bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of elastography to diagnose adenomyosis and evaluate the degree of dysmenorrhea: a prospective observational study
Authors: Ren Qianhui , Dong Xiangyi , Yuan Ming , Jiao Xue , Sun Hao , Pan Zangyu , Wang Xinyu , Tao Guowei , Guoyun Wang
Published: October 2023

Background

To determine whether there is a correlation between stiffness measured by strain elastography and the severity of dysmenorrhea and to determine the value of elastography in evaluating severe dysmenorrhea in patients with adenomyosis.

Methods

The correlation between tissue stiffness and dysmenorrhea was analyzed by performing elastography on premenopausal women diagnosed with adenomyosis. Expression levels of transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA), and protein gene product 9.5 (PGP9.5) were detected by immunohistochemistry; the correlation of TGF-β and α-SMA levels with the tissue stiffness and the degree of fibrosis was further analyzed. Also, the relationship of the PGP9.5 expression level with the tissue stiffness and degree of dysmenorrhea was determined.

Results

The degree of dysmenorrhea was significantly positively correlated with lesion stiffness in patients with adenomyosis but not with the uterine or lesion volume. The cutoff for the strain ratio was > 1.36 between the adenomyosis and control groups, with an area under the curve (AUC) of 0.987. For severe dysmenorrhea, the cutoff for the strain ratio was > 1.65 in patients with adenomyosis, with an AUC of 0.849. TGF-β, α-SMA, and PGP9.5 expression levels were higher in adenomyotic lesions than in the endometrium of the adenomyosis and control groups. Both TGF-β and α-SMA levels were positively correlated with the tissue stiffness and degree of fibrosis. Additionally, the expression level of PGP9.5 showed a positive correlation with the tissue stiffness and degree of dysmenorrhea.

Conclusions

Elastography can be used to evaluate the degree of dysmenorrhea; the greater the tissue stiffness, the greater the degree of dysmenorrhea. In addition, elastography performed well in the diagnosis of adenomyosis and the evaluation of severe dysmenorrhea in patients with adenomyosis.
HCG18, LEF1AS1 and lncCEACAM21 as biomarkers of disease severity in the peripheral blood mononuclear cells of COVID-19 patients
Authors: Greco Simona , Made’ Alisia , Mutoli Martina , Zhang Lu , Piella Santiago Nicolas , Vausort Mélanie , Lumley Andrew I. , Beltrami Antonio Paolo , Srivastava Prashant Kumar , Milani Valentina , Boveri Sara , Ranucci Marco , Renna Laura Valentina , Firat Hüseyin , Bruno Antonino , Spinetti Gaia , Emanueli Costanza , Devaux Yvan , Martelli Fabio
Published: October 2023

Background

Even after 3 years from SARS-CoV-2 identification, COVID-19 is still a persistent and dangerous global infectious disease. Significant improvements in our understanding of the disease pathophysiology have now been achieved. Nonetheless, reliable and accurate biomarkers for the early stratification of COVID-19 severity are still lacking. Long noncoding RNAs (LncRNAs) are ncRNAs longer than 200 nucleotides, regulating the transcription and translation of protein‐coding genes and they can be found in the peripheral blood, thus holding a promising biomarker potential. Specifically, peripheral blood mononuclear cells (PBMCs) have emerged as a source of indirect biomarkers mirroring the conditions of tissues: they include monocytes, B and T lymphocytes, and natural killer T cells (NKT), being highly informative for immune-related events.

Methods

We profiled by RNA-Sequencing a panel of 2906 lncRNAs to investigate their modulation in PBMCs of a pilot group of COVID-19 patients, followed by qPCR validation in 111 hospitalized COVID-19 patients.

Results

The levels of four lncRNAs were found to be decreased in association with COVID-19 mortality and disease severity: HLA Complex Group 18-242 and -244 (HCG18-242 and HCG18-244), Lymphoid Enhancer Binding Factor 1-antisense 1 (LEF1-AS1) and lncCEACAM21 (i.e. ENST00000601116.5, a lncRNA in the CEACAM21 locus). Interestingly, these deregulations were confirmed in an independent patient group of hospitalized patients and by the re-analysis of publicly available single-cell transcriptome datasets. The identified lncRNAs were expressed in all of the PBMC cell types and inversely correlated with the neutrophil/lymphocyte ratio (NLR), an inflammatory marker. In vitro, the expression of LEF1-AS1 and lncCEACAM21 was decreased upon THP-1 monocytes exposure to a relevant stimulus, hypoxia.

Conclusion

The identified COVID-19-lncRNAs are proposed as potential innovative biomarkers of COVID-19 severity and mortality.
Mitochondrial modulation with leriglitazone as a potential treatment for Rett syndrome
Authors: Musokhranova Uliana , Grau Cristina , Vergara Cristina , Rodríguez-Pascau Laura , Xiol Clara , Castells Alba A. , Alcántara Soledad , Rodríguez-Pombo Pilar , Pizcueta Pilar , Martinell Marc , García-Cazorla Angels , Oyarzábal Alfonso
Published: October 2023

Background

Rett syndrome is a neuropediatric disease occurring due to mutations in MECP2 and characterized by a regression in the neuronal development following a normal postnatal growth, which results in the loss of acquired capabilities such as speech or purposeful usage of hands. While altered neurotransmission and brain development are the center of its pathophysiology, alterations in mitochondrial performance have been previously outlined, shaping it as an attractive target for the disease treatment.

Methods

We have thoroughly described mitochondrial performance in two Rett models, patients’ primary fibroblasts and female Mecp2tm1.1Bird−/+ mice brain, discriminating between different brain areas. The characterization was made according to their bioenergetics function, oxidative stress, network dynamics or ultrastructure. Building on that, we have studied the effect of leriglitazone, a PPARγ agonist, in the modulation of mitochondrial performance. For that, we treated Rett female mice with 75 mg/kg/day leriglitazone from weaning until sacrifice at 7 months, studying both the mitochondrial performance changes and their consequences on the mice phenotype. Finally, we studied its effect on neuroinflammation based on the presence of reactive glia by immunohistochemistry and through a cytokine panel.

Results

We have described mitochondrial alterations in Rett fibroblasts regarding both shape and bioenergetic functions, as they displayed less interconnected and shorter mitochondria and reduced ATP production along with increased oxidative stress. The bioenergetic alterations were recalled in Rett mice models, being especially significant in cerebellum, already detectable in pre-symptomatic stages. Treatment with leriglitazone recovered the bioenergetic alterations both in Rett fibroblasts and female mice and exerted an anti-inflammatory effect in the latest, resulting in the amelioration of the mice phenotype both in general condition and exploratory activity.

Conclusions

Our studies confirm the mitochondrial dysfunction in Rett syndrome, setting the differences through brain areas and disease stages. Its modulation through leriglitazone is a potential treatment for this disorder, along with other diseases with mitochondrial involvement. This work constitutes the preclinical necessary evidence to lead to a clinical trial.
Psychometric properties of the Clinical Assessment Interview for Negative Symptoms (CAINS) in patients with depression and its relationship to affective symptoms
Authors: Bengtsson Johan , Rad Parya , Cernvall Martin , Bodén Robert
Published: October 2023

Background

There is a conceptual overlap between negative and depressive symptoms, requiring further exploration to advance the understanding of negative symptoms. The aim of this study was to examine psychometric properties of the Clinical Assessment Interview for Negative Symptoms (CAINS) in patients with depression, and to explore the relationship between the negative and affective symptoms domains.

Methods

Fifty-one patients with a depressive episode were included and interviewed with the CAINS and the Brief Psychiatric Rating Scale—Expanded (BPRS-E). Self-reported depressive symptoms were collected with the Montgomery-Asberg Depression Rating Scale (MADRS-S). Inter-rater agreement, internal consistency and validity measures were examined, as were correlations between negative and affective symptoms.

Results

The intraclass correlation for the CAINS motivation and pleasure subscale (CAINS-MAP) was 0.98 (95% CI 0.96–0.99) and that for the expressional subscale (CAINS-EXP) was 0.81 (95% CI 0.67–0.89). Cronbach’s alpha was 0.71 (95% CI 0.57–0.82) for the CAINS-MAP and 0.86 (95% CI 0.79–0.92) for the CAINS-EXP. The correlation with the negative symptoms subscale of the BPRS-E was 0.35 (p = 0.011, blinded/different raters) or 0.55 (p < 0.001, not blinded/same rater). The CAINS-MAP correlated with the affective symptoms subscale of the BPRS-E (r = 0.39, p = 0.005) and the MADRS-S total score (r = 0.50, p < 0.001), but not with anxiety symptoms.

Conclusions

Negative symptoms in depression can be assessed with the CAINS with good inter-rater agreement and acceptable internal consistency and validity. There are associations between negative and depressive symptoms that call for further exploration.
The chromatin architectural regulator SND1 mediates metastasis in triple-negative breast cancer by promoting CDH1 gene methylation
Authors: Zhang Huibian , Gao Min , Zhao Wenying , Yu Lin
Published: October 2023

Background

SND1 participates in tumorigenesis, tumour invasion and metastasis in different cancers. Previous studies have shown that SND1 can promote the invasion and migration of breast cancer cells. Triple-negative breast cancer (TNBC) is a specific breast cancer subtype with high metastatic potential and poor prognosis. However, the specific roles and mechanisms of SND1 in TNBC metastasis remain unaddressed.

Methods

Immunostaining was used to detect the SND1 expression in tissue samples of 58 TNBC and 10 glioblastomas (GBM) as positive control. The correlation between SND1 expression and patient prognosis was assessed using the Kaplan–Meier estimator. The gene expression was evaluated by qRT-PCR, Western blot and immunofluorescence analyses. Gene Ontology analysis, ChIP, a dual-luciferase reporter assay, EMSA, and 3C analysis were applied to identify SND1-activated target genes. Bisulfite sequencing PCR and MeDIP were used to detect DNA methylation. We also used wound healing, Transwell and orthotopic implantation assays to investigate the function of SND1 in TNBC cell migration and invasion.

Results

The data of immunohistochemistry manifested that SND1 is the overexpression in metastasized TNBC and an independent factor for TNBC prognosis. SND1 knockdown inhibited the migration and invasion of TNBC cells. We found that SND1 promotes the metastatic phenotype of TNBC cells by epigenetically altering chromatin conformational interactions, which in turn activates DNMT3A transcription. Then, DNMT3A attenuates CCND1 expression by inducing CCND1 gene methylation, leading to TNBC metastasis.

Conclusion

SND1 can promote the invasion and migration of TNBC cells by promoting DNMT3A expression and suppressing CDH1 activity. SND1 is a potential biomarker and a promising therapeutic target for TNBC.
Therapists’ experiences with implementing new documentation practices for low back pain in electronic health care records: an interview study
Authors: Toftdahl Anne Katrine Skjølstrup , Ibsen Stine , Pape-Haugaard Louise Bilenberg , Riis Allan
Published: October 2023

Objective

Clinical practice is constantly changing with new guidelines being published, changes in patients’ preferences but also by new qualitative requirements for therapists and institutional surveys on delivered care. Electronic health records (EHR) are used for all these purposes. We involved physiotherapists and occupational therapists in an intervention to change documentation practice in their electronic health record for low back pain (LBP) and later evaluated the feasibility of the new health records. The aim of the present study was to explore therapists’ experiences working with the new EHR.

Results

Three themes were identified thru interviews: (I) Facilitators and motivators towards implementation, (II) Changing routines as a group and (III) Obstacles against successful implementation. This study identifies a need for involving therapists and management for successful change of electronic health care records usage in municipalities. However, difficulties were encountered in meeting documentation of practice requirements and obtaining sufficient data quality in the EHR for data to be used for daily use, quality assessment and research. In this small descriptive study, developing an EHR that simultaneously serves treatment plans, quality assessment, and research purposes was not expressed being feasible. Further research in this area is needed.
Novel technique for arterial reconstruction in simultaneous pancreas-kidney transplantation, a randomized clinical trial
Authors: Karar Hassan , Shafiekhani Mojtaba , Mahmoudi Mohamad Mahdi , Azadeh Nazanin , Shamsaeefar Alireza , Nazari Sahar Sohrabi , Jafari Mehran , Ashrafzadeh Kiarash , Esmaeili Maryam , Nikeghbalian Saman , Nikoupour Hamed
Published: October 2023

Introduction

Simultaneous pancreas kidney (SPK) transplantation is an invaluable procedure to enhance the quality of life of insulin-dependent patients with advanced renal disease. The creation of vascular anastomoses of the donor’s pancreas vessels to the recipient’s, is of utmost importance to predict the graft outcome and surgical complications. In the study we introduce a novel technique for arterial reconstruction during SPK transplantation.

Methods

Conventionally, during the SPK transplantation, a so-called Y-graft is anastomosed between donor’s superior mesenteric and splenic artery to the recipient’s right iliac artery. In the study we adopted a new technique by preparing an extra extension using the donor’s carotid artery, to be anastomosed to the Y-graft and the iliac artery. In this non-blinded randomized clinical trial we compared the surgical complications and early outcomes between the 2 groups of patients with the traditional and new arterial reconstruction techniques during 3 months after transplantation.

Results

Thirty adult patients were included in the study. The incidence of pancreatitis, vascular thrombosis and surgical site infection was lower in the new Y-graft and extension technique, which was not statistically significant. However, the calculated Cohen’s d index showed the medium effect of new Y-graft and extension technique on complication after SPK transplantations.

Conclusion

The post-operative complications tend to be lower in the novel arterial reconstruction technique, however a study on a larger patient group is encouraged to confirm our primary results.

Trial registration

The study was registered at the Iranian Registry of Clinical Trials on 12/05/2022; IRCT 20210625051701N2; (http://www.irct.ir/).
Probiotic potential and safety analysis of lactic acid bacteria isolated from Ethiopian traditional fermented foods and beverages
Authors: Amenu Desalegn , Bacha Ketema
Published: October 2023

Background

Probiotics are live microorganisms that effectively combat foodborne pathogens, promoting intestinal health when consumed in sufficient amounts. This study evaluated the probiotic potential and safety of lactic acid bacteria isolated from selected Ethiopian traditional fermented foods and beverages (Kotcho, Bulla, Ergo, Cabbage-Shamita, Borde, and Bukuri). To assess the isolates’ probiotic activity, tolerance, and survival rate under various stressful conditions, including low pH, intestinal inhibitory substances, salt concentration, bile salt, and simulated gastric/intestinal juice. The isolates were also tested for antagonistic activities against common bacterial and fungal pathogens (Staphylococcus aureus, Salmonella Typhimurium, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans) and safety (auto-aggregation, co-aggregation, cell source hydrophobicity, hemolytic activity, DNase, and antibiotic susceptibility). The best probiotic lactic acid bacteria (LAB) were characterized to species level following standard MALDI TOF/mass spectrometry analysis.

Results

A total of 125 potentially probiotic LAB were isolated of which 17 (13.60%) isolates survived low pH (2, 2.5, and 3), bile salt (0.3%), intestinal inhibitory chemicals (phenol, bile, low acidity, pepsin, and pancreas), and simulated gastro-intestinal settings with near 60–94% survival rate. In addition, 11 best LAB isolates were further screened based on additional screening including their antimicrobial efficacy, preservative efficiency, bacteriocin production besides resistance to low acid and bile salts, and survival potential under simulated gastrointestinal conditions. All 11 LAB isolates were resistant to ampicillin, vancomycin, gentamicin, kanamycin, clindamycin, and chloramphenicol, while they were susceptible to streptomycin and tetracycline. The MALDI TOF mass spectrometry analysis result of efficient probiotic LAB grouped them under the genus Pediococcus, Enterococcus, and Lactococcus including Pediococcus pentosaceus, Enterococcus faecium, Lactococcus lactis, and Pediococcus acidilactici.

Conclusion

Ethiopian traditional fermented foods and beverages are good sources of promising probiotic lactic acid bacteria. These isolates could serve as potential starter cultures and bio-preservative for the enhancement of the shelf life of foods. This study established the groundwork for the selection of excellent probiotics for the development and application of LAB for antibacterial action, starter culture production, and preservation activities.
The pseudoenzyme ADPRHL1 affects cardiac function by regulating the ROCK pathway
Authors: Tian Lei , Guo Tianwei , Wu Fujian , Bai Rui , Ai Sinan , Wang Hongyue , Song Yuanxiu , Zhu Min , Jiang Youxu , Ma Shuhong , Zhuang Xiaofeng , Guo Shuzhen
Published: October 2023

Background

Pseudoenzymes, catalytically deficient variants of active enzymes, have a wide range of regulatory functions. ADP-ribosylhydrolase-like 1 (ADPRHL1), a pseudoenzyme belonging to a small group of ADP-ribosylhydrolase enzymes that lacks the amino acid residues necessary for catalytic activity, may have a significant role in heart development based on accumulating evidence. However, the specific function of ADPRHL1 in this process has not been elucidated. To investigate the role of ADPRHL1 in the heart, we generated the first in vitro human embryonic stem cell model with an ADPRHL1 knockout.

Method

Using the CRISPR/Cas9 system, we generated ADPRHL1 knockout in the human embryonic stem cell (hESC) H9 line. The cells were differentiated into cardiomyocytes using a chemically defined and xeno-free method. We employed confocal laser microscopy to detect calcium transients and microelectrode array (MEA) to assess the electrophysiological activity of ADPRHL1 deficiency cardiomyocytes. Additionally, we investigated the cellular mechanism of ADPRHL1 by Bulk RNA sequencing and western blot.

Results

The results indicate that the absence of ADPRHL1 in cardiomyocytes led to adhered abnormally, as well as perturbations in calcium transients and electrophysiological activity. We also revealed that disruption of focal adhesion formation in these cardiomyocytes was due to an excessive upregulation of the ROCK–myosin II pathway. Notably, inhibition of ROCK and myosin II effectively restores focal adhesions in ADPRHL1-deficient cardiomyocytes and improved electrical conduction and calcium activity.

Conclusions

Our findings demonstrate that ADPRHL1 plays a critical role in maintaining the proper function of cardiomyocytes by regulating the ROCK–myosin II pathway, suggesting that it may serve as a potential drug target for the treatment of ADPRHL1-related diseases.
Regulation of self-renewal and senescence in primitive mesenchymal stem cells by Wnt and TGFβ signaling
Authors: Mazzella Matteo , Walker Keegan , Cormier Christina , Kapanowski Michael , Ishmakej Albi , Saifee Azeem , Govind Yashvardhan , Chaudhry G. Rasul
Published: October 2023

Background

The therapeutic application of multipotent mesenchymal stem cells (MSCs) encounters significant challenges, primarily stemming from their inadequate growth and limited self-renewal capabilities. Additionally, as MSCs are propagated, their ability to self-renew declines, and the exact cellular and molecular changes responsible for this are poorly understood. This study aims to uncover the complex molecular mechanisms that govern the self-renewal of primitive (p) MSCs.

Methods

We grew pMSCs using two types of medium, fetal bovine serum (FM) and xeno-free (XM), at both low passage (LP, P3) and high passage (HP, P20). To evaluate LP and HP pMSCs, we examined their physical characteristics, cell surface markers, growth rate, colony-forming ability, BrdU assays for proliferation, telomerase activity, and potential to differentiate into three lineages. Moreover, we conducted RNA-seq to analyze their transcriptome and MNase-seq analysis to investigate nucleosome occupancies.

Results

When grown in FM, pMSCs underwent changes in their cellular morphology, becoming larger and elongated. This was accompanied by a decrease in the expression of CD90 and CD49f, as well as a reduction in CFE, proliferation rate, and telomerase activity. In addition, these cells showed an increased tendency to differentiate into the adipogenic lineage. However, when grown in XM, pMSCs maintained their self-renewal capacity and ability to differentiate into multiple lineages while preserving their fibroblastoid morphology. Transcriptomic analysis showed an upregulation of genes associated with self-renewal, cell cycle regulation, and DNA replication in XM-cultured pMSCs, while senescence-related genes were upregulated in FM-cultured cells. Further analysis demonstrated differential nucleosomal occupancies in self-renewal and senescence-related genes for pMSCs grown in XM and FM, respectively. These findings were confirmed by qRT-PCR analysis, which revealed alterations in the expression of genes related to self-renewal, cell cycle regulation, DNA replication, differentiation, and senescence. To understand the underlying mechanisms, we investigated the involvement of Wnt and TGFβ signaling pathways by modulating them with agonists and antagonists. This experimental manipulation led to the upregulation and downregulation of self-renewal genes in pMSCs, providing further insights into the signaling pathways governing the self-renewal and senescence of pMSCs.

Conclusion

Our study shows that the self-renewal potential of pMSCs is associated with the Wnt pathway, while senescence is linked to TGFβ.
The augmented value of using clinical notes in semi-automated surveillance of deep surgical site infections after colorectal surgery
Authors: Verberk Janneke D.M. , van der Werff Suzanne D. , Weegar Rebecka , Henriksson Aron , Richir Milan C. , Buchli Christian , van Mourik Maaike S.M. , Nauclér Pontus
Published: October 2023

Background

In patients who underwent colorectal surgery, an existing semi-automated surveillance algorithm based on structured data achieves high sensitivity in detecting deep surgical site infections (SSI), however, generates a significant number of false positives. The inclusion of unstructured, clinical narratives to the algorithm may decrease the number of patients requiring manual chart review. The aim of this study was to investigate the performance of this semi-automated surveillance algorithm augmented with a natural language processing (NLP) component to improve positive predictive value (PPV) and thus workload reduction (WR).

Methods

Retrospective, observational cohort study in patients who underwent colorectal surgery from January 1, 2015, through September 30, 2020. NLP was used to detect keyword counts in clinical notes. Several NLP-algorithms were developed with different count input types and classifiers, and added as component to the original semi-automated algorithm. Traditional manual surveillance was compared with the NLP-augmented surveillance algorithms and sensitivity, specificity, PPV and WR were calculated.

Results

From the NLP-augmented models, the decision tree models with discretized counts or binary counts had the best performance (sensitivity 95.1% (95%CI 83.5–99.4%), WR 60.9%) and improved PPV and WR by only 2.6% and 3.6%, respectively, compared to the original algorithm.

Conclusions

The addition of an NLP component to the existing algorithm had modest effect on WR (decrease of 1.4–12.5%), at the cost of sensitivity. For future implementation it will be a trade-off between optimal case-finding techniques versus practical considerations such as acceptability and availability of resources.
The role of short-chain fatty acids (SCFAs) in regulating stress responses, eating behavior, and nutritional state in anorexia nervosa: protocol for a randomized controlled trial
Authors: Quagebeur Robin , Dalile Boushra , Raes Jeroen , Van Oudenhove Lukas , Verbeke Kristin , Vrieze Elske
Published: October 2023

Objective

This protocol proposes investigating the effects of short-chain fatty acids (SCFAs)—namely acetate, propionate, and butyrate—as mediators of microbiota-gut-brain interactions on the acute stress response, eating behavior, and nutritional state in malnourished patients with anorexia nervosa (AN). SCFAs are produced by bacterial fermentation of dietary fiber in the gut and have recently been proposed as crucial mediators of the gut microbiota's effects on the host. Emerging evidence suggests that SCFAs impact human psychobiology through endocrine, neural, and immune pathways and may regulate stress responses and eating behavior.

Method

We will conduct a randomized, triple-blind, placebo-controlled trial in 92 patients with AN. Patients will receive either a placebo or a mixture of SCFAs (acetate propionate, butyrate) using pH-dependent colon-delivery capsules for six weeks. This clinical trial is an add-on to the standard inpatient psychotherapeutic program focusing on nutritional rehabilitation.

Hypotheses

We hypothesize that colonic SCFAs delivery will modulate neuroendocrine, cardiovascular, and subjective responses to an acute laboratory psychosocial stress task. As secondary outcome measures, we will assess alterations in restrictive eating behavior and nutritional status, as reflected by changes in body mass index. Additionally, we will explore changes in microbiota composition, gastrointestinal symptoms, eating disorder psychopathology, and related comorbidities.

Discussion

The findings of this study would enhance our understanding of how gut microbiota-affiliated metabolites, particularly SCFAs, impact the stress response and eating behavior of individuals with AN. It has the potential to provide essential insights into the complex interplay between the gut, stress system, and eating behavior and facilitate new therapeutic targets for stress-related psychiatric disorders.

This protocol is prospectively registered with ClinicalTrials.gov, with trial registration number NCT06064201.
Intratumoral and peritumoral MRI-based radiomics prediction of histopathological grade in soft tissue sarcomas: a two-center study
Authors: Zhang Liyuan , Yang Yang , Wang Ting , Chen Xi , Tang Mingyue , Deng Junnan , Cai Zhen , Cui Wei
Published: October 2023

Objectives

This study aims to develop a model based on intratumoral and peritumoral radiomics from fat-suppressed T2-weighted(FS-T2WI) images to predict the histopathological grade of soft tissue sarcoma (STS).

Methods

This retrospective study included 160 patients with STS from two centers, of which 82 were low-grade and 78were high-grade. Radiomics features were extracted and selected from the region of tumor mass volume (TMV) and peritumoral tumor volume (PTV) respectively. The TMV, PTV, and combined(TM-PTV) radiomics models were established in the training cohort (n = 111)for the prediction of histopathological grade. Finally, a radiomics nomogram was constructed by combining the TM-PTV radiomics signature (Rad-score) and the selected clinical-MRI predictor. The ROC and calibration curves were used to determine the performance of the TMV, PTV, and TM-PTV models in the training and validation cohort (n = 49). The decision curve analysis (DCA) and calibration curves were used to investigate the clinical usefulness and calibration of the nomogram, respectively.

Results

The TMV model, PTV model, and TM-PTV model had AUCs of 0.835, 0.879, and 0.917 in the training cohort and 0.811, 0.756, 0.896 in the validation cohort. The nomogram, including the TM-PTV signatures and peritumoral hyperintensity, achieved good calibration and discrimination with a C-index of 0.948 (95% CI, 0.906 to 0.990) in the training cohort and 0.921 (95% CI, 0.840 to 0.995) in the validation cohort. Decision curve analysis demonstrated the clinical usefulness of the nomogram.

Conclusion

The proposed model based on intratumoral and peritumoral radiomics showed good performance in distinguishing low-grade from high-grade STSs.
Safety design study for energy harvesters
Authors: Gaidai Oleg , Yakimov Vladimir , Wang Fang , Xing Yihan , Zhang Fuxi
Published: October 2023

Modern offshore and onshore green energy engineering includes energy harvesting—as a result, extensive experimental investigations, as well as safety and reliability analysis are crucial for design and engineering. For this study, several wind-tunnel experiments under realistic in situ wind speed conditions have been conducted to examine the performance of galloping energy harvester. Next, a novel structural reliability approach is presented here that is especially well suited for multi-dimensional energy harvesting systems that have been either numerically simulated or analog observed during the representative time lapse, yielding an ergodic system time record. As demonstrated in this study, the advocated methodology may be used for risk assessment of dynamic system structural damage or failure. Furthermore, traditional reliability methodologies dealing with time series do not easily cope with the system’s high dimensionality, along with nonlinear cross-correlations between the system’s components. This study’s objective was to assess state-of-the-art reliability method, allowing efficient extraction of relevant statistical information, even from a limited underlying dataset. The methodology described in this study aims to assist designers when assessing nonlinear multidimensional dynamic energy harvesting system’s failure and hazard risks.
The association between macronutrient intakes and coronavirus disease 2019 (COVID-19) in an Iranian population: applying a dynamical system model
Authors: Hafezi Somayeh Ghiasi , Seifi Najmeh , Bahari Hossein , Mohammadi Maryam , Ghasemabadi Atena , ferns Gordon A. , Farkhani Ehsan Mosa , Ghayour-mobarhan Majid
Published: October 2023

Aims

The possible role of lifestyle including diet on immunity led us to investigate the association between dietary macronutrient intake and COVID-19 in an Iranian population.

Methods

Dietary intakes were recorded in the first phase of the MASHAD cohort study (started in 2007), using a 24-h dietary recall. To determine the COVID-19 incidence, data from all PCR-positive patients in Mashhad were recorded between February 2020 and June 2022. Dietary macronutrients were included in the regression model, adjusting for age and sex. System dynamical models were also applied.

Results

The analysis included 1957 participants, including 193 COVID-19-positive patients. Dietary intakes of non-starch polysaccharides (NSP) and fiber were significantly lower in COVID-19 patients (P < 0.05). After adjusting for age and sex, starch and total sugar were significantly associated with COVID-19 infection ((OR = 1.0008, P = 0.001) and (OR = 1.0006, P = 0.026), respectively). There was also a significant association between dietary fiber intake and hospitalization (OR = 0.99, P = 0.018). In the dynamical system models, dietary intakes of cholesterol, polyunsaturated fatty acids (PUFA), and total sugar above 180.2 mg, 13.11 g, and 79.53 mg, respectively, were associated with an increased susceptibility to COVID-19 infection, while dietary fiber had a protective role.

Conclusion

Dietary intake of starch and total sugars was associated with increased odds of COVID-19, while fiber intake decreased the odds of hospitalization due to COVID-19. The dynamical system models showed that dietary intake of cholesterol, PUFAs, and total sugar was associated with an increased risk of COVID-19, while fiber had a protective role.
Exploring limitations in the induced polarization versus surface conductivity relationship in the case of wetland soils
Authors: Emmanuel Efemena D. , Slater Lee D. , Doro Kennedy O.
Published: October 2023

Recent induced polarization studies suggest that the real part of surface conductivity ([Formula: see text]) scales linearly with the imaginary conductivity ([Formula: see text] = [Formula: see text]) or normalized chargeability (Mn) for a range of soil types. The coefficients of this relationship l and l_Mn ( l = [Formula: see text]/[Formula: see text] or l_Mn = Mn/[Formula: see text]) allow the separation of the surface and electrolytic conductivities from the bulk conductivity. However, the dependence of these constants on varying soil physicochemical properties, including under unsaturated conditions, is yet to be assessed. Using estimates of [Formula: see text] from 18 undisturbed soil samples from a restored wetland and [Formula: see text] measured over a frequency range of 0.01 Hz to 10 kHz, the [Formula: see text] and [Formula: see text] were compared with the laboratory measurements of soil properties. Also, l and l_Mn were calculated for each soil sample and regressed them against the soil properties. We find an apparent dependence of l on soil texture, bulk density, organic matter, and moisture contents, with coefficients of determination ([Formula: see text]) ranging from 0.5 to 0.65 at low frequencies (e.g., 1 Hz) but not at high frequencies (e.g., 936 Hz). This dependence of l on soil texture results from the insensitivity of [Formula: see text] at low frequency to [Formula: see text] and, by implication, to the soil properties controlling [Formula: see text]. In contrast, l_Mn indicates no correlation with the soil properties because Mn is linearly correlated with [Formula: see text] and correlated with the soil properties controlling [Formula: see text]. Our results call for caution on the application of [Formula: see text] at a single frequency as a proxy of [Formula: see text] because [Formula: see text] is not necessarily correlated with [Formula: see text] across all soil types. Although using l_Mn derived from multifrequency measurements overcomes this limitation, field acquisition of spectral information (e.g., up to 1000 Hz) remains a challenge.
Changes in anxiety and depression during the COVID-19 pandemic in the European population: A meta-analysis of changes and associations with restriction policies
Authors: Lok Veeleah , Sjöqvist Hugo , Sidorchuk Anna , Flodin Pär , Osika Walter , Daly Michael , Hyland Philip , Andersen Lars H. , Fallesen Peter , Cabrera Marcelo C. , Knudsen Ann K.S. , Wetherall Karen , Widnall Emily , Groarke Jenny M. , Armour Cherie , Dalman Christina , Hollander Anna-Clara , Niemi Maria
Published: October 2023

Background

Early studies of common mental disorders (CMDs) during the COVID-19 pandemic mainly report increases; however, more recent findings have been mixed. Also, studies assessing the effects of restriction measures on CMDs show varied results. The aim of this meta-analysis was to assess changes in levels of CMDs from pre-/early to during the pandemic and the effects of restriction policies in the European population.

Methods

We searched for studies assessing both pre-pandemic and peri-pandemic self-reported emotional distress and symptoms of depression or anxiety among nationally/regionally representative samples in Europe and collected microdata from those studies. Estimates of corona containment index were related to changes in CMDs using random-effects meta-regression.

Results

Our search strategy resulted in findings from 15 datasets drawn from 8 European countries being included in the meta-analysis. There was no evidence of change in the prevalence of emotional distress, anxiety, or depression from before to during the pandemic; but from early pandemic periods to later periods, there were significant decreases in emotional distress and anxiety. Increased school restrictions and social distancing were associated with small increases in self-reported emotional distress.

Conclusions

Despite initial concerns of increased emotional distress and mental illness due to the COVID-19 pandemic, the results from this meta-analysis indicate that there was a decrease in emotional distress and no change in anxiety or depression in the general population in Europe. Overall, our findings support the importance of strong governance when implementing periodic and robust restriction measures to combat the spread of COVID-19.
Biospecimen Repositories in Low- and Middle-Income Countries: Insights From an American University of Beirut and Memorial Sloan Kettering Collaboration
Authors: Faraj Walid , Robson Mark , Tawil Ayman , Reuter Victor , Mahfouz Rami , Cambria Roy , Saheb Nour , Ferrer Christine S. , Vemuri Shreya , Yaghi Marita , Kanso Mariam , Abdullah Abdul , El Nounou Ghina , Jabbour Mark , Muenkel Kerri , Kaufman Kristopher , Wakim Joe-Max , Badson Sandy , Wilson Roger , Houston Collette , Drobnjak Marija , Hoballah Jamal , Ziyadeh Fuad N. , Zaatari Ghazi , Brennan Murray , O'Reilly Eileen M. , Abu-Alfa Ali K. , Abou-Alfa Ghassan K.
Published: October 2023

PURPOSE

Biobanking helps source tissue and blood for studying cancer genomics. Access to biorepository resources in low- and middle-income countries is lacking. Memorial Sloan Kettering Cancer Center (MSK) and the American University of Beirut (AUB) established a joint tissue biorepository at AUB in Beirut, Lebanon. The undertaking encountered key challenges that were unanticipated.

MATERIALS AND METHODS

Patients age 18 years or older were eligible for enrollment at AUB. After consent, biospecimens were obtained at the time of routine diagnostic and/or therapeutic interventions. Both normal and abnormal tissue and solid and/or liquid specimens were collected from varied body sites. Early on, declining consent was frequently observed, and this was highlighted for investigation to understand potential participants reasoning.

RESULTS

Of 850 patients approached, 704 (70.8%) elected to consent and 293 (29.5%) declined participation. The number of declined consents led to an amendment permitting the documentation of reasons for same. Of 100 potential participants who declined to consent and to whom outreach was undertaken, 63% indicated lack of research awareness and 27% deferral to their primary physician or family member. A financial gain for AUB was cited as concern by 5%, cultural boundaries in 4%, and 1% expressed concern about confidentiality. Of the patients who elected to consent, 682 biospecimens were procured.

CONCLUSION

The AUB-MSK biospecimen repository has provided a unique resource for interrogation. Patient participation rate was high, and analyses of those who elected not to consent (29%) provide important insights into educational need and the local and cultural awareness and norms.
Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial
Authors: Verheij Floris S. , Omer Dana M. , Williams Hannah , Lin Sabrina T. , Qin Li-Xuan , Buckley James T. , Thompson Hannah M. , Yuval Jonathan B. , Kim Jin K. , Dunne Richard F. , Marcet Jorge , Cataldo Peter , Polite Blase , Herzig Daniel O. , Liska David , Oommen Samuel , Friel Charles M. , Ternent Charles , Coveler Andrew L. , Hunt Steven , Gregory Anita , Varma Madhulika G. , Bello Brian L. , Carmichael Joseph C. , Krauss John , Gleisner Ana , Guillem José G. , Temple Larissa , Goodman Karyn A. , Segal Neil H. , Cercek Andrea , Yaeger Rona , Nash Garrett M. , Widmar Maria , Wei Iris H. , Pappou Emmanouil P. , Weiser Martin R. , Paty Philip B. , Smith J. Joshua , Wu Abraham J. , Gollub Marc J. , Saltz Leonard B. , Garcia-Aguilar Julio
Published: October 2023

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

To assess long-term risk of local tumor regrowth, we report updated organ preservation rate and oncologic outcomes of the OPRA trial (ClinicalTrials.gov identifier: NCT02008656 ). Patients with stage II/III rectal cancer were randomly assigned to receive induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Patients who achieved a complete or near-complete response after finishing treatment were offered watch-and-wait (WW). Total mesorectal excision (TME) was recommended for those who achieved an incomplete response. The primary end point was disease-free survival (DFS). The secondary end point was TME-free survival. In total, 324 patients were randomly assigned (INCT-CRT, n = 158; CRT-CNCT, n = 166). Median follow-up was 5.1 years. The 5-year DFS rates were 71% (95% CI, 64 to 79) and 69% (95% CI, 62 to 77) for INCT-CRT and CRT-CNCT, respectively ( P = .68). TME-free survival was 39% (95% CI, 32 to 48) in the INCT-CRT group and 54% (95% CI, 46 to 62) in the CRT-CNCT group ( P = .012). Of 81 patients with regrowth, 94% occurred within 2 years and 99% occurred within 3 years. DFS was similar for patients who underwent TME after restaging (64% [95% CI, 53 to 78]) and patients in WW who underwent TME after regrowth (64% [95% CI, 53 to 78]; P = .94). Updated analysis continues to show long-term organ preservation in half of the patients with rectal cancer treated with total neoadjuvant therapy. In patients who enter WW, most cases of tumor regrowth occur in the first 2 years.
Cost to Medicare from bone modifying agent overuse in castration-sensitive prostate cancer.
Authors: Mitchell Aaron Philip , Chakraborty Nirjhar , Nemirovsky David , Mishra Meza Akriti , Persaud Sonia , Farooki Azeez , Morris Michael J.
Published: October 2023

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Background: Bone modifying agents (BMAs) prevent skeletal related events among patients with castration-resistant prostate cancer (mCRPC) and bone metastasis, but not among patients with castration sensitive prostate cancer (CSPC). However, approximately 1/3 of Medicare patients with CSPC receive BMAs unnecessarily, and the costs to Medicare resulting from this overuse have not been assessed. Methods: We used linked SEER registry and Medicare claims data for persons diagnosed with stage IV prostate adenocarcinoma during 2011-2015, identified those who subsequently received a cancer therapy used exclusively for mCRPC, and measured 1) the number of doses of zoledronic acid and denosumab received between diagnosis and initiation of mCRPC therapy and 2) presence of patient comorbidities which may warrant BMA therapy for fragility fracture prevention (eg., osteoporosis, osteopenia). We estimated excess BMA costs to Medicare by assessing the proportion of patients who received BMA therapy during their CSPC interval and did NOT have an indication for fragility fracture prevention, using the Medicare fee schedule for drug prices. We estimated adverse event costs using event frequency and costs estimates drawn from the peer-reviewed literature. The modeled outcome was the cost to Medicare from excess BMA use for the cohort of patients diagnosed with stage IV prostate cancer each calendar year. We conducted one-way sensitivity analysis for each model input by using the highest and lowest estimates available from peer-reviewed sources, monthly vs. every-three-month dosing frequencies for both drugs, and by +/-20% for all other inputs. Results: The median time from diagnosis to initiation of CRPC therapy was 387 days (IQR 253,573), during which time 42% received >=1 dose of denosumab (mean doses = 7) and 18% received >=1 dose of zoledronic acid (mean doses = 7). The estimated, annual excess BMA cost to Medicare was $45,392,377, comprised of $43,303,078 and $45,512 in drug costs for denosumab and zoledronic acid, respectively, and $1,625,869 and $419,917 in adverse event costs, respectively. The estimate was most sensitive to denosumab administration schedule (monthly vs. every-three-month) [estimate range: $29,487,144 - $101,060,692] and the duration of CSPC [estimate range: $37,853,180 - $101,754,921]. Conclusions: BMA overuse in CSPC incurs substantial cost to Medicare, largely due to denosumab drug costs. Our sensitivity analyses suggest we may overestimate costs if denosumab dosing frequency is now lower than during our observation period (eg., if more providers now use 3-month dosing), and we may underestimate costs if patients now experience CSPC for a longer duration (a plausible consequence from the introduction of ARSi therapy for CSPC in the post-LATITUDE era). Avoidable costs and toxicity may be reduced by greater adherence to guideline-concordant use of BMAs.
Real-world data on immune-checkpoint inhibitors use and immune-related adverse events in lung cancer.
Authors: Hu Xiao , Pan Stacey , Salei Yana , Lin Jeffrey , Parsons Susan K.
Published: October 2023

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Background: Immune-checkpoint inhibitors (ICIs) have revolutionized lung cancer therapy. The data on the use of ICIs in underrepresented populations with lung cancer (older patients, patients with autoimmune disease (ADs), and patients with poor performance status) are limited from trials. The real-world pattern of immune-related adverse effects (irAEs) and the association between the occurrence of irAEs and prognosis remain unclear. Methods: Patients with lung cancer newly started on ICIs from 10/01/2018 to 09/30/2021 were identified in the Tufts Medical Center cancer registry. Patient information, disease characteristics, treatment history, and outcomes were collected from the electronic health record. Time to ICI treatment initiation (TTI) was analyzed via log-rank tests. Multivariable Cox regression was used to assess the impact of the occurrence of irAEs on overall survival (OS). Results: 125 lung cancer patients were identified with a median age of 70 (range 50-80) years old at time of ICIs initiation. 68 (54.4%) were males and 103 (82.4%) were White. Most of the patients were past or current smokers (95.2%). 16 (12.8%) had a history of ADs and 44 (35.2%) had an ECOG status >1. Most of the cohort had non-small cell lung cancer (80.8%) and advanced-stage diseases (stage III 20.8%, stage IV 77.6%). 37.6% had PD-L1 expression and 25.6% had detected molecular alterations. ICIs were mostly used in frontline settings (65.6%) and for palliative intent (86.4%). Pembrolizumab was used most frequently (64%), followed by durvalumab, atezolizumab, nivolumab, and ipilimumab plus nivolumab. About half (49.6%) of ICIs were delivered concurrently with chemotherapy. A total of 50 irAEs occurred in 39 (31.2%) individuals. The most common irAEs were pneumonitis, thyroid disorders, dermatitis, and gastrointestinal toxicity. TTIs were similar comparing those ≥65 vs <65 years old (median TTI: 1.4m vs 1.17m, p=0.82), those with vs without ADs (median TTI: 1.53m vs 1.27m, p=0.53), and those with ECOG >1 vs ≤1 (median TTI: 1.6m vs 1.17m, p=0.06) in newly diagnosed stage IV lung cancer patients (N=62). After adjusting for age, BMI, stage, histology, performance status, and comorbidities, no differences were found in OS between those with irAEs and those without (HR=0.84, p=0.65). Conclusions: Our findings suggested that in the real world, older patients, patients with ADs, and patients with poor performance had no significant delays in ICIs initiation. The pattern of irAEs was similar to that reported in clinical trials without erosion of OS among those with irAEs.