bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcitriol ameliorates damage in high-salt diet-induced hypertension: Evidence of communication with the gut–kidney axis
Authors: Ding Ruifeng , Xiao Zilong , Jiang Yufeng , Yang Yi , Ji Yang , Bao Xunxia , Xing Kaichen , Zhou Xinli , Zhu Sibo
Published: December 2021

Several studies have established a link between high-salt diet, inflammation, and hypertension. Vitamin D supplementation has shown anti-inflammatory effects in many diseases; gut microbiota is also associated with a wide variety of cardiovascular diseases, but potential role of vitamin D and gut microbiota in high-salt diet-induced hypertension remains unclear. Therefore, we used rats with hypertension induced by a high-salt diet as the research object and analyzed the transcriptome of their tissues (kidney and colon) and gut microbiome to conduct an overall analysis of the gut–kidney axis. We aimed to confirm the effects of high salt and calcitriol on the gut–kidney immune system and the composition of the intestinal flora. We demonstrate that consumption of a high-salt diet results in hypertension and inflammation in the colon and kidney and alteration of gut microbiota composition and function. High-salt diet-induced hypertension was found to be associated with seven microbial taxa and mainly associated with reduced production of the protective short-chain fatty acid butyrate. Calcitriol can reduce colon and kidney inflammation, and there are gene expression changes consistent with restored intestinal barrier function. The protective effect of calcitriol may be mediated indirectly by immunological properties. Additionally, the molecular pathways of the gut microbiota-mediated blood pressure regulation may be related to circadian rhythm signals, which needs to be further investigated. An innovative association analysis of the microbiota may be a key strategy to understanding the association between gene patterns and host.
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.
Corporate Core Competencies’ Essence, Contexts, Discovery, and Future: A Call to Action for Executives and Researchers
Authors: Edgar William B. , Lockwood Chris A.
Published: December 2021

Research and managerial literatures on core competencies present them as essential to corporations because these competencies, proposed by the literatures to be difficult to acquire and imitate, are applied repeatedly to produce products and services delivering value to customers and wealth to corporations. Indeed, researchers and managers consider the significance of core competencies to be immense as they are the central intellectual means through which corporations produce valuable products and services. Paradoxically, though, rather than providing a clear, focused description, or picture, of what core competencies are and how they contribute to their host corporations, these same literatures present a sprawling, even fragmented picture of core competencies’ essence and contribution.In contrast, this book presents a clear empirical model of corporations’ core competencies’ essence; provides a clear conceptual treatment of how core competencies’ contextual, corporate contributions occur; presents valid methodologies for discovering and understanding corporations’ specific core competencies; and delineates an agenda for executives and researchers to collaborate in learning about core competencies and in using them to provide value for corporate stakeholders, especially customers. The book also places core competencies within their historical and social context, and it presents conceptual and methodological tools to assist in managing and discovering them.
Sustainable Practices Through Competitive Capabilities in the Apparel Industry: Sri Lankan Experience
Authors: Jayarathne P. G. S. A. , Sachithra Vilani , Dewasiri N. J.
Published: December 2021

The study aims to explore competitive capabilities that enable sustainability practices in the Apparel Industry in the Sri Lankan context. It employs an exploratory approach using the case study method. The study discloses six competitive capabilities: organizational climate, operational flexibility, technological competency, alliance and partnership, knowledge sharing, and learning capabilities which drives twenty-four sustainable practices explored in ten categories: water conservation, energy conservation, carbon footprint reduction, fabric waste management, use of environment-friendly materials, controlling mechanism for suppliers, controlling mechanism for leasing/sub-contracting manufacturing plants, reduce the polluted air release, transportation, and ensuring the well-being of the people. Companies in the apparel industry should inculcate a supportive organizational climate, maintain operational flexibility, invest in required technology, maintain healthy relationships in the supply chain, share knowledge and encourage learning to adopt sustainable practices in the Apparel Industry. This study is the first to explore the specific competitive capabilities that bring respective sustainable practices in the Apparel Industry in a South Asian country.
Gender Inequality in STEM Employment and Earnings at Career Entry: Evidence from Millennial Birth Cohorts
Authors: VanHeuvelen Tom , Quadlin Natasha
Published: December 2021

Although science, technology, engineering, and mathematics (STEM) majors remain male dominated, women’s greater enrollment in STEM is one of the greatest transformations to occur in U.S. higher education in the past half century. But to what extent have women’s gains in STEM enrollment translated to greater parity in labor market outcomes? Although the challenges women face in STEM have been well documented, questions about the influence of gender for STEM employment and earnings differences remain. In the present research, the authors use data from recent birth cohorts in the American Community Survey between 2009 and 2018 (starting with the first year college majors were available in the survey) and a reweighting technique from labor economics to track the evolution of gender inequalities in STEM employment and earnings inequality among STEM work at the onset of labor market entry. Even among a sample expected to produce highly conservative gender differences, sizable gender inequalities in STEM employment are observed. The authors show that despite women’s gains in STEM education among recent cohorts, women with STEM degrees face employment prospects in STEM work that more closely resemble those of men without STEM degrees than men with STEM degrees. Moreover, although modest gender earnings gaps eventually emerge for those without STEM degrees, large gaps occur at the outset of employment for STEM workers. Thus, although STEM education provides important opportunities for women’s earning potential, it may be less effective in itself to address significant gender inequalities among STEM employment.
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

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

Boron-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

Background

Early-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.

Methods

UsingMecp2heterozygous 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.

Results

In 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.

Conclusions

Our 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

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

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

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

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

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.
Understanding the psycho-social context for a new early intervention for resistance to change that aims to strike a beneficial balance between structure and flexibility
Authors: Blackwell Siobhan , Zylberberg Alex , Scerif Gaia , Miller Sarah , Woodcock Kate A.
Published: December 2021

Background

Emotional and behavioural problems linked to changes to expectations – resistance to change – are linked to disability in neurodevelopmental disorders, including autism spectrum disorder (ASD), Prader-Willi (PWS) and fragile X syndromes (FXS). Structuring routines is best practice for minimising current resistance to change. But complete structure is impractical and flexibility in early life may actually reduce later resistance by supporting cognitive development. We aimed to examine the psycho-social context of families with children at risk of developing resistance to change so as to identify design requirements for an intervention that strikes a beneficial balance between structure and flexibility.

Methods

Thirty-six caregivers of children aged 4–12 years (17 ASD, 15 PWS, and 4 FXS) took part in an interview designed collaboratively with 12 professional stakeholders.

Results

Children need to feel like they are in control of flexibility but they also need support in choice making, understanding plans (using individually tailored visuals) and anxiety reduction. Caregivers need an accessible approach that they have full control over, and which they can tailor for their child. Caregivers also need clear guidance, education and support around structure and flexibility.

Conclusions

We propose a digital approach which addresses the needs identified. It tackles the most perplexing challenge by presenting flexibility to children in the context of a game that children can feel they have full control over, whilst caregivers can maintain control in reality. Furthermore, individualised support for children and caregivers would be enabled.
Correlational research on facial and clinical characteristics of adolescents with obsessive-compulsive disorder
Authors: Wang Yan-Rong , Chang Shao-hua , Ma Xiao-Min , Li Ji-Ying , Zhang Rui-Xia , Fang Jian-Qun
Published: December 2021

Background

The neurodevelopmental model of obsessive-compulsive disorder (OCD) suggests that the neurodevelopmental changes in the ventral striatal circuit of the prefrontal lobe are associated with the initial symptoms of OCD. Facial morphology is one of the most consistent anatomical phenotypes of neurodevelopmental disorders, which can reflect brain structure and function. Facial deformity, an easily measured index of brain malformation, can reflect abnormal brain structure and function. Therefore, this study aims to explore the relationship between clinical features and neurodevelopment of adolescents with OCD through facial morphology.

Methods

The enrolled study sample comprised 40 adolescents diagnosed with OCD using the Obsessive Compulsive Inventory-Child Version (OCI-CV) and 38 healthy controls (HCs). Facial photos, 21 facial diameters, and 9 facial angles were collected using image software.

Results

In males, lower lip red height was significantly lower in OCD patients than in HCs (P < 0.025); no significant differences were observed in other facial indicators (all P > 0.025). In females, the nasolabial angle was smaller in OCD patients than in HCs (P < 0.025); no significant differences were observed in other facial indicators (all P > 0.025). The difference in lower lip red height between the OCD group and HC group was positively correlated with neutralizing symptoms (r = 0.401, P < 0.05).

Conclusions

Male OCD patients had a thinner lower lip and female OCD patients had smaller nasolabial angles. The facial features of adolescents with OCD were positively correlated with lower lip redness and neutralizing symptoms.
Exploring COVID-19 patients’ experiences of psychological distress during the disease course: a qualitative study
Authors: Toulabi Tahereh , Pour Fatemeh Jafari , Veiskramian Atefeh , Heydari Heshmatolah
Published: December 2021

Background

The Coronavirus Disease 2019 (COVID-19) is an emerging disease with many unknown clinical and therapeutic dimensions. Patients with COVID-19 experience a variety of psychological problems during the disease. Understanding patients’ mental condition and their distress during the disease is the first step to help these patients. So, the aim of this study was to explain COVID-19 patients’ experiences of psychological distress during the disease course.

Methods

The present qualitative research was conducted in Iran from April 2020 to April 2021 using the conventional content analysis method. The participants included patients with COVID-19, selected by the purposeful sampling method. Data was collected through 34 telephone and in-person interviews and analyzed based on the method proposed by Lundman and Graneheim.

Results

Qualitative data analysis led to the emergence of sources of psychological distress as the main theme as well as seven categories and seven sub-categories. The categories were the disease’s nature (the subcategories of disease’s unknown dimensions, and disease severity), the anxiety caused by preventive behaviors (the subcategories of quarantine, worry about transmitting the infection to others and obsessive thoughts related to disinfection measures), the inefficient management by the health system (the subcategories of poor health care condition and lack of spiritual care), death anxiety, stigma, anxiety after recovery, and sleep pattern disturbance.

Conclusion

Patients with COVID-19 experience great psychological distress during the acute phase of the disease or even long after recovery. It is suggested that psychological and spiritual counseling, as a key element of treatment and support for these patients, is provided to patients in the acute phase of the disease, as well as after recovery. National and local media should boost awareness about the disease as a dangerous yet preventable and curable infectious disease. People should follow health instructions and leave their seeing the disease as a taboo.

Trial registration number

Not applicable.
Effect of school-based educational water, sanitation, and hygiene intervention on student’s knowledge in a resource-limited setting
Authors: Mushota Ommy , Mathur Aditya , Pathak Ashish
Published: December 2021

Background

Globally, diarrhea is one of the major causes of under-5 mortality. India accounts for the highest number of childhood deaths from diarrhea globally. Therefore, facilitating the implementation of water, sanitation, and hygiene (WASH)-related interventions in schools and communities is crucial. In the present study, we investigated the effectiveness of a school-based educational WASH intervention in improving students’ knowledge on prevention and management of diarrhea in Ujjain district, India.

Methods

The present pre–post intervention study with a two-stage (schools and classrooms) cluster sampling was conducted on 1,781 students studying in grades: 8th–12th; age: 14–19 years) in schools located in Ujjain, Madhya Pradesh, India. The intervention comprised an educational training session using a WASH training module. The means of pre- and post-intervention scores were compared using repeated measure analysis of variance. A multivariate quantile regression model was used to test the correlation between the change in score after intervention and the independent variables. A P value of <0.05 was considered statistically significant.

Results

The proportions of students possessing knowledge on the treatment of diarrhea, use of zinc tablets during an episode of diarrhea, and the symptoms and signs of severe pediatric diarrhea were 28%, 27%, and 27%, respectively, before intervention. These proportions increased (P<0.001) after the educational intervention to 72%, 73%, and 74%, respectively. The mean post-intervention knowledge score (34.13) was higher than the mean pre-intervention score (15.17) (F = 16513.36, P< 0.001). Age was associated with the knowledge score at the 25th and higher quantile (q). Gender exhibited a greater effect at q10th. School location was positively associated at q25th and higher. School type was strongly associated at low quantiles (q10th and q25th). School medium exhibited a greater association at low quantiles (≤q25th).

Conclusion

WASH- and diarrhea-related knowledge among higher secondary school students increased after the educational intervention. Further research is required to evaluate the sociodemographic characteristics associated with change in the knowledge score to better evaluate school-based educational WASH interventions and improve the management and prevention of diarrhea.
Structural family factors and bullying at school: a large scale investigation based on a Chinese adolescent sample
Authors: Wang Haoran , Wang Yuanyuan , Wang Guosheng , Wilson Amanda , Jin Tingting , Zhu Longjun , Yu Renjie , Wang Shuilan , Yin Weijia , Song Huihui , Li Shun , Jia Qiufang , Zhang Xiaobin , Yang Yong
Published: December 2021

Backgrounds

Various family factors have been identified in association with school bullying and the involvement of children and adolescents in bullying behaviors.

Methods

A total of 11,919 participants (female = 6671, mean age = 15) from 22 middle schools in Suzhou City, China completed the questionnaire. The associations between structural family factors (family socio-economic status, living arrangement, number of siblings, whether they were local residents/migrants, had an urban/ruralhukou [a household registration system in China], parental and maternal education levels, and other various bullying-related constructs (i.e. bullying witnessing, bullying involvement, bystander intervention, and fear of being bullied) were all examined. Odds ratios (ORs) adjusted for covariates were calculated for the four bullying-related constructs (bullying witness, bullying involvement, bystander intervention, and reactions to being bullied) using structural family factors.

Results

The result showed that all demographic household characteristics were associated with bullying at school except for being from a single-child family. Adolescents from rural families witnessed more bullying incidents than those from local families (OR = 1.35, 95% CI: [1.09, 1.68]). Adolescents who come from migrant families (OR = 1.12, 95% CI: [1.07, 1.43]) with a rural hukou (OR = 1.31, 95% CI: [1.00, 1.74]) and low parental education levels (OR = 1.42, 95% CI: [1.01, 2.57]) were more likely to be bullies. Adolescents who came from migrant families (OR = 1.37, 95% CI: [1.03, 1.82]), with low maternal education levels (OR = 1.42, 95% CI: [1.06, 1.91]) engaged in more negative bystander intervention behaviors. Furthermore, adolescents with less educated mothers experienced a higher fear of being bullied (neverversussometimes: OR = 1.33, 95% CI: [1.00, 1.85];neverversususuallyOR = 1.39, 95% CI: [1.01, 1.20]).

Conclusions

A systematic examination of the relationship between school bullying and demographic household characteristics may be used to inform school policies on bullying, such as training management on the importance of paying attention to adolescents from disadvantage household backgrounds. Identifying demographic factors that may predict bullying can also be used to prevent individuals from becoming involved in bullying and reduce the related negative consequences from being bullied.
Equity of health care financing in South Korea: 1990–2016
Authors: Lee Tae-Jin , Hwang Inuk , Kim Hea-Lim
Published: December 2021

Background

The National Health Insurance in Korea has been in operation for more than 30 years since having achieved universal health coverage in 1989 and has gone through several policy reforms. Despite its achievements, the Korean health insurance has some shortfalls, one of which concerns the fairness of paying for health care.

Method

Using the population representative Household Income and Expenditure Survey data in Korea, this study examined the yearly changes in the vertical equity of paying for health care between 1990 and 2016 by the source of financing using the Kakwani index, considering health insurance and other related policy reforms in Korea during this period.

Results

The study results suggest that direct tax was the most progressive mode of health care financing in all years, whereas indirect tax was proportional. The out-of-pocket payments were weakly regressive in all years. The Kakwani index for health insurance contributions was regressive but now is proportional to the ability to pay, whereas the Kakwani index for private health insurance premiums turned from progressive to weakly regressive. The Kakwani index for overall health care financing showed a weak regressivity during the study period.

Discussion

The overall health care financing in Korea has transformed from a slight regressivity to proportional over time between 1990 and 2016. It is expected that these changes were closely related to the improved equity of health insurance contributions from 1998 to 2008, which was the result of a merger of the health insurance societies and an amendment in the health insurance contribution structure. These results suggest that standardizing insurance managing organizations and financing rules potentially has positive implications for the equity of healthcare financing in a country where the major method of health care financing is social health insurance.
Relationships between developmental strategies for additional indications and price revisions for anticancer drugs in Japan
Authors: Maeda Hideki , Okabe Ayano , Sakakura Kenichi , Ng Daniel Bin , Akazawa Manabu
Published: December 2021

Background

The relationships between developmental strategies for additional indications and drug price revisions have not been thoroughly studied. Here, we investigated the price revisions for anticancer drugs approved in Japan.

Methods

The study was based on published information on anticancer drugs approved between January 2009 and March 2020 in Japan. We investigated the relationships between the pharmacological and regulatory characteristics of anticancer drugs and occurrence/non-occurrence of the Japanese National Health Insurance (NHI) price revisions.

Results

Eighty-one new anticancer drugs were given NHI price listings during the survey. On April 1, 2020, the prices of 23 anticancer drugs had been revised from the initial pricing, the prices were reduced for 21 drugs (91.3%). Several parameters showed the relationships between drug characteristics and NHI price revisions. The achievement of additional indications and compound type were identified as explanatory factors for these relationships. Additional indication profiles were defined to assess the relationships between the methods for additional indication achievement and price revisions. When the type of additional indication was “Expansion”, the percentage of drugs received NHI price revisions was the highest (P<0.001).

Conclusions

NHI price revision was significantly related to the achievement of additional indications and compound type. The strategy for additional indications was found to affect the occurrence/non-occurrence of NHI price revisions.
Wheat inositol pyrophosphate kinase TaVIH2-3B modulates cell-wall composition and drought tolerance in Arabidopsis
Authors: Shukla Anuj , Kaur Mandeep , Kanwar Swati , Kaur Gazaldeep , Sharma Shivani , Ganguli Shubhra , Kumari Vandana , Mazumder Koushik , Pandey Pratima , Rouached Hatem , Rishi Vikas , Bhandari Rashna , Pandey Ajay Kumar
Published: December 2021

Background

Inositol pyrophosphates (PP-InsPs) are high-energy derivatives of inositol, involved in different signalling and regulatory responses of eukaryotic cells. Distinct PP-InsPs species are characterized by the presence of phosphate at a variable number of the 6-carbon inositol ring backbone, and two distinct classes of inositol phosphate kinases responsible for their synthesis have been identified in Arabidopsis, namely ITPKinase (inositol 1,3,4 trisphosphate 5/6 kinase) and PP-IP5Kinase (diphosphoinositol pentakisphosphate kinases). Plant PP-IP5Ks are capable of synthesizing InsP8 and were previously shown to control defense against pathogens and phosphate response signals. However, other potential roles of plant PP-IP5Ks, especially towards abiotic stress, remain poorly understood.

Results

Here, we characterized the physiological functions of two Triticum aestivum L. (hexaploid wheat) PPIP5K homologs, TaVIH1 and TaVIH2. We demonstrate that wheat VIH proteins can utilize InsP7 as the substrate to produce InsP8, a process that requires the functional VIH-kinase domains. At the transcriptional level, both TaVIH1 and TaVIH2 are expressed in different wheat tissues, including developing grains, but show selective response to abiotic stresses during drought-mimic experiments. Ectopic overexpression of TaVIH2-3B in Arabidopsis confers tolerance to drought stress and rescues the sensitivity of Atvih2 mutants. RNAseq analysis of TaVIH2-3B-expressing transgenic lines of Arabidopsis shows genome-wide reprogramming with remarkable effects on genes involved in cell-wall biosynthesis, which is supported by the observation of enhanced accumulation of polysaccharides (arabinogalactan, cellulose, and arabinoxylan) in the transgenic plants.

Conclusions

Overall, this work identifies a novel function of VIH proteins, implicating them in modulation of the expression of cell-wall homeostasis genes, and tolerance to water-deficit stress. This work suggests that plant VIH enzymes may be linked to drought tolerance and opens up the possibility of future research into using plant VIH-derived products to generate drought-resistant plants.