bluuebunny/crossref_metadata_2025 huggingface dataset:
Motor organization of unilateral polymicrogyria associated with ipsilateral brainstem atrophy – a case report
Authors: Roh Choong-Hee , Kim Da-Sol , Kim Gi-Wook , Won Yu Hui , Ko Myoung-Hwan , Seo Jeoung-Hwan , Park Sung-Hee
Published: August 2022

Background

Polymicrogyria refers to the disruption of normal cerebral cortical development late in neuronal migration or in early cortical organization. Although patients with polymicrogyria feature relatively favorable motor outcomes, polymicrogyric lesions accompanied by extensive unilateral hemispheric atrophy and ipsilateral brainstem atrophy may induce poorer motor outcomes. This study is the first to employ transcranial magnetic stimulation (TMS) and diffusion tensor imaging (DTI) to characterize changes to motor organization and white matter tracts induced by polymicrogyria.

Case presentation

We document a case of a 16-year-old female with left hemiplegic unilateral polymicrogyria associated with ipsilateral brainstem atrophy. Magnetic resonance imaging (MRI) of the brain revealed unilateral polymicrogyria to have affected anterior cortical areas, including the perisylvian region on the right side. The right halves of the brain and brainstem were significantly smaller than the left halves. Although our patient was found to exhibit cortical dysplasia of the right frontoparietal and sylvian fissure areas and a decreased number of fibers in the corticospinal tract (CST) of the affected side on DTI, the connectivity of the CST was preserved up to the motor cortex. We also measured the cross-sectional area of the CST at the level of the pons. In TMS, contralateral motor evoked potentials (MEPs) were evoked from both hands, but the ipsilateral MEPs were evoked only from the left hand. The left hand featured a long duration, polyphasic pattern of contralateral MEPs.

Discussion and conclusion

TMS revealed that the concurrent bilateral projections to the paretic hand from the affected and unaffected hemispheres and contralateral MEPs in the paretic hand were polyphasic, indicating delayed electrophysiological maturation or a pathologic condition of the corticospinal motor pathways. In DTI, the cross-sectional area of the CST at the level of the pons on the affected side was smaller than that on the unaffected side. These DTI findings reveal an inadequate CST volume. Despite extensive brain malformation and ipsilateral brainstem atrophy, our patient had less severe motor dysfunction and presented with involuntary mirror movements. Mirror movements in the paretic hand are considered to indicate ipsilateral corticospinal projections from the unaffected hemisphere and may suggest favorable motor outcomes in early brain injury.
Phantom-based acquisition time and image reconstruction parameter optimisation for oncologic FDG PET/CT examinations using a digital system
Authors: Fragoso Costa Pedro , Jentzen Walter , Brahmer Alissa , Mavroeidi Ilektra-Antonia , Zarrad Fadi , Umutlu Lale , Fendler Wolfgang P. , Rischpler Christoph , Herrmann Ken , Conti Maurizio , Seifert Robert , Sraieb Miriam , Weber Manuel , Kersting David
Published: August 2022

Background

New-generation silicon-photomultiplier (SiPM)-based PET/CT systems exhibit an improved lesion detectability and image quality due to a higher detector sensitivity. Consequently, the acquisition time can be reduced while maintaining diagnostic quality. The aim of this study was to determine the lowest 18F-FDG PET acquisition time without loss of diagnostic information and to optimise image reconstruction parameters (image reconstruction algorithm, number of iterations, voxel size, Gaussian filter) by phantom imaging. Moreover, patient data are evaluated to confirm the phantom results.

Methods

Three phantoms were used: a soft-tissue tumour phantom, a bone-lung tumour phantom, and a resolution phantom. Phantom conditions (lesion sizes from 6.5 mm to 28.8 mm in diameter, lesion activity concentration of 15 kBq/mL, and signal-to-background ratio of 5:1) were derived from patient data. PET data were acquired on an SiPM-based Biograph Vision PET/CT system for 10 min in list-mode format and resampled into time frames from 30 to 300 s in 30-s increments to simulate different acquisition times. Different image reconstructions with varying iterations, voxel sizes, and Gaussian filters were probed. Contrast-to-noise-ratio (CNR), maximum, and peak signal were evaluated using the 10-min acquisition time image as reference. A threshold CNR value ≥ 5 and a maximum (peak) deviation of ± 20% were considered acceptable. 20 patient data sets were evaluated regarding lesion quantification as well as agreement and correlation between reduced and full acquisition time standard uptake values (assessed by Pearson correlation coefficient, intraclass correlation coefficient, Bland–Altman analyses, and Krippendorff’s alpha).

Results

An acquisition time of 60 s per bed position yielded acceptable detectability and quantification results for clinically relevant phantom lesions ≥ 9.7 mm in diameter using OSEM-TOF or OSEM-TOF+PSF image reconstruction, a 4-mm Gaussian filter, and a 1.65 × 1.65 x 2.00-mm3 or 3.30 × 3.30 x 3.00-mm3 voxel size. Correlation and agreement of patient lesion quantification between full and reduced acquisition times were excellent.

Conclusion

A threefold reduction in acquisition time is possible. Patients might benefit from more comfortable examinations or reduced radiation exposure, if instead of the acquisition time the applied activity is reduced.
The expression of Hexokinase 2 and its hub genes are correlated with the prognosis in glioma
Authors: Huang Yishan , Ouyang Fan , Yang Fengxia , Zhang Ning , Zhao Weijiang , Xu Hongwu , Yang Xiaojun
Published: August 2022

Background

Hexokinase 2 (HK2) is an enzyme that catalyses the conversion of glucose to glucose-6-phosphate, which has been found to be associated with malignant tumour growth. However, the potential immunological and clinical significance of HK2, especially in terms of prognostic prediction for patients with glioma, has not been fully elucidated.

Methods

To investigate the expression, immunological and clinical significance of HK2 in patients with glioma, several databases, including ONCOMINE, TIMER2.0, GEPIA, CGGA, UCSC, LinkedOmics, Metascape, STRING, GSCA, and TISIDB, as well as biochemical, cellular, and pathological analyses, were used in this study. In addition, we performed univariate, multivariate Cox regression and nomogram analyses of the hub genes positively and negatively correlated with HK2 to explore the potential regulatory mechanism in the initiation and development of glioma.

Results

Our results demonstrated that HK2 was highly expressed in most malignant cancers. HK2 expression was significantly higher in lower grade glioma (LGG) and glioblastoma (GBM) than in adjacent normal tissue. In addition, HK2 expression was significantly correlated with clinical parameters, histological manifestations, and prognosis in glioma patients. Specifically, the data from The Cancer Genome Atlas downloaded from UCSC Xena database analysis showed that high expression of HK2 was strongly associated with poor prognosis in glioma patients. The LinkedOmics database indicated that HK2-related genes were mainly enriched in immune-related cells. In LGG and GBM tissues, HK2 expression is usually correlated with recognized immune checkpoints and the abundance of multiple immune infiltrates. Similarly, the Metascape database revealed that HK2-related genes were mainly enriched and annotated in immune-related pathways and immune cells. Further investigations also confirmed that the inhibition of HK2 expression remarkably suppressed metastasis and vasculogenic mimicry (VM) formation in glioma cells through regulating the gene expression of inflammatory and immune modulators.

Conclusion

HK2 expression was closely associated with the malignant properties of glioma through activating multiple immune-related signalling pathways to regulate immune responses and the infiltration of immune cells. Thus, HK2 and its hub genes may be a potential target for the treatment of glioma.
Long-term visual quality after small incision lenticule extraction (SMILE) and laser assisted subepithelial keratomileusis (LASEK) for low myopia
Authors: Fu Mengjun , Li Meiyan , Wei Ruoyan , Zhang Chuanwei , Huang Yangyi , Niu Lingling , Wang Xiaoying , Zhang Haorun , Zhou Xingtao
Published: August 2022

Background

Few studies have reported the visual outcomes of small-incision lenticule extraction (SMILE) and laser-assisted subepithelial keratomileusis (LASEK) for myopia correction. This study aims to compare the visual quality and corneal wavefront aberrations after SMILE and LASEK for low-myopia correction.

Methods

In this prospective study, we included 29 eyes of 29 patients who received SMILE and 23 eyes of 23 patients who received LASEK between June 2018 and January 2019. The following measurements were assessed: uncorrected (UDVA) and corrected (CDVA) distance visual acuity, manifest refraction, corneal wavefront aberrations, and subjective visual quality. All patients were followed up for two years.

Results

All procedures were uneventful. An efficacy index of 1.19 ± 0.17 was established in the SMILE group and 1.23 ± 0.20 in the LASEK group. No eyes lost more than two lines of CDVA. We found that 93% (27/29) of the treated eyes in the SMILE group and 91% (21/23) in the LASEK group had spherical equivalent (SE) within ± 0.25D. The increases in the total corneal spherical aberration and the corneal front spherical aberration were lower in the SMILE group than in the LASEK group (P < 0.01). In contrast, the increases in the total corneal vertical coma and the corneal front vertical coma in the SMILE group were greater than those in the LASEK group (P < 0.01).

Conclusion

Both SMILE and LASEK have good safety, stability, and patient-reported satisfaction for low myopia. SMILE induced less corneal spherical aberration but greater vertical coma than LASEK.
Validation of the French version of COHIP-SF-19 among 12-years children in New Caledonia
Authors: Skandrani Amal , El Osta Nada , Pichot Hélène , Eschevins Caroline , Pereira Bruno , Tubert-Jeannin Stéphanie
Published: August 2022

Background

Assessment of oral health-related quality of life is now associated to clinical indicators in epidemiological studies. This study aimed at validating the French Short Form of the Child Oral Health Impact Profile (COHIP-SF-19) and assessing the impacts of oral diseases among schoolchildren in New Caledonia (NC).

Methods

A sample of 12-years-old children (n = 971) was selected in 2019 in NC using a random, stratified, and clustered sampling technique. Children filled the French COHIP-SF-19 questionnaire. Information on sociodemographic characteristics, oral hygiene habits, perception of oral health problems were also collected through self-administered questionnaires or from the schools’ database. Dental status (dental caries, gingival status, and dental functional units) was clinically recorded at school by four calibrated examiners. Cronbach’s alpha and intraclass correlation coefficients (ICC) were calculated. Kruskal–Wallis tests and spearman correlations were used along with multilevel mixed models taking into account the cluster and examiner effects. A confirmatory factor analysis was conducted and sensitivity analyses were performed.

Results

Among the 693 children examined, 557 children were included. Oral diseases were frequent in the study population 40% had dental caries and 55% presented gingivitis. The COHIP scores ranged from 7 to 76 (57.9 ± 9.96) with 96.4% of the children having experienced oral health problems, 81.7% reporting functional impacts and 90.5% socio-emotional impacts. Overall, the French COHIP-SF-19 showed satisfactory psychometric characteristics. Internal consistency was high (Cronbach’s alpha = 0.80) and reproducibility excellent (ICC = 0.9). Discriminant and concurrent validity were adequate. Indeed, children with less optimal social situation, impaired dental status, declaring severe dental problems or difficulties in accessing oral health care showed lower COHIP-SF-19 scores. Factor analyses suggested a four-component structure with identification of a new domain (self -image) and changes in the repartition of the items within the original domains. Sensitivity analyses showed similar results for children with partial or complete answers in the COHIP questionnaire.

Conclusions

The French COHIP-SF-19 showed satisfactory psychometric characteristics and allowed to identify the high impacts of oral diseases in New Caledonian children, namely for socially deprived children.
Healthcare providers’ perspectives of the supportive care needs of women with advanced breast cancer in Ghana
Authors: Akuoko Cynthia Pomaa , Chambers Shirley , Yates Patsy
Published: August 2022

Background

The study sought to understand the supportive care needs of women with advanced breast cancer from the perspectives of healthcare professionals (HCPs) and key informants of charitable/non-governmental organisations (NGOs), that provide supportive care services to women with advanced breast cancer, in Ghana.

Methods

A qualitative descriptive approach was employed via one-to-one semi-structured interviews with 13 HCPs and key informants of charitable/NGOs in Ghana that provide supportive care services to women with advanced breast cancer. The study was underpinned by Bradshaw’s taxonomy of social needs and Fitch’s supportive care framework. The data were analysed using a deductive content analysis approach.

Results

Healthcare providers and key informants perceived that women with advanced breast cancer in Ghana have numerous and complex supportive care needs in key areas that align with Fitch’s supportive care framework, including informational, psychological, emotional, physical, practical, social, sexuality and spiritual needs.

Conclusion

Participants perceived that women who have advanced breast cancer in Ghana require ongoing information about their condition, treatments and related effects, as well as spiritual support and guidance particularly due to the fatalistic beliefs they often associate with the condition. Tailored supportive care interventions and services, which address the unique sociocultural circumstances for this cohort, are required. Additional research is needed to explore how multidisciplinary teams can work collaboratively to provide comprehensive support to women in addressing their needs.
The lipidomic profile of the tumoral periprostatic adipose tissue reveals alterations in tumor cell’s metabolic crosstalk
Authors: Altuna-Coy Antonio , Ruiz-Plazas Xavier , Sánchez-Martin Silvia , Ascaso-Til Helena , Prados-Saavedra Manuel , Alves-Santiago Marta , Bernal-Escoté Xana , Segarra-Tomás José , R. Chacón Matilde
Published: August 2022

Background

Periprostatic adipose tissue (PPAT) plays a role in prostate cancer (PCa) progression. PPAT lipidomic composition study may allow us to understand the tumor metabolic microenvironment and provide new stratification factors.

Methods

We used ultra-high-performance liquid chromatography-mass spectrometry-based non-targeted lipidomics to profile lipids in the PPAT of 40 patients with PCa (n = 20 with low-risk and n = 20 high-risk). Partial least squares-discriminant analysis (PLS-DA) and variable importance in projection (VIP) analysis were used to identify the most relevant features of PPAT between low- and high-risk PCa, and metabolite set enrichment analysis was used to detect disrupted metabolic pathways. Metabolic crosstalk between PPAT and PCa cell lines (PC-3 and LNCaP) was studied using ex vivo experiments. Lipid uptake and lipid accumulation were measured. Lipid metabolic-related genes (SREBP1, FASN, ACACA, LIPE, PPARG, CD36, PNPLA2, FABP4, CPT1A, FATP5, ADIPOQ), inflammatory markers (IL-6, IL-1B, TNFα), and tumor-related markers (ESRRA, MMP-9, TWIST1) were measured by RT-qPCR.

Results

Significant differences in the content of 67 lipid species were identified in PPAT samples between high- and low-risk PCa. PLS-DA and VIP analyses revealed a discriminating lipidomic panel between low- and high-risk PCa, suggesting the occurrence of disordered lipid metabolism in patients related to PCa aggressiveness. Functional analysis revealed that alterations in fatty acid biosynthesis, linoleic acid metabolism, and β-oxidation of very long-chain fatty acids had the greatest impact in the PPAT lipidome. Gene analyses of PPAT samples demonstrated that the expression of genes associated with de novo fatty acid synthesis such as FASN and ACACA were significantly lower in PPAT from high-risk PCa than in low-risk counterparts. This was accompanied by the overexpression of inflammatory markers (IL-6, IL-1B, and TNFα). Co-culture of PPAT explants with PCa cell lines revealed a reduced gene expression of lipid metabolic-related genes (CD36, FASN, PPARG, and CPT1A), contrary to that observed in co-cultured PCa cell lines. This was followed by an increase in lipid uptake and lipid accumulation in PCa cells. Tumor-related genes were increased in co-cultured PCa cell lines.

Conclusions

Disturbances in PPAT lipid metabolism of patients with high-risk PCa are associated with tumor cell metabolic changes.
Mesenchymal stem cells protect against TBI-induced pyroptosis in vivo and in vitro through TSG-6
Authors: Feng Zhiming , Hua Shiting , Li Wangan , Han Jianbang , Li Feng , Chen Haijia , Zhang Zhongfei , Xie Yu , Ouyang Qian , Zou Xiaoxiong , Liu Zhizheng , Li Cong , Huang Sixian , Lai Zelin , Cai Xiaolin , Cai Yingqian , Zou Yuxi , Tang Yanping , Jiang Xiaodan
Published: August 2022

Background

Pyroptosis, especially microglial pyroptosis, may play an important role in central nervous system pathologies, including traumatic brain injury (TBI). Transplantation of mesenchymal stem cells (MSCs), such as human umbilical cord MSCs (hUMSCs), has been a focus of brain injury treatment. Recently, MSCs have been found to play a role in many diseases by regulating the pyroptosis pathway. However, the effect of MSC transplantation on pyroptosis following TBI remains unknown. Tumor necrosis factor α stimulated gene 6/protein (TSG-6), a potent anti-inflammatory factor expressed in many cell types including MSCs, plays an anti-inflammatory role in many diseases; however, the effect of TSG-6 secreted by MSCs on pyroptosis remains unclear.

Methods

Mice were subjected to controlled cortical impact injury in vivo. To assess the time course of pyroptosis after TBI, brains of TBI mice were collected at different time points. To study the effect of TSG-6 secreted by hUMSCs in regulating pyroptosis, normal hUMSCs, sh-TSG-6 hUMSCs, or different concentrations of rmTSG-6 were injected intracerebroventricularly into mice 4 h after TBI. Neurological deficits, double immunofluorescence staining, presence of inflammatory factors, cell apoptosis, and pyroptosis were assessed. In vitro, we investigated the anti-pyroptosis effects of hUMSCs and TSG-6 in a lipopolysaccharide/ATP-induced BV2 microglial pyroptosis model.

Results

In TBI mice, the co-localization of Iba-1 (marking microglia/macrophages) with NLRP3/Caspase-1 p20/GSDMD was distinctly observed at 48 h. In vivo, hUMSC transplantation or treatment with rmTSG-6 in TBI mice significantly improved neurological deficits, reduced inflammatory cytokine expression, and inhibited both NLRP3/Caspase-1 p20/GSDMD expression and microglial pyroptosis in the cerebral cortices of TBI mice. However, the therapeutic effect of hUMSCs on TBI mice was reduced by the inhibition of TSG-6 expression in hUMSCs. In vitro, lipopolysaccharide/ATP-induced BV2 microglial pyroptosis was inhibited by co-culture with hUMSCs or with rmTSG-6. However, the inhibitory effect of hUMSCs on BV2 microglial pyroptosis was significantly reduced by TSG-6-shRNA transfection.

Conclusion

In TBI mice, microglial pyroptosis was observed. Both in vivo and in vitro, hUMSCs inhibited pyroptosis, particularly microglial pyroptosis, by regulating the NLRP3/Caspase-1/GSDMD signaling pathway via TSG-6.
Total mutational load and clinical features as predictors of the metastatic status in lung adenocarcinoma and squamous cell carcinoma patients
Authors: Oróstica Karen Y. , Saez-Hidalgo Juan , de Santiago Pamela R. , Rivas Solange , Contreras Sebastian , Navarro Gonzalo , Asenjo Juan A. , Olivera-Nappa Álvaro , Armisén Ricardo
Published: August 2022

Background

Recently, extensive cancer genomic studies have revealed mutational and clinical data of large cohorts of cancer patients. For example, the Pan-Lung Cancer 2016 dataset (part of The Cancer Genome Atlas project), summarises the mutational and clinical profiles of different subtypes of Lung Cancer (LC). Mutational and clinical signatures have been used independently for tumour typification and prediction of metastasis in LC patients. Is it then possible to achieve better typifications and predictions when combining both data streams?

Methods

In a cohort of 1144 Lung Adenocarcinoma (LUAD) and Lung Squamous Cell Carcinoma (LSCC) patients, we studied the number of missense mutations (hereafter, the Total Mutational Load TML) and distribution of clinical variables, for different classes of patients. Using the TML and different sets of clinical variables (tumour stage, age, sex, smoking status, and packs of cigarettes smoked per year), we built Random Forest classification models that calculate the likelihood of developing metastasis.

Results

We found that LC patients different in age, smoking status, and tumour type had significantly different mean TMLs. Although TML was an informative feature, its effect was secondary to the "tumour stage" feature. However, its contribution to the classification is not redundant with the latter; models trained using both TML and tumour stage performed better than models trained using only one of these variables. We found that models trained in the entire dataset (i.e., without using dimensionality reduction techniques) and without resampling achieved the highest performance, with an F1 score of 0.64 (95%CrI [0.62, 0.66]).

Conclusions

Clinical variables and TML should be considered together when assessing the likelihood of LC patients progressing to metastatic states, as the information these encode is not redundant. Altogether, we provide new evidence of the need for comprehensive diagnostic tools for metastasis.
3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) Positron Emission Tomography as an In Vivo Biomarker of inhibition of CDK 4/6-Rb pathway by Palbociclib in a patient derived bladder tumor
Authors: Tatum James L. , Kalen Joseph D. , Jacobs Paula M. , Riffle Lisa A. , James Amy , Thang Lai , Sanders Chelsea , Hollingshead Melinda G. , Basuli Falguni , Shi Jianfeng , Doroshow James H.
Published: August 2022

Background

Several new generation CDK4/6 inhibitors have been developed and approved for breast cancer therapy in combination with endocrine therapeutics. Application of these inhibitors either alone or in combination in other solid tumors has been proposed, but no imaging biomarkers of response have been reported in non-breast cancer animal models. The purpose of this study was to evaluate 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) Positron Emission Tomography (PET) as in vivo biomarker of response to palbociclib in a non-breast cancer model.

Methods

Twenty-four NSG mice bearing patient derived xenografts (PDX) of a well-characterized bladder tumor were randomized into 4 treatment groups: vehicle (n = 6); palbociclib (n = 6); temozolomide (n = 6); and palbociclib plus temozolomide (n = 6) and treated with two cycles of therapy or vehicle. Tumor uptake of [18F]FLT was determined by micro-PET/CT at baseline, 3 days, and 9 days post initiation of therapy. Following the second cycle of therapy, the mice were maintained until their tumors reached a size requiring humane termination.

Results

[18F]FLT uptake decreased significantly in the palbociclib and combination arms (p = 0.0423 and 0.0106 respectively at day 3 and 0.0012 and 0.0031 at day 9) with stable tumor volume. In the temozolomide arm [18F]FLT uptake increased with day 9 uptake significantly different than baseline (p = 0.0418) and progressive tumor growth was observed during the treatment phase. All groups exhibited progressive disease after day 22, 10 days following cessation of therapy.

Conclusion

Significant decreases in [18F]FLT uptake as early as three days post initiation of therapy with palbociclib, alone or in combination with temozolomide, in this bladder cancer model correlates with an absence of tumor growth during therapy that persists until day 18 for the palbociclib group and day 22 for the combination group (6 days and 10 days) following cessation of therapy. These results support early modulation of [18F]FLT as an in vivo biomarker predictive of palbociclib therapy response in a non-breast cancer model.
Serum trimethylamine-N-oxide is associated with incident type 2 diabetes in middle-aged and older adults: a prospective cohort study
Authors: Li Shu-yi , Chen Si , Lu Xiao-ting , Fang Ai-ping , Chen Yu-ming , Huang Rong-zhu , Lin Xin-lei , Huang Zi-hui , Ma Jing-fei , Huang Bi-xia , Zhu Hui-lian
Published: August 2022

Background

The role of trimethylamine-N-oxide (TMAO) in the development of diabetes remains controversial, and prospective data are few. We aimed to investigate the association between serum TMAO and incident type 2 diabetes in middle-aged and older adults.

Methods

This study was based on the Guangzhou Nutrition and Health Study (GNHS), a community-based prospective cohort study in China. A total of 2088 diabetes-free participants aged 40–75 years were included from 2008 to 2010. Incident type 2 diabetes was ascertained during follow-up visits. Baseline serum TMAO was measured by high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for diabetes across tertiles of serum TMAO were calculated using Cox proportional hazard models. Prospective associations of serum TMAO with changes in glycemic traits (fasting glucose, HbA1c, insulin, HOMA-IR) over time were estimated using linear mixed-effects models (LMEMs).

Results

We ascertained 254 incident type 2 diabetes cases during a median follow-up of 8.9 years. The median (interquartile range) of serum TMAO was 1.54 (0.86–2.91) μmol/L. From the first to the third tertile of serum TMAO, the multivariable-adjusted HRs for diabetes were 1.00 (reference), 1.17 (95% CI: 0.84–1.61), and 1.42 (95% CI: 1.03–1.96) (P-trend = 0.031). LMEMs showed that the estimated yearly change in fasting glucose was 0.011 (0.001–0.022) mmol/L/y in the highest tertile of serum TMAO, compared with the lowest tertile (P-interaction = 0.044). Serum TMAO was not associated with longitudinal changes in HbA1c, insulin or HOMA-IR.

Conclusions

Our findings suggested that higher serum TMAO was associated with a higher risk of type 2 diabetes and an increase in fasting glucose among middle-aged and older Chinese adults.

Trial registration:NCT03179657.https://clinicaltrials.gov/ct2/show/NCT03179657?term=NCT03179657&draw=2&rank=1
Candida and the Gram-positive trio: testing the vibe in the ICU patient microbiome using structural equation modelling of literature derived data
Authors: Hurley James C.
Published: August 2022

Background

Whether Candida interacts with Gram-positive bacteria, such as Staphylococcus aureus, coagulase negative Staphylococci (CNS) and Enterococci, to enhance their invasive potential from the microbiome of ICU patients remains unclear. Several effective anti-septic, antibiotic, anti-fungal, and non-decontamination based interventions studied for prevention of ventilator associated pneumonia (VAP) and other ICU acquired infections among patients receiving prolonged mechanical ventilation (MV) are known to variably impact Candida colonization. The collective observations within control and intervention groups from numerous ICU infection prevention studies enables tests of these postulated microbial interactions in the clinical context.

Methods

Four candidate generalized structural equation models (GSEM), each with Staphylococcus aureus, CNS and Enterococci colonization, defined as latent variables, were confronted with blood culture and respiratory tract isolate data derived from 460 groups of ICU patients receiving prolonged MV from 283 infection prevention studies.

Results

Introducing interaction terms between Candida colonization and each of S aureus (coefficient + 0.40; 95% confidence interval + 0.24 to + 0.55), CNS (+ 0.68; + 0.34 to + 1.0) and Enterococcal (+ 0.56; + 0.33 to + 0.79) colonization (all as latent variables) improved the fit for each model. The magnitude and significance level of the interaction terms were similar to the positive associations between exposure to topical antibiotic prophylaxis (TAP) on Enterococcal (+ 0.51; + 0.12 to + 0.89) and Candida colonization (+ 0.98; + 0.35 to + 1.61) versus the negative association of TAP with S aureus (− 0.45; − 0.70 to − 0.20) colonization and the negative association of anti-fungal exposure and Candida colonization (− 1.41; − 1.6 to − 0.72).

Conclusions

GSEM modelling of published ICU infection prevention data enables the postulated interactions between Candida and Gram-positive bacteria to be tested using clinically derived data. The optimal model implies interactions occurring in the human microbiome facilitating bacterial invasion and infection. This interaction might also account for the paradoxically high bacteremia incidences among studies of TAP in ICU patients.
Cognitive rehabilitation in people with autism spectrum disorder: a systematic review of emerging virtual reality-based approaches
Authors: Shahmoradi Leila , Rezayi Sorayya
Published: August 2022

Introduction

Emerging virtual technologies and cognitive rehabilitation methods are two new treatment approaches that can be used to strengthen cognitive functions in Autism Spectrum Disorder (ASD). The main aim of this study was to examine the effect of using virtual reality-based approaches on cognitive disorders of children and adults with ASD.

Methods

This systematic review was conducted on scientific papers to determine the effects of virtual reality-based technologies on the cognitive functions of children and adults with ASD. We identified 688 studies related to this topic and filtered them down to 17 articles, and then extracted the effects of interventions on cognitive outcomes.

Results

A total of 17 studies met the inclusion criteria, in which 226 persons with ASD had taken place. The sample size in the selected studies ranged from 1 to 56 participants (Median: 8, Q1: 3.5, Q3: 15.5). Four of the studies were case–control studies, ten were pre-test/post-test studies, and three were Randomized Control Trials (RCTs). Results of 16 studies showed significant progress in various cognitive indexes, such as task learning, attention, executive functioning, and daily skills in people with ASD. In most studies, virtual technologies had beneficial effects on reducing cognitive problems, but existing limitations could reduce their effectiveness. These limitations included the cost of virtual reality devices, inappropriate size of software, the weight of devices, potential addiction, intolerance of wearing glasses or headsets by people with autism (especially in children), and the possibility of eye injury.

Conclusion

Applying appropriate virtual-based approaches could improve cognitive indexes in people with ASD. However, further studies are needed to investigate the real effects of these technologies in the long run.
Vitamin D status and its correlation to depression
Authors: khan Bashir , Shafiq Huma , Abbas Seyyedha , Jabeen Summeira , Khan Sikandar Ali , Afsar Tayyaba , Almajwal Ali , Alruwaili Nawaf W. , al-disi Dara , Alenezi Sultan , Parveen Zahida , Razak Suhail
Published: August 2022

Background

Vitamin D can influence more than 200 genes in various tissues showing its credibility among the fat-soluble vitamins. Vitamin D deficiency is directly proportional to major clinical conditions such as cardiovascular diseases, diabetes, malignancy, and multiple sclerosis. This study was conducted to determine the vitamin D level of individuals and its association with depression.

Methods

Vitamin D levels of 100 healthy and 100 depressed subjects were determined. The isolated subjects were screened on the Beck Depression Inventory (BDI) scale and divided into three groups according to their age. Group-I comprised subjects of age 20 years and below, Group-II included subjects of age 21 to 60, and Group-III comprised subjects of ≥ 61 years of age. A sufficient level of vitamin D in normal subjects was noted, while mild deficiency of vitamin D status was observed in depressed subjects.

Results

Our study has reported a higher percentage of vitamin D deficiency in the Peshawar region. The results of our study indicated that depression was common in individuals having vitamin D deficiency.

Conclusions

The study showed a very high frequency of vitamin D deficiency in subjects with depression in Peshawar, Pakistan. The deficiency of vitamin D was observed more in females as compared to males. Further studies should explicate whether the highly widespread vitamin D deficiency could be cost-effectively treated as part of preventive or treatment interventions for depression.
CT guided autologous blood localization of pulmonary ground glass nodules for video assisted thoracoscopic surgery compared to micro-coil localization
Authors: Xu Jianxin , Si Tingting , Zheng Maohua , Guan Jun , Li Zhixin , Xu Zhiyang
Published: August 2022

Objectives

To investigate feasibility and safety of autologous blood in preoperative computed tomography (CT)-guided localization of pulmonary ground-glass nodules (GGNs) by comparing to mico-coil prior to video-assisted thoracoscopic surgery.

Methods

Clinical data of patients with GGNs who underwent video-assisted thoracoscopic surgery followed by preoperative CT-guided autologous blood or micro-coil localization was retrospectively reviewed in our department between September 2019 and November 2021. The localization duration, localization success rate, localization-related complication, localization cost, operation time, and conversion rate were compared between the 2 localization groups.

Results

Totally 65 patients with 65 GGNs were included in our study, with 34 patients in autologous blood group (group B) and 31 patients in micro-coil group (group M). There is no conversion to thoracotomy. The age, sex, nodule location, diameter of nodule and distance from the pleura between the 2 groups were statistically comparable. Compared with group M, group B had similar localization success rate (94.1% vs 83.9%, P = 0.183) but shorter localization time (14.50 ± 2.61 min vs 16.35 ± 2.30 min, P = 0.004), lower cost ($92.4 ± 3.2 vs $475.6 ± 8.5, P = 0.001), and lower incidence of puncture complications (3.0% vs 19.3%, P = 0.042).

Conclusions

The autologous blood localization is an effective and more economical method for preoperative GGNs localization, and is associated with fewer complications compared to micro-coil localization.
MiR-19b-3p regulated by BC002059/ABHD10 axis promotes cell apoptosis in myocardial infarction
Authors: Liao Bihong , Dong Shaohong , Xu Zhenglei , Gao Fei , Zhang Suihao , Liang Ruijuan
Published: August 2022

Background

Recently, microRNAs (miRNAs), have been extensively investigated in diseases. The upregulated expression of miR-19b-3p has been validated in patients with hypertrophic cardiomyopathy. Nonetheless, it regulatory mechanism in myocardial infarction (MI) is still unclear.

Purpose

This research aimed to investigate the role and molecular regulation mechanism of miR-19b-3p in MI.

Methods

QRT-PCR and western blot assays measured RNA and protein expression. Cell apoptosis were tested by flow cytometry and TUNEL assays. Cell viability was measured by trypan blue staining method. RIP and luciferase report assays examined gene interaction. The assays were performed under hypoxia condition.

Results

MiR-19b-3p was highly expressed in myocardial cell line H9C2, primary cardiomyocytes, and tissues from MI mouse model. MiR-19b-3p inhibition suppressed the apoptosis of cardiomyocytes. BC002059 could up-regulate ABHD10 through sequestering miR-19b-3p. BC002059 upregulation was observed to repress cell apoptosis. Rescue experiments demonstrated that miR-19b-3p overexpression abrogated the suppressive impact of BC002059 on the apoptosis of MI cells, and infarct size, area at risk as well as CK-MB and LDH release of MI mouse model tissues, which was further abolished via ABHD10 increment.

Conclusion

MiR-19b-3p regulated by BC002059/ABHD10 axis promotes cell apoptosis in MI, which might provide a novel perspective for MI alleviation research.
ImpACT+, a coping intervention to improve clinical outcomes for women living with HIV and sexual trauma in South Africa: study protocol for a randomized controlled trial
Authors: Sikkema K. J. , Rabie S. , King A. , Watt M. H. , Mulawa M. I. , Andersen L. S. , Wilson P. A. , Marais A. , Ndwandwa E. , Majokweni S. , Orrell C. , Joska J. A.
Published: August 2022

Background

Addressing sexual trauma in the context of HIV care is essential to improve clinical outcomes and mental health among women in South Africa. Women living with HIV (WLH) report disproportionately high levels of sexual trauma and have higher rates of posttraumatic stress disorder. Adherence to antiretroviral therapy (ART) may be difficult for traumatized women, as sexual trauma compounds the stress associated with managing HIV and is often comorbid with other mental health disorders, further compromising care engagement and adherence. ART initiation represents a unique window of opportunity for intervention to enhance motivation, increase care engagement, and address the negative effects of trauma on avoidant coping behaviors. Mental health interventions delivered by non-specialists in low- and middle-income countries have potential to treat depression, trauma, and effects of intimate partner violence among WLH. This study will examine the effectiveness of Improving AIDS Care after Trauma (ImpACT +), a task-shared, trauma-focused coping intervention, to promote viral suppression among WLH initiating ART in a South African clinic setting.

Methods

This study will be conducted in Khayelitsha, a peri-urban settlement situated near Cape Town, South Africa. Using a hybrid type 1 effectiveness-implementation design, we will randomize 350 WLH initiating ART to the ImpACT + experimental condition or the control condition (three weekly sessions of adapted problem-solving therapy) to examine the effectiveness of ImpACT + on viral suppression, ART adherence, and the degree to which mental health outcomes mediate intervention effects. ImpACT + participants will receive six once-a-week coping intervention sessions and six monthly maintenance sessions over the follow-up period. We will conduct mental health and bio-behavioral assessments at baseline, 4, 8, and 12 months, with care engagement data extracted from medical records. We will explore scalability using the Consolidated Framework for Implementation Research (CFIR).

Discussion

This trial is expected to yield important new information on psychologically informed intervention models that benefit the mental health and clinical outcomes of WLH with histories of sexual trauma. The proposed ImpACT + intervention, with its focus on building coping skills to address traumatic stress and engagement in HIV care and treatment, could have widespread impact on the health and wellbeing of individuals and communities in sub-Saharan Africa.

Trial registration

Clinicaltrials.gov NCT04793217. Retrospectively registered on 11 March 2021.
Inflammatory cytokines and mechanical injury induce post-traumatic osteoarthritis-like changes in a human cartilage-bone-synovium microphysiological system
Authors: Dwivedi Garima , Flaman Lisa , Alaybeyoglu Begum , Struglics André , Frank Eliot H. , Chubinskya Susan , Trippel Stephen B. , Rosen Vicki , Cirit Murat , Grodzinsky Alan J.
Published: August 2022

Background

Traumatic knee injuries in humans trigger an immediate increase in synovial fluid levels of inflammatory cytokines that accompany impact damage to joint tissues. We developed a human in vitro cartilage-bone-synovium (CBS) coculture model to study the role of mechanical injury and inflammation in the initiation of post-traumatic osteoarthritis (PTOA)-like disease.

Methods

Osteochondral plugs (cartilage-bone, CB) along with joint capsule synovium explants (S) were harvested from 25 cadaveric distal femurs from 16 human donors (Collin’s grade 0–2, 23–83years). Two-week monocultures (cartilage (C), bone (B), synovium (S)) and cocultures (CB, CBS) were established. A PTOA-like disease group was initiated via coculture of synovium explants with mechanically impacted osteochondral plugs (CBS+INJ, peak stress 5MPa) with non-impacted CB as controls. Disease-like progression was assessed through analyses of changes in cell viability, inflammatory cytokines released to media (10-plex ELISA), tissue matrix degradation, and metabolomics profile.

Results

Immediate increases in concentrations of a panel of inflammatory cytokines occurred in CBS+INJ and CBS cocultures and cultures with S alone (IL-1, IL-6, IL-8, and TNF-α among others). CBS+INJ and CBS also showed increased chondrocyte death compared to uninjured CB. The release of sulfated glycosaminoglycans (sGAG) and associated ARGS-aggrecan neoepitope fragments to the medium was significantly increased in CBS and CBS+INJ groups. Distinct metabolomics profiles were observed for C, B, and S monocultures, and metabolites related to inflammatory response in CBS versus CB (e.g., kynurenine, 1-methylnicotinamide, and hypoxanthine) were identified.

Conclusion

CBS and CBS+INJ models showed distinct cellular, inflammatory, and matrix-related alterations relevant to PTOA-like initiation/progression. The use of human knee tissues from donors that had no prior history of OA disease suggests the relevance of this model in highlighting the role of injury and inflammation in earliest stages of PTOA progression.
Gingko biloba-inspired lactone prevents osteoarthritis by activating the AMPK-SIRT1 signaling pathway
Authors: Zhao Zhijian , Liu Yang , Lu Yingjie , Hou Mingzhuang , Shen Xu , Yang Huilin , Shi Qin , Zhang Yijian , He Fan , Zhu Xuesong
Published: August 2022

Background

Uncoupled extracellular matrix (ECM) causes cartilage degeneration and osteoarthritis (OA) by suppressing the synthesis and activating the degradation of ECM components.Gingko bilobais a natural Chinese herb with a variety of biological functions; however, the extent to which it can protect against OA and the mechanisms involved are unknown.

Methods

In our study, using bioinformatics tools, we were able to identify an important lactone, bilobalide (BB), fromGingko biloba. In vitro experiments were performed to evaluate the potential therapeutic effects of BB on ECM homeostasis. In vivo experiments were conducted to assess the protection of systemic administration of BB on cartilage degeneration. Molecular mechanisms underlying BB-regulated anti-arthritic role were further explored.

Results

In interleukin-1β-incubated human chondrocytes, in vitro treatment with BB increased the expression of cartilage anabolic proteins, while inhibiting the activities of ECM degrading enzymes. In a mice model, systemic administration of BB, in vivo, prevented post-traumatic cartilage erosion and attenuated the formation of abnormal osteophytes in the subchondral bone. Mechanistically, the activation of the adenosine 5′-monophosphate-activated protein kinase (AMPK)-sirtuin 1 (SIRT1) signaling pathway was involved in the anti-arthritic effects of BB. In vitro, blocking BB’s chondroprotection with the AMPK-specific inhibitor Compound C abrogated it.

Conclusions

These results demonstrated that BB extracted fromGingko bilobaregulates ECM balance to prevent OA by activating the AMPK-SIRT1 signaling pathway. This study proposed the monomer BB, a traditional Chinese medicine, as ade novotherapeutic insight for OA.

Graphical Abstract

Schematic representation of the experimental design. Based on the bioinformatic analysis, bilobalide (BB), a natural herbGingko biloba-derived ingredient, was identified as a candidate for treating osteoarthritis. In vitro, BB treatment not only facilitates cartilage extracellular matrix synthesis but also inhibits proteolytic enzyme activities. In vivo intraperitoneal injection of BB improves cartilage degeneration and subchondral bone sclerosis. BB, in particular, had anti-arthritic effects by activating the AMPK-SIRT1 signaling pathway.
Validity of an algorithm for determining sleep/wake states using FS-760 in school-aged children
Authors: Enomoto Minori , Kitamura Shingo , Nakazaki Kyoko
Published: August 2022

Background

Actigraphy is a method used for determining sleep (S)/wakefulness (W) by actigraph, a device equipped with a built-in accelerometer and an algorithm validated for each device. The S/W determination algorithm for the waist-worn actigraph FS-760 has been formulated for adults. However, the algorithm for children has not been established. The purpose of this study was to formulate an algorithm for discriminating S/W in school-aged children using FS-760 and to evaluate its validity. We further tested the generalizability of existing algorithm for adults by applying it to the children’s activity data and then examined factors associated with adult algorithm agreement rates by multiple regression analysis using combined adult and children data.

Methods

Sixty-five, healthy, school-aged children (aged 6 to 15 years) were recruited and randomly assigned to two groups: A (n= 33) and B (n= 32). They underwent 8-h polysomnography (PSG) and wore FS-760 simultaneously to obtain activity data. To determine the central epoch of the sleep/wake states (𝑥), a five-order linear discriminant analysis was conducted using the activity intensity of group A for five epochs (𝑥−2, 𝑥−1, 𝑥, 𝑥+1, 𝑥+2; 10 min) and evaluate its accuracy with the activity of group B. To reveal the factors associated with adult algorithm agreement rate, we integrated the activity, age, sleep efficiency of 15 adults (aged 20 to 39 years) and those of 65 children for multiple regression analysis.

Results

The mean agreement rate of the developed algorithm was 91.0%, with a mean sensitivity (true sleep detection rate) of 93.0% and a mean specificity (true wakefulness detection rate) of 63.9%. The agreement rate of the adult algorithm applied to children’s activity was significantly lower (81.8%) than that of the children algorithm. Multiple regression analysis showed that the agreement rates calculated by the adult algorithm were significantly related to mean activity of the 𝑥 epoch in NREM and REM sleep as well as age and sleep efficiency.

Conclusions

The S/W states in school-aged children can be reliably assessed using the developed algorithm for waist-worn actigraph FS-760. Since the accuracy of the adult algorithms decreased when applied it to children which have different activity levels during sleep, the establishment and validation of population-specific S/W algorithms should be required.