bluuebunny/crossref_metadata_2025 huggingface dataset:
H3.3 K36M Mutation as a Clinical Diagnosis Method of Suspected Chondroblastoma Cases
Authors: Mu Haoran , Jiang Yafei , Xue Linghang , Hua Yingqi , Lin Jun , Cai Zhengdong
Published: February 2021

Objective

Whether H3.3 K36M mutation (H3K36M) could be an approach if the diagnosis of chondroblastoma (CB) patients was indistinct and it was suspected to be unclear clinically.

Methods

We reviewed and compared our clinical experiences of CB cases and some suspected cases, which were not diagnosed distinctly, between 2013 to 2019. A total of 15 male and four female cases included in this study were seperated into two groups, CB group and suspected case (SC) group. The CB group included 13 men and 3 women, with an age range from 9 to 54 (mean age, 22 years old). The SC group included two men and one woman, with the age range from 13 to 25 (mean age, 19 years old). In both groups the patients had been followed‐up until December 2019 and none of the patients had prior treatment history. We evaluated the clinical complaints, radiological features, and clinical‐histological features of the cases and performed an immunohistochemical (IHC) study to detect whether the H3K36M expression of cases was different, consistent with a gene‐mutation analysis.

Results

In both groups, the radiologic features of both groups appeared as round low‐density shadow with a clear edge, pathologic features showed diffuse proliferation of neoplastic cells with multinuclear giant cells. The radiological tumor size of CB group and SC group showed little difference, which was about 29.0*21.6 mm. Clinical‐immunohistochemical features of both groups showed chondroid matrix inside with naïve tumor cells, multinucleated giant cells, and ground substance cells. Most of them showed chondro‐related antibody positive (12 cases) but some of them showed S‐100 negative (four cases). The clear difference of both groups was the result of H3K36M IHC study and gene analysis. In our cases, the CB group showed diffuse H3K36M positive and the SC group showed negative. The gene mutation analysis revealed that H3K36M‐positive CB patients had K36M mutation, which were not found in the SC group. Sanger sequencing showed an A > T substitution at codon 36 of histone H3F3B. No other types of histone H3 mutation was detected in the CB group. Particularly, one of the suspected cases showed a G34W mutation was confirmed to be a giant cell tumor of bone (GCTB).

Conclusions

Our study showed H3K36M immunohistochemistry and gene mutation analysis were specific clinical diagnostic tools to distinguish suspected CB from other giant cell‐rich or cartilage matrix‐diffuse bone tumors. The clinical‐radiological and histomorphological features of patients gave suggestions on whether the H3K36M IHC and gene analysis should be required.
Effects of UV‐filter Photostabilizers in the Photostability and Phototoxicity of Vitamin A Palmitate Combined with Avobenzone and Octyl Methoxycinnamate
Authors: Scarpin Marcela Silva , Kawakami Camila Martins , Rangel Karen Cristina , Pereira Karina de Castro , Benevenuto Carolina Gomes , Gaspar Lorena Rigo
Published: February 2021

A challenge for cosmetic and dermatologic products is to develop new high‐performance and safer anti‐aging products based on new compounds to enhance the stability of retinyl palmitate combined with broad‐spectrum UV‐filters. Consequently, the aim of this work was to evaluate the effects of three often used avobenzone photostabilizers—ethylhexyl methoxycrylene (EHMCR), tris(tetramethylhydroxypiperidinol) citrate (TTMHP) and tris‐biphenyl triazine (TBPT)—on the photostability and phototoxicity of the combination of avobenzone (AVO), octyl methoxycinnamate (OMC) and retinyl palmitate (RP). The photostability studies were performed by the exposure of formulations to UVA radiation. The phototoxicity was evaluated by the 3T3 neutral red uptake phototoxic assay (OECD TG 432). The addition of EHMCR, TBPT, and TTMHP in the formulations, with/or without RP, improved the photostability of AVO and RP, but EHMCR was the most effective in stabilizing RP. In the phototoxicity assay, the combinations AVO‐OMC containing or not RP showed phototoxic potential. EHMCR and TTMHP reduced the phototoxicity of the combination AVO‐OMC, whereas EHMCR also decreased the phototoxicity of the combination containing RP. Therefore, EHMCR might be used to the photostabilization of formulations of AVO‐OMC with/or not RP, while TTMHP can be added to this photounstable UV‐filter combination.
The effect of Q‐switched 1064‐nm Nd: YAG laser on skin barrier and collagen synthesis via miR‐663a to regulate TGFβ1/smad3/p38MAPK pathway
Authors: Yang Zhi , Duan Xiaoxia , Wang Xue , Xu Qi , Guo Birun , Xiang Shunli , Jia Xiaorong , He Li
Published: February 2021

Background

Our previous research found that Q‐switched 1064‐nm Nd: YAG laser (1064‐QSNYL) induces skin collagen synthesis by activating TGFβ1/Smad3/p38MAPKs pathway. Moreover, a lot of studies shown that MicroRNAs (miRNAs) contribute to regulate collagen synthesis and skin barrier. Therefore, we intend to explore the mechanism of 1064‐QSNYL on collagen synthesis and skin barrier through miRNAs.

Methods

We predicted the upstream miRNAs of TGFβ1 by bioinformatics databases, and verified them through dual‐luciferase reporter genes and Western blotting. The expression of collagen, skin barrier‐related protein K10 and filaggrin, TIMP‐1, and MMP‐2 were detected by RT‐qPCR and Western blotting, respectively. Moreover, we detected moisture content, elasticity value, TEWL value, SOD vitality, and hydroxyproline content to evaluate skin barrier of mice. H&E staining to observe the change of dermis thickness and inflammation and infiltration of mice skin.

Results

The results shown that TGFβ1 was target gene of miR‐663a. Moreover, we found that 1064‐QSNYL activated TGFβ1/smad3/p38MAPK pathway by down‐regulating the expression of miR‐663a in HaCaT, HDF cells, and mice, thereby promoting expression of Collagen I, Collagen IV, TIMP‐1, K10, and filaggrin and inhibiting MMP‐2. Furthermore, 1064‐QSNYL contributed to moisture content, elasticity, SOD vitality, and hydroxyproline content via miR‐663a to activate TGFβ1/smad3/p38MAPK pathway.

Conclusions

In summary, this study found for the first time that 1064‐QSNYL contributed to collagen synthesis and skin repair via miR‐663a to regulate TGFβ1/smad3/p38MAPK pathway, thereby achieving skin rejuvenation.
Expression of a high‐activity diacylglycerol acetyltransferase results in enhanced synthesis of acetyl‐TAG in camelina seed oil
Authors: Alkotami Linah , Kornacki Catherine , Campbell Shahna , McIntosh Gary , Wilson Cole , Tran Tam N.T. , Durrett Timothy P.
Published: February 2021

Acetyl‐triacylglycerols (acetyl‐TAG) contain an acetate group in the sn‐3 position instead of the long‐chain fatty acid present in regular triacylglycerol (TAG). The acetate group confers unique physical properties such as reduced viscosity and a lower freezing point to acetyl‐TAG, providing advantages for use as emulsifiers, lubricants, and ‘drop‐in’ biofuels. Previously, the synthesis of acetyl‐TAG in the seeds of the oilseed crop camelina (Camelina sativa) was achieved through the heterologous expression of the diacylglycerol acetyltransferase gene EaDAcT, isolated from Euonymus alatus seeds that naturally accumulate high levels of acetyl‐TAG. Subsequent work identified a similar acetyltransferase, EfDAcT, in the seeds of Euonymus fortunei, that possesses higher in vitro activity compared to EaDAcT. In this study, the seed‐specific expression of EfDAcT in camelina led to a 20 mol% increase in acetyl‐TAG levels over that of EaDAcT. Coupling EfDAcT expression with suppression of the endogenous competing enzyme DGAT1 further enhanced acetyl‐TAG accumulation, up to 90 mol% in the best transgenic lines. Accumulation of high levels of acetyl‐TAG was stable over multiple generations, with minimal effect on seed size, weight, and fatty acid content. Slight delays in germination were noted in transgenic seeds compared to the wild type. EfDAcT transcript and protein levels were correlated during seed development with a limited window of EfDAcT protein accumulation. In high acetyl‐TAG producing lines, EfDAcT protein expression in developing seeds did not reflect the eventual acetyl‐TAG levels in mature seeds, suggesting that other factors limit acetyl‐TAG accumulation.
Different functional roles of RTR complex factors in DNA repair and meiosis in Arabidopsis and tomato
Authors: Whitbread Amy Leanne , Dorn Annika , Röhrig Sarah , Puchta Holger
Published: February 2021

The RTR (RecQ/Top3/Rmi1) complex has been elucidated as essential for ensuring genome stability in eukaryotes. Fundamental for the dissolution of Holliday junction (HJ)‐like recombination intermediates, the factors have been shown to play further, partly distinct roles in DNA repair and homologous recombination. Across all kingdoms, disruption of this complex results in characteristic phenotypes including hyper‐recombination and sensitivity to genotoxins. The type IA topoisomerase TOP3α has been shown as essential for viability in various animals. In contrast, in the model plant species Arabidopsis, the top3α mutant is viable. rmi1 mutants are deficient in the repair of DNA damage. Moreover, as opposed to other eukaryotes, TOP3α and RMI1 were found to be indispensable for proper meiotic progression, with mutants showing severe meiotic defects and sterility. We now established mutants of both TOP3α and RMI1 in tomato using CRISPR/Cas technology. Surprisingly, we found phenotypes that differed dramatically from those of Arabidopsis: the top3α mutants proved to be embryo‐lethal, implying an essential role of the topoisomerase in tomato. In contrast, no defect in somatic DNA repair or meiosis was detectable for rmi1 mutants in tomato. This points to a differentiation of function of RTR complex partners between plant species. Our results indicate that there are relevant differences in the roles of basic factors involved in DNA repair and meiosis within dicotyledons, and thus should be taken as a note of caution when generalizing knowledge regarding basic biological processes obtained in the model plant Arabidopsis for the entire plant kingdom.
Coagulation, inflammation, and CD46 transgene expression in neonatal porcine islet xenotransplantation
Authors: Song Mingqing , Fitch Zachary W. , Samy Kannan P. , Martin Benjamin M. , Gao Qimeng , Patrick Davis Robert , Leopardi Francis V. , Huffman Niki , Schmitz Robin , Devi Gayathri R. , Collins Bradley H. , Kirk Allan D.
Published: February 2021

Background

Thrombosis is a known consequence of intraportal islet transplantation, particularly for xenogeneic islets. To define the origins of thrombosis after islet xenotransplantation and relate it to early inflammation, we examined porcine islets transplanted into non‐human primates using a dual‐transplant model to directly compare islet characteristics.

Methods

α1,3‐Galactosyltransferase gene‐knockout (GTKO) islets with and without expression of the human complement regulatory transgene CD46 (hCD46) were studied. Biologically inert polyethylene microspheres were used to examine the generic pro‐thrombotic effects of particle embolization. Immunohistochemistry was performed 1 and 24 hours after transplantation.

Results

Xeno‐islet transplantation activated both extrinsic and intrinsic coagulation pathways. The intrinsic pathway was also initiated by microsphere embolization, while extrinsic pathway tissue factor (TF) and platelet aggregation were more specific to engrafted islets. hCD46 expression significantly reduced TF, platelet, fibrin, and factor XIIIa accumulation in and around islets but did not alter intrinsic factor activation. Layers of TF+ cells emerged around islets within 24 hours, particularly co‐localized with vimentin, and identified as CD3+ and CD68+ cells inflammatory cells.

Conclusions

These findings detail the origins of thrombosis following islet xenotransplantation, relate it to early immune activation, and suggest a role for transgenic hCD46 expression in its mitigation. Layers of TF‐positive inflammatory cells and fibroblasts around islets at 24 hours may have important roles in the progressive events of thrombosis, inflammatory cell recruitment, rejection, and the ultimate outcome of transplanted grafts. These suggest that the strategies targeting these elements could yield more progress toward successful xenogeneic islet engraftment and survival.
Genomic features and antimicrobial resistance patterns of Shiga toxin‐producing Escherichia coli strains isolated from food in Chile
Authors: Sánchez Fernando , Fuenzalida Verónica , Ramos Romina , Escobar Beatriz , Neira Víctor , Borie Consuelo , Lapierre Lisette , López Paulina , Venegas Lucas , Dettleff Phillip , Johnson Timothy , Fuentes‐Castillo Danny , Lincopan Nilton , Galarce Nicolás
Published: February 2021

Shiga toxin‐producing Escherichia coli (STEC) is a zoonotic pathogen that causes severe illness in humans, often associated with foodborne outbreaks. Antimicrobial resistance among foodborne E. coli has increased over the last decades becoming a public health issue. In this study, the presence and features of STEC were investigated in samples of meat, seafood, vegetables and ready‐to‐eat street‐vended food collected in Chile, using a genomic and microbiological approach. Phenotypic and genotypic antimicrobial resistance profiles were determined, and serotype, phylogroup, sequence type (ST) and phylogenomics were predicted using bioinformatic tools. Three thousand three hundred samples collected in 2019 were screened, of which 18 were positive for STEC strains (0.5%), with stx2a (61.1%) being the predominant stx subtype. The presence of the virulence genes lpfA (100%), iha and ehaA (94.4%), and ehxA, hlyA and saa (83.3%) was confirmed among the STEC strains; the Locus of adhesion and autoaggregation (LAA) was predicted in 14 (77.8%) strains. Strains displayed resistance to colistin (100%), and intermediate resistance to enrofloxacin (11.1%) and chloramphenicol (5.6%). In this regard, mutations in the two‐component regulatory system genes pmrA (S29G), pmrB (D283G) and phoP (I44L), and the presence of the qnrB19 gene were confirmed. STEC strains belonged to ST11231 (38.9%), ST297 and ST58 (16.7% each), and ST1635, ST11232, ST446, ST442 and ST54 (5.6% each), and the most frequently detected serotypes were O113:H21 (44.4%), O130:H11 and O116:H21 (16.7% each), and O174:H21 (11.1%). Strains belonging to the international ST58 showed genomic relatedness with worldwide strains from human and non‐human sources. Our study reports for the first time the genomic profile of STEC strains isolated from food in Chile, highlighting the presence of international clones and sequence types commonly associated with human infections in different geographical regions, as well as the convergence of virulence and resistance in STEC lineages circulating in this country.
A Comparative Analysis of Macroprudential Policy across Euro Area Candidate Countries
Authors: CRISTE Adina , LUPU Iulia
Published: February 2021

Concerns to setting an appropriate overall macroprudential policy framework have taken shape at local, regional, and global level since the onset of the global financial crisis. At regional level, a particular case is that of the European Union, given the national-supranational relationship specific to this economic region. The article aims to identify the macroprudential policy condition of the Euro Area candidate countries, by using an index built on some criteria that describe on the one hand, the capacity of macroprudential policy governance and the “activism” of macroprudential authority, and, on the other hand, the degree of compliance with the European Systemic Risk Board (ESRB) recommendations for national macroprudential authorities, given that the countries under review are member states of the European Union. Our findings show that the Euro Area candidate countries have quite different macroprudential policy features, both in terms of its governance and in terms of the “convergence” towards ESRB recommendations. Although the analysis should be extended by adding other relevant criteria, we can assert that it offers an overview of the potential role of the national macroprudential policy as a shock-absorber instrument in the perspective of a future accession to the Euro Area.
Albanian Legislative Review from Gender Equality Perspective - Achievements and Challenges
Authors: Dini Elona
Published: February 2021

Gender-based and domestic violence happens in all societies all over the world. During the last decade in Albania gender - based violence has become more visible as a major problem. Domestic violence has been considered as a private matter and not a society issue. Albania did not recognize existence of domestic violence until 2006, when it adopted the Law on Measures against Violence in Family Relations. Official data show an increase in the general prevalence of violence against women in the family, from 56% in 2007 to 59.4% in 2013 and 52.9% in 2019. This legislative review presents an overview of the key legislative interventions in Albania to prevent gender-based and domestic violence and its impact in the society by highlighting main achievements and recommendations for further improvement, based on the analysis of results in the area. Methodology is based in a depth review of the key legal interventions on gender equality and domestic violence in the country. This review indicates that the response mechanisms have improved by following a multi-disciplinary point of view, however still profounder efforts are needed to provide proper services to domestic violence victims.
Entre bestias y bellezas : raza, género e identidad en Colombia
Authors: Stanfield Michael Edwar
Published: February 2021

A lo largo de la historia, la belleza ha sido muy valorada, pues ha sido de suma importancia en los ámbitos sociales, económicos, culturales y políticos en distintas sociedades. En Colombia, la belleza de sus mujeres, conocida mundialmente, se ha convertido en una fachada para problemas profundamente arraigados en su realidad nacional. Aunque ha tenido pocas dictaduras y se ha destacado por sus gobiernos democráticos, sus abundantes recursos y su economía dinámica, en toda su historia este país nunca ha tenido un Gobierno incluyente y soberano. Además, muchos de sus ciudadanos han sido pobres y excluidos, debido a políticas elitistas que favorecen a ricos y poderosos. En este libro, Michael Edward Stanfield explora cómo ha evolucionado el concepto de belleza en la historia cultural del país, revelando las nuevas facetas de las construcciones tradicionales de género, las jerarquías raciales y sus señas de identidad. Para esto, estudia el desarrollo y la transformación del Concurso Nacional de Belleza y los más de tres mil concursos regionales que se hacen cada año en el país. Justamente porque en Colombia, una nación que se caracteriza tanto por sus altos niveles de violencia e inseguridad como por su cautivadora hermosura geográfica, cultural y femenina, la belleza no solo reina, sino que cura, distrae y, a menudo, mata.
Linear Stability on the Local Thermal Nonequilibrium Model of Mixed Convection Boundary Layer Flow over a Moving Wedge in a Porous Medium: Viscous Dissipation and Radiation Effects
Authors: S. Shashi Prabha Gogate , M. C. Bharathi , Kudenatti Ramesh B.
Published: February 2021

This paper studies the local thermal nonequilibrium (LTNE) model for two-dimensional mixed convection boundary-layer flow over a wedge, which is embedded in a porous medium in the presence of radiation and viscous dissipation. It is considered that the temperature of the fluid and solid phases is not identical; hence, we require two energy equations: one for each phase. The motion of the mainstream and wedge is approximated by the power of distance from the leading boundary layer. The flow and heat transfer in the LTNE phase is governed by the coupled partial differential equations, which are then reduced to nonlinear ordinary differential equations via suitable similarity transformations. Numerical simulations show that when the interphase rate of heat transfer is large, the system attains the local thermal equilibrium (LTE) state and so is for porosity scaled conductivity. When LTNE is strong, the fluid phase reacts faster to the mainstream temperature than the corresponding solid phase. The state of LTE rather depends on radiation and viscous dissipation of the model. Further, numerical solutions successfully predicted the upper and lower branch solutions when the velocity ratio is varied. To assess which of these solutions is practically realizable, an asymptotic analysis on unsteady perturbations for a large time leading to linear stability needs to be performed. This shows that the upper branch solutions are always stable and practically realizable. The physical dynamics behind these results are discussed in detail.
Machine Learning-Based Methodology for Assessment of Doppler Reactivity of Sodium-Cooled Fast Reactor
Authors: Petrović Đorđe , Mikityuk Konstantin
Published: February 2021

In order to close nuclear fuel cycle and address the problem of sustainability, advanced nuclear reactor systems of the fourth generation are in the focus of the research for many years. With a simple goal of supporting this research, machine learning-based methodology for the assessment of the Doppler reactivity has been developed and applied to the European Sodium Fast Reactor (ESFR) in the frame of the ESFR-Safety Measures Assessment and Research Tools (SMART) Horizon-2020 project. In the scope of this study, a database of the precise Monte Carlo (MC) calculations was prepared and used to train artificial neural network (ANN) as a surrogate model to assess the Doppler reactivity across the range of reactor conditions that could occur throughout the life of the reactor core, in fast, yet accurate manner. The database was generated for all the combinations of several core parameters carefully predefined in order to account for both operational and accidental states of the core. Subsequently, Doppler reactivity change as a function of the above-mentioned parameters was assessed by herein developed methodology, as well as by widely used logarithmic dependence of the Doppler reactivity on the fuel temperature and compared to the results of the precise MC simulations. This study proves that, if certain computational resources are allocated to the database generation and ANN training, newly developed methodology yields similar or even more accurate results compared to the classical methodology and at the same time provides a tool for parameterization and interpolation of Doppler reactivity not only on the fuel temperature but also on the other parameters characterizing core of the sodium-cooled fast reactor (SFR).
Fatigue Analysis of Spherical Contact Subjected to Cyclic Elastic-Plastic Normal Loading
Authors: Chen Zhou , Jiang Yibo , Tong Zheming , Tong Shuiguang , Tan Jianrong
Published: February 2021

Surface fatigue resulting from cyclic contact loading is a main reason for the rough surface wear. Since a rough surface consists of many asperities, the fatigue in one asperity is investigated. The multiaxial Fatemi–Socie fatigue criterion is adopted to study the contact fatigue in a spherical asperity subjected to cyclic elastic-plastic normal loading. The fatigue damage in the asperity is predicted. The maximum fatigue damage occurs at the edge of the maximum contact area. Two typical patterns are found for the fatigue damage distribution. Locations and orientations of fatigue microcrack initiation are also identified. Finally, future research directions are discussed.
Stiffness Optimization of Redundant Mechanism Based on Elastic Coupling and Inertial Coupling Characteristics
Authors: Wan Xiao-Jin , Jia Dengfeng
Published: February 2021

Aiming to redundant parallel mechanism, on the basis of the kinetic energy method, virtual work principle, and perturbation method, the generalized mass matrix and generalized stiffness matrix are obtained, respectively. Two indices on inertial coupling and elastic coupling are defined to measure the decoupling level of the redundant parallel mechanism in terms of two generalized matrices. Furthermore, an algebraic solution method for natural frequency equation of the mechanism is utilized to obtain the natural frequency by means of the Cholesky decomposition method. Then, in order to minimize inertial coupling and elastic coupling and maximize the natural frequency of the mechanism, two indices and natural frequency are taken as objective functions to optimize the structural parameters of the redundant mechanism so that optimal dynamic performance of the mechanism is acquired. Two optimal solutions are selected in the optimization of natural frequency. One is to consider inertial coupling and elastic coupling, the other is to ignore inertial coupling and elastic coupling. Finally, the dynamic performance of the solution considering two indexes is better by comparing the dexterity of the two solutions.
Development of a Hydraulic Driven Bionic Soft Gecko Toe
Authors: Lu Mingyue , Chen Guangming , He Qingsong , Zong Weijia , Yu Zhiwei , Dai Zhendong
Published: February 2021

Geckos can climb freely on various types of surfaces using their flexible and adhesive toes. Gecko-inspired robots are capable of climbing on different surface conditions and have shown many important applications. Nonetheless, due to poor flexibility of toes, the movements of gecko-inspired robots are restricted to flat surfaces. To improve the flexibility, by utilizing design technique of soft actuator and incorporating the characteristics of a real gecko's toe, the design of new bionic soft toes is proposed. The abilities of this bionic toe are verified using modeling and two soft toes are manufactured. One is Type A toe having varied semi-circle cross sections as the feature of real gecko toe and the other is Type B toe with a constant semi-circle cross section. The bending behaviors of the bionic toes subjected to a range of hydraulic pressure are also experimentally studied. It demonstrated that both toes can perform similarly large bending angles for the adduction (attachment) and abduction (detachment) motions. In comparisons, Type B toe exhibits larger output force, which is ascribed to the fact that at proximal section of Type B corresponds to larger volume for bearing fluid. Both toes can not only provide sufficient adhesion but can be quickly detached with low peeling forces. Finally, different curved surfaces are used to further justify the applicability of these bionic toes. In particular, the flexible toes developed also have the advantages of low cost, lightweight, and simple control, which is desirable for wall-climbing robots.
Analysis of the Rigid Motion of a Conical Developable Mechanism
Authors: Woodland McKell , Hsiung Michelle , Matheson Erin L. , Safsten C. Alex , Greenwood Jacob , Halverson Denise M. , Howell Larry L.
Published: February 2021

We demonstrate analytically that it is possible to construct a developable mechanism on a cone that has rigid motion. We solve for the paths of rigid motion and analyze the properties of this motion. In particular, we provide an analytical method for predicting the behavior of the mechanism with respect to the conical surface. Moreover, we observe that the conical developable mechanisms specified in this article have motion paths that necessarily contain bifurcation points, which lead to an unbounded array of motion paths in the parameterization plane.
Prolonged evolution of the human B cell response to SARS-CoV-2 infection
Authors: Sakharkar Mrunal , Rappazzo C. Garrett , Wieland-Alter Wendy F. , Hsieh Ching-Lin , Wrapp Daniel , Esterman Emma S. , Kaku Chengzi I. , Wec Anna Z. , Geoghegan James C. , McLellan Jason S. , Connor Ruth I. , Wright Peter F. , Walker Laura M.
Published: February 2021

A comprehensive understanding of the kinetics and evolution of the human B cell response to SARS-CoV-2 infection will facilitate the development of next-generation vaccines and therapies. Here, we longitudinally profiled this response in mild and severe COVID-19 patients over a period of five months. Serum neutralizing antibody (nAb) responses waned rapidly but spike (S)-specific IgG
+
memory B cells (MBCs) remained stable or increased over time. Analysis of 1,213 monoclonal antibodies (mAbs) isolated from S-specific MBCs revealed a primarily de novo response that displayed increased somatic hypermutation, binding affinity, and neutralization potency over time, providing evidence for prolonged antibody affinity maturation. B cell immunodominance hierarchies were similar across donor repertoires and remained relatively stable as the immune response progressed. Cross-reactive B cell populations, likely re-called from prior endemic beta-coronavirus exposures, comprised a small but stable fraction of the repertoires and did not contribute to the neutralizing response. The neutralizing antibody response was dominated by public clonotypes that displayed significantly reduced activity against SARS-CoV-2 variants emerging in Brazil and South Africa that harbor mutations at positions 501, 484 and 417 in the S protein. Overall, the results provide insight into the dynamics, durability, and functional properties of the human B cell response to SARS-CoV-2 infection and have implications for the design of immunogens that preferentially stimulate protective B cell responses.
Effect of Itraconazole-Ezetimibe-Miltefosine Ternary Therapy in Murine Visceral Leishmaniasis
Authors: Andrade-Neto Valter V. , Rebello Karina M. , Pereira Thais M. , Torres-Santos Eduardo Caio
Published: February 2021

Drug combination therapy is an interesting approach to increase the success of drug repurposing for neglected diseases. Thus, the objective of this work was to evaluate binary and ternary therapies composed of itraconazole, ezetimibe, and miltefosine for the treatment of visceral leishmaniasis.
Listeria monocytogenes MenI Encodes a DHNA-CoA Thioesterase Necessary for Menaquinone Biosynthesis, Cytosolic Survival, and Virulence
Authors: Smith Hans B. , Li Tin Lok , Liao Man Kit , Chen Grischa Y. , Guo Zhihong , Sauer John-Demian
Published: February 2021

Listeria monocytogenes
is a Gram-positive, intracellular pathogen that is highly adapted to invade and replicate in the cytosol of eukaryotic cells. Intermediate metabolites in the menaquinone biosynthesis pathway are essential for the cytosolic survival and virulence of
L. monocytogenes
, independent of the production of menaquinone (MK) and aerobic respiration.
Identifying Potentially Beneficial Genetic Mutations Associated with Monophyletic Selective Sweep and a Proof-of-Concept Study with Viral Genetic Data
Authors: Furuse Yuki
Published: February 2021

In biology, research on evolution is important to understand the significance of genetic mutation. When there is a significantly beneficial mutation, a population of species with the mutation prospers and predominates, in a process called “selective sweep.” However, there are few methods that can find such a mutation causing selective sweep from genetic data.
Approach to patients with hip fracture and concurrent stroke
Authors: Lim Jing Wei , Ang Guat Cheng
Published: February 2021

We report a case of a 70-year-old man who presented with concomitant hip fracture and stroke. Our patient underwent surgical correction of a hip fracture despite the increased perioperative and postoperative risks associated with an acute stroke. He achieved good functional outcome after surgery and subsequent rehabilitation. There are no clear guidelines on the factors to determine whether a patient with concomitant stroke and hip fracture is a good candidate for surgical hip repair. Furthermore, there is also no consensus on the appropriate timing of surgical repair for such patients. We postulate that factors such as functional status, comorbidities, type and severity of stroke will affect the decision to proceed with surgical repair, and that there is a benefit in advocating for surgery in appropriate patients by a multidisciplinary orthogeriatric care team.
Robotic omental flap harvest for near-total anterior chest wall coverage: a potential application of robotic techniques in plastic and reconstructive surgery
Authors: Day Serena Jingxi , Dy Benzon , Nguyen Minh-Doan
Published: February 2021

We present the robotic harvest of a pedicled omentum flap for reconstruction of a near-total anterior chest wall defect. The patient was a 68-year-old woman with recurrent secondary chest wall angiosarcoma after previous mastectomy and radiation therapy. She underwent neoadjuvant chemotherapy and radiation, followed by wide radical chest wall resection with a final defect size of 15×35 cm. A one-stage reconstruction was performed with an omentum flap harvested by robotic technique and split-thickness skin grafts from thigh donor sites. The patient healed with minimal complications. Our case supports more widespread application of robotics in plastic and reconstructive surgery.
Association between splenectomy and chronic thromboembolic pulmonary hypertension: a systematic review and meta-analysis
Authors: Zhang Liyan , Yan Peijing , Yang Kehu , Wu Shanlian , Bai Yuping , Zhu Xinyu , Chen Xiaojie , Li Li , Cao Yunshan , Zhang Min
Published: February 2021

Objective

Whether splenectomy increases the risk of chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We conducted a systematic review and meta-analysis to explore the association between splenectomy and CTEPH.

Design

Systematic review and meta-analysis.

Data sources

PubMed, Embase and Cochrane Library databases.

Methods

Two authors independently searched and extracted the data. The Newcastle-Ottawa Scale and the Strengthening the Reporting of Observational Studies in Epidemiology guidelines were used to assess the quality of the included studies, and each quality item was graded as low risk or high risk. A random-effects model was used to calculate different effective values.

Results

In total, 8 trials involving 6183 participants fulfilled the inclusion criteria. The overall pooled crude prevalence of splenectomy was 4.0% (95% CI 0.03 to 0.06, I2=71.5%, p<0.001) in patients with CTEPH. Subgroup analysis showed a statistically significant high incidence of splenectomy in patients with CTEPH (OR=2.94, 95% CI 1.62 to 5.33, I2=0.0%, p<0.001) compared with patients with pulmonary arterial hypertension. There was a significantly high incidence of splenectomy in patients with CTEPH (OR=5.59, 95% CI 2.12 to 14.74, I2=0.0%, p<0.001) compared with patients with thromboembolism disease (venous thromboembolism or pulmonary embolism).

Conclusion

The prevalence of splenectomy in patients with CTEPH was 4.0% and CTEPH might be associated with splenectomy. However, high-quality prospective trials are needed.

PROSPERO registration number

CRD42020137591.
Controlled ovarian hyperstimulation for poor ovarian responders undergoing in vitro fertilisation/intracytoplasmic sperm injection: a protocol for systematic review and Bayesian network meta-analysis
Authors: Yang Huisheng , Zheng Chensi , Zheng Qiyan , Xu Huanfang , Li Xiaotong , Hao Mingzhao , Fang Yigong
Published: February 2021

Introduction

Controlled ovarian hyperstimulation (COH) is the routine regimen used to generate a sufficient number of follicles during in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatment. Poor ovarian response is a challenge encountered by many clinicians during COH and poor ovarian responders (PORs) usually have higher follicle stimulating hormone levels, lower levels of anti-Mullerian hormone and few oocytes retrieved, which have been attributed mainly to advanced maternal age and poor follicle reserve or other reasons that could impair ovarian response during ovarian stimulation. Over the last few decades, researchers have proposed a series of strategies and ovarian stimulation protocols to improve pregnancy outcomes in patients with POR during their IVF/ICSI treatment. However, clinical decisions regarding COH protocols in PORs during IVF/ICSI treatment remain controversial. Traditional pairwise meta-analysis only allows the direct comparison of two protocols in COH for patients with POR. However, many of these COH protocols have not been compared directly in randomised controlled trials (RCTs). Thus, we aim to use network meta-analysis (NMA) to assess the clinical effectiveness and safety of COH protocols and to generate treatment rankings of these COH protocols for the most clinically important and commonly reported outcomes events.

Methods and analysis

The PubMed, Embase, Cochrane Library, Web of Science, SinoMed, CNKI, WanFang database and Chongqing VIP information databases will be searched for all RCTs of COH for POR women during IVF/ICSI from inception to 31 March 2020. Primary outcomes will include live birth rate and number of oocytes retrieved. Secondary outcomes will include ongoing pregnancy rate, clinical pregnancy rate, miscarriage rate, ovarian hyperstimulation syndrome rate, multiple pregnancy rate and cycle cancellation rate. Pairwise meta-analysis and Bayesian NMA will be conducted for each outcome. Subgroup analysis, meta-regression, and sensitivity analysis will be performed to assess the robustness of the findings. The generation of NMA plots and subsequent results will be performed by using R V.4.0.1. The assessment of confidence in network estimates will use the Confidence in Network Meta-Analysis)web application (seehttps://cinema.ispm.unibe.ch/).

Ethics and dissemination

This review does not require ethics approval and the results of the NMA will be submitted to a peer-review journal.
Postlicensure herpes zoster vaccine effectiveness: systematic review protocol
Authors: Mbinta James F , Nguyen Binh P , Awuni Prosper Mandela A , Eme Paul E , Simpson Colin R
Published: February 2021

Introduction

Herpes zoster (HZ) and associated complications inflict substantial morbidity and associated healthcare and socioeconomic burdens. Current treatments are not fully effective, especially among the most vulnerable populations. Two HZ vaccines are available and are part of the national immunisation programmes in many countries. This review will evaluate the effectiveness of zoster vaccines against incident HZ and postherpetic neuralgia in adults 50 years and older.

Methods and analysis

The key information sources that will be searched include MEDLINE (Ovid), Embase (Ovid), Cochrane libraries and CINAHL. This search will consider postlicensure observational studies published in all languages between 2006 and 2020 that assessed the effectiveness of HZ/zoster vaccines in adults 50 years and older. The identification of studies will be complemented with the search of reference lists and citations, and contact with authors of papers to request missing or additional data, where required. Following the search, all identified citations will be collated, and duplicates will be removed. Titles and abstracts will then be screened by two independent reviewers for assessment against the inclusion criteria for the review. Selected studies will follow the process of critical appraisal, data extraction and data synthesis. Statistical analyses will be performed using a random-effect model.

Ethics and dissemination

Formal ethical approval is not required, as primary data will not be collected. The review will be disseminated in peer-reviewed publications and conference presentations.
Healthcare system maturity for integrated care: results of a Swiss nationwide survey using the SCIROCCO tool
Authors: Peytremann-Bridevaux Isabelle , Schusselé Filliettaz Séverine , Berchtold Peter , Grossglauser Michelle , Pavlickova Andrea , Gilles Ingrid
Published: February 2021

Objectives

To assess the maturity of the Swiss healthcare system for integrated care and to explore whether this maturity varied according to several variables.

Design

A Swiss nationwide individual electronic survey in November 2019.

Setting and population

Stakeholders identified via lists of the Swiss Forum for Integrated Care and of the integrated care unit of the Swiss Federal Office of Public Health, and representatives of 26 cantonal public health departments, were invited to participate.

Primary outcome measure

The outcome was the maturity of the Swiss healthcare system for integrated care, measured with the Scaling Integrated Care in Context maturity model tool (SCIROCCO tool), which comprises 12 dimensions and questions rated on a 6-point scale.

Analysis

Univariate analyses were first performed, followed by bivariate analyses, to find out whether maturity varied according to working linguistic region, healthcare profession, main domain of professional activity, implication in integrated care, attitude towards integrated care and attitude towards the Swiss healthcare system.

Results

The 642 respondents were 53.7 years on average, 42.5% were women, 60.0% and 20.7% worked in the German and French-speaking parts of Switzerland, respectively. Overall, the maturity of the Swiss healthcare system for integrated care was evaluated as low, with dimension means ranging from 1.0 (±1.0) for the ‘Funding’ dimension to a maximum of 2.7 (±1.1) for ‘eHealth Services’. Results only varied according to the working linguistic region.

Conclusions

Results highlight a limited maturity of the Swiss healthcare system for integrated care, as assessed at a national level by a large and varied number of healthcare stakeholders. They represent important information for the further development of integrated care in Switzerland, and should help identify areas requiring attention for a successful transformation of the Swiss healthcare system towards more integrated care.
Do medical students recognise the deteriorating patient by analysing their vital signs? A monocentric observational study based on the National Early Warning Score 2
Authors: Messerer David Alexander Christian , Fauler Michael , Horneffer Astrid , Schneider Achim , Keis Oliver , Mauder Lea-Marie , Radermacher Peter
Published: February 2021

Objective

Assessment of the expertise of medical students in evaluating vital signs and their implications for the current risk of a patient, an appropriate monitoring frequency, and a proper clinical response.

Methods

251 second-year and 267 fifth-year medical students in a curriculum consisting of 6 years of medical school at Ulm University, Germany, were interviewed in a paper-based questionnaire. The students were asked to rate their proficiency in interpreting vital signs and to give pathological thresholds of vital signs. Based on the National Early Warning Score 2 (NEWS2), nine vital signs of fictional patients were created and students were asked to comment on their clinical risk, to set an appropriate monitoring frequency as well as a clinical response.

Results

Interviewing medical students regarding each vital sign individually, the students indicated a pathological threshold in accordance with the NEWS2 for respiratory rate, temperature, and heart rate. By contrast, inappropriate pathological limits were given regarding oxygen saturation and systolic blood pressure. Translating the vital signs into nine fictional patients, fifth-year medical students overall chose an appropriate response in 78% (67%−78%, median±IQR). In detail, fifth-year students successfully identified patients at very high or low risk and allocated them accordingly. However, cases on the edge were often stratified inappropriately. For example, a fictional case with vital signs indicating a surging sepsis was frequently underappreciated (48.5%) and allocated to an insufficient clinical response by fifth-year students.

Conclusions

Recognising the healthy as well as the deteriorating patient is a key ability for future physicians. NEWS2-based education might be a valuable tool to assess and give feedback on student’s knowledge in this vital professional activity.
Protocol for a patient-reported experience measures (PREMs) survey of patients discharged during the COVID-19 pandemic and their family caregivers
Authors: Bonvin Eric , Tacchini-Jacquier Nadine , Monnay Sevrine , Verloo Henk
Published: February 2021

Introduction

In the Swiss canton of Valais, the first cases of SARS-CoV-2 were detected on 28 February 2020. Discharged patients’ and their family caregivers’ experiences in relation to safety, quality of care, trust and communication during the COVID-19 hospitalisation period remain unexplored. The study aims to collect the patient-reported experience measures (PREMs) survey of patients discharged during the COVID-19 pandemic and their family caregivers.

Methods and analysis

Patients aged ≥18 years, hospitalised between 28 February and 11 May 2020 and then discharged home, plus their family caregivers will be invited to complete a self-administrated questionnaire made up of 14 closed questions and 1 open-ended question. The questionnaire will include items on the patient’s hospital trajectory and assess the interpersonal trust placed in nurses and physicians based on Krajewska-Kułaket al’sTrust in Nurse Scaleand Andersonet al’sTrust in Physician Scale. Participants’ perceived stress will be assessed using Cohenet al’sPerceived Stress Scale. Feelings of safety will be examined based on Dryhurstet al’s questionnaire onRisk Perception During Pandemics. After ethical clearance, data will be collected using a postal paper questionnaire and via an online web link. Descriptive and inferential statistics will be computed, and the open question will undergo a qualitative thematic analysis. We will analyse perceptions of the different hospital trajectories experienced by patients undergoing surgery with and without a SARS-CoV-2 infection.

Ethics and dissemination

The Human Research Ethics Committee of Vaud (2020-02025) authorised this study. Gathering experiences and learning about the impact of the COVID-19 pandemic on the social determinants of health among discharged patients and families fit in well with the Triple Aim framework and the PREMs survey. The study will formulate recommendations to support interventions in the face of the second wave of COVID-19 pandemic and their effects on patients’ and their family caregivers’ experiences.
Do we need to improve the reporting of evidence in tendinopathy management? A critical appraisal of systematic reviews with recommendations on strength of evidence assessment
Authors: Challoumas Dimitris , Millar Neal L
Published: February 2021

Objective

To critically appraise the quality of published systematic reviews (SRs) of randomised controlled trials (RCTs) in tendinopathy with regard to handling and reporting of results with special emphasis on strength of evidence assessment.

Data sources

Medline from inception to June 2020.

Study eligibility

All SRs of RCTs assessing the effectiveness of any intervention(s) on any location of tendinopathy.

Data extraction and synthesis

Included SRs were appraised with the use of a 12-item tool devised by the authors arising from the Preferred Reporting Items in Systematic Reviews and Meta-Analyses statement and other relevant guidance. Subgroup analyses were performed based on impact factor (IF) of publishing journals and date of publication.

Results

A total of 57 SRs were included published in 38 journals between 2006 and 2020. The most commonly used risk-of-bias (RoB) assessment tool and strength of evidence assessment tool were the Cochrane Collaboration RoB tool and the Cochrane Collaboration Back Review Group tool, respectively. The mean score on the appraisal tool was 46.5% (range 0%–100%). SRs published in higher IF journals (>4.7) were associated with a higher mean score than those in lower IF journals (mean difference 26.4%±8.8%, p=0.004). The mean score of the 10 most recently published SRs was similar to that of the first 10 published SRs (mean difference 8.3%±13.7%, p=0.54). Only 23 SRs (40%) used the results of their RoB assessment in data synthesis and more than half (n=30; 50%) did not assess the strength of evidence of their results. Only 12 SRs (21%) assessed their strength of evidence appropriately.

Conclusions

In light of the poor presentation of evidence identified by our review, we provide recommendations to increase transparency and reproducibility in future SRs.