bluuebunny/crossref_metadata_2025 huggingface dataset:
How drug repurposing can advance drug discovery: challenges and opportunities
Authors: Pinzi Luca , Bisi Nicolò , Rastelli Giulio
Published: August 2024

Traditional de novo drug discovery, which typically presents an 11% approval rate from phase I trials and even higher failure rates in fields like neurodegeneration, often requires two to three billion dollars and 10–17 years per new drug. In contrast, drug repurposing can reduce risks and bring drugs to the market in 3–12 years, with an average of $300 million investment. In this article, we will outline how drug repurposing can accelerate the discovery of drugs derived from natural and synthetic products. The vast amount of chemical, biological, structural, and clinical data available in public repositories will greatly facilitate drug discovery, without the need to start a discovery campaign from scratch. In the big data era, data mining and artificial intelligence will play major roles in both drug repurposing and drug discovery. This article will provide valuable insights into how drug repurposing can support drug discovery and vice versa, emphasizing its impact in addressing unmet medical needs, achieving cost-effectiveness, and enabling faster market access. Despite legal and regulatory challenges, the cost-effectiveness, and the potential to give new life to compounds already in the pipeline make drug repurposing a crucial complement to traditional drug discovery in the era of precision medicine.
Optimizing evaluation of endometrial receptivity in recurrent pregnancy loss: a preliminary investigation integrating radiomics from multimodal ultrasound via machine learning
Authors: Yan Shanling , Xiong Fei , Xin Yanfen , Zhou Zhuyu , Liu Wanqing
Published: August 2024

Background

Recurrent pregnancy loss (RPL) frequently links to a prolonged endometrial receptivity (ER) window, leading to the implantation of non-viable embryos. Existing ER assessment methods face challenges in reliability and invasiveness. Radiomics in medical imaging offers a non-invasive solution for ER analysis, but complex, non-linear radiomic-ER relationships in RPL require advanced analysis. Machine learning (ML) provides precision for interpreting these datasets, although research in integrating radiomics with ML for ER evaluation in RPL is limited.

Objective

To develop and validate an ML model that employs radiomic features derived from multimodal transvaginal ultrasound images, focusing on improving ER evaluation in RPL.

Methods

This retrospective, controlled study analyzed data from 346 unexplained RPL patients and 369 controls. The participants were divided into training and testing cohorts for model development and accuracy validation, respectively. Radiomic features derived from grayscale (GS) and shear wave elastography (SWE) images, obtained during the window of implantation, underwent a comprehensive five-step selection process. Five ML classifiers, each trained on either radiomic, clinical, or combined datasets, were trained for RPL risk stratification. The model demonstrating the highest performance in identifying RPL patients was selected for further validation using the testing cohort. The interpretability of this optimal model was augmented by applying Shapley additive explanations (SHAP) analysis.

Results

Analysis of the training cohort (242 RPL, 258 controls) identified nine key radiomic features associated with RPL risk. The extreme gradient boosting (XGBoost) model, combining radiomic and clinical data, demonstrated superior discriminatory ability. This was evidenced by its area under the curve (AUC) score of 0.871, outperforming other ML classifiers. Validation in the testing cohort of 215 subjects (104 RPL, 111 controls) confirmed its accuracy (AUC: 0.844) and consistency. SHAP analysis identified four endometrial SWE features and two GS features, along with clinical variables like age, SAPI, and VI, as key determinants in RPL risk stratification.

Conclusion

Integrating ML with radiomics from multimodal endometrial ultrasound during the WOI effectively identifies RPL patients. The XGBoost model, merging radiomic and clinical data, offers a non-invasive, accurate method for RPL management, significantly enhancing diagnosis and treatment.
Forest structural heterogeneity positively affects bird richness and acoustic diversity in a temperate, central European forest
Authors: Shaw Taylor , Scherer-Lorenzen Michael , Müller Sandra
Published: August 2024

Introduction

Forests managed for timber production can also be managed for biodiversity conservation by retaining structures typical of old-growth forests, which provide heterogenous structures for forest-dwelling species, including birds. Ecoacoustic monitoring of forest birds is now a well-studied field, however the extent to which acoustic indices can reflect bird assemblage responses to stands of lower or higher structural heterogeneity is disputed.

Method

In this study, we acoustically surveyed 75 plots over two years in mature, previously managed forests and computed acoustic indices from the recordings. We first identified an acoustic index that significantly correlated with bird richness over more than one spring season. Next, we tested the response of bird richness to individual forest structural elements using linear regressions. We then repeated this analysis but combined the individual structural elements into one structural composition variable using an NMDS and gam smooth overlay, to compare the effect of individual forest structures versus overall forest heterogeneity on bird richness. We then repeated this analysis using our selected acoustic index, the Normalized Difference Soundscape Index (NDSI), to see if it followed the same patterns as bird richness in response to individual and collective forest structural elements.

Results

Our results showed that plots with high bird richness were also associated with high NDSI values, and high values of both variables occurred in plots with high structural heterogeneity (tree species richness, tree size variability, and snag height variability) and low amounts of standing and lying deadwood.

Discussion

Our findings suggest that once an acoustic index can be identified as a robust correlate of bird richness, it can serve as a proxy for the response of birds to differences in forest structural heterogeneity within a managed forest context. It is therefore possible for forest managers interested in conserving or increasing bird richness in their production forests to identify a robust acoustic index to track the response of bird richness to management decisions over time.
Aspergillus fumigatus antigen-reactive Th17 cells are enriched in bronchoalveolar lavage fluid in severe equine asthma
Authors: Wjst Valentin F. , Lübke Sabrina , Wagner Bettina , Rhyner Claudio , Jentsch Maria-Christin , Arnold Corinna , Lohmann Katharina L. , Schnabel Christiane L.
Published: August 2024

Introduction

Equine asthma (EA) is a common disease of adult horses with chronic respiratory pathology and common neutrophilic airway inflammation. It presents with hyperreactivity to hay dust components such as molds, and underlying dysregulated T cell responses have been suggested. Thus far, T cells have been analysed in EA with conflicting results and the antigen reactivity of T cells has not been demonstrated. Serological and epidemiological data point to the relevance of Aspergillus fumigatus as an antigen source in EA. Here, we aimed to identify and characterise Aspergillus antigen-reactive T cells in EA.

Methods

Cryopreserved bronchoalveolar lavage cells (BALC) and peripheral blood mononuclear cells (PBMC) from healthy horses (HE, n=9) and those with mild-moderate (MEA, n=3) or severe asthma (SEA, n=8) were stimulated in vitro with the recombinant A. fumigatus antigens Asp f 1, or Asp f 7 combined with Asp f 8, to assess antigen reactivity, and with phorbol-12-myristat-13-acetate and ionomycin (P/i) to assess overall T cell reactivity. Stimulated cells were analysed by flow cytometry for CD4, CD8, IL-17, IL-4, and IFN-γ. Cytokine expression in all lymphocytes, and in CD4+ or CD8+ T cells, was quantified and compared between the groups. In BAL fluid (BALF), soluble cytokines and chemokines were quantified by bead-based assays.

Results

Antigen restimulation of BALC with Asp f 1 or Asp f 7/8 provoked higher frequencies of IL-17+ lymphocytes, CD4+IL-17+ Th17 cells, and CD4+IL-4+ Th2 cells in SEA than in HE, whereas MEA and HE were similar. Antigen stimulation of PBMC did not result in group differences. P/i stimulation of BALC resulted in increased IL-17+ lymphocyte and CD4+IL-17+ Th17 cell frequencies in MEA compared with HE but the limited number of horses with MEA must be considered. P/i-stimulated PBMC from MEA or SEA contained more IL-17+ lymphocytes compared with HE. Cytokines were hardly detected in BALF and similar between the groups but CCL2 and CCL5 concentrations were increased in BALF from SEA or MEA, respectively, compared with HE.

Conclusion

Horses with SEA have increased Aspergillus antigen-reactive Th17 cells in their airways, emphasising local T cell responses to this mold, which were quantified in EA for the first time here.
Lymphocyte subsets for predicting inflammatory bowel disease progression and treatment response: a systematic review
Authors: Chen Rirong , Li Chao , Zheng Jieqi , Fan Zinan , Li Li , Chen Minhu , Chen Baili , Zhang Shenghong
Published: August 2024

Background

Lymphocytes play a key role in the pathogenesis of inflammatory bowel disease (IBD) and are widely explored as promising prognostic indicators. We aimed to outline the existing evidences on the capability of lymphocyte subpopulations to predict disease progression and treatment response in patients with IBD.

Methods

The protocol for this review was registered in PROSPERO (registration ID: CRD 42022364126). Systematic retrieval was conducted using PubMed, Embase, and Web of Science databases. Original articles on the prognostic value of lymphocyte subsets in IBD published up to April 8, 2023 were eligible for inclusion. The Newcastle–Ottawa Scale was used to evaluate the risk of bias.

Results

Twenty studies were ultimately included: eight evaluated the prediction of disease progression and 12 focused on the prediction of treatment response. According to the Newcastle–Ottawa Scale, three studies were of high quality, 16 were of moderate quality, and only one was of low quality. T-cell subpopulations, including CD4+ T cells, CD8+ T cells, and γδ T cells, are revealed to have prognostic capacity. Transmembrane tumor necrosis factor α-bearing lymphocytes, CD4+ T cells, CD8+ T cells, and Plasma cells are found to have the potential to predict the response to anti-TNFα agents. In contrast memory T cells, CD4+ T cells, and naïve B cells may predict the response to vedolizumab.

Conclusions

This systematic review identified several potential lymphocyte subset-related predictors. If verified in large cohort prospective studies, these findings could aid clinical decision-making.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022364126.
Single-cell RNA sequencing in endometrial cancer: exploring the epithelial cells and the microenvironment landscape
Authors: González-Martínez Silvia , Pérez-Mies Belén , Cortés Javier , Palacios José
Published: August 2024

Single-cell RNA sequencing (scRNA-seq) technology has emerged as a powerful tool for dissecting cellular heterogeneity and understanding the intricate biology of diseases, including cancer. Endometrial cancer (EC) stands out as the most prevalent gynecological malignancy in Europe and the second most diagnosed worldwide, yet its cellular complexity remains poorly understood. In this review, we explore the contributions of scRNA-seq studies to shed light on the tumor cells and cellular landscape of EC. We discuss the diverse tumoral and microenvironmental populations identified through scRNA-seq, highlighting the implications for understanding disease progression. Furthermore, we address potential limitations inherent in scRNA-seq studies, such as technical biases and sample size constraints, emphasizing the need for larger-scale research encompassing a broader spectrum of EC histological subtypes. Notably, a significant proportion of scRNA-seq analyses have focused on primary endometrioid carcinoma tumors, underscoring the need to incorporate additional histological and aggressive types to comprehensively capture the heterogeneity of EC. By critically evaluating the current state of scRNA-seq research in EC, this review underscores the importance of advancing towards more comprehensive studies to accelerate our understanding of this complex disease.
East meets west: integrating Yin-Yang theory with immunology teaching
Authors: Wang Zhiyong , Wang Min , Lin Mao , Lu Yanxin , Xia Qiang , Wei Pei
Published: August 2024

This perspective article delves into a novel integration of Yin-Yang theory—an ancient Chinese philosophical cornerstone—with the sophisticated realm of immunology. Given the intricate concepts inherent in immunology, many students find it challenging to comprehend the delicate mechanisms governing immune equilibrium and regulation. Given the deep-rooted understanding of Yin-Yang theory among Chinese students, we advocate for an educational strategy that contextualizes the concept of immune equilibrium within the framework of Yin-Yang, thereby offering a more intuitive and engaging learning experience. This method not only capitalizes on the cultural significance of Yin-Yang, but also corresponds to its principles of equilibrium and harmony, thus mirroring the homeostatic essence of immune responses. This article critically assesses this technique’s capacity to bolster immune comprehension amongst Chinese students, while also considering its limitations. Despite these limitations, the fusion of these seemingly divergent fields holds substantial promise for augmenting immunology education, promoting critical thinking, and advancing cross-cultural academic discourse. The amalgamation of age-old philosophical insights with modern scientific exploration prompts a reassessment of educational methodologies within immunology, underscoring a novel pedagogical approach that bridges traditional wisdom with contemporary scientific education.
Regulation of Bacteroides acidifaciens by the aryl hydrocarbon receptor in IL-22-producing immune cells has sex-dependent consequential impact on colitis
Authors: Mitchell Chandani , Staley Shanieka , Williams Michal Claire , Saxena Archana , Bogdon Raymond , Roark Kasie , Hailey Michele , Miranda Kathryn , Becker William , Dopkins Nicholas , Pena Maria Marjorette , Hogan Kristen M. , Baird Maredith , Wilson Kiesha , Nagarkatti Prakash , Nagarkatti Mitzi , Busbee Philip Brandon
Published: August 2024

Introduction

Colitis is an inflammatory bowel disease (IBD) characterized by immune cell dysregulation and alterations in the gut microbiome. In our previous report, we showed a natural product in cruciferous vegetables and ligand of the aryl hydrocarbon receptor (AhR), indole-3-carbinol (I3C), was able to reduce colitis-induced disease severity and microbial dysbiosis in an interleukin-22 (IL-22) dependent manner.

Methods

In the current study, we performed single-cell RNA sequencing (scRNAseq) from colonocytes during colitis induction and supplementation with I3C and show how this treatment alters expression of genes involved in IL-22 signaling. To further define the role of IL-22 signaling in I3C-mediated protection during colitis and disease-associated microbial dysbiosis, we generated mice with AhR deficiency in RAR-related orphan receptor c (Rorc)-expressing cells (AhRΔRorc) which depletes this receptor in immune cells involved in production of IL-22. Colitis was induced in wildtype (WT), AhRΔRorc, and littermate (LM) mice with or without I3C treatment.

Results

Results showed AhRΔRorc mice lost the efficacy effects of I3C treatment which correlated with a loss of ability to increase IL-22 by innate lymphoid type 3 (ILC3s), not T helper 22 (Th22) cells. 16S rRNA microbiome profiling studies showed AhRΔRorc mice were unable to regulate disease-associated increases in Bacteroides, which differed between males and females. Lastly, inoculation with a specific disease-associated Bacteroides species, Bacteroides acidifaciens (B. acidifaciens), was shown to exacerbate colitis in females, but not males.

Discussion

Collectively, this report highlights the cell and sex-specific role of AhR in regulating microbes that can impact colitis disease.
Assessing the prevalence of schistosomiasis and strongyloidiasis in a tuberculosis clinic: the TB-TROPIcare study
Authors: Genovese Camilla , Colaneri Marta , Pagano Simone , Schiuma Marco , Galli Lucia , Fama Federico , Antinori Spinello , Gori Andrea , Torre Alessandro
Published: August 2024

Introduction

In recent years, Europe has experienced a significant flux of migrants, often hailing from regions endemic for schistosomiasis and strongyloidiasis, diseases frequently overshadowed by tuberculosis (TB) in healthcare priorities. While TB remains a prevalent concern among this population, chronic schistosomiasis and strongyloidiasis are frequently neglected. Motivated by this observation, we aimed to investigate the prevalence of schistosomiasis and strongyloidiasis in patients attending our TB outpatient clinic.

Methods

We conducted a retrospective, observational study spanning from June 2020 to January 2024, focusing on patients attending the TB outpatient clinic of Luigi Sacco Hospital of Milan, Italy. Serology tests were performed in patients with a history suggestive of exposure to either Schistosoma spp. or Strongyloides stercoralis.

Results

Among the 228 patients included in the study, 84 (36.8%) individuals were born in Italy, one came from Spain, 80 (35.1%) from strongyloidiasis moderate or high endemic countries and 63 (27.6%) from areas endemic for schistosomiasis and strongyloidiasis. Of these patients, 160 (70.2%) were diagnosed with tuberculosis disease, while 68 (29.8%) had tuberculosis infection. The prevalence of schistosomiasis was 26.7%, while that of strongyloidiasis was 7.8%. Notably, 3 patients tested positive for both infections.

Conclusion

Our study highlights the often-underestimated prevalence of schistosomiasis and strongyloidiasis among migrants accessing healthcare for TB, underscoring the importance of increased awareness and targeted screening within this population.
Development and operation of a novel non-invasive opto-acoustic underwater fish observatory in Kiel Bight, Southwestern Baltic Sea
Authors: Gröger Joachim P. , Cisewski Boris , Badri-Hoeher Sabah , Böer Gordon , Boos Karin , Clemmesen Catriona , Cojocaru Ala , Dauben Verena , Hoeher Peter A. , Lehmann Andreas , Matz Sebastian , Mehrtens Hela , Mittermayer Felix , Renkewitz Helge , Schramm Hauke , Strickmann Tobias , Westphalen Jonni , Wilts Thomas , Winkler Julian , Wolf Dennis , Zenk Oliver
Published: August 2024

This study presents a trilateral test array of new opto-acoustic Underwater Fish Observatories (UFOs) that were operated and tested in Kiel Bight as part of the “UFOTriNet” project. While hydroacoustic and optical techniques have so far been used individually to observe and monitor fish stocks, we present a coupled hybrid system consisting of an optical device intended to scan the near-field as a subsample of a spatially larger medium-to-far-field, scanned by an acoustical device. The optical device consists of two residual light amplifying camera modules able to detect and classify various marine species at a high resolution in the range of at max 4 meters in the study area. To compensate for this spatial limitation, the acoustical component consists of a 2D imaging sonar with a maximum range of 50 m, albeit with a lower resolution. Species affiliation, morphometric characteristics of fish and other marine organisms were stereo-optically detected and classified in the nearfield, blended with acoustical activity in medium to far range, and projected onto the entire insonified area using a hybrid algorithm. Through the synchronous acquisition of multiparametric abiotic and biotic data, UFO allows an automatic, continuous, and non-invasive long-term monitoring of various fish and other marine species and their habitats at regional hotspots. An 86-day multiparametric sample revealing an abrupt shift from a clupeid fish to a gelatinous plankton dominated regime in summer/autumn 2021 in Kiel Fjord is used to demonstrate the potential of UFO for various applications.
Cultivating resilience in wheat: mitigating arsenic toxicity with seaweed extract and Azospirillum brasilense
Authors: Zaheer Muhammad Saqlain , Aijaz Nazish , Hameed Akhtar , Buttar Noman Ali , Rehman Shamsur , Riaz Muhammad Waheed , Ahmad Ajaz , Manzoor Muhammad Aamir , Asaduzzaman Muhammad
Published: August 2024

Arsenic (As) toxicity is a serious hazard to agricultural land due to growing industrialization, which has a negative effect on wheat crop yields. To address this issue, using seaweed extract and Azospirillum brasilense has emerged as an effective strategy for improving yield under stress conditions. However, the combined application of A. brasilense and seaweed extract in wheat crops under As toxicity has not been fully explored. The effectiveness of combining A. brasilense and seaweed extract in reducing As toxicity in wheat production was examined in this study through a 2-year pot experiment with nine treatments. These treatments included a control with no additives and two As concentrations (50 and 70 μM). At 50 and 70 μM, As was tested alone, with seaweed extract, with A. brasilense, and both. Significant results were achieved in reducing As toxicity in wheat crops. Arsenic at 70 μM proved more harmful than at 50 μM. The application of A. brasilense and seaweed extract was more effective in improving crop growth rates, chlorophyll levels, and stomatal conductance. The combined application notably decreased As concentration in wheat plants. It was concluded that applying A. brasilense and seaweed extract not only improves wheat growth but can also improve soil parameters under As toxicity conditions by increasing organic matter contents, boosting nutrient availability, and increasing the production of antioxidant enzymes.
Sex and age-related patterns in pediatric primary headaches: observations from an outpatient headache clinic
Authors: Faria Vanda , Höfer Berit , Klimova Anna , von der Hagen Maja , Berner Reinhard , Sabatowski Rainer , Koch Thea , Hübler Anke , Richter Matthias , Moulton Eric A. , Holmes Scott A. , Gossrau Gudrun
Published: August 2024

Background

Age reportedly affects headache prevalence differently in boys and girls. However, little empirical data exists regarding pediatric headache prevalence and headache-related burden in children and adolescents according to age and sex. In the present study, we considered age and sex while evaluating the distribution, characteristics, and impairment of primary headache disorders at a pediatric headache center in Germany.

Methods

Medical records of children and adolescents attending the headache clinic of the Interdisciplinary Pain Center of the Carl Gustav Carus University Hospital in Dresden during the period 2015–2022 were retrospectively grouped and analyzed depending on age (< or ≥14 years) and sex.

Results

The study population consisted of 652 children and adolescents, aged between 3 and 18 years. Almost two-thirds of the patients (≈60%) were females, and almost two-thirds of these females (58%) were ≥14 years of age. Generally, the most prevalent headache diagnoses as defined by the International Classification of Headache Disorders 3rd edition were episodic migraine without aura and the combination of tension-type headache and episodic migraine with or without aura i.e., mixed-type headache (each ≈27%). In the younger group (<14 years), the mixed-type headache was the most prevalent in girls (28.6%), whereas, for boys, episodic migraine without aura was the most prevalent headache diagnosis (47.4%). In the older group (≥14 years), the mixed-type headache continued to be the most prevalent for girls (30%), and it became the most prevalent for boys (26.3%). Before the age of 14, about 16% of children were severely affected by their headaches. After the age of 14, this proportion increased to roughly one-third (33%) of adolescents, driven mainly by teenage girls (26%) who were severely affected by their headaches. Furthermore, the prevalence of comorbidities was significantly higher among girls (67%), particularly in the adolescent group (74%).

Conclusions

Our data shows that headache disorders in a specialized pediatric clinic impose a significant burden, especially among teenage girls indicating high therapy needs. Enhancing awareness of early diagnosis and preventive care is crucial to mitigate the development of chronic headaches, and mitigate their adverse effects on life quality and educational capability.
Characterization of flavor profile of Steamed beef with rice flour using gas chromatography-ion mobility spectrometry combined with intelligent sensory (Electronic nose and tongue)
Authors: Wang Tianyang , Yang Lian , Xiong Yiling , Wu Baozhu , Liu Yang , Qiao Mingfeng , Zhu Chenglin , Wu Huachang , Deng Jing , Guan Ju
Published: August 2024

The intelligent senses (Electronic nose and tongue), were combined with headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) and free amino acid were used in combination to determine the aroma and taste components during the processing of Chinese traditional dish Steamed beef with rice flour (SBD). The findings revealed that E-nose and E-tongue, could clearly distinguish and identify the aroma and taste of SBD. A total of 66 volatile substances and 19 free amino acids were identified by HS-GC-IMS and amino acid analyzer, respectively. The highest contribution to aroma in the production of SBD was alcohols, esters and aldehydes. Further analysis of relative odor activity showed that 3-Methylbutanol-D, 3-Methylbutanol-M and 3-Methylthio propanal is the marinating stage (T2) main aroma components. Ethyl 3-methylbutanoate-M and Ethyl 3-methylbutanoate-D were the main aroma components in the seasoning stage (T3). Additionally, the calculation of the taste activity value showed that Glutamic contributed significantly to the umami of SBD. Alanine was a representative taste component in the marinating stage (T2), while Proline, Aspartic, Lysine, Glutamic, Valine, Arginine, and Histidine were characteristic amino acids of the seasoning stage (T3). Consequently, this study offers valuable insights into the industrial-scale production and flavor regulation of SBD products.
Effect of 5:2 intermittent fasting diet versus daily calorie restriction eating on metabolic-associated fatty liver disease—a randomized controlled trial
Authors: Wang Yuan-yuan , Tian Fang , Qian Xiao-lu , Ying Hui-min , Zhou Zhen-feng
Published: August 2024

Objective

Both 5:2 IF diet (intermittent fasting) and daily caloric restriction eating had been suggested for management of MAFLD (Metabolic-Associated Fatty Liver Disease), this study aimed to evaluate the effects of 5:2 IF diet on body weight and metabolic parameters in adults with MAFLD, in comparison to daily caloric restriction eating.

Methods

This single-center, double-blind, prospective, randomized controlled trial included 60 patients with MAFLD, who were administered either a 5:2 IF diet limited calories consumed for 2 days each week with no restrictions on the remaining 5 (Group 5:2 IF diet) or a daily calorie restriction eating (Group daily calorie restriction). Fibrotouch-B instrument assessment, ultrasound assessment of hepatic steatosis, anthropometric indices and body composition analysis, blood sample measurements were conducted during two distinct visits: initially on the day of study commencement (T1), and subsequently at the conclusion of the 12-week intervention period (T2).

Results

In comparison to daily calorie restriction eating, the 5:2 IF diet significantly decreased the proportion of hepatic steatosis ≥moderate (29.6% vs. 59.3%, p = 0.028) and the degree of hepatic fibrosis F ≥ 2 (3.7% vs. 25.9%, p = 0.05), and fewer percentage of patients were diagnosed with fatty liver via upper abdominal ultrasound in the 5:2 intermittent fasting diet group (33.3% vs. 63.0%, p = 0.029). Additionally, the CAP (controlled attenuation parameter) and LSM (liver stiffness measurements) value were significantly lower in the 5:2 IF diet group (p < 0.05). No statistically significant differences were observed between the two groups in terms of weight, BMI (body mass index), WC (waist circumference), HC (hip circumference), and WHR (waist to hip ratio). Similarly, there were no significant differences in lipid profile, glycemic indices and adverse events (p > 0.05).

Conclusion

In summary, although both 5:2 IF diet and daily caloric restriction eating achieved similar effect on body weight, liver enzymes, lipid profile and glycemic indices after 12 weeks treatment, 5:2 IF diet demonstrates better improvement in fibrosis and steatosis scores independently from weight regulation. Consequently, it is anticipated to emerge as a viable dietary modality for lifestyle intervention among patients diagnosed with MAFLD.

Clinical trial registration

https://www.crd.york.ac.uk/PROSPERO, identifier ChiCTR2400080292.
Assessing skeletal muscle mass and lean body mass: an analysis of the agreement among dual X-ray absorptiometry, anthropometry, and bioelectrical impedance
Authors: Baglietto Nicolás , Vaquero-Cristóbal Raquel , Albaladejo-Saura Mario , Mecherques-Carini Malek , Esparza-Ros Francisco
Published: August 2024

Introduction

Methods of body composition estimation such as dual-energy X-ray absorptiometry (DXA), anthropometry, and bioimpedance (BIA) are used for the estimation of skeletal muscle mass (SMM) and lean body mass (LBM). No previous studies have examined whether these methods generate comparable results, or whether they are valid by using DXA as the reference. The aims of the present investigation were: (a) to assess the differences between DXA, anthropometry, and BIA in the estimation of SMM and LBM, taking into consideration the impact of sex and hydration status; and (b) to examine the agreement of anthropometry and BIA as compared to DXA for the estimation of SMM and LBM.

Methods

A descriptive cross-sectional design was followed with 262 healthy young adults (159 males and 103 females). LBM and SMM were assessed by anthropometry with the formulas from Lee et al. and Kulkarni et al. for LBM; and Kerr (opt a), Kerr (opt b), Lee et al., Poortmans, Matiegka, Martin et al., Drinkwater and Ross, and Heymsfield et al. for SMM; by BIA with the formula reported by the TANITA MC-780-MA software for LBM and SMM; and DXA with the formula reported by the Hologic Horizon software for LBM, and the conversion by Kim et al. for SMM.

Results

Significant differences were found for both SMM and LBM in kg, and percentages between most methods and formulas for the overall sample (p < 0.001–0.003) and divided by sex (p < 0.001–0.035). Hydration status did not have a significant effect on the differences between methods and formulas (p = 0.058–0.870). Lin’s coefficient revealed limited agreement among the majority of formulas and methods (CCC = 0.007–0.880). The Bland–Altman analysis showed significant differences in most methods and formulas, both in the overall sample and divided by sex, when using SMM and LBM with DXA as the reference (p < 0.001–0.030).

Conclusion

There is a lack of agreement between methods and formulas for assessing SMM and LBM. Sex was found to be a significant factor in this analysis. Furthermore, significant differences were observed between most formulas and methods as compared to DXA, except for the equations to estimate SMM with anthropometry by Poortmans.
Food choice, activity level, and carbon footprint: exploring potential for sustainable food consumption practices in young adults
Authors: Wollmar Mari , Post Anna , Sjöberg Agneta
Published: August 2024

This study aims to explore climate consciousness in relation to food consumption in young adults, examining its relationship with physical activity level and gender. A mixed-method approach is utilized, integrating seven-day food records and semi-structured interviews, employing social practice theory in our analytical framework. Our cohort of 47 participants (25 women, 22 men) displays varied diets, from omnivores to vegans. Moderately-active women show the lowest carbon footprint, favoring climate-conscious choices related to lower energy needs and plant-based preferences. Highly-active individuals consume more energy, resulting in a higher carbon footprint. Gender differences are evident, women were inclined to climate-conscious food practices motivated by animal ethics and health concerns. Conversely, men demonstrated a tendency for meat consumption. Participants share an understanding of carbon footprint, reflecting a solid awareness of food-related climate impact but differ in priorities; performance for highly-active, and economy for moderately-active. This highlights a mix of commonalities and distinctions, informing flexible, sustainable food practices. Higher activity levels are linked to greater energy needs and a higher carbon footprint. Moderately-active women show the most climate-conscious food choices, leading to the lowest carbon footprint. Our findings indicate that highly-active individuals and men have significant potential to improve climate-adapted food consumption.
Nomograms to predict lung metastasis in malignant primary osseous spinal neoplasms and cancer-specific survival in lung metastasis subgroup
Authors: Jiang Yong , Zhu Yapeng , Ding Yongli , Lu Xinchang
Published: August 2024

Purpose

To construct and validate nomograms for predicting lung metastasis probability in patients with malignant primary osseous spinal neoplasms (MPOSN) at initial diagnosis and predicting cancer-specific survival (CSS) in the lung metastasis subgroup.

Methods

A total of 1,298 patients with spinal primary osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma were retrospectively collected. Least absolute shrinkage and selection operator (LASSO) and multivariate logistic analysis were used to identify the predictors for lung metastasis. LASSO and multivariate Cox analysis were used to identify the prognostic factors for 3- and 5-year CSS in the lung metastasis subgroup. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCA) were used to estimate the accuracy and net benefits of nomograms.

Results

Histologic type, grade, lymph node involvement, tumor size, tumor extension, and other site metastasis were identified as predictors for lung metastasis. The area under the curve (AUC) for the training and validating cohorts were 0.825 and 0.827, respectively. Age, histologic type, surgery at primary site, and grade were identified as the prognostic factors for the CSS. The AUC for the 3- and 5-year CSS were 0.790 and 0.740, respectively. Calibration curves revealed good agreements, and the Hosmer and Lemeshow test identified the models to be well fitted. DCA curves demonstrated that nomograms were clinically useful.

Conclusion

The nomograms constructed and validated by us could provide clinicians with a rapid and user-friendly tool to predict lung metastasis probability in patients with MPOSN at initial diagnosis and make a personalized CSS evaluation for the lung metastasis subgroup.
Management of undifferentiated adrenal gland metastases from malignant melanoma: case report
Authors: Shortreed Hannah , Burute Nishigandha , Aseyev Olexiy
Published: August 2024

Adrenal gland metastases from malignant melanoma are a common but poorly characterised condition. Their lack of consistent clinical features and poor response to immune checkpoint inhibitors pose a significant diagnostic and therapeutic challenge to practitioners. This case report describes a 78-year-old male with no prior history of melanoma presenting with nonspecific abdominal symptoms and unintentional weight loss who was found to have undifferentiated bilateral adrenal gland metastases from malignant melanoma. Despite ongoing investigations, the primary site of the adrenal gland metastases remained unknown, prompting the consideration of primary adrenal melanoma as a diagnosis. The patient underwent four cycles of treatment with immune checkpoint inhibitors, nivolumab and ipilimumab, followed by maintenance therapy and subsequent adrenal metastasectomy. Despite therapeutic efforts, the patient’s tumour was resistant to treatment and became undifferentiated. The patient continued with palliative care until his death, more than three years after the onset of symptoms. The clinical features, pathophysiology, diagnosis, treatment, and prognosis of this patient’s disease are discussed in detail to help inform the management of similar cases.
Pathological PCI as a prognostic marker of survival after neoadjuvant chemotherapy in patients undergoing interval cytoreduction with or without HIPEC in FIGO stage IIIC high grade serous ovarian cancer
Authors: Sinukumar Snita , Damodaran Dileep , S. Deepika , Piplani Sanjay
Published: August 2024

Objective

To determine the best possible value of pathological PCI (pPCI) as a prognostic marker for survival in high-grade serous epithelial ovarian cancer patients in patients treated with neoadjuvant chemotherapy and interval cytoreductive surgery.

Methods

All patients with FIGO stage IIIC high-grade serous ovarian carcinoma were included. Receiver operating curves (ROC) were used to determine the best possible score for pPCI in predicting survival. Survival curves were calculated using the Kaplan–Meier test, and factors affecting survival were compared using the log-rank test.

Results

From January 2018 to January 2024, 171 patients who underwent interval cytoreductive surgery were included. Complete cytoreduction was achieved in 88% of the patients. ROC curves determined a (pPCI) cut-off value of 8 as the best possible score for predicting survival with a sensitivity of 82% and specificity of 67% (Youden’s Index = 0.60). pPCI with a cut-off value of 8 showed improved OS (p = 0.002) and DFS, (p = 0.001) in both univariate and multivariate analyses.

Conclusion

Following interval cytoreductive surgery, despite optimal complete cytoreductive surgery, a pathological PCI of 8 is a poor prognostic indicator of survival and may serve as a surrogate clinical marker for guiding clinicians in adjuvant treatment, especially in resource-driven settings in the real world.
Theophylline impact on weaning in oxygen-dependent infants followed in an outpatient Kangaroo Program
Authors: Montealegre-Pomar Adriana , Charpak Nathalie , Lince-Rivera Catalina
Published: August 2024

Background

Theophylline was an orally administered xanthine used for treatment of apnea of prematurity and Bronchopulmonary Dysplasia in ambulatory follow-up of Low-Birth-Weight infants (LBWI) with oxygen-dependency in the outpatient Kangaroo Mother Care Program (KMCP). Theophylline's main metabolic product is caffeine; therefore, it was an alternative due to the frequent lack of ambulatory oral caffeine in low and middle-income countries.

Objective

To assess the effectiveness of oral theophylline in decreasing days with oxygen and to describe frequency of adverse related events.

Methods

Quasi-experiment before and after withdrawal of theophylline given systematically to LBWI with ambulatory oxygen in two KMCPs.

Results

729 patients were recruited; period 1: 319 infants when theophylline was given routinely and period 2: 410 infants when theophylline was no longer used. The theophylline cohort had less gestational age, less weight at birth, more days in Neonatal Intensive Care Unit, more days of oxygen-dependency at KMCP admission, and more frequencies of Intrauterine Growth Restriction and apneas. After adjusting with propensity score matching, multiple linear regression showed that nutrition was associated with days of oxygen-dependency, but theophylline treatment not. No differences were found in frequencies of readmissions up to 40 weeks, intraventricular hemorrhage or neurodevelopmental problems. Participants in period 2 had more tachycardia episodes.

Conclusions

We did not find association between oral theophylline treatment and the reduction of days with ambulatory oxygen. For the current management of oxygen-dependency in LBW infants, the importance of nutrition based on exclusive breast feeding whenever possible, is the challenge.
Case Report: Focal cryoablation vs. radiofrequency ablation in a pediatric patient with para-Hisian accessory pathway with effect from the non-coronary aortic cusp
Authors: Maksut Zhandos , Zhanbolatkyzy Raushan , Bakytzhanuly Abay , Bajgalkanova Almira , Ergül Yakup , Nuralinov Omirbek
Published: August 2024

A 12-lead electrocardiogram of a pediatric patient with Wolff–Parkinson–White syndrome was consistent with the anteroseptal accessory pathway. The patient had three ablation procedures because of the recurrences of the arrhythmia. In our case, successful cryoablation was performed in the non-coronary cusp of the aortic root.
Effects of transparent online open procurement on prices, volumes, and costs of medicines: an interrupted time series study in Ningxia, China
Authors: Gao Jingying , Liu Chaojie , Li Yinming , Chen Xizhuo , Xue Tianqin , Tang Yuqing
Published: August 2024

Objectives

To assess the effects of the transparent online open procurement arrangement on the prices, volumes, and costs of medicines in Ningxia, China.

Methods

Data were extracted from the Ningxia pharmaceutical procurement platform, covering 16 months of purchase orders (December 2019 to March 2021) prior to the implementation of the transparent online open procurement policy and 20 months of purchase orders after the implementation of the policy (April 2021 to November 2022). Interrupted time series (ITS) analysis was performed to evaluate the effects of the transparent online open procurement policy on the prices, volumes, and total costs of the purchase orders.

Results

After implementation of the transparent online open procurement policy, the average price of purchased medicines showed a declining trend by 0.012 Yuan per month, while the total volume of purchase orders declined at a rate by 1.741 million per month measured by the smallest formulation units and the total costs of the purchase orders decreased at a rate by 5.525 million Yuan per month.

Conclusion

The transparent online open procurement policy resulted in reduced prices, lowered volumes, and lowered total costs of purchased orders of medicines.
Review of pharmacogenetics of antiseizure medications: focusing on genetic variants of mechanistic targets
Authors: Lin Chih-Hsiang , Ho Chen-Jui , Chen Shih-Ying , Lu Yan-Ting , Tsai Meng-Han
Published: August 2024

Antiseizure medications (ASMs) play a central role in seizure management, however, unpredictability in the response to treatment persists, even among patients with similar seizure manifestations and clinical backgrounds. An objective biomarker capable of reliably predicting the response to ASMs would profoundly impact epilepsy treatment. Presently, clinicians rely on a trial-and-error approach when selecting ASMs, a time-consuming process that can result in delays in receiving alternative non-pharmacological therapies such as a ketogenetic diet, epilepsy surgery, and neuromodulation therapies. Pharmacogenetic studies investigating the correlation between ASMs and genetic variants regarding their mechanistic targets offer promise in predicting the response to treatment. Sodium channel subunit genes have been extensively studied along with other ion channels and receptors as targets, however, the results have been conflicting, possibly due to methodological disparities including inconsistent definitions of drug response, variations in ASM combinations, and diversity of genetic variants/genes studied. Nonetheless, these studies underscore the potential effect of genetic variants on the mechanism of ASMs and consequently the prediction of treatment response. Recent advances in sequencing technology have led to the generation of large genetic datasets, which may be able to enhance the predictive accuracy of the response to ASMs.
Role of mitochondria in inflammatory lung diseases
Authors: Narala Venkata Ramireddy , Narala Sahithi Reddy , Aiya Subramani Parasuraman , Panati Kalpana , Kolliputi Narasaiah
Published: August 2024

Mitochondria play a significant and varied role in inflammatory lung disorders. Mitochondria, known as the powerhouse of the cell because of their role in producing energy, are now recognized as crucial regulators of inflammation and immunological responses. Asthma, chronic obstructive pulmonary disease, and acute respiratory distress syndrome are characterized by complex interactions between immune cells, inflammatory substances, and tissue damage. Dysfunctional mitochondria can increase the generation of reactive oxygen species (ROS), triggering inflammatory pathways. Moreover, mitochondrial failure impacts cellular signaling, which in turn affects the expression of molecules that promote inflammation. In addition, mitochondria have a crucial role in controlling the behavior of immune cells, such as their activation and differentiation, which is essential in the development of inflammatory lung diseases. Their dynamic behavior, encompassing fusion, fission, and mitophagy, also impacts cellular responses to inflammation and oxidative stress. Gaining a comprehensive understanding of the intricate correlation between mitochondria and lung inflammation is essential in order to develop accurate treatment strategies. Targeting ROS generation, dynamics, and mitochondrial function may offer novel approaches to treating inflammatory lung diseases while minimizing tissue damage. Additional investigation into the precise contributions of mitochondria to lung inflammation will provide significant knowledge regarding disease mechanisms and potential therapeutic approaches. This review will focus on how mitochondria in the lung regulate these processes and their involvement in acute and chronic lung diseases.
Effects of three flavonoids on the metabolism of lenvatinib
Authors: Yang Jinzhao , Chen Jie , Li Qingqing , Xu Ren-ai , Chen Xiaohai
Published: August 2024

Lenvatinib is a first-line therapy for the treatment of hepatocellular carcinoma (HCC), an active multi-target tyrosine kinase inhibitor (TKI). The interaction between Traditional Chinese Medicine (TCM) and chemicals has increasingly become a research hotspot. The objective of this study was to pinpoint the effects of three flavonoids on the metabolism of lenvatinib. Enzyme reaction system was established and optimized in vitro, and in vivo experiments were conducted in Sprague-Dawley (SD) rats, where the analytes were detected by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). We found that among three flavonoids, luteolin and myricetin had strong inhibitory effects on lenvatinib metabolism, with half-maximal inhibitory concentration (IC50) values of 11.36 ± 0.46 µM and 11.21 ± 0.81 µM in rat liver microsomes (RLM), respectively, and 6.89 ± 0.43 µM and 12.32 ± 1.21 µM in human liver microsomes (HLM), respectively. In Sprague-Dawley rats, the combined administration of lenvatinib and luteolin obviously expanded the exposure to lenvatinib; however, co-administered with myricetin did not have any changes, which may be due to the poor bioavailability of myricetin in vivo. Furthermore, the inhibitory type of luteolin on lenvatinib showed an un-competitive in RLM and a mixed in HLM. Collectively, flavonoids with liver protection, especially luteolin, may inhibit lenvatinib metabolism in vitro and in vivo.