bluuebunny/crossref_metadata_2025 huggingface dataset:
Lower frequency of MDSCs was significantly related to functional cure in CHB patients treated with peginterferon
Authors: Zhang Yao , Han Jiajia , Zhang Xueyun , Li Fahong , Guo Yifei , He Jingjing , Mao Richeng , Zhu Haoxiang , Yu Jie , Huang Yuxian , Yang Feifei , Zhang Jiming
Published: December 2022

Background and Aims

Myeloid‐derived suppressor cells (MDSCs) and CD4+ regulatory T cells (Tregs) expand during chronic hepatitis B virus (HBV) infection and inhibit antiviral immunity. However, the relationship between antiviral effect and the frequencies of those immune suppressive cells after pegylated interferon α‐2a (PegIFNα‐2a) therapy is not clearly understood. This study aimed to investigate the contribution of monocytic MDSCs (mMDSCs) and CD4+ Tregs to functional cure (HBsAg seroclearance) after PegIFNα‐2a therapy and evaluate the effect of PegIFNα‐2a therapy on these cells.

Methods

Flow cytometry analysis was performed along with longitudinal immune monitoring of 97 hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) patients receiving PegIFNα‐2a weekly for 48 weeks.

Results

The frequencies of mMDSCs and CD4+ Tregs increased in all HBV patients, and they were higher in the HBsAg persistence group than in the HBsAg seroclearance group. A significant decline in the frequency of mMDSCs was found in patients who realized functional cure after PegIFNα‐2a treatment. In contrast, the frequency of CD4+ Tregs in both the HBsAg seroclearance and persistence groups significantly increased. Multivariate analyses indicated that the baseline serum HBsAg levels (p < .001) and mMDSCs frequency (p = .027) were independently associated with the HBsAg clearance, and the combined marker (HBsAg plus mMDSCs) displayed the highest specificity (93.1%) than any other markers in predicting HBsAg seroclearance.

Conclusions

These results suggest that a poor response to PegIFNα‐2a treatment in CHB patients may be related to the frequencies of immune suppressive cells, while the therapeutic targeting of these cells might be effective in boosting anti‐HBV immunity.
Ar‐Ar and U‐Pb ages of Chelyabinsk and a re‐evaluation of its impact chronology
Authors: Beard Sky P. , Swindle Timothy D. , Lapen Thomas J. , Kring David A.
Published: December 2022

The LL5 chondrite Chelyabinsk has had numerous isotopic studies since its fall in 2013. These data have been used to suggest ~8 impact events recorded from multiple isotopic systems (e.g., Ar‐Ar, U–Pb, Sm‐Nd, Rb‐Sr, among others). We report details of Ar‐Ar and U‐Pb results and re‐evaluate the geochronology of Chelyabinsk. Argon has the youngest Ar‐Ar age recorded in meteorites, 25 ± 11 Ma, and an older resetting event at ~2550 Ma. The U‐Pb analysis has an upper concordia age of 4456 ± 23 Ma and a lower concordia age of 184 ± 200 Ma. The lower concordia intercept represents a later thermal event (e.g., an impact), the most recent time that lead loss occurred, and could represent resetting by the youngest event recorded by Ar‐Ar. Combining our data with literature results, we find strong evidence of at least four impact events (~4450, 2550, 1700, 25 Ma), with some evidence for two additional impacts (~3700, 1000 Ma).
Learner engagement and teaching effectiveness in livestreamed versus in‐person CME
Authors: Stephenson Christopher R. , Yudkowsky Rachel , Wittich Christopher M. , Cook David A.
Published: December 2022

Introduction

Engaging learners in continuing medical education (CME) is challenging. Recently, CME courses have transitioned to livestreamed CME, with learners viewing live, in‐person courses online. The authors aimed to (1) compare learner engagement and teaching effectiveness in livestreamed with in‐person CME and (2) determine how livestream engagement and teaching effectiveness is associated with (A) interactivity metrics, (B) presentation characteristics and (C) medical knowledge.

Methods

A 3‐year, non‐randomised study of in‐person and livestream CME was performed. The course was in‐person for 2018 but transitioned to livestream for 2020 and 2021. Learners completed the Learner Engagement Inventory and Teaching Effectiveness Instrument after each presentation. Both instruments were supported by content, internal structure and relations to other variables' validity evidence. Interactivity metrics included learner use of audience response, questions asked by learners and presentation views. Presentation characteristics included presentations using audience response, using pre/post‐test format, time of day and words per slide. Medical knowledge was assessed by audience response. A repeated measures analysis of variance (anova) was used for comparisons and a mixed model approach for correlations.

Results

A total of 159 learners (response rate 27%) completed questionnaires. Engagement did not significantly differ between in‐person or livestream CME. (4.56 versus 4.53, p = 0.64, maximum 5 = highly engaged). However, teacher effectiveness scores were higher for in‐person compared with livestream (4.77 versus 4.71 p = 0.01, maximum 5 = highly effective). For livestreamed courses, learner engagement was associated with presentation characteristics, including presentation using of audience response (yes = 4.57, no = 4.45, p < .0001), use of a pre/post‐test (yes = 4.62, no = 4.54, p < .0001) and time of presentation (morning = 4.58, afternoon = 4.53, p = .0002). Significant associations were not seen for interactivity metrics or medical knowledge.

Discussion

Livestreaming may be as engaging as in‐person CME. Although teaching effectiveness in livestreaming was lower, this difference was small. CME course planners should consider offering livestream CME while exploring strategies to enhance teaching effectiveness in livestreamed settings.
Estimating intraseasonal intrinsic water‐use efficiency from high‐resolution tree‐ring δ13C data in boreal Scots pine forests
Authors: Tang Yu , Sahlstedt Elina , Young Giles , Schiestl‐Aalto Pauliina , Saurer Matthias , Kolari Pasi , Jyske Tuula , Bäck Jaana , Rinne‐Garmston Katja T.
Published: December 2022

Intrinsic water‐use efficiency (iWUE), a key index for carbon and water balance, has been widely estimated from tree‐ring δ13C at annual resolution, but rarely at high‐resolution intraseasonal scale.

We estimated high‐resolution iWUE from laser‐ablation δ13C analysis of tree‐rings (iWUEiso) and compared it with iWUE derived from gas exchange (iWUEgas) and eddy covariance (iWUEEC) data for two Pinus sylvestris forests from 2002 to 2019.

By carefully timing iWUEiso via modeled tree‐ring growth, iWUEiso aligned well with iWUEgas and iWUEEC at intraseasonal scale. However, year‐to‐year patterns of iWUEgas, iWUEiso, and iWUEEC were different, possibly due to distinct environmental drivers on iWUE across leaf, tree, and ecosystem scales. We quantified the modification of iWUEiso by postphotosynthetic δ13C enrichment from leaf sucrose to tree rings and by nonexplicit inclusion of mesophyll and photorespiration terms in photosynthetic discrimination model, which resulted in overestimation of iWUEiso by up to 11% and 14%, respectively.

We thus extended the application of tree‐ring δ13C for iWUE estimates to high‐resolution intraseasonal scale. The comparison of iWUEgas, iWUEiso, and iWUEEC provides important insights into physiological acclimation of trees across leaf, tree, and ecosystem scales under climate change and improves the upscaling of ecological models.
Effects of Allogeneic Bone Substitute Configurations on Cell Adhesion Process In Vitro
Authors: Liu Jie , Yang Li , Zhang Hao , Zhang Jing‐yu , Hu Yong‐cheng
Published: December 2022

Objective

To explore the potential effect of three allogenic bone substitute configurations on the viability, adhesion, and spreading of osteoblasts in vitro.

Methods

Freeze‐dried cortical bone were ground and fractions were divided into three groups with different sizes and shapes, defined as bone fiber (0.1 mm × 0.1 mm × 3 mm), bone powder (0.45–0.9 mm), and bone granule group (3–6 mm). MC3T3‐E1 cells were divided and co‐cultured within groups to induce cell adhesion. The configuration of allogenic bone was captured by scanning electron microscopy and confocal laser scanning microscopy, and substrate roughness values were quantified. Cell adhesion rate was assessed using the hemocyte counting method, cell viability was determined by CCK‐8 assay and live/dead staining, and cell morphology was visualized by Phalloidin and DAPI, and the mRNA expression of adhesion‐related gene (vinculin) of different substitutes were determined with quantitative real‐time polymerase chain reaction.

Results

The roughness values of bone fiber, bone powder, and bone granule group were 1.878 μm (1.578–2.415 μm), 5.066 μm (3.891–6.162 μm), and 0.860 μm (0.801–1.452 μm), respectively (bone powder group compared with bone granule group, H = 18.015, P < 0.001). Similar OD values of all groups in CCK‐8 assay indicated good biocompatibility of these substitutes (bone fiber, 0.201 ± 0.004; bone powder, 0.206 ± 0.008; bone granule group, 0.197 ± 0.006; and the control group, 0.202 ± 0.016, F = 0.7152, P > 0.05). In addition, representative cell adhesion rates at 24 h showed significantly lower cell adhesion rate in bone fiber group (20.3 ± 1.6%) compared to bone powder (29.3 ± 4.4%) and bone granule group (27.3 ± 3.2%) (F = 10.51，P = 0.009 and P = 0.034, respectively), but there was no significant difference between the latter two groups (P > 0.05). Interestingly, the expression of vinculin mRNA steadily decreased in a time‐dependent manner. The vinculin expression reached its peak at 6 h in each group, and the vinculin levels in bone fiber, bone powder, and bone granule group were 2.119 ± 0.052, 3.842 ± 0.108, and 3.585 ± 0.068 times higher than those in the control group, respectively (F = 733.643, all P < 0.001). Meanwhile, there was a significant difference in the expression of target gene between bone powder and bone granule group (P = 0.006).

Conclusion

All allogenic bone substitutes presented an excellent cell viability. Moreover, bone powder and bone granule group were more likely to promote cell adhesion and spreading compared to bone fiber group.
Computer Navigation Assisted Restricted Kinematic Alignment Improves Short‐Term Outcomes in Total Knee Arthroplasty: An Ambispective Cohort Study
Authors: Ma Ruichen , Chen Xi , Li Haolin , Wang Yiou , Li Songlin , Li Shanni , Qian Wenwei
Published: December 2022

Objectives

Mechanical alignment (MA)‐total knee arthroplasty (TKA) has been challenged due to the excessive soft tissue release and the evidence of the clinical outcomes of computer assisted navigation is still limited. The aim of this ambispective cohort study was to: (i) investigate whether computer assisted navigation is capable to achieve restricted kinematic alignment (rKA)‐TKA; and (ii) compare the short‐term outcomes between rKA‐TKA and MA‐TKA.

Methods

We retrospectively included 41 patients diagnosed with osteoarthritis who received MA‐TKA between April 2019 and January 2021 and 43 patients diagnosed with osteoarthritis who received rKA‐TKA were included in the prospective cohort from January 2021 to September 2021. Demographical, peri‐operative, and radiological data were collected and compared. Unpaired two‐sample t‐test for continuous variables and χ2 test for categorical variables were used to compare various measurements in two groups. The patient‐reported outcome measures at baseline, 10 days (T1), and 6 months (T6) after surgery were statistically analyzed by generalized estimating equation (GEE) models.

Results

Fourty‐one patients (45 knees) and 43 patients (48 knees) were included in the MA and the rKA group respectively. Three constitutional knee phenotypes (II, I, IV) were the commonest in our population. Navigation improved the surgical accuracy (1.5° vs 3.5°, p < 0.001) and precision (interquartile range 4.0 vs 2.0, p < 0.001) in the rKA group than the MA group. The changes in Knee Injury and Osteoarthritis Outcome Score 12 (KOOS12), EuroQol five‐dimension questionnaire (EQ5D) from baseline to T1 and T6 for patients with on‐target rKA were larger than on‐target MA counterparts (26.053 vs 18.607, P < 0.001(KOOS12, T1), 0.457 vs 0.367 p < 0.001(EQ5D, T1); 51.017 vs 46.896, P = 0.023(KOOS12, T6), 0.606 vs 0.565, P = 0.01(EQ5D, T6)). Patients with on‐target rKA had better Forgotten Joint Score (FJS) at T1 (54.126 vs 40.965, P = 0.002) compared with on‐target MA counterparts.

Conclusions

Computer assisted navigation achieved the level of accuracy required by rKA‐TKA. rKA‐TKA offered significantly better short‐term outcomes than MA‐TKA.
A Rare Case of Melanotic Schwannoma Occurred Intraosseous of Sacrum: A Literature Review
Authors: Yan Xiaobo , Wang Keyi , Lin Nong , Huang Xin , Fu YanBiao , Ye Zhaoming
Published: December 2022

Background

Melanotic schwannoma is a rare tumor when it occurs in the sacrum. Though it is mostly classified as benign, the prognosis is unpredictable due to the possibility of recurrence and metastasis. Here, we reported a case of intraosseous of sacrum with good results and reviewed the literature.

Case Presentation

A 33‐year‐old male patient complained of low back pain and was discovered to have an obstruction at S2. Following the necessary imaging diagnosis, we treated the patient with piecemeal excision in conjunction with extended curettage, and the frozen biopsy revealed that the tumor was melanotic schwannoma. The intraosseous portion of the lesion was curettaged using high‐speed drill to enlarge the edge of curettage, and piecemeal excision for lesion within the sacral canal. After surgery, the patient received total 56Gy radiotherapy and frequent follow‐up. After 15 months follow‐up, there was no evidence of recurrence, and the nerve function was normal.

Conclusion

Melanotic schwannoma that occurs intraosseous of the sacrum is extremely rare and lacks typical clinical manifestations; however it can be identified through careful pathological and imaging diagnosis. Intralesional extended curettage combined with radiotherapy can achieve a good local control with a satisfactory clinical effect in this rare disease.
Meliaceae genomes provide insights into wood development and limonoids biosynthesis
Authors: Cui Gaofeng , Li Yun , Yi Xin , Wang Jieyu , Lin Peifan , Lu Cui , Zhang Qunjie , Gao Lizhi , Zhong Guohua
Published: December 2022

Meliaceae is a useful plant family owing to its high‐quality timber and its many limonoids that have pharmacological and biological activities. Although some genomes of Meliaceae species have been reported, many questions regarding their unique family features, namely wood quality and natural products, have not been answered. In this study, we provide the whole‐genome sequence of Melia azedarach comprising 237.16 Mb with a contig N50 of 8.07 Mb, and an improved genome sequence of Azadirachta indica comprising 223.66 Mb with a contig N50 of 8.91 Mb. Moreover, genome skimming data, transcriptomes and other published genomes were comprehensively analysed to determine the genes and proteins that produce superior wood and valuable limonoids. Phylogenetic analysis of chloroplast genomes, single‐copy gene families and single‐nucleotide polymorphisms revealed that Meliaceae should be classified into two subfamilies: Cedreloideae and Melioideae. Although the Meliaceae species did not undergo additional whole‐genome duplication events, the secondary wall biosynthetic genes of the woody Cedreloideae species, Toona sinensis, expanded significantly compared to those of A. indica and M. azedarach, especially in downstream transcription factors and cellulose/hemicellulose biosynthesis‐related genes. Moreover, expanded special oxidosqualene cyclase catalogues can help diversify Sapindales skeletons, and the clustered genes that regulate terpene chain elongation, cyclization and modification would support their roles in limonoid biosynthesis. The expanded clans of terpene synthase, O‐methyltransferase and cytochrome P450, which are mainly derived from tandem duplication, are responsible for the different limonoid classes among the species. These results are beneficial for further investigations of wood development and limonoid biosynthesis.
Assessment of the soluble proteins HMGB1, CD40L and CD62P during various platelet preparation processes and the storage of platelet concentrates: The BEST collaborative study
Authors: Cognasse Fabrice , Hamzeh Cognasse Hind , Eyraud Marie Ange , Prier Amélie , Arthaud Charles Antoine , Tiberghien Pierre , Begue Stephane , de Korte Dirk , Gouwerok Eric , Greinacher Andreas , Aurich Konstanze , Noorman Femke , Dumont Larry , Kelly Kathleen , Cloutier Marc , Bazin Renée , Cardigan Rebecca , Huish Sian , Smethurst Peter , Devine Dana , Schubert Peter , Johnson Lacey , Marks Denese C. ,   Biomedical Excellence for Safer Transfusion (BEST) Collaborative
Published: December 2022

Background

Structural and biochemical changes in stored platelets are influenced by collection and processing methods. This international study investigates the effects of platelet (PLT) processing and storage conditions on HMGB1, sCD40L, and sCD62P protein levels in platelet concentrate supernatants (PCs).

Study Design/Methods

PC supernatants (n = 3748) were collected by each international centre using identical centrifugation methods (n = 9) and tested centrally using the ELISA/Luminex platform. Apheresis versus the buffy coat (BC‐PC) method, plasma storage versus PAS and RT storage versus cold (4°C) were investigated. We focused on PC preparation collecting samples during early (RT: day 1–3; cold: day 1–5) and late (RT: day 4–7; cold: day 7–10) storage time points.

Results

HMGB1, sCD40L, and sCD62P concentrations were similar during early storage periods, regardless of storage solution (BC‐PC plasma and BC‐PC PAS‐E) or temperature. During storage and without PAS, sCD40L and CD62P in BC‐PC supernatants increased significantly (+33% and +41%, respectively) depending on storage temperature (22 vs. 4°C). However, without PAS‐E, levels decreased significantly (−31% and −20%, respectively), depending on storage temperature (22 vs. 4°C). Contrastingly, the processing method appeared to have greater impact on HMGB1 release versus storage duration. These data highlight increases in these parameters during storage and differences between preparation methods and storage temperatures.

Conclusions

The HMGB1 release mechanism/intracellular pathways appear to differ from sCD62P and sCD40L. The extent to which these differences affect patient outcomes, particularly post‐transfusion platelet increment and adverse events, warrants further investigation in clinical trials with various therapeutic indications.
Design-as-a-Service Framework for Enabling Innovations in Small- and Medium-Sized Enterprises
Authors: Agarwal Ankit , Sorathiya Pratik C. , Vaishnav Shubham , Desai K. A. , Mears Laine
Published: December 2022

Modern manufacturing enterprises must be agile to cope with sudden demand changes arising from increased global competition, geopolitical factors, and unforeseen circumstances such as the Covid-19 pandemic. Small- and Medium-Sized Enterprises (SMEs) in the manufacturing sector lack agility due to lower penetration of Information Technology (IT) and Operational Technology (OT), the inability to employ highly skilled human capital, and the absence of a formal innovation ecosystem for new products or solutions. In recent years, Cloud-based Design and Manufacturing (CBDM) has emerged as an enabler for product realization by integrating various service-based models. However, the existing framework does not thoroughly support the innovation ecosystem from concept to product realization by formally addressing economic challenges and human skillset requirements. The present work considers the augmentation of the Design-as-a-Service (DaaS) model into the existing CBDM framework for enabling systematic product innovations. The DaaS model proposes to connect skilled human resources with enterprises interested in transforming an idea into a product or solution through the CBDM framework. The model presents an approach for integrating human resources with various CBDM elements and end-users through a service-based model. The challenges associated with successfully implementing the proposed model are also discussed. It is established that the DaaS has the potential for rapid and economical product discovery and can be readily accessible to SMEs or independent individuals.
Adaptive Fractional-Order Fast-Terminal-Type Sliding Mode Control for Underwater Vehicle-Manipulator Systems
Authors: Yu Fujie , Zhu Qilong , Chen Yuan
Published: December 2022

This article proposes an adaptive fractional-order fast-terminal-type sliding mode control method to solve the trajectory tracking problem of the underwater vehicle-manipulator system in the presence of large dynamic uncertainties and strong external disturbances. For improving the control continuity and accuracy of the conventional sliding mode control method, a modified fractional-order sliding mode control scheme with a novel fractional-order sliding manifold and a fast-terminal-type reaching law is proposed. In addition, an auto-tuning law of switching gains is presented and combined with the fractional-order sliding mode control scheme to overcome the problem that the fixed switching gain may lead to obvious tracking performance degradation under complicated lumped disturbances. Finally, the superiorities of the proposed adaptive fractional-order fast-terminal-type sliding mode control method are verified through a series of comparative simulations of a 6-degrees-of-freedom (DOF) UVMS carrying a 6DOF manipulator.
Model of Angular Object Positioning Process by a System of Oblique Friction Force Fields on Parallel Planes
Authors: Piatkowski Tomasz
Published: December 2022

The primary contribution of the paper is a proposal of a method to minimize the angular positioning error in the process of transferring cuboidal objects between oblique friction force fields generated by two conveyors located on parallel planes. The research included infeed conveyors with two variants of inputs: angular and straight. It was assumed that the object, while moving between oblique conveyors at different heights, performs a 3D movement. The object is treated as a rigid body with a soft base, edges, and corners that can be subjected to significant local deformations. A modified nonlinear Kelvin model was used to describe the normal reaction forces at the contact points of the object with the bearing surfaces of the conveyors, and the modified static Bengisu–Akay friction model represents the tangential forces. Research shows that the use of a slight offset between the bearing surfaces of the conveyors and the highest possible proportion between the motion velocities of the infeed and outfeed conveyors have positive effect on improving the angular precision of the positioned objects. This conclusion applies to both variants of the infeed conveyor inputs. The results of the research have practical application in the design of high-performance conveyor transport systems, used in the processes of picking cuboidal objects, requiring a strictly defined angular orientation.
Thermodynamic Optimization of Subcritical and Supercritical Organic Rankine Cycle Power Plants for Waste Heat Recovery in Marine Vessels
Authors: Oyekale Joseph , Mgbemena Chinedum
Published: December 2022

This study was aimed at comparing the optimal thermodynamic performance of subcritical and supercritical organic Rankine cycle (ORC) plants for waste heat recovery from ship engines. The technical impacts of adopting a supercritical ORC scheme relative to the usual subcritical one have not been explicitly reported in the literature for heat recovery in ship engines, hence this study. The fluids R245fa, R134a, and R600a were employed for analysis due to their versatility in real systems. The ORC plants were modeled and optimized in matlab using established zero-dimensional models to satisfy the first law mass and energy balances. Results showed that introducing a recuperator would increase ORC performance. For the R600a which exhibited the best performance among the three working fluids, a net power output of 488.3 kW was obtained for the subcritical ORC without a recuperator (SYS A) and 543.7 kW for the one with a recuperator (SYS B). Furthermore, a switch to a supercritical ORC configuration increased the net power by about 29% for R134a and 10% for R600a, and increased the thermal efficiency by about 2.2 percentage points for R134a and 0.5 percentage points for R600a, referencing the supercritical configuration without a recuperator (SYS C) and SYS A.
Lean-Burn Combustor Simulator for an Engine-Component Test Facility: An Experimental and Computational Study
Authors: Amend Jonas , Lubbock Roderick , Ornano Francesco , Povey Thomas
Published: December 2022

The computational and experimental assessment of a lean-burn low-NOx combustor simulator for an engine component test facility is presented. The Engine Component Aero-Thermal (ECAT) facility is a full-scale engine-parts facility, designed for the study of the aero-thermal performance of fully cooled high-pressure nozzle guide vanes (NGVs). The facility operates with non-dimensionally matched engine conditions in terms of Reynolds number, Mach number, and coolant-to-mainstream pressure ratio. The combustor simulator is designed to replicate lean-burn conditions of swirl and temperature distortion upstream of the nozzle guide vanes. The purpose is to allow the study of flow capacity, aerodynamic performance (with film cooling), and thermal performance (overall effectiveness) in the presence of engine-realistic inlet distortions. The ECAT combustor simulator design builds on the work of Hall and Povey, who developed a full-scale low-speed atmospheric-pressure combustor simulator for the preliminary design of similar simulators later implemented in the Oxford Turbine Research Facility and ECAT. This pilot facility produced non-dimensional lean-burn combustor-exit conditions closely matched to target profiles representative of modern aero engines. This design was modified and scaled for compatibility with the annulus-line and higher-pressure operating conditions of the ECAT facility. In the present study, detailed experimental measurements with multi-hole probes and thermocouples (pressure profile and temperature field) are presented and compared to results from Reynolds-Averaged Navier–Stokes Simulations. Additional simulations were performed to understand how the elevated back-pressure and vane potential field affect the non-dimensional profiles of pressure loss, residual swirl, and temperature at the combustor–turbine interface. This is perhaps the most comprehensive study to date of a combustor simulator in an engine-scale research facility, providing a unique insight into the known challenges of simulator design, scaling issues when moving from low to high Reynolds number, and limitations of computational fluid dynamics in this flow environment. The results, which will serve as boundary conditions to understand the impact of this flow on components in future studies in this facility, demonstrate the fidelity with which lean-burn target conditions can be replicated in a non-reacting environment.
Construct Validity and Test–Retest Reliability of Hip Load Compared With Playerload During Football-Specific Running, Kicking, and Jumping Tasks
Authors: Wilmes Erik , Bastiaansen Bram J.C. , de Ruiter Cornelis J. , Vegter Riemer J.K. , Brink Michel S. , Weersma Hidde , Goedhart Edwin A. , Lemmink Koen A.P.M. , Savelsbergh Geert J.P.
Published: December 2022

Purpose: To determine the test–retest reliability of the recently developed Hip Load metric, evaluate its construct validity, and assess the differences with Playerload during football-specific short-distance shuttle runs. Methods: Eleven amateur football players participated in 2 identical experimental sessions. Each session included 3 different shuttle runs that were performed at 2 pace-controlled running intensities. The runs consisted of only running, running combined with kicks, and running combined with jumps. Cumulative Playerload and Hip Loads of the preferred and nonpreferred kicking leg were collected for each shuttle run. Test–retest reliability was determined using intraclass correlations, coefficients of variation, and Bland–Altman analyses. To compare the load metrics with each other, they were normalized to their respective values obtained during a 54-m run at 9 km/h. Sensitivity of each load metric to running intensity, kicks, and jumps was assessed using separate linear mixed models. Results: Intraclass correlations were high for the Hip Loads of the preferred kicking leg (.91) and the nonpreferred kicking leg (.96) and moderate for the Playerload (.87). The effects (95% CIs) of intensity and kicks on the normalized Hip Load of the kicking leg (intensity: 0.95 to 1.50, kicks: 0.36 to 1.59) and nonkicking leg (intensity: 0.96 to 1.53, kicks: 0.06 to 1.34) were larger than on the normalized Playerload (intensity: 0.12 to 0.25, kicks: 0.22 to 0.53). Conclusions: The inclusion of Hip Load in training load quantification may help sport practitioners to better balance load and recovery.
Exceptional fracture toughness of CrCoNi-based medium- and high-entropy alloys at 20 kelvin
Authors: Liu Dong , Yu Qin , Kabra Saurabh , Jiang Ming , Forna-Kreutzer Paul , Zhang Ruopeng , Payne Madelyn , Walsh Flynn , Gludovatz Bernd , Asta Mark , Minor Andrew M. , George Easo P. , Ritchie Robert O.
Published: December 2022

CrCoNi-based medium- and high-entropy alloys display outstanding damage tolerance, especially at cryogenic temperatures. In this study, we examined the fracture toughness values of the equiatomic CrCoNi and CrMnFeCoNi alloys at 20 kelvin (K). We found exceptionally high crack-initiation fracture toughnesses of 262 and 459 megapascal-meters
½
(MPa·m
½
) for CrMnFeCoNi and CrCoNi, respectively; CrCoNi displayed a crack-growth toughness exceeding 540 MPa·m
½
after 2.25 millimeters of stable cracking. Crack-tip deformation structures at 20 K are quite distinct from those at higher temperatures. They involve nucleation and restricted growth of stacking faults, fine nanotwins, and transformed epsilon martensite, with coherent interfaces that can promote both arrest and transmission of dislocations to generate strength and ductility. We believe that these alloys develop fracture resistance through a progressive synergy of deformation mechanisms, dislocation glide, stacking-fault formation, nanotwinning, and phase transformation, which act in concert to prolong strain hardening that simultaneously elevates strength and ductility, leading to exceptional toughness.
Active DNA demethylation promotes cell fate specification and the DNA damage response
Authors: Wang Dongpeng , Wu Wei , Callen Elsa , Pavani Raphael , Zolnerowich Nicholas , Kodali Srikanth , Zong Dali , Wong Nancy , Noriega Santiago , Nathan William J. , Matos-Rodrigues Gabriel , Chari Raj , Kruhlak Michael J. , Livak Ferenc , Ward Michael , Caldecott Keith , Di Stefano Bruno , Nussenzweig André
Published: December 2022

Neurons harbor high levels of single-strand DNA breaks (SSBs) that are targeted to neuronal enhancers, but the source of this endogenous damage remains unclear. Using two systems of postmitotic lineage specification—induced pluripotent stem cell–derived neurons and transdifferentiated macrophages—we show that thymidine DNA glycosylase (TDG)–driven excision of methylcytosines oxidized with ten-eleven translocation enzymes (TET) is a source of SSBs. Although macrophage differentiation favors short-patch base excision repair to fill in single-nucleotide gaps, neurons also frequently use the long-patch subpathway. Disrupting this gap-filling process using anti-neoplastic cytosine analogs triggers a DNA damage response and neuronal cell death, which is dependent on TDG. Thus, TET-mediated active DNA demethylation promotes endogenous DNA damage, a process that normally safeguards cell identity but can also provoke neurotoxicity after anticancer treatments.
Observing the quantum topology of light
Authors: Deng Jinfeng , Dong Hang , Zhang Chuanyu , Wu Yaozu , Yuan Jiale , Zhu Xuhao , Jin Feitong , Li Hekang , Wang Zhen , Cai Han , Song Chao , Wang H. , You J. Q. , Wang Da-Wei
Published: December 2022

Topological photonics provides a powerful platform to explore topological physics beyond traditional electronic materials and shows promising applications in light transport and lasers. Classical degrees of freedom are routinely used to construct topological light modes in real or synthetic dimensions. Beyond the classical topology, the inherent quantum nature of light provides a wealth of fundamentally distinct topological states. Here we implement experiments on topological states of quantized light in a superconducting circuit, with which one- and two-dimensional Fock-state lattices are constructed. We realize rich topological physics including topological zero-energy states of the Su-Schrieffer-Heeger model, strain-induced pseudo-Landau levels, valley Hall effect, and Haldane chiral edge currents. Our study extends the topological states of light to the quantum regime, bridging topological phases of condensed-matter physics with circuit quantum electrodynamics, and offers a freedom in controlling the quantum states of multiple resonators.
In Science Journals
Authors: Brand Jennie E. , Suleymanov Yury , Hines Pamela J. , Fogg Christiana N. , Osborne Ian S. , Hurtley Stella M. , Kelly Priscilla N. , Grocholski Brent , Vignieri Sacha , Jiang Di , Smith H. Jesse , Wong Wei , Aldenderfer Mark , Ray L. Bryan
Published: December 2022

Highlights from the
Science
family of journals
Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later
Authors: Milligan Emma C. , Olstad Katherine , Williams Caitlin A. , Mallory Michael , Cano Patricio , Cross Kaitlyn A. , Munt Jennifer E. , Garrido Carolina , Lindesmith Lisa , Watanabe Jennifer , Usachenko Jodie L. , Hopkins Lincoln , Immareddy Ramya , Shaan Lakshmanappa Yashavanth , Elizaldi Sonny R. , Roh Jamin W. , Sammak Rebecca L. , Pollard Rachel E. , Yee JoAnn L. , Herbek Savannah , Scobey Trevor , Miehlke Dieter , Fouda Genevieve , Ferrari Guido , Gao Hongmei , Shen Xiaoying , Kozlowski Pamela A. , Montefiori David , Hudgens Michael G. , Edwards Darin K. , Carfi Andrea , Corbett Kizzmekia S. , Graham Barney S. , Fox Christopher B. , Tomai Mark , Iyer Smita S. , Baric Ralph , Reader Rachel , Dittmer Dirk P. , Van Rompay Koen K.A. , Permar Sallie R. , De Paris Kristina
Published: December 2022

The U.S. Food and Drug Administration only gave emergency use authorization of the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines for infants 6 months and older in June 2022. Yet questions regarding the durability of vaccine efficacy, especially against emerging variants, in this age group remain. We demonstrated previously that a two-dose regimen of stabilized prefusion Washington SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or purified S-2P mixed with 3M-052, a synthetic Toll-like receptor (TLR) 7/8 agonist, in a squalene emulsion (Protein+3M-052-SE) was safe and immunogenic in infant rhesus macaques. Here, we demonstrate that broadly neutralizing and spike-binding antibodies against variants of concern (VOCs), as well as T cell responses, persisted for 12 months. At 1 year, corresponding to human toddler age, we challenged vaccinated rhesus macaques and age-matched nonvaccinated controls intranasally and intratracheally with a high dose of heterologous SARS-CoV-2 B.1.617.2 (Delta). Seven of eight control rhesus macaques exhibited severe interstitial pneumonia and high virus replication in the upper and lower respiratory tract. In contrast, vaccinated rhesus macaques had faster viral clearance with mild to no pneumonia. Neutralizing and binding antibody responses to the B.1.617.2 variant at the day of challenge correlated with lung pathology and reduced virus replication. Overall, the Protein+3M-052-SE vaccine provided superior protection to the mRNA-LNP vaccine, emphasizing opportunities for optimization of current vaccine platforms. The observed efficacy of both vaccines 1 year after vaccination supports the implementation of an early-life SARS-CoV-2 vaccine.
Cross-Species Permissivity: Structure of a Goat Adeno-Associated Virus and Its Complex with the Human Receptor AAVR
Authors: Large Edward E. , Silveria Mark A. , Weerakoon Onellah , White Tommi A. , Chapman Michael S.
Published: December 2022

Adeno-associated virus (AAV) is a small ssDNA satellite parvovirus. As a recombinant vector with a protein shell encapsidating a transgene, recombinant AAV (rAAV) is a leading delivery vehicle for gene therapy, with two FDA-approved treatments and 150 clinical trials for 30 diseases.
Mycobacterium tuberculosis
Infection among 1,659 Silicosis Patients in Zhejiang Province, China
Authors: Yang Qingluan , Lin Miaoyao , He Zhangyufan , Liu Xuefeng , Xu Yuzhen , Wu Jing , Sun Feng , Jiang Tian , Gao Yan , Huang Xitian , Zhang Wenhong , Ruan Qiaoling , Shao Lingyun
Published: December 2022

This study evaluated the prevalence of
Mycobacterium tuberculosis
infection in silicosis patients in mainland China and identified the potential risk factors for both active tuberculosis (ATB) and latent tuberculosis infection (LTBI). We believe that our study makes a significant contribution to the literature because we demonstrated that
M. tuberculosis
prevalence was high among silicosis patients.
The Effects of Antibiotic Combination Treatments on Pseudomonas aeruginosa Tolerance Evolution and Coexistence with Stenotrophomonas maltophilia
Authors: Law Jack P. , Wood A. Jamie , Friman Ville-Petri
Published: December 2022

Cystic fibrosis (CF) is a genetic condition that results in thick mucus secretions in the lungs that are susceptible to chronic bacterial infections. The bacterial pathogenPseudomonas aeruginosais often associated with morbidity in CF and is difficult to treat due to its high resistance to antibiotics.
Validating Methods To Eradicate Plant-Pathogenic Ralstonia Strains Reveals that Growth
In Planta
Increases Bacterial Stress Tolerance
Authors: Hayes Madeline M. , Dewberry Ronnie J. , Babujee Lavanya , Moritz Rebecca , Allen Caitilyn
Published: December 2022

Bacteria in the
Ralstonia solanacearum
species complex (RSSC) are globally distributed and cause destructive vascular wilt diseases of many high-value crops. These aggressive pathogens spread in diseased plant material and via contaminated soil, tools, and irrigation water.
Bio-Organic Fertilizer Promotes Pear Yield by Shaping the Rhizosphere Microbiome Composition and Functions
Authors: Wang Zhonghua , Yang Tianjie , Mei Xinlan , Wang Ningqi , Li Xiaogang , Yang Qingsong , Dong Caixia , Jiang Gaofei , Lin Jing , Xu Yangchun , Shen Qirong , Jousset Alexandre , Banerjee Samiran
Published: December 2022

Bio-organic fertilization is a widely used, eco-friendly, sustainable approach to increasing plant productivity in the agriculture and fruit industries. However, it remains unclear whether the promotion of fruit productivity is related to specific changes in microbial inoculants, the resident microbiome, and/or the physicochemical properties of rhizosphere soils.
Methane Concentration and δ13C Isotopic Signature in Methane over Arctic Seas in Summer and Autumn 2020
Authors: Pankratova N. V. , Belikov I. B. , Skorokhod A. I. , Belousov V. A. , Muravya V. O. , Flint M. V. , Berezina E. V. , Novigatsky A. N.
Published: December 2022

We have studied the assessment of methane content in the near atmospheric layer of the Arctic seas and the sources of its emissions. Continuous atmospheric measurements of methane concentration and δ13C isotope signature in methane were carried out during two expeditions aboard the R/V Akademik Mstislav Keldysh in the summer and autumn of 2020. The minimum CH4 concentration (mean 1.937 ± 0.010 ppm) were obtained over the North and Norwegian Seas. The maximum CH4 concentration took place above the Kara (1.998 ± 0.030 ppm on average, maximum values are up to 2.000–2.040 ppm) and White (2.006 ± 0.030 ppm on average) seas. The average values of δ13C in the studied region were close to that typical for the Northern Hemisphere: –47.5‰. Regional changes in δ13C allowed CH4 sources to be identified and showed that the methane concentration in the surface atmospheric level is mainly affected by the direction of air-mass advection.
What should be measured? Nursing education institutions performance: a qualitative study
Authors: Ghofrani Marjan , Valizadeh Leila , Zamanzadeh Vahid , Ghahramanian Akram , Janati Ali , Taleghani Fariba
Published: December 2022

Objectives

In this qualitative study, we specify important domains of a nursing education institution that need to be measured to represent its performance via students’ perspectives, one of the most important stakeholders in higher education.

Setting

This study was conducted in a nursing and midwifery faculty.

Participants

Participants were bachelor’s, master’s and Ph.D. students in nursing. Convenience sampling was used. The aim and methods of the study were explained to the students, and they were invited to participate in the focus groups. Four focus groups (n=27) were held.

Results

Thirteen categories emerged that were assigned to three components of the Donabedian model. The structure component contained three categories: learning fields, equipment and facilities and human resources standards. The process component contained five categories: workshops for students and staff, student familiarity with the institution’s rules and plans, teaching, students evaluation and evaluation of teaching staff by students and peers. And outcome components contained five categories: results of self-evaluation by students, graduates’ outcomes, students’ outcomes, students surveys results and related medical centres performance.

Conclusion(s)

Based on the needs and ideas of this important group of stakeholders, we can proceed further. Once we specify what is important to be measured, then it is appropriate to develop or choose suitable and measurable performance indicators for each of the recognised categories.
Prognostic and clinicopathological significance of the Prognostic Nutritional Index in patients with gastrointestinal stromal tumours undergoing surgery: a meta-analysis
Authors: Kang Niansong , Gu Hongping , Ni Yuehan , Wei Xia , Zheng Sihui
Published: December 2022

Objectives

Previous studies have investigated the prognostic value of the Prognostic Nutritional Index (PNI) in patients with gastrointestinal stromal tumours (GISTs). However, the results have been inconsistent. We performed a meta-analysis to quantitatively determine the prognostic and clinicopathological significance of PNI in GISTs.

Design

This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Pooled HRs and 95% CIs were calculated to estimate the prognostic value of PNI in patients with GISTs. Combined ORs and corresponding 95% CIs were used to evaluate the association between the PNI and clinicopathological characteristics.

Data sources

The electronic databases PubMed, Web of Science, Embase and Cochrane Library were thoroughly searched from inception to December 2021.

Eligibility criteria

A random-effects model or fixed-effects model was selected based on the level of heterogeneity among the included studies.

Results

Eight studies comprising 2307 patients were included in this meta-analysis. A low PNI was significantly associated with worse recurrence-free survival (RFS) (HR 2.02, 95% CI 1.66 to 2.47, p<0.001) and overall survival (OS) (HR 4.35, 95% CI 1.25 to 16.83, p=0.033) in patients with GISTs. In addition, a low PNI was significantly associated with tumour size ≥5 cm (OR 1.65, 95% CI 1.21 to 2.24, p=0.002) and primary tumour site in small intestine/colorectum/extra-GISTs (OR 2.03, 95% CI 1.26 to 3.26, p=0.004).

Conclusions

Patients with GISTs and a lower PNI had inferior RFS and OS. Patients with GISTs and a low PNI may have a higher risk of tumour recurrence.
Effect of a standardised heart team protocol versus a guideline-based protocol on revascularisation decision stability in stable complex coronary artery disease: rationale and design of a randomised trial of cardiology specialists using historic cases
Authors: Ma Hanping , Lin Shen , Li Xi , Wang Yang , Xu Bo , Zheng Zhe
Published: December 2022

Introduction

A multidisciplinary heart team approach has been recommended by revascularisation guidelines, but how to organise and implement the heart team in a standardised way has not been validated. Inter-team and intra-team decision instability existed in the guideline-based heart team protocol, and our standardised heart team protocol based on a mixed method study may improve decision stability. The objective of this study is to evaluate the effect of the standardised heart team protocol versus the guideline-based protocol on decision-making stability in stable complex coronary artery disease (CAD).

Methods and analysis

Eighty-four eligible interventional cardiologists, cardiac surgeons or non-interventional cardiologists from 26 hospitals in China have been enrolled. They will be randomised to a standardised heart team protocol group or a guideline-based protocol group to make revascularisation decisions for 480 historic cases (from a prospective registry) with stable complex CAD. In the standardised group, we will establish 12 heart teams based on an evidence-based protocol, including specialist selection, specialist training, team composition, team training and a standardised meeting process. In the guideline-based group, we will organise 12 heart teams according to the guideline principles, including team composition and standardised meeting process. The primary outcome is the overall percent agreement in revascularisation decisions between heart teams within a group. To demonstrate the clinical implication of decision-making stability, we will further explore the association between decision stability and 1-year clinical outcomes.

Ethics and dissemination

The study was approved by the Institutional Review Board (IRB) of Fuwai Hospital (No. 2019-1303). All participants have provided informed consent and all patients included as historic cases provided written informed consent at the time of entry to the prospective registry. The results of this trial will be disseminated through manuscript publication and national/international conferences, and reported in the trial registry entry.

Trial registration number

NCT05039567.