bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-bacterial cystitis caused by pembrolizumab therapy for adenocarcinoma of the lung: a case report
Authors: Di Caixia , Yu Teng , Ni Lei
Published: July 2024

Immune checkpoint inhibitors (ICIs) including anti-programmed death cell protein 1 (anti-PD1) and anti-programmed cell death-ligand 1 (PD-L1), by disinhibiting the antitumor responses of lymphocytes, have extended survival benefits for patients in lung cancer. ICIs can also lead to a wide spectrum of immune-related adverse events (irAEs), due to dysregulation of immune reactions. Here, we report a 27-year-old female patient with adenocarcinoma of the lung treated with pembrolizumab-combined chemotherapy treatment, who complained of urinary irritation symptoms. No bacteria were found in multiple urine cultures. B-mode ultrasonography indicated a high echo in the right lateral wall of the bladder, about 5.6 × 4.5 mm in size. Transurethral bladder tumor resection (TURBT) was operated. At biopsy, we found CD3+ CD8+ lymphocyte, plasma cell, and eosinophil infiltration and lymphoid follicle formation in the bladder mucosal layer. This is a report of non-bacterial inflammation of the urinary tract caused by immunotherapy.
Research on scallop shells transport of the Yantai coastal region in the Bohai Sea
Authors: Chen Le , Zhang Yibo , Liu Yongzhi , Cao Ruichen , Lv Xianqing
Published: July 2024

Introduction

Bivalve aquaculture is an important pillar of China's fisheries, with over 1 million tonnes of scallop shells produced annually. However, most of these shells are directly discarded into the sea, leading to continuous pollution of the marine and coastal environments, especially the coast of Yantai in the Bohai Sea where a large number of discarded scallop shell have accumulated.

Methods

To trace the fate of scallop shells in the ocean, this study established a model for the transport of scallop shells, coupling a two-dimensional tidal current model using the adjoint method with a Lagrangian particle model. By simulating nested tidal models, the distribution of tidal residual current in the Yantai coastal region was obtained. Then, a Lagrangian particle model was used to track the transport pathways of pollutants in the sea.

Results

Driven by the residual current calculated from the tidal model with the actual situation, possible pollutant release areas were inferred. The results of Lagrangian particle tracking experiments indicate that pollutants were released from the upstream accumulation area, specifically the area near Penglai Hulushan, confirming previous speculation.

Discussion

The scallop shells transport model can accurately simulate the spatiotemporal profile of scallop shells, which is helpful for managing scallop shell resources and improving the level of shell reuse.
Three levels of discrepancies in the records of trial sites in India, registered with the European Union Clinical Trials Register
Authors: Samanta Anwesha Dhal , Borah Rishima , Saberwal Gayatri
Published: July 2024

Introduction

Clinical trial registries serve a key role in tracking the trial enterprise. We are interested in the record of trials sites in India. In this study, we focused on the European Union Clinical Trial Registry (EUCTR). This registry is complex because a given study may have records from multiple countries in the EU, and therefore a given study ID may be represented by multiple records. We wished to determine what steps are required to identify the studies that list sites in India that are registered with EUCTR.

Methods

We used two methodologies. Methodology A involved downloading the EUCTR database and querying it. Methodology B used the search function on the registry website.

Results

Discrepant information, on whether or not a given study listed a site in India, was identified at three levels: (i) the methodology of examining the database; (ii) the multiple records of a given study ID; and (iii) the multiple fields within a given record. In each of these situations, there was no basis to resolve the discrepancy, one way or another.

Discussion

This work contributes to methodologies for more accurate searches of trial registries. It also adds to the efforts of those seeking transparency in trial data.
Long COVID: cognitive, balance, and retina manifestations
Authors: Carmona-Cervelló Meritxell , León-Gómez Brenda Biaani , Dacosta-Aguayo Rosalia , Lamonja-Vicente Noemí , Montero-Alía Pilar , Molist Gemma , Ayet Aitana , Chacón Carla , Costa-Garrido Anna , López-Lifante Victor M. , Zamora-Putin Valeria , Liutsko Liudmila , García-Sierra Rosa , Fornés Antònia , Moreno-Gabriel Eduard , Massanella Marta , Muñoz-Moreno Jose A. , Rodríguez-Pérez M. Carmen , Mateu Lourdes , Prats Anna , Mataró Maria , Boigues Marc , Quirant Bibiana , Prado Julia G. , Martínez-Cáceres Eva , Violán Concepción , Torán-Monserrat Pere ,   the APC Collaborative Group
Published: July 2024

Background

The neurological symptoms of Long COVID (LC) and the impact of neuropsychological manifestations on people’s daily lives have been extensively described. Although a large body of literature describes symptoms, validating this with objective measures is important. This study aims to identify and describe the effects of Long COVID on cognition, balance, and the retinal fundus, and determine whether the duration of symptoms influences cognitive impairment.

Methods

This cross-sectional study involved LC volunteers with cognitive complaint from public health centers in northern Barcelona who participated between January 2022 and March 2023. This study collected sociodemographic characteristics, information on substance use, comorbidities, and clinical data related to COVID-19. We measured five cognitive domains using a battery of neuropsychological tests. Balance was assessed through posturography and retinal vascular involvement by retinography.

Results

A total of 166 people with LC and cognitive complaints participated, 80.72% were women and mean age was 49.28 ± 8.39 years. The most common self-reported symptoms were concentration and memory deficit (98.80%), brain fog (82.53%) and insomnia (71.17%). The 68.67% presented cognitive deficit in at least one domain, with executive functions being the most frequent (43.98%). The 51.52% of the participants exhibited a dysfunctional pattern in balance, and 9.2% showed some alteration in the retina. There were no statistically significant differences between cognitive impairment and symptom duration.

Conclusion

Our findings contribute to a more comprehensive understanding of the pathology associated with Long COVID. They highlight the diversity of self-reported symptoms, the presence of abnormal balance patterns, and some cognitive impairment. These findings underscore the necessity of addressing the clinical management of this condition in primary care through follow-up and the pursuit of multidisciplinary and comprehensive treatment.
Adherence to monitoring of patients treated with amiodarone: a nationwide study
Authors: Frenkel Amit , Smadar Shneyour Ruth , Shiloh Adi , Morad Mohammed , Shimoni-Rachmilev Orly , Dreiher Jacob
Published: July 2024

Objective

The aim of this study was to assess the adherence to monitoring guidelines regarding amiodarone treatment.

Methods

This is a retrospective cohort study of data recorded in Clalit Health Services, the largest healthcare organization in Israel. Included were individuals aged >18 years; who were prescribed amiodarone and had a documented purchase of this drug, for a minimum of 200 consecutive days; and who had less than a 100-day gap between two consecutive purchases during 2013–2021. Adherence was assessed to testing for thyroid, liver function, and electrolytes, as determined by the performance of a test every 6 months.

Results

The study included 24,094 individuals (mean age: 75 years, 53% male). The median follow-up was 2.3 years (total 73,727 person-years). The proportions of patients who performed baseline tests were: 43.4% for thyroid function, 58.3% for electrolytes, 48.6% for liver function, 20.6% for chest X-rays, and 14.9% for electrocardiograms. Adherence rates to semiannual monitoring of thyroid function, liver function, and electrolyte tests were: 70.4%, 79.4%, and 88.3%, respectively. In a multivariable analysis, the factors associated with higher adherence were male sex; older age; the presence of thyroid abnormalities, renal failure, and hypertension; and more frequent visits to the primary care physician.

Conclusions

In our country, adherence is low to monitoring risk factors for adverse effects of amiodarone therapy, especially prior to treatment initiation. Patient and primary care physicians should be educated about the importance of monitoring, particularly prior to initiation of amiodarone treatment.
Augmented reality-based software (Echo-QR) for guiding the echographic probe toward the acoustic window: a pilot study
Authors: Thevenon A. , Derache F. , Faucoz O. , Zuj K. , Chaput D. , Arbeille P.
Published: July 2024

Introduction

With current technology, ultrasound imaging in remote conditions, such as the International Space Station, is performed with vocal guidance or using a teleoperated echograph controlled by an expert. Both methods require real-time communications between the novice operator and expert to locate the probe over the appropriate acoustic windows (AW). The current study presents the development and testing of a new augmented reality software (Echo-QR) that would allow novice operators (with no medical imaging background) to correctly locate the ultrasound probe over the AW of interest without expert assistance.

Methods

On the first day of the study, the positions of the probe over the AWs were identified for each organ by an expert sonographer and saved in the Echo-QR software. On the second day, the novices independently performed the ultrasound investigation using the Echo-QR software to correctly position the probe over each organ’s AW.

Results

Using the Echo-QR software, novice operators found the AW in 73 (92%) of the 79 organs. The 2D images acquired by the novices “2D direct image” were acceptable for medical evaluation in 41% of the cases. However, when the “2D direct image” did not show the entire organ, a 3D capture of the volume below the probe was also performed, which allowed for the extraction of the appropriate 2D image “2D/3D image” for medical evaluation in 85% of the cases.

Discussion

Therefore, in the absence of real-time communication between an isolated participant and an expert sonographer, novel software (Echo-QR) and automated 3D volume capture can be used to obtain images usable for ultrasound diagnostics.
Insights from metagenomics into gut microbiome associated with acute coronary syndrome therapy
Authors: Guan Yuee , Zhao Shuru , Li Jing , Zhang Wenqian , Guo Zhonghao , Luo Yi , Jiang Xiaofei , Li Jun , Liu Jianxiong , Chen Xi , Zhao Zicheng , Zhang Zhe
Published: July 2024

Acute coronary syndrome (ACS) is a predominant cause of mortality, and the prompt and precise identification of this condition is crucial to minimize its impact. Recent research indicates that gut microbiota is associated with the onset, progression, and treatment of ACS. To investigate its role, we sequenced the gut microbiota of 38 ACS patients before and after percutaneous coronary intervention and statin therapy at three time points, examining differential species and metabolic pathways. We observed a decrease in the abundance of Parabacteroides, Escherichia, and Blautia in patients after treatment and an increase in the abundance of Gemalla, Klebsiella variicola, Klebsiella pneumoniae, and others. Two pathways related to sugar degradation were more abundant in patients before treatment, possibly correlated with disorders of sugar metabolism and risk factors, such as hyperglycemia, insulin resistance, and insufficient insulin secretion. Additionally, seven pathways related to the biosynthesis of vitamin K2 and its homolog were reduced after treatment, suggesting that ACS patients may gradually recover after therapy. The gut microbiota of patients treated with different statins exhibited notable differences after treatment. Rosuvastatin appeared to promote the growth of anti-inflammatory bacteria while reducing pro-inflammatory bacteria, whereas atorvastatin may have mixed effects on pro-inflammatory and anti-inflammatory bacteria while increasing the abundance of Bacteroides. Our research will provide valuable insights and enhance comprehension of ACS, leading to better patient diagnosis and therapy.
Degradation and mechanism analysis of protein macromolecules by functional bacteria in tobacco leaves
Authors: Jiang Chuandong , Kong Decai , Li Yangyang , Sun Jingguo , Chen Zhenguo , Yang Mingfeng , Cao Shoutao , Yu Cunfeng , Wang Zengyu , Jiang Jiazhu , Zhu Chengguang , Zhang Nan , Sun Guangwei , Zhang Qiang
Published: July 2024

Tobacco, a crop of significant economic importance, was greatly influenced in leaf quality by protein content. However, current processing parameters fail to adequately meet the requirements for protein degradation. Microorganisms possess potential advantages for degrading proteins and enhancing the quality of tobacco leaves, and hold substantial potential in the process of curing. To effectively reduce the protein content in tobacco leaves, thereby improving the quality and safety of the tobacco leaves. In this study, tobacco leaf were used as experimental material. From these, the BSP1 strain capable of effectively degrading proteins was isolated and identified as Bacillus subtilis by 16S rDNA analysis. Furthermore, the mechanisms were analyzed by integrating microbiome, transcriptome, and metabolome. Before curing, BSP1 was applied to the surface of tobacco leaves. The results indicated that BSP1 effectively improves the activity of key enzymes and the content of related substances, thereby enhancing protein degradation. Additionally, protein degradation was achieved by regulating the diversity of the microbial community on the surface of the tobacco leaves and the ubiquitin-proteasome pathway. This study provided new strategies for extracting and utilizing functional strains from tobacco leaves, opening new avenues for enhancing the quality of tobacco leaves.
Vertiginous epilepsy in the pediatric population
Authors: Wood Alexandra M. , Thompson-Harvey Adam , Kesser Bradley W.
Published: July 2024

Vertiginous epilepsy (VE) is a rare and underrecognized epilepsy subtype in the pediatric population. Vertiginous symptoms are the sole or predominant feature, arise from the vestibular cortex, and seizures are usually brief. The incidence is estimated to be between six and 15 percent of pediatric patients presenting with dizziness. Diagnosis is often delayed for many years following the onset of symptoms, as there are no widely accepted diagnostic criteria. Diagnostic work-up should include a detailed history, physical exam, EEG, and brain imaging with MRI. Vestibular testing is helpful if peripheral vestibulopathy is suspected. Vertiginous epilepsy can have many possible causes, but a large majority are idiopathic or suspected to be genetic. Most patients with vertiginous epilepsy achieve seizure freedom with anti-seizure medications.
Diet-derived circulating antioxidants and risk of epilepsy: a Mendelian randomization study
Authors: Huang Shicun , Chen Yingqi , Wang Yiqing , Pan Shengjie , Lu Yeting , Gao Wei , Hu Xiaowei , Fang Qi
Published: July 2024

Background

Previous studies suggest a link between diet-derived circulating antioxidants and epilepsy, but the causal relationship is unclear. This study aims to investigate the causal effect of these antioxidants on epilepsy.

Methods

To assess the causal link between dietary antioxidants and epilepsy risk, we conducted a two-sample Mendelian randomization (MR) analysis. This involved examining antioxidants such as zinc, selenium, α- and γ-tocopherol, vitamin A (retinol), vitamin C (ascorbate), and vitamin E (α-tocopherol). We utilized instrumental variables (IVs) which were genetic variations highly associated with these commonly used antioxidants. Exposure data were sourced from a comprehensive genome-wide association study (GWAS). We aggregated data from the International League Against Epilepsy (ILAE) Consortium sample, which included various types of epilepsy, as an outcome variable. Finally, we applied the inverse variance weighting method and conducted sensitivity analyses for further validation.

Results

Based on the primary MR estimates and subsequent sensitivity analyses, the inverse variance weighting (IVW) method revealed that a genetically predicted increase in zinc per standard deviation was positively associated with three types of epilepsy. This includes all types of epilepsy (OR = 1.06, 95% CI: 1.02–1.11, p = 0.008), generalized epilepsy (OR = 1.13, 95% CI: 1.01–1.25, p = 0.030), and focal epilepsy (documented hippocampal sclerosis) (OR = 1.01, 95% CI: 1.00–1.02, p = 0.025). However, there is no evidence indicating that other antioxidants obtained from the diet affect the increase of epilepsy either positively or negatively.

Conclusion

Our research indicates that the risk of developing epilepsy may be directly linked to the genetic prediction of zinc, whereas no such association was found for other antioxidants.
Predicting language outcome at birth
Authors: Ortiz-Barajas Maria Clemencia
Published: July 2024

Even though most children acquire language effortlessly, not all do. Nowadays, language disorders are difficult to diagnose before 3–4 years of age, because diagnosis relies on behavioral criteria difficult to obtain early in life. Using electroencephalography, I investigated whether differences in newborns’ neural activity when listening to sentences in their native language (French) and a rhythmically different unfamiliar language (English) relate to measures of later language development at 12 and 18 months. Here I show that activation differences in the theta band at birth predict language comprehension abilities at 12 and 18 months. These findings suggest that a neural measure of language discrimination at birth could be used in the early identification of infants at risk of developmental language disorders.
Advances in nutritional metabolic therapy to impede the progression of critical illness
Authors: Chen Wenwei , Song Jia , Gong Shijin
Published: July 2024

With the advancement of medical care and the continuous improvement of organ support technologies, some critically ill patients survive the acute phase of their illness but still experience persistent organ dysfunction, necessitating long-term reliance on intensive care and organ support, known as chronic critical illness. Chronic critical illness is characterized by prolonged hospital stays, high mortality rates, and significant resource consumption. Patients with chronic critical illness often suffer from malnutrition, compromised immune function, and poor baseline health, which, combined with factors like shock or trauma, can lead to intestinal mucosal damage. Therefore, effective nutritional intervention for patients with chronic critical illness remains a key research focus. Nutritional therapy has emerged as one of the essential components of the overall treatment strategy for chronic critical illness. This paper aims to provide a comprehensive review of the latest research progress in nutritional support therapy for patients with chronic critical illness.
Integrated transcriptomic and proteomic analysis of exogenous abscisic acid regulation on tuberous root development in Pseudostellaria heterophylla
Authors: Wang Chongmin , Yang Jiaotong , Pan Qi , Zhu Panpan , Li Jun
Published: July 2024

Abscisic acid (ABA) significantly regulates plant growth and development, promoting tuberous root formation in various plants. However, the molecular mechanisms of ABA in the tuberous root development of Pseudostellaria heterophylla are not yet fully understood. This study utilized Illumina sequencing and de novo assembly strategies to obtain a reference transcriptome associated with ABA treatment. Subsequently, integrated transcriptomic and proteomic analyses were used to determine gene expression profiles in P. heterophylla tuberous roots. ABA treatment significantly increases the diameter and shortens the length of tuberous roots. Clustering analysis identified 2,256 differentially expressed genes and 679 differentially abundant proteins regulated by ABA. Gene co-expression and protein interaction networks revealed ABA positively induced 30 vital regulators. Furthermore, we identified and assigned putative functions to transcription factors (PhMYB10, PhbZIP2, PhbZIP, PhSBP) that mediate ABA signaling involved in the regulation of tuberous root development, including those related to cell wall metabolism, cell division, starch synthesis, hormone metabolism. Our findings provide valuable insights into the complex signaling networks of tuberous root development modulated by ABA. It provided potential targets for genetic manipulation to improve the yield and quality of P. heterophylla, which could significantly impact its cultivation and medicinal value.
Sex differences in the association between Body Mass Index and cognitive function in Parkinson disease: a cross-sectional study
Authors: Wang QiuShuang , Bian Jing , Sun Yi , Shi YaoZhou , Zhao ZiXuan , Zhao HuaShuo
Published: July 2024

Objective

This study utilized a binary logistic regression model to explore the relationship between Body Mass Index (BMI) and cognitive function in Parkinson’s disease (PD) patients.

Methods

In this cross-sectional study, data were obtained from 1,005 Parkinson’s patients enrolled in the Parkinson’s Progression Markers Initiative (PPMI) from 2010 to 2023, including 378 females and 627 males. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and the correlation between BMI and cognitive function was determined using binary logistic regression.

Results

The median age of enrollment was 63.6 (56.2, 69.6) years old, including 378 (37.6%) females and 627 (62.4%) males. In the final adjusted model, a significant positive correlation was found between BMI and the prevalence of cognitive impairment in females (OR = 1.06, 95% CI = 1.01 ~ 1.12, p = 0.022), while no correlation was found in males (OR = 1.03, 95% CI = 0.99 ~ 1.08, p = 0.165). The results after categorizing BMI indicate that, among females, the risk of cognitive impairment increases for both groups with BMI ≥ 30 kg/m2 and those with 25 ≤ BMI < 30 kg/m2 compared to the reference group with BMI < 25 kg/m2, with a p for trend <0.001 indicating a stable and strong association between BMI and cognitive impairment in females. In males, the results were not significant. The trend of linear fitting was consistent with the above results.

Conclusion

In female Parkinson’s patients, there is a positive correlation between BMI and cognitive impairment, while no correlation was found in male patients. This study provides new evidence of sex differences in the correlation between BMI and cognitive impairment among Parkinson’s patients. The role of sex differences in the relationship between BMI and cognitive impairment should be considered in future research.
Roadmap for providing and leveraging annotated data by cytologists in the PDAC domain as open data: support for AI-based pathology image analysis development and data utilization strategies
Authors: Kim Jongkwang , Bae Sumok , Yoon Seong-Mi , Jeong Sungmoon
Published: July 2024

Pancreatic cancer is one of the most lethal cancers worldwide, with a 5-year survival rate of less than 5%, the lowest of all cancer types. Pancreatic ductal adenocarcinoma (PDAC) is the most common and aggressive pancreatic cancer and has been classified as a health emergency in the past few decades. The histopathological diagnosis and prognosis evaluation of PDAC is time-consuming, laborious, and challenging in current clinical practice conditions. Pathological artificial intelligence (AI) research has been actively conducted lately. However, accessing medical data is challenging; the amount of open pathology data is small, and the absence of open-annotation data drawn by medical staff makes it difficult to conduct pathology AI research. Here, we provide easily accessible high-quality annotation data to address the abovementioned obstacles. Data evaluation is performed by supervised learning using a deep convolutional neural network structure to segment 11 annotated PDAC histopathological whole slide images (WSIs) drawn by medical staff directly from an open WSI dataset. We visualized the segmentation results of the histopathological images with a Dice score of 73% on the WSIs, including PDAC areas, thus identifying areas important for PDAC diagnosis and demonstrating high data quality. Additionally, pathologists assisted by AI can significantly increase their work efficiency. The pathological AI guidelines we propose are effective in developing histopathological AI for PDAC and are significant in the clinical field.
The role of endothelial junctions in the regulation of the extravasation of tumor cells. A historical reappraisal
Authors: Ribatti Domenico
Published: July 2024

Endothelial cells lining the vessel wall are connected by adherent, tight and gap junctions. Adherent junctions are common to all endothelial cells, whereas tight and gap junctions graduate within different vascular segments. Endothelial cell-cell junctions sustain vascular homeostasis and to control the transendothelial migration of inflammatory cells. Tumor cells need to weaken endothelial cell-cell junctions to penetrate the endothelial barrier and transendothelial migration and metastasis of tumor cells are tightly controlled by endothelial cell-cell junctions.
Global publication productivity and research trends on recurrent ovarian cancer: a bibliometric study
Authors: Xu Hua , Wang Lijuan , Xu Dianbo
Published: July 2024

Introduction

Recurrent ovarian cancer (ROC) presents a dismal prognosis, persistently devoid of efficacious therapeutic strategies. Over the past decade, significant shifts have transpired in ROC management, marked by the identification of novel therapeutic targets and advancements in biomarker research and innovation. Since bibliometrics is an effective method for revealing scientific literature, we conducted a bibliometric analysis of literature pertaining to ROC. Our exploration encompassed identifying emerging research trends and common patterns, analyzing collaborative networks, and anticipating future directions within this clinical context.

Methods

We conducted a search in the Web of Science Core Collection (WoSCC) to acquire relevant articles as our dataset, which were then exported using R-Studio-2023.12.0–369 software. The Bibliometrix R package was utilized to perform visual analyses on countries, institutions, journals, authors, landmark articles, and keywords within this research field.

Results

A total of 1538 articles and 173 reviews published between 2014 and 2023 were eventually retrieved. The annual growth rate of scientific production was 4.27%. The USA led the way in the number of published works, total citations, and collaboration. Gynecologic Oncology was the most favoured journal in this research field. Vergote I from the University Hospital Leuven, was the most influential author. At last, the most prominent keywords were “chemotherapy” (n = 124), “bevacizumab” (n = 87), and “survival” (n = 65). Clinical outcomes (prognosis, survival), chemotherapy, bevacizumab, and PARP inhibitors (olaparib, niraparib) represented the basic and transversal themes, while antibody-drug conjugate (ADC) and drug resistance were emerging themes. Cytoreduction surgical procedures and tamoxifen were niche themes, while immunotherapy and biomarkers were motor themes and had high centrality.

Conclusion

The trends in the ROC research field over the past decade were revealed through bibliometric analysis. Platinum resistance, ADC, and immunotherapy have emerged as the current prominent research topics.
Effectiveness and safety of vascular intervention plus lenvatinib versus vascular intervention alone for hepatocellular carcinoma patients with portal vein tumor thrombus: a retrospective comparative study
Authors: Tang Saikang , Gao Yingming , Yan Xue , Zhi Weihua , Han Yue
Published: July 2024

Background

This study aimed to assess the effectiveness and safety of vascular intervention combined with lenvatinib versus vascular intervention alone in the treatment of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), and to identify prognostic factors associated with the treatment outcomes.

Methods

We conducted a retrospective analysis of data from 92 patients with advanced HCC and PVTT who were treated between February 2016 and February 2023. Among them, 56 patients underwent vascular intervention alone (transarterial chemoembolization, TACE), while 36 patients received vascular intervention (TACE or hepatic arterial infusion chemotherapy [HAIC]) combined with lenvatinib. The primary outcomes included progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Survival rates were estimated by the Kaplan-Meier method, and confounders were adjusted using inverse probability of treatment weighting (IPTW). Prognostic factors were determined through the Cox regression model.

Results

The median follow-up duration was 20.07 months (interquartile range: 6.41–25.36). The combination therapy group had a significantly longer median PFS (11.00 vs. 5.00 months, P<0.05) and OS (12.91 vs. 6.83 months, P<0.05) in comparison to the monotherapy group, and these findings remained consistent after IPTW matching. Moreover, the combination therapy group showed a higher ORR (55.56% vs. 26.79%, P<0.05) based on mRECIST criteria. Cox multivariate analysis identified extrahepatic metastasis and maximum tumor diameter as risk factors for PFS, while age, tumor number, and maximum tumor diameter influenced OS. Combined treatment emerged as a protective factor for OS. In the combination therapy group, hypertension was the most frequent adverse event, with grade 3 or 4 adverse events occurring rarely.

Conclusion

The combination of vascular intervention with lenvatinib has demonstrated improved PFS and OS in advanced HCC patients with PVTT, and its safety profile appears to be acceptable. Adoption of this combined treatment strategy at an earlier stage may enhance patient outcomes.
Getting the dose right using physiologically-based pharmacokinetic modeling: dexamethasone to prevent post-extubation stridor in children as proof of concept
Authors: van der Heijden Joyce E. M. , de Hoop-Sommen Marika , Hoevenaars Noa , Freriksen Jolien J. M. , Joosten Koen , Greupink Rick , de Wildt Saskia N.
Published: July 2024

Introduction

Critically ill patients show large variability in drug disposition due to e.g., age, size, disease and treatment modalities. Physiologically-based pharmacokinetic (PBPK) models can be used to design individualized dosing regimens taking this into account. Dexamethasone, prescribed for the prevention post-extubation stridor (PES), is metabolized by the drug metabolizing enzyme CYP3A. As CYP3A4 undergoes major changes during childhood, we aimed to develop age-appropriate dosing recommendations for children of dexamethasone for PES, as proof of concept for PBPK modeling to individualize dosing for critically ill patients.

Methods

All simulations were conducted in Simcyp™ v21 (a population-based PBPK modeling platform), using an available dexamethasone compound model and pediatric population model in which CYP3A4 ontogeny is incorporated. Published pharmacokinetic (PK) data was used for model verification. Evidence for the dose to prevent post-extubation stridor was strongest for 2–6 year old children, hence simulated drug concentrations resulting from this dose from this age group were targeted when simulating age-appropriate doses for the whole pediatric age range.

Results

Dexamethasone plasma concentrations upon single and multiple intravenous administration were predicted adequately across the pediatric age range. Exposure-matched predictions of dexamethasone PK indicated that doses (in mg/kg) for the 2–6 years olds can be applied in 3 month-2 year old children, whereas lower doses are needed in children of other age groups (60% lower for 0–2 weeks, 40% lower for 2–4 weeks, 20% lower for 1–3 months, 20% lower for 6–12 year olds, 40% lower for 12–18 years olds).

Discussion

We show that PBPK modeling is a valuable tool that can be used to develop model-informed recommendations using dexamethasone to prevent PES in children. Based on exposure matching, the dose of dexamethasone should be reduced compared to commonly used doses, in infants <3 months and children ≥6 years, reflecting age-related variation in drug disposition. PBPK modeling is an promising tool to optimize dosing of critically ill patients.
Systematic review and meta-analysis: de novo combination of nucleos(t)ide analogs and pegylated interferon alpha versus pegylated interferon alpha monotherapy for the functional cure of chronic hepatitis B
Authors: Wei Na , Zheng Bin , Cai Hongfu , Li Na , Yang Jing , Liu Maobai
Published: July 2024

Introduction: Chronic hepatitis B (CHB) is a worldwide infectious disease caused by hepatitis B virus (HBV). Optimizing antiviral treatment strategies could improve the functional cure (FC) rate of patients with CHB. This study aims to systematically review the FC rate of the de novo combination of nucleos(t)ide analogs (NAs) and pegylated interferon α (PEG-IFNα) versus that of PEG-IFNα monotherapy for CHB.

Methods: Databases were searched until 31 December 2023. Selected studies included randomized controlled trials on the de novo combination of NAs and PEG-IFNα versus PEG-IFNα monotherapy for 48 weeks in patients with CHB to achieve FC, which was defined as hepatitis B surface antigen (HBsAg) loss and/or HBsAg seroconversion. Meta-analysis was conducted in accordance with the efficacy at the end of treatment and different time points during follow-up.

Results: A total of 10 studies, encompassing 2,339 patients in total, were included. Subgroup analysis was conducted in accordance with whether first-line NAs were used. It found no statistically significant difference between HBsAg loss and HBsAg seroconversion at the end of treatment. Serum HBV DNA <500 copies/mL significantly differed between the two groups at the end of treatment and did not significantly differ during follow-up. Meanwhile, HBsAg loss and HBsAg seroconversion showed statistically significant differences at 24 weeks of follow-up. By contrast, no statistically significant difference was found in HBsAg loss at 48 weeks of follow-up.

Discussion: Without distinguishing the eligible preponderant population, the efficacy of the de novo combination of NAs and PEG-IFNα in treating patients with CHB was not superior to that of PEG-IFNα monotherapy.

Systematic Review Registration: PROSPERO, identifier CRD42022325239.
Antiviral effect of alkaloids-free Ephedra Herb extract on respiratory syncytial virus infection
Authors: Fujikane Aya , Fujikane Ryosuke , Hyuga Sumiko , Sechi Yusuke , Hiyoshi Tetsuya , Sakamoto Atsuhiko , Nishi Akinori , Odaguchi Hiroshi , Hiromatsu Kenji , Goda Yukihiro , Ishino Yoshizumi , Nabeshima Shigeki
Published: July 2024

Respiratory syncytial virus (RSV) is a major cause of respiratory tract infection in children. Despite decades of efforts, no effective therapies are available. We recently reported that extracts of Ephedra Herb and Cinnamon Bark interacted with the G attachment protein of RSV to inhibit infectivity. The present in vitro study aimed to investigate the antiviral effect of ephedrine alkaloids-free Ephedra Herb extract (EFE), which is characterized by free of harmful effects of ephedrine alkaloids in Ephedra Herb, on experimental RSV infection. Infection of RSV into A549 cells simultaneously with EFE resulted the significant reduction of RSV RNA, viral protein, and viral titers after the incubation of the cells. We found that RSV attachment to the cell surface was inhibited both in the presence of EFE and when RSV particles were pre-treated with EFE. We also found that EFE specifically interacted with the central conserved domain of RSV G protein by surface plasmon resonance, demonstrating that specific binding of G protein to the cellular receptor was inhibited by EFE. Another mechanism was found in which a higher concentration of EFE inhibited the viral load immediately after the viral entry into host cells, suggesting the inhibition of viral RNA replication. These results demonstrate that EFE worked against RSV infection through multiple antiviral mechanisms, a unique feature of this crude drug extract.
A point prevalence survey and monitoring indicator research on the second batch of national key monitoring and rational use drugs
Authors: Tang Li , Liu Hongmei , Wu Shasha , Liu Jing , Jiang Xiaoyu , Fu Yuanyuan , Tao Na , He Yong
Published: July 2024

Background

With the remarkable effect of controlling the increase in drug costs by the first batch of National Key Monitoring and Rational Use Drugs (first NKMRUDs), the National Health Commission of the People’s Republic of China releases the second NKMRUDs to further strengthen the reasonable use of drugs. Unfortunately, the second NKMRUDs include some drugs of National Volume-based Procurement and National Essential Medicines, which challenges the management of pharmaceutical affairs on the three kinds of drugs.

Objective

The main objective of this study was to investigate the prevalence of the second NKMRUDs and explore their monitoring indicators.

Methods

An adapted WHO methodology for point prevalence surveys was conducted for the second NKMRUDs. For the monitoring indicators, we sought to explore whether the defined daily dose (DDD) and days of therapy (DOT) can be suitable for the second NKMRUDs through comparing differences between DDD and DOT with the prescribed daily dose (PDD).

Results

Among the 935 included patients, 29.20% of the patients received at least one of the second NKMRUDs. A total of 273 patients were administered with 487 times of the second NKMRUDs. Among them, 162 , 62 , and 49 patients were receiving one, two, and three or more agents, respectively. The most commonly prescribed second NKMRUDs were compound amino acids, budesonide, and ceftazidime. The total DDDs and DOTs of the second NKMRUDs were 3360.68 and 1819.80, respectively, with the PDDs of 1865.26. The deviations (80.17%) of DDDs from PDDs were significantly greater than those (−2.44%) of DOTs.

Conclusion

The prevalence of the second NKMRUDs was obtained by using the adapted PPS methodology at a tertiary university hospital. The DOT indicator is found to more accurately reflect actual consumption than the DDD indicator for second NKMRUDs. It is recommended to use the DOT indicator to monitor second NKMRUDs.
Lightweight tomato ripeness detection algorithm based on the improved RT-DETR
Authors: Wang Sen , Jiang Huiping , Yang Jixiang , Ma Xuan , Chen Jiamin , Li Zhongjie , Tang Xingqun
Published: July 2024

Tomatoes, widely cherished for their high nutritional value, necessitate precise ripeness identification and selective harvesting of mature fruits to significantly enhance the efficiency and economic benefits of tomato harvesting management. Previous studies on intelligent harvesting often focused solely on identifying tomatoes as the target, lacking fine-grained detection of tomato ripeness. This deficiency leads to the inadvertent harvesting of immature and rotten fruits, resulting in economic losses. Moreover, in natural settings, uneven illumination, occlusion by leaves, and fruit overlap hinder the precise assessment of tomato ripeness by robotic systems. Simultaneously, the demand for high accuracy and rapid response in tomato ripeness detection is compounded by the need for making the model lightweight to mitigate hardware costs. This study proposes a lightweight model named PDSI-RTDETR to address these challenges. Initially, the PConv_Block module, integrating partial convolution with residual blocks, replaces the Basic_Block structure in the legacy backbone to alleviate computing load and enhance feature extraction efficiency. Subsequently, a deformable attention module is amalgamated with intra-scale feature interaction structure, bolstering the capability to extract detailed features for fine-grained classification. Additionally, the proposed slimneck-SSFF feature fusion structure, merging the Scale Sequence Feature Fusion framework with a slim-neck design utilizing GSConv and VoVGSCSP modules, aims to reduce volume of computation and inference latency. Lastly, by amalgamating Inner-IoU with EIoU to formulate Inner-EIoU, replacing the original GIoU to expedite convergence while utilizing auxiliary frames enhances small object detection capabilities. Comprehensive assessments validate that the PDSI-RTDETR model achieves an average precision mAP50 of 86.8%, marking a 3.9% enhancement over the original RT-DETR model, and a 38.7% increase in FPS. Furthermore, the GFLOPs of PDSI-RTDETR have been diminished by 17.6%. Surpassing the baseline RT-DETR and other prevalent methods regarding precision and speed, it unveils its considerable potential for detecting tomato ripeness. When applied to intelligent harvesting robots in the future, this approach can improve the quality of tomato harvesting by reducing the collection of immature and spoiled fruits.
The primary carbon metabolism in cyanobacteria and its regulation
Authors: Lucius Stefan , Hagemann Martin
Published: July 2024

Cyanobacteria are the only prokaryotes capable of performing oxygenic photosynthesis. Many cyanobacterial strains can live in different trophic modes, ranging from photoautotrophic and heterotrophic to mixotrophic growth. However, the regulatory mechanisms allowing a flexible switch between these lifestyles are poorly understood. As anabolic fixation of CO2 in the Calvin-Benson-Bassham (CBB) cycle and catabolic sugar-degradation pathways share intermediates and enzymatic capacity, a tight regulatory network is required to enable simultaneous opposed metabolic fluxes. The Entner-Doudoroff (ED) pathway was recently predicted as one glycolytic route, which cooperates with other pathways in glycogen breakdown. Despite low carbon flux through the ED pathway, metabolite analyses of mutants deficient in the ED pathway revealed a distinct phenotype pointing at a strong regulatory impact of this route. The small Cp12 protein downregulates the CBB cycle in darkness by inhibiting phosphoribulokinase and glyceraldehyde 3-phosphate dehydrogenase. New results of metabolomic and redox level analyses on strains with Cp12 variants extend the known role of Cp12 regulation towards the acclimation to external glucose supply under diurnal conditions as well as to fluctuations in CO2 levels in the light. Moreover, carbon and nitrogen metabolism are closely linked to maintain an essential C/N homeostasis. The small protein PirC was shown to be an important regulator of phosphoglycerate mutase, which identified this enzyme as central branching point for carbon allocation from CBB cycle towards lower glycolysis. Altered metabolite levels in the mutant ΔpirC during nitrogen starvation experiments confirm this regulatory mechanism. The elucidation of novel mechanisms regulating carbon allocation at crucial metabolic branching points could identify ways for targeted redirection of carbon flow towards desired compounds, and thus help to further establish cyanobacteria as green cell factories for biotechnological applications with concurrent utilization of sunlight and CO2.
Worry and ruminative brooding: associations with cognitive and physical health in older adults
Authors: Morse Rachel M. , Koutsoubelis Freya , Whitfield Tim , Demnitz-King Harriet , Ourry Valentin , Stott Josh , Chocat Anne , Devouge Eglantine Ferrand , Walker Zuzana , Klimecki Olga , Collette Fabienne , Chetelat Gael , Gonneaud Julie , Poisnel Geraldine , Marchant Natalie L. ,   for the Medit-Ageing Research Group
Published: July 2024

Introduction

Mental health conditions are associated with cognition and physical function in older adults. We examined whether worry and ruminative brooding, key symptoms of certain mental health conditions, are related to subjective and/or objective measures of cognitive and physical (cardiovascular) health.

Methods

We used baseline data from 282 participants from the SCD-Well and Age-Well trials (178 female; agemean = 71.1 years). We measured worry and ruminative brooding using the Penn State Worry Questionnaire and the Ruminative Response Scale-brooding subscale. We assessed subjective physical health using the WHOQOL-Bref physical subscale, and objective physical health via blood pressure and modified versions of the Framingham Risk Score and Charlson Comorbidity Index. With subjective and objective cognition, we utilized the Cognitive Difficulties Scale and a global composite (modified Preclinical Alzheimer’s Cognitive Composite, PACC5, with the Wechsler Adult Intelligence Scale-IV, category fluency, Mattis Dementia Rating Scale-2, and either the California Verbal Learning Test or the Rey Auditory Verbal Learning Test). We conducted linear regressions, adjusted for education, age, sex and cohort.

Results

Worry and ruminative brooding were negatively associated with subjective physical health (worry: β = −0.245, 95%CI −0.357 to −0.133, p < 0.001; ruminative brooding: β = −0.224, 95%CI −0.334 to −0.113, p < 0.001) and subjective cognitive difficulties (worry: β = 0.196, 95%CI 0.091 to 0.302, p < 0.001; ruminative brooding: β = 0.239, 95%CI 0.133 to 0.346, p < 0.001). We did not observe associations between worry or ruminative brooding and any measure of objective health.

Discussion

Worry and ruminative brooding may be common mechanisms associated with subjective but not objective health. Alternatively, cognitively unimpaired older adults may become aware of subtle changes not captured by objective measures used in this study. Interventions reducing worry and ruminative brooding may promote subjective physical and cognitive health; however, more research is needed to determine causality of the relationships.