bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of drug-induced electrolyte disorders in intensive care units: a multicenter observational study
Authors: Ayhan Yunus Emre , İlerler Enes Emir , Sosyal Damla , Bektay Muhammed Yunus , Karakurt Sait , Daşkaya Hayrettin , Karaaslan Kazım , Sancar Mesut
Published: June 2024

Objective

Electrolyte disorder (ED) is frequently encountered critically ill patients during admission or admission to the intensive care unit (ICU). This study aimed to determine the frequency of ED encountered in ICU patients to evaluate the relationship of ED with drugs.

Methods

This prospective, multicenter study was conducted in the medical and anesthesiology ICUs of two training and research hospitals and included patients with at least one ED during admission or hospitalization in the ICUs. The relationship between ED and the drug was evaluated by calculating the logistic probabilistic method scale (LPMS) and the expert panel’s evaluation. The correlation between EDs and LPMS was determined using Kendal tau. A binary logistic regression model was preferred in the analysis of factors related to ED. Statistical significance was set as p < 0.05.

Results

A total of 117 patients were included in the study. A total of 165 EDs were detected, including at least one in 88 (75.2%) patients. According to the expert panel, 61 (21.7%) of EDs were drug-related, whereas according to the LPMS, 111 (39.6%) (p < 0.001). Mortality (50% vs. 13.7%) and mechanical ventilation rates (52.2% vs. 17.2%) were significantly higher in patients with ED (p < 0.001). Patients with ED had 8.352 times higher odds of exhibiting mortality (OR: 8.352, %95 CI: 1.598–43.648, p: 0.012) and need mechanical ventilation with higher odds of 3.229 (OR: 3.229 95% CI: 0.815–12.787 p: 0.045). Patient who required enteral or parenteral feeding were associated with an increased likelihood of exhibiting ED (respectively OR: 30.057, %95 CI: 2.265–398.892, p: 0.01, OR: 5.537, %95 CI: 1.406–21.800, p: 0.014).

Conclusion

EDs are very common in the ICU. Dysnatremia was detected more commonly in other EDs. It has also been found that patients with ED are more often under mechanical ventilation, have more prolonged hospitalizations, and have higher mortality rates than patients without ED. The suitability of LPMS for assessing ED-drug relationships in the ICU context is questioned.
Identification of novel biomarkers for anti-Toxoplasma gondii IgM detection and the potential application in rapid diagnostic fluorescent tests
Authors: Nguyen Minh-Ngoc , Yeo Seon-Ju , Park Hyun
Published: June 2024

Toxoplasmosis, while often asymptomatic and prevalent as a foodborne disease, poses a considerable mortality risk for immunocompromised individuals during pregnancy. Point-of-care serological tests that detect specific IgG and IgM in patient sera are critical for disease management under limited resources. Despite many efforts to replace the T. gondii total lysate antigens (TLAs) by recombinant antigens (rAgs) in commercial kits, while IgG detection provides significant specificity and sensitivity, IgM detection remains comparatively low in sensitivity. In this study, we attempted to identify novel antigens targeting IgM in early infection, thereby establishing an IgM on-site detection kit. Using two-dimensional gel electrophoresis (2DE) and mouse serum immunoblotting, three novel antigens, including EF1γ, PGKI, and GAP50, were indicated to target T. gondii IgM. However, rAg EF1γ was undetectable by IgM of mice sera in Western blotting verification experiments, and ELISA coated with PGKI did not eliminate cross-reactivity, in contrast to GAP50. Subsequently, the lateral flow reaction employing a strip coated with 0.3 mg/mL purified rAg GAP50 and exhibited remarkable sensitivity compared with the conventional ELISA based on tachyzoite TLA, which successfully identified IgM in mouse sera infected with tachyzoites, ranging from 103 to 104 at 5 dpi and 104 at 7 dpi, respectively. Furthermore, by using standard T. gondii-infected human sera from WHO, the limit of detection (LOD) for the rapid fluorescence immunochromatographic test (FICT) using GAP50 was observed at 0.65 IU (international unit). These findings underline the particular immunoreactivity of GAP50, suggesting its potential as a specific biomarker for increasing the sensitivity of the FICT in IgM detection.
Genetically supported causality between gut microbiota, immune cells, and ischemic stroke: a two-sample Mendelian randomization study
Authors: Shuai Han , Wang Zi , Xiao Yinggang , Ge Yali , Mao Hua , Gao Ju
Published: June 2024

Background

Previous studies have highlighted a robust correlation between gut microbiota/immune cells and ischemic stroke (IS). However, the precise nature of their causal relationship remains uncertain. To address this gap, our study aims to meticulously investigate the causal association between gut microbiota/immune cells and the likelihood of developing IS, employing a two-sample Mendelian randomization (MR) analysis.

Methods

Our comprehensive analysis utilized summary statistics from genome-wide association studies (GWAS) on gut microbiota, immune cells, and IS. The primary MR method employed was the inverse variance-weighted (IVW) approach. To address potential pleiotropy and identify outlier genetic variants, we incorporated the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) technique, along with MR-Egger regression. Heterogeneity was assessed using Cochran’s Q-test. Additionally, leave-one-out analysis was conducted to pinpoint any individual genetic variant influencing the observed causal associations. Finally, a reverse MR analysis was performed to explore the potential of reverse causation.

Results

Our investigation revealed four gut microbial taxa and 16 immune cells with a significant causal relationship with IS (p < 0.05). Notably, two bacterial features and five immunophenotypes were strongly associated with a lower IS risk: genus.Barnesiella.id.944 (OR: 0.907, 95% CI: 0.836–0.983, p = 0.018), genus.LachnospiraceaeNK4A136group.id.11319 (OR: 0.918, 95% CI: 0.853–0.983, p = 0.988), Activated & resting Treg % CD4++ (OR: 0.977, 95% CI: 0.956–0.998, p = 0.028). Additionally, significant associations between IS risk and two bacterial features along with eleven immunophenotypes were observed: genus.Paraprevotella.id.962 (OR: 1.106, 95% CI: 1.043–1.172, p < 0.001), genus.Streptococcus.id.1853 (OR: 1.119, 95% CI: 1.034–1.210, p = 0.005), CD127 on granulocyte (OR: 1.039, 95% CI: 1.009–1.070, p = 0.011). Our analyses did not reveal heterogeneity based on the Cochrane’s Q-test (p > 0.05) nor indicate instances of horizontal pleiotropy according to MR-Egger and MR-PRESSO analyses (p > 0.05). Furthermore, the robustness of our MR results was confirmed through leave-one-out analysis.

Conclusion

Our study provides further evidence supporting the potential association between gut microbiota and immune cells in relation to IS, shedding light on the underlying mechanisms that may contribute to this condition. These findings lay a solid foundation for future investigations into targeted prevention strategies.
Entertainment activities and the risk of Alzheimer’s disease: a Mendelian randomization analysis
Authors: Lu Tianqi , Wang Lilin , Zheng Yunhua , Liu Hua , Liu Jianyu
Published: June 2024

Background

Effective prevention is key to addressing the increasing prevalence and mortality of Alzheimer’s disease. Assessing the causal relationship between modifiable entertainment activity factors and the risk of Alzheimer’s disease is important for developing public health measures, but establishing causal relationships in epidemiological data may be challenging.

Methods

This study using the two-sample Mendelian randomization analysis aimed to investigate the causal effect of entertainment activity factors on the risk of Alzheimer’s disease. Summary statistics from publicly available genome-wide association studies were used to analyze 14 modifiable entertainment activity. The inverse variance weighted random effects method as the primary analytical method to estimate causal effects was used. Additionally performed MR-Egger, weighted median and weighted model methods to assess the robustness of the results. The reliability of our findings was validated through systematic sensitivity analyses and tests for heterogeneity.

Results

We found significant correlation between time spent using computer (odds ratio 0.998; 95% confidence interval 0.996–0.999; p = 0.013) and Alzheimer’s disease, compared to other studied entertainment activities that had no significant causal relationship with Alzheimer’s disease.

Conclusion

Our findings support the hypothesis that increased computer use may reduce the risk of Alzheimer’s disease, providing potential strategic directions for the prevention of neurodegenerative diseases.
A framework for neurosymbolic robot action planning using large language models
Authors: Capitanelli Alessio , Mastrogiovanni Fulvio
Published: June 2024

Symbolic task planning is a widely used approach to enforce robot autonomy due to its ease of understanding and deployment in engineered robot architectures. However, techniques for symbolic task planning are difficult to scale in real-world, highly dynamic, human-robot collaboration scenarios because of the poor performance in planning domains where action effects may not be immediate, or when frequent re-planning is needed due to changed circumstances in the robot workspace. The validity of plans in the long term, plan length, and planning time could hinder the robot's efficiency and negatively affect the overall human-robot interaction's fluency. We present a framework, which we refer to as Teriyaki, specifically aimed at bridging the gap between symbolic task planning and machine learning approaches. The rationale is training Large Language Models (LLMs), namely GPT-3, into a neurosymbolic task planner compatible with the Planning Domain Definition Language (PDDL), and then leveraging its generative capabilities to overcome a number of limitations inherent to symbolic task planners. Potential benefits include (i) a better scalability in so far as the planning domain complexity increases, since LLMs' response time linearly scales with the combined length of the input and the output, instead of super-linearly as in the case of symbolic task planners, and (ii) the ability to synthesize a plan action-by-action instead of end-to-end, and to make each action available for execution as soon as it is generated instead of waiting for the whole plan to be available, which in turn enables concurrent planning and execution. In the past year, significant efforts have been devoted by the research community to evaluate the overall cognitive capabilities of LLMs, with alternate successes. Instead, with Teriyaki we aim to providing an overall planning performance comparable to traditional planners in specific planning domains, while leveraging LLMs capabilities in other metrics, specifically those related to their short- and mid-term generative capabilities, which are used to build a look-ahead predictive planning model. Preliminary results in selected domains show that our method can: (i) solve 95.5% of problems in a test data set of 1,000 samples; (ii) produce plans up to 13.5% shorter than a traditional symbolic planner; (iii) reduce average overall waiting times for a plan availability by up to 61.4%.
Association between admission serum potassium concentration and the island sign on cranial CT in HICH patients: a cross-sectional study
Authors: Wang Yanglingxi , Chen Peng , Liang Yidan , Deng Yongbing , Zhou Weiduo
Published: June 2024

Objective

This study aimed to explore the correlation between serum potassium (K+) concentration upon admission and the presence of the Island Sign (IS) in cranial CT scans of patients diagnosed with Hypertensive Intracerebral Hemorrhage (HICH), including the potential presence of a non-linear relationship.

Methods

This investigation constituted a single-center cross-sectional study. We systematically gathered comprehensive general clinical characteristics, biological indicators, and imaging data from a cohort of 330 patients diagnosed with HICH. These patients received treatment within the neurosurgery department of Chongqing Emergency Medical Center during the period spanning from July 1, 2018, to July 7, 2023. Our primary objective was to scrutinize the potential connection between serum K+ concentration upon admission and the presence of the IS observed in cranial CT scans. To meticulously address this inquiry, we employed logistic regression modeling, thereby meticulously evaluating the correlation aforementioned. Moreover, in order to delve deeper into the intricacies of the relationship, we extended our analysis by employing a smoothed curve-fitting model to meticulously authenticate the potential non-linear interrelation between these two critical variables.

Results

In this investigation, a total of 330 patients diagnosed with HICH were ultimately enrolled, exhibiting an average age of 58.4 ± 13.1 years, comprising 238 (72.1%) males and 92 (27.9%) females. Among these participants, 118 individuals (35.7%) presented with the IS upon admission cranial CT scans, while 212 patients (64.3%) did not exhibit this characteristic. Upon comprehensive multifactorial adjustments, a non-linear association was uncovered between serum K+ concentration and the presence of IS. Notably, an inflection point was identified at approximately 3.54 mmol/L for serum K+ concentration. Prior to the patient’s serum K+ concentration reaching around 3.54 mmol/L upon admission, a discernible trend was observed—every 0.1 mmol/L increment in serum K+ concentration was associated with an 8% decrease in the incidence of IS (OR: 0.914, 95% CI: 0.849–0.983, p = 0.015).

Conclusion

The findings of this study underscore a negative association between reduced serum K+ concentration upon admission and the occurrence of the IS on cranial CT scans among patients diagnosed with hypertensive cerebral hemorrhage. Furthermore, this negative correlation appears to manifest within the realm of a non-linear relationship. This study elucidates the potential significance of serum K+ concentration levels among patients with HICH, highlighting the role they play. Moreover, the maintenance of a physiological equilibrium in serum K+ concentrations emerges as a conceivable protective factor for individuals within the stroke population.
The importance of multimodal CT examination in stroke mimics diagnosis: design of prospective observational multicentre study
Authors: Dvorníková Kateřina , Kunešová Veronika , Ely Marcela , Ostrý Svatopluk , Čábal Martin , Reiser Martin , Machová Linda , Pavlínová Markéta , Kondé Adéla , Eliáš Pavel , Jonszta Tomáš , Havelka Jaroslav , Volný Ondrej , Bar Michal
Published: June 2024

Introduction

Non-contrast computed tomography (CT) and CT angiography are the gold standard in neuroimaging diagnostics in the case of suspected stroke. CT perfusion (CTP) may play an important role in the diagnosis of stroke mimics (SM), but currently, it is not a standard part of the stroke diagnostic procedure. The project is a multicentre prospective observational clinical research focused on refining the diagnostics of stroke and stroke mimics (SM) in hospital care.

Aim

This study aimed to evaluate the degree of specificity and sensitivity of multimodal CT (NCCT, CTA, and CTP) in the diagnosis of SM versus stroke.

Methodology

In this study, we will include 3,000 patients consecutively admitted to the comprehensive stroke centres with a diagnosis of suspected stroke. On the basis of clinical parameters and the results of multimodal CT and magnetic resonance imaging (MRI), the diagnosis of stroke and SM will be established. To clarify the significance of the use of the multimodal CT scan, the analysis will include a comparison of the blinded results for each imaging scan performed by radiologists and AI technology and a comparison of the initial and final diagnosis of the enrolled patients. Based on our results, we will compare the economic indicators and costs that would be saved by not providing inadequate treatment to patients with SM.

Conclusion

The expected outcome is to present an optimised diagnostic procedure that results in a faster and more accurate diagnosis, thereby eliminating the risk of inadequate treatment in patients with SM.

Clinical trial registration

clinicaltrials.gov, NCT06045455.
Multiplexing intensity and frequency sensations for artificial touch by modulating temporal features of electrical pulse trains
Authors: Ng Kevin K. W. , So Alwin , Fang Jun Yi , Birznieks Ingvars , Vickery Richard M.
Published: June 2024

In neural prostheses, intensity modulation of a single channel (i.e., through a single stimulating electrode) has been achieved by increasing the magnitude or width of each stimulation pulse, which risks eliciting pain or paraesthesia; and by changing the stimulation rate, which leads to concurrent changes in perceived frequency. In this study, we sought to render a perception of tactile intensity and frequency independently, by means of temporal pulse train patterns of fixed magnitude, delivered non-invasively. Our psychophysical study exploits a previously discovered frequency coding mechanism, where the perceived frequency of stimulus pulses grouped into periodic bursts depends on the duration of the inter-burst interval, rather than the mean pulse rate or periodicity. When electrical stimulus pulses were organised into bursts, perceived intensity was influenced by the number of pulses within a burst, while perceived frequency was determined by the time between the end of one burst envelope and the start of the next. The perceived amplitude was modulated by 1.6× while perceived frequency was varied independently by 2× within the tested range (20–40 Hz). Thus, the sensation of intensity might be controlled independently from frequency through a single stimulation channel without having to vary the injected electrical current. This can form the basis for improving strategies in delivering more complex and natural sensations for prosthetic hand users.
Spinocerebellar ataxias: from pathogenesis to recent therapeutic advances
Authors: Cui Zi-Ting , Mao Zong-Tao , Yang Rong , Li Jia-Jia , Jia Shan-Shan , Zhao Jian-Li , Zhong Fang-Tian , Yu Peng , Dong Ming
Published: June 2024

Spinocerebellar ataxia is a phenotypically and genetically heterogeneous group of autosomal dominant-inherited degenerative disorders. The gene mutation spectrum includes dynamic expansions, point mutations, duplications, insertions, and deletions of varying lengths. Dynamic expansion is the most common form of mutation. Mutations often result in indistinguishable clinical phenotypes, thus requiring validation using multiple genetic testing techniques. Depending on the type of mutation, the pathogenesis may involve proteotoxicity, RNA toxicity, or protein loss-of-function. All of which may disrupt a range of cellular processes, such as impaired protein quality control pathways, ion channel dysfunction, mitochondrial dysfunction, transcriptional dysregulation, DNA damage, loss of nuclear integrity, and ultimately, impairment of neuronal function and integrity which causes diseases. Many disease-modifying therapies, such as gene editing technology, RNA interference, antisense oligonucleotides, stem cell technology, and pharmacological therapies are currently under clinical trials. However, the development of curative approaches for genetic diseases remains a global challenge, beset by technical, ethical, and other challenges. Therefore, the study of the pathogenesis of spinocerebellar ataxia is of great importance for the sustained development of disease-modifying molecular therapies.
Magnesium status modulating the effect of serum vitamin D levels on retinopathy: National Health and Nutrition Examination Survey 2005 to 2008
Authors: Xu Lei , Yuan Penghua , Liu Wanrong , Liu Linlin , Li Xiongfeng , Xie Lianfeng
Published: June 2024

Aim

Magnesium levels may influence the effect of vitamin D levels on the body. This study aimed to assess the combined effect of magnesium status as reflected by magnesium depletion score (MDS) and vitamin D status on the risk of retinopathy.

Methods

This cross-sectional study included participants aged 40 years and older with complete information on vitamin D, MDS, and retinopathy assessment from the 2005–2008 National Health and Nutrition Examination Survey (NHANES). Logistic regression analysis was utilized to analyze the relationship of MDS and vitamin D with retinopathy and expressed as odds ratio (OR) and 95% confidence interval (CI).

Results

Of these 4,953 participants included, 602 (9.53%) participants had retinopathy. Serum vitamin D levels ≤30 nmol/L (vs. >30 nmol/L) (OR = 1.38, 95%CI: 1.05–1.81) and MDS >2 points (vs. ≤2 points) (OR = 1.47, 95%CI: 1.01–2.16) were associated with higher odds of retinopathy. There was an interaction between MDS and vitamin D on the increased odds of retinopathy (OR = 2.29, 95%CI: 1.12–4.68, Pinteraction = 0.025). In different MDS groups, serum vitamin D levels ≤30 nmol/L increased the odds of retinopathy only in the MDS >2 group (OR = 2.90, 95%CI: 1.16–7.24), but not in the MDS ≤2 group (p = 0.293). Subgroups analyses demonstrated that the interaction between MDS and serum vitamin D on retinopathy was observed in males (OR = 6.88, 95%CI: 1.41–33.66, Pinteraction = 0.019), people with diabetes (OR = 3.43, 95%CI: 1.78–6.63, Pinteraction < 0.001), and people with body mass index (BMI) ≥25 kg/m2 (OR = 2.46, 95%CI: 1.11–5.44, Pinteraction = 0.028).

Conclusion

Magnesium plays a moderating role in the relationship between serum vitamin D and retinopathy. The protective effect of vitamin D against retinopathy was primarily present among those with inadequate magnesium levels.
Microwave ablation with hydrodissection used for the treatment of vascular malformations: effectiveness and safety study
Authors: Wang Lu , Lu Man , Zhuang Min , Liang Ying , Wang Shi Shi , Li Jia Mi
Published: June 2024

Object

The aim of the study was to investigate the safety, effectiveness, and peripheral nerve protection in ultrasound-guided microwave ablation (US-guided-MWA) for vascular malformations (VMs) closely related to peripheral nerve.

Materials and methods

From August 2019 to February 2022, 31 patients with 39 VMs received US-guided-MWA. All lesions were confirmed to be closely related to the peripheral nerve by imaging evaluation. Hydrodissection was applied to protect surrounding normal tissue, including peripheral nerves. The patients were followed up at 1day, 2 days, 3 days, 1 week, 1 month, 3 months after operation. Measurements of lesion volume, volume reduction ratio (VRR), sensory and functional abnormalities of adjacent nerves, number of treatments, complication details, personal satisfaction, recurrence, and symptom improvement were recorded.

Results

Among the 39 VMs, the maximum volume is 128.58ml, while the minimum volume is 0.99ml. After a mean follow-up of 13.06 ± 4.83 months, the mean numerical rating scale (NRS) score decreased from 5.13 ± 1.65 to 0.53 ± 0.83 (P<0.0001). The mean mass volume was reduced from 18.34 ± 24.68 ml to 1.35 ± 2.09 ml (P=0.0001). The VRR of all lesions was 92.06%. However, the mean number of treatments was only 1.64 ± 0.87. All patients were satisfied with the technique, with a mean satisfaction score (SC) of 9.23 ± 1.13. There were no motor function abnormalities of the related nerves. 10 patients felt numbness in the ablation area after ablation, and gradually recovered after 1 month.

Conclusion

US-guided-MWA serves as a novel alternative approach for patients with VMs. Preoperative evaluation of the relationship between VMs and peripheral nerves combined with intraoperative hydrodissection is an effective and safe method to prevent nerve injury.
Magnetic resonance image-guided adaptive radiotherapy enables safe CTV-to-PTV margin reduction in prostate cancer: a cine MRI motion study
Authors: Westley Rosalyne L. , Alexander Sophie E. , Goodwin Edmund , Dunlop Alex , Nill Simeon , Oelfke Uwe , McNair Helen A. , Tree Alison C.
Published: June 2024

Introduction

We aimed to establish if stereotactic body radiotherapy to the prostate can be delivered safely using reduced clinical target volume (CTV) to planning target volume (PTV) margins on the 1.5T MR-Linac (MRL) (Elekta, Stockholm, Sweden), in the absence of gating.

Methods

Cine images taken in 3 orthogonal planes during the delivery of prostate SBRT with 36.25 Gray (Gy) in 5 fractions on the MRL were analysed. Using the data from 20 patients, the percentage of radiotherapy (RT) delivery time where the prostate position moved beyond 1, 2, 3, 4 and 5 mm in the left-right (LR), superior-inferior (SI), anterior-posterior (AP) and any direction was calculated.

Results

The prostate moved less than 3 mm in any direction for 90% of the monitoring period in 95% of patients. On a per-fraction basis, 93% of fractions displayed motion in all directions within 3 mm for 90% of the fraction delivery time. Recurring motion patterns were observed showing that the prostate moved with shallow drift (most common), transient excursions and persistent excursions during treatment.

Conclusion

A 3 mm CTV-PTV margin is safe to use for the treatment of 5 fraction prostate SBRT on the MRL, without gating. In the context of gating this work suggests that treatment time will not be extensively lengthened when an appropriate gating window is applied.
Quadruple primary tumors in a lynch syndrome patient surviving more than 26 years with genetic analysis: a case report and literature review
Authors: Zhu Bosen , Liu Ming , Mu Tianhao , Li Wentao , Ren Junqi , Li Xiangtao , Liang Yi , Yang Ziyi , Niu Yulin , Chen Shifu , Lin Junqiong
Published: June 2024

The incidence of multiple primary tumors(MPTs) is on the rise in recent years, but patients having four or more primary tumors is still rare. Lynch syndrome (LS) patients have a high risk of developing MPTs. NGS sequencing could identify the genetic alterations in different tumors to make a definite diagnosis of uncommon cases in clinical practice. Here, we report the case of a 66-year-old female patient who develops four MPTS between the ages of 41 and 66, that is sigmoid colon cancer, acute non-lymphocytic leukemia, urothelial carcinoma and ascending colon cancer. She has survived for more than 26 years since the first discovery of tumor. Targeted sequencing indicates that she has a pathogenic germline mutation in the exon 13 of MSH2, and her 2020 ureteral cancer sample and 2023 colon cancer sample have completely different mutation profiles. To the best of our knowledge, this is the first case of multiple primary tumors with an acute non-lymphocytic leukemia in LS patients.
Complete laparoscopic and Da Vinci robot esophagogastric anastomosis double muscle flap plasty for radical resection of proximal gastric cancer
Authors: Yang Dong , Liu Yuanlin , Meng Xiangyu , Xu Xing , Wang Chao , Zhang Meng , Zhang Tao
Published: June 2024

Objective

To investigate the application value of complete laparoscopy and Da Vinci robot esophagogastric anastomosis double muscle flap plasty in radical resection of proximal gastric cancer.

Method

A retrospective descriptive study was used. The clinicopathological data of 35 patients undergoing radical operation for proximal gastric cancer admitted to Liaoning Cancer Hospital from January 2020 to December 2023 were collected. Variables evaluated: 1. Transoperative,2. Postoperative, 3. Follow-up. In relation to follow-up, esophageal disease status reflux, anastomosis, nutritional status score, serum hemoglobin, tumor recurrence, and metastasis were investigated. The trans and postoperative variables were obtained from the clinical records and the patients were followed up in outpatient department and by telephone.

Result

Among the 35 patients, 17 underwent robotic surgery and 18 underwent laparoscopic surgery. There were 29 males and 6 females. 1) Transoperative: Robotic surgery: The operation time was (305.59 ± 22.07) min, the esophagogastric anastomosis double muscle flap plasty time was (149.76 ± 14.91) min, the average number of lymph nodes cleared was 30, and the average intraoperative blood loss was 30 ml. Laparoscopic surgery: The mean operation time was 305.17 ± 26.92min, the operation time of esophagogastric anastomosis double muscle flap was (194.06 ± 22.52) min, the average number of lymph nodes cleared was 24, and the average intraoperative blood loss was 52.5 ml. 2) Postoperative: Robotic surgery: the average time for patients to have their first postoperative anal emission was 3 days, the average time to first postoperative feeding was 4 days, and the average length of hospitalization after surgery was 8 days. Laparoscopic surgery: the average time for patients to have their first postoperative anal emission was 5 days, the average time to first postoperative feeding was 6 days, the average length of hospitalization after surgery was 10 days. 3) Follow-up: The follow-up time ranged from 1 to 42 months, with a median follow-up time of 24 months.

Conclusion

Complete Da Vinci robot and laparoscopic esophagogastric anastomosis double muscle flap plasty for radical resection of proximal gastric cancer can minimize surgical incision, reduce abdominal exposure, accelerate postoperative recovery of patients, and effectively prevent reflux esophagitis and maintain good hemoglobin concentration and nutritional status. The advantages of robotic surgery is less intraoperative bleeding and faster post-surgical recovery, but it is relatively more expensive.
Epidemiological and microbiological characteristics of S. aureus pediatric infections in Colombia 2018–2021, a national multicenter study (Staphylored Colombia)
Authors: Gutierrez-Tobar Ivan , Carvajal Cristobal , Vasquez-Hoyos Pablo , Díaz-Díaz Alejandro , Londono Ruiz Juan Pablo , Andrade Joam , Camacho-Cruz Jhon , Restrepo-Gouzy Andrea , Trujillo-Honeysberg Monica , Mesa-Monsalve Juan Gonzalo , Perez Ignacio , Von Moltke Richard , Beltran-Echeverry Maria , Toro Jessica F. , Niño Angela P. , Camacho-Moreno Germán , Calle-Giraldo Juan Pablo , Cabeza Nancy Yhomara , Sandoval-Calle Lina Marcela , Perez Camacho Paola , Patiño Niño Jaime , Araque-Muñoz Paula , Rodríguez-Peña Yazmin , Beltran-Arroyave Claudia , Chaucanez-Bastidas Yamile , Lopez Juan , Galvis-Trujillo Diego , Beltrán-Higuera Sandra , Marino Ana-Cristina , González Leal Natalia , Luengas Monroy Miguel Ángel , Hernandez-Moreno Derly Carolina , Vivas Trochez Rosalba , Garces Carlos , López-Medina Eduardo
Published: June 2024

Background

Staphylococcus aureus infections are a significant cause of morbidity and mortality in pediatric populations worldwide. The Staphylo Research Network conducted an extensive study on pediatric patients across Colombia from 2018 to 2021. The aim of this study was to describe the epidemiological and microbiological characteristics of S. aureus in this patient group.

Methods

We analyzed S. aureus isolates from WHONET-reporting centers. An “event” was a positive culture isolation in a previously negative individual after 2 weeks. We studied center characteristics, age distribution, infection type, and antibiotic susceptibilities, comparing methicillin sensitive (MSSA) and resistant S. aureus (MRSA) isolates.

Results

Isolates from 20 centers across 7 Colombian cities were included. Most centers (80%) served both adults and children, with 55% offering oncology services and 85% having a PICU. We registered 8,157 S. aureus culture isolations from 5,384 events (3,345 MSSA and 1,961 MRSA) in 4,821 patients, with a median age of 5 years. Blood (26.2%) and skin/soft tissue (18.6%) were the most common infection sources. Most isolates per event remained susceptible to oxacillin (63.2%), clindamycin (94.3%), and TMP-SMX (98.3%). MRSA prevalence varied by city (<0.001), with slightly higher rates observed in exclusively pediatric hospitals. In contrast, the MRSA rate was somewhat lower in centers with Antimicrobial Stewardship Program (ASP). MRSA was predominantly isolated from osteoarticular infections and multiple foci, while MSSA was more frequently associated with recurrent infections compared to MRSA.

Conclusions

This is the largest study of pediatric S. aureus infections in Colombia. We found MSSA predominance, but resistance have important regional variations. S. aureus remains susceptible to other commonly used antibiotics such as TMP-SMX and clindamycin. Ongoing monitoring of S. aureus infections is vital for understanding their behavior in children. Prospective studies within the Staphylored LATAM are underway for a more comprehensive clinical and genetic characterization.
Proteinuria and hematuria as early signs of renal involvement in juvenile idiopathic arthritis
Authors: Del Giudice Emanuela , Marcellino Alessia , Hoxha Sara , Martucci Vanessa , Sanseviero Mariateresa , Bloise Silvia , De Maria Sara Giovanna , Leone Maria Rita , Ventriglia Flavia , Lubrano Riccardo
Published: June 2024

Objectives

To evaluate glomerular and tubular renal functions and analyze blood pressure in a cohort of pediatric patients with juvenile idiopathic arthritis (JIA).

Methods

A total of 40 pediatric patients, 20 (50%) with JIA and 20 (50%) healthy control subjects, were studied, and performed the renal function on 24-h collection and the 24-h ambulatory blood pressure monitoring (ABPM). Moreover, we compared renal function and blood pressure trends between the groups of JIA patients with different disease activities.

Results

No statistically significant differences were observed between patients with JIA and healthy children in terms of glomerular filtration rate (GFR), fractional excretion of sodium (FENa), tubular reabsorption of phosphate (TRP), and calcium-creatinine urine ratio (CaU/CrU). In contrast, we observed significantly higher values in JIA patients than in controls for the presence of hematuria (p < 0.0001) and proteinuria (p < 0.0001). Compared to the control group there were significantly higher values of hematuria and proteinuria/day in both groups of JIA patients with low disease activity (respectively, p = 0.0001 and p = 0.0002) and moderate disease activity (respectively p = 0.0001 and p = 0.0012). Systolic and diastolic dipping were significantly reduced in patients with JIA compared with healthy controls (p < 0.0001 and p < 0.0001, respectively).

Conclusions

Our study showed that children with JIA, already in the early stages of the disease, have higher values of hematuria and proteinuria, which are early warning signs of nephropathy. Therefore, detailed screening of renal function and pressure monitoring in patients are necessary to monitor their evolution over time.
Identification of potential novel N6-methyladenosine effector-related lncRNA biomarkers for serous ovarian carcinoma: a machine learning-based exploration in the framework of 3P medicine
Authors: Ye Lele , Tong Xinya , Pan Kan , Shi Xinyu , Xu Binbing , Yao Xuyang , Zhuo Linpei , Fang Su , Tang Sangsang , Jiang Zhuofeng , Xue Xiangyang , Lu Weiguo , Guo Gangqiang
Published: June 2024

Background

Serous ovarian carcinoma (SOC) is considered the most lethal gynecological malignancy. The current lack of reliable prognostic biomarkers for SOC reduces the efficacy of predictive, preventive, and personalized medicine (PPPM/3PM) in patients with SOC, leading to unsatisfactory therapeutic outcomes. N6-methyladenosine (m6A) modification-associated long noncoding RNAs (lncRNAs) are effective predictors of SOC. In this study, an effective risk prediction model for SOC was constructed based on m6A modification-associated lncRNAs.

Methods

Transcriptomic data and clinical information of patients with SOC were downloaded from The Cancer Genome Atlas. Candidate lncRNAs were identified using univariate and multivariate and least absolute shrinkage and selection operator-penalized Cox regression analyses. The molecular mechanisms of m6A effector-related lncRNAs were explored via Gene Ontology, pathway analysis, gene set enrichment analysis, and gene set variation analysis (GSVA). The extent of immune cell infiltration was assessed using various algorithms, including CIBERSORT, Microenvironment Cell Populations counter, xCell, European Prospective Investigation into Cancer and Nutrition, and GSVA. The calcPhenotype algorithm was used to predict responses to the drugs commonly used in ovarian carcinoma therapy. In vitro experiments, such as migration and invasion Transwell assays, wound healing assays, and dot blot assays, were conducted to elucidate the functional roles of candidate lncRNAs.

Results

Six m6A effector-related lncRNAs that were markedly associated with prognosis were used to establish an m6A effector-related lncRNA risk model (m6A-LRM) for SOC. Immune microenvironment analysis suggested that the high-risk group exhibited a proinflammatory state and displayed increased sensitivity to immunotherapy. A nomogram was constructed with the m6A effector-related lncRNAs to assess the prognostic value of the model. Sixteen drugs potentially targeting m6A effector-related lncRNAs were identified. Furthermore, we developed an online web application for clinicians and researchers (https://leley.shinyapps.io/OC_m6A_lnc/). Overexpression of the lncRNA RP11-508M8.1 promoted SOC cell migration and invasion. METTL3 is an upstream regulator of RP11-508M8.1. The preliminary regulatory axis METTL3/m6A/RP11-508M8.1/hsa-miR-1270/ARSD underlying SOC was identified via a combination of in vitro and bioinformatic analyses.

Conclusion

In this study, we propose an innovative prognostic risk model and provide novel insights into the mechanism underlying the role of m6A-related lncRNAs in SOC. Incorporating the m6A-LRM into PPPM may help identify high-risk patients and personalize treatment as early as possible.
The neuroprotective effect of Chinese herbal medicine for cerebral ischemia reperfusion injury through regulating mitophagy
Authors: Chen Yanling , Zhang Yanan , Wu Qin , Chen Jing , Deng Yihui
Published: June 2024

The incidence of ischemic stroke has been increasing annually with an unfavorable prognosis. Cerebral ischemia reperfusion injury can exacerbate nerve damage. Effective mitochondrial quality control including mitochondrial fission, fusion and autophagy, is crucial for maintaining cellular homeostasis. Several studies have revealed the critical role of mitophagy in Cerebral ischemia reperfusion injury. Cerebral ischemia and hypoxia induce mitophagy, and mitophagy exhibits positive and negative effects in cerebral ischemia reperfusion injury. Studies have shown that Chinese herbal medicine can alleviate Cerebral ischemia reperfusion injury and serve as a neuroprotective agent by inhibiting or promoting mitophagy-mediated pathways. This review focuses on the mitochondrial dynamics and mitophagy-related pathways, as well as the role of mitophagy in ischemia reperfusion injury. Additionally, it discusses the therapeutic potential and benefits of Chinese herbal monomers and decoctions in the treatment of ischemic stroke.
Carvedilol increases seizure resistance in a mouse model of SCN8A-derived epilepsy
Authors: Wong Jennifer C. , Escayg Andrew
Published: June 2024

Patients with mutations that alter the function of the sodium channel SCN8A present with a range of clinical features, including mild to severe seizures, developmental delay, intellectual disability, autism, feeding dysfunction, motor impairment, and hypotonia. In an effort to identify compounds that could be potentially beneficial in SCN8A-associated epilepsy, Atkin et al. conducted an in vitro screen which resulted in the identification of 90 compounds that effectively reduced sodium influx into the cells expressing the human SCN8A R1872Q mutation. The top compounds that emerged from this screen included amitriptyline, carvedilol, and nilvadipine. In the current study, we evaluated the ability of these three compounds to increase resistance to 6 Hz or pentylenetetrazole (PTZ)-induced seizures in wild-type CF1 mice and in a mouse line expressing the human SCN8A R1620L mutation. We also evaluated the effects of fenfluramine administration, which was recently associated with a 60%–90% decrease in seizure frequency in three patients with SCN8A-associated epilepsy. While amitriptyline, carvedilol, and fenfluramine provided robust protection against induced seizures in CF1 mice, only carvedilol was able to significantly increase resistance to 6 Hz- and PTZ-induced seizures in RL/+ mutants. These results provide support for further evaluation of carvedilol as a potential treatment for patients with SCN8A mutations.
PLGA and PDMS-based in situ forming implants loaded with rosuvastatin and copper-selenium nanoparticles: a promising dual-effect formulation with augmented antimicrobial and cytotoxic activity in breast cancer cells
Authors: Maged Amr , Mabrouk Mostafa , Nour El-Din Hanzada T. , Osama Lamyaa , Badr-Eldin Shaimaa M. , Mahmoud Azza A.
Published: June 2024

Breast cancer is among the most prevalent tumors worldwide. In this study, in-situ forming implants (ISFIs) containing rosuvastatin calcium were prepared using three types of poly (D, L-lactic-co-glycolic acid) (PLGA), namely, PLGA 50/50 with ester terminal and PLGA 75/25 with ester or acid terminal. Additionally, polydimethylsiloxane (PDMS) was added in concentrations of 0, 10, 20, and 30% w/v to accelerate matrix formation. The prepared ISFIs were characterized for their rheological behaviors, rate of matrix formation, and in-vitro drug release. All the prepared formulations revealed a Newtonian flow with a matrix formation rate between 0.017 and 0.059 mm/min. Generally, increasing the concentration of PDMS increased the matrix formation rate. The prepared implants’ release efficiency values ranged between 46.39 and 89.75%. The ISFI containing PLGA 50/50 with 30% PDMS was selected for further testing, as it has the highest matrix formation rate and a promising release efficiency value. Copper-selenium nanoparticles were prepared with two different particle sizes (560 and 383 nm for CS1 and CS2, respectively) and loaded into the selected formulation to enhance its anticancer activity. The unloaded and loaded implants with rosuvastatin and copper-selenium nanoparticles were evaluated for their antibacterial activity, against Gram-positive and negative microorganisms, and anticancer efficacy, against MCF-7 and MDA-MB-231 cell lines. The results confirmed the potency of rosuvastatin calcium against cancer cells and the synergistic effect when loaded with smaller particle sizes of copper-selenium nanoparticles. This formulation holds a considerable potential for efficient breast cancer therapy.
Autophagy and inflammation an intricate affair in the management of obesity and metabolic disorders: evidence for novel pharmacological strategies?
Authors: Friuli Marzia , Sepe Christian , Panza Elisabetta , Travelli Cristina , Paterniti Irene , Romano Adele
Published: June 2024

Unhealthy lifestyle habits including a sedentary life, the lack of physical activity, and wrong dietary habits are the major ones responsible for the constant increase of obesity and metabolic disorders prevalence worldwide; therefore, the scientific community pays significant attention to the pharmacotherapy of such diseases, beyond lifestyle interventions, the use of medical devices, and surgical approaches. The intricate interplay between autophagy and inflammation appears crucial to orchestrate fundamental aspects of cellular and organismal responses to challenging stimuli, including metabolic insults; hence, when these two processes are dysregulated (enhanced or suppressed) they produce pathologic effects. The present review summarizes the existing literature reporting the intricate affair between autophagy and inflammation in the context of metabolic disorders, including obesity, diabetes, and liver metabolic diseases (non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH)). The evidence collected so far suggests that an alteration of autophagy might lead to maladaptive metabolic and inflammatory responses thus exacerbating the severity of the disease, and the most prominent conclusion underlies that autophagy might exert a protective function by contributing to balance inflammation. However, the complex nature of obesity and metabolic disorders might represent a limit of the studies; indeed, although many pharmacological treatments, producing positive metabolic effects, are also able to modulate autophagic flux and inflammation, it is not clear if the final beneficial effect might occur only by their mechanism of action, rather than because of additionally involved pathways. Finally, although future studies are needed, the observation that anti-obesity and antidiabetic drugs already on the market, including incretin mimetic agents, facilitate autophagy by dampening inflammation, strongly contributes to the idea that autophagy might represent a druggable system for the development of novel pharmacological tools that might represent an attractive strategy for the treatment of obesity and metabolic disorders.
The autophagic regulation of rosiglitazone-promoted adipocyte browning
Authors: Li Yue , Zheng Wanqing , Li Xinhang , Lue Zhengwei , Liu Yun , Wu Jiaying , Zhang Xiangnan
Published: June 2024

Objective: Browning of white adipocytes is considered an efficient approach to combat obesity. Rosiglitazone induces the thermogenetic program of white adipocytes, but the underlying mechanisms remain elusive.

Methods: Expression levels of browning and autophagy flux markers were detected by real-time PCR and immunoblotting. H&E and Oil Red O staining were performed to evaluate the lipid droplets area. Nuclear protein extraction and immunoprecipitation were used to detect the proteins interaction.

Results: In this study, we reported that rosiglitazone promoted adipocyte browning and inhibited autophagy. Rapamycin, an autophagy inducer, reversed adipocyte browning induced by rosiglitazone. Autophagy inhibition by rosiglitazone does not prevent mitochondrial clearance, which was considered to promote adipose whitening. Instead, autophagy inhibition increased p62 nuclear translocation and stabilized the PPARγ–RXRα heterodimer, which is an essential transcription factor for adipocyte browning. We found that rosiglitazone activated NRF2 in mature adipocytes. Inhibition of NRF2 by ML385 reversed autophagy inhibition and the pro-browning effect of rosiglitazone.

Conclusion: Our study linked autophagy inhibition with rosiglitazone-promoted browning of adipocytes and provided a mechanistic insight into the pharmacological effects of rosiglitazone.
Nuclear magnetic resonance studies in a model transverse field Ising system
Authors: Nian Y.-H. , Vinograd I. , Chaffey C. , Li Y. , Zic M. P. , Massat P. , Singh R. R. P. , Fisher I. R. , Curro N. J.
Published: June 2024

The suppression of ferroquadrupolar order in TmVO4 in a magnetic field is well-described by the transverse field Ising model, enabling detailed studies of critical dynamics near the quantum phase transition. We describe nuclear magnetic resonance measurements in pure and Y-doped single crystals. The non-Kramers nature of the ground state doublet leads to a unique form of the hyperfine coupling that exclusively probes the transverse field susceptibility. Our results show that this quantity diverges at the critical field, in contrast to the mean-field prediction. Furthermore, we find evidence for quantum critical fluctuations present near Tm-rich regions in Y-doped crystals at levels beyond which long-range order is suppressed, suggesting the presence of quantum Griffiths phases.