bluuebunny/crossref_metadata_2025 huggingface dataset:
One Hundred Times Better, at Home in Our Own Beds: Implementation of Home Intravenous Hydration After Chemotherapy in Children With Cancer
Authors: Orford Rebekah , Slater Penelope , Spencer Brooke , Giarola Teghan , Nicholls Wayne , Walker Rick , Foresto Steven , Bradford Natalie
Published: April 2023

Background: Home-based cancer care offers new ways of delivering supportive therapies, including post-chemotherapy hydration, traditionally delivered in hospital settings. Understanding how programs are developed and how parents perceive managing care at home offers opportunities to improve services and experiences. Aim: To describe the implementation process and evaluation of a home intravenous hydration program for children with cancer and thus to provide practical information for future initiatives. Methods: Data were prospectively collected on clinical impact, safety indicators, and estimated costs; these were tabulated and analysed. Semi-structured interviews were undertaken with a subset of parents regarding their experience and analysed using content analysis. Results: Over 34 months, 21 children were eligible, and 16 parents were educated and assessed competent with providing home care. All 16 children received home hydration with a median of 5.5 days per child (IQR 6.65 days). This avoided 116 hospital bed-days and associated costs, at an estimated total value of USD $ 105,521, on average saving USD $ 910 per day and USD $ 6,596 per child. There were no adverse events reported, and no child required re-admission to hospital while receiving home hydration. Parents were overwhelmingly positive in their feedback about the program. Verbatim quotes were synthesized under one overarching theme—supporting normality promotes recovery. Conclusion: When adequately trained and well supported, parents highly value providing home-based care to their children. This offers opportunities to improve experiences and outcomes for children and families as well as reduce costs to health services, achieving clinical impact without reducing safety.
Human CD34+ hematopoietic stem cell hierarchy: how far are we with its delineation at the most primitive level?
Authors: Anjos-Afonso Fernando , Bonnet Dominique
Published: April 2023

The ability to isolate and characterize different hematopoietic stem cell (HSC) or progenitor cell populations opens avenues to understand how hematopoiesis is regulated during development, homeostasis, and regeneration as well as in age-related conditions such as clonal hematopoiesis and leukemogenesis. Significant progress has been made in the past few decades in determining the composition of the cell types that exist in this system, but the most significant advances have come from mouse studies. However, recent breakthroughs have made significant strides that have enhanced the resolution of the human primitive hematopoietic compartment. Therefore, we aim to review this subject not only from a historical perspective but also to discuss the progress made in the characterization of the human postnatal CD34+ HSC–enriched populations. This approach will enable us to shed light on the potential future translational applicability of human HSCs.
RhoA promotes osteoclastogenesis and regulates bone remodeling through mTOR-NFATc1 signaling
Authors: Wang Jirong , Xu Chengyun , Zhang Jing , Bao Yizhong , Tang Ying , Lv Xiaoling , Ma Bo , Wu Ximei , Mao Genxiang
Published: April 2023

Background

The cytoskeletal architecture of osteoclasts (OCs) and bone resorption activity must be appropriately controlled for proper bone remodeling, which is associated with osteoporosis. The RhoA protein of GTPase plays a regulatory role in cytoskeletal components and contributes to osteoclast adhesion, podosome positioning, and differentiation. Although osteoclast investigations have traditionally been performed by in vitro analysis, however, the results have been inconsistent, and the significance of RhoA in bone physiology and pathology is still unknown.

Methods

We generated RhoA knockout mice by specifically deleting RhoA in the osteoclast lineage to understand more about RhoA’s involvement in bone remodeling. The function of RhoA in osteoclast differentiation and bone resorption and the mechanisms were assessed using bone marrow macrophages (BMMs) in vitro. The ovariectomized (OVX) mouse model was adopted to examine the pathological effect of RhoA in bone loss.

Results

Conditional deletion of RhoA in the osteoclast lineage causes a severe osteopetrosis phenotype, which is attributable to a bone resorption suppression. Further mechanistic studies suggest that RhoA deficiency suppresses Akt-mTOR-NFATc1 signaling during osteoclast differentiation. Additionally, RhoA activation is consistently related to the significant enhancement the osteoclast activity, which culminates in the development of an osteoporotic bone phenotype. Furthermore, in mice, the absence of RhoA in osteoclast precursors prevented occurring OVX-induced bone loss.

Conclusion

RhoA promoted osteoclast development via the Akt-mTOR-NFATc1 signaling pathway, resulting a osteoporosis phenotype, and that manipulating RhoA activity might be a therapeutic strategy for osteoporotic bone loss.
Comparative analysis of Fusarium crown rot resistance in synthetic hexaploid wheats and their parental genotypes
Authors: Chen Ying , Wang Yunpeng , Guan Fangnian , Long Li , Wang Yuqi , Li Hao , Deng Mei , Zhang Yazhou , Pu Zhien , Li Wei , Jiang Qiantao , Wang Jirui , Wei Yuming , Ma Jian , Xu Qiang , Kang Houyang , Qi Pengfei , Yuan Zhongwei , Zhang Lianquan , Liu Dengcai , Zheng Youliang , Chen Guoyue , Jiang Yunfeng
Published: April 2023

Background

Fusarium crown rot (FCR) is a chronic disease of cereals worldwide. Compared with tetraploid wheat, hexaploid wheat is more resistant to FCR infection. The underlying reasons for the differences are still not clear. In this study, we compared FCR responses of 10 synthetic hexaploid wheats (SHWs) and their tetraploid and diploid parents. We then performed transcriptome analysis to uncover the molecular mechanism of FCR on these SHWs and their parents.

Results

We observed higher levels of FCR resistance in the SHWs compared with their tetraploid parents. The transcriptome analysis suggested that multiple defense pathways responsive to FCR infection were upregulated in the SHWs. Notably, phenylalanine ammonia lyase (PAL) genes, involved in lignin and salicylic acid (SA) biosynthesis, exhibited a higher level of expression to FCR infection in the SHWs. Physiological and biochemical analysis validated that PAL activity and SA and lignin contents of the stem bases were higher in SHWs than in their tetraploid parents.

Conclusion

Overall, these findings imply that improved FCR resistance in SHWs compared with their tetraploid parents is probably related to higher levels of response on PAL-mediated lignin and SA biosynthesis pathways.
Anodal tDCS over the left DLPFC but not M1 increases muscle activity and improves psychophysiological responses, cognitive function, and endurance performance in normobaric hypoxia: a randomized controlled trial
Authors: Etemadi Matin , Amiri Ehsan , Tadibi Vahid , Grospretre Sidney , Valipour Dehnou Vahid , Machado Daniel Gomes da Silva
Published: April 2023

Background

Transcranial direct current stimulation (tDCS) has been shown to have positive effects on exercise performance and cognitive function in the normal ambient condition. Hypoxia is deemed a stressful situation with detrimental effects on physiological, psychological, cognitive, and perceptual responses of the body. Nevertheless, no study has evaluated the efficacy of tDCS for counteracting the negative effects of hypoxic conditions on exercise performance and cognition so far. Hence, in the present study, we investigated the effects of anodal tDCS on endurance performance, cognitive function, and perceptual responses in hypoxia.

Participants and methods

Fourteen endurance-trained males participated in five experimental sessions. After familiarization and measuring peak power output in hypoxia, in the first and second sessions, through the 3rd to 5th sessions, participants performed a cycling endurance task until exhaustion after 30 min hypoxic exposure at resting position followed by 20 min of anodal stimulation of the motor cortex (M1), left dorsolateral prefrontal cortex (DLPFC), or sham-tDCS. Color-word Stroop test and choice reaction time were measured at baseline and after exhaustion. Time to exhaustion, heart rate, saturated O2, EMG amplitude of the vastus lateralis, vastus medialis, and rectus femoris muscles, RPE, affective response, and felt arousal were also measured during the task under hypoxia.

Results

The results showed a longer time to exhaustion (+ 30.96%, p=0.036), lower RPE (− 10.23%, p = 0.045) and higher EMG amplitude of the vastus medialis muscle (+ 37.24%, p=0.003), affective response (+ 260%, p=0.035) and felt arousal (+ 28.9%, p=0.029) in the DLPFC tDCS compared to sham. The choice reaction time was shorter in DLPFC tDCS compared to sham (− 17.55%, p=0.029), and no differences were seen in the color-word Stroop test among the conditions under hypoxia. M1 tDCS resulted in no significant effect for any outcome measure.

Conclusions

We concluded that, as a novel finding, anodal stimulation of the left DLPFC might provide an ergogenic aid for endurance performance and cognitive function under the hypoxic condition probably via increasing neural drive to the working muscles, lowering RPE, and increasing perceptual responses.
Impact of chemoradiotherapy on the survival of unresectable locally advanced pancreatic cancer: a retrospective cohort analysis
Authors: Wang Zi-Meng , Ma Hong-Bin , Meng Yan
Published: April 2023

Background

The role of chemoradiotherapy in unresectable locally advanced pancreatic cancer is still unclear.

Methods

Data from patients with unresectable locally advanced pancreatic cancer were extracted from the Surveillance, Epidemiology, and End Results Program database. Univariate and multivariate Cox regression analyses were conducted to identify the independent prognostic factors of survival. Propensity score matching was carried out to minimize the interference of confounding factors. Subgroup analysis was performed to screen the characteristics of patients who would benefit from chemoradiotherapy.

Results

A total of 5002 patients with unresectable locally advanced pancreatic cancer were included. Among them, 2423 (48.4%) received chemotherapy, and 2579 (51.6%) received chemoradiotherapy. The median overall survival of all patients was 11 months. Multivariate Cox analysis showed that age (p < 0.001), marital status (p < 0.001), tumor size (p = 0.001), N stage (p = 0.015) and radiotherapy (p < 0.001) were independent prognostic factors of survival. Both before (HR, 0.817; 95% CI, 0.769–0.868; p < 0.001) and after (HR, 0.904; 95% CI, 0.876–0.933; p < 0.001) propensity score matching, chemoradiotherapy significantly improved the median overall survival of patients from 10 to 12 months. Subgroup analysis showed that chemoradiotherapy was significantly associated with improved survival regardless of sex, primary site or N stage. In addition, the following subgroups all significantly benefited from chemoradiotherapy: age ≥ 50 years, not divorced, grade 2–4, tumor size > 2 cm, adenocarcinoma, mucinous adenocarcinoma and white race.

Conclusions

Chemoradiotherapy is highly recommended for patients with unresectable locally advanced pancreatic cancer.
Rates of adverse clinical events in patients with chronic kidney disease: analysis of electronic health records from the UK clinical practice research datalink linked to hospital data
Authors: Little Dustin J. , Arnold Matthew , Hedman Katarina , Sun Ping , Haque Syed Asif , James Glen
Published: April 2023

Background

Further understanding of adverse clinical event rates in patients with chronic kidney disease (CKD) is required for improved quality of care. This study described baseline characteristics, adverse clinical event rates, and mortality risk in patients with CKD, accounting for CKD stage and dialysis status.

Methods

This retrospective, noninterventional cohort study included data from adults (aged ≥ 18 years) with two consecutive estimated glomerular filtration rates of < 60 ml/min/1.73 m2, recorded ≥ 3 months apart, from the UK Clinical Practice Research Datalink of electronic health records obtained between January 1, 2004, and December 31, 2017. Select adverse clinical events, associated with CKD and difficult to quantify in randomized trials, were assessed; defined by Read codes and International Classification of Diseases, Tenth Revision codes. Clinical event rates were assessed by dialysis status (dialysis-dependent [DD], incident dialysis-dependent [IDD], or non–dialysis-dependent [NDD]), dialysis modality (hemodialysis [HD] or peritoneal dialysis [PD]), baseline NDD-CKD stage (3a–5), and observation period.

Results

Overall, 310,953 patients with CKD were included. Comorbidities were more common in patients receiving dialysis than in NDD-CKD, and increased with advancing CKD stage. Rates of adverse clinical events, particularly hyperkalemia and infection/sepsis, also increased with advancing CKD stage and were higher in patients on HD versus PD. Mortality risk during follow-up (1–5-year range) was lowest in patients with stage 3a NDD-CKD (2.0–18.5%) and highest in patients with IDD-CKD (26.3–58.4%).

Conclusions

These findings highlight the need to monitor patients with CKD for comorbidities and complications, as well as signs or symptoms of clinical adverse events.
The evolution of the initial manifestations and renal involvement of chinese patients with classical and late-onset Fabry disease at different sexes and ages
Authors: Guo Wenkai , Xie Yuansheng , Ji Pengcheng , Li Shuang , Cai Guangyan , Chen Xiangmei
Published: April 2023

Background

Fabry disease is a rare hereditary disease involving multiple organs, and there are few reports on how the initial manifestations and renal involvement of these patients with classical and late-onset phenotype evolve with sexes and ages. To improve clinicians’ understanding of Fabry disease and avoid misdiagnoses by discussing the initial manifestations, first medical specialties visited and renal involvement development in patients.

Methods

This study collected relevant data from 311 Chinese Fabry disease patients (200 males, 111 females) and descriptive statistical analysis was used to analyze the evolution of the initial manifestations and renal involvement of patients with classical and late-onset phenotype at different sexes and ages.

Results

Regarding the age at manifestation onset, age at the first medical specialty visited and age at the diagnosis of Fabry disease, males were earlier than females, and males with classical phenotype were earlier than males with late-onset and females with classical phenotype. In both male and female patients, the initial manifestations of classical patients were mainly acroparesthesia, and the first medical specialty visited were mainly pediatrics and neurology. The initial manifestations of late-onset patients were mainly renal and cardiovascular involvement, and the first medical specialty visited were mainly nephrology and cardiology. In classical patients, both male and female, the initial manifestations of the preschool and the juvenile groups were mainly acroparesthesia, and the frequency of renal and cardiovascular involvement in the young group was higher than that in the preschool and juvenile groups. There was no obvious renal involvement in the preschool group, renal involvement was most common in the young group and the middle-aged and elderly group. Proteinuria can appear in classical male patients as early as approximately 20 years, and renal insufficiency can occur at approximately 25 years. With age, over 50% of classical male patients can develop varying degrees of proteinuria at the age of 25 and renal insufficiency at the age of 40. 15.94% of the patients progressed to dialysis or kidney transplantation, mainly classical males.

Conclusions

The initial manifestation of Fabry disease is affected by sex, age and classical/late-onset phenotype. The initial manifestations were mainly acroparesthesia and the frequency and degree of renal involvement increased gradually with aging in classical male patients.
A randomized study to compare oral potassium binders in the treatment of acute hyperkalemia
Authors: Cañas Alejandro E. , Troutt Hayden R. , Jiang Luohua , Tonthat Sam , Darwish Omar , Ferrey Antoney , Lotfipour Shahram , Kalantar-Zadeh Kamyar , Hanna Ramy , Lau Wei Ling
Published: April 2023

Background

The KBindER (K+ Binders in Emergency Room and hospitalized patients) clinical trial is the first head-to-head evaluation of oral potassium binders (cation-exchange resins) for acute hyperkalemia therapy.

Methods

Emergency room and hospitalized patients with a blood potassium level ≥ 5.5 mEq/L are randomized to one of four study groups: potassium binder drug (sodium polystyrene sulfonate, patiromer, or sodium zirconium cyclosilicate) or nonspecific laxative (polyethylene glycol). Exclusion criteria include recent bowel surgery, ileus, diabetic ketoacidosis, or anticipated dialysis treatment within 4 h of treatment drug. Primary endpoints include change in potassium level at 2 and 4 h after treatment drug. Length of hospital stay, next-morning potassium level, gastrointestinal side effects and palatability will also be analyzed. We are aiming for a final cohort of 80 patients with complete data endpoints (20 per group) for comparative statistics including multivariate adjustment for kidney function, diabetes mellitus, congestive heart failure, metabolic acidosis, renin-angiotensin-aldosterone system inhibitor prescription, and treatment with other agents to lower potassium (insulin, albuterol, loop diuretics).

Discussion

The findings from our study will inform decision-making guidelines on the role of oral potassium binders in the treatment of acute hyperkalemia.

Trial registration

ClinicalTrials.gov Identifier: NCT04585542. Registered 14 October 2020.
Amygdala signal abnormality and cognitive impairment in drug-naïve schizophrenia
Authors: Guo Huagui , Ye Haibiao , Li Zhijian , Li Xuesong , Huang Wei , Yang Yu , Xie Guojun , Xu Caixia , Li Xiaoling , Liang Wenting , Jing Huan , Zhang Chunguo , Tang Chaohua , Liang Jiaquan
Published: April 2023

Background

Recently studies had showed that the amygdala may take part in the cognitive impairment in schizophrenia (SC). However, the mechanism is still unclear, so we explored the relationship between the amygdala resting state magnetic resonance imaging (rsMRI) signal and cognitive function, to provide a reference for the follow-up study.

Methods

We collected 59 drug-naïve SCs and 46 healthy controls (HCs) from the Third People’s Hospital of Foshan. The rsMRI technique and automatic segmentation tool were used to extract the volume and functional indicators of the SC’s amygdala. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of the disease, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function. Pearson correlation analysis was used to compare the relationship between the structural and functional indicators of the amygdala and PANSS and RBANS.

Results

(1) There was no significant difference between SC and HC in age, gender and years of education. Compared with HC, the PANSS score of SC increased and the RBANS score decreased significantly. Meanwhile, the left amygdala volume decreased (t=-3.675, p < 0.001), and the Fractional amplitude of low-frequency fluctuations (FALFF) values of bilateral amygdala increased (tL=3.916, p < 0.001; tR=3.131, p = 0.002). (2) The volumes of the left amygdala were negatively correlated with the PANSS score (rL=-0.243, p = 0.039). While the FALFF values of the bilateral amygdala were positively correlated with the PANSS score (rL=0.257, p = 0.026; rR=0.259, p = 0.026). Bilateral amygdala volumes and FALFF values were positively correlated (rL=0.445, p < 0.001; rR=0.326, p = 0.006) and negatively correlated with RBANS score (rL=-0.284, p = 0.014; rR=-0.272, p = 0.020), respectively.

Conclusion

The abnormal volume and function of the amygdala play important roles in the disease process of SC, and are closely related to cognitive impairment.
Six Spain Thymus essential oils composition analysis and their in vitro and in silico study against Streptococcus mutans
Authors: Park Su-Yeon , Raka Rifat Nowshin , Hui Xiu-Li , Song Yang , Sun Jin-Long , Xiang Jie , Wang Juan , Jin Jian-Ming , Li Xu-Kai , Xiao Jun-Song , Wu Hua
Published: April 2023

Background

Streptococcus mutans is a well-known oral pathogen that plays a critical role in the development of dental caries. Many studies have been directed to discover the chemical compounds present in natural products to inhibit the growth and biofilm formation activity of S. mutans. Thymus essential oils exhibit good inhibition on the growth and pathogenesis of S. mutans. However, details about the active compounds in Thymus essential oil and the inhibition mechanism still remain unclear. The aim of this study was to investigate the antimicrobial activity of 6 Thymus species (Three samples of Thymus vulgaris, two samples of Thymus zygis, and one sample of Thymus satureioides essential oils) on S. mutans, to identify the potential active components, and to reveal the underlying mechanism.

Methods

The composition of Thymus essential oils was analyzed by gas chromatography-mass spectrometry. And its antibacterial effect was evaluated based on the bacterial growth, acid production, biofilm formation and genetic expression of virulence factors by S. mutans. Potential active components of the Thymus essential oil were identified using molecular docking and correlation analysis.

Results

GC–MS analysis showed that the major components in the 6 Spain Thymus essential oils were linalool, α-terpineol, p-cymene, thymol and carvacrol. MIC and MBC analysis showed that 3 Thymus essential oils showed very sensitive antimicrobial activity, and were chosen for further analysis. The 3 Thymus essential oil exhibited a significant inhibitory effect on acid production, adherence and biofilm formation of S. mutans and the expression of virulence genes, such as brpA, gbpB, gtfB, gtfC, gtfD, vicR, spaP and relA. Correlation analysis showed that phenolic components, such as carvacrol and thymol, were positively related to DIZ value, which suggests that they are the potential antimicrobial components. Molecular docking between the Thymus essential oil components and virulence proteins also found that carvacrol and thymol exhibited strong binding affinity with functional domains of virulence genes.

Conclusions

Thymus essential oil showed significant inhibition against the growth and pathogenesis of S. mutans depending on their composition and concentration. And phenolic compounds, such as carvacrol and thymol, are the major active components. Thymus essential oil could be used in oral healthcare products as a potential anti-caries ingredient.
Comprehensive proteomics and platform validation of urinary biomarkers for bladder cancer diagnosis and staging
Authors: Vanarsa Kamala , Castillo Jessica , Wang Long , Lee Kyung Hyun , Pedroza Claudia , Lotan Yair , Mohan Chandra
Published: April 2023

Background

Bladder cancer (BC) is among the most common cancers diagnosed in men in the USA. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease.

Methods

An aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The top hits were subjected to systems biology analyses. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. Three of these proteins were next validated in an independent BC cohort of differing ethnicity.

Results

Systems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 emerging as key molecular regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression. Of 21 urine proteins that discriminated BC from urology clinic controls (UC), urine d-dimer displayed the highest accuracy (0.96) and sensitivity of 97%. Furthermore, 8 urine proteins significantly discriminated MIBC from NMIBC (AUC = 0.75–0.99), with IL-8 and IgA being the best performers. Urine IgA and fibronectin exhibited the highest specificity of 80% at fixed sensitivity for identifying advanced BC.

Conclusions

Given the high sensitivity (97%) of urine d-dimer for BC, it may have a role in the initial diagnosis or detection of cancer recurrence. On the other hand, urine IL-8 and IgA may have the potential in identifying disease progression during patient follow-up. The use of these biomarkers for initial triage could have a significant impact as the current cystoscopy-based diagnostic and surveillance approach is costly and invasive when compared to a simple urine test.
Helicobacter pylori-induced aberrant demethylation and expression of GNB4 promotes gastric carcinogenesis via the Hippo–YAP1 pathway
Authors: Liu Duanrui , Liu Yunyun , Zhu Wenshuai , Lu Yi , Zhu Jingyu , Ma Xiaoli , Xing Yuanxin , Yuan Mingjie , Ning Bin , Wang Yunshan , Jia Yanfei
Published: April 2023

Background

Helicobacterpylori (H. pylori) infection causes aberrant DNA methylation and contributes to the risk of gastric cancer (GC). Guanine nucleotide-binding protein subunit beta-4 (GNB4) is involved in various tumorigenic processes. We found an aberrant methylation level of GNB4 in H. pylori-induced GC in our previous bioinformatic analysis; however, its expression and underlying molecular mechanisms are poorly understood.

Methods

The expression, underlying signaling pathways, and clinical significance of GNB4 were analyzed in a local cohort of 107 patients with GC and several public databases. H. pylori infection was induced in in vitro and in vivo models. Methylation-specific PCR, pyrosequencing, and mass spectrometry analysis were used to detect changes in methylation levels. GNB4, TET1, and YAP1 were overexpressed or knocked down in GC cell lines. We performed gain- and loss-of-function experiments, including CCK-8, EdU, colony formation, transwell migration, and invasion assays. Nude mice were injected with genetically manipulated GC cells, and the growth of xenograft tumors and metastases was measured. Real-time quantitative PCR, western blotting, immunofluorescence, immunohistochemistry, chromatin immunoprecipitation, and co-immunoprecipitation experiments were performed to elucidate the underlying molecular mechanisms.

Results

GNB4 expression was significantly upregulated in GC and correlated with aggressive clinical characteristics and poor prognosis. Increased levels of GNB4 were associated with shorter survival times. Infection with H. pylori strains 26695 and SS1 induced GNB4 mRNA and protein expression in GC cell lines and mice. Additionally, silencing of GNB4 blocked the pro-proliferative, metastatic, and invasive ability of H. pylori in GC cells. H. pylori infection remarkably decreased the methylation level of the GNB4 promoter region, particularly at the CpG#5 site (chr3:179451746–179451745). H. pylori infection upregulated TET1 expression via activation of the NF-κB. TET binds to the GNB4 promoter region which undergoes demethylation modification. Functionally, we identified that GNB4 induced oncogenic behaviors of tumors via the Hippo–YAP1 pathway in both in vitro and in vivo models.

Conclusions

Our findings demonstrate that H. pylori infection activates the NF-κB-TET1-GNB4 demethylation-YAP1 axis, which may be a potential therapeutic target for GC.
Hydrogel armed with Bmp2 mRNA-enriched exosomes enhances bone regeneration
Authors: Yang Zhujun , Li Xuejian , Gan Xueqi , Wei Mengying , Wang Chunbao , Yang Guodong , Zhao Yimin , Zhu Zhuoli , Wang Zhongshan
Published: April 2023

Background

Sustained release of bioactive BMP2 (bone morphogenetic protein-2) is important for bone regeneration, while the intrinsic short half-life of BMP2 at protein level cannot meet the clinical need. In this study, we aimed to design Bmp2 mRNA-enriched engineered exosomes, which were then loaded into specific hydrogel to achieve sustained release for more efficient and safe bone regeneration.

Results

Bmp2 mRNA was enriched into exosomes by selective inhibition of translation in donor cells, in which NoBody (non-annotated P-body dissociating polypeptide, a protein that inhibits mRNA translation) and modified engineered BMP2 plasmids were co-transfected. The derived exosomes were named ExoBMP2+NoBody. In vitro experiments confirmed that ExoBMP2+NoBody had higher abundance of Bmp2 mRNA and thus stronger osteogenic induction capacity. When loaded into GelMA hydrogel via ally-L-glycine modified CP05 linker, the exosomes could be slowly released and thus ensure prolonged effect of BMP2 when endocytosed by the recipient cells. In the in vivo calvarial defect model, ExoBMP2+NoBody-loaded GelMA displayed great capacity in promoting bone regeneration.

Conclusions

Together, the proposed ExoBMP2+NoBody-loaded GelMA can provide an efficient and innovative strategy for bone regeneration.
The prognostic value of quality of life in atrial fibrillation on patient value
Authors: Theunissen Luc J.H.J. , van de Pol Jeroen A.A. , van Steenbergen Gijs J. , Cremers Henricus-Paul , van Veghel Dennis , van der Voort Pepijn H. , Polak Peter E. , de Jong Sylvie F.A.M.S. , Seelig Jaap , Smits Geert , Kemps Hareld M.C. , Dekker Lukas R.C.
Published: April 2023

Background

In this study, the prognostic value of AF-related quality of life (AFEQT) at baseline on Major Adverse Cardiovascular Events (MACE) and improvement of perceived symptoms (EHRA) was assessed. Furthermore, the relationship between QoL and AF-related hospitalizations was assessed.

Methods

A cohort of AF-patients diagnosed between November 2014 and October 2019 in four hospitals embedded within the Netherlands Heart Network were prospectively followed for 12 months. MACE was defined as stroke, myocardial infarction, heart failure and/or mortality. Subsequently, MACE, EHRA score improvement and AF-related hospitalizations between baseline and 12 months of follow-up were recorded.

Results

In total, 970 AF-patients were available for analysis. In analyses with patients with complete information on the confounder subset 36/687 (5.2%) AF-patients developed MACE, 190/432 (44.0%) improved in EHRA score and 189/510(37.1%) were hospitalized during 12 months of follow-up. Patients with a low AFEQT score at baseline more often developed MACE (OR(95%CI): 2.42(1.16–5.06)), more often improved in EHRA score (OR(95%CI): 4.55(2.45–8.44) and were more often hospitalized (OR(95%CI): 4.04(2.22–7.01)) during 12 months post diagnosis, compared to patients with a high AFEQT score at baseline.

Conclusions

AF-patients with a lower quality of life at diagnosis more often develop MACE, more often improve on their symptoms and also were more often hospitalized, compared to AF-patients with a higher quality of life. This study highlights that the integration of patient-reported outcomes, such as quality of life, has the potential to be used as a prognostic indicator of the expected disease course for AF.
Child and adolescent mental health services in a devolved healthcare system: a qualitative exploration of sustainable practices
Authors: Banwell Emily , Humphrey Neil , Qualter Pamela
Published: April 2023

Background

The transference of research evidence into routine healthcare practice remains poorly understood. This includes understanding the prerequisites of longer-term viability. The present study investigated the sustainable practices of GM i-THRIVE, a programme which reconceptualizes mental health services for children and young people (CYP) in Greater Manchester, United Kingdom. We aimed to establish whether a sustainable future was likely, and to identify areas of focus to improve that likelihood.

Methods

The NHS Sustainability Model, typically completed as a questionnaire measure, was converted into interview questions. The responses of nine professionals, from a variety of roles across the CYP mental health workforce, were explored using inductive thematic framework analysis. Selected participants completed the original questionnaire.

Results

Five themes (communication; support; barriers to implementation; past, present, and future: the implementation journey; and the nuances of GM i-THRIVE) and 21 subthemes formed the final thematic framework. Relationships with senior leaders and with colleagues across the workforce were seen as important. Leaders’ roles in providing meaning and fit were emphasized. Whilst training delivered the programme’s aims well, monitoring its dissemination was challenging. Widespread issues with dedicating sufficient time to implementation were raised. The flexibility of the programme, which can be applied in multiple ways, was discussed positively. This flexibility links to the idea of GM i-THRIVE as a mindset change, and the uniqueness of this style of intervention was discussed. To varying degrees, themes were supported by responses to the quantitative measure, although several limitations to the use of the questionnaire were discovered. Consequently, they were used to infer conclusions to a lesser degree than originally intended.

Conclusions

Professionals involved with GM i-THRIVE reported many elements that indicate a positive future for the programme. However, they suggested that more attention should be given to embedding the core concepts of the model at the current stage of implementation. Limitations relating to its use within our study are discussed, but we conclude that the NHS Sustainability Model is a suitable way of guiding qualitative implementation research. It is especially valuable for localized interventions. The constraints of our small sample size on transferability are considered.
Evaluation of lateral and anterior center-edge angles according to sex and anterior pelvic plane tilt angle: a three-dimensional quantitative analysis
Authors: Hong Kee-Bum , Lee Woo-suk , Kang Kyutae , Kang Kyoung Tak , Cho Byung Woo
Published: April 2023

Background

This study aimed to quantitatively evaluate lateral center-edge angle (LCEA) and anterior center-edge angle (ACEA) according to sex and the anterior pelvic plane (APP) tilt angle and analyze the correlation between these measurements and acetabular coverage.

Methods

Computed tomography scans of 71 adults (38 men and 33 women) with normal hip joints were obtained. LCEA, anterior ACEA, and acetabular coverage were measured with APP tilt every 5° from − 30° to + 30° and were compared between the sexes. The correlation between acetabular coverage and LCEA/ACEA was also analyzed.

Results

(1) LCEA, ACEA, and acetabular coverage were statistically larger in men than in women at all APP tilt angles (with the exception of acetabular coverage ≥ 25°). (2) LCEA, ACEA, and acetabular coverage differed according to APP tilt angle. LCEA and acetabular coverage showed maximum values at 10°. ACEA showed a tendency to increase by an average of 3.6° for every 5° increase in the APP tilt angle. LCEA demonstrated strong and very strong associations across all APP tilting angles, whereas ACEA showed a moderate association at angles ≥ 15° in men and ≥ 30° in women.

Conclusions

The LCEA and ACEA are adequate measurement methods that reflect actual acetabular coverage unless the pelvis is tilted excessively anteriorly. While pelvic tilting does not need to be considered for LCEA within the physiologic range, it should always be taken into account for ACEA, as it increases by an average of 3.6° for every 5° increase in APP tilt angle.

Level of evidence

Level III: retrospective cohort study.
Graves’ disease-induced immune thrombocytopenic purpura in an African female: a case report
Authors: Agyapong Kwabena Oteng , Folson Aba A. , Fiador Kate , Kootin-Sanwu Cecilia , Tufuor Martha , Bampoh Sally Afua , Fiscian Henrietta , Wonkyi Roland
Published: April 2023

Background

Immune thrombocytopenic purpura is a condition associated with an unusual, unexplained, and sometimes very severe reduction in the level of platelets in the blood. Though documented, its association with Graves’ disease is not very common and can easily be missed or misdiagnosed, leading to excessive bleeding and mortality. Treatment with steroids and antithyroid medications has been shown to be beneficial in correcting thrombocytopenia in these patients, although the response is varied. We report on a patient with Graves’ disease who presents with immune thrombocytopenic purpura.

Case presentation

A 37-year-old Ghanaian female presented to our hospital’s emergency department with a complaint of palpitations, difficulty breathing, easy fatigue, and headaches. She had been referred from a peripheral hospital as a case of thrombocytopenia, severe anemia, and anterior neck swelling. She was diagnosed with Graves’ disease 2 years ago, became euthyroid during treatment, but defaulted. On further examination and investigation, she was diagnosed with immune thrombocytopenic purpura and was also found to have elevated free T3 and T4, and suppressed thyroid stimulating hormone. She also had high thyroid autoantibodies. She was initially started on oral prednisolone but there was no stabilization of platelets until methimazole was introduced, which improved and normalized her platelet count.

Conclusion

The association of Graves’ disease with immune thrombocytopenic purpura, though documented, is uncommon, and very few cases have been reported thus far. There have not been any reported cases in Ghana or Sub-Saharan Africa and hence, clinicians should be aware of this association when investigating immune thrombocytopenic purpura and should consider Graves’ disease as a possible cause. From this study, we observed that there was no improvement in platelet count following the use of corticosteroid therapy until methimazole was started.
Whole genome sequencing to study antimicrobial resistance and RTX virulence genes in equine Actinobacillus isolates
Authors: Vereecke Nick , Vandekerckhove Arlette , Theuns Sebastiaan , Haesebrouck Freddy , Boyen Filip
Published: April 2023

Actinobacillus equuliis mostly associated with disease in horses and is most widely known as the causative agent of sleepy foal disease. Even though existing phenotypic tools such as biochemical tests, 16S rRNA gene sequencing, and Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) can be used to identify members of theActinobacillusgenus, these methods struggle to differentiate between certain species and do not allow strain, virulence, and antimicrobial susceptibility typing. Hence, we performed in-depth analysis of 24 equineActinobacillusisolates using phenotypic identification and susceptibility testing on the one hand, and long-read nanopore whole genome sequencing on the other hand. This allowed to address strain divergence down to the whole genome single nucleotide polymorphism (SNP) level. While lowest resolution was observed for 16S rRNA gene classification, a new multi-locus sequence typing (MLST) scheme allowed proper classification up to the species level. Nevertheless, a SNP-level analysis was required to distinguishA. equulisubspeciesequuliandhaemolyticus. Our data provided first WGS data onActinobacillusgenomospecies 1,Actinobacillus genomospecies 2, andA. arthritidis, which allowed the identification of a newActinobacillusgenomospecies 1 field isolate. Also, in-depth characterization of RTX virulence genes provided information on the distribution, completeness, and potential complementary nature of the RTX gene operons within theActinobacillusgenus. Even though overall low prevalence of acquired resistance was observed, two plasmids were identified conferring resistance to penicillin-ampicillin-amoxicillin and chloramphenicol in oneA. equulistrain. In conclusion our data delivered new insights in the use of long-read WGS in high resolution identification, virulence gene typing, and antimicrobial resistance (AMR) of equineActinobacillusspecies.
A class of Schrödinger elliptic equations involving supercritical exponential growth
Authors: Leuyacc Yony Raúl Santaria
Published: April 2023

This paper studies the existence of nontrivial solutions to the following class of Schrödinger equations: $$ \textstyle\begin{cases} -\operatorname{div}(w(x)\nabla u) = f(x,u),&\ x \in B_{1}(0), \\ u = 0,&\ x \in \partial B_{1}(0), \end{cases} $$

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Examining the effect of electronic banking service quality on customer satisfaction and loyalty: an implication for technological innovation
Authors: Ayinaddis Samuel Godadaw , Taye Birhan Ambachew , Yirsaw Bantie Getnet
Published: April 2023

In this ever-growing competitive banking industry, understanding the effect of electronic banking service quality on customers’ satisfaction and loyalty is the secret to being competitive and successful in the sector. In Ethiopia, measuring service quality in the banking sector is a new paradigm. The primary purpose of this research was to examine the effect of electronic banking (e-Banking) service quality on customer satisfaction in Ethiopia’s emerging banking industry. Data were obtained using a closed-ended structured questionnaire from a total of 385 participants selected using a convenience sampling technique. Frequencies, percentage distributions, group modes, standard deviations, Chi-square correlations, and multinomial logistic regression were employed to analyze the quantitative data. The results confirmed a significant effect of the variables responsiveness, reliability, security and privacy, speed, and convenience on customer satisfaction. Similarly, customer satisfaction with the electronic banking service quality has a significant effect on customer loyalty. System availability, easiness to use, and service charge, on the other hand, have no statistically significant impact on customer satisfaction. Hence, based on the findings of this study, it is recommended that banks should focus on the factors related to responsiveness, reliability, system availability, and speed to maximize customer satisfaction and loyalty. The adoption of electronic banking service that offers a meaningful guarantee takes care of problems promptly, provides services precisely as promised, is always available and quick delivery enables customers to be better satisfied and thus create committed and loyal customers.
The inter-connection of sports bra design attributes and elderly women's perceptions
Authors: Zhou Jie , Lei Qiwen Emma , Mao Qian , Wang Aosi , Yip Joanne , Zhang Jun
Published: April 2023

As a sports facility category, a sports bra is regarded as an enabling technology garment with advanced functions and new cultural meanings. Women, particularly elderly women, are encouraged to wear a sports bra during physical activity because wearing a sports bra can not only prevent them from exercise-induced injuries but also increase the acceptance of their bodies. However, most studies usually targeted younger women. The requirements and expectations of elderly women on sports bras differ from younger individuals. Hence, this study aims to advance and explore the design demands, providing insights into age-friendly sports bra design by using more permeable physical and psychological boundaries based on conceptual frameworks. The sports bra evaluation words were extracted and calculated to construct the network. The appearance frequency of keywords, closeness centrality, betweenness centrality, and interconnection between every pair of words were illustrated and analyzed by using semantic-based network analysis. Network analysis deduced that the discomfort of sports bras was closely related with the support, tightness, cup design, and strap design. Beside, thermal management contributes significantly to the comfort. The outlook of a sports bra was associated with cup design. The Page-rank result showed that cup, tightness, hot, straps and quality were the top five important design attributes. The unobservable mechanisms underlying the keywords provide an alternative model, which can help to explore the key improvements for sports bra design.
Incidence of non-invasive all-cause pneumonia in children in the United States before and after the introduction of pneumococcal conjugate vaccines: a retrospective claims database analysis
Authors: Hu Tianyan , Sarpong Eric M. , Song Yan , Done Nicolae , Liu Qing , Lemus-Wirtz Esteban , Signorovitch James , Mohanty Salini , Weiss Thomas
Published: April 2023

Background

Pneumonia is the most serious form of acute respiratory infection and Streptococcus pneumoniae is a leading cause of pediatric bacterial pneumonia. Pneumococcal conjugate vaccines were introduced in the United States (US) in 2000 (7-valent [PCV7]) and 2010 (13-valent [PCV13]). This study estimated annual incidence rates (IRs) of all-cause pneumonia (ACP) among US children aged < 18 years before and after the introduction of PCV7 and PCV13.

Methods

ACP episodes were identified in the IBM MarketScan Commercial and Medicaid Databases using diagnosis codes. Annual IRs were calculated overall and by inpatient and outpatient settings as the number of episodes per 100,000 person-years (PY) for all children aged < 18 years and by age group (< 2, 2–4, and 5–17 years). National estimates of annual pneumonia IRs were extrapolated using Census Bureau data. Interrupted time series (ITS) analyses were used to assess immediate and gradual changes in monthly pneumonia IRs, adjusting for seasonality.

Results

In the commercially-insured population, ACP IRs declined between the pre-PCV7 period (1998–1999) and late PCV13 period (2014–2018) from 5,322 to 3,471 episodes per 100,000 PY for children aged < 2 years, from 4,012 to 3,794 episodes per 100,000 PY in children aged 2–4 years but increased slightly from 1,383 to 1,475 episodes per 100,000 PY in children aged 5–17 years. The ITS analyses indicated significant decreases in monthly ACP IRs in the early PCV7 period (2001–2005) among younger children and in the early PCV13 period (2011–2013) among all children. Increases were observed in the late PCV7 period (2006–2009) among all age groups, but were only significant among older children. IRs of inpatient ACP decreased across all age groups, but outpatient pneumonia IRs remained stable during the study timeframe, even increasing slightly in children aged 5–17 years. More prominent declines were observed for Medicaid-insured children across all age groups; however, Medicaid IRs were higher than IRs of commercially-insured children during the entire study timeframe.

Conclusions

ACP disease burden remains high in US children of all ages despite overall reductions in incidence rates during 1998–2018 following the introduction of PCV7 and PCV13.