bluuebunny/crossref_metadata_2025 huggingface dataset:
Consensus Recommendations from the 2024 Lymphoma Research Foundation Workshop on Treatment Selection and Sequencing in CLL or SLL
Authors: Soumerai Jacob D , Barrientos Jacqueline Claudia , Ahn Inhye E. , Coombs Catherine C. , Gladstone Douglas E , Hoffmann Marc S , Kittai Adam S , Jacobs Ryan W , Lipsky Andrew , Patel Krish , Rhodes Joanna M , Skarbnik Alan P , Thompson Meghan C. , Ermann Daniel A. , Reville Patrick K , Shah Harsh R. , Brown Jennifer R , Stephens Deborah M
Published: November 2024

Over the past decade, treatment recommendations for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) have shifted from traditional chemoimmunotherapy to targeted therapies. Multiple new therapies are commercially available, and in many cases a lack of randomized clinical trial data makes selection of the optimal treatment for each patient challenging. Additionally, many patients continue to receive chemoimmunotherapy in the US, suggesting a gap between guidelines and real-world practice. The Lymphoma Research Foundation convened a workshop comprised of a panel of CLL/SLL experts in the US to develop consensus recommendations for selection and sequencing of therapies for patients with CLL/SLL in the US. Herein, the recommendations are compiled for use as a practical clinical guide for treating providers caring for patients with CLL/SLL, which complement existing guidelines by providing a nuanced discussion relating how our panel of CLL/SLL experts in the US care for patients in a real-world environment.
Pre-market health systems barriers and enablers to infectious diseases point-of-care diagnostics in Australia: qualitative interviews with key informants
Authors: Lafferty Lise , Applegate Tanya L. , Lewis Sophie , Drysdale Kerryn , Monaghan Robert , Kelly-Hanku Angela , Guy Rebecca , Treloar Carla
Published: November 2024

Background

There exist multiple regulatory layers for point-of-care (POC) testing to be implemented within Australia. This qualitative analysis sought to understand the pre-market barriers and facilitators to scale-up infectious diseases POC testing in primary care settings at the national level.

Methods

Key informant interviews were undertaken with people (n = 30) working in high- level positions relevant to infectious diseases POC testing in Australia. Participants were recruited from federal and state health departments, industry, and nongovernment national peak bodies. The Unitaid scalability framework informed this analysis to understand barriers and enablers to creating access conditions and establishing country readiness for market access of POC tests.

Results

Participants identified regulatory frameworks as significant barriers to market access. National strategies and advocacy were viewed as potential enablers to establishing country readiness. It was recommended that the national system for universal health care should fund infectious disease POC tests to ensure financial sustainability, though the existing pathology infrastructure was regarded as a likely inhibitor.

Conclusions

Current regulatory frameworks inhibit market access for infectious disease POC testing devices for use in the primary care setting. National advocacy is urgently needed to gain government support and align national policies with regulatory frameworks.
Associations of multiple lifestyle behaviors with allergic disease symptoms and sensitization in 9–11-year-old Finnish children
Authors: Peltonen Henna , Kukkonen Anna Kaarina , Korkalo Liisa , Fogelholm Mikael , Mäkelä Mika J. , Erkkola Maijaliisa , Vepsäläinen Henna
Published: November 2024

Background

The increase in allergic diseases in children has coincided with the westernization of lifestyles. Although clustering of modifiable lifestyles has been frequently reported in children, there is limited research on how lifestyle factors collectively contribute to allergic conditions. Our aim was to identify lifestyle clusters among Finnish school-aged children and explore their associations with the prevalence of allergic disease symptoms and sensitization.

Methods

We used cross-sectional data from the international ISCOLE survey and its Finnish ancillary allergy study conducted in 2012–2013. We studied 148–461 children aged 9–11 years living in the metropolitan area of Finland. Parents completed a questionnaire on their child’s allergic disease symptoms, and specific IgE responses from blood samples were analyzed to determine allergic sensitization. Lifestyle factors considered in clustering were moderate-to-vigorous-physical activity (MVPA) and nighttime sleep recorded by accelerometers, screen time inquired via a questionnaire, and healthy and unhealthy dietary patterns from food frequency questionnaire data. Lifestyle clusters were identified using K-means cluster analysis, and their associations with allergic disease symptoms and sensitization were explored using logistic regression models.

Results

Two distinct and stable clusters were identified: ‘healthier lifestyle & lower MVPA’ and ‘unhealthier lifestyle & higher MVPA’. After adjustments, children in the ‘unhealthier lifestyle & higher MVPA’ cluster did not show significantly different odds for symptoms of asthma (OR: 0.80, 95% CI: 0.46–1.37), allergic rhinitis (OR: 1.32, 95% CI: 0.77–2.24), or eczema (OR: 0.89, 95% CI: 0.43–1.77) as compared to those in the ‘healthier lifestyle & lower MVPA’ cluster. Similar results were observed for sensitization to ≥ 1 inhaled allergen (OR: 1.27, 95% CI: 0.53–3.10) and sensitization to ≥ 1 food allergen (OR: 0.91, 95% CI: 0.30–2.60).

Conclusions

The results suggest that modifiable lifestyle factors may not play a significant role in allergic conditions within the examined age group. Lifestyle behaviors established in earlier childhood may serve as more credible predictors of allergic outcomes.
Periodontitis and dental quality of life predict long-term survival in head and neck cancer
Authors: Farran Mirna , Neppelberg Evelyn , Løes Sigbjørn , Aarstad Anne K. H. , Moe Svein Erik , Aarstad Hans Jørgen
Published: November 2024

Background

Our aim was to investigate oral health in newly diagnosed head and neck squamous cell carcinoma (HNSCC) patients in relation to long-term survival. We assessed whether the level of alveolar bone loss due to periodontitis at diagnosis, measured from orthopantomogram (OPG), and reported dental health-related quality of life (HRQoL) scores obtained at diagnosis contain prognostic information for HNSCC patients.

Methods

A total of 79 patients from a consecutive cohort of 106 diagnosed with HNSCC between November 2002 and June 2005 were included. All patients reported dental HRQoL, OPG-determined alveolar bone loss were measured in 79 patients at diagnosis. Reduced alveolar bone loss (≥ 4 mm) from cement-enamel junction on at least two molars or premolars registered both horizontally and vertically served as indicator of periodontal disease.

Results

With alveolar bone loss, we determined increased mortality by univariate analysis (RR = 2.28, CI: 1.22–4.28, p = 0.01) and a strong trend by multivariate analyses adjusted for standard clinical information (RR = 1.95, CI: 0.98–3.87, p = 0.056). Reported lowered dental HRQoL scores predicted long-term survival in both univariate (RR = 3.58, CI: 1.99–6.45, p < 0.001) and multivariate adjusted for standard clinical information (RR = 2.17, CI: 1.17–4.01, p = 0.014). When analyzed with Cox regression, including alveolar bone loss and dental HRQoL, both factors, adjusted by clinical variables, were significant predictors of long-term survival: dental HRQoL (p = 0.007) and present alveolar bone loss (p = 0.034). Non-HNSCC disease-specific long-term survival predicted was also predicted when alveolar bone loss and dental HRQoL were analyzed simultaneously and adjusted for standard clinical information.

Conclusions

The degree of alveolar bone loss, as determined by OPG, and dental HRQoL both obtained at the time of HNSCC diagnosis, predicted long-term survival. When analyzed simultaneously, both factors remained significant in both univariate and multivariate analyses, adjusted by pertinent clinical variables, highlighting their unique prognostic value.
Considerations in the search for epistasis
Authors: Balvert Marleen , Cooper-Knock Johnathan , Stamp Julian , Byrne Ross P. , Mourragui Soufiane , van Gils Juami , Benonisdottir Stefania , Schlüter Johannes , Kenna Kevin , Abeln Sanne , Iacoangeli Alfredo , Daub Joséphine T. , Browning Brian L. , Taş Gizem , Hu Jiajing , Wang Yan , Alhathli Elham , Harvey Calum , Pianesi Luna , Schulte Sara C. , González-Domínguez Jorge , Garrisson Erik ,   Lorentz workshop on epistasis, Al-Chalabi Ammar , Cartes Jorge Avila , Baaijens Jasmijn , von Berg Joanna , Bolognini Davide , Bonizzoni Paola , Guarracino Andrea , Koyuturk Mehmet , Markowska Magda , Dandinasivara Raghuram , van Bemmelen Jasper , Vorbrugg Sebastian , Zhang Sai , Pasanuic Bogdan , Snyder Michael P. , Schönhuth Alexander , Sng Letitia M. F. , Twine Natalie A.
Published: November 2024

Epistasis refers to changes in the effect on phenotype of a unit of genetic information, such as a single nucleotide polymorphism or a gene, dependent on the context of other genetic units. Such interactions are both biologically plausible and good candidates to explain observations which are not fully explained by an additive heritability model. However, the search for epistasis has so far largely failed to recover this missing heritability. We identify key challenges and propose that future works need to leverage idealized systems, known biology and even previously identified epistatic interactions, in order to guide the search for new interactions.
Decoding VExUS: a practical guide for excelling in point-of-care ultrasound assessment of venous congestion
Authors: Assavapokee Taweevat , Rola Philippe , Assavapokee Nicha , Koratala Abhilash
Published: November 2024

Venous congestion, often associated with elevated right atrial pressure presents a clinical challenge due to its varied manifestations and potential organ damage. Recognizing the manifestations of venous congestion through bedside physical examination or laboratory tests can be challenging. Point-of-care ultrasound (POCUS) is emerging as a valuable bedside tool for assessing venous congestion, with the Venous Excess Ultrasound (VExUS) technique gaining prominence. VExUS facilitates non-invasive quantification of venous congestion, relying on measurements of the inferior vena cava (IVC) size and Doppler assessments of the hepatic vein (HV), portal vein (PV), and intrarenal vein, thereby providing real-time insights into hemodynamic status and guiding therapeutic interventions. The grading system outlined in VExUS aids in stratifying the severity of congestion. However, achieving proficiency in VExUS requires a comprehensive understanding of Doppler techniques and their clinical applications. This review article provides practical guidance on performing VExUS, encompassing equipment requirements, preparation, machine settings, and examination techniques for assessing the inferior vena cava (IVC), hepatic vein (HV), portal vein (PV), and intrarenal vein. Potential pitfalls and troubleshooting strategies are discussed to ensure accurate interpretation of Doppler waveforms.
Unveiling the role of histone deacetylases in neurological diseases: focus on epilepsy
Authors: Cao Dan-Feng , Zhou Xin-Yu , Guo Qian , Xiang Ming-Yao , Bao Mei-Hua , He Bin-Sheng , Mao Xiao-Yuan
Published: November 2024

Epilepsy remains a prevalent chronic neurological disease that is featured by aberrant, recurrent and hypersynchronous discharge of neurons and poses a great challenge to healthcare systems. Although several therapeutic interventions are successfully utilized for treating epilepsy, they can merely provide symptom relief but cannot exert disease-modifying effect. Therefore, it is of urgent need to explore other potential mechanism to develop a novel approach to delay the epileptic progression. Since approximately 30 years ago, histone deacetylases (HDACs), the versatile epigenetic regulators responsible for gene transcription via binding histones or non-histone substrates, have grabbed considerable attention in drug discovery. There are also substantial evidences supporting that aberrant expressions and/activities of HDAC isoforms are reported in epilepsy and HDAC inhibitors (HDACi) have been successfully utilized for therapeutic purposes in this condition. However, the specific mechanisms underlying the role of HDACs in epileptic progression have not been fully understood. Herein, we reviewed the basic information of HDACs, summarized the recent findings associated with the roles of diverse HDAC subunits in epilepsy and discussed the potential regulatory mechanisms by which HDACs affected the development of epilepsy. Additionally, we also provided a brief discussion on the potential of HDACs as promising therapeutic targets for epilepsy treatment, serving as a valuable reference for basic study and clinical translation in epilepsy field.
Thangka image captioning model with Salient Attention and Local Interaction Aggregator
Authors: Hu Wenjin , Zhang Fujun , Zhao Yinqiu
Published: November 2024

Thangka image captioning aims to automatically generate accurate and complete sentences that describe the main content of Thangka images. However, existing methods fall short in capturing the features of the core deity regions and the surrounding background details of Thangka images, and they significantly lack an understanding of local actions and interactions within the images. To address these issues, this paper proposes a Thangka image captioning model based on Salient Attention and Local Interaction Aggregator (SALIA). The model is designed with a Dual-Branch Salient Attention Module (DBSA) to accurately capture the expressions, decorations of the deity, and descriptive background elements, and it introduces a Local Interaction Aggregator (LIA) to achieve detailed analysis of the characters’ actions, facial expressions, and the complex interactions with surrounding elements in Thangka images. Experimental results show that SALIA outperforms other state-of-the-art methods in both qualitative and quantitative evaluations of Thangka image captioning, achieving BLEU4: 94.0%, ROUGE_L: 95.0%, and CIDEr: 909.8% on the D-Thangka dataset, and BLEU4: 22.2% and ROUGE_L: 47.2% on the Flickr8k dataset.
Small bowel intussusception due to adenocarcinoma of ectopic pancreas in the jejunum: a case report
Authors: Yamamoto Kota , Ishimori Takahiro , Okada Taiki , Sasaki Takeshi , Mikajiri Yumi , Terashima Takahiro , Kawamoto Shunji
Published: November 2024

Introduction

We encountered a case of adenocarcinoma of the ectopic pancreas, causing intussusception.

Case presentation

A 76-year-old man presented with complaints of abdominal distention and vomiting to the emergency department in March 2022. Computed tomography showed that the small bowel piled up approximately 20 cm from the ligament of the traits. Endoscopic repair was challenging; therefore, laparoscopic repair and partial resection of the small bowel were performed. The specimen showed a mass in the small bowel arising from an ectopic pancreas that had caused accumulation. Pathological examination revealed ectopic pancreatic cancer. Two years postoperatively, no apparent recurrence has been observed. We report a relatively rare case of a cancerous ectopic jejunal pancreas causing a mass, with a discussion in the literature.

Conclusions

Detection typically requires surgery due to advanced-stage intestinal obstruction or accumulation, as observed in the present case. However, preoperative diagnosis and early detection of ectopic pancreatic cancer are challenging. The disease progresses similarly to pancreatic cancer, highlighting the need for early detection methods. Additionally, accumulating more case reports is essential for establishing an effective treatment strategy.
Image biomarkers and explainable AI: handcrafted features versus deep learned features
Authors: Rundo Leonardo , Militello Carmelo
Published: November 2024

Feature extraction and selection from medical data are the basis of radiomics and image biomarker discovery for various architectures, including convolutional neural networks (CNNs). We herein describe the typical radiomics steps and the components of a CNN for both deep feature extraction and end-to-end approaches. We discuss the curse of dimensionality, along with dimensionality reduction techniques. Despite the outstanding performance of deep learning (DL) approaches, the use of handcrafted features instead of deep learned features needs to be considered for each specific study. Dataset size is a key factor: large-scale datasets with low sample diversity could lead to overfitting; limited sample sizes can provide unstable models. The dataset must be representative of all the “facets” of the clinical phenomenon/disease investigated. The access to high-performance computational resources from graphics processing units is another key factor, especially for the training phase of deep architectures. The advantages of multi-institutional federated/collaborative learning are described. When large language models are used, high stability is needed to avoid catastrophic forgetting in complex domain-specific tasks. We highlight that non-DL approaches provide model explainability superior to that provided by DL approaches. To implement explainability, the need for explainable AI arises, also through post hoc mechanisms.

Relevance statement

This work aims to provide the key concepts for processing the imaging features to extract reliable and robust image biomarkers.

Key Points

The key concepts for processing the imaging features to extract reliable and robust image biomarkers are provided.

The main differences between radiomics and representation learning approaches are highlighted.

The advantages and disadvantages of handcrafted versus learned features are given without losing sight of the clinical purpose of artificial intelligence models.

Graphical Abstract
Thermographic and ultrasound assessment in patients with rheumatoid arthritis: can thermography detect subclinical synovitis at the wrist?
Authors: Tan York Kiat , Lim Gek Hsiang , Ooi Chin Chin , Ma Voon Chee , Vora Bimal Mayur Kumar
Published: November 2024

Background

Thermography is an emerging imaging modality which allows for a quick and objective measure of joint surface temperature in patients with rheumatoid arthritis (RA). To date, there are no published studies comparing thermography with ultrasonography in the subclinical assessment of joint inflammation at the wrist of patients with RA, and no published data on inter-rater reliability for multiple raters for thermographic assessment at the RA wrist. In our study comparing thermography and ultrasonography at the RA wrist, we aim to determine if thermography can detect subclinical synovitis. Additionally, we performed inter-reliability testing (multiple raters) for both thermography and ultrasonography.

Methods

Thermographic (average (Tavg), maximum (Tmax) and minimum (Tmin) temperatures) and ultrasound (total grey-scale (TGS) score and total power Doppler (TPD) scores) parameters were compared between two patient groups: Asymptomatic Group (with non-swollen and non-tender wrists) and Symptomatic Group (with swollen and/or tender wrists). Among Asymptomatic Group patients, thermographic parameters were compared between those with and without wrist joint recess(es) having ultrasound synovitis (PD ≥ 1 or GS ≥ 2); Spearman’s correlation and simple linear regression were used to study the relationship between thermographic and ultrasound parameters. Intra-class correlation coefficient (ICC) was used for inter-rater reliability calculation.

Results

Eighty-seven RA patients’ right wrists were imaged in this cross-sectional study. Thermographic temperatures, TPD and TGS scores were all significantly (p < 0.05) greater among Symptomatic Group versus Asymptomatic Group patients. Among Asymptomatic Group patients, thermographic temperatures were all significantly higher (P < 0.01) in wrists having joint recess(es) with ultrasound PD ≥ 1 or GS ≥ 2, while all thermographic parameters correlated significantly with TPD (correlation coefficient ranging from 0.43 to 0.48, p < 0.001) and TGS (correlation coefficient ranging from 0.33 to 0.37, p < 0.01). The ICC values based on a subset of images obtained for inter-reliability testing were high for thermography (0.994 to 0.998) and ultrasonography (0.933 to 0.952).

Conclusions

Swollen and/or tender RA wrists displayed greater thermographic and ultrasound-detected joint inflammation. At clinically quiescent (non-swollen; non-tender) wrists, thermographic temperatures significantly correlated with ultrasound-detected joint inflammation.

Clinical trial number

Not applicable.
Prevalence of insomnia among university students in Saudi Arabia: a systematic review and meta‑analysis
Authors: Baklola Mohamed , Terra Mohamed , Al-barqi Mohamed , AbdulHusain Yaqeen Hasan , Asiri Sohaila Ahmed , Jadaan Norah Saad , Haroona Ali , Almosawi Sayed , Al Ahmari Sarah Saud
Published: November 2024

Background

Insomnia is a prevalent sleep disorder affecting cognitive functions critical to academic performance. University students, particularly in high-stress academic settings, are highly vulnerable. Despite its significant impact on students' health and education, there is limited research on the prevalence of insomnia among university students in Saudi Arabia. This systematic review and meta-analysis aim to assess the prevalence of insomnia among university students in Saudi Arabia, focusing on demographic variations and academic settings, to provide evidence for targeted interventions.

Methods

A comprehensive literature search was conducted across databases including PubMed, Scopus, and Web of Science, with additional manual searches. Inclusion criteria were cross-sectional studies addressing insomnia prevalence among Saudi university students, using standard diagnostic criteria. A total of 11 studies met the inclusion criteria, comprising data from diverse faculties, including medical and non-medical disciplines. Quality assessment was conducted using the Newcastle-Ottawa Scale. Statistical analyses were performed using a random-effects model to account for heterogeneity.

Results

Eleven studies, involving a total of 8297 university students, were included in the analysis. Insomnia prevalence varied widely, ranging from 19.3% to 98.7%, with a pooled prevalence of 43.3% (95% CI 28.9–58.2%). Subgroup analyses showed a prevalence of 38.6% among medical students and 38.7% among female students. The analysis revealed high heterogeneity (I2 = 99.17%), indicating significant variability in study designs, populations, and diagnostic methods.

Conclusions

Insomnia is highly prevalent among university students in Saudi Arabia, with significant variations across demographics and academic contexts. The findings underscore the urgent need for targeted interventions, including stress management, improved sleep hygiene education, and support systems to mitigate the impact of insomnia on academic performance and overall health. Future research should explore the longitudinal impacts of insomnia and the efficacy of tailored interventions in this population.
Translocation of the Alphanucleorhabdovirus X proteins from the cytoplasm into the nucleus through interaction with nucleocapsid protein is essential for viral pathogenesis
Authors: Wang Shuo , Ni Shuang , Lou Huanhuan , Liang Yan , Li Zhenghe
Published: November 2024

The diverse rhabdoviruses infecting plants and animals have conserved genome organizations, and the functions of viral structural proteins have been extensively studied. However, increasing number of rhabdoviruses have been found to encode various accessory proteins, whose specific roles during viral infection remain poorly understood. In this study, we investigated the function of the X proteins encoded by several members of the genus Alphanucleorhabdovirus. Using the recently established eggplant mottled dwarf virus (EMDV) reverse genetics system, we found that recombinant EMDV lacking the X gene was able to systemically infect Nicotiana benthamiana plants, albeit with reduced efficiency. However, this deletion mutant was largely restricted to the veinal tissues and caused asymptomatic infections. The EMDV X protein, which localized to the cytoplasm when expressed alone, was translocated to the nucleus via a specific interaction with the nucleocapsid (N) protein. Through analyzing the interactions of the X deletion mutants and the infection phenotypes of the derived EMDV deletion mutants, we demonstrated that the carboxyl-terminal region of the X protein (amino acids 71–83) is crucial for its interaction with the N protein and for viral pathogenesis. Moreover, the X proteins encoded by related alphanucleorhabdoviruses could fully or partially complement the functions of EMDV X in viral infection. These findings provide new insights into the roles of accessory proteins in plant rhabdovirus infection.
Single-strain probiotics enhance growth, anti-pathogen immunity, and resistance to Nocardia seriolae in grey mullet (Mugil cephalus) via gut microbiota modulation
Authors: Chan Ching-Hung , Chen Li-Han , Chen Kuang-Yu , Chen I-Hung , Lee Kung-Ta , Lai Liang-Chuan , Tsai Mong-Hsun , Chuang Eric Y. , Lin Ming-Tse , Yan Tsong-Rong
Published: November 2024

Grey mullet (Mugil cephalus) aquaculture is economically vital due to the high value of its roe. However, it faces significant risks from disease outbreaks, particularly from Nocardia seriolae. Current reliance on antibiotics has drawbacks, highlighting the potential of probiotics as a promising alternative. Despite this, no studies have focused on the effects and mechanisms of probiotics in disease prevention and treatment in grey mullet. This study, therefore, investigates the efficacy of probiotics in enhancing disease resistance and promoting growth in grey mullet. Three strains of probiotics, Lacticaseibacillus rhamnosus FS3051, Limosilactobacillus reuteri FS3052, and Bacillus subtilis natto NTU-18, were selected to evaluate their anti-N. seriolae activity and hydrolytic enzyme secretion in vitro. Then, 144 grey mullet were randomly divided into four groups: control, L. rhamnosus FS3051, L. reuteri FS3052, and B. subtilis natto NTU-18. After being fed the corresponding diet for 28 days, fish were measured for immune gene expression and short-term growth followed by challenge of N. seriolae. Survival rates were recorded for 35 days post challenge. Additionally, the gut microbiota of the control and probiotic groups with effects on both growth and protection against N. seriolae were analyzed to investigate the potential role of gut microbiota. Results demonstrated that L. rhamnosus FS3051 and L. reuteri FS3052 inhibited N. seriolae, while B. subtilis natto NTU-18 did not inhibited N. seriolae. Probiotics also had the ability to secrete hydrolytic enzymes. Probiotic-fed grey mullet showed significant improvements in weight gain ratio, feed efficiency, and specific growth rate, particularly in the B. subtilis natto NTU-18 group. Immune gene expression was enhanced by probiotics, especially L. rhamnosus, FS3051, which induced IL-8, IL-1β, TNF-α, IFN-γ, and MHCI. Survival rates post-N. seriolae challenge improved significantly for L. rhamnosus FS3051-fed fish. L. rhamnosus FS3051 also altered the gut microbiota, enriching beneficial genera like Lactobacillus, which correlated positively with immune responses and growth, while reducing Mycoplasma and Rhodobacter, which were negatively correlated with immune responses. This study underscores the potential of probiotics in enhancing disease resistance and growth via regulating gut microbiota in grey mullet.
Therapeutic efficacy of amygdaline and amygdaline-loaded niosomes in a rat model of Alzheimer’s disease via oxidative stress, brain neurotransmitters, and apoptotic pathway
Authors: El-Banna Ahmed H. , Abo El-Ela Fatma I. , Abdel-Wahab Ahmed , Gamal Amr , Abdel-Razik Abdel-Razik H. , El-Banna Hossny A. , Elsamannoudy Salma.I. , Ibrahim Marwa A. , Abdelghany Asmaa K.
Published: November 2024

Background

Alzheimer’s disease (AD) is a specific form of neurodegeneration that is marked by impairments in memory and cognition. Exposure to some metal toxins, such as aluminum (AL), was directly linked to the onset of AD as it was hosted in the body via several exposure routes and can change the permeability and cross the blood–brain barrier. Due to amygdaline’s existence, apricot kernel therapy for AD is believed to have been established to be successful in numerous investigations. Amygdaline has been shown to have antioxidant effects that mitigate oxidative damage, and free radicals scavenger activity, as well as amygdaline niosomes as a nanoparticle has been found to improve the drug’s efficiency and selectivity. The objectives of this investigation are to study the neuroprotective role of amygdaline, and amygdaline-loaded niosomes formulation in the diminishment of the incidence of AD in neurotoxin (aluminum chloride; AlCl3) AD animal model.

Results

Data revealed that AlCl3 caused cognitive decline that was confirmed by cognitive behavioral tests (novel object and Y-maze); biochemical disturbances that include marked oxidative stress (elevated malondialdehyde and reduced total antioxidant capacity), reduced acetylcholinesterase, and brain monoamines levels (nor adrenalin; 4-dihydroxyphenylacetic acid; 5-hydroxytryptamine /serotonin; dopamine), and gene regulation upset (down-regulated transcript levels of acetylcholinesterase; monoamine oxidase; BCL-2 and up-regulated transcript levels of BAX), as well as neurodegenerative changes were observed in the hippocampus of AlCl3-treated rats. Treatment with amygdaline and amygdaline-loaded niosomes formulation improved working memory and recognition, alleviated oxidative stress, and restored the levels of brain monoamines and neurotransmitters. Moreover, gene expression data showed a significant down-regulation of BAX, while BCL-2, acetylcholinesterase, and monoamine oxidase were significantly up-regulated. Additionally, the histopathological examination showed reduced neurodegeneration.

Conclusion

Conclusively, it was evident that amygdaline and amygdaline-loaded niosomes formulation possess a neuroprotective and cognitive enhancement role in AD via their potent antioxidant potential, neurotransmitters, and gene expression regulations, as well as neural damage reduction capability.

Graphical abstract
Lignin-chitosan-based biocomposite film for the localized delivery of TLR7 agonist imiquimod
Authors: Jassal Aashna , Pathania Khushboo , Kumar Pankaj , Kaushik Deepender , Dhingra Simran , Salunke Deepak B. , Pawar Sandip V.
Published: November 2024

Background

As the leading form of non-melanoma skin cancer, basal cell carcinoma (BCC) presents a considerable challenge to healthcare systems, owing to its widespread occurrence. Current treatment options, such as surgical excision, cryotherapy, and localized therapies like imiquimod or 5-fluorouracil, face challenges, especially in designing drug delivery systems that provide prolonged therapeutic effects. This study aims to develop bio-composite polymeric films for localized drug delivery using natural polymers, lignin, and chitosan, to enhance the delivery of the TLR7 agonist imiquimod for BCC treatment.

Results

The optimized biofilms were prepared by adjusting the polymer ratio and drying techniques to achieve a balanced composition for localized imiquimod delivery. FTIR and DSC characterization confirmed successful drug incorporation into the biofilms, while microscopic studies revealed the biofilms homogeneity and fibrous nature. Drug release studies demonstrated pH-dependent kinetics, with higher release rates at neutral pH. The biofilms exhibited slow and sustained drug release, promising prolonged therapeutic effects. Additionally, the biofilms were non-hemolytic, showed significant antioxidant activity, and demonstrated selective cytotoxicity against B16–F10 mouse skin melanoma cells.

Conclusions

This study suggests that lignin-chitosan-based imiquimod-loaded biofilms hold potential as an effective topical treatment for BCC. The biofilm’s ability to provide sustained drug release, along with their biocompatibility and selective cytotoxicity, indicates a promising approach to enhancing BCC therapy.

Graphical abstract
Complementary interventions for cognitive rehabilitation in patients with cerebral palsy: a single-center study
Authors: Rafique Ammara
Published: November 2024

Background

Cerebral palsy (CP) is a neuromotor disorder that impairs a person’s ability to balance, stand, maintain posture, and walk. Research has indicated that Al Fatiha and negative air ion (NAI) are beneficial for ameliorating several behavioral, spiritual, physical, and societal issues. The objective of the present study was to assess the effect of Al Fatiha and NAI interventions on cognitive skills using Lumosity software.

Methods

This randomized control trial was conducted et al.-Umeed Rehabilitation Association, Karachi, Pakistan, between February and April 2021, following ethical approval (Ref: IBC-2017) from the University of Karachi. CP patients who volunteered for the study were randomly assigned to either the control group or to groups receiving interventions involving Al Fatiha and NAI exposure. Due to the limited number of consents obtained, participants were selected without consideration of age, cognition level, gender, mobility, motor type, and additional impairments. While all groups continued their regular therapies, the intervention groups underwent 31 structured sessions over a period of 6 weeks. Five Lumosity games were selected to assess the cognitive performance of all inducted participants in the three groups. Statistical analysis including paired t-tests, one-way analysis of variance (ANOVA), and post hoc tests was conducted using SPSS version 28 to compare outcomes among the three groups.

Results

Paired t-tests showed that the Al Fatiha intervention significantly enhanced selective attention (1133.3 ± 584.8, p < .05) and working memory (31,036.2 ± 4013.9, p < .001), while the NAI intervention resulted in improvements in information processing (31,036.2 ± 4013.9, p < .01), selective attention (1150.0 ± 705.3, p < .01), spatial fluency (6830.7 ± 4720.0, p < .01), and spatial reasoning (8719.3 ± 3499.5, p < .01). Apart from intervention groups, only spatial reasoning was improved in the control group (9068.3 ± 3450.1, p < 0.05). One-way ANOVA and Tukey’s post hoc analysis showed significant differences among the control and intervention groups at baseline in information processing, selective attention, and spatial fluency. These cognitive functions are likely attributable to increased neuronal activity in the prefrontal cortex and elevated serotonin levels.

Conclusion

Based on the findings, both interventions are proposed as advanced, complementary, non-pharmacological, and cost-effective cognitive rehabilitation therapies for patients with CP. We recommend further research to validate these findings through second and third-phase clinical trials.
Validation of FECPAKG2 equipment and prevalence of equine gastrointestinal parasites in Polo horses in Plateau State, Nigeria
Authors: Golshang J. G , Nanvyat N , Edeh E. R , Patrobas M. N , Oshadu D. O , Dishion C. H , Dzikwi-Emennaa A. A , Otakpa E. O , Imandeh G. N , Lombin L. H
Published: November 2024

Gastrointestinal (GI) parasites are a global concern and cause serious damage to the health of animals, including horses, because of their deleterious effects on the health of these animals. Owing to improperly diagnosing the parasitic load and the resulting incorrect treatment, anthelmintics are becoming a global problem. Although rapid diagnostic techniques such as McMaster and FECPAKG2 are available in Africa, concentration techniques, including flotation and sedimentation, are commonly used in screening for gastrointestinal parasites. In this study, we compared the sensitivity of diagnostic techniques, namely, McMaster and FECPAKG2, in quantifying and determining the prevalence of gastrointestinal parasites as an alternative to the commonly used flotation and sedimentation techniques for equine fecal samples in Jos, Plateau State, Nigeria. Three hundred fecal samples were collected from different locations. The instructions provided by the manufacturers of FECPAKG2 and McMasters were used as the methodology for egg count per gram of fecal matter, while parasite egg/ova identification was performed through sedimentation and flotation techniques. In general, a prevalence of 66.3% was recorded, with a higher prevalence on Babale ranch (84%) than on Jos Polo Club (62%) and Jos mounted troop (53%). A total of nine gastrointestinal parasites were identified via both sedimentation and flotation techniques: Strongylus spp. (19.3%) was the most prevalent parasite identified via the flotation method, whereas Gastrodiscus aegyptiacus (25.3%) was the most prevalent parasite identified via the sedimentation technique. In general, FECPAKG2 had a sensitivity of 86%, whereas McMaster had a sensitivity of 64% in terms of egg counts per gram of fecal sample. This finding suggests that equines in Jos are highly infected with a variety of gastrointestinal parasites to varying degrees, with Strongylus spp. and Gastrodiscus aegyptiacus being more prevalent. Although the parasite load was found to range from low to moderate levels, the majority of the equine samples contained < 200 eggs per gram, suggesting a low infection rate via both the McMaster technique and the FECPAKG2 technique. On the basis of these findings, FECPAKG2 is recommended for rapid diagnosis because of its prompt outcome and infestation rate as well as ease of routine examination. Additionally, routine examination should be carried out to determine infestation by gastrointestinal parasites in all equine holdings and the effectiveness of the therapeutic agents used.
Global longitudinal strain manually measured from mid-myocardial lengths is a reliable alternative to speckle tracking global longitudinal strain
Authors: Yeong Chee Cheen , Harrop Danielle L. , Ng Arnold C. T. , Wang William Y. S.
Published: November 2024

Background

Global longitudinal strain (GLS) is a useful marker for the echocardiographic evaluation of left ventricular (LV) systolic dysfunction. Presently GLS is derived from speckle tracking of LV images, but speckle tracking software is not always available. We seek to determine if manually measured GLS (MM-GLS) by assessing mid-myocardial lengths can be a reliable alternative to speckle tracking GLS (ST-GLS).

Methods

Transthoracic echocardiogram images of a tertiary hospital in Australia were retrospectively analyzed to study the relationships between ST-GLS, MM-GLS, and LV ejection fraction (LVEF). We further evaluated the impact of image quality and regional wall motion abnormalities on those relationships.

Results

Echocardiography studies from 154 patients were included (female sex, 36%; mean age, 61.7 ± 14.8 years). The average LVEF was 51.3% ± 11.3% and the average ST-GLS was 16.7 ± 3.8. MM-GLS strongly correlated with ST-GLS (intraclass correlation coefficient, 0.986; P < 0.001) and with LVEF regardless of the presence of regional wall motion abnormalities. If using GLS cutoff of more than 18% as normal, 97.5% of studies with normal ST-GLS had normal MM-GLS. If using GLS cutoff as less than 16% as abnormal, 95.5% of studies with abnormal ST-GLS had abnormal MM-GLS. There was no case with ST-GLS > 18% and MM-GLS < 16%, nor were there any case in with ST-GLS < 16% and MM-GLS > 18%.

Conclusions

MM-GLS correlates strongly with ST-GLS. If ST-GLS cannot be accurately assessed, MM-GLS may be a useful alternative to provide GLS values in both clinical and research studies.
Classifying Tumor Reportability Status From Unstructured Electronic Pathology Reports Using Language Models in a Population-Based Cancer Registry Setting
Authors: Gondara Lovedeep , Simkin Jonathan , Arbour Gregory , Devji Shebnum , Ng Raymond
Published: November 2024

PURPOSE

Population-based cancer registries (PBCRs) collect data on all new cancer diagnoses in a defined population. Data are sourced from pathology reports, and the PBCRs rely on manual and rule-based solutions. This study presents a state-of-the-art natural language processing (NLP) pipeline, built by fine-tuning pretrained language models (LMs). The pipeline is deployed at the British Columbia Cancer Registry (BCCR) to detect reportable tumors from a population-based feed of electronic pathology.

METHODS

We fine-tune two publicly available LMs, GatorTron and BlueBERT, which are pretrained on clinical text. Fine-tuning is done using BCCR's pathology reports. For the final decision making, we combine both models' output using an OR approach. The fine-tuning data set consisted of 40,000 reports from the diagnosis year of 2021, and the test data sets consisted of 10,000 reports from the diagnosis year 2021, 20,000 reports from diagnosis year 2022, and 400 reports from diagnosis year 2023.

RESULTS

The retrospective evaluation of our proposed approach showed boosted reportable accuracy, maintaining the true reportable threshold of 98%.

CONCLUSION

Disadvantages of rule-based NLP in cancer surveillance include manual effort in rule design and sensitivity to language change. Deep learning approaches demonstrate superior performance in classification. PBCRs distinguish reportability status of incoming electronic cancer pathology reports. Deep learning methods provide significant advantages over rule-based NLP.
Longitudinal Results From the Nationwide Just ASK Initiative to Promote Routine Smoking Assessment in American College of Surgeons–Accredited Cancer Programs
Authors: Burris Jessica L. , Ostroff Jamie S. , Reilly Eileen M. , Warren Graham W. , Shelton Rachel C. , Mullett Timothy W. ,   on behalf of the Just ASK Quality Improvement Task Force, Adsit Rob , Allison Lisa , Boffa Daniel , Burris Jessica , Carter Asa , Darville Audrey , Fiore Michael , Hahn Ellen , Harris James , Kirstein Laurie , McCarthy Danielle , Mullett Timothy , Nelson Heidi , Ostroff Jamie , Reilly Eileen , Reuter Erin , Shafir Sarah , Shelton Rachel , Tong Elisa , Warren Graham
Published: November 2024

PURPOSE

Persistent smoking after cancer diagnosis causes adverse outcomes while smoking cessation can improve survival. Thus, integration of smoking assessment and cessation assistance into routine cancer care is critical. Aiming for incremental practice change that could be sustained and built upon through future quality improvement (QI) projects, the American College of Surgeons initiated Just ASK in 2022 to increase implementation of smoking assessment among its accredited Cancer Programs. This manuscript describes outcomes from Just ASK.

METHODS

Seven hundred sixty-two programs enrolled in this cohort study, followed Plan Do Study Act methodology, and used local QI teams to facilitate practice change. The primary outcome was the ask rate (ie, patients asked/patients seen). Programs completed three surveys across the 1-year study (89.8% retention), answering questions about their program plus organizational readiness, implementation barriers, implementation strategies, and clinical practices related to assessing smoking among patients newly diagnosed with cancer. Data analysis involved descriptive statistics and analysis of change over time (eg, McNemar chi-squares).

RESULTS

Programs (53.1% community-based) tended to report moderate organizational readiness, multiple implementation barriers, and adoption of 4.63 ± 1.49 of eight possible implementation strategies (eg, training staff/providers). Programs reported frequency of assessing smoking status, documenting it in the electronic health record, advising patients who smoke to quit, and documenting advice and treatment increased over time (all
P
< .001). The ask rate increased from baseline to mid to final survey (
P
< .01; 87.79%
v
88.65%
v
91.92%, respectively).

CONCLUSION

Just ASK is the latest, and by far the largest, endeavor to improve assessment of cancer patients' smoking status. Participants reported significant advances within a short time span and study results underscore the potential for national accreditation organizations to transform oncology practice.
Femoral Artery Infusion of αMSH Increases Muscle Thermogenesis and Promotes Glucose Uptake in Ovariectomized Ewes
Authors: Henry Belinda A , Cowley Michael A , Andrews Zane B , Clarke Iain J
Published: November 2024

The melanocortin system is fundamental to neural control of energy balance and long-term weight regulation. Recent evidence shows that melanocortins also act at peripheral tissues to regulate metabolism, independent of the brain or the sympathetic nervous system (SNS). One such target is skeletal muscle, which contributes to energy expenditure through changes in adaptive thermogenesis. We aimed to determine 1) whether direct femoral infusion of α-melanocyte–stimulating hormone (αMSH) could increase muscle heat production independent of SNS activation and 2) if αMSH-induced skeletal muscle heat production was associated with altered mitochondrial function. Dataloggers were implanted into one hind leg of ovariectomized ewes and set to record vastus lateralis temperature every 15 minutes. A cannula was inserted into one femoral artery for infusion of either αMSH (0.1 µg/h) or saline. Femoral infusion of αMSH increased (P < .0001) skeletal muscle heat production, without effect on food intake. State 4 respiration increased (P < .05) and the respiratory control ratio decreased (P < .05) in mitochondria isolated from αMSH-treated animals. In addition, femoral infusion of αMSH reduced plasma glucose concentration in the femoral, but not the jugular vein; there was no effect of αMSH treatment on nonesterified fatty acid concentrations. These data suggest that αMSH can act locally to increase glucose uptake. We further show that blockade of the α- and β-adrenergic limbs of the SNS with either phentolamine or propranolol infusion had no effect on αMSH-induced skeletal muscle heat production. Overall, we show that αMSH acts directly at skeletal muscle to promote glucose uptake and increase energy expenditure via mitochondrial thermogenesis.