bluuebunny/crossref_metadata_2025 huggingface dataset:
A cancer stem cell-like phenotype is associated with miR-10b expression in aggressive squamous cell carcinomas
Authors: Wimmer Monika , Zauner Roland , Ablinger Michael , Piñón-Hofbauer Josefina , Guttmann-Gruber Christina , Reisenberger Manuela , Lettner Thomas , Niklas Norbert , Proell Johannes , Sajinovic Mila , De Souza Paul , Hainzl Stefan , Kocher Thomas , Murauer Eva M. , Bauer Johann W. , Strunk Dirk , Reichelt Julia , Mellick Albert Sleiman , Wally Verena
Published: April 2020

Background

Cutaneous squamous cell carcinomas (cSCC) are the primary cause of premature deaths in patients suffering from the rare skin-fragility disorder recessive dystrophic epidermolysis bullosa (RDEB), which is in marked contrast to the rarely metastasizing nature of these carcinomas in the general population. This remarkable difference is attributed to the frequent development of chronic wounds caused by impaired skin integrity. However, the specific molecular and cellular changes to malignancy, and whether there are common players in different types of aggressive cSCCs, remain relatively undefined.

Methods

MiRNA expression profiling was performed across various cell types isolated from skin and cSCCs. Microarray results were confirmed by qPCR and by an optimized in situ hybridization protocol. Functional impact of overexpression or knock-out of a dysregulated miRNA was assessed in migration and 3D-spheroid assays. Sample-matched transcriptome data was generated to support the identification of disease relevant miRNA targets.

Results

Several miRNAs were identified as dysregulated in cSCCs compared to control skin. These included the metastasis-linked miR-10b, which was significantly upregulated in primary cell cultures and in archival biopsies. At the functional level, overexpression of miR-10b conferred the stem cell-characteristic of 3D-spheroid formation capacity to keratinocytes. Analysis of miR-10b downstream effects identified a novel putative target of miR-10b, the actin- and tubulin cytoskeleton-associated protein DIAPH2.

Conclusion

The discovery that miR-10b mediates an aspect of cancer stemness – that of enhanced tumor cell adhesion, known to facilitate metastatic colonization – provides an important avenue for future development of novel therapies targeting this metastasis-linked miRNA.
In vitro cell culture of patient derived malignant pleural and peritoneal effusions for personalised drug screening
Authors: Wu Cheng-Guang , Chiovaro Francesca , Curioni-Fontecedro Alessandra , Casanova Ruben , Soltermann Alex
Published: April 2020

Background

Malignant serous effusion (MSE) denotes a manifestation of metastatic disease with typical high concentrations of both cancer and immune cells, making them an ideal resource for in vitro cytologic studies. Hence, the aim of the study was to investigate the features of 2D and 3D MSE culture systems as well as their feasibilities for in vitro drug screening.

Methods

Pleural and peritoneal effusions from 8 patients were collected and processed for 2D monolayer and 3D hanging drop cell culture into GravityPLUS™ plates. Representative markers for cell components, proliferation rate and tumour classification were investigated by immunohistochemistry, followed by absolute quantification using a digitalised image analysis approach. Further, we implemented another 3D cell culture model based on a low attachment method for in vitro drug sensitivity testing of carboplatin, pemetrexed and pembrolizumab for 5 patients.

Results

Monolayer cell culture was favourable for the growth of mesothelial cells, while hanging drop culture in GravityPLUS™ plates showed better ability for preserving cancer cells, inducing positive diagnostic markers expression and restraining the growth of mesothelial cells. For in vitro drug testing, MSE from five patients presented various drug sensitivities, and one case showed strong response to PD-1 checkpoint inhibition (pembrolizumab). For some patients, the application of combinatorial drugs had better therapeutic responses compared to monotherapy.

Conclusions

Digitalised quantification of data offers a better understanding of different MSE culture models. More importantly, the proposed platforms are practical and amenable for performing in vitro chemo-/immunotherapeutic drug testing by using routine cytologic MSE in a personalised manner. Next to cell blocks, our work demonstrates the prognostic and predictive value of cytologic effusion samples.
Misoprostol administered sublingually at a dose of 12.5 μg versus vaginally at a dose of 25 μg for the induction of full-term labor: a randomized controlled trial
Authors: Gattás Daniele S. M. B. , de Amorim Melania M. R. , Feitosa Francisco E. L. , da Silva-Junior José R. , Ribeiro Lívia C. G. , Souza Gustavo F. A. , Souza Alex S. R.
Published: April 2020

Background

Labor induction is defined as any procedure that stimulates uterine contractions before labor begins spontaneously. The vaginal and oral routes of administration of misoprostol are those most used for the induction of labor in routine practice, with the recommended dose being 25 μg. Nevertheless, the sublingual route may reduce the number of vaginal examinations required, increasing patient comfort and lowering the risk of maternal and fetal infection. Based on a previous systematic review, the objective of this study was to compare the frequency of tachysystole as the main outcome measure when misoprostol is administered sublingually at the dose of 12.5 μg versus vaginally at a dose of 25 μg to induce labor in a full-term pregnancy with a live fetus.

Methods

A randomized, placebo-controlled, triple-blind clinical trial was conducted at two maternity hospitals in northeastern Brazil. Two hundred patients with a full-term pregnancy, a live fetus, Bishop score ≤ 6 and an indication for induction of labor were included. Following randomization, one group received 12.5 μg misoprostol sublingually and a vaginal placebo, while the other group received a sublingual placebo and 25 μg misoprostol vaginally. The primary outcome was the frequency of tachysystole. Student’s t-test, the chi-square test of association and Fisher’s exact test were used, as appropriate. Risk ratios and their 95% confidence intervals were calculated.

Results

The frequency of tachysystole was lower in the group using 12.5 μg misoprostol sublingually compared to the group using 25 μg misoprostol vaginally (RR = 0.15; 95%CI: 0.02–0.97; p = 0.002). Failure to achieve vaginal delivery within 12 and 24 h was similar in both groups. Sublingual administration was preferred to vaginal administration by women in both groups; however, the difference was not statistically significant.

Conclusion

The effectiveness of labor induction with low-dose sublingual misoprostol was similar to that achieved with vaginal administration of the recommended dose; however, the rate of tachysystole was lower in the sublingual group, and this route of administration may prove a safe alternative.

Trial registration

Registration number: NCT01406392, ClinicalTrials.gov. Date of registration: August 1, 2011.
Transfer of motor skill between virtual reality viewed using a head-mounted display and conventional screen environments
Authors: Juliano Julia M. , Liew Sook-Lei
Published: April 2020

Background

Virtual reality viewed using a head-mounted display (HMD-VR) has the potential to be a useful tool for motor learning and rehabilitation. However, when developing tools for these purposes, it is important to design applications that will effectively transfer to the real world. Therefore, it is essential to understand whether motor skills transfer between HMD-VR and conventional screen-based environments and what factors predict transfer.

Methods

We randomized 70 healthy participants into two groups. Both groups trained on a well-established measure of motor skill acquisition, the Sequential Visual Isometric Pinch Task (SVIPT), either in HMD-VR or in a conventional environment (i.e., computer screen). We then tested whether the motor skills transferred from HMD-VR to the computer screen, and vice versa. After the completion of the experiment, participants responded to questions relating to their presence in their respective training environment, age, gender, video game use, and previous HMD-VR experience. Using multivariate and univariate linear regression, we then examined whether any personal factors from the questionnaires predicted individual differences in motor skill transfer between environments.

Results

Our results suggest that motor skill acquisition of this task occurs at the same rate in both HMD-VR and conventional screen environments. However, the motor skills acquired in HMD-VR did not transfer to the screen environment. While this decrease in motor skill performance when moving to the screen environment was not significantly predicted by self-reported factors, there were trends for correlations with presence and previous HMD-VR experience. Conversely, motor skills acquired in a conventional screen environment not only transferred but improved in HMD-VR, and this increase in motor skill performance could be predicted by self-reported factors of presence, gender, age and video game use.

Conclusions

These findings suggest that personal factors may predict who is likely to have better transfer of motor skill to and from HMD-VR. Future work should examine whether these and other predictors (i.e., additional personal factors such as immersive tendencies and task-specific factors such as fidelity or feedback) also apply to motor skill transfer from HMD-VR to more dynamic physical environments.
The BELT and phenoSEED platforms: shape and colour phenotyping of seed samples
Authors: Halcro Keith , McNabb Kaitlin , Lockinger Ashley , Socquet-Juglard Didier , Bett Kirstin E. , Noble Scott D.
Published: April 2020

Background

Quantitative and qualitative assessment of visual and morphological traits of seed is slow and imprecise with potential for bias to be introduced when gathered with handheld tools. Colour, size and shape traits can be acquired from properly calibrated seed images. New automated tools were requested to improve data acquisition efficacy with an emphasis on developing research workflows.

Results

A portable imaging system (BELT) supported by image acquisition and analysis software (phenoSEED) was created for small-seed optical analysis. Lentil (Lens culinaris L.) phenotyping was used as the primary test case. Seeds were loaded into the system and all seeds in a sample were automatically individually imaged to acquire top and side views as they passed through an imaging chamber. A Python analysis script applied a colour calibration and extracted quantifiable traits of seed colour, size and shape. Extraction of lentil seed coat patterning was implemented to further describe the seed coat. The use of this device was forecasted to eliminate operator biases, increase the rate of acquisition of traits, and capture qualitative information about traits that have been historically analyzed by eye.

Conclusions

Increased precision and higher rates of data acquisition compared to traditional techniques will help to extract larger datasets and explore more research questions. The system presented is available as an open-source project for academic and non-commercial use.
Hippocampal changes in inflammasomes, apoptosis, and MEMRI after radiation-induced brain injury in juvenile rats
Authors: Yang Jun , Gao Jingyan , Han Dan , Li Qinqing , Liao Chengde , Li Jindan , Wang Rui , Luo Yueyuan
Published: April 2020

Purpose

The aim of this study was to characterize changes in hippocampal inflammasomes, pyroptosis and apoptosis in juvenile rats after brain irradiation and to assess whether manganese-enhanced magnetic resonance imaging (MEMRI) reflected those changes.

Materials and methods

Four-week-old male Sprague-Dawley rats received a whole-brain radiation dose of 15 Gy or 25 Gy. Hippocampal inflammasomes and apoptosis were measured using Western blot analysis at 4 days and 8 weeks after irradiation. MEMRI and magnetic resonance spectroscopy (MRS) were performed at the same time points.

Results

Neither the 15 Gy nor 25 Gy group showed changes in the expression of inflammasome proteins absent in melanoma 2 (AIM2), gasdermin-D (GSDMD), nucleotide oligomerization domain-like receptor protein 1 (NLRP1) and NLRP3 at 4 days or 8 weeks after radiation injury (P > 0.05). Furthermore, the expression levels of the inflammatory cytokines interleukin-1β (IL-1β) and IL-18 were not significantly different among the groups (P > 0.05). The expression levels of cleaved caspase-1 and -3, indicators of apoptosis, were higher in the irradiation groups than in the control group at 4 days post irradiation, especially for caspase-3 (P < 0.05), but this increase was slightly attenuated at 8 weeks after radiation injury. Four days post irradiation, the MEMRI signal intensity (SI) in the irradiation groups, especially the 25 Gy group, was significantly lower than that in the control group (P < 0.05). Eight weeks after radiation injury, the SI of the 15 Gy group and the 25 Gy group recovered by different degrees, but the SI of the 25 Gy group was still significantly lower than that of the control group (P < 0.05). On day 4 post irradiation, the metabolic ratio of N-acetylaspartate (NAA) to creatine (Cr) in the 15 Gy group and 25 Gy group was significantly lower than that in the control group (P < 0.05). The NAA/Cr ratio in the 15 Gy group recovered to control levels at 8 weeks (P > 0.05), but the NAA/Cr ratio in the 25 Gy group remained significantly lower than that in the control group (P < 0.05).

Conclusion

Radiation-induced brain injury is dose-dependently associated with apoptosis but not inflammasomes or pyroptosis, and the change in apoptosis can be detected by MEMRI.
Primary carnitine deficiency – diagnosis after heart transplantation: better late than never!
Authors: Grünert Sarah C. , Tucci Sara , Schumann Anke , Schwendt Meike , Gramer Gwendolyn , Hoffmann Georg F. , Erbel Michelle , Stiller Brigitte , Spiekerkoetter Ute
Published: April 2020

Background

Primary carnitine deficiency due to mutations in the SLC22A5 gene is a rare but well-treatable metabolic disorder that puts patients at risk for metabolic decompensations, skeletal and cardiac myopathy and sudden cardiac death.

Results

We report on a 7-year-old boy diagnosed with primary carnitine deficiency 2 years after successful heart transplantation thanks his younger sister’s having been identified via expanded newborn screening during a pilot study evaluating an extension of the German newborn screening panel.

Conclusion

As L-carnitine supplementation can prevent and mostly reverse clinical symptoms of primary carnitine deficiency, all patients with cardiomyopathy should be investigated for primary carnitine deficiency even if newborn screening results were unremarkable.
A rare case of acute promyelocytic leukemia with ider(17)(q10)t(15;17)(q22;q21) and favorable outcome
Authors: Liu Yongming , Xu Junqing , Chu Lina , Yu Limei , Zhang Yanhong , Ma Li , Wang Weihua , Zhang Yangyang , Xu Yimin , Liu Riming
Published: April 2020

Background

Chromosomal rearrangements in addition to t(15;17) have been reported in 25-40% of APL patients, with a large predominance of trisomy 8. Other abnormalities are far less frequent, particularly as ider(17), and the prognostic significance is still unclear.

Case presentation

We present the case of a patient with t(15;17)(q22;q21), der(15)t(15;17) and ider(17)(q10)t(15;17)(q22;q21). In particular, the RT-PCR result for PML-RARA of this patient was a false negative and mutational analysis of AML-related genes showed SNP rs2454206 in the TET2 gene and yielded negative findings in other genes including AML1, ASXL1, CEBPA, DNMT3A, FLT3, KIT, NPM1, TP53, and U2AF1. After the early usage of arsenic trioxide combinated with ATRA and vigorous supportive treatment to maintain PLT ≥30×109/L and FIB >1500 mg/L, this patient was under MMR and HCR without any clinical symptoms or signs until now.

Conclusion

False negative reslults of RT-PCR analysis for PML-RARA are rare in APL and ider(17) is even more infrequent. To our knowledge, this is the first reported case of APL with ider(17) and false negative RT-PCR analysis results. The role of ider(17) in APL is still an ongoing investigation and limited by the small number of published cases. The patient reported here benefited from vigorous supportive treatment during the combination of ATRA and arsenic trioxide in induction chemotherapy and the clinical outcome was favorable.
Formononetin inhibits tumor growth by suppression of EGFR-Akt-Mcl-1 axis in non-small cell lung cancer
Authors: Yu Xinyou , Gao Feng , Li Wei , Zhou Li , Liu Wenbin , Li Ming
Published: April 2020

Background

Epidermal growth factor receptor (EGFR) activating mutations play crucial roles in the tumorigenesis of human non-small cell lung cancer (NSCLC). The mechanism regarding how EGFR signaling regulates myeloid cell leukemia sequence 1 (Mcl-1) protein stability and ubiquitination remains undefined.

Methods

MTS assay was used for natural product library screening. The effect of formononetin (Formo) on NSCLC cells was determined by MTS assay and soft agar assay. Molecular modeling was performed to analyze the potential different binding modes between Formo and EGFR WT or mutants. Mcl-1 protein level and the inhibitory effect of Formo on EGFR signaling were examined by immunoblot, in vitro kinase assay, in vitro pulldown and ATP competition assays, co-immunoprecipitation assay, ubiquitination analysis, in vivo xenograft model, and immunohistochemical staining.

Results

Formo was identified as an EGFR inhibitor by a 98 commercially available natural product screening. Formo suppresses WT and mutant EGFR kinases activity in vitro, ex vivo, and in vivo. Molecular modeling indicates that Formo docks into the ATP-binding pocket of both WT and mutant EGFR. Formo inhibits EGFR-Akt signaling, which in turn activates GSK3β and promotes Mcl-1 phosphorylation in NSCLC cells. Treatment with Formo enhances the interaction between Mcl-1 and SCFFbw7, which eventually promotes Mcl-1 ubiquitination and degradation. Depletion of either GSK3β or SCFFbw7 compromised Formo-induced Mcl-1 downregulation. Finally, Formo inhibits the in vivo tumor growth in a xenograft mouse model.

Conclusion

This study highlights the importance of promoting ubiquitination-dependent Mcl-1 turnover might be an alternative strategy to enhance the anti-tumor efficacy of EGFR-TKI.
Including oxygen supplement in the early warning score: a prediction study comparing TOKS, modified TOKS and NEWS in a cohort of emergency patients
Authors: Skov Maj Juhl , Dynesen Jacob , Jessen Marie K. , Liesanth Janet Yde , Mackenhauer Julie , Kirkegaard Hans
Published: April 2020

Background

Early warning scores (EWS) are widely used in emergency departments and on general wards to detect critical illness and deterioration. TOKS (“Tidlig Opsporing af Kritisk Sygdom”) is an early warning score used in Central Denmark Region to monitor hospitalized patients.

The objective of this study is to investigate whether inclusion of supplement in the TOKS algorithm (modified TOKS; mTOKS), would improve the ability to predict 7-day mortality. Secondarily, we compare the discriminatory ability between TOKS, mTOKS and the National Early Warning Score (NEWS).

Methods

This is a prediction study including a cohort of adult patients who attended an emergency department in Central Denmark Region during a 3-month period in 2015. The discriminatory ability of TOKS, mTOKS and NEWS was evaluated by calculating the area under the receiver operating characteristics- curve (AUROC) with 7-day mortality as outcome. mTOKS was defined by adding 2 points for oxygen supplement to the normal TOKS score.

Results

18.853 patients were included. AUROC for TOKS: 0,78 (95%-CI: 0,76-0,81). AUROC for mTOKS: 0,81 (95 %-CI: 0,78-0,83). AUROC for NEWS: 0,83 (95%-CI: 0,80-0,85). The predictive ability of all three early warning scores are statistically significantly different from each other (p-value < 0,01).

Conclusion

The discriminatory ability of TOKS improved statistically by including oxygen supplement. All models showed moderate to good discriminatory ability.
Urinary cell cycle arrest biomarkers and chitinase 3-like protein 1 (CHI3L1) to detect acute kidney injury in the critically ill: a post hoc laboratory analysis on the FINNAKI cohort
Authors:   The FINNAKI Study Group, Hoste Eric A. , Vaara Suvi T. , De Loor Jorien , Haapio Mikko , Nuytinck Lieve , Demeyere Kristel , Pettilä Ville , Meyer Evelyne
Published: April 2020

Background

Acute kidney injury (AKI) is a frequently occurring syndrome in critically ill patients and is associated with worse outcomes. Biomarkers allow early identification and therapy of AKI which may improve outcomes. Urine chitinase 3-like protein 1 (uCHI3L1) was recently identified as a promising urinary biomarker for AKI. In this multicenter study, we evaluated the diagnostic performance for AKI stage 2 or greater of uCHI3L1 in comparison with the urinary cell cycle arrest biomarkers urinary tissue inhibitor of metalloproteinases-2 (TIMP-2)•insulin-like growth factor-binding protein 7 (IGFBP7) measured by NephroCheck Risk®.

Methods

Post hoc laboratory study of the prospective observational FINNAKI study. Of this cohort, we included patients with stored admission urine samples and availability of serum creatinine at day 1 of admission. Patients who already had AKI stage 2 or 3 at ICU admission were excluded. AKI was defined and staged according to the KDIGO definition and staging system. The primary endpoint was AKI stage 2 or 3 at day 1. Biomarker performance was assessed by the area under the curve of the receiver operating characteristic curve (AUC). We assessed individual performance and different combinations of urine biomarkers.

Results

Of 660 included patients, 49 (7.4%) had AKI stages 2–3 at day 1. All urine biomarkers were increased at admission in AKI patients. All biomarkers and most combinations had AUCs < 0.700. The combination uCHI3L1•TIMP-2 was best with a fair AUC of 0.706 (0.670, 0.718). uCHI3L1 had a positive likelihood ratio (LR) of 2.25 which was comparable to that of the NephroCheck Risk® cutoff of 2.0, while the negative LR of 0.53 was comparable to that of the NephroCheck Risk® cutoff of 0.3.

Conclusions

We found that uCHI3L1 and NephroCheck Risk® had a comparable diagnostic performance for diagnosis of AKI stage 2 or greater within a 24-h period in this multicenter FINNAKI cohort. In contrast to initial discovery and validation studies, the diagnostic performance was poor. Possible explanations for this observation are differences in patient populations, proportion of emergency admissions, proportion of functional AKI, rate of developing AKI, and observation periods for diagnosis of AKI.
Enzymatic conversion reactions of 5-hydroxymethylfurfural (HMF) to bio-based 2,5-diformylfuran (DFF) and 2,5-furandicarboxylic acid (FDCA) with air: mechanisms, pathways and synthesis selectivity
Authors: Cajnko Miša Mojca , Novak Uroš , Grilc Miha , Likozar Blaž
Published: April 2020

Background

2,5-Furandicarboxylic acid (FDCA) is one of the top biomass-derived value-added chemicals. It can be produced from fructose and other C6 sugars via formation of 5-hydroxymethilfurfural (HMF) intermediate. Most of the chemical methods for FDCA production require harsh conditions, thus as an environmentally friendly alternative, an enzymatic conversion process can be applied.

Results

Commercially available horseradish peroxidase (HRP) and lignin peroxidase (LPO), alcohol (AO) and galactose oxidase (GO), catalase (CAT) and laccase (LAC) were tested against HMF, 2,5-diformylfuran (DFF), 5-hydroxymethyl-2-furoic acid (HMFA) and 5-formyl-2-furoic acid (FFA). Enzyme concentrations were determined based on the number of available active sites and reactions performed at atmospheric oxygen pressure. AO, GO, HRP and LPO were active against HMF, where LPO and HRP produced 0.6 and 0.7% of HMFA, and GO and AO produced 25.5 and 5.1% DFF, respectively. Most of the enzymes had only mild (3.2% yield or less) or no activity against DFF, HMFA and FFA, with only AO having a slightly higher activity against FFA with an FDCA yield of 11.6%. An effect of substrate concentration was measured only for AO, where 20 mM HMF resulted in 19.5% DFF and 5 mM HMF in 39.9% DFF, with a Km value of 14 mM. Some multi-enzyme reactions were also tested and the combination of AO and CAT proved most effective in converting over 97% HMF to DFF in 72 h.

Conclusions

Our study aimed at understanding the mechanism of conversion of bio-based HMF to FDCA by different selected enzymes. By understanding the reaction pathway, as well as substrate specificity and the effect of substrate concentration, we would be able to better optimize this process and obtain the best product yields in the future.
Effect of residual extractable lignin on acetone–butanol–ethanol production in SHF and SSF processes
Authors: Li Jing , Zhang Yu , Shi Suan , Tu Maobing
Published: April 2020

Background

Lignin plays an important role in biochemical conversion of biomass to biofuels. A significant amount of lignin is precipitated on the surface of pretreated substrates after organosolv pretreatment. The effect of this residual lignin on enzymatic hydrolysis has been well understood, however, their effect on subsequent ABE fermentation is still unknown.

Results

To determine the effect of residual extractable lignin on acetone–butanol–ethanol (ABE) fermentation in separate hydrolysis and fermentation (SHF) and simultaneous saccharification and fermentation (SSF) processes, we compared ABE production from ethanol-washed and unwashed substrates. The ethanol organosolv pretreated loblolly pine (OPLP) was used as the substrate. It was observed that butanol production from OPLP-UW (unwashed) and OPLP-W (washed) reached 8.16 and 1.69 g/L, respectively, in SHF. The results showed that ABE production in SHF from OPLP-UW prevents an “acid crash” as compared the OPLP-W. In SSF process, the “acid crash” occurred for both OPLP-W and OPLP-UW. The inhibitory extractable lignin intensified the “acid crash” for OPLP-UW and resulted in less ABE production than OPLP-W. The addition of detoxified prehydrolysates in SSF processes shortened the fermentation time and could potentially prevent the “acid crash”.

Conclusions

The results suggested that the residual extractable lignin in high sugar concentration could help ABE production by lowering the metabolic rate and preventing “acid crash” in SHF processes. However, it became unfavorable in SSF due to its inhibition of both enzymatic hydrolysis and ABE fermentation with low initial sugar concentration. It is essential to remove extractable lignin of substrates for ABE production in SSF processes. Also, a higher initial sugar concentration is needed to prevent the “acid crash” in SSF processes.
Modeling the transmission dynamics of varicella in Hungary
Authors: Karsai János , Csuma-Kovács Rita , Dánielisz Ágnes , Molnár Zsuzsanna , Dudás János , Borsos Teodóra , Röst Gergely
Published: April 2020

Vaccines against varicella-zoster virus (VZV) are under introduction in Hungary into the routine vaccination schedule, hence it is important to understand the current transmission dynamics and to estimate the key parameters of the disease. Mathematical models can be greatly useful in advising public health policy decision making by comparing predictions for different scenarios. First we consider a simple compartmental model that includes key features of VZV such as latency and reactivation of the virus as zoster, and exogeneous boosting of immunity. After deriving the basic reproduction number $R_{0}$R0, the model is analysed mathematically and the threshold dynamics is proven: if $R_{0}\leq 1$R0≤1 then the virus will be eradicated, while if $R_{0}>1$R0>1 then an endemic equilibrium exists and the virus uniformly persists in the population. Then we extend the model to include seasonality, and fit it to monthly incidence data from Hungary. It is shown that besides the seasonality, the disease dynamics has intrinsic multi-annual periodicity. We also investigate the sensitivity of the model outputs to the system parameters and the underreporting ratio, and provide estimates for $R_{0}$R0.
Mycoplasma gallisepticum triggers immune damage in the chicken thymus by activating the TLR-2/MyD88/NF-κB signaling pathway and NLRP3 inflammasome
Authors: Chen Chunli , Li Jichang , Zhang Wei , Shah Syed Waqas Ali , Ishfaq Muhammad
Published: April 2020

Previous studies reported that Mycoplasma gallisepticum (MG) causes immune dysregulation in chickens. However, the underlying mechanisms of immune dysregulation in chickens are still unclear. The thymus is a primary lymphoid organ where the proliferation, differentiation and selection of T-lymphocytes occur, whereas T-lymphocytes play a crucial role in innate immune responses. To evaluate the effects of MG-infection on chicken thymus, White Leghorn chickens were divided into (1) control group and (2) MG-infection group. ATPase activities were detected by commercial kits. The hallmarks of inflammation, autophagy and energy metabolism were examined in chicken thymus tissues by histopathology, transmission electron microscopy, immunofluorescence microscopy, RT-PCR and western blotting. Immunofluorescence examination revealed that the number of CD8+ lymphocytes has significantly reduced in MG-infection group. In addition, morphological analysis revealed that MG induced inflammatory cells infiltration. The mitochondria were swollen and chromatin material was condensed in MG-infection group. The mRNA and protein expression results showed that MG-infection triggered the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3) inflammasome through TLR-2/MyD88/NF-κB signaling pathway. Meanwhile, the expressions of autophagy-related genes were reduced both at mRNA and protein level in MG-infection group. While, ATPase activities and the expression of energy metabolism-related genes were reduced in the thymus of MG-infected chickens. These results showed that MG-infection triggered inflammatory response through TLR-2/MyD88/NF-κB signaling pathway, activated NLRP3 inflammasome, reduced the level of autophagy and impaired energy metabolism, which then lead to tissue damage in chicken thymus. The data provide new insights in MG-infection-mediated immune damage and provide possible therapeutic targets for future targeted therapy.
RETRACTED ARTICLE: Existence of global solutions to a quasilinear Schrödinger equation with general nonlinear optimal control conditions
Authors: Hu Yisheng , Qin Songhai , Liu Zhibin , Wang Yi
Published: April 2020

In this article, we study a modified maximum principle approach under condition on the weight of the delay term in the feedback and the weight of the term without delay. On that basis, we prove the existence of global solutions for a quasilinear Schrödinger equation in an unbounded domain with a general nonlinear nonlinear optimal control condition in the weakly nonlinear internal feedback. The equation includes many special cases such as classical Schrödinger equations, fractional Schrödinger equations, and relativistic Schrödinger equations, etc. Our results are established by means of the fixed point theory associated with the Schrödinger operator in suitable b-metric spaces. Moreover, we establish general stability estimates by using some properties of Schrödinger convex functions.
Invariant tori of full dimension for higher-dimensional beam equations with almost-periodic forcing
Authors: Rui Jie , Wang Yi
Published: April 2020

In this paper, we focus on the class of almost-periodically forced higher-dimensional beam equations $$ u_{tt}+(-\Delta +\mu )^{2}u+\psi (\omega t)u=0,\quad \mu >0, t \in \mathbb{R}, x\in \mathbb{R}^{d}, $$utt+(−Δ+μ)2u+ψ(ωt)u=0,μ>0,t∈R,x∈Rd, subject to periodic boundary conditions, where $\psi (\omega t)$ψ(ωt) is real analytic and almost-periodic in t. We show the existence of almost-periodic solutions for this equation under some suitable hypotheses. In the proof, we improve the KAM iteration to deal with the infinite-dimensional frequency $\omega =(\omega _{1},\omega _{2},\ldots)$ω=(ω1,ω2,…).
Existence of mild solutions for impulsive neutral Hilfer fractional evolution equations
Authors: Bedi Pallavi , Kumar Anoop , Abdeljawad Thabet , Khan Aziz
Published: April 2020

In this paper, we investigate the existence of mild solutions for neutral Hilfer fractional evolution equations with noninstantaneous impulsive conditions in a Banach space. We obtain the existence results by applying the theory of resolvent operator functions, Hausdorff measure of noncompactness, and Sadovskii’s fixed point theorem. We also present an example to show the validity of obtained results.
Vitamin K deficiency, evaluated with higher serum ucOC, was correlated with poor bone status in women
Authors: Tanaka Natsumi , Arima Kazuhiko , Nishimura Takayuki , Tomita Yoshihito , Mizukami Satoshi , Okabe Takuhiro , Abe Yasuyo , Kawashiri Shin-ya , Uchiyama Michiko , Honda Yuzo , Tsujimoto Ritsu , Kanagae Mitsuo , Osaki Makoto , Aoyagi Kiyoshi
Published: April 2020

Background

An increase in serum undercarboxylated osteocalcin concentrations suggests vitamin K deficiency. Clinical intervention studies suggested that the vitamin K supplementation might contribute to preventing bone loss in postmenopausal women. Evidence on the relationship between serum undercarboxylated osteocalcin (ucOC) levels and bone parameters of quantitative ultrasound (QUS) is limited. We examined the correlation between serum ucOC concentrations and bone status as measured by QUS among middle-aged and older Japanese men and women.

Methods

The subjects were community-dwelling men (n= 358) and women (n= 503) aged ≥ 40 years in Japan. Heel QUS parameters, including the stiffness index, speed of sound, and broadband ultrasound attenuation, were measured. Serum ucOC concentrations were measured by electrochemiluminescence immunoassay. Grip strength was measured in the dominant hand. Information on alcohol drinking, current smoking, exercise, and menopause in women was collected.

Results

Serum ucOC concentrations were significantly associated with age in both sexes. Serum ucOC concentrations in men were higher at ≥ 80 years than those in the age groups of 40–49, 50–59, and 60–69 years. Serum ucOC concentrations in women were higher in the age groups of 50–59 and 60–69 years than those at 40–49 years. Partial correlation analysis adjusting for covariates (age, body mass index, grip strength, alcohol drinking, current smoking, and exercise in men; age, body mass index, grip strength, alcohol drinking, current smoking, exercise, and menopause in women) showed that serum ucOC concentrations were negatively significantly correlated with all QUS parameters in women. Serum ucOC concentrations were not correlated with them in men.

Conclusions

Vitamin K deficiency, evaluated with higher serum ucOC, was correlated with poor bone status in women.
Establishment of cell lines with porcine spermatogonial stem cell properties
Authors: Zheng Yi , Feng Tongying , Zhang Pengfei , Lei Peipei , Li Fuyuan , Zeng Wenxian
Published: April 2020

Background

Spermatogonial stem cells (SSCs) are capable of both self-renewal and differentiation to mature functional spermatozoa, being the only adult stem cells in the males that can transmit genetic information to the next generation. Porcine SSCs hold great value in transgenic pig production and in establishment of porcine models for regenerative medicine. However, studies and applications of porcine SSCs have been greatly hampered by the low number of SSCs in the testis as well as the lack of an ideal stable long-term culture system to propagate porcine SSCs perpetually.

Results

In the present study, by lentiviral transduction of plasmids expressing the simian virus 40 (SV40) large T antigen into porcine primary SSCs, we developed two immortalized cell lines with porcine SSC attributes. The established cell lines, with the expression of porcine SSC and germ cell markers UCHL1, PLZF, THY1, VASA and DAZL, could respond to retinoic acid (RA), and could colonize the recipient mouse testis without tumor formation after transplantation. The cell lines displayed infinite proliferation potential, and have now been cultured for more than 7 months and passaged for over 35 times without morphological abnormalities.

Conclusions

We have for the first time established porcine SSC lines that could provide abundant cell sources for mechanistic studies on porcine SSC self-renewal and differentiation, thereby facilitating development of an optimal long-term culture system for porcine primary SSCs and their application to animal husbandry and medicine.
Cognitive fatigue in relation to depressive symptoms after treatment for childhood cancer
Authors: Irestorm Elin , Tonning Olsson Ingrid , Johansson Birgitta , Øra Ingrid
Published: April 2020

Background

Cognitive fatigue after childhood cancer is frequently overlooked despite guidelines recommending follow-up, and might be mistaken for depression due to overlapping symptoms. Our objectives were: 1) to examine ratings of fatigue in survivors of paediatric brain tumours (BT) and acute lymphoblastic leukaemia (ALL) compared to healthy controls, 2) to examine the relationship between symptoms of depression and cognitive fatigue, and 3) to evaluate parent-child concordance in ratings of cognitive fatigue.

Methods

Survivors of BT (n = 30), survivors of ALL (n = 30), and healthy controls (n = 60) aged 8–18 years completed the Pediatric Quality of Life Multidimensional Fatigue Scale and the Beck Youth Inventories. Associations between cognitive fatigue, diagnosis and depression were assessed with general linear modelling. Group differences were analysed using the Kruskal–Wallis test. Parent-child concordance was investigated with internal consistency reliability.

Results

Cognitive fatigue was prevalent in 70% of survivors of BT survivors and in 30% of survivors of ALL. Diagnosis was the main predictor of cognitive fatigue (p < .001, ηp2 = 0.178), followed by depression (p = .010, ηp2 = 0.080). Survivors of BT reported significantly more fatigue than healthy controls on all fatigue subscales. While they also expressed more symptoms of depression, we found no evidence for an interaction effect. Parent-child concordance was moderate to good among survivors, but poor for controls.

Conclusions

Survivors of BT and ALL suffer from cognitive fatigue, with survivors of BT expressing more problems. Cognitive fatigue and depression should be assessed in survivors of childhood cancer using both self-rated and proxy-rated measures, and appropriate interventions offered.
Insulin-like growth factor-1 overexpression increases long-term survival of posttrauma-born hippocampal neurons while inhibiting ectopic migration following traumatic brain injury
Authors: Littlejohn Erica L. , Scott Danielle , Saatman Kathryn E.
Published: April 2020

Cellular damage associated with traumatic brain injury (TBI) manifests in motor and cognitive dysfunction following injury. Experimental models of TBI reveal cell death in the granule cell layer (GCL) of the hippocampal dentate gyrus acutely after injury. Adult-born neurons residing in the neurogenic niche of the GCL, the subgranular zone, are particularly vulnerable. Injury-induced proliferation of neural progenitors in the subgranular zone supports recovery of the immature neuron population, but their development and localization may be altered, potentially affecting long-term survival. Here we show that increasing hippocampal levels of insulin-like growth factor-1 (IGF1) is sufficient to promote end-stage maturity of posttrauma-born neurons and improve cognition following TBI. Mice with conditional overexpression of astrocyte-specific IGF1 and wild-type mice received controlled cortical impact or sham injury and bromo-2′-deoxyuridine injections for 7d after injury to label proliferating cells. IGF1 overexpression increased the number of GCL neurons born acutely after trauma that survived 6 weeks to maturity (NeuN+BrdU+), and enhanced their outward migration into the GCL while significantly reducing the proportion localized ectopically to the hilus and molecular layer. IGF1 selectively affected neurons, without increasing the persistence of posttrauma-proliferated glia in the dentate gyrus. IGF1 overexpressing animals performed better during radial arm water maze reversal testing, a neurogenesis-dependent cognitive test. These findings demonstrate the ability of IGF1 to promote the long-term survival and appropriate localization of granule neurons born acutely after a TBI, and suggest these new neurons contribute to improved cognitive function.
Survey on categorical data for neural networks
Authors: Hancock John T. , Khoshgoftaar Taghi M.
Published: April 2020

This survey investigates current techniques for representing qualitative data for use as input to neural networks. Techniques for using qualitative data in neural networks are well known. However, researchers continue to discover new variations or entirely new methods for working with categorical data in neural networks. Our primary contribution is to cover these representation techniques in a single work. Practitioners working with big data often have a need to encode categorical values in their datasets in order to leverage machine learning algorithms. Moreover, the size of data sets we consider as big data may cause one to reject some encoding techniques as impractical, due to their running time complexity. Neural networks take vectors of real numbers as inputs. One must use a technique to map qualitative values to numerical values before using them as input to a neural network. These techniques are known as embeddings, encodings, representations, or distributed representations. Another contribution this work makes is to provide references for the source code of various techniques, where we are able to verify the authenticity of the source code. We cover recent research in several domains where researchers use categorical data in neural networks. Some of these domains are natural language processing, fraud detection, and clinical document automation. This study provides a starting point for research in determining which techniques for preparing qualitative data for use with neural networks are best. It is our intention that the reader should use these implementations as a starting point to design experiments to evaluate various techniques for working with qualitative data in neural networks. The third contribution we make in this work is a new perspective on techniques for using categorical data in neural networks. We organize techniques for using categorical data in neural networks into three categories. We find three distinct patterns in techniques that identify a technique as determined, algorithmic, or automated. The fourth contribution we make is to identify several opportunities for future research. The form of the data that one uses as an input to a neural network is crucial for using neural networks effectively. This work is a tool for researchers to find the most effective technique for working with categorical data in neural networks, in big data settings. To the best of our knowledge this is the first in-depth look at techniques for working with categorical data in neural networks.
Magnitude, risk factors and outcomes of stroke at Debre Markos Referral Hospital, Northwest Ethiopia: a retrospective observational study
Authors: Mulugeta Henok , Yehuala Amare , Haile Dessalegn , Mekonnen Nakachew , Dessie Getenet , Kassa Getachew Mullu , Kassa Zerihun Shimelis , Habtewold Tesfa Dejenie
Published: April 2020

Background

Stroke is one of the leading causes of death and disability in developing countries. The burden of stroke has varied widely in different areas, and there is a paucity of information about stroke in the selected study area.

Objectives

To assess the burden, risk factors, and outcomes of stroke at Debre Markos Referral Hospital, Northwest Ethiopia

Patients and methods

A hospital-based retrospective observational study was conducted in the medical ward of Debre Markos Referral Hospital from March 2017 to April 2019. A pretested checklist was used to extract relevant data from the chart of stroke patients. All statistical analyses were performed in the SPSS version 20 software.

Results

From a total of 2100 admissions in the medical ward, 162 of them were stroke patients, giving the in-hospital magnitude of 7.7%. The in-hospital case fatality rate was 8.6%. Additionally, 27.2% of patients were improved and 39.5% of them were referred. There was a significant association between types of stroke and risk factors such as sex, comorbid hypertension, hyperlipidemia, and atrial fibrillation (P ≤ 0.05).

Conclusion

The in-hospital period prevalence of stroke was 7.7%. Ischemic stroke was the most common type of stroke. Hypertension and hyperlipidemia were the leading identified risk factors for stroke. The overall in-hospital mortality was lower than previous studies in sub-Saharan African countries. Therefore, effective strategies and guidelines for the prevention and control of stroke and its risk factors are needed.
Frequency and Causes of Burnout in US Community Oncologists in the Era of Electronic Health Records
Authors: Gajra Ajeet , Bapat Bela , Jeune-Smith Yolaine , Nabhan Chadi , Klink Andrew J. , Liassou Djibril , Mehta Sonam , Feinberg Bruce
Published: April 2020

BACKGROUND:

Physician burnout, characterized by exhaustion of physical or emotional strength, cynicism, and lack of achievement, has become a worsening phenomenon in medicine, contributing to higher health care costs and patient/physician dissatisfaction. How burnout has affected hematologists and oncologists is not well studied.

METHODS:

US community oncologists/hematologists were queried via a Web-based survey from September-November 2018. Physicians were asked about frequency of burnout symptoms, drivers of work-related stress, and their perceptions on management of workload.

RESULTS:

Among the 163 physicians surveyed, 46% felt a substantial amount of stress at work. Most physicians felt emotionally (85%) and physically (87%) exhausted. A majority of physicians felt lethargic (67%), ineffective (64%), and/or detached (63%). In a typical workweek, 93% needed time beyond time allocated to clinical care to complete work responsibilities. Electronic health record (EHR) responsibilities caused moderate to excessive stress at work for 67% of physicians; 79% of physicians worked on EHRs outside of clinic hours. Other sources of excessive stress were changing reimbursement models (33%), interactions with payers (31%), and increasing patient and caregiver demands (31%). A third of physicians have considered retiring early or changing their career path to cope. To combat burnout, physicians’ practices have used advanced practice providers, invested in information technology, and/or hired additional administrative staff. However, the majority of physicians stated they had optimal or good control over their workload.

CONCLUSION:

Most oncologists experience burnout symptoms and require additional time beyond that allocated to clinical care to complete their workload. The discordance between oncologists’ admission of stress and exhaustion while claiming good control over those same burdens warrants exploration in future research.