bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation between spleen density and prognostic outcomes in patients with colorectal cancer after curative resection
Authors: Xiao Yunzhou , Wen Xiaoting , Ying Yingying , Zhang Xiaoyan , Li Luyao , Wang Zhongchu , Su Miaoguang , Miao Shouliang
Published: April 2024

Objective

The objective of this study was to investigate the correlation between spleen density and the prognostic outcomes of patients who underwent curative resection for colorectal cancer (CRC).

Methods

The clinical data of patients who were diagnosed with CRC and underwent radical resection were retrospectively analyzed. Spleen density was determined using computed tomography. Analysis of spleen density in relation to overall survival (OS) and disease-free survival (DFS) utilizing the Kaplan–Meier method. Univariate and multivariate Cox regression models were used to screen for independent prognostic factors, and a nomogram was constructed to predict OS and DFS. Moreover, internally validated using a bootstrap resamplling method.

Results

Two hundred twelve patients were included, of whom 23 (10.85%) were defined as having a diffuse reduction of spleen density (DROSD) based on diagnostic cutoff values (spleen density≦37.00HU). Kaplan–Meier analysis indicated that patients with DROSD had worse OS and DFS than those non-DROSD (P < 0.05). Multivariate Cox regression analysis revealed that DROSD, carbohydrate antigen 199 (CA199) > 37 U/mL, tumor node metastasis (TNM) stage III-IV, laparoscopy-assisted operation and American Society of Anesthesiology (ASA) score were independent risk factors for 3-year DFS. DROSD, CA199 > 37 U/mL, TNM stage III-IV, hypoalbuminemia, laparoscopy-assisted operation and ASA score were chosen as predictors of for 3-year OS. Nomograms showed satisfactory accuracy in predicting OS and DFS using calibration curves, decision curve analysis and bootstrap resamplling method.

Conclusion

Patients with DROSD who underwent curative resection have worse 3-year DFS and OS. The nomogram demonstrated good performance, particularly in predicting 3-year DFS with a net clinical benefit superior to well-established risk calculator.
Risk factors of internal carotid artery stenosis in patients with proliferative diabetic retinopathy: an analysis using optical coherence tomography and optical coherence tomography angiography
Authors: Lee Chae Yoon , Park Jung Min , Yeom Myeong In
Published: April 2024

Background

This research investigates the correlation between the severity of internal carotid artery (ICA) stenosis and retinal parameters in patients with proliferative diabetic retinopathy (PDR), aiming to uncover potential risk factors.

Methods

A retrospective analysis of 68 patients (136 eyes) diagnosed with bilateral PDR from January 1, 2017, to December 31, 2021, was conducted. Carotid artery stenosis (CAS) was assessed using neck computed tomography angiography (CTA) and carotid duplex ultrasound (CDUS), with stenosis classified into two groups: normal (group 1) and mild or above (group 2), based on the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria. Optical coherence tomography (OCT) and OCT angiography (OCTA) measured several retinal parameters, including sub foveal choroidal thickness (SFCT), retinal nerve fiber layer (RNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, vessel density (VD), and foveal avascular zone (FAZ) area. Statistical analyses determined correlations between ICA degrees and retinal parameters.

Results

This study showed significant differences between groups in total VD, FAZ area, total RNFL thickness, and temporal RNFL thickness, indicating that patients with more severe ICA stenosis had noticeable retinal changes. Other parameters such as hyperlipidemia, total cholesterol levels, and intraocular pressure (IOP) also differed significantly, while no notable differences were observed in SFCT, central VD, average GCIPL, and superior, nasal, and inferior RNFL thickness.

Conclusion

The study findings highlight retinal changes, such as an increased FAZ area, decreased total VD, and a total and thinner temporal RNFL, which suggest the need for carotid artery evaluation in patients. These findings have important clinical implications for the need for carotid work up in patients with PDR.
Comparison of complications of intrascleral fixation according to the extent of vitrectomy
Authors: Yamada Miho , Nishimura Eiichi , Watanabe Sayako , Yoshino Masanori , Tokunaga Yoshiro , Sugiyama Natsuko , Soda Mitsutaka
Published: April 2024

Background

Intraocular lens (IOL) fixation is performed after intraoperative anterior or total vitrectomy. This study aimed to compare the intraoperative and postoperative complications of these two techniques.

Methods

This retrospective study included 235 eyes that underwent intrascleral fixation surgery at our hospital between July 2014 and January 2021. The eyes were classified into the anterior vitrectomy group (A-vit group; 134 eyes) and the pars plana vitrectomy group (PPV group; 101 eyes). The age, preoperative and postoperative best-corrected visual acuity, observation period, preoperative and postoperative intraocular pressure, and the incidence of intraoperative and postoperative complications were assessed.

Results

Intrascleral fixation was performed more frequently in the PPV group, and a significant difference was observed between the eyes with a history of vitrectomy and eyes with scleral buckles (p = 0.00041). In terms of the incidence of postoperative complications following intrascleral fixation, the incidence of low intraocular pressure postoperative was higher in the PPV group than that in the A-vit group, and a significant difference was observed between the two groups (p = 0.01).

Conclusions

The visual outcome and complications following intrascleral fixation did not differ according to the extent of vitreous excision.
Chronic stridor in a toddler after ingestion of a discharged button battery: a case report
Authors: Oftring Zoe S. , Mehrtens Doortje M. , Mollin Julian , Hamelmann Eckard , Gaus Sebastian
Published: April 2024

Background

Button battery (BB) ingestions (BBI) are increasingly prevalent in children and constitute a significant, potentially life-threatening health hazard, and thus a pediatric emergency. Ingested BBs are usually charged and can cause severe symptom within 2 h. Discharged BBs ingestion is very rare and protracted symptom trajectories complicate diagnosis. Timely imaging is all the more important. Discharged BBs pose specific hazards, such as impaction, and necessitate additional interventions.

Case presentation

We present the case of a previously healthy 19-month-old girl who was admitted to our pediatric university clinic in Germany for assessment of a three-month history of intermittent, mainly inspiratory stridor, snoring and feeding problems (swallowing, crying at the sight of food). The child’s physical examination and vital signs were normal. Common infectious causes, such as bronchitis, were ruled out by normal lab results including normal infection parameters, negative serology for common respiratory viruses, and normal blood gas analysis, the absence of fever or pathological auscultation findings. The patient’s history contained no evidence of an ingestion or aspiration event, no other red flags (e.g., traveling, contact to TBC). Considering this and with bronchoscopy being the gold standard for foreign body (FB) detection, an x-ray was initially deferred. A diagnostic bronchoscopy, performed to check for airway pathologies, revealed normal mucosal and anatomic findings, but a non-pulsatile bulge in the trachea. Subsequent esophagoscopy showed an undefined FB, lodged in the upper third of the otherwise intact esophagus. The FB was identified as a BB by a chest X-ray. Retrieval of the battery proved extremely difficult due to its wedged position and prolonged ingestion and required a two-stage procedure with consultation of Ear Nose Throat colleagues. Recurring stenosis and regurgitation required one-time esophageal bougienage during follow-up examinations. Since then, the child has been asymptomatic in the biannual endoscopic controls and is thriving satisfactorily.

Conclusion

This case describes the rare and unusual case of a long-term ingested, discharged BB. It underscores the need for heightened vigilance among healthcare providers regarding the potential hazards posed by discharged BBIs in otherwise healthy children with newly, unexplained stridor and feeding problems. This case emphasizes the critical role of early diagnostic imaging and interdisciplinary interventions in ensuring timely management and preventing long-term complications associated even to discharged BBs.
Epidemic intelligence in Europe: a user needs perspective to foster innovation in digital health surveillance
Authors: Bouyer Fanny , Thiongane Oumy , Hobeika Alexandre , Arsevska Elena , Binot Aurélie , Corrèges Déborah , Dub Timothée , Mäkelä Henna , van Kleef Esther , Jori Ferran , Lancelot Renaud , Mercier Alize , Fagandini Francesca , Valentin Sarah , Van Bortel Wim , Ruault Claire
Published: April 2024

Background

European epidemic intelligence (EI) systems receive vast amounts of information and data on disease outbreaks and potential health threats. The quantity and variety of available data sources for EI, as well as the available methods to manage and analyse these data sources, are constantly increasing. Our aim was to identify the difficulties encountered in this context and which innovations, according to EI practitioners, could improve the detection, monitoring and analysis of disease outbreaks and the emergence of new pathogens.

Methods

We conducted a qualitative study to identify the need for innovation expressed by 33 EI practitioners of national public health and animal health agencies in five European countries and at the European Centre for Disease Prevention and Control (ECDC). We adopted a stepwise approach to identify the EI stakeholders, to understand the problems they faced concerning their EI activities, and to validate and further define with practitioners the problems to address and the most adapted solutions to their work conditions. We characterized their EI activities, professional logics, and desired changes in their activities using NvivoⓇ software.

Results

Our analysis highlights that EI practitioners wished to collectively review their EI strategy to enhance their preparedness for emerging infectious diseases, adapt their routines to manage an increasing amount of data and have methodological support for cross-sectoral analysis. Practitioners were in demand of timely, validated and standardized data acquisition processes by text mining of various sources; better validated dataflows respecting the data protection rules; and more interoperable data with homogeneous quality levels and standardized covariate sets for epidemiological assessments of national EI. The set of solutions identified to facilitate risk detection and risk assessment included visualization, text mining, and predefined analytical tools combined with methodological guidance. Practitioners also highlighted their preference for partial rather than full automation of analyses to maintain control over the data and inputs and to adapt parameters to versatile objectives and characteristics.

Conclusions

The study showed that the set of solutions needed by practitioners had to be based on holistic and integrated approaches for monitoring zoonosis and antimicrobial resistance and on harmonization between agencies and sectors while maintaining flexibility in the choice of tools and methods. The technical requirements should be defined in detail by iterative exchanges with EI practitioners and decision-makers.
Effects of health educational and participatory consumer group interventions in improving food handling practices in regional director of health services area Kalutara, Sri Lanka: non-randomized controlled community trial
Authors: Hirimuthugoda Lasantha Krishan , De Silva Padmal , Abeykoon Palitha
Published: April 2024

Introduction

Safe and nutritious food is the key to sustaining life and promoting good health. Unsafe food creates a vicious cycle of disease and malnutrition, particularly affecting infants, young children, the elderly, and the sick.

Methods

The study consisted of two phases, a descriptive cross-sectional study, and an intervention study. Both studies were conducted in the Regional Director of Health Services area, Kalutara, Sri Lanka. The descriptive cross-sectional study [food handlers (n = 904), food establishments (n = 421)] was conducted with the objective of determining factors associated with food handling practices among food handlers and in food establishments. The interventional study was a three-arm non-randomized controlled community trial (n = 50 per arm) with interventions of a participatory consumer group, educational package group, and control group.

Results

The food establishments assessment tool (FEAT) contained 11 domains including 75 items with more than a hundred assessment points with a guide to conduct an assessment of food handling. The descriptive cross-sectional study found that food handlers’ knowledge of food handling practices of storing milk, fish, and meat and fast-food items containing fish and meat was very poor (96.6%). Visibility of the last place of processing inside the food establishments to consumers was inadequate (19.2%) and the absence of the above-mentioned factor was significantly associated with an unsatisfactory level of food handling score in food establishments (p = 0.03). The unsatisfactory level of food handling was significantly higher among food establishments with non-personal ownership (p = 0.005), a low number of notices issued by legal authorities (p = 0.02), dereliction of duty by owners/managers on supervising (p < 0.001) and lack of medical certification to food handlers (p < 0.0001). Participatory consumer group intervention and educational package interventions were effective in improving food handling practices in food establishments and among food handlers (p < 0.0001). Two independent sample analysis using the Mann–Whitney U test showed, the best improvement in food handling practices was by participatory consumer group intervention (p < 0.0001) and the second was educational package intervention (p < 0.0001).

Conclusions

Knowledge and practices of food handling among participants were poor. A participatory consumer group is more effective than an educational package on improving food handling practices both among food handlers and in food establishments.
Exploring barriers of health literacy on non-communicable disease prevention and care among patients in north wollo zone public hospitals; Northeast, Ethiopia, 2023: application of socio-ecological model
Authors: Fenta Eneyew Talie , kidie Atitegeb Abera , Tiruneh Misganaw Guadie , Anagaw Tadele Fentabel , Bogale Eyob ketema , Dessie Amanuel Addisu , worku Nigus Kassie , Amera Mastewal Giza , Tesfa Hiwot , Limenh Liknaw Workie , Delie Amare Mebrate , Ayal Birtukan Gizachew
Published: April 2024

Background

Health literacy is the important for the prevention of non-communicable disease to make informed health decisions, and practice healthy and protective behaviours. Therefore, application of socioecological model to this study aimed to identify multilevel factors on health literacy among patients and develop scientific health communication interventional strategies to improve health literacy on non-communicable disease prevention and care.

Objective

To explore barriers of health literacy on non-communicable disease prevention and care among patients in north wollo zone public Hospitals, Northeast Ethiopia, 2023.

Method

In this study phenomenological study design was conducted from February 5 to 30/2023.We have used purposive sampling technique to select study participants from chronic follow up clinics. Data were collected using in-depth interview and focused group discussion in which audio was recorded, transcribed verbatim and translated to English. Thematic analysis was performed with atlas ti. 7 software.

Result

In this study four main themes with seven subthemes were developed. The main themes were factors at the organizational, community, interpersonal, and intra-personal factors. The poor knowledge, lack of enough money for transportation and medication at the hospital were identified as barrier to get early diagnosis and treatment. Some participants explored that they have no any support from family or others. The cultural norms like weeding and funeral ceremonies enforce patients to consume prohibited substances like alcohol and salty foods.

Conclusion

In this study different barriers of health literacy were explored. Lack of knowledge, economic problems, lack of social support, poor communication with health care providers, cultural influences, lack of regular health education, lack of access to health care services and poor infrastructure were main barriers of health literacy in patients with NCD. Therefore, we recommended all concerned bodies to work on social and behavioral change communication intervention focusing on awareness creation, supply of drugs and create supportive environment to get accessible and affordable health care service to decrease the impact of non-communicable disease at personal, community and national level.
Biomechanics of the lower limb in patients with mild knee osteoarthritis during the sit-to-stand task
Authors: Pan Jing , Fu Wei , Lv Jinmiao , Tang Huiyi , Huang Zhiguan , Zou Yu , Zhang Xiaohui , Liao Bagen
Published: April 2024

Background

Knee osteoarthritis (KOA) is a prevalent and debilitating condition that markedly affects the sit-to-stand (STS) activity of patients, a prerequisite for daily activities. Biomechanical recognition of movements in patients with mild KOA is currently attracting attention. However, limited studies have been conducted solely on the observed differences in sagittal plane movement and muscle activation.

Aim

This study aimed to identify three-dimensional biomechanical and muscle activation characteristics of the STS activity in patients with mild KOA.

Methods

A cross-sectional study was conducted to observe the differences between patients with mild KOA and a control group (CG). It was conducted to observe the differences in muscle activation, including root mean square (RMS%) and integrated electromyography (items), kinematic parameters like range of motion (ROM) and maximum angular velocity, as well as dynamic parameters such as joint moment and vertical ground reaction force (vGRF).

Results

Patients with mild KOA had a higher body mass index and longer task duration. In the sagittal plane, patients with KOA showed an increased ROM of the pelvic region, reduced ROM of the hip–knee–ankle joint, and diminished maximum angular velocity of the knee–ankle joint. Furthermore, patients with KOA displayed increased knee–ankle joint ROM in the coronal plane and decreased ankle joint ROM in the horizontal plane. Integrated vGRF was higher in both lower limbs, whereas the vGRF of the affected side was lower. Furthermore, patients showed a decreased peak adduction moment (PADM) and increased peak external rotation moment in the knee joint and smaller PADM and peak internal rotation moment in the ankle joint. The affected side exhibited decreased RMS% and iEMG values of the gluteus medius, vastus medialis, and vastus lateralis muscles, as well as a decreased RMS% of the rectus femoris muscle. Conversely, RMS% and iEMG values of the biceps femoris, lateral gastrocnemius, and medial gastrocnemius muscles were higher.

Conclusion

The unbalanced activation characteristics of the anterior and posterior muscle groups, combined with changes in joint moment in the three-dimensional plane of the affected joint, may pose a potential risk of injury to the irritated articular cartilage.
A cross-sectional study of the association of dental health factors with progression and all-cause mortality in men diagnosed with HPV-associated oropharyngeal cancer
Authors: Dickey Brittney L. , Gore L. Robert , Slebos Robbert , Sirak Bradley , Isaacs-Soriano Kimberly A. , Kennedy Kayoko , Otto Kristen , Wadsworth J. Trad , Chung Christine H. , Giuliano Anna R.
Published: April 2024

Background

Human Papillomavirus-associated oropharyngeal cancer (HPV-OPC) incidence is increasing among men in the United States. Poor dental health has previously been associated with risk of head and neck cancers, oral HPV infection, and persistence but it is not understood whether dental health is associated with outcomes. We sought to determine the association of dental health with progression free survival and overall mortality among men with an HPV-OPC.

Methods

A cross sectional study of men diagnosed with HPV-OPC between 2014–2020 at Moffitt Cancer Center in Tampa, FL was conducted. Dental records were abstracted for assessment of dental fitness prior to cancer treatment. Five dental factors including number of teeth lost, pocket depth, gingival score, loss of attachment, and bone loss were individually examined. Risk factor and outcome data were collected from a patient risk questionnaire and medical record. Using item response theory, an overall dental fitness score from five dental factors was developed in which missing data were multiply imputed. Cox proportional hazards model was used to assess whether dental factors were associated with progression-free survival or overall mortality.

Results

Among 206 HPV-OPC cases, median follow-up was 3.4 years (IQR: 2.4–4.4) during which 40 cases involved progression or mortality and 25 deaths occurred. Overall dentition was significantly associated with progression free survival (p = 0.04) and with overall survival (p = 0.03) though findings were not significant after adjustment for age at diagnosis, stage, and smoking history (p = 0.146 and p = 0.120, respectively). A pocket depth of 7 mm or more was associated with overall survival (HR: 5.21; 95% CI: 1.43—19.11) and this remained significant after adjustment for confounding (aHR: 4.14; 95% CI: 1.72—16.26).

Conclusions

Among men diagnosed with an HPV-associated OPC in the US, worse dental health was associated with reduced progression free survival and overall survival, but not after adjustment for confounders. Further studies are needed to examine whether dental health is associated with other prognostic factors and subsequent treatment-related outcomes.
Fully automated deep learning approach to dental development assessment in panoramic radiographs
Authors: Ong Seung-Hwan , Kim Hyuntae , Song Ji-Soo , Shin Teo Jeon , Hyun Hong-Keun , Jang Ki-Taeg , Kim Young-Jae
Published: April 2024

Background

Dental development assessment is an important factor in dental age estimation and dental maturity evaluation. This study aimed to develop and evaluate the performance of an automated dental development staging system based on Demirjian’s method using deep learning.

Methods

The study included 5133 anonymous panoramic radiographs obtained from the Department of Pediatric Dentistry database at Seoul National University Dental Hospital between 2020 and 2021. The proposed methodology involves a three-step procedure for dental staging: detection, segmentation, and classification. The panoramic data were randomly divided into training and validating sets (8:2), and YOLOv5, U-Net, and EfficientNet were trained and employed for each stage. The models’ performance, along with the Grad-CAM analysis of EfficientNet, was evaluated.

Results

The mean average precision (mAP) was 0.995 for detection, and the segmentation achieved an accuracy of 0.978. The classification performance showed F1 scores of 69.23, 80.67, 84.97, and 90.81 for the Incisor, Canine, Premolar, and Molar models, respectively. In the Grad-CAM analysis, the classification model focused on the apical portion of the developing tooth, a crucial feature for staging according to Demirjian’s method.

Conclusions

These results indicate that the proposed deep learning approach for automated dental staging can serve as a supportive tool for dentists, facilitating rapid and objective dental age estimation and dental maturity evaluation.
Assessment of dental pulp response to carries via MR T2mapping and histological analysis
Authors: Tenyi Ana , Milutinović Aleksandra , Vidmar Jernej , Serša Igor , Cankar Ksenija
Published: April 2024

Objectives

The aim of our study was to assess the correlation between T2 relaxation times and their variability with the histopathological results of the same teeth in relation to caries progression. Materials and methods: 52 extracted permanent premolars were included in the study. Prior to extractions, patients underwent magnetic resonance imaging (MRI) scanning and teeth were evaluated using ICDAS classification. Pulps of extracted teeth were histologically analysed. Results: MRI T2 relaxation times (ms) were 111,9 ± 11.2 for ICDAS 0, 132.3 ± 18.5* for ICDAS 1, 124.6 ± 14.8 for ICDAS 2 and 112. 6 ± 18.2 for ICDAS 3 group (p = 0,013). A positive correlation was observed between MRI T2 relaxation times and macrophage and T lymphocyte density in healthy teeth. There was a positive correlation between vascular density and T2 relaxation times of dental pulp in teeth with ICDAS score 1. A negative correlation was found between T2 relaxation times and macrophage density. There was a positive correlation between T2 relaxation time variability and macrophage and T lymphocyte density in teeth with ICDAS score 2. In teeth with ICDAS score 3, a positive correlation between T2 relaxation times and T2 relaxation time variability and lymphocyte B density was found. Conclusion: The results of our study confirm the applicability of MRI in evaluation of the true condition of the pulp tissue. Clinical relevance: With the high correlation to histological validation, MRI method serves as a promising imaging implement in the field of general dentistry and endodontics.
A survey of gastrointestinal helminth infestation in smallholder backyard pigs and the first molecular identification of the two zoonotic helminths Ascaris suum and Trichuris suis in Myanmar
Authors: Bawm Saw , Htun Lat Lat , Chel Hla Myet , Khaing Yadanar , Hmoon Myint Myint , Thein Su Su , Win Shwe Yee , Soe Nyein Chan , Thaw Yu Nandi , Hayashi Naoki , Win Mar Mar , Nonaka Nariaki , Katakura Ken , Nakao Ryo
Published: April 2024

Background

Parasitic infestations have a substantial economic impact on pig production. This study aimed to investigate the gastrointestinal (GI) helminths in pigs and to molecularly characterise two important nematodes, Ascaris and Trichuris species.

Materials and methods

A total of 500 pig faecal samples were collected from small holder backyard pig farms in five townships within Nay Pyi Taw, Myanmar. Microscopic examination was conducted to estimate the prevalence of GI helminth infestation in the pigs. DNA extraction and PCR were performed on faecal samples that were morphologically positive for Ascaris and Trichuris eggs. Molecular analysis was then conducted to characterise A. suum and T. suis, the most common and zoonotic helminths.

Results

According to microscopic examination, 69.2% (346/500) were positive for GI helminth eggs. The GI helminth species observed were A. suum, Strongyle, Strongyloides spp., T. suis, Metastrongylus spp., Hyostrongylus spp., Fasciolopsis spp., Paragonimus spp., and Schistosoma spp., with occurrences of 34.8%, 29.6%, 21.4%, 20.0%, 4.0%, 1.6%, 1.0%, 1.0%, and 0.4%, respectively. Mixed infections of GI helminths were noted in 31.0% of the samples. Overall, sampled pigs excreted mostly low levels (< 100 EPG) or moderate levels (> 100–500 EPG) of GI helminth eggs. The highest mean EPG for each parasite species was noted in A. suum. The presence of A. suum and T. suis was confirmed molecularly. The sequences of the internal transcribed spacer 1 (ITS1) region of A. suum showed high similarity with previously reported sequences. Likewise, the sequences of T. suis exhibited high similarity with the sequences reported from humans and pigs. Age was noted as an associated factor (P < 0.05) for GI helminth infection status.

Conclusions

In this report, A. suum and T. suis were molecularly identified for the first time in Myanmar. It is important to extend the information among the farmers to be aware of the necessity of preventing zoonotic parasites by practicing regular deworming, proper use of anthelmintics and maintaining hygienic conditions in their pig farms.
MiR-380 inhibits the proliferation and invasion of cholangiocarcinoma cells by silencing LIS1
Authors: Wei Zhicheng , Xu Bowen , Yin Yanjiang , Chang Jianping , Li Zhiyu , Zhang Yefan , Che Xu , Bi Xinyu
Published: April 2024

Background

The objective of this study was to determine the role and regulatory mechanism of miR-380 in cholangiocarcinoma.

Methods

The TargetScan database and a dual-luciferase reporter assay system were used to determine if LIS1 was a target gene of miR-380. The Cell Counting Kit 8 assay, flow cytometry, and Transwell assay were used to detect the effects of miR-380 and LIS1 on the proliferation, S-phase ratio, and invasiveness of HCCC-9810/HuCCT1/QBC939 cells. Western blotting was used to determine the effect of miR-380 on MMP-2/p-AKT. Immunohistochemistry detected the regulatory effect of miR-380 on the expression of MMP-2/p-AKT/LIS1.

Results

Expression of miR-380 in cholangiocarcinoma was decreased but expression of LIS1 was increased. LIS1 was confirmed to be a target gene of miR-380. Transfection with miR-380 mimics inhibited the proliferation, S-phase arrest, and invasion of HCCC-9810/HuCCT1/QBC939 cells, and LIS1 reversed these inhibitory effects. miR-380 inhibitor promoted proliferation, S-phase ratio, and invasiveness of HCCC-9810/HuCCT1/QBC939 cells. si-LIS1 salvaged the promotive effect of miR-380 inhibitor. Overexpression of miR-380 inhibited expression of MMP-2/p-AKT/LIS1, but miR-380 inhibitor promoted their expression.

Conclusion

An imbalance of miR-380 expression is closely related to cholangiocarcinoma, and overexpression of miR-380 inhibits the expression of MMP-2/p-AKT by directly targeting LIS1.
Genotyping Plasmodium falciparum gametocytes using amplicon deep sequencing
Authors: Vareta Jimmy , Horstman Natalie A. , Adams Matthew , Seydel Karl B. , McCann Robert S. , Cohee Lauren M. , Laufer Miriam K. , Takala-Harrison Shannon
Published: April 2024

Background

Understanding the dynamics of gametocyte production in polyclonal Plasmodium falciparum infections requires a genotyping method that detects distinct gametocyte clones and estimates their relative frequencies. Here, a marker was identified and evaluated to genotype P. falciparum mature gametocytes using amplicon deep sequencing.

Methods

A data set of polymorphic regions of the P. falciparum genome was mined to identify a gametocyte genotyping marker. To assess marker resolution, the number of unique haplotypes in the marker region was estimated from 95 Malawian P. falciparum whole genome sequences. Specificity of the marker for detection of mature gametocytes was evaluated using reverse transcription-polymerase chain reaction of RNA extracted from NF54 mature gametocytes and rings from a non-gametocyte-producing strain of P. falciparum. Amplicon deep sequencing was performed on experimental mixtures of mature gametocytes from two distinct parasite clones, as well as gametocyte-positive P. falciparum field isolates to evaluate the quantitative ability and determine the limit of detection of the genotyping approach.

Results

A 400 bp region of the pfs230 gene was identified as a gametocyte genotyping marker. A larger number of unique haplotypes was observed at the pfs230 marker (34) compared to the sera-2 (18) and ama-1 (14) markers in field isolates from Malawi. RNA and DNA genotyping accurately estimated gametocyte and total parasite clone frequencies when evaluating agreement between expected and observed haplotype frequencies in gametocyte mixtures, with concordance correlation coefficients of 0.97 [95% CI: 0.92–0.99] and 0.92 [95% CI: 0.83–0.97], respectively. The detection limit of the genotyping method for male gametocytes was 0.41 pfmget transcripts/µl [95% CI: 0.28–0.72] and for female gametocytes was 1.98 ccp4 transcripts/µl [95% CI: 1.35–3.68].

Conclusions

A region of the pfs230 gene was identified as a marker to genotype P. falciparum gametocytes. Amplicon deep sequencing of this marker can be used to estimate the number and relative frequency of parasite clones among mature gametocytes within P. falciparum infections. This gametocyte genotyping marker will be an important tool for studies aimed at understanding dynamics of gametocyte production in polyclonal P. falciparum infections.
Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in mainland Tanzania, 2018
Authors: Ngasala Billy , Chiduo Mercy G. , Bushukatale Samwel , Mmbando Bruno P. , Makene Twilumba , Kamugisha Erasmus , Ahmed Maimuna , Mandara Celine I. , Francis Filbert , Mahende Muhidin K. , Kavishe Reginald A. , Muro Florida , Ishengoma Deus S. , Mandike Renata , Molteni Fabrizio , Chacky Frank , Kitojo Chonge , Greer George , Bishanga Dunstan , Chadewa Jasmine , Njau Ritha , Warsame Marian , Kabula Bilali , Nyinondi Ssanyu S. , Reaves Erik , Mohamed Ally
Published: April 2024

Background

The use of artemisinin-based combination therapy (ACT) is recommended by the World Health Organization for the treatment of uncomplicated falciparum malaria. Artemether-lumefantrine (AL) is the most widely adopted first-line ACT for uncomplicated malaria in sub-Saharan Africa (SSA), including mainland Tanzania, where it was introduced in December 2006. The WHO recommends regular assessment to monitor the efficacy of the first-line treatment specifically considering that artemisinin partial resistance was reported in Greater Mekong sub-region and has been confirmed in East Africa (Rwanda and Uganda). The main aim of this study was to assess the efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in mainland Tanzania.

Methods

A single-arm prospective anti-malarial drug efficacy trial was conducted in Kibaha, Mlimba, Mkuzi, and Ujiji (in Pwani, Morogoro, Tanga, and Kigoma regions, respectively) in 2018. The sample size of 88 patients per site was determined based on WHO 2009 standard protocol. Participants were febrile patients (documented axillary temperature ≥ 37.5 °C and/or history of fever during the past 24 h) aged 6 months to 10 years. Patients received a 6-dose AL regimen by weight twice a day for 3 days. Clinical and parasitological parameters were monitored during 28 days of follow-up to evaluate the drug efficacy and safety.

Results

A total of 653 children were screened for uncomplicated malaria and 349 (53.7%) were enrolled between April and August 2018. Of the enrolled children, 345 (98.9%) completed the 28 days of follow-up or attained the treatment outcomes. There were no early treatment failures, but recurrent infections were higher in Mkuzi (35.2%) and Ujiji (23%). By Kaplan–Meier analysis of polymerase chain reaction (PCR) uncorrected adequate clinical and parasitological response (ACPR) ranged from 63.4% in Mkuzi to 85.9% in Mlimba, while PCR-corrected ACPR on day 28 varied from 97.6% in Ujiji to 100% in Mlimba. The drug was well tolerated; the commonly reported adverse events were cough, runny nose, and abdominal pain. No serious adverse event was reported.

Conclusion

This study showed that AL had adequate efficacy and safety for the treatment of uncomplicated falciparum malaria. The high number of recurrent infections were mainly due to new infections, indicating the necessity of utilizing alternative artemisinin-based combinations, such as artesunate amodiaquine, which provide a significantly longer post-treatment prophylactic effect.
Neoadjuvant pertuzumab plus trastuzumab in combination with chemotherapy for human epidermal growth factor receptor 2 positive breast cancer: a real-world retrospective single-institutional study in China
Authors: Peng Dong-Mei , Li Juan , Qiu Jia-Xin , Zhao Lin
Published: April 2024

Introduction

Real-world studies on neoadjuvant dual anti-HER2 therapy combined with chemotherapy for breast cancer (BC) are scarce in China. This study aimed to evaluate the efficacy and safety of neoadjuvant dual anti-HER2 therapy combined with chemotherapy in a real-world setting. Moreover, differences in estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and proliferation cell nuclear antigen (Ki-67) expression pre- and post-neoadjuvant therapy were analyzed.

Methods

Clinical and pathological data of patients with HER2-positive BC who received neoadjuvant dual anti-HER2 therapy combined with chemotherapy at Liaoning Cancer Hospital & Institute, China, between September 2021 and September 2023, were retrospectively reviewed.

Results

Among 179 included patients, a pathologic complete response (pCR) was achieved in 109 patients (60.9%). The univariate analysis results indicated that the hormone receptor (HR) status (P = 0.013), HER2 status (P = 0.003), and cycles of targeted treatment (P = 0.035) were significantly correlated with pCR. Subsequent multivariable analysis showed that HR negative and HER2 status 3 + were independent predictive factors of pCR. Anemia was the most common adverse event (62.0%), and the most common grade 3–4 adverse event was neutropenia (6.1%). The differences in HER2 (34.5%) and Ki-67 (92.7%) expression between core needle biopsy and the residual tumor after neoadjuvant therapy were statistically significant, whereas the differences were insignificant in terms of ER or PR status.

Conclusions

The combination of neoadjuvant trastuzumab and pertuzumab with chemotherapy showed good efficiency, and the toxic side effects were tolerable in patients with BC. In cases where pCR was not achieved after neoadjuvant therapy, downregulation of HER2 and Ki-67 expressions was observed.
Extracellular vesicle encapsulated Homer1a as novel nanotherapeutics against intracerebral hemorrhage in a mouse model
Authors: Fei Xiaowei , Wang Li , Dou Ya-nan , Fei Fei , Zhang Yanyu , Lv Weihao , He Xin , Wu Xiuquan , Chao Wangshu , Chen Hongqing , Wei Jialiang , Gao Dakuan , Fei Zhou
Published: April 2024

Homer1a and A2 astrocytes are involved in the regulation of inflammation induced by intracerebral hemorrhage (ICH). However, there is no anticipated treatment strategy based on the anti-inflammatory effect of Homer1a and A2 astrocytes. Here, we successfully induced A2 astrocytes in vitro, and then we report an efficient method to prepare Homer1a+ EVs derived from A2 astrocytes which making it more stable, safe, and targetable to injured neurons. Homer1a+ EVs promotes the conversion of A1 to A2 astrocytes in ICH mice. Homer1a+ EVs inhibits activation and nuclear translocation of NF-κB, thereby regulating transcription of IL-17A in neurons. Homer1a+ EVs inhibits the RAGE/NF-κB/IL-17 signaling pathway and the binding ability of IL-17A: IL17-AR and RAGE: DIAPH1. In addition, Homer1a+ EVs ameliorates the pathology, behavior, and survival rate in GFAPCreHomer1fl/−Homer1a± and NestinCreRAGEfl/fl ICH mice. Our study provides a novel insight and potential for the clinical translation of Homer1a+ EVs in the treatment of ICH.
Surgical management of multiple coronary artery to coronary sinus fistulas with giant left circumflex artery and multivalvular infective endocarditis
Authors: Shin Sang Bin , Park Won Kyoun , Choi Jae Won , Jung Jong Pil , Park Chang Ryul , Lee Yong Jik , Kim Gwan Sic
Published: April 2024

Coronary artery fistula (CAF) is characterized as a congenital or acquired abnormal communication between a coronary artery and any of the four chambers of the heart (coronary–cameral fistula) or great vessels (coronary arteriovenous fistula) bypassing the capillaries within myocardium. CAF is a rare disease, challenging to diagnose and treat depending on the anatomical location and type of the fistula and accompanying diseases. This study aims to report a case with multiple coronary artery to coronary sinus (CS) fistulas with giant left circumflex artery and multivalvular infective endocarditis.
Effective Apixaban removal using hemoadsorption during emergent open-heart surgery: a case report and narrative literature review
Authors: Mendes Vitor , Mamode Jaid , Jolou Jalal , Malki Mourad , Ellenberger Christoph , Cikirikcioglu Mustafa , Huber Christoph
Published: April 2024

Background

The management of hemostasis in patients medicated with apixaban (Eliquis) undergoing emergency cardiac surgery is exceedingly difficult. The body’s natural elimination pathways for apixaban prove ineffective in emergency situations, and the impact of hemodialysis is limited. The application of Cytosorb® may attenuate the concentration of apixaban, thereby facilitating the stabilization of these patients.

Case presentation

An 84-year-old man treated with apixaban, underwent emergency ascending aorta replacement surgery due to an acute type A aortic dissection. To address the challenges induced by apixaban, we integrated Cytosorb® cartridge into the Cardiopulmonary bypass circuit. There was a 63.7% decrease in perioperative apixaban-specific anti-factor Xa activity. The patient’s postoperative course was favourable.

Conclusion

Hemoadsorption with Cytosorb® may offers a safe and feasible approach for reducing apixaban concentration in emergency cardiac surgery, thereby mitigating the risk of hemorrhagic complications.
Serum protein profiling reveals an inflammation signature as a predictor of early breast cancer survival
Authors: Karihtala Peeter , Leivonen Suvi-Katri , Puistola Ulla , Urpilainen Elina , Jääskeläinen Anniina , Leppä Sirpa , Jukkola Arja
Published: April 2024

Background

Breast cancers exhibit considerable heterogeneity in their biology, immunology, and prognosis. Currently, no validated, serum protein-based tools are available to evaluate the prognosis of patients with early breast cancer.

Methods

The study population consisted of 521 early-stage breast cancer patients with a median follow-up of 8.9 years. Additionally, 61 patients with breast fibroadenoma or atypical ductal hyperplasia were included as controls. We used a proximity extension assay to measure the preoperative serum levels of 92 proteins associated with inflammatory and immune response processes. The invasive cancers were randomly split into discovery (n = 413) and validation (n = 108) cohorts for the statistical analyses.

Results

Using LASSO regression, we identified a nine-protein signature (CCL8, CCL23, CCL28, CSCL10, S100A12, IL10, IL10RB, STAMPB2, and TNFβ) that predicted various survival endpoints more accurately than traditional prognostic factors. In the time-dependent analyses, the prognostic power of the model remained rather stable over time. We also developed and validated a 17-protein model with the potential to differentiate benign breast lesions from malignant lesions (Wilcoxon p < 2.2*10− 16; AUC 0.94).

Conclusions

Inflammation and immunity-related serum proteins have the potential to rise above the classical prognostic factors of early-stage breast cancer. They may also help to distinguish benign from malignant breast lesions.
Utility of visual rating scales in primary progressive aphasia
Authors: Falgàs Neus , Sacchi Luca , Carandini Tiziana , Montagut Nuria , Conte Giorgio , Triulzi Fabio , Galimberti Daniela , Arighi Andrea , Sanchez-Valle Raquel , Fumagalli Giorgio Giulio
Published: April 2024

Introduction

Differential diagnosis among subjects with Primary Progressive Aphasia (PPA) can be challenging. Structural MRI can support the clinical profile. Visual rating scales are a simple and reliable tool to assess brain atrophy in the clinical setting.

The aims of the study were to establish to what extent the visual rating scales could be useful in the differential diagnosis of PPA, to compare the clinical diagnostic impressions derived from routine MRI interpretations with those obtained using the visual rating scale and to correlate results of the scales in a voxel-based morphometry (VBM) analysis.

Method

Patients diagnosed with primary progressive aphasia (PPA) according to current criteria from two centers—Ospedale Maggiore Policlinico of Milan and Hospital Clínic de Barcelona—were included in the study. Two blinded clinicians evaluated the subjects MRIs for cortical atrophy and white matter hyperintensities using two protocols: routine readings and the visual rating scale. The diagnostic accuracy between patients and controls and within PPA subgroups were compared between the two protocols.

Results

One hundred fifty Subjects were studied. All the scales showed a good to excellent intra and inter-rater agreement. The left anterior temporal scale could differentiate between semantic PPA and all other variants.

The rater impression after the protocol can increase the accuracy just for the logopenic PPA. In the VBM analysis, the scores of visual rating scales correlate with the corresponding area of brain atrophy.

Conclusion

The Left anterior temporal rating scale can distinguish semantic PPA from other variants. The rater impression after structured view improved the diagnostic accuracy of logopenic PPA compared to normal readings. The unstructured view of the MRI was reliable for identifying semantic PPA and controls. Neither the structured nor the unstructured view could identify the nonfluent and undetermined variants.
Neuropsychiatric symptoms with focus on apathy and irritability in sporadic and hereditary cerebral amyloid angiopathy
Authors: Kaushik Kanishk , de Kort Anna M. , van Dort Rosemarie , van der Zwet Reinier G.J. , Siegerink Bob , Voigt Sabine , van Zwet Erik W. , van der Plas Maaike C. , Koemans Emma A. , Rasing Ingeborg , Kessels Roy P.C. , Middelkoop Huub A.M. , Schreuder Floris H.B.M. , Klijn Catharina J.M. , Verbeek Marcel M. , Terwindt Gisela M. , van Etten Ellis S. , Wermer Marieke J.H.
Published: April 2024

Background

Neuropsychiatric symptoms (NPS) may affect cognition, but their burden in cerebral amyloid angiopathy (CAA), one of the main causes of intracerebral hemorrhage (ICH) and dementia in the elderly, remains unclear. We investigated NPS, with emphasis on apathy and irritability in sporadic (sCAA) and Dutch-type hereditary (D-)CAA.

Methods

We included patients with sCAA and (pre)symptomatic D-CAA, and controls from four prospective cohort studies. We assessed NPS per group, stratified for history of ICH, using the informant-based Neuropsychiatric Inventory (NPI-Q), Starkstein Apathy scale (SAS), and Irritability Scale. We modeled the association of NPS with disease status, executive function, processing speed, and CAA-burden score on MRI and investigated sex-differences.

Results

We included 181 participants: 82 with sCAA (mean[SD] age 72[6] years, 44% women, 28% previous ICH), 56 with D-CAA (52[11] years, 54% women, n = 31[55%] presymptomatic), and 43 controls (69[9] years, 44% women). The NPI-Q NPS-count differed between patients and controls (sCAA-ICH+:adj.β = 1.4[95%CI:0.6–2.3]; sCAA-ICH-:1.3[0.6-2.0]; symptomatic D-CAA:2.0[1.1–2.9]; presymptomatic D-CAA:1.2[0.1–2.2], control median:0[IQR:0–3]), but not between the different CAA-subgroups. Apathy and irritability were reported most frequently: n = 12[31%] sCAA, 19[37%] D-CAA had a high SAS-score; n = 12[29%] sCAA, 14[27%] D-CAA had a high Irritability Scale score. NPS-count was associated with decreased processing speed (adj.β=-0.6[95%CI:-0.8;-0.4]) and executive function (adj.β=-0.4[95%CI:-0.6;-0.1]), but not with radiological CAA-burden. Men had NPS more often than women.

Discussion

According to informants, one third to half of patients with CAA have NPS, mostly apathy, even in presymptomatic D-CAA and possibly with increased susceptibility in men. Neurologists should inform patients and caregivers of these disease consequences and treat or refer patients with NPS appropriately.