bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness analysis: nonsurgical root canal treatment versus single-tooth implant
Authors: Zang Hai-Ling , Zhang Yu , Hao Xiao-Wen , Yang Li , Liang Yu-Hong
Published: July 2023

Background

Economic evaluation of nonsurgical root canal treatment (NSRCT) and single-tooth implant (STI) provides useful information for medical decision. This retrospective study aimed to evaluate the cost-effectiveness of NSRCT versus single-tooth implant (STI) after 5-year treatment in a university affiliated hospital in Beijing, China.

Methods

211 patients who underwent NSRCT and 142 patients who had STI were included and recalled after 5-year treatment. The propensity scores were used to match the cases of two treatment modalities. At recall, outcomes were determined based on clinical and radiographical examinations. For endodontically treated cases, absence or reduction of radiolucency were defined as success. Marginal bone loss (MBL) ≤ 4 mm were determined as success for implant cases. Direct and indirect costs were calculated in China Yuan (CNY). Patients’ willingness to pay (WTP) for each treatment modality was evaluated by questionnaires. A cost-effectiveness analysis was performed from the societal perspective.

Results

170 patients with 120 NSRCT teeth and 96 STI were available at recall. Based on propensity score matching, 76 endodontically treated teeth were matched to 76 implants. Absence of the radiolucency was observed in 58 of 76 endodontically treated teeth (76%) and reduction of the radiolucency in 9 of 76 teeth (12%) and altogether the success rate was 88%. 100% implants were detected with marginal bone loss (MBL) ≤ 4 mm. The cost advantage of NSRCT (4,751 CNY) over STI (20,298 CNY) was more pronounced. Incremental cost effectiveness ratio (ICER) was 129,563 CNY (STI-NSRCT) per success rate gained. It exceeded the patients’ willingness to pay value 7,533 CNY.

Conclusions

Clinical outcomes of NSRCT and STI could be predictable after 5-year treatment. NSRCT may be more cost-effective than STI for managing endodontically diseased teeth.
Radiopacity evaluation of calcium silicate cements
Authors: Sen Havva Gozde , Helvacioglu-Yigit Dilek , Yilmaz Ayca
Published: July 2023

Background

The aim of this study was to compare the radiopacity of calcium silicate cements using a digital imaging method.

Methods

Four calcium silicate cements, NeoMTA 2, OrthoMTA, ProRoot MTA, and Biodentine, were used in this study. Disk-shaped samples were prepared from each material and placed on a plexiglass plate. An aluminum step-wedge was placed alongside the samples on a digital sensor and exposed to 70 kVp and 8 mA from 30 cm away for 0.32 s. The greyness values ​​of the tested materials were measured digitally with the system software and compared with those of the step-wedge to determine the equivalent aluminum thickness.

Results

The radiopacity values, expressed in equivalent millimetres of aluminum, of the studied materials ProRoot MTA, OrthoMTA, NeoMTA 2, and Biodentine were 4.32 ± 0.17 mm Al, 3.92 ± 0.09 mm Al, 3.83 ± 0.07 mm Al, and 2.29 ± 0.21 mm Al, respectively. Statistically significant differences were found between the mean radiographic density values of the tested materials (p < 0.05).

Conclusion

ProRoot MTA was the most radiopaque root canal filling material among the tested materials. All materials, except Biodentine, were found to be compliant with the minimum radiopacity requirements of ISO 6876 and ADA 57 standards.
Meditative and non-meditative mindfulness-based interventions for mind and body
Authors: Giannou Kyriaki , Mantzios Michail
Published: July 2023

The present editorial synopsises the benefits and challenges in meditative and non-meditative mindfulness practices and explores shorter and more creative approaches in mind–body interventions, emphasizing inclusivity and evidence-based practices. This collection, launched in BMC Complementary Medicine and Therapies, aims to bring together research on a variety of mindful practices, to discuss their role in supporting wellbeing.
Comparative anticancer effects of Annona muricata Linn (Annonaceae) leaves and fruits on DMBA-induced breast cancer in female rats
Authors: Silihe Kevine Kamga , Mbou William Defo , Ngo Pambe Judith Christiane , Kenmogne Larissa Vanelle , Maptouom Laure Fotso , Kemegne Sipping Marius Trésor , Zingue Stéphane , Njamen Dieudonné
Published: July 2023

Background

Numerous studies have reported the anti-cancer effects of different parts of Annona muricata Linn, however ; most of them focused on the in vitro evaluation of isolates. In vivo evidence on which part is best suited for breast cancer chemoprevention remains to be demonstrated. This is a comparative study of the effects of A. muricata fruit and leaves extracts on DMBA induced-breast cancer in rats.

Methods

Rats exposed to DMBA (50 mg/kg, s.c.), were treated with A. muricata fruit aqueous extract at 200 mg/kg BW (3 days/week or daily) and A. muricata Linn leaves ethanolic extract at 200 mg/kg daily. Positive control group received tamoxifen at 3.3 mg/kg, while the normal and diseased controls received vehicle. After 20 weeks of treatment, the tumor incidence, tumor burden, tumor volume, histopathology, protein and CA 15 − 3 levels as well as antioxidant status, pro-inflammatory cytokines were assessed.

Results

Thus, 100% of diseased rats presented cribriform ductal carcinoma of SBR grade III. A. muricata extracts (leaves and fruit) and tamoxifen significantly reduced death and tumor incidences, volume and weight of the tumors, total protein and CA15-3 levels compared to the DMBA group. They exhibited antioxidant activity, through an increase in the GSH level and SOD and catalase activities with reduced levels of MDA compared to DMBA group. TNF-α, IL-6 and INF-γ levels reduced with regards to A. muricata treatment.

Conclusion

These results confirm the anti-breast cancer effect of A. muricata, however, the aqueous fruit extract was more potent than the ethanolic leaves extract.
Thriving psychological well-being in undergraduate nursing student: a grounded theory study with the life grid approach
Authors: Zhou Lu , Chankoson Thitinan , Wu YuMing , Cai EnLi
Published: July 2023

Background

Psychological well-being (PWB) plays a vital role in successful adaptation to the Bachelor of Nursing journey and affects career development. However, there is little known about the functional and social processes associated with enhancing well-being specific to the subjective perspective of nursing students.

Aim

To investigate how nursing students promote their psychological well-being to conceptualize thriving psychological well-being.

Method

This qualitative study analyzed and reviewed a life grid and semi-structured in-depth interviews of 20 Chinese Nursing graduates by investigators and participants, following Charmaz's constructivist grounded theory. The constant comparative method was used to analyze data. This study took place between 2020 and 2022.

Results

All participants experienced fluctuations in psychological well-being. This study identified a new understanding of how nursing students enhance their psychological well-being. Thriving awareness was co-constructed as the core category and based on the relationship with a supportive environment, the thriving psychological well-being of nursing students is conceptualized.

Conclusions

It is imperative to enhance the psychological counseling and support for nursing students during their clinical placements, during the period just entering university as well as after repeated outbreaks of COVID-19. Nursing educators and administrators could develop appropriate educational programs and interventions based on the theoretical model—Thriving psychological well-being.
Exploring the novel SNPs in neuroticism and birth weight based on GWAS datasets
Authors: Zhou Xiao-Ying , Liu Rui-Ke , Zeng Chun-Ping
Published: July 2023

Objectives

Epidemiological studies have confirmed that low birth weight (BW) is related to neuroticism and they may have a common genetic mechanism based on phenotypic correlation research. We conducted our study on a European population with 159,208 neuroticism and 289,142 birth weight samples. In this study, we aimed to identify new neuroticism single nucleotide polymorphisms (SNPs) and pleiotropic SNPs associated with neuroticism and BW and to provide more theoretical basis for the pathogenesis of the disease.

Methods

We estimated the pleiotropic enrichment between neuroticism and BW in two independent Genome-wide association studies (GWAS) when the statistical thresholds were Conditional False Discovery Rate (cFDR) < 0.01 and Conjunctional Conditional False Discovery Rate (ccFDR) < 0.05. We performed gene annotation and gene functional analysis on the selected significant SNPs to determine the biological role of gene function and pathogenesis. Two-sample Mendelian Randomization (TSMR) analysis was performed to explore the causal relationship between the neuroticism and BW.

Results

The conditional quantile–quantile plots (Q-Q plot) indicated that neuroticism and BW have strong genetic pleiotropy enrichment trends. With the threshold of cFDR < 0.001, we identified 126 SNPs related to neuroticism and 172 SNPs related to BW. With the threshold of ccFDR < 0.05, we identified 62 SNPs related to both neuroticism and BW. Among these SNPs, rs8039305 and rs35755513 have eQTL (expressed quantitative trait loci) and meQTL (methylation quantitative trait loci) effects simultaneously. Through GO enrichment analysis we also found that the two pathways of positive regulation of “mesenchymal cell proliferation” and “DNA-binding transcription factor activity” were significantly enriched in neuroticism and BW. Mendelian randomization analysis results indicate that there is no obvious causal relationship between neuroticism and birth weight.

Conclusion

We found 126 SNPs related to neuroticism, 172 SNPs related to BW and 62 SNPs associated with both neuroticism and BW, which provided a theoretical basis for their genetic mechanism and novel potential targets for treatment/intervention development.
Glioma-BioDP: database for visualization of molecular profiles to improve prognosis of brain cancer
Authors: Deng Xiang , Das Shaoli , Kaur Harpreet , Wilson Evan , Camphausen Kevin , Shankavaram Uma
Published: July 2023

Cancer researchers often seek user-friendly interactive tools for validation, exploration, analysis, and visualization of molecular profiles in cancer patient samples. To aid researchers working on the both low- and high-grade gliomas, we developed Glioma-BioDP, a web tool for exploration and visualization of RNA and protein expression profiles of interest in these tumor types. Glioma-BioDP is user friendly application that include expression data from both the low- and high-grade glioma patient samples from The Cancer Genome Atlas and enabled querying by mRNA, microRNA, and protein level expression data from Illumina HiSeq and RPPA platforms respectively. Glioma-BioDP provides advance query interface and enables users to explore the association of genes, proteins, and miRNA expression with molecular and/or histological subtypes of gliomas, surgical resection status and survival. The prognostic significance and visualization of the selected expression profiles can be explored using interactive utilities provided. This tool may also enable validation and generation of new hypotheses of novel therapies impacting gliomas that aid in personalization of treatment for optimum outcomes.
Supra-additive effect of chronic inflammation and atherogenic dyslipidemia on developing type 2 diabetes among young adults: a prospective cohort study
Authors: Lan Yulong , Wu Dan , Cai Zhiwei , Xu Yuancheng , Ding Xiong , Wu Weiqiang , Lan Shaocong , Chen Lan , Guo Zheng , Balmer Lois , Li Xingang , Song Manshu , Wu Shouling , Gao Jingli , Wang Wei , Chen Youren
Published: July 2023

Background

Both elevated inflammation and atherogenic dyslipidemia are prominent in young-onset diabetes and are increasingly identified as biologically intertwined processes that contribute to diabetogenesis. We aimed to investigate the age-specific risks of type 2 diabetes (T2D) upon concomitant chronic inflammation and atherogenic dyslipidemia.

Methods

Age-stratified Cox regression analysis of the risk of incident diabetes upon co-exposure to time-averaged cumulative high-sensitivity C-reactive protein (CumCRP) and atherogenic index of plasma (CumAIP) among 42,925 nondiabetic participants from a real-world, prospective cohort (Kailuan Study).

Results

During a median 6.41 years of follow-up, 3987 T2D developed. Isolated CumAIP and CumCRP were significantly associated with incident T2D in the entire cohort and across all age subgroups. Both CumAIP and CumCRP were jointly associated with an increased risk of diabetes (P-interaction = 0.0126). Compared to CumAIP < -0.0699 and CumCRP < 1 mg/L, co-exposure to CumAIP ≥ − 0.0699 and CumCRP ≥ 3 mg/L had a significant hazard ratio (HR) [2.55 (2.23–2.92)] after adjusting for socio-demographic, life-style factors, family history of diabetes, blood pressure, renal function and medication use. The co-exposure-associated risks varied greatly by age distribution (P-interaction = 0.0193): < 40 years, 6.26 (3.47–11.28); 40–49 years, 2.26 (1.77–2.89); 50–59 years, 2.51 (2.00–3.16); 60–69 years, 2.48 (1.86–3.30); ≥ 70 years, 2.10 (1.29–3.40). In young adults (< 45 years), both exposures had a significant supra-additive effect on diabetogenesis (relative excess risk due to interaction: 0.80, 95% CI 0.10–1.50).

Conclusions

These findings highlight the need for age-specific combined assessment and management of chronic inflammation and dyslipidemia in primary prevention against T2D, particularly for young adults. The clinical benefit derived from dual-target intervention against dyslipidemia and inflammation will exceed the sum of each part alone in young adults.
High triglyceride-glucose index and stress hyperglycemia ratio as predictors of adverse cardiac events in patients with coronary chronic total occlusion: a large-scale prospective cohort study
Authors: Song Yanjun , Cui Kongyong , Yang Min , Song Chenxi , Yin Dong , Dong Qiuting , Gao Ying , Dou Kefei
Published: July 2023

Background

The triglyceride-glucose (TyG) index and the stress hyperglycaemia ratio (SHR) are both positively associated with cardiovascular (CV) risk in patients with coronary heart disease. However, the prognostic value of these two biomarkers has not been well elucidated in patients with chronic total occlusion (CTO). Therefore, this study aims to evaluate the association of the TyG index and the SHR with long-term prognosis in patients with CTO.

Methods

This prospective cohort study consecutively included 2740 angina patients with CTO from January 2017 to December 2018 at Fuwai Hospital. The outcomes are a composite of CV death and target vessel myocardial infarction (TVMI) and major CV cerebrovascular adverse events (MACCEs, including all-cause death, nonfatal MI, ischaemia-driven target vessel revascularization, and stroke). The association between biomarkers and prognosis was analysed by multivariable Cox proportional hazard models, and the predictive value was determined by a receiver-operating characteristic (ROC) curve.

Results

During the follow-up with a median time of 3 years, 179 (6.5%) cases of MACCEs and 47 (1.7%) cases of CV death or TVMI were recorded. Patients with a high TyG index (> 9.10) and a high SHR (> 0.87) showed a significantly increased risk of CV death/TVMI (TyG index: HR 4.23, 95% CI 1.58–11.37; SHR: HR 5.14, 95% CI 1.89–13.98) and MACCEs (TyG index: HR 2.47, 95% CI 1.54–3.97; SHR: HR 2.91, 95% CI 1.84–4.60) compared with those with a low Tyg index and a low SHR (TyG < 8.56, SHR < 0.76). The area under the curve (AUC) values were 0.623 (TyG index) and 0.589 (SHR) for CV death/TVMI and 0.659 (TyG index) and 0.624 (SHR) for MACCEs. Furthermore, patients with both a high TyG index and a high SHR showed the highest risk of clinical outcomes among patients with different levels of these two biomarkers, and the AUC for the TyG-SHR combination was larger than the TyG index alone in predicting MACCE risk.

Conclusions

The study revealed that a high TyG index and a high SHR were significantly correlated with poor prognosis in patients with CTO and suggested that these two biomarkers are reliable in predicting long-term prognosis in CTO patients.
High prevalence of colistin heteroresistance in specific species and lineages of Enterobacter cloacae complex derived from human clinical specimens
Authors: Fukuzawa Shota , Sato Toyotaka , Aoki Kotaro , Yamamoto Soh , Ogasawara Noriko , Nakajima Chie , Suzuki Yasuhiko , Horiuchi Motohiro , Takahashi Satoshi , Yokota Shin-ichi
Published: July 2023

Background

Colistin (CST) is a last-line drug for multidrug-resistant Gram-negative bacterial infections. CST-heteroresistant Enterobacter cloacae complex (ECC) has been isolated. However, integrated analysis of epidemiology and resistance mechanisms based on the complete ECC species identification has not been performed.

Methods

Clinical isolates identified as “E. cloacae complex” by MALDI-TOF MS Biotyper Compass in a university hospital in Japan were analyzed. Minimum inhibitory concentrations of CST were determined by the broth microdilution method. The population analysis profiling (PAP) was performed for detecting the heteroresistant phenotype. The heat shock protein 60 (hsp60) cluster was determined from its partial nucleotide sequence. From the data of whole-genome sequencing, average nucleotide identity (ANI) for determining ECC species, multilocus sequence type, core genome single-nucleotide-polymorphism-based phylogenetic analysis were performed. phoPQ-, eptA-, and arnT-deleted mutants were established to evaluate the mechanism underlying colistin heteroresistance. The arnT mRNA expression levels were determined by reverse transcription quantitative PCR.

Results

Thirty-eight CST-resistant isolates, all of which exhibited the heteroresistant phenotype by PAP, were found from 138 ECC clinical isolates (27.5%). The prevalence of CST-resistant isolates did not significantly differ among the origin of specimens (29.0%, 27.8%, and 20.2% for respiratory, urine, and blood specimens, respectively). hsp60 clusters, core genome phylogeny, and ANI revealed that the CST-heteroresistant isolates were found in all or most of Enterobacter roggenkampii (hsp60 cluster IV), Enterobacter kobei (cluster II), Enterobacter chuandaensis (clusters III and IX), and Enterobacter cloacae subspecies (clusters XI and XII). No heteroresistant isolates were found in Enterobacter hormaechei subspecies (clusters VIII, VI, and III) and Enterobacter ludwigii (cluster V). CST-induced mRNA upregulation of arnT, which encodes 4-amino-4-deoxy-l-arabinose transferase, was observed in the CST-heteroresistant isolates, and it is mediated by phoPQ pathway. Isolates possessing mcr-9 and mcr-10 (3.6% and 5.6% of total ECC isolates, respectively) exhibited similar CST susceptibility and PAP compared with mcr-negative isolates.

Conclusions

Significant prevalence (approximately 28%) of CST heteroresistance is observed in ECC clinical isolates, and they are accumulated in specific species and lineages. Heteroresistance is occurred by upregulation of arnT mRNA induced by CST. Acquisition of mcr genes contributes less to CST resistance in ECC.
Immunotherapy: an emerging modality to checkmate brain metastasis
Authors: Ahmad Aatiya , Khan Parvez , Rehman Asad Ur , Batra Surinder Kumar , Nasser Mohd Wasim
Published: July 2023

The diagnosis of brain metastasis (BrM) has historically been a dooming diagnosis that is nothing less than a death sentence, with few treatment options for palliation or prolonging life. Among the few treatment options available, brain radiotherapy (RT) and surgical resection have been the backbone of therapy. Within the past couple of years, immunotherapy (IT), alone and in combination with traditional treatments, has emerged as a reckoning force to combat the spread of BrM and shrink tumor burden. This review compiles recent reports describing the potential role of IT in the treatment of BrM in various cancers. It also examines the impact of the tumor microenvironment of BrM on regulating the spread of cancer and the role IT can play in mitigating that spread. Lastly, this review also focuses on the future of IT and new clinical trials pushing the boundaries of IT in BrM.
Expression of mTOR in normal and pathological conditions
Authors: Marques-Ramos A , Cervantes R
Published: July 2023

The mechanistic/mammalian target of rapamycin (mTOR), a protein discovered in 1991, integrates a complex pathway with a key role in maintaining cellular homeostasis. By comprising two functionally distinct complexes, mTOR complex 1 (mTORC1) and mTORC2, it is a central cellular hub that integrates intra- and extracellular signals of energy, nutrient, and hormone availability, modulating the molecular responses to acquire a homeostatic state through the regulation of anabolic and catabolic processes. Accordingly, dysregulation of mTOR pathway has been implicated in a variety of human diseases. While major advances have been made regarding the regulators and effectors of mTOR signaling pathway, insights into the regulation of mTOR gene expression are beginning to emerge. Here, we present the current available data regarding the mTOR expression regulation at the level of transcription, translation and mRNA stability and systematize the current knowledge about the fluctuations of mTOR expression observed in several diseases, both cancerous and non-cancerous. In addition, we discuss whether mTOR expression changes can be used as a biomarker for diagnosis, disease progression, prognosis and/or response to therapeutics. We believe that our study will contribute for the implementation of new disease biomarkers based on mTOR as it gives an exhaustive perspective about the regulation of mTOR gene expression in both normal and pathological conditions.
UTX deletion promotes M2 macrophage polarization by epigenetically regulating endothelial cell-macrophage crosstalk after spinal cord injury
Authors: Peng Wei , Xie Yong , Luo Zixiang , Liu Yudong , Xu Jiaqi , Li Chengjun , Qin Tian , Lu Hongbin , Hu Jianzhong
Published: July 2023

Macrophages polarized to the M2 subtype after spinal cord injury (SCI) are beneficial for promoting neurological recovery. The crosstalk between endothelial cells (ECs) and macrophages is crucial for the imbalance between proinflammatory and pro-resolving responses caused by macrophage heterogeneity; however, this crosstalk is strengthened post-SCI, leading to inflammatory cascades and second damage. As a powerful means to regulate gene expression, epigenetic regulation of the interaction between immune cells and ECs in SCI is still largely unknown. Our previous research demonstrated that the histone demethylase UTX deletion in ECs (UTX−/− ECs) promotes neurological recovery, while the precise mechanism is unrevealed. Here, we discovered that UTX−/− ECs polarize macrophages toward the M2 subtype post-SCI. Macrophage deficiency could block the neurological recovery caused by the knockdown of UTX. The exosomes from UTX−/− ECs mediate this crosstalk. In addition, we found UTX, H3K27, and miR-467b-3p/Sfmbt2 promoters forming a regulatory complex that upregulates the miR-467b-3p in UTX−/− ECs. And then, miR-467b-3p transfers to macrophages by exosomes and activates the PI3K/AKT/mTOR signaling by decreasing PTEN expression, finally polarizing macrophage to the M2 subtype. This study reveals a mechanism by epigenetic regulation of ECs-macrophages crosstalk and identifies potential targets, which may provide opportunities for treating SCI.

Graphical Abstract
Development and validation of a blood biomarker score for predicting mortality risk in the general population
Authors: Yang Jing , Lu Jiayi , Miao Junyan , Li Jiacong , Zhu Meng , Dai Juncheng , Ma Hongxia , Jin Guangfu , Hang Dong
Published: July 2023

Background

Blood biomarkers for multiple pathways, such as inflammatory response, lipid metabolism, and hormonal regulation, have been suggested to influence the risk of mortality. However, few studies have systematically evaluated the combined predictive ability of blood biomarkers for mortality risk.

Methods

We included 267,239 participants from the UK Biobank who had measurements of 28 blood biomarkers and were free of cardiovascular disease (CVD) and cancer at baseline (2006–2010). We developed sex-specific blood biomarker scores for predicting all-cause mortality risk in a training set of 247,503 participants from England and Wales, and validated the results in 19,736 participants from Scotland. Cox and LASSO regression analyses were performed to identify independent predictors for men and women separately. Discrimination and calibration were evaluated by C-index and calibration plots, respectively. We also assessed mediating effects of the biomarkers on the association between traditional risk factors (current smoking, obesity, physical inactivity, hypertension, diabetes) and mortality.

Results

A total of 13 independent predictive biomarkers for men and 17 for women were identified and included in the score development. Compared to the lowest tertile of the score, the highest tertile showed a hazard ratio of 5.36 (95% confidence interval [CI] 5.04–5.71) in men and 4.23 (95% CI 3.87–4.62) in women for all-cause mortality. In the validation set, the score yielded a C-index of 0.73 (95% CI 0.72–0.75) in men and 0.70 (95% CI 0.68–0.73) in women for all-cause mortality; it was also predictive of CVD (C-index of 0.76 in men and 0.79 in women) and cancer (C-index of 0.70 in men and 0.67 in women) mortality. Moreover, the association between traditional risk factors and all-cause mortality was largely mediated by cystatin C, C-reactive protein, 25-hydroxyvitamin D, and hemoglobin A1c.

Conclusions

We established sex-specific blood biomarker scores for predicting all-cause and cause-specific mortality in the general population, which hold the potential to identify high-risk individuals and improve targeted prevention of premature death.
Clinicopathological features of incidentally detected metastatic thyroid papillary carcinoma in cervical lymph nodes of non-thyroid cancer patients: a retrospective analysis of 31cases
Authors: Hu Chunfang , Zhang Haifeng , Chu Lixia , Qiu Tian , Lu Haizhen
Published: July 2023

Background

The incidental finding of thyroid inclusions in lymph nodes of neck dissections of non-thyroid cancer patients is an unusual event. It is still controversial for pathologists about whether this represents benign inclusions or metastatic papillary thyroid carcinoma (PTC). This study is to analyze clinicopathological features of such cases in an attempt to explore their clinical implications.

Methods

Pathological data were searched for incidentally detected PTC of cervical lymph nodes in non-thyroid cancer cases. Clinicopathological characteristics were reevaluated and recorded. BRAF V600E protein expression and sequencing analysis was then performed in cases with sufficient tissues.

Results

31 patients had an incidental finding of PTC in lymph nodes of patients with non-thyroid cancer. BRAF immunohistochemical staining were performed in 17 metastatic lymph nodes with sufficient tumor tissues, and 6 were positive. BRAF V600E point mutation was detected in 5 of 6 BRAF V600E positive cases. Subsequent imaging examinations of the thyroid showed no nodules or calcifications/benign nodules in 20 patients, and suspected malignant nodules in 5 patients. 12 patients underwent total thyroidectomy or ipsilateral lobectomy, and 6 showed PTC in postoperative pathological examinations. The remaining 19 patients without surgery were kept under active surveillance, and no one had recurrence of PTC.

Conclusion

Incidentally discovered PTC in lymph nodes has usually interpreted as metastasis from a clinical occult thyroid primary cancer, but primary PTC was not always detected. This suggests it could be double occult lesions. With regards to concurrence with highly malignant tumor, most patients could keep regular surveillance.
Metanephric stromal tumor in an adult with PDGFRA mutation: a case report
Authors: Guo Sanjun , Qian Huan , Zhu Hong , Yang Yue , Yang Xudan , Sun Huajun
Published: July 2023

Background

Metanephric stromal tumors (MST) are rare benign renal tumors that mainly occur in infants and children. Approximately 72% of MST in children have the B-Raf proto-oncogene serine/threonine kinase(BRAF)V600E mutation. To date, only five cases of adult MSTs have been reported and no clear genetic alterations have been found.

Case presentation

We report a case of MST in a 45-year-old woman who complained of left lower back pain for a week, accompanied by hypertension (150/79 mmHg). Magnetic resonance imaging (MRI) showed an abnormally enhanced nodule (1.1 cm in the middle of the left kidney), which was histopathologically consistent with an MST. TheBRAFV600E mutation was not detected in tumor cells using PCR and next-generation sequencing (NGS). However, a platelet-derived growth factor receptor alpha (PDGFRA) mutation was detected in this case using NGS. The patient showed no recurrence or metastasis nine months after partial nephrectomy, and her blood pressure was consistently normal.

Conclusion

This is the first report of alterations inPDGFRAin MSTs. This result advances our knowledge of genetic variations in adult MSTs, which may have different gene alterations from MSTs in children.
Comparative fixation devices for preventing migration of the proximal tibiofibular joint during tibial lengthening: a tether versus screw fixation
Authors: Wongcharoenwatana Jidapa , Hoellwarth Jason S. , Greenstein Michael D. , Reif Taylor J. , Fragomen Austin T. , Rozbruch S. Robert
Published: July 2023

Background

When lengthening the tibia segment using motorized internal lengthening nails (MILN), undesired distal migration of the proximal fibula segment is prevented by tibiofibular stabilization, traditionally using a screw. A tightened cortical suspensory fixation rope (tether) is an alternative option, but its appropriateness has never been studied. The primary outcome was comparing the amount of proximal fibular migration between patients who were stabilized with either a tether or a screw. The secondary outcome was to evaluate the effect of fibular migration on the clinical outcome between both groups.

Methods

A retrospective study was conducted on patients who underwent tibial lengthening with MILN between April 2016 and June 2022. Two cohorts were compared: 18 limbs with tether fixation versus 29 limbs with screw fixation. Data on the patient's age, sex, etiologies, and clinical outcomes were collected. Radiographic measurements included the lengthening distance and the amount of proximal fibular migration.

Results

In total, 47 limbs from 41 patients, with average age 35.01 ± 13.72 years old. There were 28 males (68.29%) and 13 females (31.71%). The tether group demonstrated a statistically significant greater distance of migration than the screw group (p < 0.001), with an average migration distance of 8.39 ± 5.09 mm and 2.59 ± 3.06 mm, respectively. No correlation was found between the amount of tibial lengthening and the distance of proximal fibular migration in both the tether group (p = 0.96) and the screw group (p = 0.32). There was no significant difference in the change of knee extension between both groups (p = 0.3), and no patients reported knee pain or tightness.

Conclusion

A screw provides better resistance to proximal tibiofibular joint migration during MILN lengthening, but the difference appears clinically inconsequential. Either option appears suitable.
Osteoarthritis and sarcopenia-related traits: the cross-sectional study from NHANES 2011–2014 and Mendelian randomization study
Authors: Chen Shuai , Han Huawei , Jin Jie , Zhou Guowei , Li Zhiwei
Published: July 2023

Background

Osteoarthritis (OA) and sarcopenia are common musculoskeletal disorders in the aged population, and a growing body of evidence indicated that they mutually influence one another. Nevertheless, there was still substantial controversy and uncertainty about the causal relationship between sarcopenia and OA. We explored the complex association between sarcopenia-related traits and OA using cross-sectional analysis and Mendelian randomization (MR).

Methods

The cross-sectional study used the data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014. Weighted multivariable-adjusted logistic regression and subgroup analyses were used to evaluate the correlation between sarcopenia, grip, appendicular lean mass (ALM) and the risk of OA. Then, we further performed MR analysis to examine the causal effect of sarcopenia-related traits (grip strength, ALM) on OA. Instrumental variables for grip strength and ALM were from the UK Biobank, and the summary-level data for OA was derived from the Genetics of Osteoarthritis (GO) Consortium GWAS (n = 826,690).

Results

In this cross-sectional analysis, we observed that sarcopenia, grip were significantly linked with the risk of OA (OR 1.607, 95% CI 1.233–2.094, P < 0.001), (OR 0.972, 95% CI 0.964–0.979, P < 0.001). According to subgroup analyses stratified by gender, body mass index (BMI), and age, the significant positive relationship between sarcopenia and OA remained in males, females, the age (46–59 years) group, and the BMI (18.5–24.9 kg/m2) group (P < 0.05). Furthermore, MR analysis and sensitivity analyses showed causal associations between right grip, left grip and KOA (OR 0.668; 95% CI 0.509 to 0.877; P = 0.004), (OR 0.786; 95% CI 0.608 to 0.915; P = 0.042). Consistent directional effects for all analyses were observed in both the MR-Egger and weighted median methods. Subsequently, sensitivity analyses revealed no heterogeneity, directional pleiotropy or outliers for the causal effect of grip strength on KOA (P > 0.05).

Conclusions

Our research provided evidence that sarcopenia is correlated with an increased risk of OA, and there was a protective impact of genetically predicted grip strength on OA. These findings needed to be verified in further prospective cohort studies with a large sample size.
Icariin promotes the proliferation and osteogenic differentiation of bone-derived mesenchymal stem cells in patients with osteoporosis and T2DM by upregulating GLI-1
Authors: Xia Sheng-li , Ma Zi-yuan , Wang Bin , Gao Feng , Guo Sheng-yang , Chen Xu-han
Published: July 2023

Background

The function of mesenchymal stem cells (MSCs) from patients with osteoporosis (OP) is impaired and worsens in patients with type 2 diabetes mellitus (T2DM). Icariin (ICA) is the major active flavonoid glucoside isolated from traditional Chinese herbal Epimedium pubescens, and confirmed able to improve bone mass of OP patients.

Objective

To investigate the effect of ICA on the proliferation and osteogenic differentiation of bone-derived MSCs (BMSCs) from patients with OP and T2DM and uncover the potential mechanism.

Methods

BMSCs were treated with ICA, and proliferation and osteogenic potency were evaluated using the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and detection of osteogenic markers (ALP, RUNX2, SPP1, COL1A1, and mineralized nodules) was performed. RNA sequencing and bioinformatic analysis were performed to identify differentially expressed genes (DEGs) after ICA treatment and screen proliferation- and osteogenic differentiation-related processes. Gene gain and loss were performed to confirm the role of the key candidate gene.

Results

ICA significantly promoted the proliferation and osteogenic differentiation of BMSCs. A total of 173 DEGs were identified after ICA treatment. Six DEGs (GLI-1, IGF2, BMP6, WNT5A, PTHLH, and MAPK14) enriched in both proliferation- and osteogenic differentiation-related processes were screened; GLI-1 had the highest validated |log2FC| value. Overexpression of GLI-1 enhanced the proliferation and osteogenic differentiation of BMSCs, and knockdown of GLI-1 weakened the positive effect of ICA on BMSCs.

Conclusion

ICA promoted the proliferation and osteogenic differentiation of impaired BMSCs by upregulating GLI-1.
The mental health toll of COVID-19: significant increase in admissions to ICU for voluntary self-inflicted injuries after the beginning of the pandemic
Authors: Mongodi Silvia , Salve Giulia , Ravasi Marta , Rizzi Damiano , Mangiagalli Matteo , Musella Valeria , Klersy Catherine , Ansaloni Luca , Mojoli Francesco
Published: July 2023

Background

COVID-19 outbreak deeply impacted on mental health, with high rate of psychological distress in healthcare professionals, patients and general population. Current literature on trauma showed no increase in ICU admissions for deliberate self-inflicted injuries in the first weeks after the beginning of COVID-19.

Objectives

We tested the hypothesis that self-inflicted injuries/harms of any method requiring ICU admission increased in the year following COVID-19 outbreak.

Methods

Retrospective cohort single-center study comparing admissions to ICU the year before and the year after the pandemic start. All patients admitted to polyvalent ICUs—Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy from February 21st, 2019 to February 21st, 2020 (pre-COVID) and from February 22nd, 2020 to February 22nd, 2021 (post-COVID) were enrolled.

Results

We enrolled 1038 pre-COVID and 854 post-COVID patients. In post-COVID, the incidence of self-inflicted injuries was 32/854 (3.8% [2.5–5.1]), higher than in pre-COVID (23/1038, 2.2%–p = 0.0014—relative increase 72.7%). The increase was more relevant when excluding COVID-19 patients (suicide attempts 32/697 (4.6% [3.0–6.2])–relative increase 109.1%; p < 0.0001).

Both in pre-COVID and post-COVID, the most frequent harm mean was poisoning [15 (65.2%) vs. 25 (78.1%), p = 0.182] and the analysed population was younger than general ICU population (p = 0.0015 and < 0.0001, respectively). The distribution of admissions for self-inflicted injuries was homogeneous in pre-COVID along the year. In post-COVID, no admissions were registered during the lockdown; an increase was observed in summer with pandemic curve at minimal levels.

Conclusions

An increase in ICU admissions for self-inflicted injuries/harms was observed in the year following COVID-19 outbreak.
Study of novel bidentate heterocyclic amine-based metal complexes and their biological activities: cytotoxicity and antimicrobial activity evaluation
Authors: Fahmy Heba M. , Abdel-Rahman Fatma M. , El-Sayed Anwar A. , El-Sherif Ahmed A.
Published: July 2023

Metallic antitumor drugs with heterocyclic ligands, such as novel AMI (amino methyl imidazole) complexes [Pd(AMI)Cl2](1), [Cu(AMI)L1](2), and [Cu(AMI)L2·2H2O](3) where L1 = oxalate and L2 = malonate, were synthesized and characterized. Assessments included elemental analyses, mass spectrometry, Fourier transform-infrared spectroscopy, ultraviolet–visible spectroscopy, and thermal analysis. The cytotoxicity of AMI complexes compared to cisplatin was assessed using MTT (3-[4,5-dimethylthiazol-2-yl] 2,5diphenyl tetrazolium bromide) assay with breast (MCF-7) and cervical (HeLa) cancer cell lines. After treating these cells with the AMI complexes' IC50 values for 48 h, malondialdehyde levels and catalase activity were used to assess oxidative stress, antioxidant activity was evaluated with DPPH radical scavenging method, comet assays assessed DNA damage, and DNA fragmentation was evaluated using the gel electrophoresis. In vitro, antimicrobial activity was assessed using a disc diffusion method. The anticancer activity results showed that IC50 (half-maximal inhibitory concentration) values of complex one, two, and three against MCF-7 and HeLa cancer cells are 0.156 ± 0.0006, 0.125 ± 0.001, 0.277 ± 0.002 μM respectively for MCF-7 cells and 0.222 ± 0.0005, 0.126 ± 0.0009, 0.152 ± 0.001 μM respectively for HeLa cells. Complex two demonstrated strong anticancer activity against MCF-7 and Hela cells. The study of oxidative stress parameters revealed that Malondialdehyde levels increased in cancer cell lines treated with complexes compared to untreated cells. Catalase activity decreased in cells treated with palladium chelate. The DPPH radical scavenging assay results identified that complex one was a more potent antioxidant in MCF-7 and Hela cells than other complexes with SC50 values of 227.5 ± 0.28 and 361 ± 1.2 μL/mL, respectively. The comet assay results showed that complex two caused significant DNA damage in MCF-7 and HeLa cancer cells treated. Antimicrobial assays identified complex three as the most effective. Copper complexes give better antifungal activity against A. flavus than the palladium complex. We conclude that complex two is the most active in both cell types and might be assessed as a clinically useful drug for breast cancer treatment. The significance of the current study is the synthesis of antitumor drugs containing heterocyclic ligands, such as novel AMI complexes, and the study of their biological activities.
Potential diagnostic value of CSF metabolism-related proteins across the Alzheimer’s disease continuum
Authors: Paciotti Silvia , Wojdała Anna Lidia , Bellomo Giovanni , Toja Andrea , Chipi Elena , Piersma Sander R. , Pham Thang V. , Gaetani Lorenzo , Jimenez Connie R. , Parnetti Lucilla , Chiasserini Davide
Published: July 2023

Background

Alzheimer’s disease (AD) cerebrospinal fluid (CSF) core biomarkers (Aβ42/40 ratio, p-tau, and t-tau) provide high diagnostic accuracy, even at the earliest stage of disease. However, these markers do not fully reflect the complex AD pathophysiology. Recent large scale CSF proteomic studies revealed several new AD candidate biomarkers related to metabolic pathways. In this study we measured the CSF levels of four metabolism-related proteins not directly linked to amyloid- and tau-pathways (i.e., pyruvate kinase, PKM; aldolase, ALDO; ubiquitin C-terminal hydrolase L1, UCHL1, and fatty acid-binding protein 3, FABP3) across the AD continuum. We aimed at validating the potential value of these proteins as new CSF biomarkers for AD and their possible involvement in AD pathogenesis, with specific interest on the preclinical phase of the disease.

Methods

CSF PKM and ALDO activities were measured with specific enzyme assays while UCHL1 and FABP3 levels were measured with immunoassays in a cohort of patients composed as follows: preclinical AD (pre-AD, n = 19, cognitively unimpaired), mild cognitive impairment due to AD (MCI-AD, n = 50), dementia due to AD (ADdem, n = 45), and patients with frontotemporal dementia (FTD, n = 37). Individuals with MCI not due to AD (MCI, n = 30) and subjective cognitive decline (SCD, n = 52) with negative CSF AD-profile, were enrolled as control groups.

Results

CSF UCHL1 and FABP3 levels, and PKM activity were significantly increased in AD patients, already at the pre-clinical stage. CSF PKM activity was also increased in FTD patients compared with control groups, being similar between AD and FTD patients. No difference was found in ALDO activity among the groups.

UCHL1 showed good performance in discriminating early AD patients (pre-AD and MCI-AD) from controls (AUC ~ 0.83), as assessed by ROC analysis. Similar results were obtained for FABP3. Conversely, PKM provided the best performance when comparing FTD vs. MCI (AUC = 0.80). Combination of PKM, FABP3, and UCHL1 improved the diagnostic accuracy for the detection of patients within the AD continuum when compared with single biomarkers.

Conclusions

Our study confirmed the potential role of UCHL1 and FABP3 as neurodegenerative biomarkers for AD. Furthermore, our results validated the increase of PKM activity in CSF of AD patients, already at the preclinical phase of the disease. Increased PKM activity was observed also in FTD patients, possibly underlining similar alterations in energy metabolism in AD and FTD.
High-strength and flexible mechanism for body weight support
Authors: Sugiura Sojiro , Unde Jayant , Zhu Yaonan , Hasegawa Yasuhisa
Published: July 2023

Wearable body weight support systems can assist individuals with mobility impairments in performing daily living activities with greater ease and independence. However, existing systems have limitations in terms of balancing their strength, compact size, interaction with the ground, and driving. In this paper, we present the High-Strength and Flexible Mechanism (HSFM) designed for body weight support. The HSFM utilizes a coiling truss mechanism to perform flexible transformation between a straight and spiral shape. Its complex linkages create the mechanical constraints of the structure and enhance its stiffness. Additionally, the HSFM achieved a high extension rate, effective wire-driven mechanism, and smooth shift of the grounding point. We provide a detailed description of the HSFM, including the simplest 4-linkage mechanism, its mechanical constraints, and the wire-driven mechanism. Moreover, we conducted parametric analysis and geometric calculation on the link structure. The results justified the mechanical constraints of the HSFM and ensured the high extension rate. Further, its functionality for body weight support was evaluated with the hardware and showed sufficient results in terms of strength, smooth grounding, and wire-driven. This novel mechanism has the potential to develop a wearable body weight support robot enhancing daily living activities such as sit-to-stand transfer and walking.
Adherence to Injury Prevention Exercise Programmes in Amateur Adolescent and Adult Football: A Detailed Description of Programme Use from a Randomised Study
Authors: Lindblom Hanna , Waldén Markus , Hägglund Martin
Published: July 2023

Background

Injury prevention exercise programmes (IPEPs) efficaciously reduce injuries. However, it is challenging to achieve sufficient adherence across a season. The main aim was to describe adherence to IPEPs in three groups of coaches and players partaking in a cluster randomised trial. Secondary aims were to describe perceptions of IPEPs, use of programme material, and overall preventive strategies.

Methods

This is a sub-study analysing data from a three-armed randomised trial with teams randomised to use either a comprehensive IPEP (extendedKnee Control) or an adductor strength programme, and non-randomised teams that already used a self-chosen IPEP regularly at study start (comparison group). Teams were instructed to use their respective intervention across the 2020 football season. Male and female, adolescent (≥ 14 years of age), and adult amateur players took part. Coaches and players responded to weekly and end-of-season questionnaires. Data were presented descriptively.

Results

Weekly player data were reported by 502 players (weekly response rate 65%), 289 (58%) responded to end-of-season questionnaires. Teams in the extendedKnee Controland comparison group used their respective IPEP in 483/529 (91%) and 585/641 (91%) of training sessions, and teams in the adductor group in in 199/315 (63%) sessions. Regarding utilisation fidelity, 42–52% of players in each group used 1–10 repetitions per exercise. Seven out of 17 teams in the adductor group had progressed as recommended in terms of number of repetitions. Two teams (10%) in the extendedKnee Controlgroup, and 7/24 of comparison teams used the same exercises across the season. Coaches accessed the IPEPs by different means (printed material, films, workshops, etc.), but half did not use the provided digital material. The players appreciated that the IPEPs could reduce injury risk and that they improved their exercise performance, but disliked that they had less time for football and that the exercises were boring. Forty-nine players had experienced pain during IPEP performance.

Conclusions

Adherence with the IPEPs was generally high. To meet different coach needs, programme material should be available via different digital and printed resources. The number of players reporting pain during IPEP performance is a noteworthy finding.

Trial registration

Clinical Trials gov identifier: NCT04272047. Registered February 17, 2020.https://clinicaltrials.gov/ct2/show/NCT04272047.