bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of antiseizure medications effects on the EEG neurodynamic by fractal dimension
Authors: Porcaro Camillo , Seppi Dario , Pellegrino Giovanni , Dainese Filippo , Kassabian Benedetta , Pellegrino Luciano , De Nardi Gianluigi , Grego Alberto , Corbetta Maurizio , Ferreri Florinda
Published: June 2024

Objectives

An important challenge in epilepsy is to define biomarkers of response to treatment. Many electroencephalography (EEG) methods and indices have been developed mainly using linear methods, e.g., spectral power and individual alpha frequency peak (IAF). However, brain activity is complex and non-linear, hence there is a need to explore EEG neurodynamics using nonlinear approaches. Here, we use the Fractal Dimension (FD), a measure of whole brain signal complexity, to measure the response to anti-seizure therapy in patients with Focal Epilepsy (FE) and compare it with linear methods.

Materials

Twenty-five drug-responder (DR) patients with focal epilepsy were studied before (t1, named DR-t1) and after (t2, named DR-t2) the introduction of the anti-seizure medications (ASMs). DR-t1 and DR-t2 EEG results were compared against 40 age-matched healthy controls (HC).

Methods

EEG data were investigated from two different angles: frequency domain—spectral properties in δ, θ, α, β, and γ bands and the IAF peak, and time-domain—FD as a signature of the nonlinear complexity of the EEG signals. Those features were compared among the three groups.

Results

The δ power differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, p < 0.01 and DR-t2 vs. HC, p < 0.01). The θ power differed between DR-t1 and DR-t2 (p = 0.015) and between DR-t1 and HC (p = 0.01). The α power, similar to the δ, differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, p < 0.01 and DR-t2 vs. HC, p < 0.01). The IAF value was lower for DR-t1 than DR-t2 (p = 0.048) and HC (p = 0.042). The FD value was lower in DR-t1 than in DR-t2 (p = 0.015) and HC (p = 0.011). Finally, Bayes Factor analysis showed that FD was 195 times more likely to separate DR-t1 from DR-t2 than IAF and 231 times than θ.

Discussion

FD measured in baseline EEG signals is a non-linear brain measure of complexity more sensitive than EEG power or IAF in detecting a response to ASMs. This likely reflects the non-oscillatory nature of neural activity, which FD better describes.

Conclusion

Our work suggests that FD is a promising measure to monitor the response to ASMs in FE.
Can repetitive mechanical motion cause structural damage to axons?
Authors: Coppini Allegra , Falconieri Alessandro , Mualem Oz , Nasrin Syeda Rubaiya , Roudon Marine , Saper Gadiel , Hess Henry , Kakugo Akira , Raffa Vittoria , Shefi Orit
Published: June 2024

Biological structures have evolved to very efficiently generate, transmit, and withstand mechanical forces. These biological examples have inspired mechanical engineers for centuries and led to the development of critical insights and concepts. However, progress in mechanical engineering also raises new questions about biological structures. The past decades have seen the increasing study of failure of engineered structures due to repetitive loading, and its origin in processes such as materials fatigue. Repetitive loading is also experienced by some neurons, for example in the peripheral nervous system. This perspective, after briefly introducing the engineering concept of mechanical fatigue, aims to discuss the potential effects based on our knowledge of cellular responses to mechanical stresses. A particular focus of our discussion are the effects of mechanical stress on axons and their cytoskeletal structures. Furthermore, we highlight the difficulty of imaging these structures and the promise of new microscopy techniques. The identification of repair mechanisms and paradigms underlying long-term stability is an exciting and emerging topic in biology as well as a potential source of inspiration for engineers.
Exercise-induced neuroplasticity: a new perspective on rehabilitation for chronic low back pain
Authors: Zou Jianpeng , Hao Shijie
Published: June 2024

Chronic low back pain patients often experience recurrent episodes due to various peripheral and central factors, leading to physical and mental impairments, affecting their daily life and work, and increasing the healthcare burden. With the continuous advancement of neuropathological research, changes in brain structure and function in chronic low back pain patients have been revealed. Neuroplasticity is an important mechanism of self-regulation in the brain and plays a key role in neural injury repair. Targeting neuroplasticity and regulating the central nervous system to improve functional impairments has become a research focus in rehabilitation medicine. Recent studies have shown that exercise can have beneficial effects on the body, such as improving cognition, combating depression, and enhancing athletic performance. Exercise-induced neuroplasticity may be a potential mechanism through which exercise affects the brain. This article systematically introduces the theory of exercise-induced neuroplasticity, explores the central effects mechanism of exercise on patients with chronic low back pain, and further looks forward to new directions in targeted neuroplasticity-based rehabilitation treatment for chronic low back pain.
Flight to insight: maximizing the potential of Drosophila models of C9orf72-FTD
Authors: d’Almeida Nicole A. , Tipping Marla
Published: June 2024

Advancements in understanding the pathogenesis of C9orf72-associated frontotemporal dementia (C9orf72-FTD) have highlighted the role of repeat-associated non-ATG (RAN) translation and dipeptide repeat proteins (DPRs), with Drosophila melanogaster models providing valuable insights. While studies have primarily focused on RAN translation and DPR toxicity, emerging areas of investigation in fly models have expanded to neuronal dysfunction, autophagy impairment, and synaptic dysfunction, providing potential directions for new therapeutic targets and mechanisms of neurodegeneration. Despite this progress, there are still significant gaps in Drosophila models of C9orf72-FTD, namely in the areas of metabolism and circadian rhythm. Metabolic dysregulation, particularly lipid metabolism, autophagy, and insulin signaling, has been implicated in disease progression with findings from animal models and human patients with C9orf72 repeat expansions. Moreover, circadian disruptions have been observed in C9of72-FTD, with alterations in rest-activity patterns and cellular circadian machinery, suggesting a potential role in disease pathophysiology. Drosophila models offer unique opportunities to explore these aspects of C9orf72-FTD and identify novel therapeutic targets aimed at mitigating neurodegeneration.
Vitamin D status, vitamin D receptor, CYP2R1, and CYP24A1 profiles in children
Authors: Iriani Anggraini , Rachman Andhika , Fatina Marsya Kaila , Gemilang Rizka Kurnia , Trisnandi Andi , Muskananfola Fiona Valerie , Nugraha Media Fitri Isma
Published: June 2024

Introduction

Vitamin D plays a major role in the musculoskeletal and immune system. Understanding the comprehensive mechanism of vitamin D receptors and the enzyme of vitamin D induction (CYP2R1) and inhibition (CYP24A1) in its metabolism is interesting. This study aims to understand vitamin D metabolism in Indonesian pediatrics, specifically in Jakarta, which has abundant sun exposure.

Methodology

A cross-sectional study with comparative, correlative, and multivariate analysis on vitamin D, vitamin D receptor, CYP2R1, and CYP24A1 levels was conducted on 46 children with no known morbidity.

Result

Subjects were mostly male (52.2%), age group of 2–6 years (34.8%), and had sufficient vitamin D status (43.5%, median 27.55 ng/mL). Age was found to have a negative correlation with vitamin D levels (p < 0.001; r = −0.625) and CYP2R1 (p = 0.035; r = −0.311). Significant positive associations were found between CYP24A1 and CYP2R1 (p = 0.046; r = 0.296). Participants aged 0–2 are more likely to have a higher level of vitamin D status compared to those aged >2 years (OR 42.092, 95% CI [4.532–390.914], p = 0.001). VDR levels were significantly lower in insufficient vitamin D levels than in the sufficient group (p = 0.018). VDR and vitamin D status had a positive relation (OR 7.023, 95% CI [1.864–26.453], p = 0.004).

Conclusion

Vitamin D levels decrease with the increase in age. Vitamin D receptor level has an inline-level progression with vitamin D level. CYP2R1 and CYP24A1 suggest a directly proportional relationship. Vitamin D screening and supplementation in children older than 2 years old are suggested.
Colorimetric detection of the potent carcinogen aflatoxin B1 based on the aggregation of L-lysine-functionalized gold nanoparticles in the presence of copper ions
Authors: Sánchez-Carrillo Kaori , Quintanar-Guerrero David , José-Yacamán Miguel , Méndez-Albores Abraham , Vázquez-Durán Alma
Published: June 2024

L-lysine functionalized gold nanoparticles (AuNPs-Lys) have been widely used for the detection of worldwide interest analytes. In this work, a colorimetric assay for the detection of the carcinogen aflatoxin B1 (AFB1) based on the aggregation of AuNPs-Lys in the presence of copper ions was developed. For this purpose, AuNPs were synthesized in citrate aqueous solution, functionalized, and further characterized by UV–Vis, fluorescence, Fourier transform infrared spectroscopy (FTIR), nanoparticle tracking analysis (NTA), dynamic light scattering (DLS), and transmission electron microscopy (TEM). In general, AuNPS-Lys (~2.73 × 1011 particles) offered a clear colorimetric response in the presence of AFB1 and Cu2+ ions showing linearity in the range of 6.25 to 200 ng AFB1/mL, with a detection limit of 4.18 ng AFB1/mL via photometric inspection. Moreover, the performance of the proposed methodology was tested using the 991.31 AOAC official procedure based on monoclonal antibodies in maize samples artificially contaminated with AFB1. There was a good agreement between the measured AFB1 concentrations in both assays, the average recoveries for the colorimetric and immunoaffinity assays were between 91.2–98.4% and 96.0–99.2%, respectively. These results indicated that the colorimetric assay could be used as a rapid, eco-friendly, and cost-effective platform for the quantification of AFB1 in maize-based products.
Effect of frozen gloves on chemotherapy-induced neurotoxicity in breast cancer patients: a systematic review and meta-analysis
Authors: Wu Hongting , Jin Ying , Song Jiaqing , Gao Xiufei
Published: June 2024

Background

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a dose-limiting side effect observed in breast cancer patients. Its primary clinical manifestations include limb numbness, tingling sensations, hypoesthesia, or paresthesia. In severe instances, some patients may also encounter muscle cramps, weakness, and pain, leading to potential paralysis. The onset of CIPN significantly impacts the quality of life for cancer patients. Hence, it is imperative to explore preventive strategies for managing CIPN.

Methods

We searched for relevant randomized controlled trials (RCTs) and non-randomized controlled trials (non-RCTs) in several databases. The primary outcome measures encompassed the Patient Neurotoxicity Questionnaire (PNQ), the Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane), and the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Secondary outcomes aimed to evaluate the quality of life and the tolerability of ice gloves. Meta-analysis was conducted using RevMan 5.3 software to determine the relative risk ratio (RR) and 95% confidence interval (CI).

Results

We conducted an analysis involving 372 patients across seven trials. In our meta-analysis, the use of ice gloves demonstrated non-significant results in reducing the incidence of both motor and sensory neuropathy, as assessed through CTCAE (sensory: RR: 0.94; 95% CI: 0.85 to 1.02; P = 0.15; motor: RR: 1.04; 95% CI: 0.88 to 1.22; P = 0.64). Similarly, when evaluated using the PNQ, there was no significant reduction observed in the incidence of sensory and motor neuropathy (sensory: RR: 0.49; 95% CI: 0.20 to 1.20; P = 0.12; motor: RR: 0.71; 95% CI: 0.26 to 1.99; P = 0.52). Consistently, our conclusions remained unchanged when employing the FACT-Taxane assessment. Regarding the evaluation of the quality of life, our observations suggested a potential improvement with the use of ice gloves, and participants exhibited moderate tolerance towards them.

Conclusion

Ice gloves are a reasonable option for the treatment of CIPN in patients undergoing chemotherapy for breast cancer. However, the effectiveness of ice gloves in combating CIPN remains inconclusive at this time due to the low quality and limited number of clinical trials on this topic.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023457045, identifier CRD42023457045.
Cranial Rosai-Dorfman disease: a case report and literature review
Authors: Lv JunBo , Hu JiBo , Xu Houyun , Yu Xiping
Published: June 2024

Rosai-Dorfman Disease (RDD) is a rare, benign, idiopathic histiocytic proliferative disorder, with its occurrence in the cranial bones being particularly uncommon and prone to misdiagnosis in preoperative radiological examinations. This article reports a case of RDD in the left temporal bone. The radiological presentation of intraosseous RDD includes osteolytic bone destruction, infrequent periosteal reaction, clearly defined tumor margins, and marked uniform enhancement on contrast-enhanced scans. However, these radiological features lack specificity, highlighting the necessity of histopathological examination for a definitive diagnosis, especially for the rarer extranodal subtypes of RDD. Surgical excision of the lesion can lead to favorable therapeutic outcomes.
Recurrent mucinous carcinoma with sarcomatoid and sarcomatous mural nodules: a case report and literature review
Authors: Li Simin , Zhu Jingyu , Jiang Na , Guo Yanping , Hou Meng , Liu Xi , Yang Jin , Yang Xiaofeng
Published: June 2024

Ovarian mucinous tumors with sarcomatous mural nodules are rare. Sarcomatous nodules have a bad prognosis. Its diagnosis and treatment are controversial.It is still controversial whether malignant mural nodules represent a dedifferentiated form of mucinous tumors or collisional tumors. This is a case report of a 32-year-old female diagnosed with ovarian mucinous tumor recurred as a mucinous carcinoma combined with sarcomatoid and undifferentiated sarcoma mural nodules after surgery and chemotherapy. The primary lesion did not have a sarcomatous component after comprehensive sampling and repeated review, while the recurrent lesion had a predominantly sarcomatous component. The patient received a second operation and postoperative chemotherapy plus Anlotinib with no progression at 16 months of follow-up. Primary mucinous carcinoma and sarcomatous mural nodules revealed the same K-RAS mutation(c.35G>T, pG12V), TP53 mutation (c.817C>T, p.R273C), MLL2 mutation(c.13450C>T, p.R4484) and NF1 mutation(c.7876A>G, p.S2626G). We present a comprehensive analysis on morphologic characteristics, molecular detection results, clinical management, and prognosis of ovarian mucinous tumors with mural nodules of sarcomatoid and undifferentiated sarcoma. Mutation sharing between primary mucinous carcinoma and recurrent sarcomatous nodules supports monoclonal origin of primary and recurrent tumors, suggesting a tendency for sarcomatous differentiation during the progression of epithelial tumors. Malignant mural nodules represent dedifferentiation in mucinous ovarian tumors rather than collision of two different tumor types. Therefore, it is imperative to conduct comprehensive sampling, rigorous clinical examination, and postoperative follow-up in order to thoroughly evaluate all mural nodules of ovarian mucinous tumors due to their potential for malignancy and sarcomatous differentiation.
A case of surgically treated non-metastatic SMARCA4-deficient undifferentiated thoracic tumor: a case report and literature review
Authors: Yin Cong , Liu Zheng-jia , He Chao , Yu Hai-xiang
Published: June 2024

SMARCA4-deficient undifferentiated thoracic tumor (SMARCA4-UT) is a rare malignant tumor characterized by inactivation of the SMARCA4 gene and the presence of undifferentiated or rhabdoid morphology in the tissue. This tumor is highly invasive, typically diagnosed at advanced stages III or IV, and commonly involves thoracic structures, such as the mediastinum and chest wall. Reported cases are limited and treatment guidelines have not yet been established. Here, we present a rare case of surgically treated non-metastatic SMARCA4-UT. The patient presented with blood-tinged sputum, dyspnea, and a history of heavy smoking, and underwent surgery after preoperative evaluation ruled out contraindications. The tumor was successfully removed along with the relevant lymph nodes; analysis determined it to be stage IIB T3N0M0. No recurrence was detected at two months post-surgery. However, four months after surgery, the tumor recurred and invaded the adjacent ribs. The diagnosis, differential diagnosis, and treatment of SMARCA4-deficient undifferentiated lung tumors is considered. The combination of chemotherapy and immunotherapy has shown efficacy, and other treatments such as anti-angiogenic drugs, histone deacetylase inhibitors (HDACi), enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors, and oxidative phosphorylation (OXPHOS) inhibitors may also be beneficial in treating SMARCA4-UT.
Placental co-transcriptional activator Vestigial-like 1 (VGLL1) drives tumorigenesis via increasing transcription of proliferation and invasion genes
Authors: Sonnemann Heather M. , Pazdrak Barbara , Nassif Barbara , Sun Yimo , Elzohary Lama , Talukder Amjad H. , Katailiha Arjun S. , Bhat Krishna , Lizée Gregory
Published: June 2024

Introduction

Vestigial-like 1 (VGLL1) is a co-transcriptional activator that binds to TEA domain-containing transcription factors (TEADs). Its expression is upregulated in a variety of aggressive cancer types, including pancreatic and basal-like breast cancer, and increased transcription of VGLL1 is strongly correlated with poor prognosis and decreased overall patient survival. In normal tissues, VGLL1 is most highly expressed within placental trophoblast cells, which share the common attributes of rapid cellular proliferation and invasion with tumor cells. The impact of VGLL1 in cancer has not been fully elucidated and no VGLL1-targeted therapy currently exists.

Methods

The aim of this study was to evaluate the cellular function and downstream genomic targets of VGLL1 in placental, pancreatic, and breast cancer cells. Functional assays were employed to assess the role of VGLL1 in cellular invasion and proliferation, and ChIP-seq and RNAseq assays were performed to identify VGLL1 target genes and potential impact using pathway analysis.

Results

ChIP-seq analysis identified eight transcription factors with a VGLL1-binding motif that were common between all three cell types, including TEAD1-4, AP-1, and GATA6, and revealed ~3,000 shared genes with which VGLL1 interacts. Furthermore, increased VGLL1 expression led to an enhancement of cell invasion and proliferation, which was supported by RNAseq analysis showing transcriptional changes in several genes known to be involved in these processes.

Discussion

This work expands our mechanistic understanding of VGLL1 function in tumor cells and provides a strong rationale for developing VGLL1-targeted therapies for treating cancer patients.
Evaluating the strengths and limitations of multimodal ChatGPT-4 in detecting glaucoma using fundus images
Authors: AlRyalat Saif Aldeen , Musleh Ayman Mohammed , Kahook Malik Y.
Published: June 2024

Overview

This study evaluates the diagnostic accuracy of a multimodal large language model (LLM), ChatGPT-4, in recognizing glaucoma using color fundus photographs (CFPs) with a benchmark dataset and without prior training or fine tuning.

Methods

The publicly accessible Retinal Fundus Glaucoma Challenge “REFUGE” dataset was utilized for analyses. The input data consisted of the entire 400 image testing set. The task involved classifying fundus images into either ‘Likely Glaucomatous’ or ‘Likely Non-Glaucomatous’. We constructed a confusion matrix to visualize the results of predictions from ChatGPT-4, focusing on accuracy of binary classifications (glaucoma vs non-glaucoma).

Results

ChatGPT-4 demonstrated an accuracy of 90% with a 95% confidence interval (CI) of 87.06%-92.94%. The sensitivity was found to be 50% (95% CI: 34.51%-65.49%), while the specificity was 94.44% (95% CI: 92.08%-96.81%). The precision was recorded at 50% (95% CI: 34.51%-65.49%), and the F1 Score was 0.50.

Conclusion

ChatGPT-4 achieved relatively high diagnostic accuracy without prior fine tuning on CFPs. Considering the scarcity of data in specialized medical fields, including ophthalmology, the use of advanced AI techniques, such as LLMs, might require less data for training compared to other forms of AI with potential savings in time and financial resources. It may also pave the way for the development of innovative tools to support specialized medical care, particularly those dependent on multimodal data for diagnosis and follow-up, irrespective of resource constraints.
Pathophysiological changes and injury markers for acute lung injury from blunt impact in infant rabbits
Authors: Wang Ke , Huang ZhenPeng , He JiaWei , Kong LingWang , Chen Mingwei
Published: June 2024

Background

Traffic accidents, particularly blunt impacts, cause serious injuries in children. We aimed to assess inflammatory and injury responses in infant rabbits subjected to acute lung injury resulting from blunt impact, with the goal of identifying potential circulatory injury markers.

Methods

Forty 4-week-old infant rabbits were subjected to a right chest impact using a Hopkinson bar with 2,600 g. Computed tomography was employed to assess injury severity. Pathological changes were observed using hematoxylin and eosin staining in the control, 0, 24, and 72 h groups, post-injury. Immunohistochemistry was used to examine surfactant protein A (SP-A) changes in right lung tissues and upper main bronchi. Serum levels of interleukin-6 (IL-6), IL-8, and SP-A were measured using ELISA within 24 h post-injury in the control, 0 h, and 24 h groups.

Results

Following blunt injury, significant increases were observed in blood white blood cell count (F = 101.556, P < 0.01) and neutrophil percentage (F = 104.228, P < 0.01), which gradually decreased after 24 and 72 h. The lung wet/dry weight ratio indicated significant edema (F = 79.677, P < 0.01), corroborated by hematoxylin and eosin staining showing edema, exudation, and marked granulocyte infiltration in the control, 0 h, 24 h and 72 h groups. SP-A levels decreased rapidly at 0 h, and recovered between 24 and 72 h in the right lung tissues (F = 6.7, P < 0.05), left lung (F = 15.825, P < 0.05) and upper main bronchi (F = 59.552, P < 0.01). The ELISA results showed increasing trends for the control and 0 h groups, while decreasing trends were observed in 24 h group for IL-6 (F = 58.328, P < 0.01) and IL-8 (F = 41.802, P < 0.01). Conversely, SP-A exhibited a decreasing trend in the control and 0 h groups but increased in the serum of 24 h group (F = 52.629, P < 0.01).

Discussion

In cases of direct chest trauma in infant rabbits, particularly mild injuries without rib fractures. SP-A levels correlated with pathological changes across all groups and may serve as biomarkers for pediatric blunt lung impact.
A computerized tool for the systematic visual quality assessment of infant multiple-breath washout measurements
Authors: Oestreich Marc-Alexander , Doswald Isabelle , Salem Yasmin , Künstle Noëmi , Wyler Florian , Frauchiger Bettina S. , Kentgens Anne-Christianne , Latzin Philipp , Yammine Sophie
Published: June 2024

Background

Multiple-breath washout (MBW) is a sensitive method for assessing lung volumes and ventilation inhomogeneity in infants, but remains prone to artefacts (e.g., sighs). There is a lack of tools for systematic retrospective analysis of existing datasets, and unlike N2-MBW in older children, there are few specific quality control (QC) criteria for artefacts in infant SF6-MBW.

Aim

We aimed to develop a computer-based tool for systematic evaluation of visual QC criteria of SF6-MBW measurements and to investigate interrater agreement and effects on MBW outcomes among three independent examiners.

Methods

We developed a software package for visualization of raw Spiroware (Eco Medics AG, Switzerland) and signal processed WBreath (ndd Medizintechnik AG, Switzerland) SF6-MBW signal traces. Interrater agreement among three independent examiners (two experienced, one novice) who systematically reviewed 400 MBW trials for visual artefacts and the decision to accept/reject the washin and washout were assessed.

Results

Our tool visualizes MBW signals and provides the user with (i) display options (e.g., zoom), (ii) options for a systematic QC assessment [e.g., decision to accept or reject, identification of artefacts (leak, sigh, irregular breathing pattern, breath hold), and comments], and (iii) additional information (e.g., automatic identification of sighs). Reviewer agreement was good using pre-defined QC criteria (κ 0.637–0.725). Differences in the decision to accept/reject had no substantial effect on MBW outcomes.

Conclusion

Our visual quality control tool supports a systematic retrospective analysis of existing data sets. Based on predefined QC criteria, even inexperienced users can achieve comparable MBW results.
Efficacy of an online lung ultrasound module on skill acquisition by clinician: a new paradigm
Authors: Sharma Alok , Kumar Gunjana , Nagpal Rema , Naranje Kirti , Sengupta Arnab , Jagannath Vanitha , Suryawanshi Sonali , Suryawanshi Pradeep
Published: June 2024

Introduction

Lung ultrasound (LUS) as an assessment tool has seen significant expansion in adult, paediatric, and neonatal populations due to advancements in point-of-care ultrasound over the past two decades. However, with fewer experts and learning platforms available in low- and middle-income countries and the lack of a standardised supervised training programme, LUS is not currently effectively used to the best of its potential in neonatal units.

Methodology

A cross-sectional survey assessed the efficacy of learning LUS via a mentor-based online teaching module (NEOPOCUS). The questionnaire comprised the clinicians’ demographic profile, pre-course skills, and self-assessment of skill acquisition after course completion with ongoing hands-on practice.

Results

A total of 175 clinicians responded to the survey, with the majority (87.9%) working in level 3 and 4 neonatal intensive care units. Clinicians had variable clinical experience. Of them, 53.2% were consultant paediatricians/neonatologists with over 10 years of experience. After the course, there was a significant increase in clinician confidence levels in diagnosing and assessing all LUS pathology, as evidenced by the increase in median cumulative scores [from baseline 6 (interquartile range, IQR, 6–9) to 20 (IQR 16–24), p < 0.001] with half of them gaining confidence within 3 months of the course.

Conclusion

An online curriculum-based neonatal lung ultrasound training programme with clinician image demonstration and peer review of images for image optimisation increases self-reported confidence in diagnosing and managing neonatal lung pathology. Web-based online training in neonatal lung ultrasound has merits that can help with the delivery of training globally, and especially in low- and middle-income countries.
Delayed colonization of Bifidobacterium spp. and low prevalence of B. infantis among infants of Asian ancestry born in Singapore: insights from the GUSTO cohort study
Authors: Xu Jia , Duar Rebbeca M. , Quah Baoling , Gong Min , Tin Felicia , Chan Penny , Sim Choon Kiat , Tan Kok Hian , Chong Yap Seng , Gluckman Peter D. , Frese Steven A. , Kyle David , Karnani Neerja
Published: June 2024

Background

The loss of ancestral microbes, or the “disappearing microbiota hypothesis” has been proposed to play a critical role in the rise of inflammatory and immune diseases in developed nations. The effect of this loss is most consequential during early-life, as initial colonizers of the newborn gut contribute significantly to the development of the immune system.

Methods

In this longitudinal study (day 3, week 3, and month 3 post-birth) of infants of Asian ancestry born in Singapore, we studied how generational immigration status and common perinatal factors affect bifidobacteria and Bifidobacterium longum subsp. infantis (B. infantis) colonization. Cohort registry identifier: NCT01174875.

Results

Our findings show that first-generation migratory status, perinatal antibiotics usage, and cesarean section birth, significantly influenced the abundance and acquisition of bifidobacteria in the infant gut. Most importantly, 95.6% of the infants surveyed in this study had undetectable B. infantis, an early and beneficial colonizer of infant gut due to its ability to metabolize the wide variety of human milk oligosaccharides present in breastmilk and its ability to shape the development of a healthy immune system. A comparative analysis of B. infantis in 12 countries by their GDP per capita showed a remarkably low prevalence of this microbe in advanced economies, especially Singapore.

Conclusion

This study provides new insights into infant gut microbiota colonization, showing the impact of generational immigration on early-life gut microbiota acquisition. It also warrants the need to closely monitor the declining prevalence of beneficial microbes such as B. infantis in developed nations and its potential link to increasing autoimmune and allergic diseases.
Analysis of adverse drug reactions of Denosumab (Prolia) in osteoporosis based on FDA adverse event reporting system (FAERS)
Authors: Li Ruibo , Yuan Xingyue , Chen Xi , Ou Yili , Chen Jin
Published: June 2024

Objective

To comprehensively analyze the ADRs associated with Denosumab (Prolia) in the treatment of osteoporosis using data from the FAERS database, and gain a better understanding of the potential risks and side effects of Denosumab (Prolia) therapy.

Methods

Data of Denosumab (Prolia) were collected from the FAERS database covering the period from first quarter of 2010 to the third quarter of 2023. Disproportionality analysis was performed by calculating the reporting odds ratios (ROR), proportional reporting ratio (PRR), and Bayesian analysis confidence propagation neural network (BCPNN) to detect positive signals.

Results

Totally, 17,985,365 reports were collected from the FAERS database, 1,97,807 reports of Denosumab (Prolia) were identified as the “primary suspected (PS)” ADRs. Denosumab (Prolia) induced ADRs occurred in 27 organ systems. 38 significant disproportionality PTs satisfying with the three algorithms were retained at the same time. Unexpected significant ADRs such as bone density abnormal and immobile also occur. The majority of the ADRs occurred within the first 30 days after Denosumab (Prolia) initiation.

Conclusion

Based on the American FAERS database, the high frequency ADRs of Denosumab (Prolia) were hypocalcaemia, bone density abnormal, eczema, rebound effect, spinal deformity, etc. Clinical use of this drug should focus on this part of ADRs. Attention should also be paid to newly discovered ADRs, such as immobile, menopausal symptoms, etc., to avoid more serious consequences. Cohort studies, more detailed and comprehensive case information, and long-term clinical investigations are needed to confirm these results and to further understand the safety profile of Denosumab (Prolia).
Exploring the role of trifarotene against RAR-α: an investigation of expression pattern and clinicopathological significance of RAR-α in breast cancer
Authors: Jan Nusrat , Sofi Shazia , Abo Mansoor Adel , Abdelrahim Adil , Ahmad Irshad , Almilabairy Abdullah , Ahmad Fuzail , Mir Manzoor Ahmad
Published: June 2024

Introduction

The members retinoic acid receptors (RARs) (α, β, and γ) and retinoid X receptors (RXRs) (α, β, and γ) belong to the retinoid receptor family. They regulate the biological action of classical retinoids through nuclear retinoid receptors, a transcription factor that is regulated by ligands. Through the binding of particular retinoic acid-responsive elements (RAREs) located in target gene promoters, RARs and members of the RXRs form heterodimers. By binding to its nuclear receptors and triggering the transcription of the target genes downstream, retinoic acid (RA) mediates the expression of certain genes. Retinoids so mainly control gene expression to carry out their biological actions. RARs are essential for many biological processes, such as development, immunity, reproduction, organogenesis, and homeostasis. Apart from their physiological functions, RARs are also linked to pathologies and tumors due to mutations, protein fusions, changes in expression levels, or abnormal post-translational changes that lead to aberrant functions and homeostasis breakdown. The oncogenic development of animal tissues or cultured cells is linked to altered expression of retinoid receptors. The RAR-α is over-expressed in several malignancies. Increased invasion and migration in several cancer forms, including HNSC carcinoma, pediatric low-grade gliomas, lung adenocarcinoma, and breast cancer, have been linked to its upregulated expression. Numerous approved therapeutic regimens targeting RAR-α have been developed, improving patient survival rates.

Objective

This study’s main objective was to identify novel RAR-α-targeting drugs and evaluate the expression patterns of RAR-α in breast cancer patients.

Methodology

In-silico investigation using a variety of bioinformatics tools like UALCAN, TISCH, TIMER 2.0, ENRICHR, and others were employed to examine the expression of RAR-α. Further we evaluated in-silico inhibition of RAR-α with trifarotene and also tested the cytotoxicity of trifarotene in breast cancer cells.

Results

Our research indicates that RAR-α is upregulated in several malignancies including Breast Cancer. It regulates granulocyte differentiation and has an association with the retinoic acid receptor signaling pathway and cellular response to estrogen stimulus. Furthermore, trifarotene was found as a potential synthetic compound that targets RAR-α through in silico and in-vitro study.

Discussion

Overall, this research indicates that elevated expression of RAR-α enhances the onset of breast cancer. Using trifarotene medication to target RAR-α will significantly boost the response of breast cancer individuals to treatment and delay the development of resistance to drugs.
Intravenous thrombolysis versus dual antiplatelet therapy for patients with acute minor ischaemic stroke: a systematic review and meta-analysis
Authors: Qin Bin , Fu Lin , Qin Huixun , Liang Yuming , Qin Cheng , Zhang Jiede , Gao Wen
Published: June 2024

Background and purpose

The efficacy of intravenous thrombolysis (IVT) in patients with acute minor ischaemic stroke (AMIS) remains unclear. We performed a meta-analysis to compare the efficacy and safety of IVT and dual antiplatelet therapy (DAPT) in patients with AMIS.

Methods

The Embase, Cochrane Library, PubMed, and Web of Science databases were searched up to 10 October, 2023. Prospective and retrospective studies comparing the clinical outcomes of IVT and DAPT were included. Odds ratios (ORs) and 95% confidence intervals (CIs) for early neurological deterioration (END), excellent and favourable functional outcomes, recurrent ischaemic stroke at 3 months, mortality at 3 months, and symptomatic intracranial haemorrhage (ICH) were pooled using a random-effects model.

Results

Of the five included studies, 6,340 patients were included. In patients with AMIS, IVT was not significantly associated with excellent and favourable functional outcomes, recurrent ischaemic stroke, or all-cause mortality at 3 months compared to early DAPT. However, a higher risk of symptomatic ICH (OR, 9.31; 95% CI, 3.39–25.57) and END (OR, 2.75; 95% CI, 1.76–4.30) were observed with IVT.

Conclusion

This meta-analysis indicated that IVT was not superior to DAPT in patients with AMIS, especially in those with nondisabling AIS. However, these findings should be interpreted with caution and have some limitations. Further, well-designed randomised controlled trials are warranted.
Clinical significance and biological function of interferon regulatory factor 1 in non-small cell lung cancer
Authors: Su Jialin , Tan Shuhua , Li Yuning , Chen Xinglong , Liu Jiasi , Luo Yongzhong , Pan Changqie , Zhang Lemeng
Published: June 2024

The clinical application and biological function of interferon regulatory factor 1 (IRF1) in non-small cell lung cancer (NSCLC) patients undergoing chemoimmunotherapy remain elusive. The aim of this study was to investigate the predictive and prognostic significance of IRF1 in NSCLC patients. We employed the cBioPortal database to predict frequency changes in IRF1 and explore its target genes. Bioinformatic methods were utilized to analyze the relationship between IRF1 and immune regulatory factors. Retrospective analysis of clinical samples was conducted to assess the predictive and prognostic value of IRF1 in chemoimmunotherapy. Additionally, A549 cells with varying IRF1 expression levels were constructed to investigate its effects on NSCLC cells, while animal experiments were performed to study the role of IRF1 in vivo. Our findings revealed that the primary mutation of IRF1 is deep deletion and it exhibits a close association with immune regulatory factors. KRAS and TP53 are among the target genes of IRF1, with interferon and IL-2 being the predominantly affected pathways. Clinically, IRF1 levels significantly correlate with the efficacy of chemoimmunotherapy. Patients with high IRF1 levels exhibited a median progression-free survival (mPFS) of 9.5 months, whereas those with low IRF1 levels had a shorter mPFS of 5.8 months. IRF1 levels positively correlate with PD-L1 distribution and circulating IL-2 levels. IL-2 enhances the biological function of IRF1 and recapitulates its role in vivo in the knockdown group. Therefore, IRF1 may possess predictive and prognostic value for chemoimmunotherapy in NSCLC patients through the regulation of the IL-2 inflammatory pathway.
Correlation and singular optics for diagnostics of structured light and condensed matter: time-stationary and spatio-temporal approaches
Authors: Angelsky O. V. , Bekshaev A. Y. , Maksimyak P. P. , Mokhun I. I. , Zenkova C. Y. , Gotsulskiy V. Y. , Ivanskyi D. I. , Zheng Jun
Published: June 2024

The review describes the principles and examples of practical realization of diagnostic approaches based on the coherence theory, optical singularities and interference techniques. The presentation is based on the unified correlation-optics and coherence-theory concepts. The applications of general principles are demonstrated by several examples including the study of inhomogeneities and fluctuations in water solutions and methods for sensitive diagnostics of random phase objects (e.g., rough surfaces). The specific manifestations of the correlation-optics paradigms are illustrated in applications to non-monochromatic fields structured both in space and time. For such fields, the transient patterns of the internal energy flows (Poynting vector distribution) and transient states of polarization are described. The single-shot spectral interference is analyzed as a version of the correlation-optics approach adapted to ultra-short light pulses. As a characteristic example of such pulses, uniting the spatio-temporal and singular properties, the spatio-temporal optical vortices are considered in detail; their properties, methods of generation, diagnostics, and possible applications are exposed and characterized. Prospects of further research and applications are discussed.
Combined subsoiling and ridge–furrow rainfall harvesting during the summer fallow season improves wheat yield, water and nutrient use efficiency, and quality and reduces soil nitrate-N residue in the dryland summer fallow–winter wheat rotation
Authors: Wu Jinzhi , Wang Rongrong , Zhao Wenxin , Zhao Kainan , Wu Shanwei , Zhang Jun , Wang Hezheng , Fu Guozhan , Huang Ming , Li Youjun
Published: June 2024

Both subsoiling tillage (ST) and ridge and furrow rainfall harvesting (RF) are widely implemented and play an important role in boosting wheat productivity. However, information about the effects of ST coupled with RF during the summer fallow season on wheat productivity and environmental issues remains limited. This study aims to explore the effects of ST coupled with RF on water harvesting, wheat productivity–yield traits, water and nutrient use efficiency and quality, and soil nitrate-N residue in dryland winter wheat–summer fallow rotation at the intersection of southern Loess Plateau and western Huang–Huai–Hai Plain in China in 2018–2022. Three tillage practices—deep plowing with straw turnover (PTST), subsoiling with straw mulching (STSM), and STSM coupled with RF (SRFSM)—are conducted during the summer fallow season. The results indicated that tillage practices during the summer fallow season significantly impacted wheat productivity and soil nitrate-N residue. Compared to PTST, STSM significantly enhanced rainfall fallow efficiency and water use efficiency by 7.0% and 14.2%, respectively, as well as N, P, and K uptake efficiency by 16.9%, 16.2%, and 15.3%, and thus increased grain yield by 14.3% and improved most parameters of protein components and processing quality, albeit with an increase in nitrate-N residue in the 0- to 300-cm soil depth by 12.5%. SRFSM, in turn, led to a further increase in water storage at sowing, resulting in an increase of water use efficiency by 6.8%, as well as N, P, and K uptake efficiency and K internal efficiency by 11.8%, 10.4%, 8.8%, and 4.7%, thereby significantly promoting grain yield by 10.2%, and improving the contents of all the protein components and enhancing the processing quality in grain, and simultaneously reducing the nitrate-N residue in the 0- to 300-cm soil layer by 16.1%, compared to STSM. In essence, this study posits that employing subsoiling coupled with ridge–furrow rainfall harvesting (SRFSM) during the summer fallow season is a promising strategy for enhancing wheat yield, efficiency, and quality, and simultaneously reducing soil nitrate-N residue within the dryland summer fallow–winter wheat rotation system.
Online inspection of blackheart in potatoes using visible-near infrared spectroscopy and interpretable spectrogram-based modified ResNet modeling
Authors: Guo Yalin , Zhang Lina , He Yakai , Lv Chengxu , Liu Yijun , Song Haiyun , Lv Huangzhen , Du Zhilong
Published: June 2024

Introduction

Blackheart is one of the most common physiological diseases in potatoes during storage. In the initial stage, black spots only occur in tissues near the potato core and cannot be detected from an outward appearance. If not identified and removed in time, the disease will seriously undermine the quality and sale of theentire batch of potatoes. There is an urgent need to develop a method for early detection of blackheart in potatoes.

Methods

This paper used visible-near infrared (Vis/NIR) spectroscopy to conduct online discriminant analysis on potatoes with varying degrees of blackheart and healthy potatoes to achieve real-time detection. An efficient and lightweight detection model was developed for detecting different degrees of blackheart in potatoes by introducing the depthwise convolution, pointwise convolution, and efficient channel attention modules into the ResNet model. Two discriminative models, the support vector machine (SVM) and the ResNet model were compared with the modified ResNet model.

Results and discussion

The prediction accuracy for blackheart and healthy potatoes test sets reached 0.971 using the original spectrum combined with a modified ResNet model. Moreover, the modified ResNet model significantly reduced the number of parameters to 1434052, achieving a substantial 62.71% reduction in model complexity. Meanwhile, its performance was evidenced by a 4.18% improvement in accuracy. The Grad-CAM++ visualizations provided a qualitative assessment of the model’s focus across different severity grades of blackheart condition, highlighting the importance of different wavelengths in the analysis. In these visualizations, the most significant features were predominantly found in the 650–750 nm range, with a notable peak near 700 nm. This peak was speculated to be associated with the vibrational activities of the C-H bond, specifically the fourth overtone of the C-H functional group, within the molecular structure of the potato components. This research demonstrated that the modified ResNet model combined with Vis/NIR could assist in the detection of different degrees of black in potatoes.
Research on fertilization decision method for rice tillering stage based on the coupling of UAV hyperspectral remote sensing and WOFOST
Authors: Li Shilong , Jin Zhongyu , Bai Juchi , Xiang Shuang , Xu Chenyi , Yu Fenghua
Published: June 2024

Introduction

The use of chemical fertilizers in rice field management directly affects rice yield. Traditional rice cultivation often relies on the experience of farmers to develop fertilization plans, which cannot be adjusted according to the fertilizer requirements of rice. At present, agricultural drones are widely used for early monitoring of rice, but due to their lack of rationality, they cannot directly guide fertilization. How to accurately apply nitrogen fertilizer during the tillering stage to stabilize rice yield is an urgent problem to be solved in the current large-scale rice production process.

Methods

WOFOST is a highly mechanistic crop growth model that can effectively simulate the effects of fertilization on rice growth and development. However, due to its lack of spatial heterogeneity, its ability to simulate crop growth at the field level is weak. This study is based on UAV remote sensing to obtain hyperspectral data of rice canopy and assimilation with the WOFOST crop growth model, to study the decision-making method of nitrogen fertilizer application during the rice tillering stage. Extracting hyperspectral features of rice canopy using Continuous Projection Algorithm and constructing a hyperspectral inversion model for rice biomass based on Extreme Learning Machine. By using two data assimilation methods, Ensemble Kalman Filter and Four-Dimensional Variational, the inverted biomass of the rice biomass hyperspectral inversion model and the localized WOFOST crop growth model were assimilated, and the simulation results of the WOFOST model were corrected. With the average yield as the goal, use the WOFOST model to formulate fertilization decisions and create a fertilization prescription map to achieve precise fertilization during the tillering stage of rice.

Results

The research results indicate that the training set R2 and RMSE of the rice biomass hyperspectral inversion model are 0.953 and 0.076, respectively, while the testing set R2 and RMSE are 0.914 and 0.110, respectively. When obtaining the same yield, the fertilization strategy based on the ENKF assimilation method applied less fertilizer, reducing 5.9% compared to the standard fertilization scheme.

Discussion

This study enhances the rationality of unmanned aerial vehicle remote sensing machines through data assimilation, providing a new theoretical basis for the decision-making of rice fertilization.