bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasound-Based Quantification of Cartilage Damage After In Vivo Articulation With Metal Implants
Authors: Pastrama Maria , Spierings Janne , van Hugten Pieter , Ito Keita , Lopata Richard , van Donkelaar Corrinus C. 
Published: December 2021

Objective This study aims to evaluate the applicability of the ultrasound roughness index (URI) for quantitative assessment of cartilage quality ex vivo (post-mortem), after 6 months of in vivo articulation with a Focal Knee Resurfacing Implant (FKRI). Design Goats received a metal FKRI ( n = 8) or sham surgery ( n = 8) in the medial femoral condyles. After 6 months animals were sacrificed, tibial plateaus were stained with Indian ink, and macroscopic scoring of the plateaus was performed based on the ink staining. The URI was calculated from high-frequency ultrasound images at several sections, covering both areas that articulated with the implant and non-articulating areas. Cartilage quality at the most damaged medial location was evaluated with a Modified Mankin Score (MMS). Results The URI was significantly higher in the FKRI-articulating than in the sham plateaus at medial articulating sections, but not at sections that were not in direct contact with the implant, for example, under the meniscus. The mean macroscopic score and MMS were significantly higher in the FKRI-articulating group than in the sham group ([Formula: see text], [Formula: see text], respectively). Correlation coefficients between URI and macroscopic score were significant in medial areas that articulated with the implant. A significant correlation between URI and MMS was found at the most damaged medial location ([Formula: see text]). Conclusions This study demonstrates the potential of URI to evaluate cartilage roughness and altered surface morphology after in vivo articulation with a metal FKRI, rendering it a promising future tool for quantitative follow-up assessment of cartilage quality.
Comparison of Outcomes Between Suture Button Technique and Screw Fixation Technique in Patients With Acute Syndesmotic Diastasis: A Meta-analysis of Randomized Controlled Trials
Authors: Ramadanov Nikolai , Bueschges Simon , Dimitrov Dobromir 
Published: December 2021

Background: Our aim was to compare the outcome between suture button (SB) stabilization and syndesmotic screw fixation (SF) in patients with acute syndesmotic diastasis. Methods: A systematic literature search up to June 30, 2021, was performed to identify randomized controlled trials (RCTs) comparing outcomes of SB with SF techniques in patients with acute syndesmotic diastasis. We calculated mean differences for continuous outcomes, using the Hartung-Knapp-Sidik-Jonkman method, and odds ratio for dichotomous outcomes, using the Mantel-Haenszel method. Results: Eight RCTs involving 569 patients met the inclusion criteria, 1 RCT with level I evidence, and 7 RCTs with level II evidence. The meta-analysis showed that the SB technique had a higher AOFAS score <6 months and 12 months postoperatively (MD = 4.74, 95% CI 1.68-7.80, P = .01; and MD = 5.42, 95% CI 1.50-9.33, P = .02) and reduced the risk of implant irritation (OR = 0.31, 95% CI 0.11-0.89, P = .03), implant failure (OR = 0.06, 95% CI 0.02-0.23, P < .01), and reoperation (OR = 0.43, 95% CI 0.22-0.83, P = .01). The 2 approaches did not differ in further functional outcomes or postoperative complications. Conclusion: Because functional outcomes showed no relevant difference between both SB and SF, the advantage of SB appears to be in the lower risk for postoperative complications. The SB technique led to fewer cases of implant irritation, implant failure, and reoperation compared with SF. Level of Evidence: Level I, meta-analysis of RCTs.
Metformin alleviates the calcification of aortic valve interstitial cells through activating the PI3K/AKT pathway in an AMPK dependent way
Authors: En Qiao , Zeping Huang , Yuetang Wang , Xu Wang , Wei Wang 
Published: December 2021

Abstract
Background
Calcific aortic valve disease (CAVD) is the most prevalent valvular disease worldwide. However, no effective treatment could delay or prevent the progression of the disease due to the poor understanding of its pathological mechanism. Many studies showed that metformin exerted beneficial effects on multiple cardiovascular diseases by mediating multiple proteins such as AMPK, NF-κB, and AKT. This study aims to verify whether metformin can inhibit aortic calcification through the PI3K/AKT signaling pathway.

Methods
We first analyzed four microarray datasets to screen differentially expressed genes (DEGs) and signaling pathways related to CAVD. Then aortic valve samples were used to verify selected genes and pathways through immunohistochemistry (IHC) and western blot (WB) assays. Aortic valve interstitial cells (AVICs) were isolated from non-calcific aortic valves and then cultured with phosphate medium (PM) with or without metformin to verify whether metformin can inhibit the osteogenic differentiation and calcification of AVICs. Finally, we used inhibitors and siRNA targeting AMPK, NF-κB, and AKT to study the mechanism of metformin.

Results
We screened 227 DEGs; NF-κB and PI3K/AKT signaling pathways were implicated in the pathological mechanism of CAVD. IHC and WB experiments showed decreased AMPK and AKT and increased Bax in calcific aortic valves. PM treatment significantly reduced AMPK and PI3K/AKT signaling pathways, promoted Bax/Bcl2 ratio, and induced AVICs calcification. Metformin treatment ameliorated AVICs calcification and apoptosis by activating the PI3K/AKT signaling pathway. AMPK activation and NF-κB inhibition could inhibit AVICs calcification induced by PM treatment; however, AMPK and AKT inhibition reversed the protective effect of metformin.

Conclusions
This study, for the first time, demonstrates that metformin can inhibit AVICs in vitro calcification by activating the PI3K/AKT signaling pathway; this suggests that metformin may provide a potential target for the treatment of CAVD. And the PI3K/AKT signaling pathway emerges as an important regulatory axis in the pathological mechanism of CAVD.
Boron Carbon Oxynitride as a Novel Metal-Free Photocatalyst
Authors: Chien Liang Cheng , Chiang Chen Wei , Lao Chou Chio , Lin Yung-I , Lin Hao-Wu , Keng Pei Yuin 
Published: December 2021

AbstractBoron-based nanomaterials are emerging as non-toxic, earth-abundant (photo)electrocatalyst materials in solar energy conversion for the production of solar hydrogen fuel and environmental remediation. Boron carbon oxynitride (BCNO) is a quaternary semiconductor with electronic, optical, and physicochemical properties that can be tuned by varying the composition of boron, nitrogen, carbon, and oxygen. However, the relationship between BCNO's structure and -photocatalytic activity relationship has yet to be explored. We performed an in-depth spectroscopic analysis to elucidate the effect of using two different nitrogen precursors and the effect of annealing temperatures in the preparation of BCNO. BCNO nanodisks (D = 6.7 ± 1.1 nm) with turbostratic boron nitride diffraction patterns were prepared using guanidine hydrochloride as the nitrogen source precursor upon thermal annealing at 800°C. The X-ray photoelectron spectroscopy (XPS) surface elemental analysis of the BCNO nanodisks revealed the B, C, N, and O compositions to be 40.6%, 7.95%, 37.7%, and 13.8%, respectively. According to the solid-state 11B NMR analyses, the guanidine hydrochloride-derived BCNO nanodisks showed the formation of various tricoordinate BNx(OH)3−x species, which also served as one of the photocatalytic active sites. The XRD and in-depth spectroscopic analyses corroborated the preparation of BCNO-doped hexagonal boron nitride nanodisks. In contrast, the BCNO annealed at 600 °C using melamine as the nitrogen precursor consisted of layered nanosheets composed of B, C, N, and O atoms covalently bonded in a honeycomb lattice as evidence by the XRD, XPS, and solid-state NMR analysis (11B and 13C) analyses. The XPS surface elemental composition of the melamine-derived BCNO layered structures consisted of a high carbon composition (75.1%) with a relatively low boron (5.24%) and nitrogen (7.27%) composition, which indicated the formation of BCNO-doped graphene oxides layered sheet structures. This series of melamine-derived BCNO-doped graphene oxide layered structures were found to exhibit the highest photocatalytic activity, exceeding the photocatalytic activity of graphitic carbon nitride. In this layered structure, the formation of the tetracoordinate BNx(OH)3−x(CO) species and the rich graphitic domains were proposed to play an important role in the photocatalytic activity of the BCNO-doped graphene oxides layered structures. The optical band gap energies were measured to be 5.7 eV and 4.2 eV for BCNO-doped hexagonal boron nitride nanodisks and BCNO-doped graphene oxides layered structures, respectively. Finally, BCNO exhibited an ultralong photoluminescence with an average decay lifetime of 1.58, 2.10, 5.18, and 8.14 µs for BGH01, BGH03, BMH01, BMH03, respectively. This study provides a novel metal-free photocatalytic system and provides the first structural analysis regarding the origin of BCNO-based photocatalyst.

Graphical Abstract
MeCP2 haplodeficiency and early-life stress interaction on anxiety-like behavior in adolescent female mice
Authors: Abellán-Álvaro María , Stork Oliver , Agustín-Pavón Carmen , Santos Mónica 
Published: December 2021

AbstractBackgroundEarly-life stress can leave persistent epigenetic marks that may modulate vulnerability to psychiatric conditions later in life, including anxiety, depression and stress-related disorders. These are complex disorders with both environmental and genetic influences contributing to their etiology. Methyl-CpG Binding Protein 2 (MeCP2) has been attributed a key role in the control of neuronal activity-dependent gene expression and is a master regulator of experience-dependent epigenetic programming. Moreover, mutations in theMECP2gene are the primary cause of Rett syndrome and, to a lesser extent, of a range of other major neurodevelopmental disorders. Here, we aim to study the interaction of MeCP2 with early-life stress in variables known to be affected by this environmental manipulation, namely anxiety-like behavior and activity of the underlying neural circuits.MethodsUsingMecp2heterozygous and wild-type female mice we investigated the effects of the interaction ofMecp2haplodeficiency with maternal separation later in life, by assessing anxiety-related behaviors and measuring concomitant c-FOS expression in stress- and anxiety-related brain regions of adolescent females. Moreover, arginine vasopressin and corticotropin-releasing hormone neurons of the paraventricular hypothalamic nucleus were analyzed for neuronal activation.ResultsIn wild-type mice, maternal separation caused a reduction in anxiety-like behavior and in the activation of the hypothalamic paraventricular nucleus, specifically in corticotropin-releasing hormone-positive cells, after the elevated plus maze. This effect of maternal separation was not observed inMecp2heterozygous females that per se show decreased anxiety-like behavior and concomitant decreased paraventricular nuclei activation.ConclusionsOur data supports that MeCP2 is an essential component of HPA axis reprogramming and underlies the differential response to anxiogenic situations later in life.
A re-assessment of 4CMenB vaccine effectiveness against serogroup B invasive meningococcal disease in England based on an incidence model
Authors: Argante Lorenzo , Abbing-Karahagopian Victoria , Vadivelu Kumaran , Rappuoli Rino , Medini Duccio 
Published: December 2021

Abstract
Background
The four-component serogroup B meningococcal 4CMenB vaccine (Bexsero, GSK) has been routinely given to all infants in the United Kingdom at 2, 4 and 12 months of age since September 2015. After 3 years, Public Health England (PHE) reported a 75% [95% confidence interval 64%; 81%] reduction in the incidence of serogroup B invasive meningococcal disease (IMD) in age groups eligible to be fully vaccinated. In contrast, vaccine effectiveness (VE) evaluated in the same immunization program applying the screening method was not statistically significant. We re-analyzed the data using an incidence model.

Methods
Aggregate data—stratified by age, year and doses received—were provided by PHE: serogroup B IMD case counts for the entire population of England (years 2011–2018) and 4CMenB vaccine uptake in infants. We combined uptake with national population estimates to obtain counts of vaccinated and unvaccinated person-time by age and time. We re-estimated VE comparing incidence rates in vaccinated and non-vaccinated subjects using a Bayesian Poisson model for case counts with person-time data as an offset. The model was adjusted for age, time and number of doses received.

Results
The incidence model showed that cases decreased until 2013–2014, followed by an increasing trend that continued in the non-vaccinated population during the immunization program. VE in fully vaccinated subjects (three doses) was 80.1% [95% Bayesian credible interval (BCI): 70.3%; 86.7%]. After a single dose, VE was 33.5% [12.4%; 49.7%]95%BCI and after two doses, 78.7% [71.5%; 84.5%]95%BCI. We estimated that vaccination averted 312 cases [252; 368]95%BCI between 2015 and 2018. VE was in line with the previously reported incidence reduction.

Conclusions
Our estimates of VE had higher precision than previous estimates based on the screening method, which were statistically not significant, and in line with the 75% incidence reduction previously reported by PHE. When disease incidence is low and vaccine uptake is high, the screening method applied to cases exclusively from the population eligible for vaccination may not be precise enough and may produce misleading point-estimates. Precise and accurate VE estimates are fundamental to inform public health decision making. VE assessment can be enhanced using models that leverage data on subjects not eligible for vaccination.
A novel MAGED2 variant in a Chinese preterm newborn with transient antenatal Bartter’s syndrome with 4 years follow-up
Authors: Ma Mingsheng , Zhang Mengqi , Zhou Yu , Yao Fengxia , Wei Min , Li Zhenghong , Qiu Zhengqing 
Published: December 2021

Abstract
Background
Transient antenatal Bartter’s syndrome caused by MAGED2 mutation is a rare X-linked recessive renal tubular disorder. Cases reported are mostly infants, and the long-term prognosis of the disease is still under investigation.

Case presentation
We encountered a preterm male infant with polyhydramnios, polyuria, salt loss, hypercalciuria, nephrocalcinosis and alkalosis. Antenatal Bartter’s syndrome was suspected, but these clinical symptoms surprisingly disappeared after about 2 months. This led to the clinical diagnosis of transient antenatal Bartter’s syndrome. Gene analysis in this patient disclosed a novel variant (c.1598C > T, p.Ala533Val) in exon 12 of MAGED2 gene, and his mother was a heterozygous carrier. This patient was followed up in clinic for 4 years without recurrence of imbalance of potassium, sodium and chloride. His height and weight were in normal range, and all laboratory examinations and nephrotic ultrasound were also normal.

Conclusions
We reported the first Chinese case of transient antenatal Bartter’s syndrome caused by MAGED2 mutation. The 4-year follow-up of our case further demonstrates the benign prognosis of the disease and indicates that early recognition of this phenotype could avoid unnecessary treatments.
Intraventricular hemorrhage clot clearance rate as an outcome predictor in patients with aneurysmal subarachnoid hemorrhage: A retrospective study
Authors: Park Hae Gi , Kim Sunghan , Chung Joonho , Jang Chang Ki , Park Keun Young , Lee Jae Whan 
Published: December 2021

Abstract
Background
The development of intraventricular hemorrhage (IVH) in aneurysmal subarachnoid hemorrhage (aSAH) is linked with higher mortality and poor neurological recovery. Previous studies have investigated the effect of the amount and distribution of the initial IVH on the prognosis of aSAH. However, no studies have assessed the relationship between the changes in IVH over time and the prognosis of aSAH. The aim of this study was to analyze the effect of the clearance rate of IVH, which can be represented by the IVH clot clearance rate (CCR), on the outcomes of aSAH.

Methods
The IVH CCR was calculated based on the difference between the initial and follow-up modified Graeb scores (mGS), which were assessed by initial and 7-day follow-up brain computed tomography, respectively. Poor functional outcome was defined as a modified Rankin Scale score of 3-6. Univariate and multivariable analyses were performed to assess the relationships between IVH CCR and other risk factors and the prognosis of patients. Receiver operating characteristic curve analysis was performed to identify cut-off values of IVH CCR for predicting poor functional outcome.

Results
In total, 196 consecutive patients were diagnosed with aSAH between January 2014 and March 2018. According to the inclusion and exclusion criteria, 67 patients were finally included in the study. The univariate analysis revealed that a lower IVH CCR (p<0.001), higher initial mGS (p<0.001), older age (p<0.001), higher initial Hunt and Hess grade (p<0.001), presence of delayed infarction (p=0.03), and presence of shunt-dependent hydrocephalus (p=0.004) were significantly related to poor functional outcome. The multivariable analysis revealed that IVH CCR (odds ratio [OR] 0.941; p=0.029), initial mGS (OR 1.632; p=0.043), age (OR 1.561; p=0.007), initial Hunt and Hess grade (OR 227.296; p=0.030), and delayed infarction (OR 5310.632; p=0.023) were independent predictors of poor functional outcome. Optimal cut-off values of IVH CCR and mGS for poor outcome were 36.27%, and 13.5, respectively (all p< 0.001).

Conclusions
The IVH CCR might have an important predictive value on poor functional outcome in patients with aSAH and IVH, along with initial mGS, age, initial Hunt and Hess grade, and delayed infarction.
Immune landscape of advanced gastric cancer tumor microenvironment identifies immunotherapeutic relevant gene signature
Authors: Zhang Simeng , Lv Mengzhu , Cheng Yu , Wang Shuo , Li Ce , Qu Xiujuan 
Published: December 2021

Abstract
Background
Advanced gastric cancer (AGC) is a disease with poor prognosis due to the current lack of effective therapeutic strategies. Immune checkpoint blockade treatments have shown effective responses in patient subgroups but biomarkers remain challenging. Traditional classification of gastric cancer (GC) is based on genomic profiling and molecular features. Therefore, it is critical to identify the immune-related subtypes and predictive markers by immuno-genomic profiling.

Methods
Single-sample gene-set enrichment analysis (ssGSEA) and ESTIMATE algorithm were used to identify the immue-related subtypes of AGC in two independent GEO datasets. Weighted gene co-expression network analysis (WGCNA) and Molecular Complex Detection (MCODE) algorithm were applied to identify hub-network of immune-related subtypes. Hub genes were confirmed by prognostic data of KMplotter and GEO datasets. The value of hub-gene in predicting immunotherapeutic response was analyzed by IMvigor210 datasets. MTT assay, Transwell migration assay and Western blotting were performed to confirm the cellular function of hub gene in vitro.

Results
Three immune-related subtypes (Immunity_H, Immunity_M and Immunity_L) of AGC were identified in two independent GEO datasets. Compared to Immunity_L, the Immuntiy_H subtype showed higher immune cell infiltration and immune activities with favorable prognosis. A weighted gene co-expression network was constructed based on GSE62254 dataset and identified one gene module which was significantly correlated with the Immunity_H subtype. A Hub-network which represented high immune activities was extracted based on topological features and Molecular Complex Detection (MCODE) algorithm. Furthermore, ADAM like decysin 1 (ADAMDEC1) was identified as a seed gene among hub-network genes which is highly associated with favorable prognosis in both GSE62254 and external validation datasets. In addition, high expression of ADAMDEC1 correlated with immunotherapeutic response in IMvigor210 datasets. In vitro, ADAMDEC1 was confirmed as a potential protein in regulating proliferation and migration of gastric cancer cell. Deficiency of ADAMDEC1 of gastric cancer cell also associated with high expression of PD-L1 and Jurkat T cell apoptosis.

Conclusions
We identified immune-related subtypes and key tumor microenvironment marker in AGC which might facilitate the development of novel immune therapeutic targets.
Osteomyelitis in Immunocompromised children and neonates, a case series
Authors: Foong Bryan , Wong Kenneth Pak Leung , Jeyanthi Carolin Joseph , Li Jiahui , Lim Kevin Boon Leong , Tan Natalie Woon Hui 
Published: December 2021

Abstract
Background
Osteomyelitis in immunocompromised children can present differently from immunocompetent children and can cause devastating sequelae if treated inadequately. We aim to review the aetiology, clinical profile, treatment and outcomes of immunocompromised children with osteomyelitis.

Methods
Retrospective review of all immunocompromised children aged < 16 years and neonates admitted with osteomyelitis in our hospital between January 2000 and January 2017, and referred to the Paediatric Infectious Disease Service.

Results
Fourteen patients were identified. There were 10 boys (71%), and the median age at admission was 70.5 months (inter-quartile range: 12.3–135.0 months). Causal organisms included, two were Staphylococcus aureus, two were Mycobacterium bovis (BCG), and one each was Mycobacterium tuberculosis, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Burkholderia pseudomallei and Rhizopus sp. One patient had both Clostridium tertium and Clostridium difficile isolated. Treatment involved appropriate antimicrobials for a duration ranging from 6 weeks to 1 year, and surgery in 11 patients (79%). Wherever possible, the patients received treatment for their underlying immunodeficiency. For outcomes, only three patients (21%) recovered completely. Five patients (36%) had poor bone growth, one patient had recurrent discharge from the bone and one patient had palliative care for underlying osteosarcoma.

Conclusions
Although uncommon, osteomyelitis in immunocompromised children and neonates can be caused by unusual pathogens, and can occur with devastating effects. Treatment involves prolonged administration of antibiotics and surgery. Immune recovery also seems to be an important factor in bone healing.