bluuebunny/crossref_metadata_2025 huggingface dataset:
The E3 ligase NEURL3 suppresses epithelial-mesenchymal transition and metastasis in nasopharyngeal carcinoma by promoting vimentin degradation
Authors: Zhou Shi-Qing , Feng Ping , Ye Ming-Liang , Huang Sheng-Yan , He Shi-Wei , Zhu Xun-Hua , Chen Jun , Zhang Qun , Li Ying-Qing
Published: January 2024

Background

Metastasis has emerged as the major reason of treatment failure and mortality in patients with nasopharyngeal carcinoma (NPC). Growing evidence links abnormal DNA methylation to the initiation and progression of NPC. However, the precise regulatory mechanism behind these processes remains poorly understood.

Methods

Bisulfite pyrosequencing, RT-qPCR, western blot, and immunohistochemistry were used to test the methylation and expression level of NEURL3 and its clinical significance. The biological function of NEURL3 was examined both in vitro and in vivo. Mass spectrometry, co-immunohistochemistry, immunofluorescence staining, and ubiquitin assays were performed to explore the regulatory mechanism of NEURL3.

Results

The promoter region of NEURL3, encoding an E3 ubiquitin ligase, was obviously hypermethylated, leading to its downregulated expression in NPC. Clinically, NPC patients with a low NEURL3 expression indicated an unfavorable prognosis and were prone to develop distant metastasis. Overexpression of NEURL3 could suppress the epithelial mesenchymal transition and metastasis of NPC cells in vitro and in vivo. Mechanistically, NEURL3 promoted Vimentin degradation by increasing its K48-linked polyubiquitination at lysine 97. Specifically, the restoration of Vimentin expression could fully reverse the tumor suppressive effect of NEURL3 overexpression in NPC cells.

Conclusions

Collectively, our study uncovers a novel mechanism by which NEURL3 inhibits NPC metastasis, thereby providing a promising therapeutic target for NPC treatment.
The morphokinetic signature of human blastocysts with mosaicism and the clinical outcomes following transfer of embryos with low-level mosaicism
Authors: Zou Yaoyu , Sui Yilun , Fu Jing , Ge Naidong , Sun Xiaoxi , Sun Yijuan
Published: January 2024

Background

Genetic mosaicism is commonly observed in human blastocysts. Embryos’ morphokinetic feature observed from time-lapse monitoring (TLM) is helpful to predict the embryos’ ploidy status in a non-invasive way. However, morphokinetic research on mosaic embryos is extremely limited. Moreover, transfer of mosaic embryos is a new attempt in reproductive medicine, while studies regarding the clinical and neonatal outcomes following transfer of embryos with different levels and types of mosaicism are needed. This study aimed to investigate the morphokinetic characteristics of mosaic blastocysts, uncover clinical outcomes of mosaic embryos, and evaluate the effect of level and type of mosaicism on transfer outcomes.

Results

A total of 923 blastocysts from 229 preimplantation genetic testing cycles were cultured in TLM incubators in a single fertilization center between July 2016 and July 2021. Multivariate logistic regression models showed mosaic embryos had significantly shorter time to reach morula when compared with euploid (P = 0.002), mosaic with aneuploid (P = 0.005), and aneuploid (P = 0.005) embryos after adjusting the potential confounders. KIDScore is an artificial intelligence scoring program from time lapse incubation system to predict embryo implantation potential. Mosaic with aneuploid embryos had significantly lower KIDScore than euploid (P = 6.47e−4), mosaic (P = 0.005), and aneuploid (P = 0.004) embryos after adjustment. Meanwhile, we compared the clinical outcomes following transfer of low-level (< 50%) mosaic embryos (N = 60) with euploid embryos (N = 1301) matched using propensity scoring collected from September 2020 to January 2023. Mosaic embryos had significantly lower clinical pregnancy rate (41.67% vs. 57.65%, P = 0.015) and live birth rate (38.33% vs. 51.35%, P = 0.048) than the euploid embryos. Subgroup analyses showed the whole, segmental, and complex chromosome mosaic embryos had the similar clinical outcomes.

Conclusions

The shortened time to reach morula in mosaic embryos and the low KIDScore in mosaic with aneuploid embryos revealed innovative clues to embryo selection with the non-invasive TLM and provided new insights into biological mechanism of chromosomal abnormality. The analyses of overall and subgroups of mosaic embryo transfer outcomes helped to optimize embryo transfer scheme for in-vitro fertilization procedures. Multi-center prospective studies with large sample sizes are warranted to validate our results in the future.
InterVFast—effectiveness and acceptance of intermittent fasting in cardiac rehabilitation patients: study protocol of a randomized controlled trial
Authors: Pieper Claudia , Kaistha Florian Tim Hitesh , Schroeer Sarah , Borgert Maria , Michalsen Andreas , Mayer-Berger Wolfgang
Published: January 2024

Background

Research on intermittent fasting has shown that it can improve a variety of health outcomes, including blood sugar control, blood lipid levels and blood pressure. Only few studies document longer periods of fasting, especially in rehabilitation participants. Cardiac inpatient rehabilitation follows a multidisciplinary approach including change of health behaviour to reduce patients’ risk of future cardiovascular events. To date, evidence suggests that intermittent fasting can be an effective way to improve health and well-being, but more research is needed to fully understand its long-term effects and factors that promote the implementation. Therefore, the aim of the ongoing InterVFast trial is to investigate the effectiveness of intermittent fasting amongst cardiac rehabilitation patients after 4-week inpatient rehabilitation as well as 3 and 12 months subsequently including patients’ perspective.

Methods

This single-centre randomized controlled trial evaluates the effectiveness of the InterVFast intervention in weight loss (primary outcome). We also examine patients’ acceptance and the effect on relevant outcomes as blood glucose and triglyceride levels, cholesterol and high-sensitivity C-reactive protein. Weight, blood samples and clinical data are collected as part of the initial and final examination during inpatient rehabilitation. During inpatient rehabilitation, participants daily note fasting intervals and meals eaten as well as practicability in a fasting diary. In addition, interviews about perceived advantages and disadvantages and acceptance are carried out with the participants in the IG. A standardized follow-up examination (weight, blood samples) will be carried out by the family doctor after 3 and 12 months (t2 and t3).

Discussion

Compared to other weight-loss intervention studies, our study addresses patients with coronary heart disease and includes patients’ acceptance as well as long-term maintenance. It is hypothesized that participation in the InterVfast intervention will improve relevant health outcomes in a sample of cardiac rehabilitation patients and thus constitute a behavioural prevention strategy to reduce the risk of future cardiac events and improve overall health and quality of life.

Trial registration

ClinicalTrials.gov DRKS00023983. Registered on February 17, 2022.
Determining the effects of targeted high-definition transcranial direct current stimulation on reducing post-stroke upper limb motor impairments—a randomized cross-over study
Authors: Peng Rita Huan-Ting , He Dorothy , James Shirley A. , Williamson Jordan N. , Skadden Carly , Jain Sanjiv , Hassaneen Wael , Miranpuri Amrendra , Kaur Amandeep , Sarol Jesus N. , Yang Yuan
Published: January 2024

Background

Stroke is one of the leading causes of death in the USA and is a major cause of serious disability for adults. This randomized crossover study examines the effect of targeted high-definition transcranial direct current transcranial brain stimulation (tDCS) on upper extremity motor recovery in patients in the post-acute phase of stroke recovery.

Methods

This randomized double-blinded cross-over study includes four intervention arms: anodal, cathodal, and bilateral brain stimulation, as well as a placebo stimulation. Participants receive each intervention in a randomized order, with a 2-week washout period between each intervention. The primary outcome measure is change in Motor Evoked Potential. Secondary outcome measures include the Fugl-Meyer Upper Extremity (FM-UE) score, a subset of FM-UE (A), related to the muscle synergies, and the Modified Ashworth Scale.

Discussion

We hypothesize that anodal stimulation to the ipsilesional primary motor cortex will increase the excitability of the damaged cortico-spinal tract, reducing the UE flexion synergy and enhancing UE motor function. We further hypothesize that targeted cathodal stimulation to the contralesional premotor cortex will decrease activation of the cortico-reticulospinal tract (CRST) and the expression of the upper extremity (UE) flexion synergy and spasticity. Finally, we hypothesize bilateral stimulation will achieve both results simultaneously. Results from this study could improve understanding of the mechanism behind motor impairment and recovery in stroke and perfect the targeting of tDCS as a potential stroke intervention. With the use of appropriate screening, we anticipate no ethical or safety concerns. We plan to disseminate these research results to journals related to stroke recovery, engineering, and medicine.

Trial registration

ClinicalTrials.gov NCT05479006. Registered on 26 July 2022.
Transcriptional signals of transformation in human cancer
Authors: Kildisiute Gerda , Kalyva Maria , Elmentaite Rasa , van Dongen Stijn , Thevanesan Christine , Piapi Alice , Ambridge Kirsty , Prigmore Elena , Haniffa Muzlifah , Teichmann Sarah A. , Straathof Karin , Cortés-Ciriano Isidro , Behjati Sam , Young Matthew D.
Published: January 2024

Background

As normal cells transform into cancers, their cell state changes, which may drive cancer cells into a stem-like or more primordial, foetal, or embryonic cell state. The transcriptomic profile of this final state may encode information about cancer’s origin and how cancers relate to their normal cell counterparts.

Methods

Here, we used single-cell atlases to study cancer transformation in transcriptional terms. We utilised bulk transcriptomes across a wide spectrum of adult and childhood cancers, using a previously established method to interrogate their relationship to normal cell states. We extend and validate these findings using single-cell cancer transcriptomes and organ-specific atlases of colorectal and liver cancer.

Results

Our bulk transcriptomic data reveals that adult cancers rarely return to an embryonic state, but that a foetal state is a near-universal feature of childhood cancers. This finding was confirmed with single-cell cancer transcriptomes.

Conclusions

Our findings provide a nuanced picture of transformation in human cancer, indicating cancer-specific rather than universal patterns of transformation pervade adult epithelial cancers.
The association between plasma free amino acids and type 2 diabetes mellitus complicated with infection in Chinese patients
Authors: Zhang Jing-Xi , Luo Wei-Ming , Wang Bo-Wen , Li Ru-Tao , Zhang Qian , Zhang Xiang-Yu , Fang Zhong-Ze , Zhang Zhi-Peng
Published: January 2024

Background

Type 2 diabetes mellitus (T2DM), one of the most common public diseases threatening human health, is always accompanied by infection. Though there are still a variety of flaws in the treatment of some infectious diseases, metabolomics provides a fresh perspective to explore the relationship between T2DM and infection. Our research aimed to investigate the association between plasma free amino acids (PFAAs) and T2DM complicated with infection in Chinese patients.

Methods

A cross-sectional study was conducted from May 2015 to August 2016. We retrieved the medical records of 1032 inpatients with T2DM from Liaoning Medical University First Affiliated Hospital and we used mass spectrometry to quantify 23 PFAAs. Infections contained 15 individual categories that could be retrieved from the database. Principal component analysis was used to extract factors of PFAAs. Multi-variable binary logistic regression was used to obtain odds ratios (OR) and their 95% confidence intervals (CI).

Results

Among 1032 inpatients,109 (10.6%) had infectious diseases. Six factors, accounting for 68.6% of the total variance, were extracted. Factor 4 consisted of Glu, Asp and Orn. Factor 5 consisted of Hcy and Pip. After adjusting for potential confounders, factor 4 was positively correlated with T2DM complicated with infection in Chinese T2DM patients (OR: 1.27, 95%CI: 1.06–1.52). Individual Hcy in factor 5 was positively associated with T2DM complicated with infection (OR: 1.33, 95%CI: 1.08–1.64). Furthermore, factor 4 (OR: 1.44, 95%CI: 1.11–1.87), Orn (OR: 1.01, 95%CI: 1.00-1.02) and Hcy (OR: 1.56, 95%CI: 1.14–3.14) were positively associated with bacterial infection in Chinese T2DM patients, while factor 5 (OR: 0.71, 95%CI: 0.50-1.00) was negatively associated with bacterial infection.

Conclusions

Urea cycle-related metabolites (Orn, Asp, Glu) and Hcy were positively associated with T2DM complicated with infection in China. Orn and Hcy were positively associated with bacterial infection in T2DM patients in China.
Lipid-lowering drugs and inflammatory bowel disease’s risk: a drug-target Mendelian randomization study
Authors: Zhao Jiaxi , Chen Rong , Luo Mengqi , Gong Hongping , Li Kaixin , Zhao Qian
Published: January 2024

Background

Inflammatory bowel disease (IBD) has been associated with lipid-lowering drugs in observational studies. Drug-target Mendelian randomization (MR) was utilized in this study to examine the causal relationship between lipid-lowering drugs and incidence of IBD, aiming to identify new preventive uses for the drugs.

Methods

We identified instrumental variables for three classes of lipid-lowering drugs: HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors, using data from the Global Lipids Genetics Consortium. Summary statistics of IBD were obtained from UK Inflammatory Bowel Disease Genetics. The summary-data-based MR (SMR) and the inverse-variance weighted (IVW) MR were used for analysis. Sensitivity analyses were performed by conventional MR methods.

Results

The SMR analysis showed no significant genetic association between increased gene expression of HMGCR, PCSK9, and NPC1L1 and IBD, Crohn’s disease (CD) and ulcerative colitis (UC). According to IVW-MR analysis, increased HMGCR expression is associated with a reduced risk of IBD (OR = 0.73, 95% confidence interval (CI) 0.59–0.90, P = 0.003) and CD (OR = 0.75, 95% CI 0.57–0.97, P = 0.03), but not with UC. Additionally, increased NPC1L1 gene expression was associated with elevated risk of IBD (OR = 1.60, 95% CI 1.07–2.40, P = 0.023), but not with CD and UC. However, no significant causal relationships were found between PCSK9 gene expression and IBD, CD, and UC. The sensitivity analysis demonstrated no evidence of heterogeneity or pleiotropy among the reported results.

Conclusions

The heightened expression of genetic variations in HMGCR inhibitor targets could potentially reduce the risk of IBD and CD, while genetic variation in the expression of NPC1L1 targets was positively associated with IBD.
Transformed Salmonella typhimurium SL7207/pcDNA-CCOL2A1 as an orally administered DNA vaccine
Authors: Long Juan , Zeng Yang , Liang Fei , Liu Nan , Xi Yongzhi , Sun Yuying , Zhao Xiao
Published: January 2024

The use of attenuated bacteria for oral delivery of DNA vaccines is a recent innovation. We designed and constructed the naked plasmid DNA vaccine pcDNA-CCOL2A1, which effectively prevented and treated a rheumatoid arthritis model by inducing immunotolerance. We aimed to ensure a reliable, controllable dosage of this oral DNA vaccine preparation and establish its stability. We transformed pcDNA-CCOL2A1 via electroporation into attenuated Salmonella typhimurium SL7207. A resistant plate assay confirmed the successful construction of the transformed strain of the SL7207/pcDNA-CCOL2A1 oral DNA vaccine. We verified its identification and stability in vitro and in vivo. Significant differences were observed in the characteristics of the transformed and blank SL7207 strains. No electrophoretic restriction patterns or direct sequencing signals were observed in the original extract of the transformed strain. However, target gene bands and sequence signals were successfully detected after PCR amplification. CCOL2A1 expression was detected in the ilea of BALB/c mice that were orally administered SL7207/pcDNA-CCOL2A1. The pcDNA-CCOL2A1 plasmid of the transformed strain was retained under the resistant condition, and the transformed strain remained stable at 4 °C for 100 days. The concentration of the strain harboring the pcDNA-CCOL2A1 plasmid was stable at 109 CFU/mL after 6–8 h of incubation. The results demonstrated that the transformed strain SL7207/pcDNA-CCOL2A1 can be expressed in vivo, has good stability, and may be used to prepare the oral DNA vaccine pcDNA-CCOL2A1 with a stable, controllable dosage and the capacity to provide oral immunization. This vehicle can effectively combine both oral immunotolerance and DNA vaccination.
The association of medical, social, and normative factors with the implementation of end-of-life care practices
Authors: Ziv Arnona , Shaulov Adir , Rubin Carmit , Oberman Bernice , Tawil Yoel , Kaplan Giora , Velan Baruch , Bodas Moran
Published: January 2024

Background

End-of-life (EoL) care practices (EoLCP) are procedures carried out at the EoL and bear directly on this stage in the patient’s life. Public support of these practices in Israel is far from uniform. Previous studies show that while ∼30% of participants support artificial respiration or feeding of terminally ill patients, 66% support analgesic treatment, even at the risk of shortening life. This study aimed to create a typology of six end-of-life care practices in Israel and assess the association of medical, social, and normative factors with the implementation of those practices. These practices included mechanical ventilation, artificial feeding, deep sedation, providing information to the patient and family caregivers, including family caregivers in EoL decision-making, and opting for death at home.

Methods

This cross-sectional study was performed as an online survey of 605 adults aged 50 or more in Israel, of which ~ 50% (n = 297) reported supporting a dying terminally ill relative in the last 3 years. Participants were requested to provide their account of the EoL process of their relative dying from a terminal illness in several aspects, as well as the EoL care practices utilized by them.

Results

The accounts of the 297 interviewees who supported a dying relative reveal a varied EoL typology. The utilization of end-of-life care practices was associated with the socio-normative beliefs of family caregivers but not with their socioeconomic status. Strong correlations were found between family caregiver support for three key practices (mechanical ventilation, artificial feeding, and family involvement in EoL) and the actual utilization of these practices in the care of dying patients.

Conclusions

The findings portray an important image of equity in the utilization of EoLCP in Israel, as the use of these practices was not associated with socioeconomic status. At the same time, the study found substantial diversity in family caregivers’ preferences regarding EoL care practices use not related to socioeconomic status. We believe that differences in preferences that do not lead to problems with equity or other important societal values should be respected. Accordingly, policymakers and health system leaders should resist calls for legislation that would impose uniform EoL practices for all Israelis. Instead, they should take concrete steps to preserve and enhance the widespread current practice of practitioners to adapt EoL care to the varied needs and preferences of Israeli families and cultural, social, and religious subgroups. These steps should include providing frameworks and tools for family caregivers to support their loved ones close to their deaths, such as educational programs, seminars, supportive care before and during the end of life of their loved ones, etc.
Modulation of fracture healing by senescence-associated secretory phenotype (SASP): a narrative review of the current literature
Authors: Zhao Shangkun , Qiao Zhi , Pfeifer Roman , Pape Hans-Christoph , Mao Keya , Tang Hai , Meng Bin , Chen Songfeng , Liu Hongjian
Published: January 2024

The senescence-associated secretory phenotype (SASP) is a generic term for the secretion of cytokines, such as pro-inflammatory factors and proteases. It is a crucial feature of senescent cells. SASP factors induce tissue remodeling and immune cell recruitment. Previous studies have focused on the beneficial role of SASP during embryonic development, wound healing, tissue healing in general, immunoregulation properties, and cancer. However, some recent studies have identified several negative effects of SASP on fracture healing. Senolytics is a drug that selectively eliminates senescent cells. Senolytics can inhibit the function of senescent cells and SASP, which has been found to have positive effects on a variety of aging-related diseases. At the same time, recent data suggest that removing senescent cells may promote fracture healing. Here, we reviewed the latest research progress about SASP and illustrated the inflammatory response and the influence of SASP on fracture healing. This review aims to understand the role of SASP in fracture healing, aiming to provide an important clinical prevention and treatment strategy for fracture. Clinical trials of some senolytics agents are underway and are expected to clarify the effectiveness of their targeted therapy in the clinic in the future. Meanwhile, the adverse effects of this treatment method still need further study.
Quantifying the climate change impacts on the magnitude and timing of hydrological extremes in the Baro River Basin, Ethiopia
Authors: Kassaye Shimelash Molla , Tadesse Tsegaye , Tegegne Getachew , Hordofa Aster Tesfaye
Published: January 2024

Extreme hydrological events, like floods and droughts, exert considerable effects on both human and natural systems. The frequency, intensity, and duration of these events are expected to change due to climate change, posing challenges for water resource management and adaptation. In this study, the Soil and Water Assessment Tool plus (SWAT +) model was calibrated and validated to simulate flow under future shared socioeconomic pathway (SSP2-4.5 and SSP5-8.5) scenarios in the Baro River Basin with R2 values of 0.88 and 0.83, NSE of 0.83 and 0.74, and PBIAS of 0.39 and 8.87 during calibration and validation. Six bias-corrected CMIP6 Global Climate Models (GCM) were selected and utilized to investigate the effects of climate change on the magnitude and timing of hydrological extremes. All climate model simulation results suggest a general increase in streamflow magnitude for both emission scenarios (SSP2-4.5 and SSP5-8.5). The multi-model ensemble projections show yearly flow increases of 4.8% and 12.4% during the mid-term (MT) (2041–2070) and long-term (LT) (2071–2100) periods under SSP2-4.5, and 15.7% and 35.6% under SSP5-8.5, respectively. Additionally, the analysis revealed significant shifts in the projected annual 1 day, 3 day, 7 day, and 30 day maximum flows, whereas the annual 3 day and 7 day minimum flow fluctuations do not present a distinct trend in the future scenario compared to the baseline (1985–2014). The study also evaluated the timing of hydrological extremes, focusing on low and peak flow events, utilizing the annual 7 day maximum and minimum flow for this analysis. An earlier occurrence was noted for both peak and low flow in the SSP2-4.5 scenario, while a later occurrence was observed in the SSP5-8.5 scenario compared to the baseline. In conclusion, this study showed the significant effect of climate change on river hydrology and extreme flow events, highlighting their importance for informed water management and sustainable planning.
Reconsideration of the energy balance in earthquake faulting
Authors: Matsu’ura Mitsuhiro
Published: January 2024

The occurrence of earthquakes is now understood as brittle shear fracture releasing the elastic potential energy stored in the earth. Since the 1950s, many studies on the energy balance in earthquake faulting have been done, but there seems to be some incoherence among them. The essential reason is because various changes in conceptual framework happened during the last six decades, specifically the introduction of the new paradigm of plate tectonics in the 1960s, the concept of moment tensor as source representation in the 1970s, and the fault constitutive law governing rupture growth in the 1990s. Therefore, it will be worthwhile to reconsider the energetics of earthquake faulting from a current perspective. For this purpose, first of all, we summarize the basic concepts of elastic potential energy and moment tensor and review the general representation of earthquake sources and the origin of background crustal stress to confirm that the effect of earth’s self-gravitation is negligible in the energetics of shear faulting. Next, as a starting point for discussion, we directly derive a basic equation of mechanical energy balance in dynamic shear faulting from the equation of motion for an elastic body subjected to tectonic-origin deviatoric stress. Then, we review the widely accepted formula for indirectly evaluating radiated seismic energy from a simplified energy balance equation and compare with the direct evaluation based on the analytical solution of displacement fields for a point dislocation source in order to call attention to inconsistency between them. The inconsistency comes from the omission of the effects of rupture growth rate in the simplified energy balance equation. So, finally, we review the energy balance at the tips of a propagating shear crack, which naturally leads to the introduction of the slip-weakening fault constitutive law as a fundamental equation governing earthquake rupture. Then, we discuss the whole process of earthquake rupture, consisting of initiation, acceleration, steady propagation, deceleration, and termination from the viewpoint of energy balance.
Deep learning based joint fusion approach to exploit anatomical and functional brain information in autism spectrum disorders
Authors: Saponaro Sara , Lizzi Francesca , Serra Giacomo , Mainas Francesca , Oliva Piernicola , Giuliano Alessia , Calderoni Sara , Retico Alessandra
Published: January 2024

Background:

The integration of the information encoded in multiparametric MRI images can enhance the performance of machine-learning classifiers. In this study, we investigate whether the combination of structural and functional MRI might improve the performances of a deep learning (DL) model trained to discriminate subjects with Autism Spectrum Disorders (ASD) with respect to typically developing controls (TD).

Material and methods

We analyzed both structural and functional MRI brain scans publicly available within the ABIDE I and II data collections. We considered 1383 male subjects with age between 5 and 40 years, including 680 subjects with ASD and 703 TD from 35 different acquisition sites. We extracted morphometric and functional brain features from MRI scans with the Freesurfer and the CPAC analysis packages, respectively. Then, due to the multisite nature of the dataset, we implemented a data harmonization protocol. The ASD vs. TD classification was carried out with a multiple-input DL model, consisting in a neural network which generates a fixed-length feature representation of the data of each modality (FR-NN), and a Dense Neural Network for classification (C-NN). Specifically, we implemented a joint fusion approach to multiple source data integration. The main advantage of the latter is that the loss is propagated back to the FR-NN during the training, thus creating informative feature representations for each data modality. Then, a C-NN, with a number of layers and neurons per layer to be optimized during the model training, performs the ASD-TD discrimination. The performance was evaluated by computing the Area under the Receiver Operating Characteristic curve within a nested 10-fold cross-validation. The brain features that drive the DL classification were identified by the SHAP explainability framework.

Results

The AUC values of 0.66±0.05 and of 0.76±0.04 were obtained in the ASD vs. TD discrimination when only structural or functional features are considered, respectively. The joint fusion approach led to an AUC of 0.78±0.04. The set of structural and functional connectivity features identified as the most important for the two-class discrimination supports the idea that brain changes tend to occur in individuals with ASD in regions belonging to the Default Mode Network and to the Social Brain.

Conclusions

Our results demonstrate that the multimodal joint fusion approach outperforms the classification results obtained with data acquired by a single MRI modality as it efficiently exploits the complementarity of structural and functional brain information.
Juvenile polyposis syndrome with gastric and duodenal polyposis presenting with refractory anemia and protein-leakage gastroenteropathy in a patient with SMAD4 mutation: a case report
Authors: Nakamura Kenya , Kubota Koji , Shimizu Akira , Notake Tsuyoshi , Ikehara Tomohiko , Umemura Kentaro , Kamachi Atsushi , Goto Takamune , Tomida Hidenori , Takahashi Yoshiyuki , Nagaya Tadanobu , Umemura Takeji , Soejima Yuji
Published: January 2024

Background

Juvenile polyposis syndrome (JPS) is an autosomal dominant, inherited disorder characterized by multiple hyperproliferative polyps of the gastrointestinal tract, particularly of the colon, rectum, and stomach. SMAD4 mutations are frequently associated with multiple polyposis of the stomach; the condition causes severe bleeding and hypoproteinemia, which may progress to severe dysplasia and adenocarcinoma formation. We report our experience with the first case of total gastrectomy with pancreaticoduodenectomy following two partial jejunectomies for JPS, who presented with refractory anemia and protein-losing gastroenteropathy due to polyposis of the stomach and duodenum.

Case presentation

A 33-year-old Japanese man presented with the chief complaint of shortness of breath on exertion. His family history included gastric polyposis (mother, aunt, and cousin) and cerebral infarction (grandmother). Blood testing at the initial visit indicated iron-deficiency anemia, whereas endoscopy revealed multiple polyps in the duodenum and jejunum. Genetic testing revealed a 4 bp deletion (TGAA) in exon 5 of the SMAD4 gene; two partial small bowel resections were performed, but polyps grew in the remaining stomach, duodenum, and small intestine. The patient developed hypoalbuminemia and anemia, and required central venous nutrition and blood transfusion. However, because the hyponutrition and anemia remained poorly controlled, a total gastrectomy with concomitant pancreaticoduodenectomy was performed. Malnutrition and anemia improved, and there was no polyp recurrence in the remaining intestinal tract at 18 months after the surgery.

Conclusions

We report a case of JPS with refractory anemia and protein-losing gastroenteropathy that was treated with total gastrectomy with concomitant pancreaticoduodenectomy. Although the surgery was highly invasive, the patient’s nutritional status and anemia improved postoperatively, and the treatment was successful. However, to determine the appropriate surgical procedure, a detailed examination of the gastrointestinal lesions and the effects of the surgical invasion on nutritional status must be undertaken.
The impact of prestigious attorneys on IPO withdrawal in the global primary market
Authors: Jamaani Fouad , Alidarous Manal
Published: January 2024

This study aims to determine whether the involvement of prestigious attorneys in issuing companies affects withdrawals in the initial public offering (IPO) market. There is little evidence on how the involvement of famous lawyers affects IPO withdrawal. The study considers a large dataset consisting of 24,312 IPOs that were either successful or withdrawn from 22 distinct IPO marketplaces between January 1995 and December 2019. We find that IPO issuers may benefit from engaging with reputed attorneys by leveraging exceptional legal or negotiating abilities as quality certification signals to reduce IPO investors’ ex-ante uncertainty. Here, the objective is to protect their IPOs from withdrawal of at least by 22%. Multiple robustness tests validate the reliability of the results of this study. These findings have significant implications for researchers, legislators, investors, and issuers.
Public health expenditure and household poverty: case study of Egypt
Authors: Biltagy Marwa , Hamdi Manar
Published: January 2024

The insufficient and inefficient public expenditure on health services by any health system creates physical and financial barriers to using health care services, especially for poor people and uncovered informal sector workers. This leads to the appearance of household direct out-of-pocket (OOP) payments on health services. OOP will push households into poverty if it exceeds their monetary income, as they cut their spending on other essential needs such as food, clothing, or education fees. The main objective of studying public health expenditure is to provide essential health services to all citizens equally without pushing them into poverty due to health payments OOP. This paper examines the average coverage of Reproductive, Maternal, and Child Health (RMNCH) services according to place of residence and wealth quintile from 2005 to 2015. The rationale for choosing RMNCH only as an indication of health coverage is due to data limitations. This paper depends on World Health Organization (WHO) data. The paper evaluates poverty impact by using poverty head counts and poverty gaps before and after OOP through using nationally representative surveys of Egypt for the years 2005, 2009, 2011, 2013, and 2015. Results show a gap in covering RMNCH services among different groups, but the gap is decreasing over time. Results also show that OOP payments pushed on average 30% of Egyptian households into poverty during the period of the study.
Auditory cognitive assessment in post COVID-19 patients: a case control study
Authors: Weheiba Hoda Mahmoud , Kabarity Rasha Hamdi E. L. , Shaheen Heba Magdy , EL-Gendy Abeer Mohamed Mohamed
Published: January 2024

Background

There is increasing evidence suggesting that individuals with coronavirus disease 2019 (COVID-19) may experience symptoms that persist beyond the initial acute phase commonly referred to as “Long COVID.” Cognitive deficits were among the frequently reported long-lasting symptoms post-COVID-19. Consequently, the study was designed to evaluate cognitive-communicative abilities in post COVID-19 patients focusing on auditory memory and auditory attention and to study the effect of different variables on these abilities in post COVID-19 patients.

Methods

Eighty adult subjects were divided equally according to the presence or absence of a history of COVID-19 infection into the study and control group, respectively. All subjects were submitted to thorough history taking, basic audiological evaluation, auditory cognitive psychophysical tests including Auditory Continuous Performance test, Speech Intelligibility in Noise, Recognition memory, Memory for content and for sequence tests, digit span forward and backward tests, and electrophysiological auditory event-related potential (P300).

Results

Post COVID-19 group showed significantly lower scores compared to the control group in all psychophysical auditory cognitive tests for attention and memory and significantly prolonged P300 wave latency and smaller amplitude. None of the variables measured (including duration passed from infection, severity, and number of infection) showed significant relations to test results except a significant negative correlation between the number of infections and memory for sequence results.

Conclusion

Single infection with COVID-19 can have a prolonged impact on auditory cognitive abilities which were not related to the degree of severity of COVID-19. Thus, patients recovered from COVID-19 should receive auditory cognitive evaluations to detect even mild cognitive deficits that can affect quality of life.
Automatic Detection of Distant Metastasis Mentions in Radiology Reports in Spanish
Authors: Ahumada Ricardo , Dunstan Jocelyn , Rojas Matías , Peñafiel Sergio , Paredes Inti , Báez Pablo
Published: January 2024

PURPOSE

A critical task in oncology is extracting information related to cancer metastasis from electronic health records. Metastasis-related information is crucial for planning treatment, evaluating patient prognoses, and cancer research. However, the unstructured way in which findings of distant metastasis are often written in radiology reports makes it difficult to extract information automatically. The main aim of this study was to extract distant metastasis findings from free-text imaging and nuclear medicine reports to classify the patient status according to the presence or absence of distant metastasis.

MATERIALS AND METHODS

We created a distant metastasis annotated corpus using positron emission tomography-computed tomography and computed tomography reports of patients with prostate, colorectal, and breast cancers. Entities were labeled M1 or M0 according to affirmative or negative metastasis descriptions. We used a named entity recognition model on the basis of a bidirectional long short-term memory model and conditional random fields to identify entities. Mentions were subsequently used to classify whole reports into M1 or M0.

RESULTS

The model detected distant metastasis mentions with a weighted average F1score performance of 0.84. Whole reports were classified with an F1score of 0.92 for M0 documents and 0.90 for M1 documents.

CONCLUSION

These results show the usefulness of the model in detecting distant metastasis findings in three different types of cancer and the consequent classification of reports. The relevance of this study is to generate structured distant metastasis information from free-text imaging reports in Spanish. In addition, the manually annotated corpus, annotation guidelines, and code are freely released to the research community.
Normal Risk Ovarian Screening Study: 21-Year Update
Authors: Han Chae Young , Lu Karen H. , Corrigan Gwen , Perez Alexandra , Kohring Sharlene D. , Celestino Joseph , Bedi Deepak , Bedia Enrique , Bevers Therese , Boruta David , Carlson Matthew , Holman Laura , Leeds Leroy , Mathews Cara , McCann Georgia , Moore Richard G. , Schlumbrecht Matthew , Slomovitz Brian , Tobias Dan , Williams-Brown Yvette , Bevers Michael W. , Liu Jinsong , Gornet Terrie G. , Handy Beverly C. , Lu Zhen , Bedia Jacob S. , Skates Steven J. , Bast Robert C.
Published: January 2024

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.

PURPOSE

The Normal Risk Ovarian Screening Study (NROSS) tested a two-stage screening strategy in postmenopausal women at conventional hereditary risk where significantly rising cancer antigen (CA)-125 prompted transvaginal sonography (TVS) and abnormal TVS prompted surgery to detect ovarian cancer.

METHODS

A total of 7,856 healthy postmenopausal women were screened annually for a total of 50,596 woman-years in a single-arm study (ClinicalTrials.gov identifier: NCT00539162 ). Serum CA125 was analyzed with the Risk of Ovarian Cancer Algorithm (ROCA) each year. If risk was unchanged and <1:2,000, women returned in a year. If risk increased above 1:500, TVS was undertaken immediately, and if risk was intermediate, CA125 was repeated in 3 months with a further increase in risk above 1:500 prompting referral for TVS. An average of 2% of participants were referred to TVS annually.

RESULTS

Thirty-four patients were referred for operations detecting 15 ovarian cancers and two borderline tumors with 12 in early stage (I-II). In addition, seven endometrial cancers were detected with six in stage I. As four ovarian cancers and two borderline tumors were diagnosed with a normal ROCA, the sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23), and 70% of ROCA-detected cases (12 of 17) were in stage I-II. NROSS screening reduced late-stage (III-IV) disease by 34% compared with UKCTOCS controls and by 30% compared with US SEER values. The positive predictive value (PPV) was 50% (17 of 34) for detecting ovarian cancer and 74% (25 of 34) for any cancer, far exceeding the minimum acceptable study end point of 10% PPV.

CONCLUSION

While the NROSS trial was not powered to detect reduced mortality, the high specificity, PPV, and marked stage shift support further development of this strategy.
Genomic Classification and Individualized Prognosis in Multiple Myeloma
Authors: Maura Francesco , Rajanna Arjun Raj , Ziccheddu Bachisio , Poos Alexandra M. , Derkach Andriy , Maclachlan Kylee , Durante Michael , Diamond Benjamin , Papadimitriou Marios , Davies Faith , Boyle Eileen M. , Walker Brian , Hultcrantz Malin , Silva Ariosto , Hampton Oliver , Teer Jamie K. , Siegel Erin M. , Bolli Niccolò , Jackson Graham H. , Kaiser Martin , Pawlyn Charlotte , Cook Gordon , Kazandjian Dickran , Stein Caleb , Chesi Marta , Bergsagel Leif , Mai Elias K. , Goldschmidt Hartmut , Weisel Katja C. , Fenk Roland , Raab Marc S. , Van Rhee Fritz , Usmani Saad , Shain Kenneth H. , Weinhold Niels , Morgan Gareth , Landgren Ola
Published: January 2024

PURPOSE

Outcomes for patients with newly diagnosed multiple myeloma (NDMM) are heterogenous, with overall survival (OS) ranging from months to over 10 years.

METHODS

To decipher and predict the molecular and clinical heterogeneity of NDMM, we assembled a series of 1,933 patients with available clinical, genomic, and therapeutic data.

RESULTS

Leveraging a comprehensive catalog of genomic drivers, we identified 12 groups, expanding on previous gene expression–based molecular classifications. To build a model predicting individualized risk in NDMM (IRMMa), we integrated clinical, genomic, and treatment variables. To correct for time-dependent variables, including high-dose melphalan followed by autologous stem-cell transplantation (HDM-ASCT), and maintenance therapy, a multi-state model was designed. The IRMMa model accuracy was significantly higher than all comparator prognostic models, with a c-index for OS of 0.726, compared with International Staging System (ISS; 0.61), revised-ISS (0.572), and R2-ISS (0.625). Integral to model accuracy was 20 genomic features, including 1q21 gain/amp, del 1p,
TP53
loss,
NSD2
translocations, APOBEC mutational signatures, and copy-number signatures (reflecting the complex structural variant chromothripsis). IRMMa accuracy and superiority compared with other prognostic models were validated on 256 patients enrolled in the GMMG-HD6 (ClinicalTrials.gov identifier:
NCT02495922
) clinical trial. Individualized patient risks were significantly affected across the 12 genomic groups by different treatment strategies (ie, treatment variance), which was used to identify patients for whom HDM-ASCT is particularly effective versus patients for whom the impact is limited.

CONCLUSION

Integrating clinical, demographic, genomic, and therapeutic data, to our knowledge, we have developed the first individualized risk-prediction model enabling personally tailored therapeutic decisions for patients with NDMM.
Population-Based Data Linkage Describing Patterns of Cancer Clinical Trial Enrollment Among Children and Adolescents
Authors: Siegel David A. , Durbin Eric B. , Pollock Brad H. , Grimes Allison , Ji Lingyun , Alonzo Todd A. , Vargas Sarah L. , Huang Bin , McDowell Jaclyn R. , Lycan Ellen , Ransdell Peter , Tai Eric , Roth Michael E. , Freyer David R.
Published: January 2024

PURPOSE

Database linkage between cancer registries and clinical trial consortia has the potential to elucidate referral patterns of children and adolescents with newly diagnosed cancer, including enrollment into cancer clinical trials. This study's primary objective was to assess the feasibility of this linkage approach.

METHODS

Patients younger than 20 years diagnosed with incident cancer during 2012-2017 in the Kentucky Cancer Registry (KCR) were linked with patients enrolled in a Children's Oncology Group (COG) study. Matched patients between databases were described by sex, age, race and ethnicity, geographical location when diagnosed, and cancer type. Logistic regression modeling identified factors associated with COG study enrollment. Timeliness of patient identification by KCR was reported through the Centers for Disease Control and Prevention's Early Case Capture (ECC) program.

RESULTS

Of 1,357 patients reported to KCR, 47% were determined by matching to be enrolled in a COG study. Patients had greater odds of enrollment if they were age 0-4 years ( v 15-19 years), reported from a COG-affiliated institution, and had renal cancer, neuroblastoma, or leukemia. Patients had lower odds of enrollment if Hispanic ( v non-Hispanic White) or had epithelial (eg, thyroid, melanoma) cancer. Most (59%) patients were reported to KCR within 10 days of pathologic diagnosis.

CONCLUSION

Linkage of clinical trial data with cancer registries is a feasible approach for tracking patient referral and clinical trial enrollment patterns. Adolescents had lower enrollment compared with younger age groups, independent of cancer type. Population-based early case capture could guide interventions designed to increase cancer clinical trial enrollment.
Energy Requirements of Paralympic Athletes: Insights from the Doubly Labeled Water Approach
Authors: WEIJER VERA C. R. , JONVIK KRISTIN L. , VAN DAM LOTTE , RISVANG LINN , PLASQUI GUY , SANDBAKK ØYVIND , RAASTAD TRULS , VAN LOON LUC J. C. , VAN DIJK JAN-WILLEM
Published: January 2024

Purpose

Advanced insight in energy requirements of Paralympic athletes is imperative for optimizing their nutritional counseling. Given the lack of accurate data on total daily energy expenditure (TDEE) of Paralympic athletes, this study aimed to assess energy expenditure and nutritional intake of a large cohort of Paralympic athletes, across different sports and disabilities.

Methods

In this cross-sectional study, 48 Dutch and Norwegian Paralympic athletes (19 male/29 female) with various disabilities, competing in Para cycling, wheelchair tennis, wheelchair basketball, Para Nordic skiing, and alpine skiing participated. TDEE was assessed by the gold standard doubly labeled water method over a 14-d period, resting metabolic rate by ventilated hood indirect calorimetry, energy intake by three unannounced 24-h dietary recalls, body composition by dual-energy x-ray absorptiometry, and exercise training duration by a training log.

Results

Mean TDEE was 2908 ± 797 kcal·d−1, ranging from 2322 ± 340 kcal·d−1 for wheelchair basketball players to 3607 ± 1001 kcal·d−1 for Para cyclists. Regression analysis identified fat-free mass, exercise duration, and the presence of a spinal cord disorder as the primary predictors of TDEE, explaining up to 73% of the variance in TDEE. Athletes’ energy intake (2363 ± 905 kcal·d−1) was below their TDEE, whereas their body mass remained constant, indicating underreporting. Carbohydrate intake (4.1 ± 1.9 g·kg−1 body mass) was low, even when considering underreporting, whereas protein intake (1.8 ± 0.6 g·kg−1 body mass) was relatively high.

Conclusions

Paralympic athletes display moderate- to high-energy expenditure, varying across sports and individuals. Much of the variation in TDEE can be attributed to individual differences in fat-free mass and exercise duration. This study establishes the benchmarks for energy requirements of Paralympic athletes, serving as the foundation for future dietary guidelines within this population.