivatives in the Riemann–Liouville settings and is subject to boundary conditions in the form of integrals.
Certain new weighted estimates proposing generalized proportional fractional operator in another sense
Authors: Abdeljawad Thabet , Rashid Saima , El-Deeb A. A. , Hammouch Zakia , Chu Yu-Ming
Published: September 2020

The present work investigates the applicability and effectiveness of generalized proportional fractional integral ($\mathcal{GPFI}$
GPFI
) operator in another sense. We aim to derive novel weighted generalizations involving a family of positive functions n ($n\in \mathbb{N}$
n
∈
N
) for this recently proposed operator. As applications of this operator, we can generate notable outcomes for Riemann–Liouville ($\mathcal{RL}$
RL
) fractional, generalized $\mathcal{RL}$
RL
-fractional operator, conformable fractional operator, Katugampola fractional integral operator, and Hadamard fractional integral operator by changing the domain. The proposed strategy is vivid, explicit, and it can be used to derive new solutions for various fractional differential equations applied in mathematical physics. Certain remarkable consequences of the main theorems are also figured.
Effects of decitabine on allogeneic immune reactions of donor lymphocyte infusion via activation of dendritic cells
Authors: Kwon Yong-Rim , Kim Hye Joung , Sohn Min-Jung , Lim Ji-Young , Park Kyung-Shin , Lee Seok , Chung Nack-Gyun , Jeong Dae-Chul , Min Chang-Ki , Kim Yoo-Jin
Published: September 2020

Background

Successful prevention of post-transplantation relapse after donor lymphocyte infusion (DLI) depends on its capability to mediate an effective graft-versus-leukemia (GVL) response while minimizing DLI-related toxicity, including graft-versus-host disease (GVHD).

Methods

We assessed the effects of decitabine (DEC), a hypomethylating agent, upon allogeneic immune reaction in a murine model of DLI.

Results

Significantly greater tumor growth retardation and survival prolongation occurred in mice administered with 1.0 mg/kg DEC for 5 days (DEC-1.0) than in control or DEC-0.1 mice. Upon prompt DEC and DLI co-administration, dendritic cells (DCs) were activated; DEC-1.0/DLI induced severe GVHD, and survival was significantly lower than with DLI alone or DEC-0.1/DLI treatments. IFN-γ and CD28 levels were higher in splenic DCs of DEC-1.0 mice than in those of control mice. Assessment of delayed DLI co-administration with DEC, when IFN-γ levels were normalized to control levels, revealed that DEC-1.0/DLI successfully facilitated tumor management without causing severe GVHD.

Conclusions

Our results suggest that DEC primes allogeneic immune reactions of DLI via DC activation, and GVHD and GVL effects are separable through optimal DLI timing based on DEC-induced increase in IFN-γ expression levels.
“I’m not a teenager, I’m 22. Why can’t I snap out of it?”: a qualitative exploration of seeking help for a first-episode eating disorder during emerging adulthood
Authors: Potterton Rachel , Austin Amelia , Allen Karina , Lawrence Vanessa , Schmidt Ulrike
Published: September 2020

Background

Eating disorders (EDs) typically have their onset during adolescence or the transition to adulthood. Emerging adulthood (~ 18–25 years) is a developmental phase which conceptually overlaps with adolescence but also has unique characteristics (e.g. increased independence). Emerging adults tend to come to ED services later in illness than adolescents, and emerging adulthood’s unique characteristics may contribute to such delays.

Objective

This study aimed to explore attitudes towards ED symptoms, and their implications for help-seeking, amongst emerging adults receiving ED treatment through FREED, an early intervention care pathway.

Method

Participants were 14 emerging adults (mean age 20.9 years; SD = 2.0), all currently receiving specialist treatment for a first-episode, recent-onset (< 3 years) ED. Semi-structured interviews relating to experiences of help-seeking were conducted, and data were analysed thematically.

Results

Symptom egosyntonicity, gradual reappraisal and feelings of exclusion from ED discourse were key attitudinal phases prior to help-seeking, each of which had distinct implications for help-seeking.

Conclusions

Emerging adults with first-episode EDs show a distinct set of help-seeking-related challenges and opportunities (e.g. help-seeking for others; help-seeking at transitions; self-sufficiency). This research might be used to inform the development and evaluation of interventions which aim to facilitate help-seeking amongst emerging adults with first-episode recent-onset EDs.