bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of GlideScope™ visualization and neck flexion with lateral neck pressure nasogastric tube insertion techniques in anesthetized patients: a randomized clinical study
Authors: Purngpipattrakul Pitchaporn , Petsakul Suttasinee , Chatmonkolchart Sunisa , Nuanjun Kanjana , Boonchuduang Somrutai
Published: November 2020

Objective

Nasogastric tube (NGT) insertion in anesthetized and intubated patients can be challenging, even for experienced anesthesiologists. Various techniques have been proposed to facilitate NGT insertion in these patients. This study aimed to compare the success rate and time required for NGT insertion between GlideScope™ visualization and neck flexion, with lateral neck pressure techniques.

Material and methods

This randomized clinical trial was performed at a teaching hospital on 86 adult patients undergoing abdominal surgery, under relaxant general anesthesia, who required intraoperative NGT insertion. The patients were randomized into two groups, the GlideScope™ group (group G) and the neck flexion with lateral neck pressure group (group F). The success rate of the first and second attempts, duration of insertion, and complications were recorded.

Results

The total success rate was 79.1% in group G, compared with 76.7% in group F (P = 1). The median time required for NGT insertion was significantly longer in group G, for both first and second attempts (97 vs 42 s P < 0.001) and (70 vs 48.5 s P = 0.015), respectively. Complications were reported in 23 patients (53.5%) in group G and 13 patients (30.2%) in group F. Bleeding and kinking were the most common complications for both techniques.

Conclusion

Using GlideScope™ visualization to facilitate NGT insertion was comparable to neck flexion with lateral neck pressure technique, in the degree of success rates of insertion. Although complications were not statistically significant between groups, neck flexion with lateral neck pressure technique was significantly less time-consuming for both first and second attempts.

Trial registration

Retrospectively registered: Thai Clinical Trial Registry (TCTR)20171229003. Registered on 19 December 2017
Evaluation of the effect of curcumin and zinc co-supplementation on glycemic measurements, lipid profiles, and inflammatory and antioxidant biomarkers in overweight or obese prediabetic patients: a study protocol for a randomized double-blind placebo-controlled phase 2 clinical trial
Authors: Karandish Majid , Mozaffari-khosravi Hassan , Mohammadi Seyed Mohammad , Azhdari Maryam , Cheraghian Bahman
Published: November 2020

Background

The prevalence of prediabetes is increasing worldwide. Unfortunately, prediabetes is related to non-communicable diseases. A high risk of developing type 2 diabetes mellitus (T2DM) is reported in people with prediabetes. Curcumin, a polyphenol, might lead to its therapeutic role in obesity and some obesity-related metabolic diseases. Zinc is a trace element that plays a key role in the synthesis and action of insulin, carbohydrate metabolism, and decreasing inflammation. There has been no clinical trial of zinc and curcumin co-supplementation in patients with prediabetes. In previous studies, the single administration of zinc or curcumin has not been conducted on many of the studied markers in prediabetic patients.

Methods

The purpose of this randomized double-blind placebo-controlled clinical trial is to investigate the effect of curcumin and zinc co-supplementation on glycemic measurements, lipid profiles, and inflammatory and antioxidant biomarkers among 84 prediabetic patients with body mass index (BMI) between 25 and 35. Also, liver enzyme, serum zinc, urine zinc, blood pressure, anthropometric parameters, quality of life, adherence to co-supplementation, the side effects of co-supplementation, physical activity, and dietary intake will be assessed. Women or men (18–50 years old for men and 18 years to before menopause for women) will be followed for 3 months (90 days). This study will be conducted at Yazd Diabetes Research Clinic, Shahid Sadoughi University of Medical Sciences.

Discussion

A diet rich in antioxidants, polyphenols, and phytochemicals has been shown to have a beneficial role in prediabetes. According to the beneficial properties of curcumin or zinc and inadequate evidence, RCTs are needed to assess the effect of curcumin and zinc co-supplementation in native prediabetes patients. We hope the results of the present trial, negative or positive, fill this gap in the literature and facilitate the approach for a much larger, multi-center clinical trial. In conclusion, a synergic effect of co-supplementation along with a weight-loss diet may delay the progression to type 2 diabetes mellitus.

Trial registration

Iranian Registry of Clinical Trials (IRCT) IRCT20190902044671N1. Registered on 11 October 2019
A thermostable bacterial lytic polysaccharide monooxygenase with high operational stability in a wide temperature range
Authors: Tuveng Tina Rise , Jensen Marianne Slang , Fredriksen Lasse , Vaaje-Kolstad Gustav , Eijsink Vincent G. H. , Forsberg Zarah
Published: November 2020

Background

Lytic polysaccharide monooxygenases (LPMOs) are oxidative, copper-dependent enzymes that function as powerful tools in the turnover of various biomasses, including lignocellulosic plant biomass. While LPMOs are considered to be of great importance for biorefineries, little is known about industrial relevant properties such as the ability to operate at high temperatures. Here, we describe a thermostable, cellulose-active LPMO from a high-temperature compost metagenome (called mgLPMO10).

Results

MgLPMO10 was found to have the highest apparent melting temperature (83 °C) reported for an LPMO to date, and is catalytically active up to temperatures of at least 80 °C. Generally, mgLPMO10 showed good activity and operational stability over a wide temperature range. The LPMO boosted cellulose saccharification by recombinantly produced GH48 and GH6 cellobiohydrolases derived from the same metagenome, albeit to a minor extent. Cellulose saccharification studies with a commercial cellulase cocktail (Celluclast®) showed that the performance of this thermostable bacterial LPMO is comparable with that of a frequently utilized fungal LPMO from Thermoascus aurantiacus (TaLPMO9A).

Conclusions

The high activity and operational stability of mgLPMO10 are of both fundamental and applied interest. The ability of mgLPMO10 to perform oxidative cleavage of cellulose at 80 °C and the clear synergy with Celluclast® make this enzyme an interesting candidate in the development of thermostable enzyme cocktails for use in lignocellulosic biorefineries.
Whole blood DNA methylation aging markers predict colorectal cancer survival: a prospective cohort study
Authors: Gào Xīn , Zhang Yan , Boakye Daniel , Li Xiangwei , Chang-Claude Jenny , Hoffmeister Michael , Brenner Hermann
Published: November 2020

Background

Blood DNA methylation-based aging algorithms predict mortality in the general population. We investigated the prognostic value of five established DNA methylation aging algorithms for patients with colorectal cancer (CRC).

Methods

AgeAccelHorvath, AgeAccelHannum, DNAmMRscore, AgeAccelPheno and AgeAccelGrim were constructed using whole blood epi-genomic data from 2206 CRC patients. After a median follow-up of 6.2 years, 1079 deaths were documented, including 596 from CRC. Associations of the aging algorithms with survival outcomes were evaluated using the Cox regression and survival curves. Harrell’s C-statistics were computed to investigate predictive performance.

Results

Adjusted hazard ratios (95% confidence intervals) of all-cause mortality for patients in the third compared to the first tertile were 1.66 (1.32, 2.09) for the DNAmMRscore, 1.35 (1.14, 1.59) for AgeAccelPheno and 1.65 (1.37, 2.00) for AgeAccelGrim, even after adjustment for age, sex and stage. AgeAccelHorvath and AgeAccelHannum were not associated with all-cause or CRC-specific mortality. In stage-specific analyses, associations were much stronger for patients with early or intermediate stage cancers (stages I, II and III) than for patients with metastatic (stage IV) cancers. Associations were weaker and less often statistically significant for CRC-specific mortality. Adding DNAmMRscore, AgeAccelPheno or AgeAccelGrim to models including age, sex and tumor stage improved predictive performance moderately.

Conclusions

DNAmMRscore, AgeAccelPheno and AgeAccelGrim could serve as non-invasive CRC prognostic biomarkers independent of other commonly used markers. Further research should aim for tailoring and refining such algorithms for CRC patients and to explore their value for enhanced prediction of treatment success and treatment decisions.
Developmental programming in human umbilical cord vein endothelial cells following fetal growth restriction
Authors: Terstappen Fieke , Calis Jorg J. A. , Paauw Nina D. , Joles Jaap A. , van Rijn Bas B. , Mokry Michal , Plösch Torsten , Lely A. Titia
Published: November 2020

Background

Fetal growth restriction (FGR) is associated with an increased susceptibility for various noncommunicable diseases in adulthood, including cardiovascular and renal disease. During FGR, reduced uteroplacental blood flow, oxygen and nutrient supply to the fetus are hypothesized to detrimentally influence cardiovascular and renal programming. This study examined whether developmental programming profiles, especially related to the cardiovascular and renal system, differ in human umbilical vein endothelial cells (HUVECs) collected from pregnancies complicated by placental insufficiency-induced FGR compared to normal growth pregnancies. Our approach, involving transcriptomic profiling by RNA-sequencing and gene set enrichment analysis focused on cardiovascular and renal gene sets and targeted DNA methylation assays, contributes to the identification of targets underlying long-term cardiovascular and renal diseases.

Results

Gene set enrichment analysis showed several downregulated gene sets, most of them involved in immune or inflammatory pathways or cell cycle pathways. seven of the 22 significantly upregulated gene sets related to kidney development and four gene sets involved with cardiovascular health and function were downregulated in FGR (n = 11) versus control (n = 8). Transcriptomic profiling by RNA-sequencing revealed downregulated expression ofLGALS1,FPR3andNRMand upregulation of lincRNARP5-855F14.1in FGR compared to controls. DNA methylation was similar forLGALS1between study groups, but relative hypomethylation ofFPR3and hypermethylation ofNRMwere present in FGR, especially in male offspring. Absolute differences in methylation were, however, small.

Conclusion

This study showed upregulation of gene sets related to renal development in HUVECs collected from pregnancies complicated by FGR compared to control donors. The differentially expressed gene sets related to cardiovascular function and health might be in line with the downregulated expression ofNRMand upregulated expression of lincRNARP5-855F14.1in FGR samples; NRM is involved in cardiac remodeling, and lincRNAs are correlated with cardiovascular diseases. Future studies should elucidate whether the downregulatedLGALS1andFPR3expressions in FGR are angiogenesis-modulating regulators leading to placental insufficiency-induced FGR or whether the expression of these genes can be used as a biomarker for increased cardiovascular risk. Altered DNA methylation might partly underlieFPR3andNRMdifferential gene expression differences in a sex-dependent manner.
Epigenetic regulation of inflammation in periodontitis: cellular mechanisms and therapeutic potential
Authors: Jurdziński Krzysztof T. , Potempa Jan , Grabiec Aleksander M.
Published: November 2020

Epigenetic mechanisms, namely DNA and histone modifications, are critical regulators of immunity and inflammation which have emerged as potential targets for immunomodulating therapies. The prevalence and significant morbidity of periodontitis, in combination with accumulating evidence that genetic, environmental and lifestyle factors cannot fully explain the susceptibility of individuals to disease development, have driven interest in epigenetic regulation as an important factor in periodontitis pathogenesis. Aberrant promoter methylation profiles of genes involved in inflammatory activation, includingTLR2,PTGS2,IFNG,IL6,IL8,andTNF, have been observed in the gingival tissue, peripheral blood or buccal mucosa from patients with periodontitis, correlating with changes in expression and disease severity. The expression of enzymes that regulate histone acetylation, in particular histone deacetylases (HDACs), is also dysregulated in periodontitis-affected gingival tissue. Infection of gingival epithelial cells, gingival fibroblasts and periodontal ligament cells with the oral pathogensPorphyromonas gingivalisorTreponema denticolainduces alterations in expression and activity of chromatin-modifying enzymes, as well as site-specific and global changes in DNA methylation profiles and in histone acetylation and methylation marks. These epigenetic changes are associated with excessive production of inflammatory cytokines, chemokines, and matrix-degrading enzymes that can be suppressed by small molecule inhibitors of HDACs (HDACi) or DNA methyltransferases. HDACi and inhibitors of bromodomain-containing BET proteins ameliorate inflammation, osteoclastogenesis, and alveolar bone resorption in animal models of periodontitis, suggesting their clinical potential as host modulation therapeutic agents. However, broader application of epigenomic methods will be required to create a comprehensive map of epigenetic changes in periodontitis. The integration of functional studies with global analyses of the epigenetic landscape will provide critical information on the therapeutic and diagnostic potential of epigenetics in periodontal disease.
Interventional radiology and artificial intelligence in radiology: Is it time to enhance the vision of our medical students?
Authors: Auloge Pierre , Garnon Julien , Robinson Joey Marie , Dbouk Sarah , Sibilia Jean , Braun Marc , Vanpee Dominique , Koch Guillaume , Cazzato Roberto Luigi , Gangi Afshin
Published: November 2020

Objectives

To assess awareness and knowledge of Interventional Radiology (IR) in a large population of medical students in 2019.

Methods

An anonymous survey was distributed electronically to 9546 medical students from first to sixth year at three European medical schools. The survey contained 14 questions, including two general questions on diagnostic radiology (DR) and artificial intelligence (AI), and 11 on IR. Responses were analyzed for all students and compared between preclinical (PCs) (first to third year) and clinical phase (Cs) (fourth to sixth year) of medical school. Of 9546 students, 1459 students (15.3%) answered the survey.

Results

On DR questions, 34.8% answered that AI is a threat for radiologists (PCs: 246/725 (33.9%); Cs: 248/734 (36%)) and 91.1% thought that radiology has a future (PCs: 668/725 (92.1%); Cs: 657/734 (89.5%)). On IR questions, 80.8% (1179/1459) students had already heard of IR; 75.7% (1104/1459) stated that their knowledge of IR wasn’t as good as the other specialties and 80% would like more lectures on IR. Finally, 24.2% (353/1459) indicated an interest in a career in IR with a majority of women in preclinical phase, but this trend reverses in clinical phase.

Conclusions

Development of new technology supporting advances in artificial intelligence will likely continue to change the landscape of radiology; however, medical students remain confident in the need for specialty-trained human physicians in the future of radiology as a clinical practice. A large majority of medical students would like more information about IR in their medical curriculum; almost a quarter of students would be interested in a career in IR.
Genetic and histopathological analysis of transverse testicular ectopia without persistent Müllerian duct syndrome: two case reports
Authors: Nagai Takashi , Mizuno Kentaro , Usami Masayuki , Nishio Hidenori , Kato Taiki , Nakane Akihiro , Matsumoto Daisuke , Kurokawa Satoshi , Kamisawa Hideyuki , Maruyama Tetsuji , Yasui Takahiro , Hayashi Yutaro
Published: November 2020

Background

Transverse testicular ectopia (TTE) is a rare anomaly in which both testes descend through a single inguinal canal into the same hemiscrotum. Although almost 20–50% of patients with TTE exhibit persistent Müllerian duct syndrome (PMDS) and many genetic analyses have been performed, no reports have described the genes contributing to TTE without PMDS. Here, we report two cases of TTE without PMDS using immunohistochemical staining and genetic analysis.

Case presentation

Two Asian patients with TTE without PMDS were subjected to orchiopexy. We performed testicular biopsies during operation and obtained blood samples before the operation. Testicular tissues were stained for c-kit, placental alkaline phosphatase (PLAP), and undifferentiated embryonic cell transcription factor 1 (UTF1) to evaluate the presence of intratubular malignant germ cells. Additionally, we performed polymerase chain reaction-based direct sequencing to identify single nucleotide polymorphisms in genes associated with regression of the Müllerian duct and testicular descent (that is, anti-Müllerian hormone [AMH], AMH receptor 2 [AMHR2], insulin-like 3 [INSL3], and relaxin family peptide receptor 2 [RXFP2]). The three-dimensional structures of proteins were predicted using SWISS-MODEL. In immunohistochemical analysis, c-kit and UTF1 were positive, whereas PLAP was negative in three testicular tissue samples from the two patients. These features were also detected on the unaffected side. In variant analysis, common missense variants in the AMH gene (g.365G>T; c.165G>T; p.Ser49Ile [rs10407022]) were observed. All variants in INSL3 and RXFP2 genes were intronic or silent.

Conclusions

Because UTF1, a specific marker of spermatogonial stem cell activity, was expressed in both the affected and unaffected sides in the testicular tissues of two patients, the risk of malignancy may be high in these patients. Although the etiology of TTE without PMDS remains unclear, our variant analysis results were consistent with previous reports, and variants in the AMH gene (rs10407022) may contribute to the specific phenotype of TTE without PMDS.
Oracle inequalities for weighted group lasso in high-dimensional misspecified Cox models
Authors: Xiao Yijun , Yan Ting , Zhang Huiming , Zhang Yuanyuan
Published: November 2020

We study the nonasymptotic properties of a general norm penalized estimator, which include Lasso, weighted Lasso, and group Lasso as special cases, for sparse high-dimensional misspecified Cox models with time-dependent covariates. Under suitable conditions on the true regression coefficients and random covariates, we provide oracle inequalities for prediction and estimation error based on the group sparsity of the true coefficient vector. The nonasymptotic oracle inequalities show that the penalized estimator has good sparse approximation of the true model and enables to select a few meaningful structure variables among the set of features.
The functional inequality for the mixed quermassintegral
Authors: Chen Fangwei , Fang Jianbo , Luo Miao , Yang Congli
Published: November 2020

In this paper, the functional Quermassintegrals of a log-concave function in $\mathbb{R}^{n}$

R
n

are discussed. The functional inequality for the ith mixed Quermassintegral is established. Moreover, as a special case, a weaker log-Quermassintegral inequality in $\mathbb{R}^{n}$

R
n

is obtained.
Down syndrome cell adhesion molecule like-1 (DSCAML1) links the GABA system and seizure susceptibility
Authors: Hayase Yoneko , Amano Shigeru , Hashizume Koichi , Tominaga Takashi , Miyamoto Hiroyuki , Kanno Yukie , Ueno-Inoue Yukiko , Inoue Takayoshi , Yamada Mayumi , Ogata Shigehiro , Balan Shabeesh , Hayashi Ken , Miura Yoshiki , Tokudome Kentaro , Ohno Yukihiro , Nishijo Takuma , Momiyama Toshihiko , Yanagawa Yuchio , Takizawa Akiko , Mashimo Tomoji , Serikawa Tadao , Sekine Akihiro , Nakagawa Eiji , Takeshita Eri , Yoshikawa Takeo , Waga Chikako , Inoue Ken , Goto Yu-ichi , Nabeshima Yoichi , Ihara Nobuo , Yamakawa Kazuhiro , Taya Shinichiro , Hoshino Mikio
Published: November 2020

The Ihara epileptic rat (IER) is a mutant model with limbic-like seizures whose pathology and causative gene remain elusive. In this report, via linkage analysis, we identified Down syndrome cell adhesion molecule-like 1(Dscaml1) as the responsible gene for IER. A single base mutation in Dscaml1 causes abnormal splicing, leading to lack of DSCAML1. IERs have enhanced seizure susceptibility and accelerated kindling establishment. Furthermore, GABAergic neurons are severely reduced in the entorhinal cortex (ECx) of these animals. Voltage-sensitive dye imaging that directly presents the excitation status of brain slices revealed abnormally persistent excitability in IER ECx. This suggests that reduced GABAergic neurons may cause weak sustained entorhinal cortex activations, leading to natural kindling via the perforant path that could cause dentate gyrus hypertrophy and epileptogenesis. Furthermore, we identified a single nucleotide substitution in a human epilepsy that would result in one amino acid change in DSCAML1 (A2105T mutation). The mutant DSCAML1A2105T protein is not presented on the cell surface, losing its homophilic cell adhesion ability. We generated knock-in mice (Dscaml1A2105T) carrying the corresponding mutation and observed reduced GABAergic neurons in the ECx as well as spike-and-wave electrocorticogram. We conclude that DSCAML1 is required for GABAergic neuron placement in the ECx and suppression of seizure susceptibility in rodents. Our findings suggest that mutations in DSCAML1 may affect seizure susceptibility in humans.
Plasticiser loss in heritage collections: its prevalence, cause, effect, and methods for analysis
Authors: King Rose , Grau-Bové Josep , Curran Katherine
Published: November 2020

Plasticiser loss is a topic frequently mentioned in discussions on the degradation of plastic artefacts in museum collections, particularly for plasticised poly (vinyl chloride) and cellulose acetate. Plasticisers may migrate to the plastic’s surface and remain as a deposit, or volatilise into the surrounding environment, both presenting an aesthetic issue and impacting the future stability of the plastic. This paper draws on the work of conservation science, materials degradation, and indoor air quality/emissions studies, to review our current understanding of plasticiser loss. The influence of the material’s intrinsic properties, and environmental factors on migration rates are discussed and related to preventive conservation practices. The methods by which plasticiser migration is studied, including characterisation, are also reviewed, with a particular focus on minimally invasive and non-destructive methods suitable for heritage science research.
Ionospheric disturbance caused by artificial plasma clouds under different release conditions
Authors: Zhu Xiaoli , Hu Yaogai , Zhao Zhengyu , Ni Binbin , Zhang Yuannong
Published: November 2020

The generation and evolution of artificial plasma clouds is a complicated process that is strongly dependent on the background environment and release conditions. In this paper, based on a three-dimensional two-species fluid model, the evolution characteristics of artificial plasma clouds under various release conditions were analyzed numerically. In particular, the effect of ionospheric density gradient and ambient horizontal wind field was taken into account in our simulation. The results show that an asymmetric plasma cloud structure occurs in the vertical direction when a nonuniform ionosphere is assumed. The density, volume, and expansion velocity of the artificial plasma cloud vary with the release altitude, mass, and initial ionization rate. The initial release velocity can change the cloud's movement and overall distribution. With an initial velocity perpendicular to the magnetic field, an O+ density cavity and two bumps exist. When there is an initial velocity parallel to the magnetic field, the generated plasma cloud is bulb-shaped, and only one O+ density cavity and one density bump are created. Compared to the cesium case, barium clouds expand more rapidly. Moreover, Cs+ clouds have a higher density than Ba+ clouds, and the snowplow effect of Cs+ is also stronger.
Few self-citations among Chilean ecologists
Authors: Rau Jaime R. , Jaksic Fabian M.
Published: November 2020

Background

We determine the occurrence of self-citations among 36 Chilean ecologists with the highest h index values recorded in Web of Science. Because the practice of self-citation is perceived as negative by inflating a given researcher’s impact factor, we evaluate if those ecologists (five of them having been awarded the National Prize in Natural Sciences) tend unduly to self-citation, or alternately, receive citations from others ostensibly because their peers recognize their theoretical and empirical output.

Methods and findings

We use a recently proposed self-citation estimate easily calculated from h index values recorded in the restricted-access Web of Science (Wos) database and the open-access Google Scholar’s (GS) Researcher Profiles and compare these metrics.

Conclusions

The Chilean ecologists showed low self-citation values, independently of their status as National Prize awardees. Their publications were highly cited by unrelated peers, likely on account of their novelty or quality. Among middle-aged (50–60 year) and young (< 50 year) Chilean ecologists open-access GS h index values are significantly correlated with those from WoS, thus rendering expeditious this method of citation assessment.
Screening for Ames mutagenicity of food flavor chemicals by (quantitative) structure-activity relationship
Authors: Honma Masamitsu , Kitazawa Airi , Kasamatsu Toshio , Sugiyama Kei-ichi
Published: November 2020

Background

(Quantitative) Structure-Activity Relationship ((Q)SAR) is a promising approach to predict the potential adverse effects of chemicals based on their structure without performing toxicological studies. We evaluate the mutagenicity of food flavor chemicals by (Q) SAR tools, identify potentially mutagenic chemicals, and verify their mutagenicity by actual Ames test.

Results

The Ames mutagenicity of 3942 food flavor chemicals was predicted using two (Q)SAR) tools, DEREK Nexus and CASE Ultra. Three thousand five hundred seventy-five chemicals (91%) were judged to be negative in both (Q) SAR tools, and 75 chemicals (2%) were predicted to be positive in both (Q) SAR tools. When the Ames test was conducted on ten of these positive chemicals, nine showed positive results.

Conclusion

The (Q) SAR method can be used for screening the mutagenicity of food flavors.
Effect of the versatile bifunctional chelator AAZTA5 on the radiometal labelling properties and the in vitro performance of a gastrin releasing peptide receptor antagonist
Authors: Hofstetter Michael , Moon Euy Sung , D’Angelo Fabio , Geissbühler Lucien , Alberts Ian , Afshar-Oromieh Ali , Rösch Frank , Rominger Axel , Gourni Eleni
Published: November 2020

Background

Gastrin Releasing Peptide receptor (GRPr)-based radioligands have shown great promise for diagnostic imaging of GRPr-positive cancers, such as prostate and breast.

The present study aims at developing and evaluating a versatile GRPr-based probe for both PET/SPECT imaging as well as intraoperative and therapeutic applications. The influence of the versatile chelator AAZTA5 on the radiometal labelling properties and the in vitro performance of the generated radiotracers were thoroughly investigated.

The GRPr-based antagonist D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 was functionalized with the chelator 6-[Bis (carboxymethyl)amino]-1,4-bis (carboyxmethyl)-6-methyl-1,4-diazepane (AAZTA5) through the spacer 4-amino-1-carboxymethyl-piperidine (Pip) to obtain AAZTA5-Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (LF1). LF1 was radiolabelled with gallium-68 (PET), indium-111 (SPECT, intraoperative applications) and lutetium-177 (therapy, SPECT). In vitro evaluation included stability studies, determination of lipophilicity, protein-binding studies, determination of Kd and Bmax as well as internalization studies using the epithelial human prostate cancer cell line PC3. In vitro monotherapy as well as combination therapy studies were further performed to assess its applicability as a theranostic compound.

Results

LF1 was labelled with gallium-68, indium-111 and lutetium-177 within 5 min at room temperature (RT). The apparent molar activities (Am) were ranging between 50 and 60 GBq/μmol for the 68Ga-labelled LF1, 10–20 GBq/μmol for the 111In- and 177Lu-labelled LF1. The radiotracers were stable for a period of 4 h post labeling exhibiting a hydrophilic profile with an average of a LogDoctanol/PBS of − 3, while the bound activity to the human serum protein was approximately 10%. 68/natGa-LF1, 177/natLu-LF1 and 111/natIn-LF1 exhibited high affinity for the PC3 cells, with Kd values of 16.3 ± 2.4 nM, 10.3 ± 2.73 nM and 5.2 ± 1.9 nM, respectively, and the required concentration of the radiotracers to saturate the receptors (Bmax) was between 0.5 and 0.8 nM which corresponds to approximately 4 × 105 receptors per cell. Low specific internalization rate was found in cell culture, while the total specific cell surface bound uptake always exceeded the internalized activity. In vitro therapy studies showed that inhibition of PC3 cells growth is somewhat more efficient when combination of 177Lu-labelled LF1 with rapamycin is applied compared to 177Lu-laballed LF1 alone.

Conclusion

Encouraged by these promising in vitro data, preclinical evaluation of the LF1 precursor are planned in tumour models in vivo.
Ex vivo generation of platelet products from human iPS cells
Authors: Nakamura Sou , Sugimoto Naoshi , Eto Koji
Published: November 2020

Platelet products are used in treatments for thrombocytopenia caused by hematopoietic diseases, chemotherapy, massive hemorrhages, extracorporeal circulation, and others. Their manufacturing depends on volunteers who donate blood. However, it is becoming increasingly necessary to reinforce this blood donation system with other blood sources due to the increase in demand and shortage of supply accompanying aging societies. In addition, blood-borne infections and alloimmune platelet transfusion refractoriness are not completely resolved. Since human induced pluripotent stem cell (iPSC)-platelet products can be supplied independently from the donor, it is expected to complement current platelet products. One big hurdle with iPSC-based systems is the production of 10 units, which is equivalent to 200 billion platelets. To overcome this issue, we established immortalized megakaryocyte cell lines (imMKCLs) by introducing three transgenes, c-MYC, BMI1, and BCL-XL, sequentially into hematopoietic and megakaryocytic progenitor stage cells derived from iPSCs. The three transgenes are regulated in a Tet-ON manner, enabling the addition and depletion of doxycycline to expand and maturate the imMKCLs, respectively. In addition, we succeeded in discovering drug combinations that enable feeder-free culture conditions in the imMKCL cultivation. Furthermore, we discovered the importance of turbulence in thrombopoiesis through live bone marrow imaging and developed a bioreactor based on the concept of turbulent flow. Eventually, through the identification of two key fluid physic parameters, turbulent energy and shear stress, we succeeded in scaling up the bioreactor to qualitatively and quantitatively achieve clinically applicable levels. Interestingly, three soluble factors released from imMKCLs in the turbulent flow condition, macrophage migration inhibitory factor (MIF), insulin growth factor binding protein 2 (IGFBP2), and nardilysin (NRDC), enhanced platelet production. Based on these developments, we initiated the first-in-human clinical trial of iPSC-derived platelets to a patient with alloimmune platelet transfusion refractoriness (allo-PTR) using an autologous product. In this review, we detail current research in this field and our study about the ex vivo production of iPSC-derived platelets.
Acute abdomen in children due to different presentations of complicated Meckel’s diverticulum: a case series
Authors: Almetaher Hisham A. , Mansour Mohammed Awad
Published: November 2020

Background

Meckel’s diverticulum (MD) is the commonest congenital abnormality of the gastrointestinal tract that occurs in 2% of general population. It remains asymptomatic, but it may lead to life-threatening complications. These complications may be misdiagnosed with other gastrointestinal disorders like acute appendicitis, making its diagnosis challenging among pediatricians and pediatric surgeons. In this study, we reported five cases with different presentations of complicated MD in children.

Results

Five patients with different presentations of MD were reported during the period from January 2016 to January 2020. Patients’ demographics, clinical presentations, investigations, operative data, and postoperative outcome were recorded and analyzed.

Conclusions

The present study highlights different presentations of MD. Surgical interference is the main key of treatment of symptomatic MD either by wedge resection of a small base diverticulum or by resection anastomosis of the small intestine in wide base and inflamed diverticulum.
What Makes a Rule Complex?
Authors: Oprea Ryan
Published: November 2020

We study the complexity of rules by paying experimental subjects to implement a series of algorithms and then eliciting their willingness-to-pay to avoid implementing them again in the future. The design allows us to examine hypotheses from the theoretical “automata” literature about the characteristics of rules that generate complexity costs. We find substantial aversion to complexity and a number of regularities in the characteristics of rules that make them complex and costly for subjects. Experience with a rule, the way a rule is represented, and the context in which a rule is implemented (mentally versus physically) also influence complexity. (JEL C73, D11, D12, D83, D91)
Female pelvic congestion syndrome: how can CT and MRI help in the management decision?
Authors: Osman Ahmed M. , Mordi Ahmed , Khattab Rasha
Published: November 2020

Objective:

Diagnosis of female pelvic congestion syndrome (PCS) is challenging. Although invasive venography is the gold-standard for diagnosis, however, CT and MRI are important in the assessment. In this study, we tried to highlight the role of CT and MRI as non-invasive tools in the diagnosis and management of PCS.

Methods and material:

This was a retrospective study of 50 patients confirmed clinically to have PCS. These patients had already done CT and MRI before venography or surgery.

Results:

The mean age of the patients was 48 years ± 12 years SD. Vaginal discharge and pelvic heaviness were the commonest symptoms (46 and 42% respectively). The commonest risk factor was multiparity (56%) followed by the RVF uterus (26%). No significant difference was found between CT, MRI, and venography as regarding the diameter of the ovarian vein, diameter, and the number of the varicose veins. The sensitivity of CT and MRI was 94.8 and 96%. CT and MRI discovered five cases with local pelvic obstructing cause,14 cases with evidence of vascular compression syndrome, and the rest 31 cases diagnosed to have primary non-obstructing PCS which was effective in decision-making with the surgery indicated in the first group while stenting of the vascular obstruction followed by bilateral ovarian veins coiling was the better option for the second group and only bilateral coiling was needed for the last group.

Conclusion:

CT and MRI play important roles in the diagnosis and even management decision in cases of PCS.

Advances in knowledge: :

Identification of the importance of diagnostic radiology before management decisions of cases with PCS.
Η έννοια της "Αιώνιας" Ειρήνης κατά τον Kant και η συμφωνία Ηθικής και Πολιτικής
Authors: Γούναρης Αλκιβιάδης Κ.
Published: November 2020

Δεν διατίθεται περίληψη
Λόγος, νους και ψυχή στη Hannah Arendt
Authors: Μπούρα Σύνη
Published: November 2020

Δεν διατίθεται περίληψη
Social Entrepreneurship as a Tool of Sustainable Development
Authors: Bľanda Jozef , Urbančíková Nataša
Published: November 2020

Purpose: The article deals with the analysis of the perception of social entrepreneurship in Slovakia by social entrepreneurs. The main aim is to identify how social entrepreneurs perceive individual aspects of social entrepreneurship in Slovakia, including the role of social entrepreneurship in sustainable development.Methodology/Approach: The analysis was based on data obtained from a questionnaire survey conducted among social entrepreneurs in Slovakia. The survey was attended by representatives of 35 social enterprises from Slovakia. A seven-point rating of Likert scale used within the questionnaire. The mode, median and interquartile range of answers were used to evaluate the questionnaire.Findings: Social entrepreneurs pointed out that social entrepreneurship is still in development in Slovakia and several obstacles causing this situation. They also agreed that the most important benefit of social entrepreneurship in Slovakia is the effort to solve social problems. The research results show that the priority of social entrepreneurs in Slovakia is not to support sustainable development.Research Limitation/implication: The research was limited by the number of social entrepreneurs who participated in the survey. More than half of social enterprises, registered in Slovakia were not willing to participate in the survey.Originality/Value of paper: The article brings important findings in the field of social entrepreneurship, which are based on the practical experience of social entrepreneurs in Slovakia.
Does Foreign Direct Investment Boost Innovation? The Case of the Visegrad and Baltic Countries
Authors: Bobenič Hintošová Aneta , Bruothová Michaela , Vasková Iveta
Published: November 2020

Purpose: The purpose of the paper is to examine the impact of inward and outward foreign direct investment on innovation performance of the Visegrad and Baltic countries.Methodology/Approach: The study follows an open-system approach to consider the determinants of national innovation performance, taking into account both inward and outward FDI. We use two-step analysis that combines panel data regression analysis with the design of two FDI – innovation performance matrixes.Findings: The results of the study provide evidence that only outward foreign direct investment of domestic firms contributes significantly to the innovation performance of these countries and that this effect is more visible in the case of the Visegrad countries.Research Limitation/Implication: The limitations of the study are associated in particular with the selection of SII as a measure of national innovation performance. The use of this indicator is also related to the relatively short period of availability of consistent data, especially in connection with changes in the methodology of SII calculation.Originality/Value of paper: The policy implications of the paper suggest the need for stronger support of domestic bearers of cross-border capital movements in an attempt to boost national innovation performance.
Estudo transversal sobre uso de ferramentas virtuais para orientar a atividade física durante a COVID-19
Authors: Guimarães Jean Augusto Coelho , Guerra Paulo Henrique , Ueno Deisy Terumi , Christofoletti Ana Elisa Messetti , Nakamura Priscila Missaki
Published: November 2020

A elevada taxa de transmissão e mortalidade pela COVID-19 acarretou o fechamento de centros de movimentação social, dentre eles locais para prática de atividade física.  Com isso, o objetivo do estudo foi identificar as principais estratégias e ferramentas tecnológicas virtuais, percepção dos profissionais de educação física (PEF) acerca das adaptações, pontos positivos, negativos e feedbacks dos clientes para orientar a prática de atividade física durante o isolamento social/restrição de circulação devido ao vírus SARS-COV-2. Optou-se pela pesquisa transversal, quanti-qualitativa, com técnica de amostragem “bola de neve”, sendo recrutados PEF das cinco regiões do Brasil. Os participantes responderam um questionário online com questões sociodemográficas, uso das ferramentas tecnológicas virtuais, perfil dos clientes e questões discursivas acerca da orientação online à atividade física. Foi realizada estatística descritiva e análise por codificação simples. Participaram 110 PEF de 65 cidades do país, os quais geralmente atendem em academias de ginástica (59,8%) e ao ar livre (34,5%), tendo clientes adultos (92,9%), do sexo feminino (51,8%). Dentre as ferramentas tecnológicas virtuais utilizadas estão “vídeos” (60,9%) e “Whatsapp web” (60,0%), geralmente ferramentas gratuitas (67,5%) e, para que o trabalho ocorra, são necessárias adaptações estruturais/materiais e profissionais. Embora haja aspectos negativos e dificuldades na orientação remota à prática de atividade física, os aspectos positivos e facilidades permitem que o PEF se conecte com seus respectivos clientes mesmo durante a pandemia, estimulando e, orientando de forma segura, a prática de atividade física. Esta temática necessita ser mais explorada para que essas ferramentas auxiliem os PEF.
Role of cats in human toxocarosis
Authors: Castro Pablo David Jimenez , Sapp Sarah GH
Published: November 2020

Toxocara cati, the feline ascarid, is ubiquitous in domestic cats globally and is increasingly recognised as an important zoonotic species. In the definitive host, infections with the adult ascarid usually do not present any clinical signs; if clinical signs do appear, it is usually in kittens infected with T. cati, especially by the trans-mammary route. Diseases may include cachexia, a pot-bellied appearance, respiratory disorders, diarrhoea, vomiting, among other signs, and these may present as early as 3 weeks of age. However, infections with Toxocara spp. larvae in paratenic hosts (including humans and many other animals), can result in serious complications from the migration of larvae. Historically, there has been an assumption that Toxocara canis was the most likely cause of Toxocara spp.-related disease; while it is probably true that T. canis is responsible for the majority of infections, it is important that those caused by T. cati are accurately identified so that the contribution of this parasite to human disease can be established and then handled appropriately. Overall, the detection of infections in cats and the control of parasite stages in the environment are essential to minimise the infection risk to other animals or humans.
Factors associated with delirium and cognitive decline following hip fracture surgery
Authors: Uzoigwe Chika E. , O'Leary Lawrence , Nduka Jude , Sharma Daman , Melling David , Simmons Damon , Barton Simon
Published: November 2020

Aims

Postoperative delirium (POD) and postoperative cognitive decline (POCD) are common surgical complications. In the UK, the Best Practice Tariff incentivizes the screening of delirium in patients with hip fracture. Further, a National Hip Fracture Database (NHFD) performance indicator is the reduction in the incidence of POD. To aid in its recognition, we sought to determine factors associated with POD and POCD in patients with hip fractures.

Methods

We interrogated the NHFD data on patients presenting with hip fractures to our institution from 2016 to 2018. POD was determined using the 4AT score, as recommended by the NHFD and UK Department of Health. POCD was defined as a decline in Abbreviated Mental Test Score (AMTS) of two or greater. Using logistic regression, we adjusted for covariates to identify factors associated with POD and POCD.

Results

Of the 1,224 patients presenting in the study period, 1,023 had complete datasets for final analysis. POD was observed in 242 patients (25%). On multivariate analysis only preoperative AMTS and American Society of Anesthesiologists grade (ASA) were independent predictors of POD. Every point increase in AMTS was associated with a fall in the odds of POD by a factor of 0.60 (95% confidence interval (CI) 0.56 to 0.63, p < 0.001). Every grade increase in ASA led to a 1.7-fold increase in the odds of POD (95% CI 1.13 to 2.50, p = 0.009). A preoperative AMTS of less than 8 was strongly predictive of POD with area under the receiver operating characteristic of 0.86 (95% CI 0.84 to 0.89). Only ASA was predictive of POCD—every grade increase in ASA led to a 2.6-fold increase in the odds of POCD (95% CI 1.7 to 4.0, p < 0.001).

Conclusion

POD and POCD are common in the hip fracture patients. Preoperative AMTS and ASA are strong predictors of POD, and ASA predictive of POCD. This may aid in the earlier identification of those most at risk and suited for the patient consent and decision-making process. Cite this article: Bone Joint J 2020;102-B(12):1675–1681.
The induced membrane technique for the management of long bone defects
Authors: Fung Benjamin , Hoit Graeme , Schemitsch Emil , Godbout Charles , Nauth Aaron
Published: November 2020

Aims

The purpose of this study was to: review the efficacy of the induced membrane technique (IMT), also known as the Masquelet technique; and investigate the relationship between patient factors and technique variations on the outcomes of the IMT.

Methods

A systematic search was performed in CINAHL, The Cochrane Library, Embase, Ovid MEDLINE, and PubMed. We included articles from 1 January 1980 to 30 September 2019. Studies with a minimum sample size of five cases, where the IMT was performed primarily in adult patients (≥ 18 years old), in a long bone were included. Multivariate regression models were performed on patient-level data to determine variables associated with nonunion, postoperative infection, and the need for additional procedures.

Results

A total of 48 studies were included, with 1,386 cases treated with the IMT. Patients had a mean age of 40.7 years (4 to 88), and the mean defect size was 5.9 cm (0.5 to 26). In total, 82.3% of cases achieved union after the index second stage procedure. The mean time to union was 6.6 months (1.4 to 58.7) after the second stage. Our multivariate analysis of 450 individual patients showed that the odds of developing a nonunion were significantly increased in those with preoperative infection. Patients with tibial defects, and those with larger defects, were at significantly higher odds of developing a postoperative infection. Our analysis also demonstrated a trend towards the inclusion of antibiotics in the cement spacer having a protective effect against the need for additional procedures.

Conclusion

The IMT is an effective management strategy for complex segmental bone defects. Standardized reporting of individual patient data or larger prospective trials is required to determine the optimal implementation of this technique. This is the most comprehensive review of the IMT, and the first to compile individual patient data and use regression models to determine predictors of outcomes. Cite this article: Bone Joint J 2020;102-B(12):1723–1734.