bluuebunny/crossref_metadata_2025 huggingface dataset:
Current and Emerging Methods for the Synthesis of Single-Stranded DNA
Authors: Hao Min , Qiao Jianjun , Qi Hao
Published: January 2020

Methods for synthesizing arbitrary single-strand DNA (ssDNA) fragments are rapidly becoming fundamental tools for gene editing, DNA origami, DNA storage, and other applications. To meet the rising application requirements, numerous methods have been developed to produce ssDNA. Some approaches allow the synthesis of freely chosen user-defined ssDNA sequences to overcome the restrictions and limitations of different length, purity, and yield. In this perspective, we provide an overview of the representative ssDNA production strategies and their most significant challenges to enable the readers to make informed choices of synthesis methods and enhance the availability of increasingly inexpensive synthetic ssDNA. We also aim to stimulate a broader interest in the continued development of efficient ssDNA synthesis techniques and improve their applications in future research.
Using Mixed Probability Distribution Functions for Modelling Non-Zero Sub-Daily Rainfall in Australia
Authors: Hasan Md Masud , Croke Barry F. W. , Liu Shuangzhe , Shimizu Kunio , Karim Fazlul
Published: January 2020

Probabilistic models for sub-daily rainfall predictions are important tools for understanding catchment hydrology and estimating essential rainfall inputs for agricultural and ecological studies. This research aimed at achieving theoretical probability distribution to non-zero, sub-daily rainfall using data from 1467 rain gauges across the Australian continent. A framework was developed for estimating rainfall data at ungauged locations using the fitted model parameters from neighbouring gauges. The Lognormal, Gamma and Weibull distributions, as well as their mixed distributions were fitted to non-zero six-minutes rainfall data. The root mean square error was used to evaluate the goodness of fit for each of these distributions. To generate data at ungauged locations, parameters of well-fit models were interpolated from the four closest neighbours using inverse weighting distance method. Results show that the Gamma and Weibull distributions underestimate and lognormal distributions overestimate the high rainfall events. In general, a mixed model of two distributions was found better compared to the results of an individual model. Among the five models studied, the mixed Gamma and Lognormal (G-L) distribution produced the minimum root mean square error. The G-L model produced the best match to observed data for high rainfall events (e.g., 90th, 95th, 99th, 99.9th and 99.99th percentiles).
Review of Explosive Hydrovolcanism
Authors: Németh Károly , Kósik Szabolcs
Published: January 2020

Hydrovolcanism is a type of volcanism where magma and water interact either explosively or non-explosively. The less frequently used term, hydromagmatism, includes all the processes responsible for magma and water interaction in a magmatic system. Hydrovolcanism is commonly used as a synonym for phreatomagmatism. However, in recent years phreatomagmatism appears more in association with volcanic eruptions that occur in shallow subaqueous or terrestrial settings and commonly involves molten fuel-coolant interaction (MFCI) driven processes. Here a revised and reviewed classification scheme is suggested on the basis of the geo-environment in which the magma-water interaction takes place and the explosivity plus mode of energy transfer required to generate kinetic energy to produce pyroclasts. Over the past decade researchers have focused on the role hydrovolcanism/phreatomagmatism plays in the formation of maar craters, the evolution of diatremes and the signatures of magma—water interaction in the geological record. In the past five years, lithofacies-characterization is the most common approach to studying hydrovolcanism. By far mafic monogenetic volcanic fields generated the greatest number of research results. Significant knowledge gaps are identified, especially in developing tools to identify the textural signatures hydrovolcanism leave behind on eruptive products and exploring the role of hydrovolcanism in the growth of intermediate and silicic small volume volcanoes.
Big Data Analytics and Sensor-Enhanced Activity Management to Improve Effectiveness and Efficiency of Outpatient Medical Rehabilitation
Authors: Jones Mike , Collier George , Reinkensmeyer David J. , DeRuyter Frank , Dzivak John , Zondervan Daniel , Morris John
Published: January 2020

Numerous societal trends are compelling a transition from inpatient to outpatient venues of care for medical rehabilitation. While there are advantages to outpatient rehabilitation (e.g., lower cost, more relevant to home and community function), there are also challenges including lack of information about how patient progress observed in the outpatient clinic translates into improved functional performance at home. At present, outpatient providers must rely on patient-reported information about functional progress (or lack thereof) at home and in the community. Information and communication technologies (ICT) offer another option—data collected about the patient’s adherence, performance and progress made on home exercises could be used to help guide course corrections between clinic visits, enhancing effectiveness and efficiency of outpatient care. In this article, we describe our efforts to explore use of sensor-enhanced home exercise and big data analytics in medical rehabilitation. The goal of this work is to demonstrate how sensor-enhanced exercise can improve rehabilitation outcomes for patients with significant neurological impairment (e.g., from stroke, traumatic brain injury, and spinal cord injury). We provide an overview of big data analysis and explain how it may be used to optimize outpatient rehabilitation, creating a more efficient model of care. We describe our planned development efforts to build advanced analytic tools to guide home-based rehabilitation and our proposed randomized trial to evaluate effectiveness and implementation of this approach.
Implementation of KEIGAAF in Primary Schools: A Mutual Adaptation Physical Activity and Nutrition Intervention
Authors: Verjans-Janssen Sacha R.B. , Gerards Sanne M.P.L. , Verhees Anke H. , Kremers Stef P.J. , Vos Steven B. , Jansen Maria W.J. , Van Kann Dave H.H.
Published: January 2020

School health promotion is advocated. Implementation studies on school health promotion are less often conducted as effectiveness studies and are mainly conducted conventionally by assessing fidelity of “one size fits all” interventions. However, interventions that allow for local adaptation are more appropriate and require a different evaluation approach. We evaluated a mutual adaptation physical activity and nutrition intervention implemented in eight primary schools located in low socioeconomic neighborhoods in the Netherlands, namely the KEIGAAF intervention. A qualitative, multiple-case study design was used to evaluate implementation and contextual factors affecting implementation. We used several qualitative data collection tools and applied inductive content analysis for coding the transcribed data. Codes were linked to the domains of the Consolidated Framework for Implementation Research. NVivo was used to support data analysis. The implementation process varied greatly across schools. This was due to the high level of bottom-up design of the intervention and differing contextual factors influencing implementation, such as differing starting situations. The mutual adaptation between top-down and bottom-up influences was a key element of the intervention. Feedback loops and the health promotion advisors played a crucial role by navigating between top-down and bottom-up. Implementing a mutual adaptation intervention is time-consuming but feasible.
Train Like You Compete? Physical and Physiological Responses on Semi-Professional Soccer Players
Authors: Castillo-Rodríguez Alfonso , Cano-Cáceres Francisco Javier , Figueiredo António , Fernández-García José Carlos
Published: January 2020

Background: Decision-making in soccer has repercussions and depends on the environment of training or competition. The demands on the players can reveal if the decision-making is similar or different from that required during competition. Objectives: The aim of this study was to assess the physical and physiological responses of players in training matches (TM) and official competition matches (CM) according to the playing position (external defenders, internal defenders, midfielders, and forwards/extremes). Methods: Twenty semi-professional male soccer players and 10 CM (n = 40) and 10 TM (n = 40) were studied using global positioning system technology, and paired and one-way ANOVA tests were carried out to compare physical (distances and number of sprints) and physiological (heart rates) responses with the factors a) match environments (TM and CM) and b) the playing position, respectively. Results: The results revealed that during CM, players covered higher total distance, partial distances, and sprints at different speeds (0–21 km/h) and produced higher physiological responses. Midfielders covered the greatest total distance in both TM (7227.6 m) and CM (11,225.9 m), in comparison to the other playing positions. However, forwards and extremes spent more time (56.8% of the CM [d = 0.78]) at 76% to 84% of their maximal heart rates. Conclusions: First, the physical and physiological responses in TM were significantly lower than in CM. Second, these responses were different according to the playing position, so this study was able to verify the exact amount of variation between the load produced in TM and CM. These results will help the coach and technical staff to design training tasks to complement the responses found in TM.
Spatial Analysis of Seasonal Precipitation over Iran: Co-Variation with Climate Indices
Authors: Dehghani Majid , Salehi Somayeh , Mosavi Amir , Nabipour Narjes , Shamshirband Shahaboddin , Ghamisi Pedram
Published: January 2020

Temporary changes in precipitation may lead to sustained and severe drought or massive floods in different parts of the world. Knowing the variation in precipitation can effectively help the water resources decision-makers in water resources management. Large-scale circulation drivers have a considerable impact on precipitation in different parts of the world. In this research, the impact of El Niño-Southern Oscillation (ENSO), Pacific Decadal Oscillation (PDO), and North Atlantic Oscillation (NAO) on seasonal precipitation over Iran was investigated. For this purpose, 103 synoptic stations with at least 30 years of data were utilized. The Spearman correlation coefficient between the indices in the previous 12 months with seasonal precipitation was calculated, and the meaningful correlations were extracted. Then, the month in which each of these indices has the highest correlation with seasonal precipitation was determined. Finally, the overall amount of increase or decrease in seasonal precipitation due to each of these indices was calculated. Results indicate the Southern Oscillation Index (SOI), NAO, and PDO have the most impact on seasonal precipitation, respectively. Additionally, these indices have the highest impact on the precipitation in winter, autumn, spring, and summer, respectively. SOI has a diverse impact on winter precipitation compared to the PDO and NAO, while in the other seasons, each index has its special impact on seasonal precipitation. Generally, all indices in different phases may decrease the seasonal precipitation up to 100%. However, the seasonal precipitation may increase more than 100% in different seasons due to the impact of these indices. The results of this study can be used effectively in water resources management and especially in dam operation.
Effects of Natural Progesterone and Synthetic Progestin on Germ Layer Gene Expression in a Human Embryoid Body Model
Authors: Kim Yoon Young , Kim Hoon , Suh Chang Suk , Liu Hung-Ching , Rosenwaks Zev , Ku Seung-Yup
Published: January 2020

Natural progesterone and synthetic progestin are widely used for the treatment of threatened abortion or in in vitro fertilization (IVF) cycles. This in vitro study aimed to assess whether the treatment with natural progesterone or synthetic progestin influences the germ layer gene expression on the early human embryonic development using human embryonic stem cells (hESCs)-derived embryoid bodies (hEBs) as a surrogate of early stage human embryonic development. Human EBs derived from hESCs were cultured for nine days, and were treated with natural progesterone (P4) or synthetic progestin, medroxyprogesterone acetate (MPA) at 10–7 M for five days. To reverse the effects of treatment, mifepristone (RU486) as progesterone antagonist was added to the hEBs for four days starting one day after the initiation of treatment. Mouse blastocysts (mBLs) were cultured in vitro for 24 h, and P4 or MPA at 10−7 M was treated for an additional 24 h. The treated embryos were further transferred onto in vitro cultured endometrial cells to evaluate chorionic gonadotropin (CG) expression. To analyze the effects of P4 or MPA, the expression of differentiation genes representing the three germ layers was investigated, GATA-binding factor 4 (GATA4), α-fetoprotein (AFP), hepatocyte nuclear factor (HNF)-3β, hepatocyte nuclear factor (HNF)-4α (endoderm), Brachyury, cardiac actin (cACT) (mesoderm), and Nestin (ectoderm), using quantitative reverse transcription PCR (qRT-PCR) and immunostaining. Significantly lower expressions of HNF-3β, HNF-4α, Brachyury, and Nestin were observed in MPA-treated hEBs (all p < 0.05), which was negated by RU486 treatment. This inhibitory effect of MPA was also observed in mouse embryos. Conclusively, the effects of natural progesterone and synthetic progestin may differ in the germ layer gene expression in the hEB model, which suggests that caution is necessary in the use of progestogen.
Activities of Chromatin Remodeling Factors and Histone Chaperones and Their Effects in Root Apical Meristem Development
Authors: Kang Huijia , Wu Di , Fan Tianyi , Zhu Yan
Published: January 2020

Eukaryotic genes are packaged into dynamic but stable chromatin structures to deal with transcriptional reprogramming and inheritance during development. Chromatin remodeling factors and histone chaperones are epigenetic factors that target nucleosomes and/or histones to establish and maintain proper chromatin structures during critical physiological processes such as DNA replication and transcriptional modulation. Root apical meristems are vital for plant root development. Regarding the well-characterized transcription factors involved in stem cell proliferation and differentiation, there is increasing evidence of the functional implications of epigenetic regulation in root apical meristem development. In this review, we focus on the activities of chromatin remodeling factors and histone chaperones in the root apical meristems of the model plant species Arabidopsis and rice.
Transcriptome Analysis Reveals the Different Response to Toxic Stress in Rootstock Grafted and Non-Grafted Cucumber Seedlings
Authors: Xiao Xuemei , Lv Jian , Xie Jianming , Feng Zhi , Ma Ning , Li Ju , Yu Jihua , Calderón-Urrea Alejandro
Published: January 2020

Autotoxicity of root exudates is one of the main reasons for consecutive monoculture problem (CMP) in cucumber under greenhouse cultivation. Rootstock grafting may improve the tolerance of cucumber plants to autotoxic stress. To verify the enhanced tolerance to autotoxic stress and illuminate relevant molecular mechanism, a transcriptomic comparative analysis was performed between rootstock grafted (RG) and non-grafted (NG) cucumber plants by a simulation of exogenous cinnamic acid (CA). The present study confirmed that relatively stable plant growth, biomass accumulation, chlorophyll content, and photosynthesis was observed in RG than NG under CA stress. We identified 3647 and 2691 differentially expressed genes (DEGs) in NG and RG cucumber plants when compared to respective control, and gene expression patterns of RNA-seq was confirmed by qRT-PCR. Functional annotations revealed that DEGs response to CA stress were enriched in pathways of plant hormone signal transduction, MAPK signaling pathway, phenylalanine metabolism, and plant-pathogen interaction. Interestingly, the significantly enriched pathway of photosynthesis-related, carbon and nitrogen metabolism only identified in NG, and most of DEGs were down-regulated. However, most of photosynthesis, Calvin cycle, glycolysis, TCA cycle, and nitrogen metabolism-related DEGs exhibited not or slightly down-regulated in RG. In addition, several stress-related transcription factor families of AP2/ERF, bHLH, bZIP, MYB. and NAC were uniquely triggered in the grafted cucumbers. Overall, the results of this study suggest that rootstock grafting improve the tolerance of cucumber plants to autotoxic stress by mediating down-regulation of photosynthesis, carbon, and nitrogen metabolism-related DEGs and activating the function of stress-related transcription factor. The transcriptome dataset provides an extensive sequence resource for further studies of autotoxic mechanism at molecular level.
Noncovalent Sericin-Chitosan Scaffold: Physical Properties and Low Cytotoxicity Effect
Authors: Chollakup Rungsima , Uttayarat Pimporn , Chworos Arkadiusz , Smitthipong Wirasak
Published: January 2020

This research aims to utilize sericin, which is the waste from boiling silk cocoon, for the supramolecular scaffold preparation with chitosan. A suitable method for the self-assembled scaffold formation of sericin and chitosan at 1:1 stoichiometry is presented and the morphological and physical properties of the scaffold are studied. The effect of an alcohol/NaOH solution on the secondary structure of sericin protein within the sericin-chitosan scaffold, with adjusted pH, was investigated. Additionally, the scaffold was tested in a native phosphate buffer solution (PBS). The results show that sericin increases the porosity of scaffold while chitosan increases the rigidity. The self-assembled sericin and chitosan material is nontoxic to human cells and which can adhere and spread well on such support. For the effect of the molecular weight of chitosan (15,000 and 100,000 g/mol), the scaffold made from lower molecular weight (MW) chitosan provides a somewhat smaller porosity, but a similar swelling ratio and water uptake. On the basis of this research, sericin, which is a silk waste from the textile industry, can be utilized to produce a self-assembled scaffold with chitosan in order to increase the porosity of the scaffold. This type of scaffold is not toxic and can be used for the adhesion of fibroblast cells.
Screening Readthrough Compounds to Suppress Nonsense Mutations: Possible Application to β-Thalassemia
Authors: Borgatti Monica , Altamura Emiliano , Salvatori Francesca , D’Aversa Elisabetta , Altamura Nicola
Published: January 2020

Several types of thalassemia (including β039-thalassemia) are caused by nonsense mutations in genes controlling globin production, leading to premature translation termination and mRNA destabilization mediated by the nonsense mediated mRNA decay. Drugs (for instance, aminoglycosides) can be designed to suppress premature translation termination by inducing readthrough (or nonsense suppression) at the premature termination codon. These findings have introduced new hopes for the development of a pharmacologic approach to cure this genetic disease. In the present review, we first summarize the principle and current status of the chemical relief for the expression of functional proteins from genes otherwise unfruitful for the presence of nonsense mutations. Second, we compare data available on readthrough molecules for β0-thalassemia. The examples reported in the review strongly suggest that ribosomal readthrough should be considered as a therapeutic approach for the treatment of β0-thalassemia caused by nonsense mutations. Concluding, the discovery of molecules, exhibiting the property of inducing β-globin, such as readthrough compounds, is of great interest and represents a hope for several patients, whose survival will depend on the possible use of drugs rendering blood transfusion and chelation therapy unnecessary.
Differences in Aortopathy in Patients with a Bicuspid Aortic Valve with or without Aortic Coarctation
Authors: Duijnhouwer Anthonie , van den Hoven Allard , Merkx Remy , Schokking Michiel , van Kimmenade Roland , Kempers Marlies , van Dijk Arie , de Boer Menko-Jan , Roos-Hesselink Jolien
Published: January 2020

Objective: The combination of aortic coarctation (CoA) and bicuspid aortic valve (BAV) is assumed to be associated with a higher risk of ascending aortic dilatation and type A dissection, and current European Society of Cardiology (ESC) guidelines advise therefore to operate at a lower threshold in the presence of CoA. The aim of our study is to evaluate whether the coexistence of CoA in BAV patients is indeed associated with a higher risk of ascending aortic events (AAE). Methods: In a retrospective study, all adult BAV patients visiting the outpatient clinic of our tertiary care center between February 2003 and February 2019 were included. The primary end point was an ascending aortic event (AAE) defined as ascending aortic dissection/rupture or preventive surgery. The secondary end points were aortic dilatation and aortic growth. Results: In total, 499 BAV patients (43.7% female, age 40.3 ± 15.7 years) were included, of which 121 (24%) had a history of CoA (cBAV). An aortic event occurred in 38 (7.6%) patients at a mean age of 49.0 ± 13.6 years. In the isolated BAV group (iBAV), significantly more AAE occurred, but this was mainly driven by aortic valve dysfunction as indication for aortic surgery. There was no significant difference in the occurrence of dissection or severely dilated ascending aorta (>50 mm) between the iBAV and cBAV patients (p = 0.56). The aortic diameter was significantly smaller in the cBAV group (30.3 ± 6.9 mm versus 35.7 ± 7.6 mm; p < 0.001). The median aortic diameter increase was 0.23 (interquartile range (IQR): 0.0–0.67) mm/year and was not significantly different between both groups (p = 0.74). Conclusion: Coexistence of CoA in BAV patients was not associated with a higher risk of aortic dissection, preventive aortic surgery, aortic dilatation, or more rapid aorta growth. This study suggests that CoA is not a risk factor in BAV patients, and the advice to operate at lower diameter should be reevaluated.
Manipulating the Perceived Shape and Color of a Virtual Limb Can Modulate Pain Responses
Authors: Matamala-Gomez Marta , Nierula Birgit , Donegan Tony , Slater Mel , Sanchez-Vives Maria V.
Published: January 2020

Changes in body representation may affect pain perception. The effect of a distorted body image, such as the telescoping effect in amputee patients, on pain perception, is unclear. This study aimed to investigate whether distorting an embodied virtual arm in virtual reality (simulating the telescoping effect in amputees) modulated pain perception and anticipatory responses to pain in healthy participants. Twenty-seven right-handed participants were immersed in virtual reality and the virtual arm was shown with three different levels of distortion with a virtual threatening stimulus either approaching or contacting the virtual hand. We evaluated pain/discomfort ratings, ownership, and skin conductance responses (SCRs) after each condition. Viewing a distorted virtual arm enhances the SCR to a threatening event with respect to viewing a normal control arm, but when viewing a reddened-distorted virtual arm, SCR was comparatively reduced in response to the threat. There was a positive relationship between the level of ownership over the distorted and reddened-distorted virtual arms with the level of pain/discomfort, but not in the normal control arm. Contact with the threatening stimulus significantly enhances SCR and pain/discomfort, while reduced SCR and pain/discomfort were seen in the simulated-contact condition. These results provide further evidence of a bi-directional link between body image and pain perception.
Adjustable Versus Nonadjustable Sutures in Strabismus Surgery—Who Benefits the Most?
Authors: Gawęcki Maciej
Published: January 2020

Background: Adjustable sutures have been used in strabismus surgery for more than 40 years, but controversy remains regarding their application. This review sought to analyze studies comparing the efficacy of adjustable sutures (AS) and nonadjustable sutures (NAS) in the treatment of different ocular deviations. Materials and Methods: The PubMed literature database was searched using the keywords ‘adjustable sutures’ and ‘strabismus surgery’, yielding a total of 209 results. Only comparative studies were extracted, and the results were divided into three categories: Adult comitant strabismus, childhood comitant strabismus, and paretic/restrictive strabismus. Results: The search revealed eleven comparative studies on AS versus NAS in adult strabismus, including only one randomized controlled trial. Five of these studies analyzed just the postoperative success rate, three studies analyzed just the reoperation rate, two studies analyzed both the postoperative success and reoperation rates, and one study evaluated achievement of the postoperative target angle. Three of seven studies analyzing postoperative success reported the statically significant superiority of AS over NAS, while four of five studies analyzing reoperation rate indicated a significantly smaller percentage of reoperations with the use of AS. The study covering postoperative target angle as an outcome favored the AS technique. Separately, the search revealed three comparative studies on AS versus NAS in childhood strabismus, one of which reported a statistically significant advantage with AS. Only four comparative studies on AS versus NAS in paretic or restrictive strabismus were found; all showed a tendency for better results with the use of AS but not in a statistically significant fashion. Overall, out of 18 studies analyzed in this review, 17 suggested better clinical results followed the application of AS versus NAS; however, only a minority had statistically significant results. Conclusion: The analysis of available research failed to support AS as the preferable surgery technique over NAS in cases of simple and predictive strabismus. Further research is needed to more precisely determine the group of patients able to benefit the most from AS.
Female Specific Association of Low Insulin-Like Growth Factor 1 (IGF1) Levels with Increased Risk of Premature Mortality in Renal Transplant Recipients
Authors: Klont Frank , Kieneker Lyanne M. , Gomes-Neto Antonio W. , Stam Suzanne P. , ten Hacken Nick H. T. , Kema Ido P. , van Beek André P. , van den Berg Else , Horvatovich Péter , Bischoff Rainer , Bakker Stephan J. L.
Published: January 2020

Associations between insulin-like growth factor 1 (IGF1) and mortality have been reported to be female specific in mice and in human nonagenarians. Intervention in the growth hormone (GH)-IGF1 axis may particularly benefit patients with high risk of losing muscle mass, including renal transplant recipients (RTR). We investigated whether a potential association of circulating IGF1 with all-cause mortality in stable RTR could be female specific and mediated by variation in muscle mass. To this end, plasma IGF1 levels were measured in 277 female and 343 male RTR by mass spectrometry, and their association with mortality was assessed by Cox regression. During a median follow-up time of 5.4 years, 56 female and 77 male RTR died. In females, IGF1 was inversely associated with risk (hazard ratio (HR) per 1-unit increment in log2-transformed (doubling of) IGF1 levels, 95% confidence interval (CI)) of mortality (0.40, 0.24–0.65; p < 0.001), independent of age and the estimated Glomerular filtration rate (eGFR). In equivalent analyses, no significant association was observed for males (0.85, 0.56–1.29; p = 0.44), for which it should be noted that in males, age was negatively and strongly associated with IGF1 levels. The association for females remained materially unchanged upon adjustment for potential confounders and was furthermore found to be mediated for 39% by 24 h urinary creatinine excretion. In conclusion, low IGF1 levels associate with an increased risk of all-cause mortality in female RTR, which may link to conditions of low muscle mass that are known to be associated with poor outcomes in transplantation patients. For males, the strongly negative association of age with IGF1 levels may explain why low IGF1 levels were not found to be associated with an increased risk of all-cause mortality.
Role and Mechanism of LIF in Oral Squamous Cell Carcinoma Progression
Authors: Lin Ting-An , Wu Tai-Sheng , Li Yue-Ju , Yang Cheng-Ning , Illescas Ralda Monica Maria , Chang Hao-Hueng
Published: January 2020

Background: Metastasis is a severe problem in patients with oral squamous cell carcinoma (OSCC), which is the fifth most common cancer worldwide. Leukemia inhibitory factor (LIF) has been studied in different cancers, while the role of LIF in OSCC remains unclear. Methods: LIF expression was detected in 100 OSCC samples by immunohistochemistry. Effects of LIF on cell motility were evaluated in OSCC cell lines. High-throughput microarray analysis was also conducted. The correlation between LIF and the downstream effector was analyzed by real-time quantitative reverse transcription PCR. Results: Patients with OSCC who had lymph node metastasis or advanced cancer stages showed high LIF expression. OSCC patients with higher LIF expression, advanced stage, large tumor size, or lymph node metastasis had significantly shorter overall survival. LIF regulated cancer cell motilities through outside-in signaling. The inhibin beta A subunit (INHBA) gene was identified as a crucial downstream effector of LIF-promoted OSCC progression and restored migration and invasion abilities in LIF knockdown transfectants. Conclusion: LIF enhances regional lymphatic spread, thus leading to an advanced cancer stage. Regulation of LIF downstream molecules such as INHBA inhibits the invasion or migration ability of cancer cells. Thus, LIF can be a potential target in preventing cancer metastasis and spread.
The Effect of the Paleolithic Diet vs. Healthy Diets on Glucose and Insulin Homeostasis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Jamka Małgorzata , Kulczyński Bartosz , Juruć Agata , Gramza-Michałowska Anna , Stokes Caroline S. , Walkowiak Jarosław
Published: January 2020

Recently, the Paleolithic diet became popular due to its possible health benefits. Several, albeit not all, studies suggested that the consumption of the Paleolithic diet might improve glucose tolerance, decrease insulin secretion, and increase insulin sensitivity. Therefore, the aim of this meta-analysis was to compare the effect of the Paleolithic diet with other types of diets on glucose and insulin homeostasis in subjects with altered glucose metabolism. Four databases (PubMed, Web of Sciences, Scopus, and the Cochrane Library) were searched to select studies in which the effects of the Paleolithic diet on fasting glucose and insulin levels, glycated hemoglobin (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), and area under the curve (AUC 0–120) for glucose and insulin during the oral glucose tolerance test were assessed. In total, four studies with 98 subjects which compared the effect of the Paleolithic diet with other types of diets (the Mediterranean diet, diabetes diet, and a diet recommended by the Dutch Health Council) were included in this meta-analysis. The Paleolithic diet did not differ from other types of diets with regard to its effect on fasting glucose (standardized mean difference (SMD): −0.343, 95% confidence interval (CI): −0.867, 0.181, p = 0.200) and insulin (SMD: −0.141; 95% CI: −0.599, 0.318; p = 0.548) levels. In addition, there were no differences between the Paleolithic diet and other types of diets in HOMA-IR (SMD: −0.151; 95% CI: −0.610, 0.309; p = 0.521), HbA1c (SMD: −0.380; 95% CI: −0.870, 0.110; p = 0.129), AUC 0–120 glucose (SMD: −0.558; 95% CI: −1.380, 0.264; p = 0.183), and AUC 0–120 insulin (SMD: −0.068; 95% CI: −0.526, 0.390; p = 0.772). In conclusion, the Paleolithic diet did not differ from other types of diets commonly perceived as healthy with regard to effects on glucose and insulin homeostasis in subjects with altered glucose metabolism.
Improved Left Atrial Function in CRT Responders: A Systematic Review and Meta-Analysis
Authors: Bytyçi Ibadete , Bajraktari Gani , Lindqvist Per , Henein Michael Y.
Published: January 2020

Cardiac resynchronization therapy (CRT) is associated with reverse left atrial (LA) remodeling. The aim of this meta-analysis was to assess the relationship between clinical response to CRT and LA function changes. We conducted a systematic search of all electronic databases up to September 2019 which identified 488 patients from seven studies. At (mean) 6 months follow-up, LA systolic strain and emptying fraction (EF) were increased in CRT responders, with a −5.70% weighted mean difference (WMD) [95% confidence interval (CI) −8.37 to −3.04, p < 0.001 and a WMD of −8.98% [CI −15.1 to −2.84, p = 0.004], compared to non-responders. The increase in LA strain was associated with a fall in left ventricle (LV) end-systolic volume (LVESV) r = −0.56 (CI −0.68 to −0.40, p < 0.001) and an increase in the LV ejection fraction (LVEF) r = 0.58 (CI 0.42 to 0.69, p < 0.001). The increase in LA EF correlated with the fall in LVESV r = −0.51 (CI −0.63 to −0.36, p < 0.001) and the increase in the LVEF r = 0.48 (CI 0.33 to 0.61, p = 0.002). The increase in LA strain correlated with the increase in the LA EF, r = 0.57 (CI 0.43 to 0.70, p < 0.001). Thus, the improvement of LA function in CRT responders reflects LA reverse remodeling and is related to its ventricular counterpart.
Increased Diagnostic Accuracy of Adnexal Tumors with A Combination of Established Algorithms and Biomarkers
Authors: Lycke Maria , Ulfenborg Benjamin , Kristjansdottir Björg , Sundfeldt Karin
Published: January 2020

Ovarian cancer is the most lethal gynecologic cancer. Pre-diagnostic testing lacks sensitivity and specificity, and surgery is often the only way to secure the diagnosis. Exploring new biomarkers is of great importance, but the rationale of combining validated well-established biomarkers and algorithms could be a more effective way forward. We hypothesized that we can improve differential diagnostics and reduce false positives by combining (a) risk of malignancy index (RMI) with serum HE4, (b) risk of ovarian malignancy algorithm (ROMA) with a transvaginal ultrasound score or (c) adding HE4 to CA125 in a simple algorithm. With logistic regression modeling, new algorithms were explored and validated using leave-one-out cross validation. The analyses were performed in an existing cohort prospectively collected prior to surgery, 2013–2016. A total of 445 benign tumors and 135 ovarian cancers were included. All presented models improved specificity at cut-off compared to the original algorithm, and goodness of fit was significant (p < 0.001). Our findings confirm that HE4 is a marker that improves specificity without hampering sensitivity or diagnostic accuracy in adnexal tumors. We provide in this study “easy-to-use” algorithms that could aid in the triage of women to the most appropriate level of care when presenting with an unknown ovarian cyst or suspicious ovarian cancer.
Genetic Landscape of Nonobstructive Azoospermia and New Perspectives for the Clinic
Authors: Cerván-Martín Miriam , Castilla José A. , Palomino-Morales Rogelio J. , Carmona F. David
Published: January 2020

Nonobstructive azoospermia (NOA) represents the most severe expression of male infertility, involving around 1% of the male population and 10% of infertile men. This condition is characterised by the inability of the testis to produce sperm cells, and it is considered to have an important genetic component. During the last two decades, different genetic anomalies, including microdeletions of the Y chromosome, karyotype defects, and missense mutations in genes involved in the reproductive function, have been described as the primary cause of NOA in many infertile men. However, these alterations only explain around 25% of azoospermic cases, with the remaining patients showing an idiopathic origin. Recent studies clearly suggest that the so-called idiopathic NOA has a complex aetiology with a polygenic inheritance, which may alter the spermatogenic process. Although we are far from a complete understanding of the molecular mechanisms underlying NOA, the use of the new technologies for genetic analysis has enabled a considerable increase in knowledge during the last years. In this review, we will provide a comprehensive and updated overview of the genetic basis of NOA, with a special focus on the possible application of the recent insights in clinical practice.
Affinity-Enhanced CTC-Capturing Hydrogel Microparticles Fabricated by Degassed Mold Lithography
Authors: Lee Nak Jun , Maeng Sejung , Kim Hyeon Ung , Roh Yoon Ho , Hwang Changhyun , Kim Jongjin , Hwang Ki-Tae , Bong Ki Wan
Published: January 2020

Technologies for the detection and isolation of circulating tumor cells (CTCs) are essential in liquid biopsy, a minimally invasive technique for early diagnosis and medical intervention in cancer patients. A promising method for CTC capture, using an affinity-based approach, is the use of functionalized hydrogel microparticles (MP), which have the advantages of water-like reactivity, biologically compatible materials, and synergy with various analysis platforms. In this paper, we demonstrate the feasibility of CTC capture by hydrogel particles synthesized using a novel method called degassed mold lithography (DML). This technique increases the porosity and functionality of the MPs for effective conjugation with antibodies. Qualitative fluorescence analysis demonstrates that DML produces superior uniformity, integrity, and functionality of the MPs, as compared to conventional stop flow lithography (SFL). Analysis of the fluorescence intensity from porosity-controlled MPs by each reaction step of antibody conjugation elucidates that more antibodies are loaded when the particles are more porous. The feasibility of selective cell capture is demonstrated using breast cancer cell lines. In conclusion, using DML for the synthesis of porous MPs offers a powerful method for improving the cell affinity of the antibody-conjugated MPs.
Comparison between Micro-Computed Tomography and Cone-Beam Computed Tomography in the Assessment of Bone Quality and a Long-Term Volumetric Study of the Augmented Sinus Grafted with an Albumin Impregnated Allograft
Authors: Kivovics Márton , Szabó Bence Tamás , Németh Orsolya , Iványi Dóra , Trimmel Bálint , Szmirnova Ilona , Orhan Kaan , Mijiritsky Eitan , Szabó György , Dobó-Nagy Csaba
Published: January 2020

The purpose of our study was to compare micromorphometric data obtained by cone-beam computed-tomography (CBCT) and microcomputed-tomography (micro-CT) of the augmented sinus and to evaluate the long-term stability of the bone gain achieved using BoneAlbumin. Sinus lifts, and after 6-months, healing bone-biopsy and implant placement were carried out. Specimens were analyzed by micro-CT. A total of 16 samples were collected from nine patients (mean age 54.7 ± 6.5 years). Pre-, postoperative, and 3-year control CBCT-data were registered to determine from where the biopsy samples were harvested. Micromorphometric variables were calculated from the micro-CT- and CBCT-data, and their correlation was determined by Spearman’s test. The volume of augmented bone was calculated at the time of implant placement and after 3 years. A positive correlation was found between bone-volume fraction, trabecular-separation, open-, and total-porosity, while a negative correlation was found between trabecular-thickness obtained from CBCT- and micro-CT-data (p < 0.05). Mean volumetric reduction of 39.28% (11.88–60.02%) was observed. Correlation of CBCT- and micro-CT-data suggested that micromorphometric analysis of CBCT reconstructions of the augmented sinuses provided reliable information on the microarchitecture of augmented bone. CBCT as a modality might be adequate in the analysis of bone quality in the augmented sinus. At the 3-year, control sinus grafts showed volumetric stability.
Surrogate Markers of Neutrophil Extracellular Trap Formation are Associated with Ischemic Outcomes and Platelet Activation after Peripheral Angioplasty and Stenting
Authors: Demyanets Svitlana , Stojkovic Stefan , Mauracher Lisa-Marie , Kopp Christoph W. , Wojta Johann , Thaler Johannes , Panzer Simon , Gremmel Thomas
Published: January 2020

Neutrophil extracellular traps (NETs) are supposed to play a central role in atherothrombosis. We measured circulating citrullinated histone H3 (H3Cit) and cell-free DNA (cfDNA), which serve as surrogate markers of NET formation, in 79 patients with peripheral artery disease (PAD) following infrainguinal angioplasty with stent implantation. Analysis of cfDNA and H3Cit was performed using Quant-iT™ PicoGreen® dsDNA Assay Kit or an ELISA, respectively. Within two years of follow-up, the primary endpoint defined as nonfatal myocardial infarction, stroke or transient ischemic attack, cardiovascular death, and >80% target vessel restenosis occurred in 34 patients (43%). Both H3Cit (HR per 1-SD: 2.72; 95% CI: 1.2–6.3; p = 0.019) and cfDNA (HR per 1-SD: 2.15; 95% CI: 1.1–4.2; p = 0.028) were associated with the primary endpoint in a univariate Cox regression analysis. Multivariate linear regression analyses showed associations between cfDNA and platelet surface expression of P-selectin (p = 0.006) and activated glycoprotein IIb/IIIa (p < 0.001) in response to arachidonic acid (AA) after adjustment for age, sex, clinical risk factors, and inflammatory markers. H3Cit was also associated with P-selectin expression in response to thrombin-receptor activating peptide (p = 0.048) and AA (p = 0.032). Circulating H3Cit and cfDNA predict ischemic outcomes after peripheral angioplasty with stent implantation, and are associated with on-treatment platelet activation in stable PAD.
Arginase 2 Deficiency Promotes Neuroinflammation and Pain Behaviors Following Nerve Injury in Mice
Authors: Yin Yuhua , Phạm Thuỳ Linh , Shin Juhee , Shin Nara , Kang Dong-Wook , Lee Sun Yeul , Lee Wonhyung , Kim Cuk-Seong , Kim Sang Ryong , Hong Jinpyo , Kim Dong-Woon
Published: January 2020

Microglia, the resident macrophages, act as the first and main form of active immune defense in the central nervous system. Arginase 2 (Arg2) is an enzyme involved in L-arginine metabolism and is expressed in macrophages and nervous tissue. In this study, we determined whether the absence of Arg2 plays a beneficial or detrimental role in the neuroinflammatory process. We then investigated whether the loss of Arg2 potentiated microglia activation and pain behaviors following nerve injury-induced neuropathic pain. A spinal nerve transection (SNT) experimental model was used to induce neuropathic pain in mice. As a result of the peripheral nerve injury, SNT induced microgliosis and astrogliosis in the spinal cord, and upregulated inflammatory signals in both wild-type (WT) and Arg2 knockout (KO) mice. Notably, inflammation increased significantly in the Arg2 KO group compared to the WT group. We also observed a more robust microgliosis and a lower mechanical threshold in the Arg2 KO group than those in the WT group. Furthermore, our data revealed a stronger upregulation of M1 pro-inflammatory cytokines, such as interleukin (IL)-1β, and a stronger downregulation of M2 anti-inflammatory cytokines, including IL4 and IL-10, in Arg2 KO mice. Additionally, stronger formation of enzyme-inducible nitric oxide synthase, oxidative stress, and decreased expression of CD206 were detected in the Arg2 KO group compared to the WT group. These results suggest that Arg2 deficiency contributes to inflammatory response. The reduction or the loss of Arg2 results in the stronger neuroinflammation in the spinal dorsal horn, followed by more severe pain behaviors arising from nerve injury-induced neuropathic pain.
Changes in Indocyanine Green Lymphography Patterns after Physical Treatment in Secondary Upper Limb Lymphedema
Authors: Medina-Rodríguez María Elena , de-la-Casa-Almeida María , González Martín Jesús , Hermida Anllo María , Medrano-Sánchez Esther M.
Published: January 2020

Indocyanine green (ICG) lymphography is used to evaluate the lymphatic function before and after pneumatic compression or post-manual lymphatic drainage. The aim of this study was to ascertain the changes in the fluoroscopic pattern produced by the provision of complex physical therapy. This prospective analytic (pretest-posttest) study was conducted in 19 patients with upper lymphedema secondary to breast cancer. Nine patients were excluded due to ICG found after 3 weeks. The ICG patterns were analyzed under basal conditions and after three weeks of treatment. After the treatment, 45% of the patients presented tracer remains in the affected limb, and this finding was significantly related to time of the lymphedema development. In one subject, the patterns remain unchanged or cannot be defined. Three of the ten patients observed present the worsening of at least 1 of the patterns and in the rest of the subjects, six cases, the improvement of the patterns is observed. In 60% of the cases, the most severe pattern reversed towards slight (splash) cases, and moderate cases reversed towards a slight case in 70% of cases. Therefore, after treatment with complex physical therapy, the pathological patterns observed in the pretest, which evolved positively, reverted their severity toward milder disease patterns or towards normality.
Changes in the Physical Function and Psychological Distress from Pre-Implant to 1, 6, and 12 Months Post-Implant in Patients Undergoing Implantable Cardioverter Defibrillator Therapy
Authors: Kim JinShil , Park Jin-Kyu , Choi Jiin , Kim Sun Hwa , On Young Keun , Shin Mi-Seung , Choi NaYeon , Heo Seongkum
Published: January 2020

Recipients of implantable cardioverter-defibrillator (ICD) therapy in Western countries often experience distressful physical and psychological adjustments. Sociocultural influences on post-implant recovery are likely; however, evidence from other ethnic/cultural backgrounds is lacking. This study aimed to examine the changes in physical function and psychological distress (anxiety and depressive symptoms) from pre-implant to one, six, and 12 months post-implant in Korean patients undergoing ICD therapy. A total of 34 patients underwent pre- to post-implant longitudinal assessments of physical and psychological function using mixed modeling procedures. Physical function significantly declined from pre-implant to one month post-implant (B = −10.05, p = 0.004) and then nearly returned to the pre-implant level at six months post-implant (B = 8.34, p = 0.028). This level of improvement continued through 12 months post-implant. In psychological distress, significant improvements were observed from pre-implant to one month (anxiety (B = −1.20, p = 0.020) and in depressive symptoms (B = −1.15, p = 0.037)), which then plateaued without significant changes from one to 12 months. We concluded that physical function recovery occurred six months post-implant, but function remained poor until 12 months post-implant. Psychological distress improved one month post-implant and it was maintained. Clinicians must provide more intensive interventions to improve long-term physical function after ICD therapy.