bluuebunny/crossref_metadata_2025 huggingface dataset:
LncRNA HOTAIR-mediated MTHFR methylation inhibits 5-fluorouracil sensitivity in esophageal cancer cells
Authors: Zhang Shuyao , Zheng Fuchun , Zhang Liqun , Huang Zuojun , Huang Xiaoshan , Pan Zhen , Chen Shuang , Xu Chenchen , Jiang Yi , Gu Shuyi , Zhao Chengkuan , Zhang Qiuzhen , Shi Ganggang
Published: July 2020

Background

Esophageal cancer (EC) represents one of the most aggressive digestive neoplasms globally, with marked geographical variations in morbidity and mortality. Chemoprevention is a promising approach for cancer therapy, while acquired chemoresistance is a major obstacle impeding the success of 5-fluorouracil (5-FU)-based chemotherapy in EC, with the mechanisms underlying resistance not well-understood. In the present study, we focus on exploring the role of long non-coding RNA (lncRNA) HOTAIR in EC progression and sensitivity of EC cells to 5-FU.

Methods

Paired cancerous and pre-cancerous tissues surgically resected from EC patients were collected in this study. Promoter methylation of the MTHFR was assessed by methylation-specific PCR. RIP and ChIP assays were adopted to examine the interaction of DNA methyltransferases (DNMTs) with lncRNA HOTAIR and MTHFR, respectively. EC cells resistant to 5-FU were induced by step-wise continuous increasing concentrations of 5-FU. The sensitivity of EC cells to 5-FU in vivo was evaluated in nude mice treated with xenografts of EC cells followed by injection with 5-FU (i.p.).

Results

We found reciprocal expression patterns of lncRNA HOTAIR and MTHFR in EC tissues and human EC cells. Interference with lncRNA HOTAIR enhanced 5-FU-induced apoptosis, exhibited anti-proliferative activity, and reduced promoter methylation of the MTHFR in EC cells. Besides, overexpression of MTHFR attenuated the acquired chemoresistance induced by overexpression of lncRNA HOTAIR in EC cells. At last, enhanced chemosensitivity was observed in vivo once nude mice xenografted with lncRNA HOTAIR-depleted EC cells.

Conclusion

Together, our study proposes that pharmacologic targeting of lncRNA HOTAIR sensitizes EC cells to 5-FU-based chemotherapy by attenuating the promoter hypermethylation of the MTHFR in EC.
CPEB3 inhibits epithelial-mesenchymal transition by disrupting the crosstalk between colorectal cancer cells and tumor-associated macrophages via IL-6R/STAT3 signaling
Authors: Zhong Qian , Fang Yuxin , Lai Qiuhua , Wang Shanci , He Chengcheng , Li Aimin , Liu Side , Yan Qun
Published: July 2020

Background

Crosstalk between cancer cells and tumor-associated macrophages (TAMs) mediates tumor progression in colorectal cancer (CRC). Cytoplasmic polyadenylation element binding protein 3 (CPEB3) has been shown to exhibit tumor-suppressive role in CRC.

Methods

The expression of CPEB3, CD68, CD86 and CD163 was determined in CRC tissues. SW480 or HCT116 cells overexpressing CPEB3 and LoVo or RKO cells with CPEB3 knockdown were constructed. Stably transfected CRC cells were co-cultured with THP-1 macrophages to determine the malignant phenotype of CRC cells, macrophage polarization, and secretory signals. The inhibition of CPEB3 on tumor progression and M2-like TAM polarization was confirmed in nude mice.

Results

Decreased CPEB3 expression in CRC was associated with fewer CD86+ TAMs and more CD163+ TAMs. CPEB3 knockdown in CRC cells increased the number of CD163+ TAMs and the expression of IL1RA, IL-6, IL-4 and IL-10 in TAM supernatants. TAMs enhanced CRC cell proliferation and invasion via IL-6, and then activated the IL-6R/STAT3 pathway in CRC cells. However, CPEB3 reduced the IL-6R protein levels by directly binding to IL-6R mRNA, leading to decreased phosphorylated-STAT3 expression in CRC cells. CCL2 was significantly increased in CPEB3 knockdown cells, while CCL2 antibody treatment rescued the effect of CPEB3 knockdown in promoting CD163+ TAM polarization. Eventually, we confirmed that CPEB3 inhibits tumor progression and M2-like TAM polarization in vivo.

Conclusions

CPEB3 is involved in the crosstalk between CRC cells and TAMs by targeting IL-6R/STAT3 signaling.
Higher plasma cystatin C is associated with mortality after acute respiratory distress syndrome: findings from a Fluid and Catheter Treatment Trial (FACTT) substudy
Authors: Hendrickson Carolyn M. , Kwong Yuenting D. , Belzer Annika G. , Shlipak Michael G. , Matthay Michael A. , Liu Kathleen D.
Published: July 2020

Background

Cystatin C is a well-validated marker of glomerular filtration rate in chronic kidney disease. Higher plasma concentrations of cystatin C are associated with worse clinical outcomes in heterogenous populations of critically ill patients and may be superior to creatinine in identifying kidney injury in critically ill patients. We hypothesized that elevated levels of plasma cystatin C in patients with acute respiratory distress syndrome (ARDS) would be associated with mortality risk.

Methods

In a retrospective study, cystatin C was measured by nephelometry on plasma obtained at enrollment from 919 patients in the Fluid and Catheter Treatment Trial. Multivariable logistic regression was performed testing the association between quartiles of cystatin C and 60-day mortality. Analyses were stratified by acute kidney injury (AKI) status identified in the first 7 days after enrollment by Kidney Disease: Improving Global Outcomes (KDIGO) criteria.

Results

Cystatin C was significantly higher among those patients who died compared to those who survived to 60 days [1.2 (0.9–1.9) mg/L vs. 0.8 (0.6–1.2) mg/L, p < 0.001]. Compared to the lower three quartiles, subjects in the highest quartile of cystatin C had a significantly higher odds of death at 60 days [OR 1.8 (1.2–2.6), p = 0.003 in adjusted analyses]; the odds of death incrementally rose in higher cystatin C quartiles compared to the lowest quartile (OR 1.1, 1.8, and 2.5). In adjusted analyses stratified by AKI status, compared to subjects in the lower three quartiles, subjects in the highest quartile of cystatin C with AKI had a significantly higher odds of death at 60 days both in participants with AKI [OR 1.6 (1.0–2.4), p = 0.048] and those without AKI [OR 2.4 (1.2–5.0), p = 0.017]. In adjusted analyses, there was no significant association between sex-stratified baseline creatinine quartiles and mortality.

Conclusions

Higher plasma levels of cystatin C on enrollment were strongly associated with mortality at 60 days in patients with ARDS with and without AKI identified by creatinine-based definitions. Compared to creatinine, cystatin C may be a better biomarker of kidney function in patients with ARDS and therefore identify patients with multiple organ failure at higher risk of death.
Bedside calculation of mechanical power during volume- and pressure-controlled mechanical ventilation
Authors: Chiumello Davide , Gotti Miriam , Guanziroli Mariateresa , Formenti Paolo , Umbrello Michele , Pasticci Iacopo , Mistraletti Giovanni , Busana Mattia
Published: July 2020

Background

Mechanical power (MP) is the energy delivered to the respiratory system over time during mechanical ventilation. Our aim was to compare the currently available methods to calculate MP during volume- and pressure-controlled ventilation, comparing different equations with the geometric reference method, to understand whether the easier to use surrogate formulas were suitable for the everyday clinical practice. This would warrant a more widespread use of mechanical power to promote lung protection.

Methods

Forty respiratory failure patients, sedated and paralyzed for clinical reasons, were ventilated in volume-controlled ventilation, at two inspiratory flows (30 and 60 L/min), and pressure-controlled ventilation with a similar tidal volume. Mechanical power was computed both with the geometric method, as the area between the inspiratory limb of the airway pressure and the volume, and with two algebraic methods, a comprehensive and a surrogate formula.

Results

The bias between the MP computed by the geometric method and by the comprehensive algebraic method during volume-controlled ventilation was respectively 0.053 (0.77, − 0.81) J/min and − 0.4 (0.70, − 1.50) J/min at low and high flows (r2 = 0.96 and 0.97, p < 0.01). The MP measured and computed by the two methods were highly correlated (r2 = 0.95 and 0.94, p < 0.01) with a bias of − 0.0074 (0.91, − 0.93) and − 1.0 (0.45, − 2.52) J/min at high-low flows. During pressure-controlled ventilation, the bias between the MP measured and the one calculated with the comprehensive and simplified methods was correlated (r2 = 0.81, 0.94, p < 0.01) with mean differences of − 0.001 (2.05, − 2.05) and − 0.81 (2.11, − 0.48) J/min.

Conclusions

Both for volume-controlled and pressure-controlled ventilation, the surrogate formulas approximate the reference method well enough to warrant their use in the everyday clinical practice. Given that these formulas require nothing more than the variables already displayed by the intensive care ventilator, a more widespread use of mechanical power should be encouraged to promote lung protection against ventilator-induced lung injury.
Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis
Authors: Lecronier Marie , Beurton Alexandra , Burrel Sonia , Haudebourg Luc , Deleris Robin , Le Marec Julien , Virolle Sara , Nemlaghi Safaa , Bureau Côme , Mora Pierre , De Sarcus Martin , Clovet Olivier , Duceau Baptiste , Grisot Paul Henri , Pari Marie Hélène , Arzoine Jérémy , Clarac Ulrich , Boutolleau David , Raux Mathieu , Delemazure Julie , Faure Morgane , Decavele Maxens , Morawiec Elise , Mayaux Julien , Demoule Alexandre , Dres Martin
Published: July 2020

Background

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients.

Methods

The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7.

Results

Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively (p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7.

Conclusion

In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.
Evaluation of the VETSCAN IMAGYST: an in-clinic canine and feline fecal parasite detection system integrated with a deep learning algorithm
Authors: Nagamori Yoko , Hall Sedlak Ruth , DeRosa Andrew , Pullins Aleah , Cree Travis , Loenser Michael , Larson Benjamin S. , Smith Richard Boyd , Goldstein Richard
Published: July 2020

Background

Fecal examination is an important component of routine companion animal wellness exams. Sensitivity and specificity of fecal examinations, however, are influenced by sample preparation methodologies and the level of training and experience of personnel who read fecal slides. The VETSCAN IMAGYST system consists of three components: a sample preparation device, a commercially available scanner, and an analysis software. The VETSCAN IMAGYST automated scanner and cloud-based, deep learning algorithm, locates, classifies, and identifies parasite eggs found on fecal microscopic slides. The main study objectives were (i) to qualitatively evaluate the capabilities of the VETSCAN IMAGYST screening system and (ii) to assess and compare the performance of the VETSCAN IMAGYST fecal preparation methods to conventional fecal flotation techniques.

Methods

To assess the capabilities of VETSCAN IMAGYST screening components, fecal slides were prepared by the VETSCAN IMAGYST centrifugal and passive flotation techniques with 100 pre-screened fecal samples collected from dogs and cats and examined by both the algorithm and parasitologists. To determine the diagnostic sensitivity and specificity of the VETSCAN IMAGYST sample preparation techniques, fecal flotation slides were prepared by four different techniques (VETSCAN IMAGYST centrifugal and passive flotations, conventional centrifugal flotation, and passive flotation using OVASSAY® Plus) and examined by parasitologists. Additionally, required sample preparation and scanning times were estimated on a subset of samples to evaluate VETSCAN IMAGYST ease-of-use.

Results

The algorithm performance of the VETSCAN IMAGYST closely matched that of the parasitologists, with Pearsonʼs correlation coefficient (r) ranging from 0.83–0.99 across four taxa of parasites, Ancylostoma, Toxocara, Trichuris and Taeniidae. Both VETSCAN IMAGYST centrifugal and passive flotation methods correlated well with conventional preparation methods on all targeted parasites (diagnostic sensitivity of 75.8–100%, specificity of 91.8–100%, qualitative agreement between methods of 93.8–94.5%). Sample preparation, slide scan and image analysis were completed within 10–14 min by VETSCAN IMAGYST centrifugal and passive flotations, respectively.

Conclusions

The VETSCAN IMAGYST scanning system with the VETSCAN IMAGYST sample preparation methods demonstrated a qualitative match in comparison to the results of parasitologists’ examinations with conventional fecal flotation techniques. The VETSCAN IMAGYST is an easy-to-use, next generation qualitative and possibly quantitative diagnostic platform that brings expert clinical results into the hands of veterinary clinics.
Initiating guideline-concordant gout treatment improves arterial endothelial function and reduces intercritical inflammation: a prospective observational study
Authors: Toprover Michael , Shah Binita , Oh Cheongeun , Igel Talia F. , Romero Aaron Garza , Pike Virginia C. , Curovic Fatmira , Bang Daisy , Lazaro Deana , Krasnokutsky Svetlana , Katz Stuart D. , Pillinger Michael H.
Published: July 2020

Background

Patients with gout have arterial dysfunction and systemic inflammation, even during intercritical episodes, which may be markers of future adverse cardiovascular outcomes. We conducted a prospective observational study to assess whether initiating guideline-concordant gout therapy with colchicine and a urate-lowering xanthine oxidase inhibitor (XOI) improves arterial function and reduces inflammation.

Methods

Thirty-eight untreated gout patients meeting American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria for gout and ACR guidelines for initiating urate-lowering therapy (ULT) received colchicine (0.6 mg twice daily, or once daily for tolerance) and an XOI (allopurinol or febuxostat) titrated to ACR guideline-defined serum urate (sU) target. Treatment was begun during intercritical periods. The initiation of colchicine and XOI was staggered to permit assessment of a potential independent effect of colchicine. Brachial artery flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) assessed endothelium-dependent and endothelium-independent (smooth muscle) arterial responsiveness, respectively. High-sensitivity C-reactive protein (hsCRP), IL-1β, IL-6, myeloperoxidase (MPO) concentrations, and erythrocyte sedimentation rate (ESR) assessed systemic inflammation.

Results

Four weeks after achieving target sU concentration on colchicine plus an XOI, FMD was significantly improved (58% increase, p = 0.03). hsCRP, ESR, IL-1β, and IL-6 also all significantly improved (30%, 27%, 19.5%, and 18.8% decrease respectively; all p ≤ 0.03). Prior to addition of XOI, treatment with colchicine alone resulted in smaller numerical improvements in FMD, hsCRP, and ESR (20.7%, 8.9%, 13% reductions, respectively; all non-significant), but not IL-1β or IL-6. MPO and NMD did not change with therapy. We observed a moderate inverse correlation between hsCRP concentration and FMD responsiveness (R = − 0.41, p = 0.01). Subgroup analyses demonstrated improvement in FMD after achieving target sU concentration in patients without but not with established cardiovascular risk factors and comorbidities, particularly hypertension and hyperlipidemia.

Conclusions

Initiating guideline-concordant gout treatment reduces intercritical systemic inflammation and improves endothelial-dependent arterial function, particularly in patients without established cardiovascular comorbidities.
LINE-1 ORF1p does not determine substrate preference for human/orangutan SVA and gibbon LAVA
Authors: Damert Annette
Published: July 2020

Background

Non-autonomous VNTR (Variable Number of Tandem Repeats) composite retrotransposons – SVA (SINE-R-VNTR-Alu) and LAVA (L1-Alu-VNTR-Alu) – are specific to hominoid primates. SVA expanded in great apes, LAVA in gibbon. Both SVA and LAVA have been shown to be mobilized by the autonomous LINE-1 (L1)-encoded protein machinery in a cell-based assay in trans. The efficiency of human SVA retrotransposition in vitro has, however, been considerably lower than would be expected based on recent pedigree-based in vivo estimates. The VNTR composite elements across hominoids – gibbon LAVA, orangutan SVA_A descendants and hominine SVA_D descendants – display characteristic structures of the 5′ Alu-like domain and the VNTR. Different partner L1 subfamilies are currently active in each of the lineages. The possibility that the lineage-specific types of VNTR composites evolved in response to evolutionary changes in their autonomous partners, particularly in the nucleic acid binding L1 ORF1-encoded protein, has not been addressed.

Results

Here I report the identification and functional characterization of a highly active human SVA element using an improved mneo retrotransposition reporter cassette. The modified cassette (mneoM) minimizes splicing between the VNTR of human SVAs and the neomycin phosphotransferase stop codon. SVA deletion analysis provides evidence that key elements determining its mobilization efficiency reside in the VNTR and 5′ hexameric repeats. Simultaneous removal of the 5′ hexameric repeats and part of the VNTR has an additive negative effect on mobilization rates. Taking advantage of the modified reporter cassette that facilitates robust cross-species comparison of SVA/LAVA retrotransposition, I show that the ORF1-encoded proteins of the L1 subfamilies currently active in gibbon, orangutan and human do not display substrate preference for gibbon LAVA versus orangutan SVA versus human SVA. Finally, I demonstrate that an orangutan-derived ORF1p supports only limited retrotransposition of SVA/LAVA in trans, despite being fully functional in L1 mobilization in cis.

Conclusions

Overall, the analysis confirms SVA as a highly active human retrotransposon and preferred substrate of the L1-encoded protein machinery. Based on the results obtained in human cells coevolution of L1 ORF1p and VNTR composites does not appear very likely. The changes in orangutan L1 ORF1p that markedly reduce its mobilization capacity in trans might explain the different SVA insertion rates in the orangutan and hominine lineages, respectively.
High sustained viral response among HCV genotype 3 patients with advanced liver fibrosis: real-world data of HCV elimination program in Georgia
Authors: Butsashvili Maia , Gvinjilia Lia , Kamkamidze George , Metreveli David , Dvali Shorena , Rukhadze Tamar , Gamkrelidze Amiran , Nasrullah Muazzam , Shadaker Shaun , Morgan Juliette , Averhoff Francisco
Published: July 2020

Objective

In 2015, Georgia launched HCV elimination program. Initially, patients with advanced liver disease were treated with sofosbuvir-based regimen—the only DAA available for all genotypes. Purpose of the study was assessing real-world data of treatment outcome among patients with HCV GEN3 and advanced liver fibrosis with sofosbuvir-based regimens.

Results

Totally 1525 genotype 3 patients were eligible for analysis; most (72.6%) were aged > 45 years, majority were males (95.1%), and all (100%) had advanced liver disease (F3 or F4 by METAVIR score based on elastography). Of those who received sofosbuvir/ribavirin (SOF/RBV) for 24 weeks, 79.3% achieved SVR, while 96.5% who received sofosbuvir/pegylated interferon/ribavirin (SOF/PEG/RBV) for 12 weeks achieved SVR (p < 0.01). Among patients with liver cirrhosis (defined as F4) overall cure rate was 85.7% as opposed to 96.4% for those with F3. Females were more likely to be cured (98.7% vs 89.7%; OR = 8.54). Patients aged 31–45 years had higher likelihood of achieving SVR compared to patients aged 46-60 years (95.7% vs 87.4%; OR = 0.32,). Independent predictors of SVR were treatment with SOF/PEG/RBV (aOR = 6.72) and lower fibrosis stage (F3) (aOR = 4.18). Real-world experience among HCV GEN3 patients with advanced liver fibrosis and treated by sofosbuvir regimen w/o PEGIFN, demonstrated overall high SVR rate.
Characterization of yellow root cassava and food products: investigation of cyanide and β-carotene concentrations
Authors: Odoemelam Chiemela S. , Percival Benita , Ahmad Zeeshan , Chang Ming-Wei , Scholey Dawn , Burton Emily , Okafor Polycarp N. , Wilson Philippe B.
Published: July 2020

Objective

Cyanide is a highly toxic compound, and the consumption of products containing cyanide is a significant public health concern. Conversely, β-carotene possesses essential nutritional attributes for human health, therefore the characterisation and quantification of both compounds in food products is fundamental. Herein, cyanide and β-carotene levels in two flours produced from the roots of two varieties of cassava (Manihot esculenta crantz), namely UMUCASS-38(TMS 01/1371) and NR-8082, and their associated food products were detected and quantified.

Results

The cyanide content of NR-8082 and UMUCASS-38 flours was determined at 18.01 ± 0.01 ppm and 17.02 ± 0.02 ppm (mean ± SD), respectively. These flours contained significantly higher (p < 0.05) than the residual cyanide levels determined in the cookies and cake produced therefrom with levels of 10.00 ± 0.00 ppm and 7.10 ± 0.14 ppm (mean ± SD), respectively. The levels of β-carotene determined in both the cake and cookie samples varied significantly (p < 0.05). The highest levels of β-carotene at 6.53 ± 0.02 µg/g (mean ± SD) were determined in raw roots of UMUCASS-38. While NR-8082 levels of β-carotene were less than UMUCASS-38 at 1.12 ± 0.02 µg/g (mean ± SD). Processing the roots into flour reduced the β-carotene content to 4.78 ± 0.01 µg/g and 0.76 ± 0.02 µg/g (mean ± SD) in UMUCASS-38 and NR-8082 flours, respectively. Cookies and cake produced from flour derived from the UMUCASS-38 variety had (mean ± SD) 2.15 ± 0.01 µg/g and 2.84 ± 0.04 µg/g of β-carotene, respectively.
Functional conservation of mitochondrial RNA levels despite divergent mtDNA organization
Authors: Held James P. , Patel Maulik R.
Published: July 2020

Objective

Mitochondria-encoded ribosomal RNA (rRNA) genes in humans are expressed at a higher rate than protein coding genes of the mitochondria. The organization of the human mitochondrial genome (mtDNA) is amenable to differential expression of rRNAs as the rRNA encoding genes lie in tandem immediately downstream of the promoter-containing region. However, mtDNA is not organized in the same way as humans in all metazoans. In the nematode, Caenorhabditis elegans, the rRNA genes are on opposite sides of the mtDNA molecule and there are no obvious promoter sequences specific to the rRNA genes. Thus, we asked whether rRNA levels are higher relative to mRNAs in mitochondria of C. elegans as they are in humans.

Results

Using droplet digital PCR, we discovered that steady-state mitochondrial rRNA transcript levels are approximately 120 times higher than the levels of mitochondrial mRNAs. These data demonstrate that despite the lack of conservation in mitochondrial genome organization, a high mitochondrial rRNA-to-mRNA ratio is a conserved feature of metazoans.
The role of DNA methylation in the pathogenesis of type 2 diabetes mellitus
Authors: Ahmed Sanabil Ali Hassan , Ansari Suraiya Anjum , Mensah-Brown Eric P. K. , Emerald Bright Starling
Published: July 2020

Diabetes mellitus (DM) is a chronic condition characterised by β cell dysfunction and persistent hyperglycaemia. The disorder can be due to the absence of adequate pancreatic insulin production or a weak cellular response to insulin signalling. Among the three types of DM, namely, type 1 DM (T1DM), type 2 DM (T2DM), and gestational DM (GDM); T2DM accounts for almost 90% of diabetes cases worldwide.

Epigenetic traits are stably heritable phenotypes that result from certain changes that affect gene function without altering the gene sequence. While epigenetic traits are considered reversible modifications, they can be inherited mitotically and meiotically. In addition, epigenetic traits can randomly arise in response to environmental factors or certain genetic mutations or lesions, such as those affecting the enzymes that catalyse the epigenetic modification. In this review, we focus on the role of DNA methylation, a type of epigenetic modification, in the pathogenesis of T2DM.
Bilateral ovarian edema with unilateral ovarian leiomyoma and double inferior vena cava: a case report
Authors: Shrestha Suraj , Homagain Sushan , Kandel Suraj , Jha Pooja , Gurung Geeta
Published: July 2020

Background

Ovarian edema, ovarian leiomyoma, and double inferior vena cava are all rare clinical entities. The coexistence of all these entities has not been yet reported in the literature.

Case presentation

We report a case of a 25-year-old nulliparous tamang woman with all these rare clinical entities, who presented with a complaint of right-sided lower abdominal pain. After examination and investigation, an ovarian tumor was suspected and laparotomy was performed during which bilateral ovarian edema with a solid tumor on the left side was identified and left salpingo-oophorectomy was done preserving her right ovary. A histopathological examination confirmed the clinical findings.

Conclusions

As ovarian edema is a rare entity, due to lack of clinical suspicion it is often overdiagnosed as a malignant tumor leading to radical surgery with subsequent loss of hormonal function and early infertility. A high degree of clinical suspicion during the intraoperative period is helpful for diagnosis to avoid unnecessary oophorectomy and infertility.
Salient context-based semantic matching for information retrieval
Authors: Qi Yuanyuan , Zhang Jiayue , Xu Weiran , Guo Jun
Published: July 2020

Neural networks provide new possibilities to uncover semantic relationships between words by involving contextual information, and further a way to learn the matching pattern from document-query word contextual similarity matrix, which has brought promising results in IR. However, most neural IR methods rely on the conventional word-word matching framework for finding a relevant document for a query. Its effect is limited due to the wide gap between the lengths of query and document. To address this problem, we propose a salient context-based semantic matching (SCSM) method to build a bridge between query and document. Our method locates the most relevant context in the document using a shifting window with adapted length and then calculates the relevance score within it as the representation of the document. We define the notion of contextual salience and the corresponding measures to calculate the relevance of a context to a given query, in which the interaction between the query and the context is modeled by semantic similarity. Experiments on various collections from TREC show the effectiveness of our model as compared to the state-of-the-art methods.
Local solvability and stability of the inverse problem for the non-self-adjoint Sturm–Liouville operator
Authors: Bondarenko Natalia P.
Published: July 2020

We consider the non-self-adjoint Sturm–Liouville operator on a finite interval. The inverse spectral problem is studied, which consists in recovering this operator from its eigenvalues and generalized weight numbers. We prove local solvability and stability of this inverse problem, relying on the method of spectral mappings. Possible splitting of multiple eigenvalues is taken into account.
On a strong-singular fractional differential equation
Authors: Baleanu Dumitru , Ghafarnezhad Khadijeh , Rezapour Shahram , Shabibi Mehdi
Published: July 2020

It is important we try to solve complicate differential equations specially strong singular ones. We investigate the existence of solutions for a strong-singular fractional boundary value problem under some conditions. In this way, we provide a new technique for our study. We provide an example to illustrate our main result.
Dynamics of a delayed SIR model for the transmission of PRRSV among a swine population
Authors: Zou Junchen , Upadhyay Ranjit Kumar , Pratap A. , Zhang Zizhen
Published: July 2020

The objective of this paper is to propose a delayed susceptible-infectious-recovered (SIR) model for the transmission of porcine reproductive respiratory syndrome virus (PRRSV) among a swine population, including the latent period delay of the virus and the time delay due to the period the infectious swines need to recover. By taking different combinations of the two delays as the bifurcation parameter, local stability of the disease-present equilibrium and the existence of Hopf bifurcation are analyzed. Sufficient conditions for global stability of the disease-present equilibrium are derived by constructing a suitable Lyapunov function. Directly afterwards, properties of the Hopf bifurcation such as direction and stability are studied with the aid of the normal form theory and center manifold theorem. Finally, numerical simulations are presented to justify the validity of the derived theoretical results.
The 2017 global point prevalence survey of antimicrobial consumption and resistance in Canadian hospitals
Authors: Frenette Charles , Sperlea David , German Greg J. , Afra Kevin , Boswell Jennifer , Chang Sandra , Goossens Herman , Grant Jennifer , Lefebvre Marie-Astrid , McGeer Allison , Mertz Dominic , Science Michelle , Versporten Ann , Thirion Daniel J. G.
Published: July 2020

Background

Patient-level surveillance (indication, appropriate choice, dosing, route, duration) of antimicrobial use in Canadian hospitals is needed to reduce antimicrobial overuse and misuse. Patient-level surveillance has not been performed on a national level in Canada. The Global Point Prevalence Survey of Antimicrobial Consumption and Resistance (Global-PPS) is an international collaborative to monitor antimicrobial use and resistance in hospitals worldwide. Global-PPS locally documents on a single day patient-level antimicrobial prescribing practices. This article presents the results of the 2017 Global-PPS in Canadian hospitals with established antimicrobial stewardship programs.

Methods

Hospitals part of the Canadian Nosocomial Infection Surveillance Program were invited to participate. Surveys could be performed any time in the 2017 calendar year. All in-patient wards in each hospital were surveyed by a physician, pharmacist or nurse with infectious disease training.

Results

Fourteen Canadian hospitals participated in the survey. Of 4118 patients, 1400 patients (34.0%) received a total of 2041 antimicrobials. Overall, 73.1% (n = 1493) of antimicrobials were for therapeutic use, 14.2% (n = 288) were for medical prophylaxis, 8.3% (n = 170) were for surgical prophylaxis, 1.8% (n = 37) were for other reasons, and 0.2% (n = 3) were used as prokinetic agents. Only 2.5% (n = 50) were for unknown reasons. For antimicrobials for therapeutic use, 29.9% of patients were treated for lower respiratory tract (343/1147), 10.5% for intra-abdominal (120/1147), 9.3% for skin and soft tissue (107/1147) and 7.5% for gastro-intestinal (86/1147) infections.

Conclusions

Standardized methodology amongst Global-PPSs allows the comparison of our results to the 2015 Global-PPS. The prevalence of antimicrobial use on medical, surgical, and intensive care wards are similar to those previously observed in North America. Indication of antimicrobials has not been previously reported on such a large scale in Canadian hospitals. This report serves as a comparison for further point prevalence surveys that are currently underway. It will be used for identifying opportunities and benchmarking in antibiotic stewardship.
A population-base survey on knowledge, attitude and awareness of the general public on antibiotic use and resistance
Authors: Effah Clement Yaw , Amoah Adwoa Nyantakyiwaa , Liu Hong , Agboyibor Clement , Miao Lijun , Wang Jing , Wu Yongjun
Published: July 2020

Objectives

This study was designed to assess the awareness and knowledge of antibiotic usage and antibiotic resistance among the general public in the Cape Coast metropolis of Ghana. It also tries to decipher whether the level of education and the professional status of an individual has a positive association with the level of knowledge on antibiotic resistance.

Methods

A population-base survey involving members of the public was conducted from August to November 2019. A structured questionnaire was developed to collect data from 632 respondents. Data were analyzed through SPSS v.21 using Chi square statistics and multivariate regression. Differences in knowledge were evaluated using ANOVA and the assumption of equal variance was tested with Levene statistics.

Results

The response rate was 74.3%. Lower educational status group had a greater knowledge level (39.7%) on antibiotic resistance. Despite the high score, the lowest educational status group, (M = 1.82, SD = 0.769), middle educational status group (M = 1.98, SD = 0.748), and the high educational status group (M = 1.88, SD = 0.773) were not significantly different from each other with regard to their general knowledge level on antibiotic resistance (P < 0.05). The study revealed that, working in the healthcare sector is a major contributor to the level of knowledge on antibiotic resistance.

Conclusion

Given the scale of the issue on antibiotic resistance and the fact that attempts to resolve it will involve efforts on the part of all, it is important that the public is aware of the importance of the issue of antibiotic resistance, its implications and what they can do to address it. The level of knowledge among respondents with lower educational status should be enough evidence to introduce more educational campaigns on antibiotic resistance.
Universities as catalysts of social innovation in health systems in low-and middle-income countries: a multi-country case study
Authors: van Niekerk Lindi , Mathanga Don Pascal , Juban Noel , Castro-Arroyave Diana Maria , Balabanova Dina
Published: July 2020

Background

Social innovation (SI) in health holds potential to contribute to health systems strengthening and universal health coverage (UHC). The role of universities in SI has been well described in the context of high-income countries. An evidence gap exits on SI in healthcare delivery in the context of low- and middle-income countries (LMICs) as well as on the engagement of universities from these contexts. There is thus a need to build capacity for research and engagement in SI in healthcare delivery within these universities. The aim of this study was to examine the adoption and implementation of network of university hubs focused on SI in healthcare delivery within five countries across Africa, Asia and Latin America. The objectives were to describe the model, components and implementation process of the hubs; identify the enablers and barriers experienced and draw implications that could be relevant to other LMIC universities interested in SI.

Methods

A case study design was adopted to study the implementation process of a network of university hubs. Data from documentation, team discussions and post-implementation surveys were collected from 2013 to 2018 and analysed with aid of a modified policy analysis framework.

Results/discussion

SI university-based hubs serve as cross-disciplinary and cross-sectoral platforms, established to catalyse SI within the local health system through four core activities: research, community-building, storytelling and institutional embedding, and adhering to values of inclusion, assets, co-creation and hope. Hubs were implemented as informal structures, managed by a small core team, in existing department. Enablers of hub implementation and functioning were the availability of strong in-country social networks, legitimacy attained from being part of a global network on SI in health and receiving a capacity building package in the initial stages. Barriers encountered were internal institutional resistance, administrative challenges associated with university bureaucracy and annual funding cycles.

Conclusions

This case study shows the opportunity that reside within LMIC universities to act as eco-system enablers of SI in healthcare delivery in order to fill the evidence gap on SI and enhance cross-sectoral participation in support of achieving UHC.
Oral intermittent vitamin D substitution: influence of pharmaceutical form and dosage frequency on medication adherence: a randomized clinical trial
Authors: Rothen Jean-Pierre , Rutishauser Jonas , Walter Philipp N. , Hersberger Kurt E. , Arnet Isabelle
Published: July 2020

Background

To assess adherence to and preference for vitamin D substitution with different pharmaceutical forms and frequencies of administration.

Methods

A focus group of stakeholders aimed at preparing the design of an interventional, randomized, cross-over study with 2 × 2 groups obtaining monthly or weekly vitamin D products in liquid or solid form for 3 months each. Dosage corresponds to cumulated amount of recommended 800 IU daily (5.600 IU weekly / 24.000 IU monthly). Main inclusion criteria were a vitamin D serum value < 50 nmol/l and age ≥ 18 years. Primary endpoint was adherence, secondary endpoints were preferences and vitamin D serum levels.

Results

The focus group reached consensus for preference of a monthly administration of solid forms to adults.

Full datasets were obtained from 97 participants. Adherence was significantly higher with monthly (79.5–100.0%) than weekly (66.4–98.1%) administration. Vitamin D levels increased significantly (p < 0.001) in all participants. An optimal value of > 75 nmol/l was achieved by 32% after 3 months and by 50% after 6 months. Preferred formulation was solid form (tablets, capsules) for 71% of participants, and preferred dosage frequency was monthly for 39% of participants.

Conclusions

Monthly oral vitamin D in solid form lead to the highest adherence, and is preferred by the participants. However, only one third of study participants achieved values in the optimal range of > 75 nmol/l cholecalciferol using weekly or monthly administration providing an average daily cholecalciferol dose of 800 IU.

Trial registration

NCT03121593 | SNCTP000002251. Registered 30. May 2017,. Prospectively registered.
Predictability and controlling factors of overpressure in the North Alpine Foreland Basin, SE Germany: an interdisciplinary post-drill analysis of the Geretsried GEN-1 deep geothermal well
Authors: Drews Michael C. , Hofstetter Peter , Zosseder Kai , Shipilin Vladimir , Stollhofen Harald
Published: July 2020

The North Alpine Foreland Basin in SE Germany is Germany’s most active deep geothermal province. However, in its southern and eastern part the basin is considerably overpressured, which is a significant challenge for drilling deep geothermal wells. In this study, we combine drilling data and velocity-based pore pressure analyses with 3D basin modeling to assess the predictability and controlling factors of overpressure in the sub-regional context (area of 80 km × 50 km) around the Geretsried GEN-1 well, a deep geothermal exploration well in the southern part of the North Alpine Foreland Basin in SE Germany. Drilling data and velocity-based pore pressure analyses indicate overpressure maxima in the Lower Oligocene (Rupelian and Schoeneck Formation) and up to mild overpressure in the Upper Oligocene (Chattian) and Upper Cretaceous, except for the hydrostatically pressured northwestern part of the study area. 3D basin modeling calibrated to four hydrocarbon wells surrounding the Geretsried GEN-1 well demonstrates the dominating role of disequilibrium compaction and low permeability units related to overpressure generation in the North Alpine Foreland Basin. However, secondary overpressure generation mechanisms are likely contributing. Also, the impact of Upper Cretaceous shales, which are eroded in the northwestern part of the study area, on overpressure maintenance is investigated. The calibrated basin model is tested against the drilling history and velocity (VSP) data-based pore pressure estimate of the Geretsried GEN-1 well and reveals that pore pressure prediction is generally possible using 3D basin modeling in the North Alpine Foreland Basin, but should be improved with more detailed analysis of lateral drainage systems and facies variations in the future. The results of the study are of relevance to future well planning and drilling as well as to geomechanical modeling of subsurface stresses and deep geothermal production in the North Alpine Foreland Basin.
Saudi Arabia, pharmacists and COVID-19 pandemic
Authors: Ahmad Ajaz , Alkharfy Khalid M. , Alrabiah Ziyad , Alhossan Abdulaziz
Published: July 2020

The latest outbreak of Covid-19 pandemic has placed a significant effect on health care system around the world. This article discusses the role of pharmacists in Saudi Arabia during the current Covid-19 pandemic. Pharmacists are an important part of everyday healthcare in Saudi Arabia. Pharmacists helped to protect the public from Covid-19 pandemic disease by participating in various initiatives including health education and promotion, medication dispensing, medication reconciliation, medication and patient counselling, training for self-management in current outbreak and emergency preparedness. Full utilization of skills of pharmacists boosted the safety response of Saudi Arabia to Covid-19 pandemic.
AusLAMP 3D MT imaging of an intracontinental deformation zone, Musgrave Province, Central Australia
Authors: Thiel Stephan , Goleby Bruce R. , Pawley Mark J. , Heinson Graham
Published: July 2020

The central Australian Musgrave Province at the junction of the South, North and West Australian cratons has undergone and continues to retain evidence of significant whole-of-crust, and most likely ‘whole-of-lithosphere’ tectono-magmatic processes. The area is known for some of the largest geophysical anomalies related to significant Moho offsets of up to 15 km, which resulted from repeated intracratonic reworking since the Neoproterozoic. New magnetotelluric (MT) data have been collected across the Musgrave Province in Western Australia and South Australia as part of the Australian Lithospheric Architecture Magnetotelluric Project (AusLAMP). Station spacing was $$\sim 50\,\hbox {km}$$

∼
50

km

between 96 sites over an area of 500 × 700 km. Long-period MT impedance and tipper data over a bandwidth of 8 s to 10,000 s period have been inverted using a smooth 3D inverse algorithm. The 3D model shows two predominant resistivity trends. There are deep ($$>65\,\hbox {km}$$

>
65

km

) north–south mantle conductors that we infer to be related to the Palaeo- to Mesoproterozoic north-trending arc-related rocks that experienced ultra-high temperature metamorphism and widespread magmatism during the Mesoproterozoic Musgravian Orogeny. These conductors are preserved in the crust south of the Musgrave Province. The upper mantle also contains a localised resistive zone that possibly represents generation of mafic- to ultramafic magmas during the c. 1090–1040 Ma Giles Event. The crust ($$<65\,\hbox {km}$$

<
65

km

depth) contains strong east–west crustal conductors interpreted to reflect the east–west structural grain that initiated during the c. 1090–1040 Ma Giles Event and overprinted the older N–S-oriented mantle anomalies. These E–W crustal conductors coincide with magnetic anomalies that represent crustal-scale structures, and high gravity anomalies associated with significant Moho offsets resulting from further reactivation during the c. 630–520 Ma Petermann and c. 450–300 Ma Alice Springs orogenies.
Thoracoscopic repair of diaphragmatic hernia following ventricular assist device implantation
Authors: Saka Ryuta , Sakai Takaaki , Kanaya Tomomitsu , Tazuke Yuko , Kugo Yosuke , Taira Masaki , Ueno Takayoshi , Okuyama Hiroomi
Published: July 2020

Background

Diaphragmatic hernia is a rare complication of ventricular assist device (VAD), mainly developing after explantation of the device. We herein report a case of diaphragmatic hernia that developed following the implantation of VAD.

Case presentation

A 4-month-old girl with a diagnosis of dilated cardiomyopathy underwent VAD implantation for a bridge to heart transplantation. Three months later, intermittent vomiting developed, and left-sided diaphragmatic hernia was confirmed on plain X-ray and computed tomography. Without any findings of ischemia, we performed elective thoracoscopic repair of the diaphragmatic hernia. In the right decubitus position, thoracoscopy revealed the small intestine to be herniated into the left thorax. After reduction of the herniated intestine, the defect of the diaphragm (3 × 2 cm in size) was directly closed with interrupted non-absorbable sutures. Her postoperative course was uneventful.

Conclusion

Thoracoscopic repair of diaphragmatic hernia associated with VAD implantation may be a safe approach.