bluuebunny/crossref_metadata_2025 huggingface dataset:
DDX10 promotes the proliferation and metastasis of colorectal cancer cells via splicing RPL35
Authors: Zhou Xin , Liu Zhihong , He Tengfei , Zhang Cuifeng , Jiang Manman , Jin Yuxiao , Wu Ziyu , Gu Changji , Zhang Wei , Yang Xiaodong
Published: February 2022

Background

Colorectal cancer (CRC) has become the second deadliest cancer in the world and severely threatens human health. An increasing number of studies have focused on the role of the RNA helicase DEAD-box (DDX) family in CRC. However, the mechanism of DDX10 in CRC has not been elucidated.

Methods

In our study, we analysed the expression data of CRC samples from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Subsequently, we performed cytological experiments and animal experiments to explore the role of DDX10 in CRC cells. Furthermore, we performed Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein–protein interaction (PPI) network analyses. Finally, we predicted the interacting protein of DDX10 by LC–MS/MS and verified it by coimmunoprecipitation (Co-IP) and qPCR.

Results

In the present study, we identified that DDX10 mRNA was extremely highly expressed in CRC tissues compared with normal colon tissues in the TCGA and GEO databases. The protein expression of DDX10 was measured by immunochemistry (IHC) in 17 CRC patients. The biological roles of DDX10 were explored via cell and molecular biology experiments in vitro and in vivo and cell cycle assays. We found that DDX10 knockdown markedly reduced CRC cell proliferation, migration and invasion. Then, we constructed a PPI network with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). GO and KEGG enrichment analysis and gene set enrichment analysis (GSEA) showed that DDX10 was closely related to RNA splicing and E2F targets. Using LC–MS/MS and Co-IP assays, we discovered that RPL35 is the interacting protein of DDX10. In addition, we hypothesize that RPL35 is related to the E2F pathway and the immune response in CRC.

Conclusions

In conclusion, provides a better understanding of the molecular mechanisms of DDX10 in CRC and provides a potential biomarker for the diagnosis and treatment of CRC.
CD4+ICOS+Foxp3+: a sub-population of regulatory T cells contribute to malaria pathogenesis
Authors: Chauhan Rubika , Awasthi Vikky , Thakur Reva Sharan , Pande Veena , Chattopadhyay Debprasad , Das Jyoti
Published: February 2022

Background

Regulatory T cells are known to play a key role to counter balance the protective immune response and immune mediated pathology. However, the role of naturally occurring regulatory cells CD4+CD25+Foxp3+in malaria infection during the disease pathogenesis is controversial. Beside this, ICOS molecule has been shown to be involved in the development and function of regulatory T cell enhance IL-10 production. Therefore, possible involvement of the ICOS dependent regulatory CD4+ICOS+Foxp3+T cells in resistance/susceptibility during malaria parasite is explored in this study.

Methods

5 × 105red blood cells infected with non-lethal and lethal parasites were inoculated in female Balb/c mice by intra-peritoneal injection. Infected or uninfected mice were sacrificed at early (3rd day post infection) and later stage (10th day post infection) of infection. Harvested cells were analysed by using flow cytometer and serum cytokine by Bioplex assay.

Results

Thin blood films show that percentages of parasitaemia increases with disease progression in infections with the lethal malaria parasite and mice eventually die by day 14th post-infection. Whereas in case of non-lethal malaria parasite, parasitaemia goes down by 7th day post infection and gets cleared within 13th day. The number of CD4+ICOS+T cells increases in lethal infection with disease progression. Surprisingly, in non-lethal parasite, ICOS expression decreases after day 7th post infection as parasitaemia goes down. The frequency of CD4+ICOS+FoxP3+Tregs was significantly higher in lethal parasitic infection as compared to the non-lethal parasite. The level of IL-12 cytokine was remarkably higher in non-lethal infection compared to the lethal infection. In contrast, the level of IL-10 cytokines was higher in lethal parasite infection compared to the non-lethal parasite.

Conclusion

Taken together, these data suggest that lethal parasite induce immunosuppressive environment, protecting from host immune responses and help the parasite to survive whereas non-lethal parasite leads to low frequencies of Treg cells seldom impede immune response that allow the parasite to get self-resolved.

Graphical Abstract
Functional nanovesicles displaying anti-PD-L1 antibodies for programmed photoimmunotherapy
Authors: Chen Hu , Zhang Pengfei , Shi Yesi , Liu Chao , Zhou Qianqian , Zeng Yun , Cheng Hongwei , Dai Qixuan , Gao Xing , Wang Xiaoyong , Liu Gang
Published: February 2022

Background

Photoimmunotherapy is one of the most promising strategies in tumor immunotherapies, but targeted delivery of photosensitizers and adjuvants to tumors remains a major challenge. Here, as a proof of concept, we describe bone marrow mesenchymal stem cell-derived nanovesicles (NVs) displaying anti-PD-L1 antibodies (aPD-L1) that were genetically engineered for targeted drug delivery.

Results

The high affinity and specificity between aPD-L1 and tumor cells allow aPD-L1 NVs to selectively deliver photosensitizers to cancer tissues and exert potent directed photothermal ablation. The tumor immune microenvironment was programmed via ablation, and the model antigen ovalbumin (OVA) was designed to fuse with aPD-L1. The corresponding membrane vesicles were then extracted as an antigen–antibody integrator (AAI). AAI can work as a nanovaccine with the immune adjuvant R837 encapsulated. This in turn can directly stimulate dendritic cells (DCs) to boast the body's immune response to residual lesions.

Conclusions

aPD-L1 NV-based photoimmunotherapy significantly improves the efficacy of photothermal ablation and synergistically enhances subsequent immune activation. This study describes a promising strategy for developing ligand-targeted and personalized cancer photoimmunotherapy.

Graphic Abstract
Prevalence of autoantibodies in patients with juvenile idiopathic arthritis: results from the German inception cohort ICON-JIA
Authors: Schulz Caroline , Fuehner Sabrina , Schlüter Bernhard , Fobker Manfred , Sengler Claudia , Klotsche Jens , Niewerth Martina , Minden Kirsten , Foell Dirk
Published: February 2022

Background

An association of different autoimmune diseases is suspected. In juvenile idiopathic arthritis (JIA), only few and partially conflicting data on the co-existence of other autoimmune disorders are available. The prevalence of autoantibodies in patients with JIA in Germany is not known.

Methods

Samples from 499 patients (median age at time of blood collection 11 years, median disease duration 4.4 years) in the prospective, multicenter inception cohort of children newly diagnosed with JIA (ICON-JIA) were analysed for the presence of anti-thyroid antibodies, celiac disease-specific antibodies (anti-tTG IgA, anti-tTG IgG), and connective tissue disease-associated antibodies (CTD-screen).

Results

A total of 76 (15.2%) patients had either clinically diagnosed autoimmune comorbidity or elevated autoantibodies. Of 21 patients with clinical autoimmune comorbidity, only 8 were also serologically positive at the time of testing, while 55 patients had autoantibodies without clinical diagnosis. Thus, 63 patients (12.6%) had at least one elevated autoantibody. Antibodies against thyroglobulin were found in 3% and against thyreoperoxidase in 4% of the samples. TSH receptor antibodies could not be detected in any of the 499 patients. Tissue transglutaminase antibodies were elevated in 0.4% of the patients. A positive screen for CTD-specific antinuclear antibodies was found in 7%, but only rarely specific antibodies (anti-dsDNA 1.4%, anti-SS-A and -SS-B 0.2% each, anti-CENP-B 0.4%) were confirmed.

Conclusions

In our study, a specific correlation between JIA and other autoimmune phenomena could not be confirmed. The lack of well-matched control groups makes interpretation challenging. Further data need to corroborate the suspected increased risk of developing other autoimmune phenomena in JIA patients.
Elevated proportion of TLR2- and TLR4-expressing Th17-like cells and activated memory B cells was associated with clinical activity of cerebral cavernous malformations
Authors: Castro Camilla , Oyamada Hugo A. A. , Cafasso Marcos Octávio S. D. , Lopes Lana M. , Monteiro Clarice , Sacramento Priscila M. , Alves-Leon Soniza Vieira , da Fontoura Galvão Gustavo , Hygino Joana , de Souza Jorge Paes Barreto Marcondes , Bento Cleonice A. M.
Published: February 2022

Background

Recent evidences have suggested the involvement of toll-like receptor (TLR)-4 in the pathogenesis of cerebral cavernous malformations (CCM). Elevated frequency of TLR+T-cells has been associated with neurological inflammatory disorders. As T-cells and B-cells are found in CCM lesions, the objective of the present study was to evaluate the cytokine profile of T-cells expressing TLR2 and TLR4, as well as B-cell subsets, in asymptomatic (CCMAsympt) and symptomatic (CCMSympt) patients.

Methods

For our study, the cytokine profile from TLR2+ and TLR4+ T-cell and B-cell subsets in CCMAsympt and CCMSympt patients was investigated using flow cytometry and ELISA. T-cells were stimulated in vitro with anti-CD3/anti-CD28 beads or TLR2 (Pam3C) and TLR4 (LPS) ligands.

Results

CCMSymptc patients presented a higher frequency of TLR4+(CD4+ and CD8+) T-cells and greater density of TLR4 expression on these cells. With regard to the cytokine profile, the percentage of TLR2+ and TLR4+ Th17 cells was higher in CCMSympt patients. In addition, an elevated proportion of TLR4+ Tc-1 cells, as well as Tc-17 and Th17.1 cells expressing TLR2 and TLR4, was observed in the symptomatic patients. By contrast, the percentage of TLR4+ IL-10+CD4+ T cells was higher in the CCMAsympt group. Both Pam3C and LPS were more able to elevate the frequency of IL-6+CD4+T cells and Th17.1 cells in CCMSympt cell cultures. Furthermore, in comparison with asymptomatic patients, purified T-cells from the CCMSympt group released higher levels of Th17-related cytokines in response to Pam3C and, mainly, LPS, as well as after activation via TCR/CD28. Concerning the B-cell subsets, a higher frequency of memory and memory activated B-cells was observed in CCMSympt patients.

Conclusions

Our findings reveal an increase in circulating Th17/Tc-17 cell subsets expressing functional TLR2 and, mainly, TLR4 molecules, associated with an increase in memory B-cell subsets in CCM patients with clinical activity of the disease.
Neurodegeneration in the centrally-projecting Edinger–Westphal nucleus contributes to the non-motor symptoms of Parkinson’s disease in the rat
Authors: Ujvári Balázs , Pytel Bence , Márton Zsombor , Bognár Máté , Kovács László Ákos , Farkas József , Gaszner Tamás , Berta Gergely , Kecskés Angéla , Kormos Viktória , Farkas Boglárka , Füredi Nóra , Gaszner Balázs
Published: February 2022

Background

The neuropathological background of major depression and anxiety as non-motor symptoms of Parkinson’s disease is much less understood than classical motor symptoms. Although, neurodegeneration of the Edinger–Westphal nucleus in human Parkinson’s disease is a known phenomenon, its possible significance in mood status has never been elucidated. In this work we aimed at investigating whether neuron loss and alpha-synuclein accumulation in the urocortin 1 containing (UCN1) cells of the centrally-projecting Edinger–Westphal (EWcp) nucleus is associated with anxiety and depression-like state in the rat.

Methods

Systemic chronic rotenone administration as well as targeted leptin–saporin-induced lesions of EWcp/UCN1 neurons were conducted. Rotarod, open field and sucrose preference tests were performed to assess motor performance and mood status. Multiple immunofluorescence combined with RNAscope were used to reveal the functional–morphological changes. Two-sample Student’s t test, Spearman’s rank correlation analysis and Mann–Whitney U tests were used for statistics.

Results

In the rotenone model, besides motor deficit, an anxious and depression-like phenotype was detected. Well-comparable neuron loss, cytoplasmic alpha-synuclein accumulation as well as astro- and microglial activation were observed both in the substantia nigra pars compacta and EWcp. Occasionally, UCN1-immunoreactive neuronal debris was observed in phagocytotic microglia. UCN1 peptide content of viable EWcp cells correlated with dopaminergic substantia nigra cell count. Importantly, other mood status-related dopaminergic (ventral tegmental area), serotonergic (dorsal and median raphe) and noradrenergic (locus ceruleus and A5 area) brainstem centers did not show remarkable morphological changes. Targeted partial selective EWcp/UCN1 neuron ablation induced similar mood status without motor symptoms.

Conclusions

Our findings collectively suggest that neurodegeneration of urocortinergic EWcp contributes to the mood-related non-motor symptoms in toxic models of Parkinson’s disease in the rat.
A CBCT based analysis of the correlation between volumetric morphology of the frontal sinuses and the facial growth pattern in caucasian subjects. A cross-sectional study
Authors: Abate Andrea , Gaffuri Francesca , Lanteri Valentina , Fama Andrea , Ugolini Alessandro , Mannina Laura , Maspero Cinzia
Published: February 2022

Background

The aim of this study was to evaluate the relationship between frontal sinus shape and facial growth pattern.

Methods

The three-dimensional examination was carried out by means of 80 CBCT scans selected from a sample of 1247 records of patients treated, for different reason, at the Department of Biomedical Surgical and Dental Sciences at University of Milan, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico Milan. The sample (age ranges between 12 and 40 years) was divided according to gender and age in four groups (12-17, 18-20, 21-30, 31-40). Left and right frontal sinus volume (VOL), surface (SUP) and linear maximum width (XMAX), depth (ZMAX) and height (YMAX) were calculated using Mimics Research 17.0 (Materialise N.V., Leuven, Belgium). Cephalometric analysis has been performed for all subjects to categorize the patients depending on their facial growth pattern. Univariate and multivariate regression analysis were performed to investigate any association of frontal sinuses measurements (height, width, depth, volume and surface) and cephalometric variables. P value < 0.05 was considered statistically significant.

Results

A total of 160 frontal sinuses were measures in 80 patients: 40 men and 40 women, average age of 23.5 ±14.6. Globally the frontal sinuses had the following average dimensions: volumes of 9055.8 ± 6505 mm3 and surfaces of 3820.3 ± 2125 mm2. The statistical analysis showed that frontal sinus volume was statistically significant (p=0.003) greater for male (11,425 mm3) than female (6597.5 mm3). Similarly, the surface showed to be greater in men than in women (p=0.005). No correlation between age and frontal sinuses characteristics has been found. A statistically significant (p<0.05) increase of frontal sinus depth, surface and volume was correlated with SNB angle. In addition, frontal sinus volume increased in subjects with greater anterior skeletal dimension values and with a superior length of the cranial base. Furthermore, a decrease of ANB has been found related to an increase in frontal sinus volume (p=0.04).

Conclusions

The present study showed a correlation between frontal sinuses dimensions and craniofacial aspects, despite the inter-individual variability of their morphology. The results suggested that young adults in whom the frontal sinuses have reached their maximum size, while vertical growth continues, a larger frontal sinus may be associated with future vertical growth.
High-throughput phenotyping allows the selection of soybean genotypes for earliness and high grain yield
Authors: Santana Dthenifer Cordeiro , de Oliveira Cunha Marcos Paulo , dos Santos Regimar Garcia , Cotrim Mayara Fávero , Teodoro Larissa Pereira Ribeiro , da Silva Junior Carlos Antonio , Baio Fabio Henrique Rojo , Teodoro Paulo Eduardo
Published: February 2022

Background

Precision agriculture techniques are widely used to optimize fertilizer and soil applications. Furthermore, these techniques could also be combined with new statistical tools to assist in phenotyping in breeding programs. In this study, the research hypothesis was that soybean cultivars show phenotypic differences concerning wavelength and vegetation index measurements.

Results

In this research, we associate variables obtained via high-throughput phenotyping with the grain yield and cycle of soybean genotypes. The experiment was carried out during the 2018/2019 and 2019/2020 crop seasons, under a randomized block design with four replications. The evaluated soybean genotypes included 7067, 7110, 7739, 8372, Bonus, Desafio, Maracai, Foco, Pop, and Soyouro. The phenotypic traits evaluated were: first pod height (FPH), plant height (PH), number of branches (NB), stem diameter (SD), days to maturity (DM), and grain yield (YIE). The spectral variables evaluated were wavelengths and vegetation indices (NDVI, SAVI, GNDVI, NDRE, SCCCI, EVI, and MSAVI). The genotypes Maracai and Foco showed the highest grain yields throughout the crop seasons, in addition to belonging to the groups with the highest means for all VIs. YIE was positively correlated with the NDVI and certain wavelengths (735 and 790 nm), indicating that genotypes with higher values for these spectral variables are more productive. By path analyses, GNDVI and NDRE had the highest direct effects on the dependent variable DM, while NDVI had a higher direct effect on YIE.

Conclusions

Our findings revealed that early and productive genotypes can be selected based on vegetation indices and wavelengths. Soybean genotypes with a high grain yield have higher means for NDVI and certain wavelengths (735 and 790 nm). Early genotypes have higher means for NDRE and GNDVI. These results reinforce the importance of high-throughput phenotyping as an essential tool in soybean breeding programs.
Spinopelvic mobility is influenced by pre-existing contralateral hip arthroplasty: a matched-pair analysis in patients undergoing hip replacement
Authors: Muellner Maximilian , Becker Luis , Wang Zhen , Hu Zhouyang , Hardt Sebastian , Pumberger Matthias , Haffer Henryk
Published: February 2022

Background

Spinopelvic mobility gained increased attention as a contributing factor for total hip arthroplasty (THA) instability. However, it is unknown how a pre-existing THA affects spinopelvic mobility. Therefore, a propensity-score-matched analysis of primary THA patients comparing the individual segments of spinopelvic mobility between patients with pre-existing THA and no-existing THA was conducted. Consequently, the study aimed to discuss (1) whether patients with a pre-existing THA have altered spinopelvic mobility compared to the control group and (2) if spinopelvic mobility changes after THA.

Methods

A prospective observational study enrolled 197 elective primary THA patients, including N = 44 patients with a pre-existing unilateral THA. Using propensity-score matching adapted for age, sex, and BMI, N = 44 patients without a pre-existing THA were determined. The patients received stereoradiography in standing and relaxed sitting position pre- and postoperatively. Assessed parameters were lumbar lordosis (LL), pelvic tilt (PT), and pelvic femoral angle (PFA). Key parameters of the spinopelvic mobility were defined as lumbar flexibility (∆LL = LLstanding − LLsitting), pelvic mobility (∆PT = PTstanding − PTsitting) and hip motion (∆PFA = PFAstanding − PFAsitting). Pelvic mobility was classified as stiff (∆PT < 10°), normal (∆PT ≥ 10°–30°) and hypermobile (∆PT > 30°). The Wilcoxon rank sum test for dependent samples was used.

Results

Pelvic mobility was significantly increased in the pre-existing THA group (∆PT 18.2° ± 10.7) compared to the control group (∆PT 7.7° ± 8.0; p < 0.001) preoperatively and postoperatively (pre-existing: 22.2° ± 9.3; control: 17.0° ± 9.2, p = 0.022). Lumbar flexibility was significantly increased in the pre-existing THA group (∆LL 21.6° ± 11.8) compared to the control group (∆LL 12.4° ± 7.8; p < 0.001) preoperatively and postoperatively (pre-existing: 25.7° ± 11.0; control: 19.0° ± 10.2; p = 0.011). The contribution of stiff pelvic mobility is distinctly smaller in the pre-existing THA group (25%) than in the control group (75%) preoperatively.

Conclusions

Pre-existing THA is associated with significantly enhanced pelvic mobility and lumbar flexibility. Accordingly, we identified the patients without a pre-existing THA as risk candidates with higher likelihood for pathological spinopelvic mobility. This information will assist arthroplasty surgeons in deciding which THA candidates require preoperative radiological screening for pathologic spinopelvic mobility.

Level of evidence

Level II prospective cohort study.
Effectiveness of motor imagery for improving functional performance after total knee arthroplasty: a systematic review with meta-analysis
Authors: Li Ran , Du Jubao , Yang Kun , Wang Xue , Wang Wenjiao
Published: February 2022

Background

The aim of this study was to appraise the effects of motor imagery on the functional performance improvement among total knee arthroplasty patients systematically. We hypothesized a relatively greater recovery in the motor imagery group.

Methods

Medline (Ovid), Embase and Cochrane Controlled Register of Trials (CENTRAL) were searched from inception to October 1st, 2021. We included randomized controlled trials evaluating the effects of motor imagery on the functional recovery among total knee arthroplasty patients. Measurements included range of motion, strength intensity, Visual Analogue Scale, Time Up and Go Test, Oxford Knee Score, Western Ontario and McMaster Universities Osteoarthritis Index, all of which were evaluated before and after intervention. Mean differences (MD) or standard mean differences (SMD) and 95% confidence intervals (CI) were calculated. The Cochrane risk of bias tool was used to assess the risk of bias.

Results

Six studies with 168 patients were included for the meta-analysis. The SMD of strength intensity was increased (SMD = 0.90, 95% CI = [0.47]–[1.32], P < 0.001). The SMD of Visual Analogue Scale was reduced (SMD =  − 0.91; 95% CI = [− 1.29]–[− 0.52], P < 0.001). The SMD of Time Up and Go Test was reduced (SMD =  − 0.56, 95% CI = [− 0.94]–[− 0.19], P = 0.003). The MD of Oxford Knee Score was slightly increased (MD = 0.79-point, 95% CI = [− 0.31]–[1.88], P = 0.159). The outcomes of range of motion, Western Ontario and McMaster Universities Osteoarthritis Index were described according to the original data.

Conclusion

Compared with control therapy, motor imagery in the intervention group achieved an effective treatment for strength enhancement, pain reduction and physical activities improvement. More large-scale, prospective researches are needed in the future.

Trial registration: The PROSPERO trial registration number is CRD42021250996.
Pegs not superior to screws for fixation of fractures of the proximal humerus
Authors: Bønes Ingrid , Karlberg Anna Cecilie , Liljeholm Maria , Fraser Alexander Nilsskog , Madsen Jan Erik , Fjalestad Tore
Published: February 2022

Background

Angular stable plates were introduced two decades ago as a promising treatment for fixation of displaced fractures of the proximal humerus (PHF). However, high rates of adverse events and reoperations have been reported. One frequent reason is secondary penetration of screws into the glenohumeral joint, due to sinking of the fracture or avascular head necrosis. To prevent joint penetrations angular stable plates with smooth locking pegs instead of locking screws have been developed. The aim of the present study was to investigate whether blunt pegs instead of pointed screws reduced the risk of secondary penetration into the glenohumeral joint during fracture healing after operatively treated PHFs.

Methods

From two different patient cohorts with displaced PHFs (60 treated with PHILOS plate with screws and 50 with ALPS-PHP plate with pegs), two groups were matched according to fracture type AO/OTA 11-B2 and 11-C2 and age (55–85 years). They were followed up at 3, 6 and 12 months. Primary outcome was radiographic signs of peg or screw penetrations into the glenohumeral joint at 12 months. Secondary outcomes were Oxford shoulder score (OSS) and Constant Score (CS) and radiographic signs of avascular humeral head necrosis (AVN).

Results

Eighteen PHILOS patients with B2 and C2 fractures could be matched with a corresponding group of 18 operated with ALPS-PHP with pegs. The number of penetrations of pegs and screws were equal between the two groups and the development of avascular head necrosis did not differ either. The functional outcomes for both OSS and CS at 12 months was clearly in favor of patients without joint penetrations in both groups.

Conclusion

We found no differences in the number of screw or peg penetrations in the PHILOS and ALPS-PHP group and the occurrence of AVN was equal. Joint penetrations led to inferior functional outcomes at 1 year.

The ClinicalTrials.gov identifier 20/11/12 prospectively for the Philos Group is NCT01737060, and for the ALPS group 11/03/20 retrospectively is NCT04622852.
3D-printed porous Ti6Al4V scaffolds for long bone repair in animal models: a systematic review
Authors: Gu Yifei , Sun Yi , Shujaat Sohaib , Braem Annabel , Politis Constantinus , Jacobs Reinhilde
Published: February 2022

Background

Titanium and its alloys have been widely employed for bone tissue repair and implant manufacturing. The rapid development of three-dimensional (3D) printing technology has allowed fabrication of porous titanium scaffolds with controllable microstructures, which is considered to be an effective method for promoting rapid bone formation and decreasing bone absorption. The purpose of this systematic review was to evaluate the osteogenic potential of 3D-printed porous Ti6Al4V (Ti64) scaffold for repairing long bone defects in animal models and to investigate the influential factors that might affect its osteogenic capacity.

Methods

Electronic literature search was conducted in the following databases: PubMed, Web of Science, and Embase up to September 2021. The SYRCLE's tool and the modified CAMARADES list were used to assess the risk of bias and methodological quality, respectively. Due to heterogeneity of the selected studies in relation to protocol and outcomes evaluated, a meta-analysis could not be performed.

Results

The initial search revealed 5858 studies. Only 46 animal studies were found to be eligible based on the inclusion criteria. Rabbit was the most commonly utilized animal model. A pore size of around 500–600 µm and porosity of 60–70% were found to be the most ideal parameters for designing the Ti64 scaffold, where both dodecahedron and diamond pores optimally promoted osteogenesis. Histological analysis of the scaffold in a rabbit model revealed that the maximum bone area fraction reached 59.3 ± 8.1% at weeks 8–10. Based on micro-CT assessment, the maximum bone volume fraction was found to be 34.0 ± 6.0% at weeks 12.

Conclusions

Ti64 scaffold might act as a promising medium for providing sufficient mechanical support and a stable environment for new bone formation in long bone defects.

Trail registration The study protocol was registered in the PROSPERO database under the number CRD42020194100.
Operational assessment tool for forest carbon dynamics for the United States: a new spatially explicit approach linking the LUCAS and CBM-CFS3 models
Authors: Sleeter Benjamin M. , Frid Leonardo , Rayfield Bronwyn , Daniel Colin , Zhu Zhiliang , Marvin David C.
Published: February 2022

Background

Quantifying the carbon balance of forested ecosystems has been the subject of intense study involving the development of numerous methodological approaches. Forest inventories, processes-based biogeochemical models, and inversion methods have all been used to estimate the contribution of U.S. forests to the global terrestrial carbon sink. However, estimates have ranged widely, largely based on the approach used, and no single system is appropriate for operational carbon quantification and forecasting. We present estimates obtained using a new spatially explicit modeling framework utilizing a “gain–loss” approach, by linking the LUCAS model of land-use and land-cover change with the Carbon Budget Model of the Canadian Forest Sector (CBM-CFS3).

Results

We estimated forest ecosystems in the conterminous United States stored 52.0 Pg C across all pools. Between 2001 and 2020, carbon storage increased by 2.4 Pg C at an annualized rate of 126 Tg C year−1. Our results broadly agree with other studies using a variety of other methods to estimate the forest carbon sink. Climate variability and change was the primary driver of annual variability in the size of the net carbon sink, while land-use and land-cover change and disturbance were the primary drivers of the magnitude, reducing annual sink strength by 39%. Projections of carbon change under climate scenarios for the western U.S. find diverging estimates of carbon balance depending on the scenario. Under a moderate emissions scenario we estimated a 38% increase in the net sink of carbon, while under a high emissions scenario we estimated a reversal from a net sink to net source.

Conclusions

The new approach provides a fully coupled modeling framework capable of producing spatially explicit estimates of carbon stocks and fluxes under a range of historical and/or future socioeconomic, climate, and land management futures.
Selective reduction of astrocyte apoE3 and apoE4 strongly reduces Aβ accumulation and plaque-related pathology in a mouse model of amyloidosis
Authors: Mahan Thomas E. , Wang Chao , Bao Xin , Choudhury Ankit , Ulrich Jason D. , Holtzman David M.
Published: February 2022

Background

One of the key pathological hallmarks of Alzheimer disease (AD) is the accumulation of the amyloid-β (Aβ) peptide into amyloid plaques. The apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset AD and has been shown to influence the accumulation of Aβ in the brain in an isoform-dependent manner. ApoE can be produced by different cell types in the brain, with astrocytes being the largest producer of apoE, although reactive microglia also express high levels of apoE. While studies have shown that altering apoE levels in the brain can influence the development of Aβ plaque pathology, it is not fully known how apoE produced by specific cell types, such as astrocytes, contributes to amyloid pathology.

Methods

We utilized APOE knock-in mice capable of having APOE selectively removed from astrocytes in a tamoxifen-inducible manner and crossed them with the APP/PS1-21 mouse model of amyloidosis. We analyzed the changes to Aβ plaque levels and assessed the impact on cellular responses to Aβ plaques when astrocytic APOE is removed.

Results

Tamoxifen administration was capable of strongly reducing apoE levels in the brain by markedly reducing astrocyte apoE, while microglial apoE expression remained. Reduction of astrocytic apoE3 and apoE4 led to a large decrease in Aβ plaque deposition and less compact plaques. While overall Iba1+ microglia were unchanged in the cortex after reducing astrocyte apoE, the expression of the disease-associated microglial markers Clec7a and apoE were lower around amyloid plaques, indicating decreased microglial activation. Additionally, astrocyte GFAP levels are unchanged around amyloid plaques, but overall GFAP levels are reduced in the cortex of female apoE4 mice after a reduction in astrocytic apoE. Finally, while the amount of neuritic dystrophy around remaining individual plaques was increased with the removal of astrocytic apoE, the overall amount of cortical amyloid-associated neuritic dystrophy was significantly decreased.

Conclusion

This study reveals an important role of astrocytic apoE3 and apoE4 on the deposition and accumulation of Aβ plaques as well as on certain Aβ-associated downstream effects.
Transition age youth mental health: addressing the gap with telemedicine
Authors: Khetarpal Susheel K. , Auster Lauren S. , Miller Elizabeth , Goldstein Tina R.
Published: February 2022

Transition age youth (TAY), a demographic spanning ages 15–26, navigate a myriad of developmental transitions, ranging from identity formation and intimate relationships to substance use. Unfortunately, many young adults continue to have a dearth of mental health services and programing tailored to their unique developmental needs. Moreover, the systems of care in place are generally designed for treating traditional pediatric and adult patients but not ideally suited to meet the needs of TAY. Given the additional stressors from the COVID-19 pandemic, TAY are now, more than ever, in need of routine mental health care. We posit that the rapid expansion of telemedicine programming developed in response to the pandemic could be beneficial in mitigating this historic gap in care. In this commentary, we call on mental health providers and researchers to expand and invest in the growing number of telemedicine interventions and programming for this population so that TAY can begin to receive the care they so desperately need.
HDAC6 involves in regulating the lncRNA-microRNA-mRNA network to promote the proliferation of glioblastoma cells
Authors: Wu An-Chih , Yang Wen-Bin , Chang Kwang-Yu , Lee Jung-Shun , Liou Jing-Ping , Su Ruei-Yuan , Cheng Siao Muk , Hwang Daw-Yang , Kikkawa Ushio , Hsu Tsung-I , Wang Chih-Yang , Chang Wen-Chang , Chen Pin-Yuan , Chuang Jian-Ying
Published: February 2022

Background

Glioblastoma (GBM) is the most aggressive and lethal brain tumor. Although the histone deacetylase (HDAC)/transcription factor axis promotes growth in GBM, whether HDACs including HDAC6 are involved in modulating long non-coding RNAs (lncRNAs) to affect GBM malignancy remains obscure.

Methods

Integrative analysis of microarray and RNA-seq was performed to identify lncRNAs governed by HDAC6. Half-life measurement and RNA-protein pull-down assay combined with isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis were conducted to identify RNA modulators. The effect of LINC00461 on GBM malignancy was evaluated using animal models and cell proliferation-related assays. Functional analysis of the LINC00461 downstream networks was performed comprehensively using ingenuity pathway analysis and public databases.

Results

We identified a lncRNA, LINC00461, which was substantially increased in stem-like/treatment-resistant GBM cells. LINC00461 was inversely correlated with the survival of mice-bearing GBM and it was stabilized by the interaction between HDAC6 and RNA-binding proteins (RBPs) such as carbon catabolite repression—negative on TATA-less (CCR4-NOT) core exoribonuclease subunit 6 and fused in sarcoma. Targeting LINC00461 using azaindolylsulfonamide, an HDAC6 inhibitor, decreased cell-division-related proteins via the lncRNA-microRNA (miRNA)-mRNA networks and caused cell-cycle arrest, thereby suppressing proliferation in parental and drug-resistant GBM cells and prolonging the survival of mice-bearing GBM.

Conclusions

This study sheds light on the role of LINC00461 in GBM malignancy and provides a novel therapeutic strategy for targeting the HDAC6/RBP/LINC00461 axis and its downstream effectors in patients with GBM.
Evaluating statistical approaches to define clonal origin of tumours using bulk DNA sequencing: context is everything
Authors: Kader Tanjina , Zethoven Magnus , Gorringe Kylie L.
Published: February 2022

Clonal analysis of tumour sequencing data enables the evaluation of the relationship of histologically distinct synchronous lesions, such as co-existing benign areas, and temporally distinct tumours, such as primary-recurrence comparisons. In this review, we summarise statistical approaches that are commonly employed to define tumour clonal relatedness using data from bulk DNA technologies. We discuss approaches using total copy number, allele-specific copy number and mutation data, and the relative genomic resolution required for analysis and summarise some of the current tools for inferring clonal relationships. We argue that the impact of the biological context is critical in selecting any particular approach, such as the relative genomic complexity of the lesions being compared, and we recommend considering this context before employing any method to a new dataset.
Treatment of Impetigo with Antiseptics—Replacing Antibiotics (TIARA) trial: a single blind randomised controlled trial in school health clinics within socioeconomically disadvantaged communities in New Zealand
Authors: Primhak Sarah , Gataua Alicia , Purvis Diana , Thompson John M. D. , Walker Cameron , Best Emma , Leversha Alison
Published: February 2022

Background

Impetigo is a common and contagious bacterial skin infection, affecting children worldwide, but it is particularly prevalent in socioeconomically disadvantaged communities. In New Zealand, widespread prescribing of the topical antibiotic fusidic acid had led to an increase in antimicrobial resistance ofStaphylococcus aureus. Alternative treatments are urgently being sought, and as impetigo is a superficial infection, it has been suggested that topical antiseptics such as hydrogen peroxide or simple wound care alone may treat impetigo while avoiding the risk of increased antimicrobial resistance.

Methods

This protocol for a non-inferiority, single-blind randomised controlled trial compares topical fusidic acid with topical hydrogen peroxide and with simple wound care in the treatment of childhood impetigo. Participants are randomised to one of the three treatments for 5 days. The primary outcome is clinical improvement assessed through paired photographs analysed by graders blinded to treatment arm. The trial is based in school health clinics in an urban centre in New Zealand. Comparison of antimicrobial resistance patterns pre- and post-treatment is also performed.

Discussion

Special note is made of the need to involve the communities most affected by impetigo in the design and implementation of the clinical trial to recruit the children most in need of safe and effective treatments.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR)12616000356460. Registered on March 10, 2016 

Protocol amendment number: 05

EB and AL contributed equally as senior authors.
Effects of Tai Chi on the neuromuscular function of the patients with functional ankle instability: a study protocol for a randomized controlled trial
Authors: Tang Huiru , Mao Min , Fong Daniel T. P. , Song Qipeng , Chen Yan , Zhou Zhipeng , Zhang Cui , Wang Jiangna , Tian Xuewen , Sun Wei
Published: February 2022

Background

Ankle instability limits physical activities and undermines a person’s quality of life. Tai Chi’s health benefits have been reported in different population groups. However, the effects of Tai Chi on neuromuscular function among young adults with functional ankle instability (FAI) remain unclear. Therefore, we aim to investigate the effect of Tai Chi on young adults with FAI.

Methods

This study will be conducted as a randomized controlled trial with blinded assessors. A total of 104 young adults with FAI will be recruited and randomly assigned to intervention and control groups. The participants in the simplified Tai Chi exercise program (STCEP) group will receive a 12-week Tai Chi training. The participants in the control group will receive a low-intensity exercise program and health education for 12 weeks. The primary and secondary outcomes will be assessed at baseline, 4th, 8th, and 12th weeks. Primary outcome measures will include the Cumberland Ankle Instability Tool (CAIT) score, kinematics/kinetics data, electromyography during single-leg landing tasks, and the modified Star Excursion Balance Test (mSEBT). Secondary outcome measures will include the total time of Dynamic Leap and Balance Test (DLBT), ankle muscle strength, and ankle proprioception.

Discussion

This study will investigate the effects of Tai Chi exercise on the neuromuscular function of patients with FAI, as indicated by ankle joint biomechanics, ankle proprioception, balance, ankle muscle strength, and ankle muscle activation. Results will demonstrate that Tai Chi can be an effective exercise for young adults with FAI.

Trial registration

Chinese Clinical Trial Registry ChiCTR2100044089. Registered on 10 March 2021
Associations between cardiorespiratory fitness, fatness, hemodynamic characteristics, and sedentary behaviour in primary school-aged children
Authors: Pepera Garyfallia , Hadjiandrea Savvas , Iliadis Ilias , Sandercock Gavin R. H. , Batalik Ladislav
Published: February 2022

Background

Low cardiorespiratory fitness (CRF) is associated with the development of cardiovascular diseases during childhood, adolescence and older ages. The purpose of the study was to investigate associations between fatness, hemodynamic characteristics and secondary time with CRF in primary school-aged children.

Methods

Height, weight, body mass index (BMI), blood pressure (BP), heart rate (HR), CRF (20 m shuttle-run) and sedentary time were measured for 105 children (categorized as normal, overweight, obese). The independent sample t-test checked for differences and one-way ANOVA—Post Hoc Test and stepwise linear regression analysis assessed the 20 m shuttle-run performance predictors.

Results

There was a statistically significant difference in CRF between boys and girls. There was a statistically significant difference between (p < 0.05) CRF for Normal weight (M = 47.58 ± 3.26 kg m−2) and Obese (M = 44.78 ± 3.23 kg m−2). CRF correlated with age, BMI and sedentary time (r > 0.3; p < 0.05). BMI is the best independent predictor of CRF.

Conclusions

Children with normal BMI tend to present better CRF performance than obese and overweight children. Sedentary behaviour is associated with lower CRF in primary school-aged children.
Ablation of typical atrial flutter as therapeutic component in carcinoid heart disease: a case report
Authors: Groschke Susann , Weinert Rolf , Becker Björn , Richardt Gert , Tölg Ralph , Iden Leon , Borlich Martin
Published: February 2022

Background

Carcinoid heart disease is the cardiac manifestation of carcinoid syndrome. There is limited research on rhythm management in patients with carcinoid heart disease. The association of typical atrial flutter and carcinoid heart disease in particular is poorly described.

Case presentation

Here we present a case of a 77-year-old German woman with carcinoid heart disease and recurrent typical atrial flutter complicating the postoperative course after tricuspid valve replacement and its successful long-term rhythm control by ablation therapy.

Conclusion

There is limited evidence on rhythm management in patients with the rare diagnosis of carcinoid heart disease. Typical atrial flutter repeatedly complicated the postoperative course of our patient with carcinoid heart disease and could finally be treated curatively by ablation. Radiofrequency ablation should be considered as a valuable therapeutic component in the challenging therapy of this disease.
Efficient models for enhancing the link adaptation performance of LTE/LTE-A networks
Authors: Bin-Salem Ali Abdulqader , Wan Tat-Chee , Naeem Hamad , Anbar Mohammed , Hanshi Sabri M. , Redjaimia Abdellah
Published: February 2022

Link adaptation (LA) is the ability to adapt the modulation scheme (MS) and the coding rate of the error correction in accordance with the quality of the radio link. The MS plays an important role in enhancing the performance of LTE/LTE-A, which is typically dependent on the received signal to noise ratio (SNR). However, using the SNR to select the proper MSs is not enough given that adaptive MSs are sensitive to error. Meanwhile, non-optimal MS selection may seriously impair the system performance and hence degrades LA. In LTE/ LTE-A, the LA system must be designed and optimized in accordance with the characteristics of the physical (e.g., MSs) and MAC layers (e.g., Packet loss) to enhance the channel efficiency and throughput. Accordingly, this study proposes using two LA models to overcome the problem. The first model, named the cross-layer link adaptation (CLLA) model, is based on the downward cross-layer approach. This model is designed to overcome the accuracy issue of adaptive modulation in existing systems and improve the channel efficiency and throughput. The second model, named the Markov decision process over the CLLA (MDP-CLLA) model, is designed to improve on the selection of modulation levels. Besides that, our previous contribution, namely the modified alpha-Shannon capacity formula, is adopted as part of the MDP-CLLA model to enhance the link adaptation of LTE/LTE-A. The effectiveness of the proposed models is evaluated in terms of throughput and packet loss for different packet sizes using the MATLAB and Simulink environments for the single input single output (SISO) mode for transmissions over Rayleigh fading channels. In addition, phase productivity, which is defined as the multiplication of the total throughput for a specific modulation with the difference between adjacent modulation SNR threshold values, is used to determine the best model for specific packet sizes in addition to determine the optimal packet size for specific packet sizes among models. Results generally showed that the throughput improved from 87.5 to 89.6% for (QPSK $$\rightarrow$$
→
16-QAM) and from 0 to 43.3% for (16-QAM $$\rightarrow$$
→
64-QAM) modulation transitions, respectively, using the CLLA model when compared with the existing system. Moreover, the throughput using the MDP-CLLA model was improved by 87.5–88.6% and by 0–43.2% for the (QPSK $$\rightarrow$$
→
16-QAM)and (16-QAM $$\rightarrow$$
→
64-QAM) modulation transitions, respectively, when compared with the CLLA model and the existing system. Results were also validated for each model via the summation of the phase productivity for every modulation at specific packet sizes, followed by the application one-way analysis of variance (ANOVA) statistical analysis with a post hoc test, to prove that the MDP-CLLA model improves with best high efficiency than the CLLA model and the existing system.
Russian meat price transmission and policy interventions in 2014
Authors: Loginova Daria , Irek Judith
Published: February 2022

This article investigates price relationships in the Russian meat markets in 2011–2017. We use vector autoregression specifications to predict the transmission between consumer, producer, and import prices in the Russian pork, beef, and poultry markets. We consider the possible effects of substitution (between domestic product and import as well as between products in domestic markets), market protection in meat markets, short-term exchange rate policy, and trade price incentives. Our results suggest that meat producer prices responded to import prices, but not vice versa. Poultry and pork producers responded to all market protection measures—the ban of pork imports from the EU and the food embargo. Beef producer prices responded to the embargo. We also find that the single meat market segments may help predict price effects for substitutes. For instance, we find that the poultry consumer prices responded to consumer price changes in the beef and pork markets owing to assumed demand redistribution, but—in contrast to beef and pork—poultry consumer prices were not correlated with the lagged import and producer prices.