bluuebunny/crossref_metadata_2025 huggingface dataset:
Topography-guided photorefractive keratectomy combined with accelerated corneal collagen cross-linking versus cross-linking alone for progressive keratoconus: a long-term prospective cohort study
Authors: Dai Zhihao , Liu Ziyuan , Zhang Yu , Yuan Yufei , Liu Yan , Wang Yuexin , Yu Shuo , Chen Yueguo
Published: August 2024

Purpose

To comprehensively compare the long-term outcome of the combined topography guided photorefractive keratectomy (TG-PRK) with accelerated corneal cross-linking (ACXL) and ACXL alone in eyes with progressive keratoconus. The analysis focused on the changes in the detailed corneal aberrometric values.

Methods

This single-center, prospective cohort study included 28 patients (30 eyes) of the TG-PRK plus ACXL group and 14 patients (15 eyes) of the ACXL alone group. The mean duration of the follow-up was 44 ± 10.18 months (ranged from 31 to 65 months). The preoperative data and the postoperative measurement data at the last follow-up visit, including demographic data, uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction, corneal topography, pachymetry, aberrometry and densitometry were analyzed.

Results

The CDVA significantly improved in the TG-PRK plus ACXL group at the last follow-up visit (p = 0.006), while no significant improvement was found in the ACXL alone group (p = 0.432). The maximal keratometry of the anterior corneal surface (Kmax) of both groups significantly decreased at the last follow-up visit (p < 0.05). Compared with the ACXL alone group, the Kmax of the TG-PRK plus ACXL group showed a greater decline (p = 0.008). The total corneal aberrations, the corneal lower-order aberrations (LOAs), the corneal higher order aberrations (HOAs), the vertical coma and the spherical aberration (SA) at the 4.0 mm and 6.0 mm zone of the TG-PRK plus ACXL group significantly decreased at the last follow-up visit (all p < 0.05). The declines of the total corneal aberrations, the corneal LOAs, the corneal HOAs and the vertical coma at the 4.0 mm and 6.0 mm zone of the TG-PRK plus ACXL group were significantly higher than those in the ACXL alone group (p < 0.001).

Conclusion

Compared with ACXL alone, combined TG-PRK with ACXL procedure had a significantly higher reduction in the corneal HOAs and better CDVA, while providing a similar long-term stability and safety. For progressive keratoconus patients with adequate corneal thickness, the combined procedure might be a recommended treatment option.
A stochastic model-based control methodology for glycemic management in the intensive care unit
Authors: Sirlanci Melike , Hripcsak George , Low Wang Cecilia C. , Stroh J. N. , Wang Yanran , Bennett Tellen D. , Stuart Andrew M. , Albers David J.
Published: August 2024

Introduction: Intensive care unit (ICU) patients exhibit erratic blood glucose (BG) fluctuations, including hypoglycemic and hyperglycemic episodes, and require exogenous insulin delivery to keep their BG in healthy ranges. Glycemic control via glycemic management (GM) is associated with reduced mortality and morbidity in the ICU, but GM increases the cognitive load on clinicians. The availability of robust, accurate, and actionable clinical decision support (CDS) tools reduces this burden and assists in the decision-making process to improve health outcomes. Clinicians currently follow GM protocol flow charts for patient intravenous insulin delivery rate computations.

Methods: We present a mechanistic model-based control algorithm that estimates the optimal intravenous insulin rate to keep BG within a target range; the goal is to develop this approach for eventual use within CDS systems. In this control framework, we employed a stochastic model representing BG dynamics in the ICU setting and used the linear quadratic Gaussian control methodology to develop a controller.

Results: We designed two experiments, one using virtual (simulated) patients and one using a real-world retrospective dataset. Using these, we evaluated the safety and efficacy of this model-based glycemic control methodology. The presented controller avoids hypoglycemia and hyperglycemia in virtual patients, maintaining BG levels in the target range more consistently than two existing GM protocols. Moreover, this methodology could theoretically prevent a large proportion of hypoglycemic and hyperglycemic events recorded in a real-world retrospective dataset.

Discussion: The current version of the methodology shows potential usefulness in GM of ICU patients. However, it is limited to a subgroup of the ICU patient population, who are fed through and enteral tube and delivered intravenous insulin. After extending to a broader ICU patient population who can consume oral nutrition and are delivered subcutaneous insulin for GM, the methodology could be tested with pilot studies and clinical trials for eventual use as a CDS tool.
Rel-dependent decrease in the expression of ribosomal protein genes by inhibition of the respiratory electron transport chain in Mycobacterium smegmatis
Authors: Kim Na-Kyeong , Baek Jong-Eun , Lee Ye-Jin , Oh Yuna , Oh Jeong-Il
Published: August 2024

In this study, we demonstrated that both the expression of most ribosomal protein genes and the amount of ribosomes were decreased in the Δaa3 mutant of Mycobacterium smegmatis, in which the major terminal oxidase (aa3 cytochrome c oxidase) of the respiratory electron transport chain (ETC) is inactivated, compared to those in the wild-type strain. Deletion of the rel gene encoding the major (p)ppGpp synthetase in the background of the Δaa3 mutant restored the reduced expression of ribosomal protein genes, suggesting that inhibition of the respiratory ETC leads to the Rel-dependent stringent response (SR) in this bacterium. Both a decrease in the expression of ribosomal protein genes by overexpression of rel and the increased expression of rel in the Δaa3 mutant relative to the wild-type strain support the Rel-dependent induction of SR in the Δaa3 mutant. We also demonstrated that the expression of ribosomal protein genes was decreased in M. smegmatis exposed to respiration-inhibitory conditions, such as KCN and bedaquiline treatment, null mutation of the cytochrome bcc1 complex, and hypoxia. The MprBA-SigE-SigB regulatory pathway was implicated in both the increased expression of rel and the decreased expression of ribosomal protein genes in the Δaa3 mutant of M. smegmatis.
The downregulation of tight junction proteins and pIgR in the colonic epithelium causes the susceptibility of EpCAM+/− mice to colitis and gut microbiota dysbiosis
Authors: Nie Ya , Lin Ting , Yang Yanhong , Liu Wanwan , Hu Qing , Chen Guibin , Huang Li , Wu Huijuan , Kong Cunjie , Lei Zili , Guo Jiao
Published: August 2024

Background

The genetic factors play important roles on the pathogenesis of inflammatory bowel disease (IBD). EpCAM is highly expressed in the intestinal epithelium. It is still unclear if the decrease or somatic mutation of EpCAM could cause IBD.

Methods

The WT and EpCAM+/− mice were administrated with DSS intermittently for nearly 8 weeks. The colon, liver and feces were harvested to check the morphological and histological changes, the expression of inflammatory genes and the gut microbiota via H&E staining, immunofluorescence, qPCR, western blot and 16S rDNA sequence assays.

Results

The DSS administration induced more serious inflammation in the colon of EpCAM+/− mice than WT mice. Compared to DSS-induced WT mice, the transcriptional levels of IL-6, F4/80, Ly6g, Ly6d and Igha were significantly higher in the colon of DSS-induced EpCAM+/− mice. The protein levels of MMP7 and MMP8 and the activation of JNK, ERK1/2 and p38 were significantly increased in the colon of DSS-induced EpCAM+/− mice. The protein levels of CLDN1, CLDN2, CLDN3, CLDN7, OCLD, ZO-1 and pIgR were significantly decreased in the colon of DSS-induced EpCAM+/− mice. The serum concentration of LPS was significantly higher in the DSS-induced EpCAM+/− mice which caused the acute inflammation in the liver of them. The expression of Pigr was significantly reduced in the liver of DSS-induced EpCAM+/− mice. The ratio of Firmicutes/Bacteroidetes at the phylum level was higher in the gut microbiota of EpCAM+/− mice than WT mice.

Conclusion

In conclusion, the heterozygous mutation of EpCAM increased the susceptibility to colitis, gut microbiota dysbiosis and liver injury.
Effectiveness of computed tomography perfusion imaging in stroke management
Authors: Cviková Martina , Haršány Michal , Vinklárek Jan , Štefela Jakub , Fojtová Iva , Mikulík Robert
Published: August 2024

Objectives

Current guidelines do not support the use of computed tomography perfusion (CTP) in stroke, except when identifying the penumbra during an extended treatment window. Therefore, this study aimed to define the yield of CTP in diagnosing a stroke diagnosis beyond the imaging of the penumbra in the hyperacute phase (0–6 h) and an extended time window (6–24 h).

Materials and methods

All consecutive patients with acute onset of symptoms within a 24-h window underwent CTP imaging. The diagnostic value of CTP was calculated against the clinical and radiological diagnoses of stroke. A positive CTP result was determined by the presence of either a core or penumbra on the RAPID summary. Clinical diagnoses corresponded to discharge diagnoses of stroke. A radiological diagnosis was established if early ischemic changes [Alberta Stroke Program Early CT Score (ASPECTS) <10] were observed on the baseline CT scan, acute infarction was confirmed on follow-up imaging, or symptomatic occlusion was evident on baseline CTA.

Results

Between November 2018 and November 2019, 585 consecutive patients with an acute neurological deficit underwent multimodal CT imaging. A total of 500 patients (85%) were included, where 274 (55%) were within the hyperacute phase, 153 (31%) had a radiological diagnosis of stroke, and 122 (24%) had a clinical diagnosis of stroke. CTP yielded positive results only in patients with a confirmed stroke (positive predictive value and specificity of 100%). When CTP results were negative, 43% of the cases turned out to stroke mimics. Patients with stroke mimics were younger (66 ± 17 vs. 73 ± 13) and had lower scores on the National Institutes of Health Stroke Scale [median 0; interquartile range (IQR) 0–2 vs. median 4; IQR 2–6] compared to patients with CTP-negative strokes.

Conclusion

In our study, CTP consistently indicated brain ischemia; therefore, in stroke management, CTP is most beneficial when it yields a positive result. A positive CTP result should prompt adequate stroke management actions without any delay. Conversely, a negative CTP result necessitates the consideration of both stroke and non-stroke diagnoses.
Executive functions in children with developmental language disorder: a systematic review and meta-analysis
Authors: Niu Tengfei , Wang Shiqiang , Ma Jingxi , Zeng Xiaoping , Xue Ruiling
Published: August 2024

Background

The purpose of the current study was to assess the differences between children with developmental language disorder (DLD) and typically developing (TD) children in their performance of executive functions from working memory, inhibitory control, and cognitive flexibility.

Methods

We performed a systematical search of PubMed, Embase, Cochrane, and Web of Science for case control studies (published in English between January 1, 1950, and October 11, 2023) comparing the differences in the performance of executive functions between DLD and TD children.

Results

Forty eligible studies were included in the present study (N = 3,168 participants). In comparison with TD children, DLD children exhibited significantly poorer performances in all six verbal working memory tasks (backward digit recall task, SMD –1.4321, 95% CI –2.2692 to –0.5950; listening recall task, SMD –1.4469, 95% CI –1.7737 to –1.1202; counting recall task, SMD –0.9192, 95% CI –1.4089 to –0.4295; digit recall task, SMD –1.2321, 95% CI –1.4397 to –1.0244; word list recall task, SMD –1.1375, 95% CI –1.5579 to –0.7171; non-word recall task, SMD –1.5355, 95% CI –1.8122 to –1.2589). However, regarding inhibitory control and cognitive flexibility, the differences between DLD and TD children depended on specific circumstances. In subgroup analyses of all verbal working memory tasks, DLD children presented notably lower performance than TD children in both the monolingual English and monolingual non-English groups, and in both the preschooler and school-aged groups.

Conclusion

This study proves that verbal working memory deficits can be seen as a marker for children with DLD and are not affected by age or language type.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=391070, CRD42023391070.
Altered brain function during movement programming is linked with motor deficits after stroke: a high temporal resolution study
Authors: Delcamp Célia , Chalard Alexandre , Srinivasan Ramesh , Cramer Steven C.
Published: August 2024

Introduction

Stroke leads to motor deficits, requiring rehabilitation therapy that targets mechanisms underlying movement generation. Cortical activity during the planning and execution of motor tasks can be studied using EEG, particularly via the Event Related Desynchronization (ERD). ERD is altered by stroke in a manner that varies with extent of motor deficits. Despite this consensus in the literature, defining precisely the temporality of these alterations during movement preparation and performance may be helpful to better understand motor system pathophysiology and might also inform development of novel therapies that benefit from temporal resolution.

Methods

Patients with chronic hemiparetic post-stroke (n = 27; age 59 ± 14 years) and age-matched healthy right-handed control subjects (n = 23; 59 ± 12 years) were included. They performed a shoulder rotation task following the onset of a stimulus. Cortical activity was recorded using a 256-electrode EEG cap. ERD was calculated in the beta frequency band (15–30 Hz) in ipsilesional sensorimotor cortex, contralateral to movement. The ERD was compared over time between stroke and control subjects using permutation tests. The correlation between upper extremity motor deficits (assessed by the Fugl-Meyer scale) and ERD over time was studied in stroke patients using Spearman and permutation tests.

Results

Patients with stroke showed on average less beta ERD amplitude than control subjects in the time window of −350 to 50 ms relative to movement onset (t(46) = 2.8, p = 0.007, Cohen’s d = 0.31, 95% CI [0.22: 1.40]). Beta-ERD values correlated negatively with the Fugl-Meyer score during the time window −200 to 400 ms relative to movement onset (Spearman’s r = −0.54, p = 0.003, 95% CI [−0.77 to −0.18]).

Discussion

Our results provide new insights into the precise temporal changes of ERD after hemiparetic stroke and the associations they have with motor deficits. After stroke, the average amplitude of cortical activity is reduced as compared to age-matched controls, and the extent of this decrease is correlated with the severity of motor deficits; both were true during motor programming and during motor performance. Understanding how stroke affects the temporal dynamics of cortical preparation and execution of movement paves the way for more precise restorative therapies. Studying the temporal dynamics of the EEG also strengthens the promising interest of ERD as a biomarker of post-stroke motor function.
Retrospective review of bladder biopsy instead of skin biopsy provided clue for the diagnosis of neuronal intranuclear inclusion disease
Authors: Liu Jun , Hu Zhenzhu , Tan Weihong , Li Ying , Chen Hao
Published: August 2024

The purpose of this study is to present a case of a patient with a negative skin biopsy who was diagnosed with neuronal intranuclear inclusion disease (NIID) through a retrospective review of a bladder biopsy specimen obtained 10 years ago. The patient initially presented with encephalitis-like symptoms, including fever, headache, and abnormal mental behavior. However, the DWI hyperintensity in the corticomedullary junction indicated the possibility of NIID. Due to the negative results of the skin biopsy, we initially refrained from hastily diagnosing the patient with NIID. However, 6 months later, the patient was readmitted to the hospital due to similar symptoms, and a follow-up MRI showed significant enlargement of the lesions at the corticomedullary junction. This time we identified intranuclear inclusions in her tissue specimens from bladder surgery. Subsequently, genetic testing was performed, leading to the diagnosis of NIID in the patient. Our case report indicates that detecting intranuclear inclusions from previous surgical specimens, rather than relying solely on skin biopsy, could significantly enhance diagnostic methods for NIID.
Retrospective case study: ketogenic metabolic therapy in the effective management of treatment-resistant depressive symptoms in bipolar disorder
Authors: Laurent Nicole
Published: August 2024

This retrospective case study assessed Ketogenic Metabolic Therapy’s (KMT) efficacy in a bipolar disorder patient with treatment-resistant depressive symptoms insufficiently controlled by weekly ketamine treatments. Monitoring included relevant biomarkers of ketone production and macronutrient levels, alongside mood evaluations through the Generalized Anxiety Disorder-7 (GAD-7), Depression Anxiety Stress Scales (DASS), and PTSD Checklist for DSM-5 (PCL-5), showing mood stabilization and improved functionality. Qualitative analysis revealed sub-stantial enhancements in functioning, life quality, and mental well-being. This study enriches the metabolic psychiatry literature, emphasizing KMT’s potential benefits by integrating quantitative data from recognized psychiatric assessment tools and qualitative insights.
Polyphenols alleviate metabolic disorders: the role of ubiquitin-proteasome system
Authors: Gu Wei , Wu Guohuo , Chen Guijie , Meng Xianghui , Xie Zhongwen , Cai Shanbao
Published: August 2024

Metabolic disorders include obesity, nonalcoholic fatty liver disease, insulin resistance and type 2 diabetes. It has become a major health issue around the world. Ubiquitin-proteasome system (UPS) is essential for nearly all cellular processes, functions as a primary pathway for intracellular protein degradation. Recent researches indicated that dysfunctions in the UPS may result in the accumulation of toxic proteins, lipotoxicity, oxidative stress, inflammation, and insulin resistance, all of which contribute to the development and progression of metabolic disorders. An increasing body of evidence indicates that specific dietary polyphenols ameliorate metabolic disorders by preventing lipid synthesis and transport, excessive inflammation, hyperglycemia and insulin resistance, and oxidative stress, through regulation of the UPS. This review summarized the latest research progress of natural polyphenols improving metabolic disorders by regulating lipid accumulation, inflammation, oxidative stress, and insulin resistance through the UPS. In addition, the possible mechanisms of UPS-mediated prevention of metabolic disorders are comprehensively proposed. We aim to provide new angle to the development and utilization of polyphenols in improving metabolic disorders.
Extensive ICP-MS and HPLC-QQQ detections reveal the content characteristics of main metallic elements and polyphenols in the representative commercial tea on the market
Authors: An Yanlin , Qiao Dahe , Jing Tingting , Li Shize
Published: August 2024

The content of polyphenols and metal elements in tea has an important impact on the choice of consumers. In this study, we conducted a comparative analysis of ten elements including Fe, Mg, Al, Zn, Cu, Mn, Ni, Cr, Pb, and As in 122 representative tea samples from 20 provinces. The results showed that the difference of metal content among six tea categories was greater than that among provinces, and the overall metal content of black tea was relatively higher. The contents of all elements from high to low were: Mg > Mn > Al > Fe > Zn > Cu > Ni > Cr > Pb > As. The contents of Ni, Fe, Al, Zn and Mn showed significant differences among multiple types of tea categories. While the detection rates of Pb and As were 10.7 and 24.6%, respectively. The contents of all elements were in line with the national limit standards. Meanwhile, the relative contents of theanine, caffeine and a total of 53 polyphenolic compounds in 122 tea samples were detected. The analysis showed that the content of these compounds differed least between green and yellow tea, and the largest difference between black tea and oolong tea. This study provides important support for consumers to choose tea rationally.
Sacituzumab govitecan response in extensive leptomeningeal carcinomatosis from triple-negative breast cancer: a case report
Authors: Yaringaño Jesús , Roca-Herrera María , Eremiev Simeón , Mascaró-Baselga Pau , Benito Pau , Núñez Fidel , Benavente Sergi , Pimentel Isabel
Published: August 2024

Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate (ADC), was the first ADC approved for patients with metastatic triple-negative breast cancer (mTNBC) who had received at least two prior lines of therapy for advanced disease. Although SG has shown promising clinical activity in treating brain metastases in both ASCENT randomized trials and real-world analysis, its utility in leptomeningeal carcinomatosis (LC) remains underexplored. We report the diagnostic and therapeutic process of a patient who develops extensive LC from TNBC treated with SG. She presented a clinical response after the first cycle of SG with a PFS of 6 months. This case report highlights the need for further inquiry into the use of SG in LC.
The impact of neoadjuvant relugolix on multi-dimensional patient-reported fatigue
Authors: Hsueh Jessica Y. , Gallagher Lindsey , Koh Min Ji , Shah Sarthak , Danner Malika , Zwart Alan , Ayoob Marilyn , Kumar Deepak , Leger Paul , Dawson Nancy A. , Suy Simeng , Collins Sean P.
Published: August 2024

Introduction

Androgen deprivation therapy has been shown to improve cancer control when combined with radiotherapy. Relugolix is an oral GnRH receptor antagonist that achieves rapid profound testosterone suppression, which may increase the perception and/or impact of fatigue. This study sought to evaluate neoadjuvant relugolix-induced fatigue in prostate cancer patients prior to the start of stereotactic body radiation therapy (SBRT).

Methods

Relugolix was initiated at least two months before SBRT. The 13-item Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire was collected at baseline and one hour prior to SBRT initiation. A five-point scale was used to score individual items. Overall scores range from 0-52 and individual item scores were converted to 0-100, with higher scores reflecting less fatigue. Five “experience” items explored self-perceptions of fatigue, and eight “impact” items sought to evaluate the effect of fatigue on daily activities. Items were evaluated for statistical significance (paired t-test, p < 0.05) and clinical significance (minimally important difference (MID); 0.5 standard deviation from baseline).

Results

Between March 2021 to December 2023, 89 men were treated at Georgetown with neoadjuvant relugolix and SBRT. Mean age was 71 years (range: 49-87). Median initiation of relugolix was 4.5 months prior to SBRT (range: 2-14.2 months). 93% patients achieved castration (testosterone levels ≤ 50 ng/dL) and 85% patients achieved profound castration (testosterone levels ≤ 20 ng/dL). 87 patients completed the FACIT-F questionnaire, with an average overall score of 45.6 at baseline and 41.0 at SBRT initiation. This difference was statistically and clinically significant (p < 0.01, MID = 3.55). Patients experienced an increase in fatigue for 12 of 13 items, with statistically significant changes for 11 items. Three of five experience items showed a clinically significant increase in fatigue. Only two of eight impact items were clinically significant.

Discussion

Our study shows that relugolix significantly increases fatigue, affecting multiple areas of life. While the fatigue does not appear to generally impact a patient’s ability to carry out normal activities, patients demonstrate frustration with being too tired for these activities. It is essential for clinicians to counsel prostate cancer patients on the impact of neoadjuvant relugolix on quality-of-life issues like fatigue.
The value of computed tomography-based radiomics for predicting malignant pleural effusions
Authors: Xing Zhen-Chuan , Guo Hua-Zheng , Hou Zi-Liang , Zhang Hong-Xia , Zhang Shuai
Published: August 2024

Background

Malignant pleural effusion (MPE) is a common clinical problem that requires cytological and/or histological confirmation obtained by invasive examination to establish a definitive diagnosis. Radiomics is rapidly evolving and can provide a non-invasive tool to identify MPE.

Objectives

We aimed to develop a model based on radiomic features extracted from unenhanced chest computed tomography (CT) images and investigate its value in predicting MPE.

Method

This retrospective study included patients with pleural effusions between January 2016 and June 2020. All patients underwent a chest CT scanning and medical thoracoscopy after artificial pneumothorax. Cases were divided into a training cohort and a test cohort for modelling and verifying respectively. The Mann-Whitney U test and the least absolute shrinkage and selection operator (LASSO) were applied to determine the optimal features. We built a radiomics model based on support vector machines (SVM) and evaluated its performance using ROC and calibration curve analysis.

Results

Twenty-nine patients with MPE and fifty-two patients with non-MPE were enrolled. A total of 944 radiomic features were quantitatively extracted from each sample and reduced to 14 features for modeling after selection. The AUC of the radiomics model was 0.96 (95% CI: 0.912-0.999) and 0.86 (95% CI: 0.657~1.000) in the training and test cohorts, respectively. The calibration curves for model were in good agreement between predicted and actual data.

Conclusions

The radiomics model based on unenhanced chest CT has good performance for predicting MPE and may provide a powerful tool for doctors in clinical decision-making.
Progression of fertility-sparing treatment for atypical endometrial hyperplasia in a woman with lynch syndrome: a case report and review of the literature
Authors: Hsu Ya-Ting , Chen Chi-Hau
Published: August 2024

Endometrial cancer in Lynch syndrome is characterized by a higher incidence, younger age at onset, and increased recurrence rates compared to sporadic cases, while the safety and efficacy of fertility-sparing treatments remain uncertain. This case report presents the oncology outcome of fertility-preserving treatment in a 39-year-old woman diagnosed with Lynch syndrome and atypical endometrial hyperplasia. Initially, she responded favorably to fertility-preserving treatment but subsequently experienced disease relapse and rapid progression during retreatment. Final pathology revealed endometrial cancer with metastasis to the right ovary, categorized as FIGO 2023 stage IIIA1. This population’s unique molecular mechanisms and genetic mutations warrant special consideration when opting for fertility-sparing treatment. We have reviewed and summarized the oncology and pregnancy outcomes among Lynch syndrome and MMR-deficient patients through previous literature. However, no studies have investigated retreatment after recurrence in Lynch syndrome. Our case highlights the potential risks associated with retreatment following relapse. Vigilant monitoring and prompt consideration of surgical intervention are recommended upon disease relapse.
Biological functions and therapeutic potential of CKS2 in human cancer
Authors: Lai Yueliang , Lin Ye
Published: August 2024

The incidence of cancer is increasing worldwide and is the most common cause of death. Identification of novel cancer diagnostic and prognostic biomarkers is important for developing cancer treatment strategies and reducing mortality. Cyclin-dependent kinase subunit 2 (CKS2) is involved in cell cycle and proliferation processes, and based on these processes, CKS2 was identified as a cancer gene. CKS2 is expressed in a variety of tissues in the human body, but its abnormal expression is associated with cancer in a variety of systems. CKS2 is generally elevated in cancer, plays a role in almost all aspects of cancer biology (such as cell proliferation, invasion, metastasis, and drug resistance) through multiple mechanisms regulating certain important genes, and is associated with clinicopathological features of patients. In addition, CKS2 expression patterns are closely related to cancer type, stage and other clinical variables. Therefore, CKS2 is considered as a tool for cancer diagnosis and prognosis and may be a promising tumor biomarker and therapeutic target. This article reviews the biological function, mechanism of action and potential clinical significance of CKS2 in cancer, in order to provide a new theoretical basis for clinical molecular diagnosis, molecular targeted therapy and scientific research of cancer.
Efficacy of immune checkpoint inhibitors combined with bevacizumab in MSS/pMMR advanced colorectal cancer after first-line treatment failure
Authors: Chen Xiaoqian , Li Wenkui , Lei Xiaogai , Li Zhanhong , Guo Qijing , Ma Xinfu , Luo Yushuang , Wang Liang
Published: August 2024

Objective

To investigate the effects of a PD-1 inhibitor combined with a bevacizumab monoclonal antibody on tumor immune cells in patients with first-line treatment failure in MSS/pMMR advanced colorectal cancer.

Methods

Control group consisted of 50 patients treated with the FOLFIRI combined with Bevacizumab regimen. The experimental group consisted of 60 patients treated with the Sintilimab combined with Bevacizumab regimen. By comparing the expression levels of CD8+ T lymphocytes, TAMs, and CAFs before and after treatment, short-term efficacy after treatment, and adverse drug reactions between the two groups, we comprehensively evaluated the impact of Sintilimab combined with Bevacizumab on patients with MSS/pMMR advanced colorectal cancer who failed first-line treatment.

Results

There was a statistically significant difference in the percentage of CD8+ T lymphocytes, TAMs, and CAFs before and after treatment between the two groups (P<0.05);Immunohistochemical scoring of CD8+ T lymphocytes, TAMs, and CAFs showed significant differences between the groups post-treatment (P<0.05). The experimental group demonstrated statistically significant differences in immunohistochemical scoring of CD8+ T lymphocytes, TAMs, and CAFs before and after treatment (P<0.05). There was a statistically significant difference in the therapeutic effect between the two groups of tumors (P<0.05). The experimental group had greater PFS, mPFS, ORR, and DCR than did the control group. There was no statistically significant difference in the occurrence rate of drug-related adverse reactions after treatment between the two groups (P>0.05). The results of the Cox proportional hazards model analysis indicate that age, gender, and group are independent risk factors affecting MSS/pMMR advanced colorectal cancer patients treated with second-line therapy in this study. Patients aged ≤60 years, male patients, and those in the experimental group showed better treatment responses in this study.

Conclusion

By administering immune checkpoint inhibitors in combination with bevacizumab to patients with advanced colorectal cancer with MSS/pMMR disease for whom first-line treatment failed, not only did the patients’ prognosis improve, but the adverse drug reactions were also safe and controllable.
Application of artificial intelligence in the diagnosis and treatment of urinary tumors
Authors: Zhu Mengying , Gu Zhichao , Chen Fang , Chen Xi , Wang Yue , Zhao Guohua
Published: August 2024

Diagnosis and treatment of urological tumors, relying on auxiliary data such as medical imaging, while incorporating individual patient characteristics into treatment selection, has long been a key challenge in clinical medicine. Traditionally, clinicians used extensive experience for decision-making, but recent artificial intelligence (AI) advancements offer new solutions. Machine learning (ML) and deep learning (DL), notably convolutional neural networks (CNNs) in medical image recognition, enable precise tumor diagnosis and treatment. These technologies analyze complex medical image patterns, improving accuracy and efficiency. AI systems, by learning from vast datasets, reveal hidden features, offering reliable diagnostics and personalized treatment plans. Early detection is crucial for tumors like renal cell carcinoma (RCC), bladder cancer (BC), and Prostate Cancer (PCa). AI, coupled with data analysis, improves early detection and reduces misdiagnosis rates, enhancing treatment precision. AI’s application in urological tumors is a research focus, promising a vital role in urological surgery with improved patient outcomes. This paper examines ML, DL in urological tumors, and AI’s role in clinical decisions, providing insights for future AI applications in urological surgery.
Immunometabolism of ferroptosis in the tumor microenvironment
Authors: Lupica-Tondo Gian Luca , Arner Emily N. , Mogilenko Denis A. , Voss Kelsey
Published: August 2024

Ferroptosis is an iron-dependent form of cell death that results from excess lipid peroxidation in cellular membranes. Within the last decade, physiological and pathological roles for ferroptosis have been uncovered in autoimmune diseases, inflammatory conditions, infection, and cancer biology. Excitingly, cancer cell metabolism may be targeted to induce death by ferroptosis in cancers that are resistant to other forms of cell death. Ferroptosis sensitivity is regulated by oxidative stress, lipid metabolism, and iron metabolism, which are all influenced by the tumor microenvironment (TME). Whereas some cancer cell types have been shown to adapt to these stressors, it is not clear how immune cells regulate their sensitivities to ferroptosis. In this review, we discuss the mechanisms of ferroptosis sensitivity in different immune cell subsets, how ferroptosis influences which immune cells infiltrate the TME, and how these interactions can determine epithelial-to-mesenchymal transition (EMT) and metastasis. While much focus has been placed on inducing ferroptosis in cancer cells, these are important considerations for how ferroptosis-modulating strategies impact anti-tumor immunity. From this perspective, we also discuss some promising immunotherapies in the field of ferroptosis and the challenges associated with targeting ferroptosis in specific immune cell populations.
Navigating the shadows: medical professionals’ values and perspectives on end-of-life care within pediatric intensive care units in Croatia
Authors: Curkovic Marko , Rubic Filip , Jozepovic Ana , Novak Milivoj , Filipovic-Grcic Boris , Mestrovic Julije , Lah Tomulic Kristina , Peter Branimir , Spoljar Diana , Grosek Štefan , Janković Sunčana , Vukovic Jurica , Kujundžić Tiljak Mirjana , Štajduhar Andrija , Borovecki Ana
Published: August 2024

Background and aim

This study explores healthcare professionals’ perspectives on end-of-life care in pediatric intensive care units (ICUs) in Croatia, aiming to illuminate their experiences with such practices, underlying attitudes, and major decision-making considerations. Amid the high variability, complexity, and emotional intensity of pediatric end-of-life decisions and practices, understanding these perspectives is crucial for improving care and policies.

Methods

The study utilized a cross-sectional survey intended for physicians and nurses across all pediatric ICUs in Croatia. It included healthcare professionals from six neonatal and four pediatric ICUs in total. As the data from neonatal and pediatric ICUs were examined jointly, the term pediatric ICU was used to denominate both types of ICUs. A statistical analysis was performed using Python and JASP, focusing on professional roles, professional experience, and regional differences.

Results

The study included a total of 103 participants (with an overall response rate—in relation to the whole target population—of 48% for physicians and 29% for nurses). The survey revealed diverse attitudes toward and experiences with various aspects of end-of-life care, with a significant portion of healthcare professionals indicating infrequent involvement in life-sustaining treatment (LST) limitation discussions and decisions, as well as somewhat ambiguous attitudes regarding such practices. Notably, discrepancies emerged between different professional roles and, in particular, regions, underscoring the high variability of LST limitation-related procedures.

Conclusions

The findings highlight a pressing need for more straightforward guidelines, legal frameworks, support mechanisms, and communication strategies to navigate the complex terrain of rather burdensome end-of-life pediatric care, which is intrinsically loaded with profound ethical quandaries.
Systematic bioinformatics analysis reveals the role of shikonin in blocking colon cancer progression by identifying senescence-induced genes
Authors: Liu Wenna , Zhao Yujia , Liu Qingqing , Wu Dan , Li Wenxuan , Fu Zhenkai , Yang Le , Liang Ying
Published: August 2024

Shikonin, a naturally occurring naphthoquinone compound extracted from comfrey plants, has antitumor, anti-inflammatory, and antimicrobial properties. Cell senescence plays a key role in preventing tumor progression. It is unclear whether shikonin has an effect on cell senescence in colon cancer. In the current study, we first determine the IC50 values of shikonin on colon cancer cell lines HT29 and HCT116. Then, we verified the inhibitory effects of shikonin on the proliferation and migration abilities of colon cancer cell lines HT29 and HCT116 using cell counting kit-8, colony formation, and wound healing assays. Next, we identified a series of potential targets using high-throughput mRNA sequencing and identified 210 upregulated and 296 downregulated genes. KEGG profiling revealed eight downregulated genes associated with cell senescence: CCNB3, IL-1α, CXCL8, CDKN2A, MYC, IGFBP3, SQSTM1, and GADD45G. Among them, CXCL8 and CDKN2A were associated with poor prognosis in patients with colon cancer, suggesting that their downregulation by shikonin could improve patient survival. Furthermore, SA-β-galactosidase staining revealed that the percentage of cellular senescence in colon cancer cells was significantly increased after shikonin treatment. Molecular docking revealed that shikonin suppressed colon cancer progression by blocking CXCL8 activity. Based on these findings, we deem that shikonin might induce senescence and exert antitumor activity in colon cancer cells by downregulating CDKN2A and CXCL8. This provides a new molecular mechanism and potential therapeutic target for shikonin to inhibit colon cancer progression.
Licochalcone A: a review of its pharmacology activities and molecular mechanisms
Authors: Liu Meihua , Du Yang , Gao Dejiang
Published: August 2024

Licorice, derived from the root of Glycyrrhiza uralensis Fisch, is a key Traditional Chinese Medicine known for its detoxifying, spleen-nourishing, and qi-replenishing properties. Licochalcone A (Lico A), a significant component of licorice, has garnered interest due to its molecular versatility and receptor-binding affinity. This review explores the specific roles of Lico A in various diseases, providing new insights into its characteristics and guiding the rational use of licorice. Comprehensive literature searches using terms such as “licorice application” and “pharmacological activity of Lico A” were conducted across databases including CNKI, PubMed, and Google Scholar to gather relevant studies on Lico A’s pharmacological activities and mechanisms. Lico A, a representative chalcone in licorice, targets specific mechanisms in anti-cancer and anti-inflammatory activities. It also plays a role in post-transcriptional regulation. This review delineates the similarities and differences in the anti-cancer and anti-inflammatory mechanisms of Lico A, concluding that its effects on non-coding RNA through post-transcriptional mechanisms deserve further exploration.
Poloidally asymmetric potential formation on plasma boundary in axisymmetric magnetic field
Authors: Le Trang , Suzuki Yasuhiro , Ohtani Hiroaki , Hasegawa Hiroki , Moritaka Toseo
Published: August 2024

To study the symmetry of electrical potential, we model plasma transport in the edge region of a toroidal device with two spatial dimensions (2D) and three coordinates for velocities (3V) using a Particle-In-Cell (PIC) code. A two-dimensional magnetic field is applied, including poloidal and toroidal components, which are periodic in the poloidal direction. We discover relationships between the magnetic gradient drift and potential formation using PIC simulation, which has not been captured in other numerical models. We find that the inverse aspect ratio influences the asymmetry of the potential in an axisymmetric magnetic configuration.
Intracranial pressure-flow relationships in traumatic brain injury patients expose gaps in the tenets of models and pressure-oriented management
Authors: Stroh J. N. , Foreman Brandon , Bennett Tellen D. , Briggs Jennifer K. , Park Soojin , Albers David J.
Published: August 2024

Background: The protocols and therapeutic guidance established for treating traumatic brain injury (TBI) in neurointensive care focus on managing cerebral blood flow (CBF) and brain tissue oxygenation based on pressure signals. The decision support process relies on assumed relationships between cerebral perfusion pressure (CPP) and blood flow, pressure-flow relationships (PFRs), and shares this framework of assumptions with mathematical intracranial hemodynamics models. These foundational assumptions are difficult to verify, and their violation can impact clinical decision-making and model validity.

Methods: A hypothesis- and model-driven method for verifying and understanding the foundational intracranial hemodynamic PFRs is developed and applied to a novel multi-modality monitoring dataset.

Results: Model analysis of joint observations of CPP and CBF validates the standard PFR when autoregulatory processes are impaired as well as unmodelable cases dominated by autoregulation. However, it also identifies a dynamical regime -or behavior pattern-where the PFR assumptions are wrong in a precise, data-inferable way due to negative CPP-CBF coordination over long timescales. This regime is of both clinical and research interest: its dynamics are modelable under modified assumptions while its causal direction and mechanistic pathway remain unclear.

Conclusion: Motivated by the understanding of mathematical physiology, the validity of the standard PFR can be assessed a) directly by analyzing pressure reactivity and mean flow indices (PRx and Mx) or b) indirectly through the relationship between CBF and other clinical observables. This approach could potentially help to personalize TBI care by considering intracranial pressure and CPP in relation to other data, particularly CBF. The analysis suggests a threshold using clinical indices of autoregulation jointly generalizes independently set indicators to assess CA functionality. These results support the use of increasingly data-rich environments to develop more robust hybrid physiological-machine learning models.
Model-driven engineering for digital twins: a graph model-based patient simulation application
Authors: Trevena William , Zhong Xiang , Lal Amos , Rovati Lucrezia , Cubro Edin , Dong Yue , Schulte Phillip , Gajic Ognjen
Published: August 2024

Introduction

Digital twins of patients are virtual models that can create a digital patient replica to test clinical interventions in silico without exposing real patients to risk. With the increasing availability of electronic health records and sensor-derived patient data, digital twins offer significant potential for applications in the healthcare sector.

Methods

This article presents a scalable full-stack architecture for a patient simulation application driven by graph-based models. This patient simulation application enables medical practitioners and trainees to simulate the trajectory of critically ill patients with sepsis. Directed acyclic graphs are utilized to model the complex underlying causal pathways that focus on the physiological interactions and medication effects relevant to the first 6 h of critical illness. To realize the sepsis patient simulation at scale, we propose an application architecture with three core components, a cross-platform frontend application that clinicians and trainees use to run the simulation, a simulation engine hosted in the cloud on a serverless function that performs all of the computations, and a graph database that hosts the graph model utilized by the simulation engine to determine the progression of each simulation.

Results

A short case study is presented to demonstrate the viability of the proposed simulation architecture.

Discussion

The proposed patient simulation application could help train future generations of healthcare professionals and could be used to facilitate clinicians’ bedside decision-making.
Body position and cuff size influence lower limb arterial occlusion pressure and its predictors: implications for standardizing the pressure applied in training with blood flow restriction
Authors: de Queiros Victor S. , Rolnick Nicholas , Kamiş Okan , Formiga Magno F. , Rocha Roberto F. C. , Alves Júlio César Medeiros , Vieira João Guilherme , Vianna Jeferson Macedo , Wilk Michal , Fostiak Krzysztof , Cabral Breno Guilherme de Araújo Tinôco , Dantas Paulo Moreira Silva
Published: August 2024

Background:Arterial occlusion pressure (AOP) is a relevant measurement for individualized prescription of exercise with blood flow restriction (BFRE). Therefore, it is important to consider factors that may influence this measure.

Purpose:This study aimed to compare lower limb AOP (LL-AOP) measured with 11 cm (medium) and 18 cm (large) cuffs, in different body positions, and explore the predictors for each of the LL-AOP measurements performed. This information may be useful for future studies that seek to develop approaches to improve the standardization of pressure adopted in BFRE, including proposals for equations to estimate LL-AOP.

Methods:This is a cross-sectional study. Fifty-one healthy volunteers (males,n= 25, females,n= 26; Age: 18–40 years old) underwent measurement of thigh circumference (TC), brachial blood pressure, followed by assessments of LL-AOP with medium and large cuffs in positions supine, sitting and standing positions.

Results:The large cuff required less external pressure (mmHg) to elicit arterial occlusion in all three-body positions when compared to the medium cuff (p < 0.001). The LL-AOP was significantly lower in the supine position, regardless of the cuff used (p < 0.001). Systolic blood pressure was the main predictor of LL-AOP in the large cuff, while TC was the main predictor of LL-AOP with the medium cuff. Body position influenced strength of the LL-AOP predictors.

Conclusion:Our results indicate that LL-AOP and its predictors are substantially influenced by body position and cuff width. Therefore, these variables should be considered when standardizing the pressure prescribed in BFRE.