bluuebunny/crossref_metadata_2025 huggingface dataset:
T1ρ, T2 and T2* mapping of lumbar intervertebral disc degeneration: a comparison study
Authors: Yang Li , Sun Cong , Gong Tao , Li Quanlin , Chen Xin , Zhang Xinjuan
Published: December 2022

Background

Early and accurate assessment of lumbar intervertebral disc degeneration (IVDD) is very important to therapeutic strategy. This study aims to correlate and compare the performances of T1ρ, T2 and T2* mapping for Pfirrmann grades and morphologic changes in the IVDD.

Methods

This prospective study included 39 subjects with 195 lumbar discs. T1ρ, T2 and T2* mapping were performed, and T1ρ, T2 and T2* values of nucleus pulposus (NP), and anterior and posterior annulus fibrosus were measured. IVDD was assessed with Pfirrmann grading and morphologic changes (normal, bulging, herniation and annular fissure). The performances of T1ρ, T2 and T2* relaxation times were compared for detecting early (Pfirrmann grade II-III) and advanced degeneration (Pfirrmann grade IV–V), as well as for morphologic changes.

Results

T2 relaxation times was strongly corelated with T1ρ and T2* relaxation times. Areas under the curves (AUCs) of T1ρ, T2 and T2* relaxation times of NP were 0.70, 0.87 and 0.80 for early degeneration, and 0.91, 0.95 and 0.82 for advanced degeneration, respectively. AUCs of T1ρ, T2 and T2* relaxation times of NP were 0.78, 0.83 and 0.64 for bulging discs, 0.87, 0.89 and 0.69 for herniated discs, and 0.79, 0.82 and 0.69 for annular tearing, respectively. The AUC of T2 relaxation time was significantly higher than those of T1ρ relaxation times (both P < 0.01) for early IVDD, and the AUCs of T1ρ and T2 relaxation times for assessing advanced degeneration and morphologic changes were similar (P > 0.05) but significantly higher than that of T2*relaxation time (P < 0.01).

Conclusions

T2 mapping performed better than T1ρ mapping for the detection of early IVDD. T1ρ and T2 mapping performed similarly but better than T2* mapping for advanced degeneration and morphologic changes of IVDD.
Low back pain is associated with sleep disturbance: a 3-year longitudinal study after the Great East Japan Earthquake
Authors: Yabe Yutaka , Hagiwara Yoshihiro , Sugawara Yumi , Tsuji Ichiro
Published: December 2022

Background

Low back pain and sleep disturbance are common health problems worldwide which are also commonly observed among people after natural disasters. These symptoms are well known to coexist, and recent reports have indicated that sleep disturbance is a risk factor for low back pain. However, the influence of low back pain on sleep disturbance has rarely been assessed; therefore, this study aimed to clarify the association of low back pain with sleep disturbance, especially focusing on the frequency of low back pain, using 3-year cohort data after the Great East Japan Earthquake.

Methods

This study used the data obtained from people living in the disaster-affected areas after the Great East Japan Earthquake (n = 2,097). Low back pain and sleep disturbance were assessed at 4, 5, 6, and 7 years after the disaster. The frequency of low back pain was defined as the number of low back pain episodes at and before the evaluation time point and categorized into five groups such as absence, 1, 2, 3, and 4 at the fourth time point and four groups such as absence, 1, 2, and 3 at the third time point. Multivariate logistic regression analyses were conducted to assess the association of low back pain with sleep disturbance.

Results

Low back pain was significantly associated with sleep disturbance, and the association was stronger in participants with more frequent low back pain (adjusted odds ratios [95% confidence intervals],1.46 [1.10–1.95] in “1”; 2.02 [1.49–2.74] in “2”; 2.38 [1.67–3.40] in “3”; and 4.08 [2.74–6.06] in “4” in the frequency of low back pain) (P for trend < 0.001). Furthermore, antecedent low back pain was significantly associated with new-onset sleep disturbance, and the association was robust in more frequent low back pain (adjusted odds ratios [95% confidence intervals],1.60 [1.05–2.44] in “1”; 1.96 [1.20–3.21] in “2”; and 2.17 [1.14–4.14] in “3” in the frequency of low back pain) (P for trend = 0.007).

Conclusion

Our study showed that low back pain is strongly associated with sleep disturbance. Attention should be paid to low back pain to prevent and treat sleep disturbance, especially focusing on chronicity of low back pain.
Constructing and validating nomograms to predict risk and prognostic factors of distant metastasis in urothelial bladder cancer patients: a population-based retrospective study
Authors: Chen Di , Luo Zhihua , Ye Chaoping , Luo Quanhai , Fan Wenji , Chen Changsheng , Liu Gang
Published: December 2022

Background

Urothelial carcinoma is the most common type of bladder cancer worldwide and it has a poor prognosis for patients with distant metastasis. Nomograms are frequently used in clinical research, but no research has evaluated the diagnostic and prognostic factors of distant metastasis in urothelial bladder cancer (UBC).

Methods

The Surveillance, Epidemiology, and End Results database was used to analyze all patients diagnosed with UBC between 2000 and 2017. Lasso regression was used to identify the potential risk predictive factors for distant metastasis in UBC. Univariate and multivariate Cox proportional hazard regression analyses were performed to determine independent prognostic factors for distant metastasis urothelial bladder cancer (DMUBC). Subsequently, two nomograms were constructed based on the above models. The receiver operating characteristic (ROC), and calibration curves were performed to evaluate the two nomograms.

Results

The study included 73,264 patients with UBC, with 2,129 (2.9%) having distant metastasis at the time of diagnosis. In the diagnostic model, tumor size, histologic type, and stage N and T were all important risk predictive factors for distant metastasis of UBC. In the prognostic model, age, tumor size, surgery, and chemotherapy were independent factors affecting the prognosis of DMUBC. DCA, ROC, calibration, and Kaplan–Meier (K–M) survival curves reveal that the two nomograms can effectively predict the diagnosis and prognosis of DMUBC.

Conclusion

The developed nomograms are practical methods for predicting the occurrence risk and prognosis of distant metastasis urothelial bladder cancer patients, which may benefit the clinical decision-making process.
Comprehensive analysis of M2 macrophage-derived exosomes facilitating osteogenic differentiation of human periodontal ligament stem cells
Authors: Liao Xian-min , Guan Zheng , Yang Zhen-jin , Ma Li-ya , Dai Ying-juan , Liang Cun , Hu Jiang-tian
Published: December 2022

Background

The role of periodontal ligament stem cells (PDLSCs) and macrophage polarization in periodontal tissue regeneration and bone remodeling during orthodontic tooth movement (OTM) has been well documented. Nevertheless, the interactions between macrophages and PDLSCs in OTM remain to be investigated. Consequently, the present study was proposed to explore the effect of different polarization states of macrophages on the osteogenic differentiation of PDLSCs.

Methods

After M0, M1 and M2 macrophage-derived exosomes (M0-exo, M1-exo and M2-exo) treatment of primary cultured human PDLSCs, respectively, mineralized nodules were observed by Alizarin red S staining, and the expression of ALP and OCN mRNA and protein were detected by RT-qPCR and Western blotting, correspondingly. Identification of differentially expressed microRNAs (DE-miRNA) in M0-exo and M2-exo by miRNA microarray, and GO and KEGG enrichment analysis of DE-miRNA targets, and construction of protein–protein interaction networks.

Results

M2-exo augmented mineralized nodule formation and upregulated ALP and OCN expression in PDLSCs, while M0-exo had no significant effect. Compared to M0-exo, a total of 52 DE-miRNAs were identified in M2-exo. The expression of hsa-miR-6507-3p, hsa-miR-4731-3p, hsa-miR-4728-3p, hsa-miR-3614-5p and hsa-miR-6785-3p was significantly down-regulated, and the expression of hsa-miR-6085, hsa-miR-4800-5p, hsa-miR-4778-5p, hsa-miR-6780b-5p and hsa-miR-1227-5p was significantly up-regulated in M2-exo compared to M0-exo. GO and KEGG enrichment analysis revealed that the downstream targets of DE-miRNAs were mainly involved in the differentiation and migration of multiple cells.

Conclusions

In summary, we have indicated for the first time that M2-exo can promote osteogenic differentiation of human PDLSCs, and have revealed the functions and pathways involved in the DE-miRNAs of M0-exo and M2-exo and their downstream targets.
Substantivity of mouth-rinse formulations containing cetylpyridinium chloride and O-cymen-5-ol: a randomized-crossover trial
Authors: Aguilera Felipe-Rodrigo , Viñas Miguel , Sierra Josep M. , Vinuesa Teresa , R. Fernandez de Henestrosa Antonio , Furmanczyk Marta , Trullàs Carles , Jourdan Eric , López-López José , Jorba Marta
Published: December 2022

Background

The efficacy of mouth-rinses strongly depends upon their substantivity. The use of natural and non-toxic products that avoid secondary effects is gaining interest in preventive dentistry. The purpose of this study was to evaluate the substantivity of two formulations of mouth-washing solutions based on cetylpyridinium (CPC) and O-cymen-5-ol.

Methods

This was a randomized, double-blind, crossover trial conducted at the Faculty of Medicine and Health Sciences of the University of Barcelona. Bacterial re-colonization was followed by live/dead (SYTOTM9 + propidium iodide) bacterial staining and measured by confocal laser scanning microscopy and fluorometry. Unstimulated saliva samples were collected from 16 healthy individuals at baseline saliva and then, at 15 min, 30 min and 1, 2, 3, and 4 h after the following mouth-rinses: (i) a single, 1-min mouth-rinse with 15 ml of placebo (negative control); (ii) a single, 1-min mouth-rinse with 15 ml of CPC (0.05%) ; (iii) a single, 1-min mouth-rinse with 15 ml of O-cymen-5-ol (0.09%); (iv) a single, 1-min mouth-rinse with 15 ml of CPC (0.05%) + O-cymen-5-ol (0.09%).

Results

Proportion of dead bacteria was significantly higher for all mouthrinses during the first 15 min compared to baseline (CPC = 48.0 ± 13.9; 95% CI 40.98–56.99; p < 0.001, O-cymen-5-ol = 79.8 ± 21.0; 95% CI 67.71–91.90; p < 0.05, CPC + O-cymen-5-ol = 49.4 ± 14; 95% CI 40.98–56.99; p < 0.001 by fluorometry and 54.8 ± 23.0; 95% CI 41.50–68.06; p < 0.001, 76.3 ± 17.1; 95% CI 66.36–86.14; p < 0.001, 47.4 ± 11.9; 95% CI 40.49–54.30; p < 0.001 by confocal laser scanning microscopy, respectively). Nevertheless, after 4 h, CPC + O-cymen-5-ol was the only one that obtained significant values as measured by the two quantification methods used (80.3 ± 22.8; 95% CI 67.15–93.50; p < 0.05 and 81.4 ± 13.8; 95% CI 73.45–89.43; p < 0.05). The combined use of CPC + O-cymen-5-ol increased the substantivity of the mouthrinse with respect to mouthrinses prepared with either of the two active products alone.

Conclusion

The synergistic interaction of CPC and O-cymen-5-ol prolongs their substantivity. The resulting formulation may be as effective as other antimicrobials, such as triclosan or chlorhexidine, but without their undesirable secondary effects. Thus, mouthrinsing products based on Combinations of CPC and O-cymen-5-ol may replace in the near future Triclosan and Chlorhexidine—based mouthrinses.
Reasons for early marriage of women in Zahedan, Iran: a qualitative study
Authors: Hosseini Maryam , Asadisarvestani Khadijeh
Published: December 2022

Background

Early marriage occurs in some regions of the world. Given that early marriage can have many negative consequences for girls by affecting their physical, mental, and social health, the purpose of this study was to investigate the reasons for early marriage from the perspective of women who had experienced it in Zahedan, Iran.

Methods

This qualitative research was conducted based on the qualitative content analysis method in 2020–2021. The target population included women aged 18–35 living in Zahedan who were married under the age of 18 years. Purposeful sampling was used to select the participants. In order to collect data, in-depth interviews were performed to decipher the reasons for early marriage from these women’s perspectives. A total of 36 interviews were conducted from October to December 2020 until reaching theoretical saturation. Conventional content analysis was used to analyze the data and extract the relevant concepts and categories.

Results

The analysis of the interviews in this study revealed three main categories:(1) “early marriage as a transcendental coercion” ( early marriage as a cultural heritage and early marriage as a control tool, girls’ weaknesses and inability to resist, dominant attitudes toward gender and gender restrictions), (2) “early marriage as a solution or a kind of problem solving” (escape from undesirable family environment, escape from financial poverty, and strategic escape from an unpleasant situation), and (3) “early marriage as a voluntary act” (real agency and imaginary agency). To substantiate these findings, we presented excerpts from the interviews conducted with the participants.

Conclusion

The results of this study suggest a multidimensional picture of early marriage. It seems that improving cultural conditions and empowering families and girls in various areas, including marriage, can reduce the rate of early marriage and/or at least mitigate its undesirable consequences.
Combination of Quercetin or/and siRNA-loaded DDAB-mPEG-PCL hybrid nanoparticles reverse resistance to Regorafenib in colon cancer cells
Authors: Shahidi Shabnam , Rostamizadeh Kobra , Fathi Mojtaba , Nedaei Keivan , Ramazani Ali
Published: December 2022

Background

Colorectal cancer (CRC) is the second leading cause of cancer death. Although Regorafenib showed survival benefits in patients with CRC, reports imply the recurrence of malignant phenotype resulting from chemotherapy. Evidence demonstrated that a5β1 integrin plays an important role in the Regorafenib treatment, which, may be led to resistance. In this study, the effects of /siRNA or/ and Quercetin loaded DDAB-mPEG-PCLnanoparticles could reverse this resistance phenotype in colon cancer cells in vitro.

Methods

Regorafenib-resistant Ls-180 colon cancer cell line was developed by long-term exposure to Regorafenib. Quercetin and Regorafenib were separately encapsulated into mPEG-PCL micelles through the nano-precipitation method and characterized by DLS. Optimized doses of Quercetin and Regorafenib were used for combination therapy of resistant cells followed cytotoxicity study using MTT. Gene expression levels of the β1 subunit of integrin were determined by the real-time method of RT-PCR.

Results

Developed Regorafenib resistant LS-180 showed to have Regorafenib IC50 of 38.96 ± 1.72 µM whereas IC50 in non-resistant cells were 8.51 ± 0.29 µM, which meaningful was lower statistically compared to that of a resistant one. The β1 mRNA level of whole α5β1 integrin was significantly higher in the resistant cells compared to those of non-resistant ones. Gene expression levels in each siRNA-loaded nanoparticle and Quercetin-loaded one were lower than that in mock experiments. Finally, when these two types of nanoparticles were used to treat resistant cells, gene expression decrease of integrin indicated a greater effect that could be capable of reverse resistancy.

Conclusion

Results of this study demonstrated another confirmation of involving integrins in cancer resistance following chemotherapy using Regorafenib. Also, it indicated how using siRNA targeting integrin could enhance the plant derivatives like Quercetin effects to reverse resistance in vitro.
Red algae acclimate to low light by modifying phycobilisome composition to maintain efficient light harvesting
Authors: Voerman Sofie E. , Ruseckas Arvydas , Turnbull Graham A. , Samuel Ifor D. W. , Burdett Heidi L.
Published: December 2022

Background

Despite a global prevalence of photosynthetic organisms in the ocean’s mesophotic zone (30–200+ m depth), the mechanisms that enable photosynthesis to proceed in this low light environment are poorly defined. Red coralline algae are the deepest known marine benthic macroalgae — here we investigated the light harvesting mechanism and mesophotic acclimatory response of the red coralline alga Lithothamnion glaciale.

Results

Following initial absorption by phycourobilin and phycoerythrobilin in phycoerythrin, energy was transferred from the phycobilisome to photosystems I and II within 120 ps. This enabled delivery of 94% of excitations to reaction centres. Low light intensity, and to a lesser extent a mesophotic spectrum, caused significant acclimatory change in chromophores and biliproteins, including a 10% increase in phycoerythrin light harvesting capacity and a 20% reduction in chlorophyll-a concentration and photon requirements for photosystems I and II. The rate of energy transfer remained consistent across experimental treatments, indicating an acclimatory response that maintains energy transfer.

Conclusions

Our results demonstrate that responsive light harvesting by phycobilisomes and photosystem functional acclimation are key to red algal success in the mesophotic zone.
Multi-omics gut microbiome signatures in obese women: role of diet and uncontrolled eating behavior
Authors: Barone Monica , Garelli Silvia , Rampelli Simone , Agostini Alessandro , Matysik Silke , D’Amico Federica , Krautbauer Sabrina , Mazza Roberta , Salituro Nicola , Fanelli Flaminia , Iozzo Patricia , Sanz Yolanda , Candela Marco , Brigidi Patrizia , Pagotto Uberto , Turroni Silvia
Published: December 2022

Background

Obesity and related co-morbidities represent a major health challenge nowadays, with a rapidly increasing incidence worldwide. The gut microbiome has recently emerged as a key modifier of human health that can affect the development and progression of obesity, largely due to its involvement in the regulation of food intake and metabolism. However, there are still few studies that have in-depth explored the functionality of the human gut microbiome in obesity and even fewer that have examined its relationship to eating behaviors.

Methods

In an attempt to advance our knowledge of the gut-microbiome-brain axis in the obese phenotype, we thoroughly characterized the gut microbiome signatures of obesity in a well-phenotyped Italian female cohort from the NeuroFAST and MyNewGut EU FP7 projects. Fecal samples were collected from 63 overweight/obese and 37 normal-weight women and analyzed via a multi-omics approach combining 16S rRNA amplicon sequencing, metagenomics, metatranscriptomics, and lipidomics. Associations with anthropometric, clinical, biochemical, and nutritional data were then sought, with particular attention to cognitive and behavioral domains of eating.

Results

We identified four compositional clusters of the gut microbiome in our cohort that, although not distinctly associated with weight status, correlated differently with eating habits and behaviors. These clusters also differed in functional features, i.e., transcriptional activity and fecal metabolites. In particular, obese women with uncontrolled eating behavior were mostly characterized by low-diversity microbial steady states, with few and poorly interconnected species (e.g., Ruminococcus torques and Bifidobacterium spp.), which exhibited low transcriptional activity, especially of genes involved in secondary bile acid biosynthesis and neuroendocrine signaling (i.e., production of neurotransmitters, indoles and ligands for cannabinoid receptors). Consistently, high amounts of primary bile acids as well as sterols were found in their feces.

Conclusions

By finding peculiar gut microbiome profiles associated with eating patterns, we laid the foundation for elucidating gut-brain axis communication in the obese phenotype. Subject to confirmation of the hypotheses herein generated, our work could help guide the design of microbiome-based precision interventions, aimed at rewiring microbial networks to support a healthy diet-microbiome-gut-brain axis, thus counteracting obesity and related complications.
Distinct metabolic biomarkers to distinguish IgG4-related disease from Sjogren’s syndrome and pancreatic cancer and predict disease prognosis
Authors: Yan Songxin , Peng Yu , Wu Ziyan , Cheng Linlin , Li Haolong , Xu Honglin , Huang Yuan , Zhang Wen , Li Yongzhe
Published: December 2022

Background

The pathogenesis of immunoglobulin G4-related disease (IgG4-RD) remains unclear. IgG4-RD often mimics other diseases, including pancreatic cancer (PC) and Sjogren’s syndrome (SS), which may easily lead to misdiagnosis. This study was performed to explore the metabolite changes and potential biomarkers of IgG4-RD and other misdiagnosed diseases.

Methods

Untargeted liquid chromatography–tandem mass spectrometry metabolomics profiling of plasma samples from a cohort comprising healthy controls (HCs) and patients with IgG4-RD (n = 87), PC (n = 33), and SS (n = 31) was performed. A random forest machine learning model was used to verify the relevance of the identified metabolites in the diagnosis of different diseases and the prediction of disease prognosis.

Results

The ATP-binding cassette transporter pathway was found to be most closely related to IgG4-RD, which was significantly up-regulated in the IgG4-RD group than in all the matched groups. Five metabolites were proved to be valuable biomarkers for IgG4-RD. Caftaric acid, maltotetraose, d-glutamic acid, 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphoserine, and hydroxyproline were useful in distinguishing between IgG4-RD, PC, SS, and HC [area under the curve (AUC) = 1]. A combination of phenylalanine betaine, 1-(1z-hexadecenyl)-sn-glycero-3-phosphocholine, Pi 40:8, uracil, and N1-methyl-2-pyridone-5-carboxamide showed a moderate value in predicting relapse in patients with IgG4-RD (AUC = 0.8).

Conclusions

Our findings revealed the metabolite changes of IgG4-RD and provide new insights for deepening our understanding of IgG4-RD despite the lack of validation in external cohorts. Metabolomic biomarkers have significance in the clinical diagnosis and disease prognosis of IgG4-RD.
Ethical and regulatory issues of stem cell-derived 3-dimensional organoid and tissue therapy for personalised regenerative medicine
Authors: Harris Alexander R. , Walker Mary Jean , Gilbert Frederic
Published: December 2022

Background

Regenerative medicine has the potential to treat genetic disorders and replace damaged or missing tissue. The use of donor or animal tissue raises many well-known issues, including limited tissue availability, the possibility of rejection and patient infection. Stem cell therapy raised hope of overcoming these issues, but created new risks including tumour formation and limited benefit if the desired target tissue does not form. The recent development of 3-dimensional tissues, including organoids, allows the creation of more complex tissues for personalised regenerative medicine.

Methods

This article details the potential health risks of 3-dimensional organoid and tissue therapy versus dissociated stem cell therapy. The current ethical and regulatory issues surrounding 3-dimensional organoid and tissue therapy are presented with a focus on the highly influential FDA and International Society of Stem Cell Research (ISSCR) guidelines.

Conclusions

The potential use of 3-dimensional organoid and tissue therapy may deliver greater patient benefits than other regenerative medicine approaches, but raises new health and ethical risks. Preclinical testing of these therapies will not mitigate some of their risks; they may only be understood after first-in-human trials. The potential irreversibility and high risk of these therapies affects how clinical trials should be structured, including post-trial care for participants.
Protective effects of Gypenoside XVII against cerebral ischemia/reperfusion injury via SIRT1-FOXO3A- and Hif1a-BNIP3-mediated mitochondrial autophagy
Authors: Xie Weijie , Zhu Ting , Zhang Shuxia , Sun Xiaobo
Published: December 2022

Background

Mitochondrial autophagy maintains mitochondrial function and cellular homeostasis and plays a critical role in the pathological process of cerebral ischemia/reperfusion injury (CIRI). Whether Gypenoside XVII (GP17) has regulatory effects on mitochondrial autophagy against CIRI remains unclear. The purpose of this study was to investigate the pharmacodynamic effects and mechanisms of GP17 on mitochondrial autophagy after CIRI.

Methods

A rat middle cerebral artery occlusion/reperfusion (MCAO/R) model was used to assess the effects of GP17 against CIRI and to explore the underlying mechanisms. An oxygen-glucose deprivation/reoxygenation (OGD/R) cell model was used to verify the ameliorative effects on mitochondrial damage and to probe the autophagy pathways involved in combating neural injuries.

Results

The in vivo results showed that GP17 significantly improved mitochondrial metabolic functions and suppressed cerebral ischemic injury, possibly via the autophagy pathway. Further research revealed that GP17 maintains moderate activation of autophagy under ischemic and OGD conditions, producing neuroprotective effects against CIRI, and that the regulation of mitochondrial autophagy is associated with crosstalk between the SIRT1-FOXO3A and Hif1a-BNIP3 signalling pathway that is partially eliminated by the specific inhibitors AGK-7 and 2-ME.

Conclusion

Overall, this work offers new insights into the mechanisms by which GP17 protects against CIRI and highlights the potential of therapy with Notoginseng leaf triterpene compounds as a novel clinical strategy in humans.
Non-invasive intravoxel incoherent motion MRI in prediction of histopathological response to neoadjuvant chemotherapy and survival outcome in osteosarcoma at the time of diagnosis
Authors: Baidya Kayal Esha , Bakhshi Sameer , Kandasamy Devasenathipathy , Sharma Mehar Chand , Khan Shah Alam , Kumar Venkatesan Sampath , Khare Kedar , Sharma Raju , Mehndiratta Amit
Published: December 2022

Background

Early prediction of response to neoadjuvant chemotherapy (NACT) is important to aid personalized treatment in osteosarcoma. Diffusion-weighted Intravoxel Incoherent Motion (IVIM) MRI was used to evaluate the predictive value for response to NACT and survival outcome in osteosarcoma.

Methods

Total fifty-five patients with biopsy-proven osteosarcoma were recruited prospectively, among them 35 patients were further analysed. Patients underwent 3 cycles of NACT (Cisplatin + Doxorubicin) followed by surgery and response adapted adjuvant chemotherapy. Treatment outcomes were histopathological response to NACT (good-response ≥ 50% necrosis and poor-response < 50% necrosis) and survival outcome (event-free survival (EFS) and overall survival (OS)). IVIM MRI was acquired at 1.5T at baseline (t0), after 1-cycle (t1) and after 3-cycles (t2) of NACT. Quantitative IVIM parameters (D, D*, f&D*.f) were estimated using advanced state-of-the-art spatial penalty based IVIM analysis method bi-exponential model with total-variation penalty function (BETV) at 3 time-points and histogram analysis was performed.

Results

Good-responders: Poor-responders ratio was 13 (37%):22 (63%). EFS and OS were 31% and 69% with 16.27 and 25.9 months of median duration respectively. For predicting poor-response to NACT, IVIM parameters showed AUC = 0.87, Sensitivity = 86%, Specificity = 77% at t0, and AUC = 0.96, Sensitivity = 86%, Specificity = 100% at t1. Multivariate Cox regression analysis showed smaller tumour volume (HR = 1.002,p = 0.001) higherADC-25th-percentile (HR = 0.047,p = 0.005) &D-Mean (HR = 0.1,p = 0.023) and lowerD*-Mean (HR = 1.052,p = 0.039) were independent predictors of longer EFS (log-rankp-values: 0.054, 0.0034, 0.0017, 0.0019 respectively) and non-metastatic disease (HR = 4.33,p < 10–3), smaller tumour-volume (HR = 1.001,p = 0.042), lowerD*-Mean (HR = 1.045,p = 0.056) and higherD*.f-skewness (HR = 0.544,p = 0.048) were independent predictors of longer OS (log-rankp-values: < 10–3, 0.07, < 10–3, 0.019 respectively).

Conclusion

IVIM parameters obtained with a 1.5T scanner along with novel BETV method and their histogram analysis indicating tumour heterogeneity were informative in characterizing NACT response and survival outcome in osteosarcoma.
Describing the safety of abortion at the population level using network-based survey approaches
Authors: Rossier Clémentine , Owolabi Onikepe , Kouanda Seni , Bangha Martin , Kim Caron R. , Ganatra Bela , Feehan Dennis , Breen Casey , Zan Moussa , Compaoré Rachidatou , Baguiya Adama , Ouédraogo Ramatou , Oduor Clement , Bagnoa Vincent , Athero Sherine
Published: December 2022

Background

Despite the negative impact of unsafe abortions on women's health and rights, the degree of abortion safety remains strikingly undocumented for a large share of abortions globally. Data on how women induce abortions (method, setting, provider) are central to the measurement of abortion safety. However, health-facility statistics and direct questioning in population surveys do not yield representative data on abortion care seeking pathways in settings where access to abortion services is highly restricted. Recent developments in survey methodologies to study stigmatized / illegal behaviour and hidden populations rely on the fact that such information circulates within social networks; however, such efforts have yet to give convincing results for unsafe abortions.

Objective

This article presents the protocol of a study whose purpose is to apply and develop further two network-based methods to contribute to the generation of reliable population-level information on the safety of abortions in contexts where access to legal abortion services is highly restricted.

Methods

This study plans to obtain population-level data on abortion care seeking in two Health and Demographic Surveillance Systems in urban Kenya and rural Burkina Faso by applying two methods: Anonymous Third-Party Reporting (ATPR) (also known as confidantes’ method) and Respondent Driven Sampling (RDS). We will conduct a mixed methods formative study to determine whether these network-based approaches are pertinent in the study contexts. The ATPR will be refined notably by incorporating elements of the Network Scale-Up Method (NSUM) to correct or account for certain of its biases (transmission, barrier, social desirability, selection). The RDS will provide reliable alternative estimates of abortion safety if large samples and equilibrium can be reached; an RDS multiplex variant (also including social referents) will be tested.

Discussion

This study aims at documenting abortion safety in two local sites using ATPR and RDS. If successful, it will provide data on the safety profiles of abortion seekers across sociodemographic categories in two contrasted settings in sub-Saharan Africa. It will advance the formative research needed to determine whether ATPR and RDS are applicable or not in a given context. It will improve the questionnaire and correcting factors for the ATPR, improve the capacity of RDS to produce quasi-representative data on abortion safety, and advance the validation of both methods.
Ureteral tumor with morphological features analogous to phyllodes tumor: a unique case with concomitant urothelial carcinoma
Authors: Zhou Wei , Dang Linlin , Chong Chuangang , Cheng Xiankui , Qin Yejun , Su Wenjing
Published: December 2022

Background

Phyllodes tumors belong to a spectrum of biphasic fibroepithelial lesions and are most commonly found in the breast. They are extremely rare in the urinary tract and only one case of bladder phyllodes tumor has been reported.

Case presentation

We present a 69-year-old man with gross hematuria without an apparent cause. Computed tomography-urography and cystoscopic examination revealed a 5 × 4 cm lesion in the right ureteral orifice. He underwent a laparoscopic nephroureterectomy and partial cystectomy. Postoperative pathology confirmed a leaf-like structure consisting of myxoid stroma and peripheral urothelium. Stromal cells were spindle-shaped and stellate in appearance with no conspicuous cytological atypia or mitosis. The outlining urothelium had varying degrees of dysplasia, while in areas with moderate-to-severe dysplasia, active mitotic activity, abnormal giant cells, and focal early infiltration were observed. Overall, this case had the morphological features of benign phyllodes tumors and concomitant invasive urothelial carcinoma inside. The patient remained disease-free at 7 months after surgery.

Conclusion

We report the first ureteral tumor with the morphological characteristics of a phyllodes tumor and concomitant invasive urothelial carcinoma inside. Considering the potential for local recurrence of phyllodes tumors and invasive urothelial carcinoma, long-term clinical and radiological follow-up of such lesions are advisable.
Machine learning models predict overall survival and progression free survival of non-surgical esophageal cancer patients with chemoradiotherapy based on CT image radiomics signatures
Authors: Cui Yongbin , Li Zhengjiang , Xiang Mingyue , Han Dali , Yin Yong , Ma Changsheng
Published: December 2022

Purpose

To construct machine learning models for predicting progression free survival (PFS) and overall survival (OS) with esophageal squamous cell carcinoma (ESCC) patients.

Methods

204 ESCC patients were randomly divided into training cohort (n = 143) and test cohort (n = 61) according to the ratio of 7:3. Two radiomics models were constructed by radiomics features, which were selected by LASSO Cox model to predict PFS and OS, respectively. Clinical features were selected by univariate and multivariate Cox proportional hazards model (p < 0.05). Combined radiomics and clinical model was developed by selected clinical and radiomics features. The receiver operating characteristic curve, Kaplan Meier curve and nomogram were used to display the capability of constructed models.

Results

There were 944 radiomics features extracted based on volume of interest in CT images. There were six radiomics features and seven clinical features for PFS prediction and three radiomics features and three clinical features for OS prediction; The radiomics models showed general performance in training cohort and test cohort for prediction for prediction PFS (AUC, 0.664, 0.676. C-index, 0.65, 0.64) and OS (AUC, 0.634, 0.646.C-index, 0.64, 0.65). The combined models displayed high performance in training cohort and test cohort for prediction PFS (AUC, 0.856, 0.833. C-index, 0.81, 0.79) and OS (AUC, 0.742, 0.768. C-index, 0.72, 0.71).

Conclusion

We developed combined radiomics and clinical machine learning models with better performance than radiomics or clinical alone, which were used to accurate predict 3 years PFS and OS of non-surgical ESCC patients. The prediction results could provide a reference for clinical decision.
Traumatic blunt thoracic aortic injury: a 10-year single-center retrospective analysis
Authors: Sun Jingwei , Ren Kai , Zhang Liyun , Xue Chao , Duan Weixun , Liu Jincheng , Cong Ren
Published: December 2022

Background

Approximately 80% of patients with blunt thoracic aortic injury (BTAI) die before reaching the hospital. Most people who survive the initial injury eventually die without appropriate treatment. This study analyzed and reported the treatment strategy of a single center for BTAI in the last 10 years and the early and middle clinical results.

Methods

This retrospective study included patients diagnosed with BTAI at Xijing Hospital from 2013 to 2022. All inpatients with BTAI aged ≥ 18 years were included in this study. The clinical data, imaging findings, and follow-up results were retrospectively collected and analyzed. The Kaplan–Meier curve and multivariate logistic regression were used to compare survivors and nonsurvivors.

Results

A total of 72 patients (57% men) were diagnosed with BTAI, with a mean age of 54.2 ± 9.1 years. The injury severity score was 24.3 ± 18, with Grade I BTAI1 (1.4%), Grade II 17 (23.6%), Grade III 52 (72.2%), and Grade IV 2 (2.8%) aortic injuries. Traffic accidents were the main cause of BTAI in 32 patients (44.4%). Most patients had trauma, 37 had rib fractures (51.4%), Sixty patients (83.3%) underwent thoracic endovascular aortic repair (TEVAR) surgery, eight (11.1%) underwent conservative treatment, and only four (5.6%) underwent open surgery. The overall hospitalization mortality was 12.5%. In multivariate logistic regression, elevated creatinine levels (P = 0.041) and high Glasgow coma scale (GCS) score (P = 0.004) were the predictors of hospital mortality. The median follow-up period was 57 (28–87) months. During the follow-up period, all-cause mortality was 5.6% and no aortic-related deaths were reported. Three patients (4.2%) needed secondary surgery and two of them underwent endovascular repair.

Conclusion

Although TEVAR surgery may be associated with intra- or postoperative dissection rupture or serious complications in the treatment of Grade III BTAI, the incidence rate was only 8.9%. Nevertheless, TEVAR surgery remains a safe and feasible approach for the treatment of Grade II or III BTAI, and surgical treatment should be considered first,. A high GCS score and elevated creatinine levels in the emergency department were closely associated with hospital mortality. Younger patients need long-term follow-up after TEVAR.
Quercetin alleviates cyclophosphamide-induced premature ovarian insufficiency in mice by reducing mitochondrial oxidative stress and pyroptosis in granulosa cells
Authors: Chen Yun , Zhao Ying , Miao Chenyun , Yang Liuqing , Wang Ruye , Chen Bixia , Zhang Qin
Published: December 2022

Background

Exposure to cyclophosphamide (CTX) induces premature ovarian insufficiency (POI). Quercetin is a natural flavonoid that exhibits anti-inflammatory and antioxidant properties, and its antioxidant activity is correlated with POI. However, the mechanism underlying its protective role in CTX-induced ovarian dysfunction is unclear. This study aimed to explore whether quercetin can protect ovarian reserves by activating mitochondrial biogenesis and inhibiting pyroptosis.

Methods

Thirty-six female C57BL/6 mice were randomly subdivided into six groups. Except for the control group, all groups were injected with 90 mg/kg CTX to establish a POI model and further treated with coenzyme 10 or various doses of quercetin. The mice were sacrificed 48 h after 10 IU pregnant mare serum gonadotropin was injected four weeks after treatments. We used enzyme-linked immunosorbent assays to detect serum hormone expression and light and transmission electron microscopy to assess ovarian tissue morphology and mitochondria. Additionally, we tested oxidant and antioxidant levels in ovarian tissues and mitochondrial function in granulosa cells (GCs). The expression of mitochondrial biogenesis and pyroptosis-related proteins and mRNA was analyzed using western blotting and RT-qPCR.

Results

Quercetin elevated serum anti-Müllerian hormone, estradiol, and progesterone levels, decreased serum follicle-stimulating hormone and luteinizing hormone levels, and alleviated ovarian pathology. It reduced the mitochondrial DNA content and mitochondrial membrane potential. Furthermore, it upregulated ATP levels and the mRNA and protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), mitochondrial transcription factor A, and superoxide dismutase 2. In addition, it suppressed NOD-like receptor pyrin domain containing 3, caspase-1, interleukin-1β, and gasdermin D levels in the GCs of POI mice.

Conclusions

Quercetin protected the ovarian reserve from CTX-induced ovarian damage by reversing mitochondrial dysfunction and activating mitochondrial biogenesis via the PGC1-α pathway. Moreover, quercetin may improve ovarian functions by downregulating pyroptosis in the CTX-induced POI model. Thus, quercetin can be considered a potential agent for treating POI.
A good use of time? Providing evidence for how effort is invested in primary and secondary outcome data collection in trials
Authors: Gardner Heidi , Elfeky Adel , Pickles David , Dawson Annabel , Gillies Katie , Warwick Violet , Treweek Shaun
Published: December 2022

Background

Data collection is a substantial part of trial workload for participants and staff alike. How these hours of work are spent is important because stakeholders are more interested in some outcomes than others. The ORINOCO study compared the time spent collecting primary outcome data to the time spent collecting secondary outcome data in a cohort of trials.

Methods

We searched PubMed for phase III trials indexed between 2015 and 2019. From these, we randomly selected 120 trials evaluating a therapeutic intervention plus an additional random selection of 20 trials evaluating a public health intervention. We also added eligible trials from a cohort of 189 trials in rheumatology that had used the same core outcome set.

We then obtained the time taken to collect primary and secondary outcomes in each trial. We used a hierarchy of methods that included data in trial reports, contacting the trial team and approaching individuals with experience of using the identified outcome measures. We calculated the primary to secondary data collection time ratio and notional data collection cost for each included trial.

Results

We included 161 trials (120 phase III; 21 core outcome set; 20 public health), which together collected 230 primary and 688 secondary outcomes. Full primary and secondary timing data were obtained for 134 trials (100 phase III; 17 core outcome set; 17 public health). The median time spent on primaries was 56.1 h (range: 0.0–10,746.7, IQR: 226.89) and the median time spent on secondaries was 190.7 hours (range: 0.0–1,356,832.9, IQR: 617.6). The median primary to secondary data collection time ratio was 1.0:3.0 (i.e. for every minute spent on primary outcomes, 3.0 were spent on secondaries). The ratio varied by trial type: phase III trials were 1.0:3.1, core outcome set 1.0:3.4 and public health trials 1.0:2.2. The median notional overall data collection cost was £8015.73 (range: £52.90–£31,899,140.70, IQR: £20,096.64).

Conclusions

Depending on trial type, between two and three times as much time is spent collecting secondary outcome data than collecting primary outcome data. Trial teams should explicitly consider how long it will take to collect the data for an outcome and decide whether that time is worth it given importance of the outcome to the trial.
A mental health-informed, online health promotion programme targeting physical activity and healthy eating for adults aged 60+ years: study protocol for the MovingTogether randomised controlled trial
Authors: Mastrogiovanni Chiara , Rosenbaum Simon , Delbaere Kim , Tiedemann Anne , Teasdale Scott , McGavin Annaliese , Briggs Nancy , McKeon Grace
Published: December 2022

Background

The COVID-19 pandemic and associated social distancing regulations have led to an increased risk of social isolation and physical inactivity, particularly among older adults. The benefits of physical activity for reducing fall risk and improving mood and mental functioning have been well documented. The aim of this trial is to investigate the effect of the MovingTogether programme on psychological distress (primary outcome) and physical activity, social capital, cognition, concern about falling, loneliness, physical functioning, quality of life and physical activity enjoyment (secondary outcomes).

Methods

A randomised controlled trial with a waitlist control will be conducted, recruiting 80 adults aged 60+ years with access to Facebook and a computer or tablet and not currently meeting the aerobic physical activity guidelines. Randomisation will be completed using REDCap. The intervention group (n = 40) will join a private Facebook group where allied health facilitators will provide targeted healthy lifestyle education throughout the 10-week programme with weekly telehealth group calls. Intervention participants will also be provided access to tailored strength and aerobic exercise guidance and an evidence-based eHealth balance exercise programme. Psychological distress and secondary outcomes will be assessed at baseline, 11 weeks (post-intervention) and 16 weeks (1-month follow-up). Linear mixed models will be applied for each outcome measure as per an intention-to-treat approach to determine the between-group differences. Secondary analyses are planned in people with greater adherence and those with higher psychological distress.

Discussion

COVID-19 has highlighted the need for scalable, effective and novel methods to improve and protect the health of older adults. The integration of an evidence-based fall prevention programme with a mental health-informed online health promotion programme may help to improve mental and physical health outcomes among older adults.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621001322820p. Registered on 29 September 2021
Effectiveness of a 6-week specific rehabilitation program combining education and exercises on walking capacity in patients with lumbar spinal stenosis with neurogenic claudication: a randomized controlled clinical trial protocol
Authors: Houle Mariève , Tétreau Charles , Châtillon Claude-Édouard , Marchand Andrée-Anne , Descarreaux Martin
Published: December 2022

Background

Lumbar spinal stenosis (LSS) causing neurogenic claudication (NC) is a leading cause of disability which is intimately related to a decrease in walking capacity. Walking limitation has negative physical and mental impacts on patients. Recent guidelines recommend the use of conservative treatment options such as exercises before considering surgery. Unfortunately, dedicated healthcare resources for the conservative management of patients with LSS causing NC are uncommon. Thus, it is important to develop accessible and specific rehabilitation programs aimed at improving patients’ self-management, especially with regard to walking capacity. The aim of this study is to evaluate the effectiveness of a 6-week specific rehabilitation program combining education and exercises on walking capacity in patients with LSS causing NC.

Methods/design

This is a prospective randomized controlled parallel-group clinical trial. Sixty-six patients with LSS causing NC will be recruited from identified clinics and local advertisements. The intervention group will receive standardized education and specific exercises while the control group will only receive a standardized education. The program in both groups will last for 6 weeks with 5 evaluation time points (baseline, week 2, week 4, week 6, and week 12). The primary outcome will be walking capacity measured with the Self-Paced Walking Test, and the secondary outcomes will be back and leg pain intensity, LSS-related disability, self-efficacy, level of physical activity, anxiety, depression, gait pattern characteristics, balance, and global perceived change.

Discussion

This study will assess the effectiveness of a 6-week specific rehabilitation program combining education and exercises on walking capacity in patients with LSS causing NC. By measuring objective gait pattern characteristics, the study will also provide new information about the impact of NC on gait pattern that could eventually improve the evaluation and the management of LSS.

Trial registration

ClinicalTrials.govNCT05513326. Registered on August 22, 2022