bluuebunny/crossref_metadata_2025 huggingface dataset:
Repulsive Guidance Molecule A Regulates Adult Neurogenesis Via the Neogenin Receptor
Authors: Isaksen Toke Jost , Yamashita Toshihide
Published: August 2020

Repulsive guidance molecule A (RGMa) exhibits repulsive guidance of axonal growth and regulates neuronal differentiation during development of the mammalian brain. In this commentary, we describe the findings of our recent paper, “Repulsive Guidance Molecule A Suppresses Adult Neurogenesis,” and discuss a possible model for RGMa suppression of newborn neurons that fail to properly migrate into the granular cell layer. In the study, we provided evidence that RGMa suppressed neurite growth and survival of newborn neurons in the adult dentate gyrus. This effect depends on the multifunctional Neogenin receptor expressed in adult neural stem cells through activation of the Rho-associated protein kinase leading to neurite growth inhibition and ultimately cell death. It should be noted that both RGMa and Neogenin interact with several well-described molecules, including bone morphogenetic proteins, that regulate neuronal development. Thus, it is likely that RGMa interacts with other intricate molecular networks that regulate adult neurogenesis.
Conformation-dependent blockage of activated VWF improves outcomes of traumatic brain injury in mice
Authors: Xu Xin , Wang Chenyu , Wu Yingang , Houck Katie , Hilton Tristan , Zhou Ashley , Wu Xiaoping , Han Cha , Yang Mengchen , Yang Wei , Shi Fu-Dong , Stolla Moritz , Cruz Miguel A. , Li Min , Zhang Jianning , Dong Jing-fei
Published: August 2020

Traumatic brain injury-induced coagulopathy (TBI-IC) causes life-threatening secondary intracranial bleeding. Its pathogenesis differs mechanistically from that of coagulopathy arising from extracranial injuries and hemorrhagic shock, but it remains poorly understood. We report results of a study designed to test the hypothesis that von Willebrand factor (VWF) released during acute TBI is intrinsically hyperadhesive because its platelet-binding A1-domain is exposed and contributes to TBI-induced vascular leakage and consumptive coagulopathy. This hyperadhesive VWF can be selectively blocked by a VWF A2-domain protein to prevent TBI-IC and to improve neurological function with a minimal risk of bleeding. We demonstrated that A2 given through intraperitoneal injection or IV infusion reduced TBI-induced death by >50% and significantly improved the neurological function of C57BL/6J male mice subjected to severe lateral fluid percussion injury. A2 protected the endothelium from extracellular vesicle-induced injury, reducing TBI-induced platelet activation and microvesiculation, and preventing a TBI-induced hypercoagulable state. A2 achieved this therapeutic efficacy by specifically blocking the A1 domain exposed on the hyperadhesive VWF released during acute TBI. These results suggest that VWF plays a causal role in the development of TBI-IC and is a therapeutic target for this life-threatening complication of TBI.
Genetic Dissection of Seed Dormancy in Rice (Oryza sativa L.) by Using Two Mapping Populations Derived from Common Parents
Authors: Zhang Chaopu , Yuan Zhiyang , Wang Yuntong , Sun Wenqiang , Tang Xinxin , Sun Yongjian , Yu Sibin
Published: August 2020

Background

Seed dormancy, a quality characteristic that plays a role in seed germination, seedling establishment and grain yield, is affected by multiple genes and environmental factors. The genetic and molecular mechanisms underlying seed dormancy in rice remain largely unknown.

Results

Quantitative trait loci (QTLs) for seed dormancy were identified in two different mapping populations, a chromosome segment substitution line (CSSL) and backcross inbred line (BIL) population, both derived from the same parents Nipponbare, a japonica cultivar with seed dormancy, and 9311, an indica cultivar lacking seed dormancy. A total of 12 and 27 QTL regions for seed dormancy were detected in the CSSLs and BILs, respectively. Among these regions, four major loci (qSD3.1, qSD3.2, qSD5.2 and qSD11.2) were commonly identified for multiple germination parameters associated with seed dormancy in both populations, with Nipponbare alleles delaying the seed germination percentage and decreasing germination uniformity. Two loci (qSD3.1 and qSD3.2) were individually validated in the near-isogenic lines containing the QTL of interest. The effect of qSD3.2 was further confirmed in a CSSL-derived F2 population. Furthermore, both qSD3.1 and qSD3.2 were sensitive to abscisic acid and exhibited a significant epistatic interaction to increase seed dormancy.

Conclusions

Our results indicate that the integration of the developed CSSLs and BILs with high-density markers can provide a powerful tool for dissecting the genetic basis of seed dormancy in rice. Our findings regarding the major loci and their interactions with several promising candidate genes that are induced by abscisic acid and specifically expressed in the seeds will facilitate further gene discovery and a better understanding of the genetic and molecular mechanisms of seed dormancy for improving seed quality in rice breeding programs.
GPU accelerated adaptive banded event alignment for rapid comparative nanopore signal analysis
Authors: Gamaarachchi Hasindu , Lam Chun Wai , Jayatilaka Gihan , Samarakoon Hiruna , Simpson Jared T. , Smith Martin A. , Parameswaran Sri
Published: August 2020

Background

Nanopore sequencing enables portable, real-time sequencing applications, including point-of-care diagnostics and in-the-field genotyping. Achieving these outcomes requires efficient bioinformatic algorithms for the analysis of raw nanopore signal data. However, comparing raw nanopore signals to a biological reference sequence is a computationally complex task. The dynamic programming algorithm called Adaptive Banded Event Alignment (ABEA) is a crucial step in polishing sequencing data and identifying non-standard nucleotides, such as measuring DNA methylation. Here, we parallelise and optimise an implementation of the ABEA algorithm (termed f5c) to efficiently run on heterogeneous CPU-GPU architectures.

Results

By optimising memory, computations and load balancing between CPU and GPU, we demonstrate how f5c can perform ∼3-5 × faster than an optimised version of the original CPU-only implementation of ABEA in the Nanopolish software package. We also show that f5c enables DNA methylation detection on-the-fly using an embedded System on Chip (SoC) equipped with GPUs.

Conclusions

Our work not only demonstrates that complex genomics analyses can be performed on lightweight computing systems, but also benefits High-Performance Computing (HPC). The associated source code for f5c along with GPU optimised ABEA is available at https://github.com/hasindu2008/f5c.
Exploring the possibility of predicting human head hair greying from DNA using whole-exome and targeted NGS data
Authors: Pośpiech Ewelina , Kukla-Bartoszek Magdalena , Karłowska-Pik Joanna , Zieliński Piotr , Woźniak Anna , Boroń Michał , Dąbrowski Michał , Zubańska Magdalena , Jarosz Agata , Grzybowski Tomasz , Płoski Rafał , Spólnicka Magdalena , Branicki Wojciech
Published: August 2020

Background

Greying of the hair is an obvious sign of human aging. In addition to age, sex- and ancestry-specific patterns of hair greying are also observed and the progression of greying may be affected by environmental factors. However, little is known about the genetic control of this process. This study aimed to assess the potential of genetic data to predict hair greying in a population of nearly 1000 individuals from Poland.

Results

The study involved whole-exome sequencing followed by targeted analysis of 378 exome-wide and literature-based selected SNPs. For the selection of predictors, the minimum redundancy maximum relevance (mRMRe) method was used, and then two prediction models were developed. The models included age, sex and 13 unique SNPs. Two SNPs of the highest mRMRe score included whole-exome identified KIF1A rs59733750 and previously linked with hair loss FGF5 rs7680591. The model for greying vs. no greying prediction achieved accuracy of cross-validated AUC = 0.873. In the 3-grade classification cross-validated AUC equalled 0.864 for no greying, 0.791 for mild greying and 0.875 for severe greying. Although these values present fairly accurate prediction, most of the prediction information was brought by age alone. Genetic variants explained < 10% of hair greying variation and the impact of particular SNPs on prediction accuracy was found to be small.

Conclusions

The rate of changes in human progressive traits shows inter-individual variation, therefore they are perceived as biomarkers of the biological age of the organism. The knowledge on the mechanisms underlying phenotypic aging can be of special interest to the medicine, cosmetics industry and forensics. Our study improves the knowledge on the genetics underlying hair greying processes, presents prototype models for prediction and proves hair greying being genetically a very complex trait. Finally, we propose a four-step approach based on genetic and epigenetic data analysis allowing for i) sex determination; ii) genetic ancestry inference; iii) greying-associated SNPs assignment and iv) epigenetic age estimation, all needed for a final prediction of greying.
Analyses of key genes involved in Arctic adaptation in polar bears suggest selection on both standing variation and de novo mutations played an important role
Authors: Samaniego Castruita Jose Alfredo , Westbury Michael V. , Lorenzen Eline D.
Published: August 2020

Background

Polar bears are uniquely adapted to an Arctic existence. Since their relatively recent divergence from their closest living relative, brown bears, less than 500,000 years ago, the species has evolved an array of novel traits suited to its Arctic lifestyle. Previous studies sought to uncover the genomic underpinnings of these unique characteristics, and disclosed the genes showing the strongest signal of positive selection in the polar bear lineage. Here, we survey a comprehensive dataset of 109 polar bear and 33 brown bear genomes to investigate the genomic variants within these top genes present in each species. Specifically, we investigate whether fixed homozygous variants in polar bears derived from selection on standing variation in the ancestral gene pool or on de novo mutation in the polar bear lineage.

Results

We find that a large number of sites fixed in polar bears are biallelic in brown bears, suggesting selection on standing variation. Moreover, we uncover sites in which polar bears are fixed for a derived allele while brown bears are fixed for the ancestral allele, which we suggest may be a signal of de novo mutation in the polar bear lineage.

Conclusions

Our findings suggest that, among other mechanisms, natural selection acting on changes in genes derived from a combination of variation already in the ancestral gene pool, and from de novo missense mutations in the polar bear lineage, may have enabled the rapid adaptation of polar bears to their new Arctic environment.
Transcriptomic profiling revealed key signaling pathways for cold tolerance and acclimation of two carp species
Authors: Ge Guodong , Long Yong , Shi Lianyu , Ren Jing , Yan Junjun , Li Chitao , Li Qing , Cui Zongbin
Published: August 2020

Background

Closely related species of the carp family (Cyprinidae) have evolved distinctive abilities to survive under cold stress, but molecular mechanisms underlying the generation of cold resistance remain largely unknown. In this study, we compared transcriptomic profiles of two carp species to identify key factors and pathways for cold tolerance and acclimation.

Results

Larvae of Songpu mirror carp and Barbless carp that were pretreated at 18 °C for 24 h significantly improved their survival rates under lethal cold temperature at 8 °C or 10 °C, indicating that two carp species possess the ability of cold acclimation. However, Songpu mirror carp exhibited stronger abilities of cold tolerance and acclimation than Barbless carp. Transcriptomic profiles of Songpu mirror carp and Barbless carp larvae at 28 °C and 18 °C were compared during cold acclimation through RNA-seq. Differentially expressed genes that are closely associated with the differences in cold acclimation between two carp species were identified through bioinformatics and Venn’s diagram analysis. GO enrichment analysis of these genes indicated that cellular component assembly involved in morphogenesis, secondary alcohol metabolism and drug transport were the most up-regulated biological processes during cold acclimation of Songpu mirror carp. Conversely, positive regulation of macroautophagy, intracellular protein transport, and organonitrogen compound catabolism were the most down-regulated biological processes during cold acclimation of Barbless carp. KEGG enrichment analysis revealed that factors in the FoxO-related signaling pathways are mainly responsible for the development of differences in cold tolerance and acclimation between two carp species since altering the phosphorylation of key proteins in the FoxO-related signaling pathways with inhibitors or an activator significantly decreased the cold tolerance and acclimation of Songpu mirror carp. These data provided key clues for dissection of molecular mechanisms underlying the development of cold tolerance and acclimation in carps.

Conclusions

These findings indicate that larvae of two carp species possess different abilities of cold tolerance and can build cold acclimation under mild low temperature. Multiple biological processes and FoxO-related signaling pathways are closely associated with the development of differences in cold tolerance and acclimation between two carp species.
Electronic cigarette extract induced toxic effect in iPS-derived cardiomyocytes
Authors: Basma Hesham , Tatineni Swetha , Dhar Kajari , Qiu Fang , Rennard Stephen , Lowes Brian D.
Published: August 2020

Background

Cigarette smoking is an important risk factor for cardiac diseases. In the current study, we sought to assess the effect of electronic cigarette extract (ECE) and conventional cigarette smoke extract (CSE) on cardiomyocytes.

Methods

iPSCs-derived cardiomyocytes were used in the study to evaluate cellular toxicities. Cells were exposed to either ECE or CSE for two consecutive days as an acute exposure or every other day for 14 days. Concentration of nicotine in both ECE and CSE were measured by Mass-Spectrometry and Q-Exactive-HF was used to identify other ingredients in both extracts. Fluorescent microscopy was used to measure the oxidative stress after ECE and CSE exposure. Motility and beat frequency of cardiomyocytes were determined using the Sisson-Ammons Video Analysis system. Heart failure target panel genes of exposed cardiomyocytes were compared to control unexposed cells.

Results

Despite nicotine concentration in CSE being six-fold higher than ECE (50 μg in CSE and 8 μg in ECE), ECE had similar toxic effect on cardiomyocytes. Both CSE and ECE generate significant cellular reactive oxygen species. The Sisson-Ammons Video Analysis (SAVA) analysis showed significant changes in myocyte function with both CSE and ECE slowing beating and increasing cell death. Chronic exposure of both ECE and CSE significantly decreased cardiomyocytes viability long term at all doses.

Target panel gene expression profiles of both ECE and CSE exposed cardiomyocytes were different from controls with distinct pattern of genes that involved cell proliferation, inflammation, and apoptosis.

Conclusion

ECE and CSE produce similar cardiomyocyte toxicities which include generating oxidative stress, negative chronotropic effects, adverse changes in myocardial gene expression and ultimately cell death.
Potentially inappropriate prescribing to older patients receiving multidose drug dispensing
Authors: Josendal Anette Vik , Bergmo Trine Strand , Granas Anne Gerd
Published: August 2020

Background

Multidose drug dispensing (MDD) is an adherence aid that provides patients with machine-dispensed medicines in disposable unit bags, usually for a 14 day period. Previous studies have suggested that the quality of prescribing, with time, is lower for MDD users, compared to patients receiving prescriptions dispensed as usual. This study aimed to examine the quality of prescribing to Norwegian elderly home care service patients receiving MDD.

Methods

A cross-sectional study comprising 45,593 MDD patients aged ≥70 years was performed. The proportion of potentially inappropriate medications (PIMs) was assessed using the Norwegian General Practice Criteria, and drug-drug interactions (DDI) were investigated using the Norwegian Medicines Agency database.

Results

On average, patients were prescribed 10.6 drugs (SD = 5.0), of which 6.1 were dispensed via MDD. Men used on average fewer drugs than women (10.7 vs 11.1), Twenty-seven percent of patients used at least one PIM. Concomitant use of three or more psychotropic drugs (10.8%), and prescribing of diazepam (6.4%) was the most commonly identified inappropriate prescribing. DDIs affected 59% of the patients, however, only 2.7% had serious interactions. Women were more frequently exposed to both PIMs and DDIs than men, with an odds ratio of 1.50 (95% CI: 1.43–1.58) and 1.43 (95% CI: 1.37–1.50), respectively.

Conclusions

Polypharmacy is common in elderly Norwegian patients using MDD. About one-fourth of the patients were exposed to PIMs, and over half were exposed to DDI.
Depression does not predict clinical outcome of Chinese peritoneal Dialysis patients after adjusting for the degree of frailty
Authors: Chan Gordon Chun-Kau , Ng Jack Kit-Chung , Chow Kai-Ming , Kwan Bonnie Ching-Ha , Kwong Vickie Wai-Ki , Pang Wing-Fai , Cheng Phyllis Mei-Shan , Law Man-Ching , Leung Chi-Bon , Li Philip Kam-Tao , Szeto Cheuk-Chun
Published: August 2020

Background

Depression and frailty contribute to the adverse clinical outcome of peritoneal dialysis (PD) patients. However, the interaction between depression and frailty in PD patients remains uncertain. We determined the prevalence of depression and frailty in prevalent Chinese PD patients, dissected the internal relationship between depression and frailty, and determined their relative contribution to the adverse clinical outcome in PD patients.

Methods

In a prospective observational study, we recruited 267 prevalent PD patients. Depression was identified by Patient Health Questionnaire (PHQ-9). Frailty was identified by a validated Frailty Score. All cases were followed for one year. Outcome measures included number and duration of hospitalization, peritonitis rate, and all-cause mortality.

Results

Of the 267 patients, 197 patients (73.8%) were depressed, and 157 (58.8%) were frail. There was a substantial overlap between depression and frailty. Although depression and frailty were associated the number and duration of hospitalization by univariate analysis, the association became insignificant after adjusting for confounding factors by multivariate analysis. Both depression and frailty were associated with one-year mortality by univariate analysis. One-year patient survival was 95.9, 86.5, 82.4 and 71.0% for patients with nil, mild, moderate and severe frailty, respectively (p = 0.001). Frailty was an independent predictor of patient survival by multivariate analysis (adjusted hazard ratio 1.424, 95% confidence interval 1.011–2.005. p = 0.043), while the prognostic effect of depression disappears after adjusting for frailty score.

Conclusion

Depression and frailty were common among Chinese PD patients. Frailty, but not depression, was an independent predictor of one-year mortality.
Does domestic violence during pregnancy influence the beginning of complementary feeding?
Authors: Caprara Gabriele Luiza , Bernardi Juliana Rombaldi , Bosa Vera Lúcia , da Silva Clécio Homrich , Goldani Marcelo Zubaran
Published: August 2020

Background

This study investigate the influence of domestic violence against pregnant women on early complementary feeding and associated factors.

Methods

A longitudinal observational study was conducted with a convenience sample recruited from three public hospitals in Porto Alegre, Rio Grande do Sul, Brazil. Data on maternal age, education, marital status, breastfeeding, introduction of complementary feeding and domestic violence during pregnancy were investigated at four follow-ups points. Data on domestic violence was collected through a self-report questionnaire based on the Abuse Assessment Screen. The early introduction of complementary feeding, characterized as occurring before or at 3 months of life, was verified through a questionnaire prepared by the research group. Data analysis involved Student’st-test, the chi-square test and Cox regression and was carried out in Statistical Package for the Social Sciences program. The significance level was set at 5%.

Results

A total of 232 mother-infant pairs participated in the analyses, and 15.1% of the mothers reported suffering some form of violence. Domestic violence was directly associated with maternal education, marital status, and health status during pregnancy. Domestic violence was not associated with maternal age or breastfeeding at 3 months after delivery. In the univariate analysis, domestic violence during pregnancy was associated with early complementary feeding (RR = 1.74; CI: 1.01–2.98). This effect disappeared after the model was adjusted in multivariate analysis.

Conclusions

There was no relationship between domestic violence during pregnancy and early complementary feeding.
Clinical impact of PSMA PET/CT in primary prostate cancer compared to conventional nodal and distant staging: a retrospective single center study
Authors: Donswijk Maarten L. , van Leeuwen Pim J. , Vegt Erik , Cheung Zing , Heijmink Stijn W. T. P. J. , van der Poel Henk G. , Stokkel Marcel P. M.
Published: August 2020

Background

To evaluate the impact of Gallium-68 [68Ga] labeled prostate specific membrane antigen (PSMA) positron emission tomography (PET)/X-ray computed tomography (CT) compared with conventional imaging on staging and clinical management of men evaluated for primary prostate cancer (PCa).

Methods

Men with newly diagnosed biopsy-proven PCa who had been staged with a conventional staging protocol including bone scintigraphy (BS) and additionally underwent [68Ga]PSMA PET/CT, were evaluated retrospectively. Imaging findings from BS, magnetic resonance imaging (MRI) and/or CT were categorized regarding locoregional nodal (N) and distant metastasis (M) status as negative, positive or equivocal before and after addition of the information of PET/CT. Also, the imaging-based level of confidence (LoC) in correct assessment of N and M status was scored. Impact of PET/CT on clinical management was evaluated by the percentage of treatment category changes after PET/CT as determined in the multidisciplinary tumour board.

Results

Sixty-four men with intermediate and high-risk PCa were evaluated. With additional information of PET/CT, N status was upstaged in 23%, and downstaged in 9%. M status was upstaged in 13%, and downstaged in 23%. A net increase in LoC of 20% was noted, mainly regarding M status.

Treatment category changed from palliative to curative in 9%, and from curative to palliative in 3%. An undecided treatment plan changed to curative in 14%, as well as to palliative in another 9%. In total, a 36% treatment category change was noted.

High negative predictive value of PET/CT for M status was indicated by 27 patients that underwent robot-assisted radical prostatectomy and reached postoperative biochemical disease-free status or had a likely other site of disease recurrence.

Conclusions

PSMA PET/CT can cause considerable changes in N and M staging, as well as in management compared to conventional staging. Findings of this study support the replacement of BS and CT by PSMA PET/CT in staging primary PCa.
Clinical outcomes of immune checkpoint inhibitors for patients with recurrent or metastatic head and neck cancer: real-world data in Korea
Authors: Kim Hyera , Kwon Minsuk , Kim Binnari , Jung Hyun Ae , Sun Jong-Mu , Lee Se-Hoon , Park Keunchil , Ahn Myung-Ju
Published: August 2020

Background

Anti-PD1 inhibitors have been approved for the treatment of recurrent or metastatic head and neck cancer (HNC), as a result of Global Phase III trials. However, the clinical outcomes of immune checkpoint inhibitors in patients who are not eligible for clinical trials or have various medical conditions have not been fully elucidated.

Methods

We retrospectively reviewed 46 patients with recurrent or metastatic HNC who received pembrolizumab or nivolumab between June 2016 and June 2019.

Results

Thirty-five patients had head and neck squamous cell carcinoma (HNSCC) affecting the oropharynx, oral cavity, hypopharynx, larynx, nasal cavity, or paranasal sinuses, and eleven patients had nasopharyngeal cancer (NPC). The median progression-free survival (PFS) and overall survival (OS) were 3.7 months and 6.8 months, respectively, for patients with HNSCC, and 4.3 months and 11.8 months, respectively, for patients with NPC. The objective response rate (ORR) in all patients was 21%. Of 30 patients with HNSCC, 5 patients achieved complete response and 2 achieved partial response (ORR 23%); 1 of 8 NPC patients achieved partial response (13%). Patients who previously underwent radiotherapy had better OS than those who did not (median OS, 7.6 months vs. 2.3 months, p = 0.006). OS was longer in patients treated with pembrolizumab than in those treated with nivolumab (median OS, 11.8 months vs. 6.8 months, p = 0.017).

Conclusion

Consistent with previous reports, immune checkpoint inhibitors showed promising efficacy in patients with previously treated recurrent or metastatic HNC in a real-world setting.
Visualization of deep choroidal vasculatures and measurement of choroidal vascular density: a swept-source optical coherence tomography angiography approach
Authors: Wang Erqian , Zhao Xinyu , Yang Jingyuan , Chen Youxin
Published: August 2020

Background

To investigate swept-source optical coherence tomography angiography (SS-OCTA) for deep choroid visualization and choroidal vascular density (CVD) measurement.

Methods

Healthy subjects and central serous chorioretinopathy (CSC) patients were recruited for macular SS-OCTA scans. We evaluated OCTA images at various depths to determine an optimal depth for visualizing choroidal vasculatures. We measured CVD with binarized OCTA images at the optimal depth. In healthy subjects, CVD was studied for its correlation with age, axial length (AL), and subfoveal choroidal thickness (SCT). In CSC eyes, CVD was compared with matched controls.

Results

Ninety-one healthy eyes and 22 CSC eyes were included. SS-OCTA could display deep choroidal vasculatures as dark signals, with 100 μm beneath BM as the optimal depth. In healthy subjects, the CVD at 100 μm beneath BM (56.5 ± 10.9%) was significantly correlated with SCT (P = 0.004) but not with age (P = 0.49) or AL (P = 0.72). In CSC eyes, the CVD at 100 μm beneath BM (62.3 ± 6.6%) was larger than that in 22 matched controls (54.1 ± 8.0%) (P = 0.001). The difference remained statistically significant after adjusting for SCT (P = 0.02).

Conclusions

SS-OCTA can be used for visualizing deep choroidal vasculatures. CVD measured by OCTA at 100 μm beneath BM is a useful parameter for quantifying choroidal vascular status.
Successful treatment of neonatal atrial flutter by synchronized cardioversion: case report and literature review
Authors: Wójtowicz-Marzec Monika , Wysokińska Barbara , Respondek-Liberska Maria
Published: August 2020

Background

Atrial flutter (AFL) is a supraventricular tachyarrhythmia. In the ECG tracing, it is marked by a fast, irregular atrial activity of 280–500 beats per minute. AFL is known to be a rare and also life-threatening rhythm disorder both at the fetus and neonatal period. AFL may result in circulatory failure, and in a more severe form, it may lead to a non-immune fetal hydrops. However, with early prenatal diagnosis and proper treatment, the majority of AFL cases show a good prognosis.

Case presentation

We report a case of a neonate who was born at 34 weeks of gestational age by C-section because of risk for birth asphyxia, based on abnormal CTG tracing, which had no characteristic rhythms for fetal decelerations. A third day his heart rate was 220/bpm. ECG has shown supraventricular tachycardia with narrow QRS. The administration of adenosine resulted in the obvious appearance of “sawtooth wave” typical for AFL. Arrhythmia was resistant to the therapy of amiodaron. Then cardioversion was performed and the rhythm converted to normal.

Conclusions

As neonatal AFL might be resistant to conventional pharmacotherapy, one needs to remember about the possibility of electrical cardioversion in the pediatric cardiology referral center. Moreover, CTG monitoring is of limited use because it does not record fetal heart rhythms > 200/min and echocardiography at the reference center is practically the only method to monitor the condition of the fetus with abnormal rapid heart rhythm.
Early onset children’s Gitelman syndrome with severe hypokalaemia: a case report
Authors: Chen Hanjiang , Ma Rong , Du Hongzhe , Liu Jin , Jin Li
Published: August 2020

Background

Hypokalaemia is a common condition among paediatric patients, but severe hypokalaemia is rare and can be life-threatening if not treated properly. The causes of hypokalaemia are complex. Finding the root cause is the key.

Case presentation

This article reports on a 2-year-old boy with severe hypokalaemia who was diagnosed with pneumonia. The child’s lab findings were low blood potassium minimum level of 1.7 mmol/L, hypomagnesemia, and metabolic alkalosis. However, he was without the common features of hypokalaemia, such as respiratory paralysis, severe arrhythmia, weakness and decreased blood pressure. After recovering from pneumonia, his potassium levels did not return to normal. This outcome was suspected to be due to chronic renal loss of potassium. After undergoing second-generation gene sequencing tests, it was discovered he carried the SLC12A3 gene mutation with an Asp486Asn mutation site, which he had inherited from his mother. The final diagnosis was made, confirming the child suffered from Gitelman syndrome.

Conclusions

Genetic predisposition is an important cause of hypokalaemia in children. Children with unexplained persistent hypokalaemia should be examined for the possibility of Gitelman syndrome, which should be distinguished from Bartter syndrome. Genetic testing is the gold standard.
Mechanical wear analysis helps understand a mechanism of failure in retrieved magnetically controlled growing rods: a retrieval study
Authors: Wei Jack Z. , Hothi Harry S. , Morganti Holly , Bergiers Sean , Dal Gal Elisabetta , Likcani Doris , Henckel Johann , Hart Alister J.
Published: August 2020

Background

To assess the relationship between mechanical wear and the failure of the internal lengthening mechanism in retrieved MAGnetic Expansion Control (MAGEC) growing rods.

Methods

This study included 34 MAGEC rods retrieved from 20 patients. The state of the internal mechanism and mechanical wear were assessed in all the rods using plain radiographs and visual inspection. Metrology was then performed to assess the topography and mechanical wear of the telescopic bars, using a Talyrond 365 (Taylor Hobson, Leicester, UK) roundness measuring machine.

Results

Plain radiographs showed evidence of a broken internal mechanism in 29% of retrieved rods. Single-side wear marks were found in 97% of retrieved rods. Material loss was found to significantly increase in rods with a damaged internal mechanism (p < 0.05) and rods with longer time in situ (r = 0.692, p < 0.05).

Conclusions

We found an association between damage to the internal mechanism of the rods and (1) patterns of single-side longitudinal wear marks and (2) increased material loss. As the material loss was also found to increase over time of rod in situ, we emphasise the importance of early detection and revision of failed MAGEC rods in clinical practice.
Clinical and volumetric outcomes after vertical ridge augmentation using computer-aided-design/computer-aided manufacturing (CAD/CAM) customized titanium meshes: a pilot study
Authors: Cucchi Alessandro , Bianchi Alessandro , Calamai Paolo , Rinaldi Lisa , Mangano Francesco , Vignudelli Elisabetta , Corinaldesi Giuseppe
Published: August 2020

Background

One of the most recent innovations in bone augmentation surgery is represented by computer-aided-design/computer-aided-manufacturing (CAD/CAM) customized titanium meshes, which can be used to restore vertical bone defects before implant-prosthetic rehabilitations. The aim of this study was to evaluate the effectiveness/reliability of this technique in a consecutive series of cases.

Methods

Ten patients in need of bone augmentation before implant therapy were treated using CAD/CAM customized titanium meshes. A digital workflow was adopted to design virtual meshes on 3D bone models. Then, Direct Metal Laser Sintering (DMLS) technology was used to produce the titanium meshes, and vertical ridge augmentation was performed according to an established surgical protocol. Surgical complications, healing complications, vertical bone gain (VBG), planned bone volume (PBV), lacking bone volume (LBV), regenerated bone volume (RBV), average regeneration rate (RR) and implant success rate were evaluated.

Results

All augmented sites were successfully restored with definitive implant-supported fixed partial dentures. Measurements showed an average VBG of 4.5 ± 1.8 mm at surgical re-entry. Surgical and healing complications occurred in 30% and 10% of cases, respectively. Mean values of PBV, LBV, and RBV were 984, 92, and 892 mm3, respectively. The average RR achieved was 89%. All 26 implants were successfully in function after 1 year of follow-up.

Conclusions

The results of this study suggest that the bone augmentation by means of DMLS custom-made titanium meshes can be considered a reliable and effective technique in restoring vertical bone defects.
Haimufang decoction, a Chinese medicine formula for lung cancer, arrests cell cycle, stimulates apoptosis in NCI-H1975 cells, and induces M1 polarization in RAW 264.7 macrophage cells
Authors: Ma Wei-Ping , Hu Shu-Man , Xu Yan-Lai , Li Hai-Hua , Ma Xiao-Qing , Wei Bao-Hong , Li Fu-Yu , Guan Hua-Shi , Yu Guang-Li , Liu Ming , Liu Hong-Bing
Published: August 2020

Background

Lung cancer has the highest morbidity and mortality in the world and novel treatment strategies are still needed. Haimufang decoction (HMF) is a patented clinical prescription of traditional Chinese medicine for lung cancer treatment. HMF is composed of four herbs and has been applied clinically in advanced cancer patients. However, its therapeutic mechanisms are still unclear. This study aims to elucidate the possible mechanisms of HMF for the treatment of lung cancer.

Methods

3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay was applied for evaluating the proliferative effect of HMF in lung cancer cells and monocyte macrophage RAW264.7 cells. Flow cytometer was used to detect the effects of HMF on cell cycle and apoptosis, and western blotting was employed to explore the potential apoptotic mechanisms of HMF on lung cancer cells. For immunomodulatory effect, co-culture system was used to detect the activation of macrophage RAW264.7 cells when treated with HMF, and neutral red assay was used to measure the effect of HMF on the phagocytosis of the activated macrophages. Enzyme linked immunosorbent assay, flow cytometer, and immunofluorescence staining method were employed for the investigation on the underlying mechanisms of the immunomodulatory effect on RAW264.7 induced by HMF.

Results

HMF inhibited the proliferation, induced S phase cell cycle arrest, and stimulated apoptosis in lung cancer NCI-H1975 cells, while had negligible cytotoxicity on macrophage RAW264.7 cells. Moreover, HMF could activate macrophage RAW264.7 cells and promote the inhibition activity of RAW264.7 cells against lung cancer cells. And also, HMF activated macrophages and increased their phagocytic activity in a concentration-dependent manner. HMF increased the expression of macrophage activation marker CD40, the level of nitric oxide, the generation of intracellular reactive oxygen species, as well as M1 macrophages cytokines including tumor necrosis factor-α, interleukin-1β, interleukin 12 p70, and interleukin 6. Further investigation showed that HMF induced M1 but not M2 phenotype polarization in RAW264.7 cells.

Conclusions

HMF can mainly exert anticancer activity via (1) cytotoxicity to human lung cancer cells by proliferation inhibition, cell cycle arrest, and apoptosis induction; and also via (2) immunomodulation via macrophage cells activation and M1 phenotype polarization induction.

Graphical Abstract
First report and genetic characterization of bovine torovirus in diarrhoeic calves in China
Authors: Shi Zhihai , Wang Wenjia , Chen Chaoxi , Zhang Xiaozhan , Wang Jing , Xu Zhaoxue , Lan Yali
Published: August 2020

Background

Coronaviruses are notorious pathogens that cause diarrheic and respiratory diseases in humans and animals. Although the epidemiology and pathogenicity of coronaviruses have gained substantial attention, little is known about bovine coronavirus in cattle, which possesses a close relationship with human coronavirus. Bovine torovirus (BToV) is a newly identified relevant pathogen associated with cattle diarrhoea and respiratory diseases, and its epidemiology in the Chinese cattle industry remains unknown.

Results

In this study, a total of 461 diarrhoeic faecal samples were collected from 38 different farms in three intensive cattle farming regions and analysed. Our results demonstrated that BToV is present in China, with a low prevalence rate of 1.74% (8/461). The full-length spike genes were further cloned from eight clinical samples (five farms in Henan Province). Phylogenetic analysis showed that two different subclades of BToV strains are circulating in China. Meanwhile, the three BToV strains identified from dairy calves, 18,307, 2YY and 5YY, all contained the amino acid variants R614Q, I801T, N841S and Q885E.

Conclusions

This is the first report to confirm the presence of BToV in beef and dairy calves in China with diarrhea, which extend our understanding of the epidemiology of BToVs worldwide.
Metformin treatment in heart failure with preserved ejection fraction: a systematic review and meta-regression analysis
Authors: Halabi Amera , Sen Jonathan , Huynh Quan , Marwick Thomas H.
Published: August 2020

Background

Observational series suggest a mortality benefit from metformin in the heart failure (HF) population. However, the benefit of metformin in HF with preserved ejection fraction (HFpEF) has yet to be explored. We performed a systematic review and meta-analysis to identify whether variation in EF impacts mortality outcomes in HF patients treated with metformin.

Methods

MEDLINE and EMBASE were searched up to October 2019. Observational studies and randomised trials reporting mortality in HF patients and the proportion of patients with an EF > 50% at baseline were included. Other baseline variables were used to assess for heterogeneity in treatment outcomes between groups. Regression models were used to determine the interaction between metformin and subgroups on mortality.

Results

Four studies reported the proportion of patients with a preserved EF and were analysed. Metformin reduced mortality in both preserved or reduced EF after adjustment with HF therapies such as angiotensin converting enzyme inhibitors (ACEi) and beta-blockers (β = − 0.2 [95% CI − 0.3 to − 0.1], p = 0.02). Significantly greater protective effects were seen with EF > 50% (p = 0.003). Metformin treatment with insulin, ACEi and beta-blocker therapy were also shown to have a reduction in mortality (insulin p = 0.002; ACEi p < 0.001; beta-blocker p = 0.017), whereas female gender was associated with worse outcomes (p < 0.001).

Conclusions

Metformin treatment is associated with a reduction in mortality in patients with HFpEF.
A cluster randomized trial of delivery of intermittent preventive treatment of malaria in pregnancy at the community level in Burkina Faso
Authors: Gutman Julie R. , Stephens Daniel K. , Tiendrebeogo Justin , Badolo Ousmane , Dodo Mathurin , Burke Danielle , Williamson John , Vibbert Kristen , Youll Susan J. , Savadogo Yacouba , Brieger William R.
Published: August 2020

Background

Malaria in pregnancy is responsible for 8–14% of low birth weight and 20% of stillbirths in sub-Saharan Africa. To prevent these adverse consequences, the World Health Organization recommends intermittent preventive treatment of pregnant women (IPTp) with sulfadoxine–pyrimethamine be administered at each ANC visit starting as early as possible in the second trimester. Global IPTp coverage in targeted countries remains unacceptably low. Community delivery of IPTp was explored as a means to improve coverage.

Methods

A cluster randomized, controlled trial was conducted in 12 health facilities in a 1:1 ratio to either an intervention group (IPTp delivered by CHWs) or a control group (standard practice, with IPTp delivered at HFs) in three districts of Burkina Faso to assess the effect of IPTp administration by community health workers (CHWs) on the coverage of IPTp and antenatal care (ANC). The districts and facilities were purposively selected taking into account malaria epidemiology, IPTp coverage, and the presence of active CHWs. Pre- and post-intervention surveys were carried out in March 2017 and July–August 2018, respectively. A difference in differences (DiD) analysis was conducted to assess the change in coverage of IPTp and ANC over time, accounting for clustering at the health facility level.

Results

Altogether 374 and 360 women were included in the baseline and endline surveys, respectively. At baseline, women received a median of 2.1 doses; by endline, women received a median of 1.8 doses in the control group and 2.8 doses in the intervention group (p-value < 0.0001). There was a non-statistically significant increase in the proportion of women attending four ANC visits in the intervention compared to control group (DiD = 12.6%, p-value = 0.16). By the endline, administration of IPTp was higher in the intervention than control, with a DiD of 17.6% for IPTp3 (95% confidence interval (CI) − 16.3, 51.5; p-value 0.31) and 20.0% for IPTp4 (95% CI − 7.2, 47.3; p-value = 0.15).

Conclusions

Community delivery of IPTp could potentially lead to a greater number of IPTp doses delivered, with no apparent decrease in ANC coverage.
Cannabis health knowledge and risk perceptions among Canadian youth and young adults
Authors: Leos-Toro Cesar , Fong Geoffrey T. , Meyer Samantha B. , Hammond David
Published: August 2020

Background

Although recreational cannabis is now legal in Canada, little empirical evidence exists regarding young Canadians’ cannabis literacy, cannabis-related risk perceptions, and risk of different forms of cannabis or the effect that public health education may have on these perceptions. The present study sought to address these knowledge gaps to examine health knowledge and risk perceptions associated with cannabis use.

Methods

An online survey was conducted with a national sample (N = 870) of Canadians aged 16 to 30 years in October 2017 using a commercial panel. The study examined young Canadians’ awareness of negative health effects related to cannabis, evaluation of known risks, and risk perceptions of different forms of administration.

Results

Most respondents were aware of a cannabis-related physical health effect (78.0%). Approximately one-third reported having been exposed to public health messaging about cannabis; digital media was reported most frequently. Compared to never users, ever users were less likely to report general likelihood of addiction (p < 0.001) and harm to mental health (p < 0.001). Approximately one-quarter of past 3-month cannabis users reported they were at least “a little” addicted. Respondents who reported using a particular form of cannabis self-administration (e.g., edibles, smokables) were less likely to perceive harm than those who did not use each form (p < 0.001).

Conclusions

The current study is among the first to measure the knowledge and perceptions of risks of Canadian youth about cannabis. The study, conducted in the time immediately preceding legalization, may serve as a reference point for future studies examining changes in cannabis knowledge and risk perceptions. This will be important in addressing the need for monitoring and enhancing public awareness of the impact and potential harms of this newly legalized substance.
Aptamers: a novel targeted theranostic platform for pancreatic ductal adenocarcinoma
Authors: Li Q. , Maier S. H. , Li P. , Peterhansl J. , Belka C. , Mayerle J. , Mahajan U. M.
Published: August 2020

Pancreatic ductal adenocarcinoma (PDAC) is an extremely challenging disease with a high mortality rate and a short overall survival time. The poor prognosis can be explained by aggressive tumor growth, late diagnosis, and therapy resistance. Consistent efforts have been made focusing on early tumor detection and novel drug development. Various strategies aim at increasing target specificity or local enrichment of chemotherapeutics as well as imaging agents in tumor tissue. Aptamers have the potential to provide early detection and permit anti-cancer therapy with significantly reduced side effects. These molecules are in-vitro selected single-stranded oligonucleotides that form stable three-dimensional structures. They are capable of binding to a variety of molecular targets with high affinity and specificity. Several properties such as high binding affinity, the in vitro chemical process of selection, a variety of chemical modifications of molecular platforms for diverse function, non-immunoreactivity, modification of bioavailability, and manipulation of pharmacokinetics make aptamers attractive targets compared to conventional cell-specific ligands. To explore the potential of aptamers for early diagnosis and targeted therapy of PDAC - as single agents and in combination with radiotherapy - we summarize the generation process of aptamers and their application as biosensors, biomarker detection tools, targeted imaging tracers, and drug-delivery carriers. We are furthermore discussing the current implementation aptamers in clinical trials, their limitations and possible future utilization.