bluuebunny/crossref_metadata_2025 huggingface dataset:
Postoperative Neovascularization, Cerebral Hemodynamics and Clinical Prognosis Between Combined and Indirect bypass Revascularization Procedures in Hemorrhagic Moyamoya Disease.
Authors: Sun Jun , Li Yu Zhang , Chen Chuan , Ling Cong , Li Hao , Wang Hui
Published: July 2020

BACKGROUND: Present primary focus was rebleeding and prognosis of hemorrhagic moyamoya disease (MMD), while limited researches emphasized the postoperative collateral formation and cerebral hemodynamics. OBJECTIVE: To compare the diverse effects of combined (CB) and indirect (IB) bypass revascularization procedures on the postoperative collateral formation and hemodynamics in hemorrhagic MMD patients.METHODS: Hemorrhagic MMD patients treated surgically were retrospectively collected and dichotomized into CB and IB group. Postoperative complications and clinical prognosis, as well as pre- and post-operative Modified Rankin Scale (mRS), collateral circulation status and cerebral hemodynamics were observed and compared between the CB and IB groups. RESULTS: A total of 37 patients with hemorrhagic MMD were identified. Of 68 cerebral hemispheres, 47(69.1%) were combined revascularization and the rest indirect. During an average follow-up of 16.5±8.7 months, the recurrent stroke events were significantly lower, as well as postoperative mRS scores≤2, satisfactory postoperative collateral formation, improved dilation or extension of anterior choroidal /posterior communication artery (AchA/PcoA) were significantly higher in the CB group than in the IB group (all P< .05). Compared with preoperative cerebral hemodynamics, relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), mean transit time (MTT) and relative time to peak (rTTP) in the CB group; but in the IB group, rCBF, rCBV and MTT were significantly improved (all P< .001). The CB group’s postoperative rCBF was significantly improved as compared with the IB group (P< .001).CONCLUSION: CB can obtain better postoperative collateral formation, cerebral hemodynamics, and clinical prognosis as compared with IB.
Synergistic photoredox and copper catalysis by diode-like coordination polymer with twisted and polar copper-dye conjugation
Authors: Shi Yusheng , Zhang Tiexin , Jiang Xiao-Ming , Xu Gang , He Cheng , Duan Chunying
Published: July 2020

Synergistic photoredox and copper catalysis confers new synthetic possibilities in pharmaceutical field, but is seriously affected by the consumptive fluorescence quenching of Cu(II). By decorating bulky auxiliaries into photoreductive triphenylamine-based ligand to twist the conjugation between triphenylamine-based ligand and polar Cu(II)-carboxylate node in coordination polymer, we reported a heterogeneous approach to directly confronting this inherent problem. The twisted and polar Cu(II)-dye conjunction endowed coordination polymer with diode-like photoelectronic behaviours, which hampered the inter- and intramolecular photoinduced electron transfer from triphenylamine-moiety to Cu(II) site and permitted the reversed-directional ground-state electronic conductivity, rectifying the productive loop circuit for synergising photoredox and copper catalysis in pharmaceutically valuable decarboxylative C(sp3)-heteroatom couplings. The well-retained Cu(II) sites during photoirradiation exhibited unique inner-spheric modulation effects, which endowed the couplings with adaptability to different types of nucleophiles and radical precursors under concise reaction conditions, and distinguished the multi-olefinic moieties of biointeresting steride derivatives in their late-stage trifluoromethylation-chloration difunctionalisation.
Early detection of COVID-19 pandemic: evidence from Baidu Index
Authors: Tu Bizhi , Wei Laifu , Jia Yaya , Qian Jun
Published: July 2020

Background: New coronavirus disease 2019 (COVID-19) poses a severe threat to human life, and causes a global pandemic. The purpose of current research is to explore the onset and progress of the pandemic with a novel perspective using Baidu Index.Methods: We collected the confirmed data of COVID-19 infection between January 11, 2020, and April 22, 2020, from the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). Based on known literature, we obtained the search index values of the most common symptoms of COVID-19, including fever, cough, fatigue, sputum production, and shortness of breath. Spearman's correlation analysis was used to analyze the association between the Baidu index values for each COVID-19-related symptoms and the number of confirmed cases. Regional differences among 34 provinces/ regions were also analyzed. Results: Daily growth of confirmed cases and Baidu index values for each symptoms presented a robust positive correlation during the outbreak (fever: rs=0.705, p=9.623×10-6; cough: rs=0.592, p=4.485×10-4; fatigue: rs=0.629, p=1.494×10-4; sputum production: rs=0.648, p=8.206×10-5; shortness of breath: rs=0.656, p=6.182×10-5). The average search-to-confirmed interval is 19.8 days in China (fever: 22 days, cough: 19 days, fatigue: 20 days, sputum production: 19 days, and shortness of breath: 19 days). We discovered similar results in the top 10 provinces/regions, which had the highest cumulative cases. Conclusion: Search terms of COVID-19- related symptoms on the Baidu search engine can be used to early warn the outbreak of the epidemic. Relevant departments need to pay more attention to areas with high search index and take precautionary measures to prevent these potentially infected persons from spreading further. Baidu search engine can reflect the public's attention to the pandemic and regional epidemics of viruses. Based on changes in the Baidu index value, we can predict the arrival of the peak confirmed cases. The clinical characteristics related to COVID-19- including fever, cough, fatigue, shortness of breath, deserve more attention during the pandemic.
Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice
Authors: Arsenault Dany , Tremblay Cyntia , Emond Vincent , Calon Frederic
Published: July 2020

While the higher prevalence of Alzheimer Disease (AD) is clear, studies suggest that biological sex may also influence its pathogenesis . However, mechanisms behind these differences are not clear. To investigate physiological differences between sexes at the cellular level in the brain, we investigated the intrinsic and synaptic properties of entorhinal cortex neurons in heterozygous 3xTg-AD mice of both sexes at the age of 20 months. This brain region was selected because of its early association with AD symptoms . First, we found physiological differences between male and female non-transgenic mice, providing indirect evidence of axonal alterations in old females. Second, we observed a transgene-dependent elevation of the firing activity, post-burst after hyperpolarization (AHP) and spontaneous excitatory postsynaptic current (EPSC) activity, without any effect of sex. Third, the passive properties and the hyperpolarization-activated current (Ih) were altered by transgene expression only in female mice, whereas paired-pulse ratio (PPR) of evoked EPSC was changed only in males. Fourth, both sex and transgene expression were associated with changes in action potential properties. Consistent with previous work, higher levels of Aβ neuropathology were detected in 3xTg-AD females, whereas tau deposition was similar . In summary, our results support the idea that aging and AD neuropathology differentially alter the physiology of entorhinal cortex neurons in males and females.
Early Tracheal Extubation for Postoperative Recovery in Cardiac Surgery: Systematic Review and Meta-Analysis
Authors: Zhao Yi-Fan , Huang Zhen-Dong , Gu Hui-Yun , Zhang Chao , Guo Guang-Ling
Published: July 2020

Background: How to promote the rapid recovery of patients undergoing cardiac surgery and quality of life has been the focus of doctors’ attention. To compare the safety and efficacy of early cardiac extubation with conventional extubation (late extubation) in patients undergoing cardiac surgery.Methods: Ovid MEDLINE, Ovid Embase, EBSCOhost, Cochrane Library and ISIWeb of Science (1946–November 25, 2019) were searched to obtain randomized controlled trials of early tracheal extubation in patients undergoing cardiac surgery.Results: Compared with the conventional care group, in terms of effectiveness, the intensive care unit (ICU) stay and hospital length of stay in the early tracheal extubation was significantly shorter. In terms of security, most outcomes, including mortality, bleeding, stroke, acute renal failure and arrhythmia, were not statistically significant, except for myocardial infarction. However, the risk of re-intubation in the early tracheal extubation was higher than that of conventional extubation.Conclusions: This meta-analysis confirmed that early tracheal extubation may effectively reduce ICU hospitalization time, hospital length of stay and the risk of myocardial infarction. Although early tracheal extubation does not increase the risk of safety events, the clinicians need to pay more attention to be aware of possible risk of re-intubation. Meanwhile, as a key time point for extubation within 4 hours, it may help a little to reduce the risk of re-intubation and myocardial infarction.
Knowledge in Pain and Palliative Care in Medical Students From 2 Universities in Mozambique: A Cross Sectional Study
Authors: Pinto Emília , Schwalbach Teresa , Gonçalves Ferraz , Sacarlal Jahit , Castro Luisa , Rego Guilhermina
Published: July 2020

Background: Palliative Care (PC) needs have been increasing in low- and middle-income countries. The education of its contents avoids the patients and families´ suffering and therapeutic futility. Aim: to assess the pain and palliative care´s knowledge in Mozambican medical students of the fifth and sixth years. Methods: A cross–sectional study was conducted between August 2018 and July 2019. Data was collected by applying a self-administered survey directed to students from 2 medical schools in Mozambique. Comparison of answer’s frequencies between hospitals was performed using chi-square and Fisher’s exact test. Results: From the 146 participants, 52.7% were female and the median age was 24 years old. Regarding general knowledge: 90.1% think they need to improve their knowledge on pain management, 50.3% of the participants did not know the palliative care World Health Organization´s (WHO) definition. Concerning to therapeutic approach, 36.4% did not have knowledge in control of symptoms, 43.7% did not know the WHO pain management scale, 65.3% did not know how to initiate analgesia for cancer pain. There are significant differences between universities in training related to medical posture on communication to bad news to patients and family as well as training in terminally ill patients. Conclusion: Results show that students from these 2 medical schools have gaps in pain and palliative care knowledge. There is a need to introduce palliative care education in medical training in Mozambique.
The Fibronectin Type-III (FNIII) Domain of ATF7IP Contributes to Efficient Transcriptional Silencing Mediated by The SETDB1 Complex
Authors: Tsusaka Takeshi , Fukuda Kei , Shimura Chikako , Kato Masaki , Shinkai Yoichi
Published: July 2020

Background: The histone methyltransferase SETDB1 (also known as ESET) represses genes and various types of transposable elements, such as endogenous retroviruses (ERVs) and integrated exogenous retroviruses, through a deposition of trimethylation on lysine 9 of histone H3 (H3K9me3) in mouse embryonic stem cells (mESCs). ATF7IP (also known as MCAF1 or AM), a binding partner of SETDB1, regulates the nuclear localization and enzymatic activities of SETDB1 and plays a crucial role in SETDB1-mediated transcriptional silencing. In this study, we further dissected the ATF7IP function with its truncated mutants in Atf7ip knockout (KO) mESCs.Results: We demonstrated that the SETDB1-interaction region within ATF7IP is essential for ATF7IP-dependent SETDB1 nuclear localization and silencing of both ERVs and integrated retroviral transgenes, whereas its C-terminal fibronectin type-III (FNIII) domain is dispensable for both these functions; rather, it has a role in efficient silencing mediated by the SETDB1 complex. Proteomic analysis identified a number of FNIII domain-interacting proteins, some of which have a consensus binding motif. We showed that one of the FNIII domain-binding proteins, ZMYM2, was involved in the efficient silencing of a transgene by ATF7IP. RNA-seq analysis of Atf7ip KO and WT or the FNIII domain mutant of ATF7IP-rescued Atf7ip KO mESCs showed that the FNIII domain mutant re-silenced most de-repressed SETDB1/ATF7IP-targeted ERVs compared to the WT. However, the silencing activity of the FNIII domain mutant was weaker than that of the ATF7IP WT, and some of the de-repressed germ cell-related genes in Atf7ip KO mESCs were not silenced by the FNIII domain mutant. Such germ cell-related genes are targeted and silenced by the MAX/MGA complex, and MGA was also identified as another potential binding molecule of the ATF7IP FNIII domain in the proteomic analysis. This suggests that the FNIII domain of ATF7IP acts as a binding hub of ATF7IP-interacting molecules possessing a specific interacting motif we named FAM and contributes to one layer of the SETDB1/ATF7IP complex-mediated silencing mechanisms.Conclusions: Our findings contributed to further understanding the function of ATF7IP in the SETDB1 complex, revealed the role of the FNIII domain of ATF7IP in transcriptional silencing, and suggested a potential underlying molecular mechanism for it.
Integrated analytical approach to unveil the secrets of the recently discovered “Sphinx Room”: a new piece of Domus Aurea puzzle.
Authors: Caggiani Maria Cristina , Coccato Alessia , Mazzoleni Paolo , D’Alessio Alessandro , Russo Alfonsina , Barone Germana
Published: July 2020

The recent discovery of the Sphinx Room, belonging to the Domus Aurea Esquiline wing, thanks to the framework given by the project “Non-destructive analytical studies at Parco Archeologico del Colosseo (Rome, Italy)”, allowed to perform an analytical campaign, both in situ and on micro-fragments.
The first aim was the archaeometrical characterisation of the painting materials. In fact, the analytical information on the wall decorations contributes to the overall comprehension of this extraordinary imperial architecture, and allows to contextualize the newly-discovered room inside the Domus Aurea complex. Moreover, further knowledge on the painting technique is achieved, which is of relevance for the general understanding of Roman mural decorations. The palette, composed of Egyptian blue, green earths, iron- and lead-based red, orange and yellow, calcite, carbon black, allowed to compare the Sphinx Room to Corridor 92 and Room 114 of Domus Aurea and to other sites in Rome. Furthermore, the employ of an organic binder in some spots can be put forward based on spectroscopic results, which does not exclude a wider use of the a fresco.
Furthermore, a complementary methodological strategy was designed, in order to achieve a complete characterization of the materials. In addition to the well-known combination of in situ Raman and X-ray fluorescence analyses, Infrared Fourier Transform Spectroscopy was used, both in situ (Diffuse Reflectance) and in the lab (Attenuated Total Reflectance). The results confirm the suitability of this approach for the characterization of Roman wall paintings, where both inorganic and organic materials are simultaneously present.
C. elegans colony formation as a phase separation phenomenon
Authors: Chen Yuping , Ferrell James
Published: July 2020

Phase separation at the molecular scale affects many biological processes. The theoretical requirements for phase separation are fairly minimal, and analogous phenomena may occur at other scales in biology. Here we have examined colony formation in the nematode C. elegans as a possible example of phase separation by a population of organisms. Experimental data and mathematical modeling indicated that, similar to physical condensation processes like phase separation and micelle formation, the population density of worms determines colony formation in a thresholded fashion, with the threshold correctly predicted by phase separation theory. Furthermore, we found that a phenomenon akin to Ostwald ripening – a coarsening seen in many systems that undergo phase separation – occurs. Our results show that populations of organisms can undergo condensation phenomena and phase separation.
Multilingual topic modelling for tracking COVID-19 trends based on Facebook data analysis
Authors: AMARA Amina , TAIEB Mohamed Ali HADJ , AOUICHA Mohamed BEN
Published: July 2020

Social data has shown important role in tracking, monitoring and risk management of disasters. Indeed, several works focused on the benets of social data analysis to the healthcare practices and curing. Similarly, these data are exploited now for tracking the COVID-19 pandemic but the majority of works exploited twitter as source. In this paper, we choose to exploit Facebook, rarely used, for tracking the evolution of COVID-19 related trends. In fact, a multilingual dataset covering 7 languages (English (EN), Arabic (AR), Spanish (ES), Italian (IT), German (DE), French (FR) and Japanese (JP)) is extracted from Facebook public posts. The proposal is an analytics process including a data gathering step, pre-processing, LDA-based topic modelling and presentation module using graph structure. Data analysing covers the duration spanned from January 1st, 2020 to May 15, 2020 divided on three periods in cumulative way: rst period January-February, second period March-April and the last one to 15 May. The results showed that the extracted topics correspond to the chronological development of what has been circulated around the pandemic and the measures that have been taken in the various languages under discussion.
Anemarrhenae Rhizoma: Material Basis and Mechanism of Its Renal-Yin-Deficiency Syndrome Treating Effect and Its Effect Enhancement after Salt Stir-frying
Authors: Han Shu , Xu Jinkai , Li Weifei , Lu Xiaoyan , Zhi Meiru , Liu Kaiyang , Han Xitao , Tang Ya’nan , Liu Ziqin , Wang Hongyue , Yang Zhigang , Li Fei , Du Hong
Published: July 2020

Background This study aims to find out renal-yin-deficiency syndrome (RYDS) treating component of Anemarrhenae Rhizoma (AR) and its RYDS-treating mechanism, the contents of neomangiferin and mangiferin in raw AR after salt stir-frying, and the cause of enhancement of RYDS-treating effect of salt stir-fried AR.Methods HPLC method was used for determining contents of mangiferin and neomangiferin in the various AR samples and simulative salt stir-fried neomangiferin. Western Blot, ELISA, RT-PCR and some conventional methods were used to investigate the RYDS-treating effect of raw AR, salt stir-fried AR and mangiferin.Results Content of neomangiferin decreased and that of mangiferin increased in water stir-fried AR and salt stir-fried AR; HPLC chromatogram showed a mangiferin peak in simulative salt stir-fried neomangiferin; both AR samples and mangiferin exerted RYDS-treating effect by reducing/increasing certain general and specific physiological indexes, reducing levels of T3, T4, FT3, FT4, cAMP, and the ratio of cAMP/cGMP; elevating levels of TSH and cGMP; and increasing mRNA and protein expressions of PI3K/AKT/mTOR pathway in kidney in RYDS rats. The RYDS-treating effect of salt stir-fried AR and mangiferin was stronger than that of raw AR.Conclusions Results of the study show that mangiferin in AR is the material basis of the RYDS-treating effect, the mechanism of the effect is rectifying and adjusting a series of physiological, endocrino-immunological and genetic abnormalities caused by RYDS, and enhancement of effect of salt stir-fried AR is because of the increase in the content of mangiferin.
Functional Profiling of Saliva Microbiome is Essential for Oral Cancer Prediction
Authors: Chen Jiung-Wen , Chiang Wei-Fan , Wu Jer-Horng , Chen Yuh-Ling , Wu Wei-Sheng , Wu Li-Wha
Published: July 2020

Background: The association between microbiome and host disease has been documented in oral cancer, one of the leading cancers worldwide. Huge efforts are made to use the profile of oral microbiome and distinct signature species as markers to distinguish oral cancer patients from healthy individuals. The previous results, however, remain inconclusive. The assembly mechanisms of oral microbiome and their response to changes in oral carcinogenesis also have not been characterized. Here, using 16S rRNA gene amplicon sequencing and in-silico function prediction approaches, we analyzed the saliva microbiome in cohorts of orally healthy, oral verrucous hyperplasia, and oral cancer at taxon and function levels, and compared their corresponding predictive performance of oral cancer using machine learning algorithms.Results: Analyses of diversity and phylogenetic profiles of bacterial communities in saliva showed that microbiome dysbiosis was significantly linked to oral health status. As oral health deteriorated, the number of core species (>75% prevalence) as a percentage of overall species richness declined. In line with the null model-based analysis, taxonomic and functional assemblies of saliva microbiomes were primarily governed by the stochastic processes. Correspondingly, the quantitative assessment of partitioned beta-diversity suggested extremely high species turnover but low function turnover, revealing a functional redundancy of the oral ecosystem. Functional beta-diversity in salvia microbiome shifted from turnover to nestedness during carcinogenesis of oral verrucous hyperplasia, but this pattern was not observed at the taxon level. Moreover, using both taxon and function data as training features for machine learning-aided prediction on host health status supports a superior predictive performance when using functional profiling. Similar results were also obtained and validated using publicly accessible data.Conclusions: Our results suggest that altered oral bacterial communities are highly associated with carcinogenesis of oral verrucous hyperplasia. Partly owing to high taxonomic turnover and stochastic assembly processes of the oral ecosystem, discovering oral microbial consortia as universal biomarkers for oral cancer may prove difficult and arduous. Functional profiles are relatively stable and evolve a nestedness pattern during oral carcinogenesis, serving as a new benchmark to study the interplay of the oral microbiome and host health in the future.
Salivary cytokines as biomarkers of oral cancer: a systematic review
Authors: Chiamulera Mayara Martina Abatti , Zancan Caroline Biazzolo , Remor Aline Pertile , Gleber-Netto Frederico Omar , Baptistella Antuani Rafael
Published: July 2020

Background: Oral cancer (OC) is usually diagnosed at advanced clinical stages due to its asymptomatic nature and absence of pathognomonic signs in its early development phase. Delayed diagnosis is one of the major causes of OC treatment failure and poor prognosis. Development of alternative diagnostic approaches are imperative for improving early detection and therapeutic success rates. Salivary cytokines (SC) have been studied as potential diagnostic biomarkers for OC and may represent a potential tool for improvement of OC early detection. Methods: In this systematic review we identified SC studied as OC biomarker by systematically reviewing the PubMed and Cochrane Library databases using the terms: “oral cancer”, “cytokine”, and “saliva”, and also combined with “interleukin” or “interferon”. Only case-control studies that measured SC by ELISA from treatment naïve patients were included. Results: A total of 28 articles (from 2004 to 2018) were included, describing 10 different SC, which IL-8 and IL-6 were the most studied ones. SC levels were consistently higher among OC patients when compared to healthy controls and to patients with non-malignant oral conditions such as leukoplakia, lichen planus and gingivitis, irrespective of its inflammatory role. Conclusions: Our analysis suggests SC are consistently up-regulated among OC patients and may represent ideal biomarkers to be translated to the clinical practice.
A new alternative for corneal endothelial regeneration using autologous dental pulp stem cells
Authors: Bosch Begoña M , Salero Enrique , Núñez-Toldrà Raquel , Sabater Alfonso L , Gil Francesc J , Perez Roman A
Published: July 2020

Background
Failure of the corneal endothelium cell (CEC) monolayer is the main cause leading to corneal transplantation. Autologous cell-based therapies are required to reconstruct in vitro the cell monolayer. For this purpose, we propose the use of dental pulp stem cells isolated from the third molars to form CEC monolayer. We hypothesize that by using dental pulp stem cells (DPSC) that share an embryological origin with CEC, as they both arise from the neural crest, may allow a direct differentiation process avoiding the use of reprogramming techniques, such as induced pluripotent stem cells (iPSC).
Methods
In this work, we report a two-step differentiation protocol, where dental pulp stem cells are derived into neural crest stem cells and, then, into CEC.
Results
Initially, we compared the efficiency of direct differentiation of DPSC with the differentiation of iPSC to express NCSC related genes in adhesion culture, showing significantly higher levels of early stage marker AP2 for the DPSC compared to iPSC. To provide better environment for NCSC gene expression, suspension method was performed, which induced the formation of neurospheres. The results showed neurosphere formation after few days, obtaining the peak of NCSC marker expression after 4 days, showing overexpression of AP2, p75 and CHD7 markers, confirming the formation of NCSC like cells. Furthermore, pluripotent markers Oct4, Nanog and Sox2 were as well upregulated in suspension culture. Neurospheres were then directly cultured in CEC conditioned medium for the second differentiation, showing the conversion of DPSC into polygonal like cells expressing higher levels of ZO-1, ATP1A1, COL4A2 and COL8A1 markers, providing proof of the successful conversion into CEC.
Conclusions
Therefore, our findings demonstrate that patient-derived dental pulp stem cells represent an autologous cell source for corneal endothelial regeneration that avoids actual transplantation limitations as well as reprogramming techniques.
Factor XII in PMM2-CDG patients: role of N-glycosylation in the secretion and function of the first element of the contact pathway.
Authors: Gálvez Raquel López , Morena-Barrio María Eugenia de la , López-Lera Alberto , Pathak Monika , Miñano Antonia , Serrano Mercedes , Borgel Delphine , Roldán Vanessa , Vicente Vicente , Emsley Jonas , Corral Javier
Published: July 2020

Background. Congenital disorders of glycosylation (CDG) are rare diseases with impaired glycosylation and multiorgan disfunction, including hemostatic and inflammatory disorders. Factor XII (FXII), the first element of the contact phase, has an emerging role in hemostasia and inflammation. FXII deficiency protects against thrombosis and the p.Thr309Lys variant is involved in hereditary angioedema through the hyperreactivity caused by the associated defective O-glycosylation. We studied FXII in CDG aiming to supply further information of the glycosylation of this molecule, and its functional and clinical effects. Plasma FXII from 46 PMM2-CDG patients was evaluated by coagulometric and by Western Blot in basal conditions, treated with N-glycosydase F or activated by silica or dextran sulfate. A recombinant FXII expression model was used to validate the secretion and glycosylation of wild-type and variants targeting the two described FXII N-glycosylation sites (p.Asn230Lys; p.Asn414Lys) as well as the p.Thr309Lys variant. Results. PMM2-CDG patients had normal FXII levels (117%) but high proportions of a form lacking N-glycosylation at Asn414. Recombinant FXII p.Asn230Lys, and p.Asn230Lys&p.Asn414Lys had impaired secretion and increased intracellular retention compared to wild-type, p.Thr309Lys and p.Asn414Lys variants. The hypoglycosylated form of PMM2-CDG activated similarly than FXII fully glycosylated. Accordingly, no PMM2-CDG had angioedema. FXII levels did not associate to vascular events, but hypoglycosylated FXII, like hypoglycosylated transferrin, antithrombin and FXI levels did it. Conclusions. N-glycosylation at Asn230 is essential for FXII secretion. PMM2-CDG have high levels of FXII lacking N-glycosylation at Asn414, but this glycoform displays similar activation than fully glycosylated, explaining the absence of angioedema in CDG.
Elasticity Spectra as a Tool to Investigate Actin Cortex Mechanics
Authors: Lüchtefeld Ines , Bartolozzi Alice , Morales Julian Mejia , Dobre Oana , Basso Michele , Zambelli Tomaso , Vassalli Massimo
Published: July 2020

Background

The mechanical properties of single living cells have proven to be a powerful marker of the cell physiological state. The use of nanoindentation-based single cell force spectroscopy provided a wealth of information on the elasticity of cells, which is still largely to be exploited. The simplest model to describe cell mechanics is to treat them as a homogeneous elastic material and describe it in terms of the Young's modulus. Beside its simplicity, this approach proved to be extremely informative, allowing to assess the potential of this physical indicator towards high throughput phenotyping in diagnostic and prognostic applications.

Results

Here we propose an extension of this analysis to explicitly account for the properties of the actin cortex. We present a method, the Elasticity Spectra, to calculate the apparent stiffness of the cell as a function of the indentation depth and we suggest a simple phenomenological approach to measure the thickness and stiffness of the actin cortex, in addition to the standard Young's modulus.

Conclusions

The Elasticity Spectra approach is tested and validated on a set of cells treated with cytoskeleton-affecting drugs, showing the potential to extend the current representation of cell mechanics, without introducing a detailed and complex description of the intracellular structure.
Complex Foot Deformities Associated With Lower Limb Deformities: a New Therapeutic Strategy for Simultaneous Correction Using Ilizarov Procedure Together With Osteotomy and Soft Tissue Release
Authors: Boquan Qin , Yi Ren , Tingjiang Gan , Xi Liu , Hui Zhang
Published: July 2020

Aim The aim of the current study is to introduce a new therapeutic strategy for simultaneous correction of complex foot deformities (CFD) and the associated lower limb deformities (LLD) by using Ilizarov technique with osteotomy and soft tissue procedure and to report its early clinical results.Methods A retrospective review of CFD associated with LLD simultaneous correction utilizing Ilizarov procedure together with osteotomy and soft tissue balance from 2015 to 2019 was conducted.Results Thirty-two patients were followed for an average of 42.8 months. The mean external fixation time (EFT) was 6.5 months. The mean healing index (HI) was 1.7 months/cm. At the time of fixator removal, plantigrade feet were achieved in all patient, lower limb deformities were corrected. No recurrence of the deformities occurred. The mean LLRS AIM score was improved from 7.5 to 0.3. At the final follow-up, ASAMI-Paley score was graded as excellent in all limbs in the aspect of bone results, and functional results were defined as excellent in 29 (90.6%) limbs and good in 3 (9.4%) limbs. The mean Modified Dimeglio score was significantly improved from 7.2 to 1.3. No deep infection of the osteotomy site or nonunion was noted in the current study.Conclusion The therapeutic strategy by using Ilizarov procedure together with osteotomy and soft tissue balance is a safe and effective way to simultaneously correct CFD and LLD.Level of Evidence Level IV, retrospective case series
The predictive value of D-dimer test for venous thromboembolism during puerperium in women age 35 or older: A prospective cohort study
Authors: Hu Wen , Xu Dong , Li Juan , Chen Cheng , Chen Yuan , Xi Fangfang , Zhou Feifei , Guo Xiaohan , Zhao Baihui , Luo Qiong
Published: July 2020

Background
This study aimed to investigate the predictive value of the D-dimer for venous thromboembolism (VTE) events during puerperium of women age at 35 years or older, as well as to identify other risk factors associated with the occurrence of VTE.
Methods
It was a prospective observational cohort study, from January 2014 to December 2018, which involved 12451 women age 35 or older who delivered after 28 weeks of gestation at Women’s Hospital of Zhejiang University, School of Medicine. The maternal and fetal demographic characteristics, pregnancy complications, imaging finding and results of laboratory test within postpartum 24 hours including D-dimer, platelet and fibrinogen were collected for analyses.
Results
30(2.4‰) women were identified as VTE, including 1 PE event and 29 DVT events. The receiver operating characteristic (ROC) curve analysis suggested the best cutoff point for D-dimer level within postpartum 24 hours of women age 35 or older was 5.545 mg/L, with a specificity of 70.0% and a sensitivity of 75.4%. Besides, there was no statistical correlation between platelets and VTE, as well as between fibrinogen and VTE. On multivariate analysis, D-dimer ≥ 5.50 mg/L (OR = 5.874, 95%CI: 2.678–12.886) and emergency cesarean section (OR = 11.965, 95%CI: 2.732–52.401) were independently associated with VTE in puerperium of women age 35 or older.
Conclusions
We concluded that D-dimer ≥ 5.50 mg/L was an independent predictor of VTE in puerperium with maternal age 35 or older and D-dimer testing was a necessary examination for perinatal women.
Characterization of the ‘White’ Appearing Clots that Cause Acute Ischemic Stroke
Authors: Mereuta Oana Madalina , Fitzgerald Seán , Rossi Rosanna , Douglas Andrew , Pandit Abhay , McCarthy Ray , Gilvarry Michael , Brinjikji Waleed , Kallmes David F , O’Hare Alan , Power Sarah , Brennan Paul , Alderson Jack , Murphy Blathnaid , Davidson Maria , Brederlau Anke , Allardt Arne , Gunnarsson Thorsteinn , Tatlisumak Turgut , Rentzos Alexandros , Thornton John , Doyle Karen M
Published: July 2020

Background: Most clots retrieved from patients with acute ischemic stroke are ‘red’ in color and are predominantly composed of red blood cells and fibrin. ‘White’ clots represent a less common entity and their histological composition is largely unknown.The aim of this study was to investigate the composition, imaging and procedural characteristics of ‘white’ clots retrieved by mechanical thrombectomy.Materials and Methods:Nineteen ‘white’ thrombi selected by visual inspection from 293 cases were collected as part of the multi-institutional RESTORE registry. Non-contrast computed tomography (NCCT), histological and immunohistochemical analyses were performed. Components were quantified using Orbit Image Analysis.Results:Quantification of Martius Scarlett Blue stain identified platelets/other as the major component in ‘white’ clots’ (63%) followed by fibrin (26%), red blood cells (7%) and white blood cells (4%). ‘White’ clots presented significantly more platelets/other and less red blood cells compared to the ‘red’ clots which showed a mean of 23% and 44%, respectively. The mean platelet (CD42b) content in ‘white’ clots was 43%; von Willebrand Factor (vWF) mean expression was 38%.Collagen and calcification were associated in one case. Fatty acid binding protein 4 was expressed in two cases.‘White’ clots were also significantly smaller (9.5 versus 12 mm) and less hyperdense (52 versus 61 Hounsfield Units) on NCCT compared to the other cases.Conclusions:‘White’ clots represented 6% of our cohort and are platelet and vWF-rich. Calcification, collagen and adipocytes were found occasionally. ‘White’ clots differ from other clots in composition, size and density on NCCT.
Effectiveness of Exercise on Osteosarcopenia in Elderly People: A Protocol Systematic Review
Authors: Vinícius-Souza Guilherme Elias , Noll Matias , Silveira Erika Aparecida
Published: July 2020

Background: Osteosarcopenia is defined as the concomitant occurrence of sarcopenia and osteopenia or osteoporosis. Older adults with this syndrome have greater fragility and chances of mortality compared to those without these conditions. Exercise has been recommended as a treatment for osteosarcopenia based on interventions with sarcopenic and osteoporotic individuals separately. However, there is no evidence that physical exercise can really be an effective treatment for osteosarcopenia. Our objective is to identify whether physical exercise can improve the osteosarcopenia in older adults and lead to good health outcomes. Methods: We will perform a systematic review on the follow databases: PubMed, Embase, Cochrane, and Scopus. The criterion of inclusion will be clinical trial studies in which the interventions were physical exercises in older adults diagnosed with osteosarcopenia. To assess the risk of bias, the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) and the Black and Downs tools will be used. For each search result, the quality of the evidence will ultimately receive one of four grades: high quality, moderate quality, low quality, or very low quality. Discussion: Through this systematic review protocol, an article on physical exercise recommendations for osteosarcopenia in older adults will be prepared. The results of this study may lead to recommendations for physical exercise as a non-pharmacological treatment or complementary therapy for the prevention of osteosarcopenia.Systematic review registration: Ongoing on Prospero.Ethics and dissemination: Protocol written according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).
Fear response-based prediction for stress susceptibility to PTSD-like phenotypes
Authors: Jeong Min-Jae , Lee Changhee , Sung Ki-Bong , Jung Jung Hoon , Kim Joung-Hun
Published: July 2020

Most individuals undergo traumatic stresses at some points in their life, but only a small proportion develop stress-related disorders such as anxiety diseases and posttraumatic stress disorder (PTSD). Although stress susceptibility is one determinant of mental disorders, the underlying mechanisms and functional implication remain unclear yet. We found that an increased amount of freezing that animals exhibited in the intertrial interval (ITI) of a stress-enhanced fear learning paradigm, predicts ensuing PTSD-like symptoms whereas resilient mice show ITI freezing comparable to that of unstressed mice. To examine the behavioral features, we developed a systematic analytical approach for ITI freezing and stress susceptibility. Thus, we provide a behavioral parameter for prognosis to stress susceptibility of individuals in the development of PTSD-like symptoms as well as a new mathematical means to scrutinize freezing behavior.
Dissecting the Mechanism of Yuzhi Zhixue Granule on Ovulatory Dysfunctional Uterine Bleeding by Network Pharmacology and Molecular Docking
Authors: Li Jialin , Luo Hua , Liu Xinkui , Zhang Jingyuan , Zhou Wei , Guo Siyu , Chen Xiuping , Liu Yingying , Jia Shanshan , Wang Haojia , Li Bingbing , Cheng Guoliang , Wu Jiarui
Published: July 2020

Background: Yuzhi Zhixue Granule (YZG)is a traditional Chinese patent medicine for treating excessive menstrual flow caused by ovulatory dysfunctional uterine bleeding (ODUB) accompanied by heat syndrome. However, the underlying molecular mechanisms, potential targets, and active ingredients of this prescription are still unknown. Therefore, it is imperative to explore the molecular mechanism of YZG.Methods: The putative targets of YZG based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Search Tool for Interacting Chemicals (STITCH) databases were collected. The Therapeutic Target Database (TTD) and Pharmacogenomics Knowledgebase (PharmGKB) databases were used to identify the therapeutic targets of ODUB. A protein-protein interaction (PPI) network containing both the putative targets of YZG and known therapeutic targets of ODUB was built. Furthermore, bioinformatics resources from the database for annotation, visualization and integrated discovery (DAVID) were utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking was performed to verify the binding effect between the YZG screened compounds and potential therapeutic target molecules.Results: The study employed a network pharmacology method, mainly containing target prediction, network construction, functional enrichment analysis, and molecular docking to systematically research the mechanisms of YZG in treating ODUB. The putative targets of YZG that treat ODUB mainly involved PTGS1, PTGS2, ALOX5, CASP3, LTA4H, F7 and F10. The functional enrichment analysis suggested that the produced therapeutic effect of YZG against ODUB is mediated by synergistical regulation of several biological pathways, including apoptosis arachidonic acid (AA) metabolism, serotonergic synapse, complement and coagulation cascades and C-type lectin receptor signaling pathways. Molecular docking simulation revealed good binding afﬁnity of the seven putative targets with the corresponding compounds.Conclusion: This novel and scientific network pharmacology-based study holistically elucidated the basic pharmacological effects and the underlying mechanisms of YZG in the treatment of ODUB.
Analysis of Y Chromosome Microdeletion and Karyotype in 516 Patients With Azoospermia
Authors: Wu Lihua , Hu Jingjing , He Yiqun , Zhang Yicong , Liang Kailing , Guo Li , Chen Hanbiao , Wang Ting
Published: July 2020

Background: To investigate the correlation between Y chromosome microdeletion and cytogenetic analysis in patients with azoospermia.Methods: A total of 516 patients with azoospermia were enrolled from March 2015 to December 2019. Karyotype analysis(G-banding) was performed with peripheral blood.Y-chromosome azoospermia factor (AZF) were detected by quantitative fluorescent polymerase chain reaction (QF-PCR).Results: Chromosome abnormality was detected in 66 of the 516 azoospermia patients, with an abnormal rate of 12.8% In addition, 7.8% cases(40/516) presented with Y-chromosome AZF microdeletions, in which 27 cases patients with karyotype of 46,XY(67.5%,27/40) and 13 cases of chromosome abnormalities (32.5%,13/40).Conclusion: The incidence of Y chromosome microdeletion was higher in the patients with karyotype of 46,XY. Conventional cytogenetics cannot directly reflect the microdeletions of Y chromosome. Therefore, the combination of this two detection methods can help to clarify the genetic causes of patients with azoospermia and provide a theoretical basis for clinical assisted reproductive technology.
Acceptability and feasibility of S-1 plus cisplatin adjuvant chemotherapy for completely resected non-small cell lung cancer: an open-label, single arm, multicenter, phase 2 trial
Authors: Uematsu Shugo , Sano Atsushi , Isobe Kazutoshi , Usui Kazuhiro , Matsumoto Jun , Kiribayashi Takaharu , Obara Kiyohaya , Kitami Akihiko , Murakami Yoshitaka , Iyoda Akira
Published: July 2020

Background

Although platinum-based chemotherapy is accepted as adjuvant chemotherapy for resectable advanced non-small cell lung cancer (NSCLC), its completion rate is low due to severe adverse events. S-1 plus cisplatin is associated with relatively low toxicity and an unimpaired quality of life, and has been used for unresectable advanced lung cancer. We investigated the acceptability and feasibility of combination therapy with S-1 plus cisplatin as postoperative adjuvant chemotherapy following complete resection of pathological stage II-IIIA NSCLC.
Methods

Enrolled patients received oral S-1 at a dose depending on their body weight twice daily for 21 days with intravenous cisplatin 60 mg/m2 on day 8, with 1 cycle comprising 5 weeks and 4 cycles. Patients received standard precautions against adverse events and received standard treatment when adverse events occurred. The primary endpoint was completion rate; secondary endpoints included safety, status of drug administration, disease-free survival, and overall survival.
Results

A total of 19 patients [14 men, 5 women; mean age, 59.1 years; mean body surface area, 1.688 m2; 17 with an Eastern Cooperative Oncology Group performance status (PS) of 0 and 2 with a PS of 1; 7 (36.8%) with stage II disease and 12 (63.2%) with stage IIIA disease] were enrolled. The rate of completion of 4 cycles was 68.4%. Grade 3 adverse events that occurred in ≥10% of patients included neutropenia (21.1%), nausea (21.1%), and anorexia (15.8%). No grade 4 adverse events, febrile neutropenia, or treatment-related deaths occurred. The mean relative dose intensity was 79% for S-1 and 80% for cisplatin. The 2-year disease-free survival rate was 42.1%, and 2-year overall survival rate was 83.3%.
Conclusion

This study demonstrated the acceptability and feasibility of using S-1 plus cisplatin as adjuvant chemotherapy.
The effect of primary granulocyte-colony stimulating factor prophylaxis on the incidence of febrile neutropenia in patients with testicular germ cell tumors
Authors: Hapakova Nikola , Chovanec Michal , Rejlekova Katarina , Kalavska Katarina , Obertova Jana , Palacka Patrik , De Angelis Valentina , Světlovská Daniela , Sycova-Mila Zuzana , Mardiak Jozef , Mego Michal
Published: July 2020

Background: Testicular germ cell tumors (GCTs) are the most common solid malignancy in men 15-35 years old. Febrile neutropenia (FN) is a grievous complication of chemotherapy, frequently occurring in GCT patients. The aim of this retrospective study was to assess the effect of primary granulocyte-colony stimulating factor (G-CSF) prophylaxis on the incidence of FN in GCT patients. Patients and methods: This study was conducted from medical records database of GCTs patients treated with first line/adjuvant chemotherapy from January 2000 to December 2017. Starting in January 2006, patients received G-CSF prophylaxis after every cycle of chemotherapy. Results: Out of 393 patients, 265 patients received primary G-CSF prophylaxis and 128 patients did not receive prophylaxis. During the study period, 71 patients (18.1%) suffered FN events. Out of 128 patients who did not receive primary prophylaxis, 42 patients suffered FN, while only 29 patients with primary prophylaxis suffered FN (32.8% vs 10.9%, P = 0.0000001). On subgroup analysis, FN incidence decreased in all groups with primary prophylaxis, except for patients with stage I GCT receiving adjuvant chemotherapy. Patients receiving G-CSF prophylaxis had significantly longer overall survival when compared to patients without prophylaxis. (HR = 0.44, 95% CI 0.26-0.75; P = 0.0009).Conclusions: Primary G-CSF prophylaxis was associated with significantly decreased FN incidence in patients treated with first line chemotherapy for metastatic disease. Patients receiving G-CSF prophylaxis had significantly longer overall survival. We suggest, that primary G-CSF prophylaxis should be considered in GCT patients receiving first line chemotherapy.