bluuebunny/crossref_metadata_2025 huggingface dataset:
The mechanosensory world in aquatic snakes: corporal scale sensilla in three species of Neotropical freshwater dipsadine
Authors: Velasquez-Cañon Valeria , Bravo-Vega Carlos , Galeano Sandra P. , Molina Jorge , Salazar-Guzmán Alejandra María , García-Cobos Daniela
Published: July 2024

Snakes have diverse and unique sensory systems that make them extremely efficient at moving through the environment while detecting prey and predators and performing courtship behaviors. In recent years, the number of studies on the mechanoreception of aquatic snakes has increased, principally focusing on the ecological and sexual roles of cephalic mechanoreceptors or sensilla. However, few studies have focused on the presence and role of corporal mechanoreceptors sensilla in freshwater snakes. This study describes the morphology of dome-shaped corporal scale sensilla for the first time in three species of aquatic Neotropical snakes (Helicops angulatus, Helicops danieli, and Helicops pastazae), using histological sections and Scanning Electron Microscopy (SEM). Histological sections revealed that the corporal sensilla resemble the previously described cephalic sensilla with a thinner beta keratin layer above the sensillum, and a group of central cells. Further, SEM images show dome-shaped protuberant organs with concentric rings. To infer possible ecological and sexual roles in corporal sensilla, we employed mixed ANOVA permutation tests to assess for differences in the number and area of sensilla between the dorsal and lateral position of the scales, and the anterior and posterior corporal region, as well as among species and sexes. Our results show that individuals across all species consistently exhibited a higher number of mechanoreceptors sensilla in the anterior and lateral region when compared to the posterior or midbody dorsal region. We qualitatively identified that scale sensilla are usually restricted to the keeled portion of the scale in the dorsal region, but are spread out throughout the scale in the lateral region. We also found differences in the average sensillum area between species, with H. angulatus exhibiting larger sensilla than H. danieli. Our results showed no evidence of sexual dimorphism in the number or area of corporal sensilla. These findings are the first to report corporal dome shaped mechanoreceptors in freshwater snakes and contribute to the understanding of mechanosensory systems in these organisms by elucidating the morphology, quantity, distribution and possible function of these corporal scale sensilla.
Methylome-wide analysis in systemic microbial-induced experimental periodontal disease in mice with different susceptibility
Authors: Hernandez Martinez Cristhiam de Jesus , Glessner Joseph , Finoti Livia Sertori , Silva Pedro Felix , Messora Michel , Coletta Ricardo Della , Hakonarson Hakon , Palioto Daniela Bazan
Published: July 2024

Objective

The study delved into the epigenetic factors associated with periodontal disease in two lineages of mice, namely C57bl/6 and Balb/c. Its primary objective was to elucidate alterations in the methylome of mice with distinct genetic backgrounds following systemic microbial challenge, employing high-throughput DNA methylation analysis as the investigative tool.

Methods

Porphyromonas gingivalis (Pg)was orally administered to induce periodontitis in both Balb/c and C57bl/6 lineage. After euthanasia, genomic DNA from both maxilla and blood were subjected to bisulfite conversion, PCR amplification and genome-wide DNA methylation analysis using the Ovation RRBS Methyl-Seq System coupled with the Illumina Infinium Mouse Methylation BeadChip.

Results

Of particular significance was the distinct methylation profile observed within the Pg-induced group of the Balb/c lineage, contrasting with both the control and Pg-induced groups of the C57bl/6 lineage. Utilizing rigorous filtering criteria, we successfully identified a substantial number of differentially methylated regions (DMRs) across various tissues and comparison groups, shedding light on the prevailing hypermethylation in non-induced cohorts and hypomethylation in induced groups. The comparison between blood and maxilla samples underscored the unique methylation patterns specific to the jaw tissue. Our comprehensive methylome analysis further unveiled statistically significant disparities, particularly within promoter regions, in several comparison groups.

Conclusion

The differential DNA methylation patterns observed between C57bl/6 and Balb/c mouse lines suggest that epigenetic factors contribute to the variations in disease susceptibility. The identified differentially methylated regions associated with immune regulation and inflammatory response provide potential targets for further investigation. These findings emphasize the importance of considering epigenetic mechanisms in the development and progression of periodontitis.
Treatment of infections caused by carbapenem-resistant Acinetobacter baumannii
Authors: Zhang Siqin , Di Lingfang , Qi Yan , Qian Xiang , Wang Siwei
Published: July 2024

Patients with severe carbapenem-resistant Acinetobacter baumannii (CRAB) infections currently face significant treatment challenges. When patients display signs of infection and the clinical suspicion of CRAB infections is high, appropriate treatment should be immediately provided. However, current treatment plans and clinical data for CRAB are limited. Inherent and acquired resistance mechanisms, as well as host factors, significantly restrict options for empirical medication. Moreover, inappropriate drug coverage can have detrimental effects on patients. Most existing studies have limitations, such as a restricted sample size, and are predominantly observational or non-randomized, which report significant variability in patient infection severity and comorbidities. Therefore, a gold-standard therapy remains lacking. Current and future treatment options of infections due to CRAB were described in this review. The dose and considerable side effects restrict treatment options for polymyxins, and high doses of ampicillin-sulbactam or tigecycline appear to be the best option at the time of initial treatment. Moreover, new drugs such as durlobactam and cefiderocol have substantial therapeutic capabilities and may be effective salvage treatments. Bacteriophages and antimicrobial peptides may serve as alternative treatment options in the near future. The advantages of a combination antimicrobial regimen appear to predominate those of a single regimen. Despite its significant nephrotoxicity, colistin is considered a primary treatment and is often used in combination with antimicrobials, such as tigecycline, ampicillin-sulbactam, meropenem, or fosfomycin. The Infectious Diseases Society of America (IDSA) has deemed high-dose ampicillin-sulbactam, which is typically combined with high-dose tigecycline, polymyxin, and other antibacterial agents, the best option for treating serious CRAB infections. A rational combination of drug use and the exploration of new therapeutic drugs can alleviate or prevent the effects of CRAB infections, shorten hospital stays, and reduce patient mortality.
AI-based avatars are changing the way we learn and teach: benefits and challenges
Authors: Fink Maximilian C. , Robinson Seth A. , Ertl Bernhard
Published: July 2024

Advancements in the generative AI field have enabled the development of powerful educational avatars. These avatars embody a human and can, for instance, listen to users’ spoken input, generate an answer utilizing a large-language model, and reply by speaking with a synthetic voice. A theoretical introduction summarizes essential steps in developing AI-based educational avatars and explains how they differ from previously available educational technologies. Moreover, we introduce GPTAvatar, an open-source, state-of-the-art AI-based avatar. We then discuss the benefits of using AI-based educational avatars, which include, among other things, individualized and contextualized instruction. Afterward, we highlight the challenges of using AI-based educational avatars. Major problems concern incorrect and inaccurate information provided, as well as insufficient data protection. In the discussion, we provide an outlook by addressing advances in educational content and educational technology and identifying three crucial open questions for research and practice.
Analysis of the contribution of critical thinking and psychological well-being to academic performance
Authors: Guamanga Miguel H. , Saiz Carlos , Rivas Silvia F. , Almeida Leandro S.
Published: July 2024

This study examines the influence of critical thinking and psychological well-being on the academic performance of first-year college students. It emphasizes the importance of a model of psychological well-being focused on self-acceptance, environmental mastery and purpose in life, along with a critical thinking approach oriented to problem solving and decision making. A total of 128 first-year psychology students from a Spanish public university participated, assessed by means of Ryff’s psychological well-being scale (PWBS) and the PENCRISAL critical thinking test, complemented with grades obtained in a critical thinking course. The results show positive correlations between psychological well-being, critical thinking and academic performance, with a stronger relationship between critical thinking and academic performance. However, psychological well-being also plays a significant role in academic performance. The findings highlight the need for holistic pedagogical approaches that combine cognitive skills and personal development to enhance first-year students’ learning.
Coordination of oxysterol binding protein 1 and VAP-A/B modulates the generation of cholesterol and viral inclusion bodies to promote grass carp reovirus replication
Authors: Li Jia Qi , Zhang Jie , Chen Yang , Le Tao , Chang Ming Xian
Published: July 2024

Similar to other RNA viruses, grass carp reovirus, the causative agent of the hemorrhagic disease, replicates in cytoplasmic viral inclusion bodies (VIBs), orchestrated by host proteins and lipids. The host pathways that facilitate the formation and function of GCRV VIBs are poorly understood. This work demonstrates that GCRV manipulates grass carp oxysterol binding protein 1 (named as gcOSBP1) and vesicle-associated membrane protein–associated protein A/B (named as gcVAP-A/B), 3 components of cholesterol transport pathway, to generate VIBs. By siRNA-mediated knockdown, we demonstrate that gcOSBP1 is an essential host factor for GCRV replication. We reveal that the nonstructural proteins NS80 and NS38 of GCRV interact with gcOSBP1, and that the gcOSBP1 is recruited by NS38 and NS80 for promoting the generation of VIBs. gcOSBP1 increases the expression of gcVAP-A/B and promotes the accumulation of intracellular cholesterol. gcOSBP1 also interacts with gcVAP-A/B for forming gcOSBP1-gcVAP-A/B complexes, which contribute to enhance the accumulation of intracellular cholesterol and gcOSBP1-mediated generation of VIBs. Inhibiting cholesterol accumulation by lovastatin can completely abolish the effects of gcOSBP1 and/or gcVAP-A/B in promoting GCRV infection, suggesting that cholesterol accumulation is vital for gcOSBP1- and/or gcVAP-A/B-mediated GCRV replication. Thus, our results, which highlight that gcOSBP1 functions in the replication of GCRV via its interaction with essential viral proteins for forming VIBs and with host gcVAP-A/B, provide key molecular targets for obtaining anti-hemorrhagic disease grass carp via gene editing technology.
A nanoparticle vaccine displaying varicella-zoster virus gE antigen induces a superior cellular immune response than a licensed vaccine in mice and non-human primates
Authors: Li Yuanyuan , Tian Siyu , Ai Yuanbao , Hu Zhulong , Ma Chao , Fu Meijuan , Xu Zhenqian , Li Yan , Liu Shuyun , Zou Yongjuan , Zhou Yu , Jin Jing
Published: July 2024

Herpes zoster (HZ), also known as shingles, remains a significant global health issue and most commonly seen in elderly individuals with an early exposure history to varicella-zoster virus (VZV). Currently, the licensed vaccine Shingrix, which comprises a recombinant VZV glycoprotein E (gE) formulated with a potent adjuvant AS01B, is the most effective shingles vaccine on the market. However, undesired reactogenicity and increasing global demand causing vaccine shortage, prompting the development of novel shingles vaccines. Here, we developed novel vaccine candidates utilising multiple nanoparticle (NP) platforms to display the recombinant gE antigen, formulated in an MF59-biosimilar adjuvant. In naïve mice, all tested NP vaccines induced higher humoral and cellular immune responses than Shingrix, among which, the gEM candidate induced the highest cellular response. In live attenuated VZV (VZV LAV)-primed mouse and rhesus macaque models, the gEM candidate elicited superior cell-mediated immunity (CMI) over Shingrix. Collectively, we demonstrated that NP technology remains a suitable tool for developing shingles vaccine, and the reported gEM construct is a highly promising candidate in the next-generation shingles vaccine development.
The role of WTAP in regulating macrophage-mediated osteoimmune responses and tissue regeneration in periodontitis
Authors: Li Yuman , Yang Yue , Niu Yuting , Li Yao , Hu Zhewen , Sun Shiyu , Chen Yiming , Hu Bo , Huang Ying , Deng Xuliang
Published: July 2024

Periodontitis, delineated by the destruction of structures that support teeth, is predominantly propelled by intricate immune responses. Immunomodulatory treatments offer considerable promise for the management of this ailment; however, the modulation of the periodontal immune microenvironment to facilitate tissue regeneration presents a substantial biomedical challenge. Herein, our study investigates the role of Wilms’ tumor 1-associating protein (WTAP), a critical m6A methyltransferase, in the immunomodulation of periodontitis and assesses its viability as a therapeutic target. We observed heightened expression of WTAP in macrophages extracted from gingival tissues impacted by periodontitis, with a strong association with M1 polarization. Via loss-of-function experiments, we demonstrated that diminishing WTAP expression precipitates a transition from M1 to M2 macrophage phenotypes amidst inflammatory conditions, thus improving the periodontal immune landscape. Further, RNA sequencing and indirect co-culture assays indicated that suppressing of WTAP expression modulates osteoimmune responses and enhances the osteogenic differentiation of bone marrow stromal cells. The local deployment of adeno-associated virus-shWTAP in murine models of periodontitis robustly validated the therapeutic promise of targeting WTAP in this disease. Collectively, our findings highlight the crucial role of WTAP in orchestrating macrophage-mediated osteoimmune responses and tissue regeneration in periodontitis, proposing novel avenues for immunotherapeutic interventions in its treatment.
A viral vaccine design harnessing prior BCG immunization confers protection against Ebola virus
Authors: Ng Tony W. , Furuyama Wakako , Wirchnianski Ariel S. , Saavedra-Ávila Noemí A. , Johndrow Christopher T. , Chandran Kartik , Jacobs William R. , Marzi Andrea , Porcelli Steven A.
Published: July 2024

Previous studies have demonstrated the efficacy and feasibility of an anti-viral vaccine strategy that takes advantage of pre-existing CD4+ helper T (Th) cells induced by Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination. This strategy uses immunization with recombinant fusion proteins comprised of a cell surface expressed viral antigen, such as a viral envelope glycoprotein, engineered to contain well-defined BCG Th cell epitopes, thus rapidly recruiting Th cells induced by prior BCG vaccination to provide intrastructural help to virus-specific B cells. In the current study, we show that Th cells induced by BCG were localized predominantly outside of germinal centers and promoted antibody class switching to isotypes characterized by strong Fc receptor interactions and effector functions. Furthermore, BCG vaccination also upregulated FcγR expression to potentially maximize antibody-dependent effector activities. Using a mouse model of Ebola virus (EBOV) infection, this vaccine strategy provided sustained antibody levels with strong IgG2c bias and protection against lethal challenge. This general approach can be easily adapted to other viruses, and may be a rapid and effective method of immunization against emerging pandemics in populations that routinely receive BCG vaccination.
Insights into the tissue repair features of MAIT cells
Authors: Gao Mengge , Zhao Xiaosu
Published: July 2024

Mucosa-associated invariant T (MAIT) cells are a subset of innate-like non-conventional T cells characterized by multifunctionality. In addition to their well-recognized antimicrobial activity, increasing attention is being drawn towards their roles in tissue homeostasis and repair. However, the precise mechanisms underlying these functions remain incompletely understood and are still subject to ongoing exploration. Currently, it appears that the tissue localization of MAIT cells and the nature of the diseases or stimuli, whether acute or chronic, may induce a dynamic interplay between their pro-inflammatory and anti-inflammatory, or pathogenic and reparative functions. Therefore, elucidating the conditions and mechanisms of MAIT cells’ reparative functions is crucial for fully maximizing their protective effects and advancing future MAIT-related therapies. In this review, we will comprehensively discuss the establishment and potential mechanisms of their tissue repair functions as well as the translational application prospects and current challenges in this field.
Chemokines in the tumor microenvironment: implications for lung cancer and immunotherapy
Authors: Jung Haebeen , Paust Silke
Published: July 2024

The tumor microenvironment (TME) is a complex interconnected network of immune cells, fibroblasts, blood vessels, and extracellular matrix surrounding the tumor. Because of its immunosuppressive nature, the TME can pose a challenge for cancer immunotherapies targeting solid tumors. Chemokines have emerged as a crucial element in enhancing the efficacy of cancer immunotherapy, playing a direct role in immune cell signaling within the TME and facilitating immune cell migration towards cancer cells. However, chemokine ligands and their receptors exhibit context-dependent diversity, necessitating evaluation of their tumor-promoting or inhibitory effects based on tumor type and immune cell characteristics. This review explores the role of chemokines in tumor immunity and metastasis in the context of the TME. We also discuss current chemokine-related advances in cancer immunotherapy research, with a particular focus on lung cancer, a common cancer with a low survival rate and limited immunotherapy options.
Extrauterine leiomyomas in uncommon locations: two case reports and literature review
Authors: Yavuz Onur , Kula Ali Hakan , Bayramoğlu Zeynep , Aydin Nur Yağ mur , Mankan Kadir Alper , Akdöner Aslı
Published: July 2024

Objectives

This study aims to provide an overview of the diagnosis, treatment, and follow-up management of vulvar and vaginal leiomyomas through the presentation of two rare cases.

Methods

Detailed clinical presentations, surgical procedures, histopathological examinations, and follow-up outcomes of two cases of vulvar and vaginal leiomyomas are described. Relevant literature is also reviewed to contextualize the findings.

Results

Both patients underwent successful surgical excision of the leiomyomas with no perioperative or postoperative complications. Histopathological examinations confirmed the diagnosis of leiomyoma based on characteristic microscopic features and immunohistochemical analyses.

Conclusion

Vulvar and vaginal leiomyomas are rare benign tumors that require careful evaluation for accurate diagnosis and appropriate management. Surgical excision remains the primary treatment modality, and long-term follow-up is essential for monitoring recurrence and ensuring favorable outcomes.
A reference architecture for personal health data spaces using decentralized content-addressable storage networks
Authors: Klementi Toomas , Piho Gunnar , Ross Peeter
Published: July 2024

Introduction

This paper addresses the dilemmas of accessibility, comprehensiveness, and ownership related to health data. To resolve these dilemmas, we propose and justify a novel, globally scalable reference architecture for a Personal Health Data Space (PHDS). This architecture leverages decentralized content-addressable storage (DCAS) networks, ensuring that the data subject retains complete control and ownership of their personal health data. In today's globalized world, where people are increasingly mobile for work and leisure, healthcare is transitioning from episodic symptom-based treatment toward continuity of care. The main aims of this are patient engagement, illness prevention, and active and healthy longevity. This shift, along with the secondary use of health data for societal benefit, has intensified the challenges associated with health data accessibility, comprehensiveness, and ownership.

Method

The study is structured around four health data use case scenarios from the Estonian National Health Information System (EHIS): primary medical use, medical emergency use, secondary use, and personal use. We analyze these use cases from the perspectives of accessibility, comprehensiveness, and ownership. Additionally, we examine the security, privacy, and interoperability aspects of health data.

Results

The proposed architectural solution allows individuals to consolidate all their health data into a unified Personal Health Record (PHR). This data can come from various healthcare institutions, mobile applications, medical devices for home use, and personal health notes.

Discussions

The comprehensive PHR can then be shared with healthcare providers in a semantically interoperable manner, regardless of their location or the information systems they use. Furthermore, individuals maintain the autonomy to share, sell, or donate their anonymous or pseudonymous health data for secondary use with different systems worldwide. The proposed reference architecture aligns with the principles of the European Health Data Space (EHDS) initiative, enhancing health data management by providing a secure, cost-effective, and sustainable solution.
BlpU is a broad-spectrum bacteriocin in Streptococcus thermophilus
Authors: Renye John A. , Somkuti George A. , Qi Phoebe X. , Steinberg Dennis H. , McAnulty Michael J. , Miller Amanda L. , Guron Giselle K. P. , Oest Adam M.
Published: July 2024

Streptococcus thermophilus strain B59671 naturally produces thermophilin 110, a broad-spectrum bacteriocin encoded within the bacteriocin-like peptide (blp) gene cluster, and thermophilin 13 from a separate chromosomal locus. Analysis of the blp gene cluster revealed two genes, blpU and blpK, as potentially encoding bacteriocins. Deletion of blpK from the B59671 chromosome did not result in a loss of antimicrobial activity against either S. thermophilus ST113 or Pediococcus acidilactici F. A deletion mutant of blpU could not be generated in B59671, but the mature BlpU peptide obtained through overexpression in E. coli BL21 or chemical synthesis inhibited the growth of S. thermophilus strains, Streptococcus mutans UA159, P. acidilactici F, and Listeria innocua GV9 L-S, evidencing as a broad-spectrum bacteriocin that does not require modification for activity. This study also showed that the transcription of blpU was approximately 16-fold higher in B59671 than in an induced culture of S. thermophilus LMD-9, which produces a blp-encoded bacteriocin. The increased expression of BlpU in B59671 may explain the unique antimicrobial spectrum associated with this strain. Additionally, it was shown that a blpC deletion mutant of B59671, which prevents expression of BlpU and BlpK, inhibited the growth of other S. thermophilus strains and Bacillus cereus, suggesting that thermophilin 13 produced by B59671 possessed both intra- and interspecies antimicrobial activity. While this study confirmed that BlpU can function as an independent antimicrobial peptide, further studies are required to determine if BlpK can function independently as a broad-spectrum antimicrobial.
Single Neuroform Atlas stent: a reliable approach for treating complex wide-neck bifurcated aneurysms
Authors: Ahn Hong Suk , Jeon Hong Jun , Cho Byung Moon , Park Se Hyuck
Published: July 2024

Background

Treating wide-neck bifurcated cerebral aneurysms (WNBAs) using various techniques and new devices has shown favorable outcomes. However, endovascular coiling can be technically challenging when the aneurysm neck is incorporated into the parent vessel. Furthermore, although recent research has reported favorable outcomes of Neuroform Atlas stent (NAS)-assisted coiling, broad inclusion criteria have hampered precise evaluations of their effectiveness and safety for treating complex WNBAs. Therefore, this study evaluated whether the use of a single NAS is a safe and effective approach for treating complex WNBAs.

Methods

We treated 76 complex WNBAs (unruptured, n = 49; ruptured, n = 27) using single NAS-assisted coil embolization and retrospectively analyzed the clinical and angiographic outcomes.

Results

In a cohort of 68 patients (mean age, 58.3 ± 11.6 years; males n = 20, 29.4%; females, n = 48, 70.6%), 76 stents were successfully delivered to the target aneurysms, yielding a technical success rate of 98.6%. Complete occlusion was evident in 59 (77.6%) of 76 aneurysms, with neck remnants found in 16 (21.1%) and partial occlusion in 1 (1.3%). Treatment-related morbidities comprised one branch occlusion and one parenchymal hemorrhage. However, no new neurological symptoms of unruptured aneurysms were evident at discharge. The outcomes of 20 of the 27 ruptured aneurysms were favorable (Glasgow Outcome Scale scores of 4 or 5) at the final follow-up assessment (mean 12.2 [6–29] months), except for one initial subarachnoid hemorrhage. Post-treatment angiography revealed complete occlusion in 89.1%, neck remnants in 7.8%, and incomplete occlusion in 3.1% of the aneurysms. Approximately 88.2% of the patients were assessed at least once by follow-up diagnostic or magnetic resonance angiography (mean, 12.5 ± 4.3 [range, 6–29] months), with five (7.8%) minor and two (3.1%) major recurrences.

Conclusion

A single NAS is safe and effective for treating WNBAs incorporated into parent vessels.
Bidirectional remodeling of the central auditory system caused by unilateral auditory deprivation
Authors: Ge Xinying , Xu Cong , Dai Jinsheng , Zhou Mo , Liu Jinfeng , Wang Ningyu
Published: July 2024

Unilateral auditory deprivation (UAD) results in cross-modal reorganization of the auditory cortex (AC), which can impair auditory and cognitive functions and diminish the recovery effect of cochlear implantation. Moreover, the subcortical areas provide extensive ascending projections to the AC. To date, a thorough systematic study of subcortical auditory neural plasticity has not been undertaken. Therefore, this review aims to summarize the current evidence on the bidirectional remodeling of the central auditory system caused by UAD, particularly the changes in subcortical neural plasticity. Lateral changes occur in the cochlear nucleus, lateral superior olive, medial nucleus of the trapezoid body, inferior colliculus, and AC of individuals with UAD. Moreover, asymmetric neural activity becomes less prominent in the higher auditory nuclei, which may be due to cross-projection regulation of the bilateral pathway. As a result, subcortical auditory neural plasticity caused by UAD may contribute to the outcomes of cochlear implantation in patients with single-sided deafness (SSD), and the development of intervention strategies for patients with SSD is crucial. Considering that previous studies have focused predominantly on the neural plasticity of the AC, we believe that bidirectional remodeling of subcortical areas after UAD is also crucial for investigating the mechanisms of interventions.
Physicochemical, microbiological, and sensory properties of healthy juices containing aloe vera gel and probiotics and their antidiabetic effects on albino rats
Authors: Moselhy Sara Naiim , Al-Nashwi Ahmed Aladdin , Raya-Álvarez Enrique , Abu Zaid Fouad Omar , Shalaby Hanan Said Tawfik , El-Khadragy Manal F. , Shahein Magdy Ramadan , Hafiz Amin A. , Aljehani Abeer A. , Agil Ahmad , Elmahallawy Ehab Kotb
Published: July 2024

The consumption of fruit and vegetable juices is widely recognized as a healthy choice across all age groups. Orange, carrot, and aloe vera are renowned for their functional properties and health benefits. In this study, we investigated the potential incorporation of aloe vera gel into blended orange and carrot juices. We also evaluated the resulting mixed probiotic juices (chemical, microbiological, and sensory aspects) during a 14-day storage period at refrigerator temperature. The chemical composition and phytochemical structure of aloe vera gel were examined, followed by an assessment of the biological effects of these healthy juices on diabetic albino rats. The results indicated improvements in total soluble solids, reducing sugars, and total sugars with increasing storage duration. Furthermore, the study demonstrated that incorporating aloe vera into the natural mixed juices enhanced their phytochemical quality. The treatment supplemented with aloe vera gel gave the highest total content of phenolic and flavonoid substances, which were 310 mg of GAE/100 g and 175 mg of quercetin/100 g, respectively. Probiotic strains (Bifidobacterium animalis subsp lactis Bb12, Lactiplantibacillus plantarum 299V, and Lactobacillus acidophilus L10) exhibited good viable cell counts in orange and mixed orange and carrot probiotics juices with viable counts of 7.42–8.07 log CFU/mL. Regarding sensory attributes, the study found that increasing the ratio of orange juice improved the taste while increasing the ratio of carrot juice enhanced the color in juice mixtures. Incorporation of aloe vera into mixed natural juices also enhanced the reduction of blood glucose, triglyceride, cholesterol, LDL, creatinine, ALT, AST, and urea levels while increasing total protein and HDL levels in diabetic rats. Based on these findings, oranges, carrots, and aloe vera offer the potential to produce new, flavorful, nutritious, and appealing juices. Moreover, this study determined that a functional juice with favorable sensory properties can be created by blending 75% orange juice, 20% carrot juice, and 5% aloe vera gel. Additionally, aloe vera demonstrated greater efficacy as an antidiabetic agent in rats. Further research is suggested to explore the potential advantages of aloe vera gel and probiotic juices in mitigating diabetes and other metabolic syndromes.
Acute physiological effects on macromolecule digestion following oral ingestion of the enzyme blend Elevase® in individuals that had undergone an ileostomy, but were otherwise healthy—a randomized, double blinded, placebo-controlled exploratory study
Authors: Mazhar Shahneela , Simon Annie , Colom Joan , Khokhlova Ekaterina , Buckley Martin , Phipps Christopher , Deaton John , Rea Kieran
Published: July 2024

Digestive enzymes can selectively degrade proteins, carbohydrates and lipids; and their supplementation alongside food may accelerate the breakdown of complex food matrices, facilitate greater nutrient absorption, decrease food sensitivities and aid in the management of certain disease states. Several intrinsic and extrinsic factors govern food digestion and for every individual this phenomenon is unique. This study was conducted as a randomized, crossover, placebo-controlled design where each participant served as their own control. This post-hoc analysis investigated the impact of a dietary enzyme supplementation blend known as Elevase® on dietary macromolecule digestion in samples from otherwise healthy participants that had previously undergone a small bowel resection, resulting in an ileostomy (NCT04489810). This is the first time this study-paradigm has been used for the assessment of in vivo dietary breakdown following enzyme supplementation. Arguably, this technique offers superior data when compared to that generated in artificial gut digestion models, preclinical animal models, or indeed conventional clinical studies using stool analyses, as it allows real-time access to samples in situ in the small intestine where the majority of nutritional absorption takes place. It was demonstrated that after 4 h, Elevase® significantly increased monosaccharide levels (predominantly glucose and fructose) in the ileostomy samples taken from the same individuals on the same diet on a different day. In addition, the bile salt taurohyodeoxycholic acid was also increased, suggesting a physiological host response to the macromolecule digestion induced by the enzymatic blend. Overall, these findings suggest Elevase® could accelerate food digestion and potentially increase nutrient availability from the diet.
Neoadjuvant targeted therapy versus targeted combined with chemotherapy for resectable EGFR-mutant non–small cell lung cancer: a retrospective controlled real-world study
Authors: Shao Weipeng , Liu Zhan , Li Bobo , Chen Feng , Liu Jie , Li Hui , Guo Hongbo
Published: July 2024

Background

This study aimed to assess the role and effect of neoadjuvant targeted therapy (TT) versus targeted combined with chemotherapy (TC) for resectable EGFR-mutant non–small cell lung cancer (NSCLC).

Methods

Between March 2021 and June 2023, 20 patients with stage IA3-IIIB NSCLC were enrolled in the study. Eleven patients received EGFR-TKIs in the TT group, while nine patients received EGFR-TKIs and two cycles of cisplatin-based doublet chemotherapy (TC group). We compare the differences between the two groups through the following variables, including age, sex, surgical approach, postoperative complications, neoadjuvant therapy adverse events, complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR), major pathologic response (MPR), and pathologic complete response (pCR).

Results

Patients were predominantly female (75%) and never-smokers (95%). The average age was 59.2 years (range 46-79 years). Fifty-five percent harbored an exon 19 EGFR mutation and 45% an exon 21 mutation. The average targeted drug dosing time was 2.91 ± 1.7 (range 1-6) months in the TT group and 3.56 ± 3.54 (range 1-12) months in the TC group (P=0.598). The most common side effects were rash and diarrhea. No grade 5 events with neoadjuvant therapy were observed. The rate of R0 resection was 100% in all patients. Among the 11 patients in the TT group, 6 achieved a PR and 5 had SD, resulting in an ORR of 54.5%. Among the 9 patients in the TC group, 6 had PR and the remaining 3 had SD, resulting in an ORR of 66.6%. one patient (11.1%) in the TC group achieved pCR, while no patients in the TT group achieved pCR (P = 0.142). Two patients (18.2%) in the TT group reached MPR, and 2 patients (22.2%) in the TC group reached MPR (P = 0.257). The overall clinical downstage rate is 60%. Only 9 (45%) cases of yield clinical TNM (ycTNM) were consistent with yield pathologic TNM (ypTNM).

Conclusion

Results from this retrospective controlled research indicate that the neoadjuvant TT group is likely to be more effective outcomes and has safer profile in patients with EGFR-positive NSCLC than the neoadjuvant TC group. However, our results need to be validated in a multicenter, large sample prospective study.
Recent advances in immunotherapy and its combination therapies for advanced melanoma: a review
Authors: Xu Jiamin , Mu Shukun , Wang Yun , Yu Suchun , Wang Zhongming
Published: July 2024

The incidence of melanoma is increasing year by year and is highly malignant, with a poor prognosis. Its treatment has always attracted much attention. Among the more clinically applied immunotherapies are immune checkpoint inhibitors, bispecific antibodies, cancer vaccines, adoptive cell transfer therapy, and oncolytic virotherapy. With the continuous development of technology and trials, in addition to immune monotherapy, combinations of immunotherapy and radiotherapy have shown surprising efficacy. In this article, we review the research progress of immune monotherapy and combination therapy for advanced melanoma, with the aim of providing new ideas for the treatment strategy for advanced melanoma.
Neurodivergent patient experience in a tertiary children's hospital-a qualitative analysis
Authors: Talley Michele , Brown Chelsea , Wingo Nancy , Conway Jennifer , Maha Julian , Kong Michele
Published: July 2024

Introduction

Sensory processing challenges are commonly encountered in pediatric patients, particularly in those who are neurodivergent. We previously developed a novel clinical pathway (named “Sensory Pathway”) which aimed at improving patient care for those with sensory barriers via staff training, provision of sensory toolkits and early integration of families throughout the hospital stay. We hypothesized that utilization of this pathway will result in improved patient experience and provide valuable feedback to improve care.

Methods

A voluntary survey was made available to all patients who utilized this resource as part of our hospital wide patient satisfaction survey. Qualitative data was coded using open coding as part of the constant comparison method data using NVivo 12 for Windows software for analysis. Software was used to create word clouds and clusters for visualization, which confirmed the themes and patterns that were noted from initial open coding.

Results

Between 2021 and 2022, surveys were obtained from 160 patients who utilized the Sensory Pathway. More than 50% reported that the most helpful components of the pathway were the approach by the staff and sensory tools. The three major themes identified from the survey were (1) Tools and techniques that benefited their children; (2) Positive interactions and communication with the hospital staff, and (3) Suggestions for future improvement.

Conclusion

The survey results highlight the importance of having tools readily available to aid with sensory regulation and comfort of patients during healthcare encounters, the value of a positive patient and staff encounter, as well as opportunities for improvement.
The multifaceted effects of fluoxetine treatment on cognitive functions
Authors: Ampuero Estíbaliz , Luarte Alejandro , Flores Francisca Sofia , Soto Antonia Ignacia , Pino Catalina , Silva Viviana , Erlandsen Macarena , Concha Teresita , Wyneken Ursula
Published: July 2024

Fluoxetine, the prototypical selective serotonin reuptake inhibitor (SSRI), is widely used to treat major depressive disorder (MDD) and a variety of other central nervous system conditions, primarily due to its established clinical safety profile. Although its efficacy in treating depression is well-recognized, the impact of fluoxetine on cognitive functions remains inconsistent and elusive. In this review, we first examine the well-substantiated biological mechanisms underlying fluoxetine’s antidepressant effects, which include serotonin reuptake inhibition and activation of TrkB receptors—key to brain-derived neurotrophic factor (BDNF) signaling. Subsequently, we delve into the cognitive side effects observed in both preclinical and clinical studies, affecting domains such as memory, attention, and executive functions. While certain studies indicate cognitive improvements in patients with underlying disorders, there is also evidence of negative effects, influenced by variables like gender, duration of treatment, age, disease pathology, and the specifics of cognitive testing. Significantly, the negative cognitive outcomes reported in preclinical research often involve healthy, non-diseased animals. This review underscores the necessity for heightened caution in fluoxetine prescription and further investigation into its potentially detrimental cognitive effects, even when used prophylactically.
Real-world evidence of characteristics and factors influencing herbal medicine use for weight loss in adults
Authors: Lee Boram , Yang Changsop , Yim Mi Hong
Published: July 2024

Background

Obesity imposes a significant socioeconomic burden owing to its high prevalence. In response to the adverse outcomes associated with conventional pharmacotherapy and the challenges of low adherence to lifestyle interventions, herbal medicine has surfaced as an actively utilized approach for weight loss. Therefore, this study aimed to analyze the characteristics and influencing factors of herbal medicine users for weight loss in adults.

Methods

Overall, 22,080 participants were included based on data from the Korea National Health and Nutrition Examination Survey from 2010 to 2019. Simple logistic regression analyses were used to derive the associations between herbal medicine use for weight loss and individual characteristics. Three models were constructed utilizing multiple logistic regression analyses to assess the associations between herbal medicine use for weight loss and the combined characteristics of predisposing, enabling, and need factors according to Andersen’s model.

Results

In the full adjustment model, women, younger adults, those with higher incomes, and individuals reporting higher levels of perceived stress were more prone to use herbal medicine for weight loss in the past year. Adults who identified body image as being fat/very fat, those who consumed alcohol, and those classified as severely obese by body mass index were also more prone to use herbal medicine for weight loss. In particular, adults with a higher rate and amount of weight loss in the past year were more likely to use herbal medicine for weight loss compared to those experiencing weight gain/no changes/loss of 0–3 kg.

Conclusion

Our study was the first to derive the characteristics and influencing factors of herbal medicine users for weight loss among adults. These findings hold significant promise for informing future research endeavors and policy decision-making for effective resource distribution for obesity treatment.
Understanding the roles of salt-inducible kinases in cardiometabolic disease
Authors: Shi Fubiao
Published: July 2024

Salt-inducible kinases (SIKs) are serine/threonine kinases of the adenosine monophosphate-activated protein kinase family. Acting as mediators of a broad array of neuronal and hormonal signaling pathways, SIKs play diverse roles in many physiological and pathological processes. Phosphorylation by the upstream kinase liver kinase B1 is required for SIK activation, while phosphorylation by protein kinase A induces the binding of 14-3-3 protein and leads to SIK inhibition. SIKs are subjected to auto-phosphorylation regulation and their activity can also be modulated by Ca2+/calmodulin-dependent protein kinase in response to cellular calcium influx. SIKs regulate the physiological processes through direct phosphorylation on various substrates, which include class IIa histone deacetylases, cAMP-regulated transcriptional coactivators, phosphatase methylesterase-1, among others. Accumulative body of studies have demonstrated that SIKs are important regulators of the cardiovascular system, including early works establishing their roles in sodium sensing and vascular homeostasis and recent progress in pulmonary arterial hypertension and pathological cardiac remodeling. SIKs also regulate inflammation, fibrosis, and metabolic homeostasis, which are essential pathological underpinnings of cardiovascular disease. The development of small molecule SIK inhibitors provides the translational opportunity to explore their potential as therapeutic targets for treating cardiometabolic disease in the future.
Relationship between visual ability assessment and punch performance in competition in male amateur boxers
Authors: Wu Rui , Yang Qingyuan , Cui Weijia , Gao Dongxu , Luo Yifei , Wang Dexin
Published: July 2024

Sport visual ability plays an important role in the performance of elite athletes in competition. However, its relationship with boxers’ performance has not been fully understood. This study investigated the relationship between sports visual abilities and in-competition punching performance in 26 highly trained male amateur boxers. Ten visual abilities of the boxers were tested using the Senaptec Sensory Station (Senaptec, Beaverton, OR, United States), including Visual Clarity (VC), Contrast Sensitivity (CS), Depth Perception (DP), Near Far Quickness (NFQ), Target Capture (TC), Perception Span (PS), Multiple Object Tracking (MOT), Eye-Hand Coordination (EHC), Go/No Go (GNG), and Reaction Time (RT). Performance analyses were conducted on national boxing championships conducted by the boxers to analyze their punching accuracy. Correlation and regression analyses showed that punch performance %Hit was very strong correlated with DP, EHC, GNG, and RT, and showed a strong correlation with VC, CS, and PS. %Hit was moderate correlated with MOT, while there was no correlation with NFQ and TC. In addition, RT, EHC, and DP are important visual ability variables for boxers. The results of this study indicate that there is an overall relationship between sports visual ability and boxing performance, but there is also a specific relationship between variables in visual ability and boxing performance, especially faster reaction times, better processing of visual information, and decision-making abilities, and the ability to accurately recognize the distance and position of an opponent and their punches are essential for enhancing boxing performance. Further studies are needed to investigate the relationship between sport visual ability and more comprehensive performance in boxers, and the possibility of enhancing performance through specific visual training.
A novel exopolysaccharide-producing bacterium, Pseudescherichia liriopis sp. nov. isolated from Liriope platyphylla, enhances the growth of Daucus carota subsp. sativus under drought and salinity stress
Authors: Kim Inhyup , Woo Haejin , Chhetri Geeta , Park Sunho , Seo Taegun
Published: July 2024

Biological and abiotic stresses in plant growth are associated with reduced crop yields. Therefore, improving plant stress resistance can be a crucial strategy to improve crop production. To overcome these problems, plant growth-promoting bacteria are emphasized as one of the alternative tools for sustainable agriculture. This study found a novel strain (L3T) of a plant growth-promoting bacterium in fermented Liriope platyphylla fruit. Strain L3T showed the ability to promote plant growth. The L3T strain promoted plant growth of D. carota subsp. sativus, increasing the length (increase rate compared to the control group, 36.98%), diameter (47.06%), and weight of carrots (81.5%), ultimately increasing the edible area. In addition, we confirmed that plant growth was improved even in situations that inhibited plant growth, such as salinity and drought stress. Strain L3T performed indole production, siderophore production, phosphate solubilization, and nitrogen fixation, all characteristics of a strain that promotes plant growth. Genome analysis revealed genes involved in the growth promotion effects of strain L3T. Additionally, the properties of exopolysaccharides were identified and characterized using FTIR, TGA, and UHPLC. Our results demonstrated that L3 isolated from fermented L. platyphylla fruit can be used to simultaneously alleviate drought and NaCl stress.