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IntroductionThis study develops two new multi-institutional hippocampal-sparing whole-brain RapidPlan™ models (HLS-EC-WB and HMS-EC-WB) inspired by CCTG-CE.7 featuring enhanced target coverage with varying hippocampal sparing (limited and moderate).MethodsNew dosimetric scorecards were created to quantify the models’ clinical intent. The models were trained using a multi-institution dataset, and a recursive method was employed to generate consistent, high-quality plans. The models were validated using a five-case set and compared at 20- and 30-Gy prescriptions.ResultsEach model scored highest on its associated dosimetric scorecard. The new models achieved higher brain PTV prescription coverage (98%–99%) compared to the previous HSWBv2 model (95.12%), with some trade-off in hippocampal sparing.ConclusionsThree high-quality automated RapidPlan™ models for hippocampal-sparing whole brain are now available, each with a distinct dosimetric scorecard. The new models prioritize increased PTV coverage at some expense to hippocampal sparing. All models, example plans, scorecards, and scoring tools are freely available online.

Purpose: The Adaptive Radiation Therapy Individualized Approach-Cervix clinical trial uses predefined clinical directive templates (CDTs) combined with RapidPlan dose-volume histogram estimations (DVHe) to guide plan optimization in the Ethos treatment planning system. The dosimetric scorecard is a scoring tool that quantifies improvements in plan quality after physicians have precisely expressed their complete clinical intent. To our knowledge, this is the first study to use the dosimetric scorecard tool to tune an Ethos CDT to improve resulting plan quality. Methods and Materials: Iterative replanning was used to modify the draft CDT (CDT-1) in Ethos 1.1 to generate a new CDT (CDT-2) that maximized the clinical consensus scorecard's total score compared with CDT-1. CDT-2 was established, and resulting plans were compared with and without a DVHe. Additional fixed field intensity modulated radiation therapy beam geometries were compared between CDT-1 and CDT-2, both with DVHe. After obtaining favorable results when comparing CDT-1 versus CDT-2 for 2 test cases, 10 additional cases were retrospectively identified and tested. Results: CDT-2 reduced organ at risk doses without compromising planning target volume coverage in the initial test cases. When combined with DVHe, CDT-2 marginally outperformed CDT-1. Plan quality further improved with a 19-field geometry. In the expanded analysis, CDT-2 achieved higher scores than CDT-1 in most cases, with the 19-field approach showing superiority. Optimization and calculation time increased by 1.9 minutes, monitor unit (MU)/field decreased by 44.4, whereas beam-on time increased by 2.8 minutes when increasing fields to 19 from 9. Reoptimization with Ethos 1.1 Maintenance Release 1 resulted in decreased MU and minimal score changes. Conclusions: The scorecard is an effective tool to adjust an Ethos CDT to improve the average calculated plan quality. It also allowed for easy evaluation of the dosimetric impact of other planning parameters (beam arrangements and use of DVHe) to identify the best approach. Using a finely tuned CDT is expected to improve planning efficiency and decrease intrainstitutional plan quality variability, benefiting cone beam computed tomography–guided adaptive radiation therapy.

The objective of this study was to assess the occurrence and seasonal frequency of human adenovirus (HAdV), human polyomavirus (HPyV), and human papillomavirus (HPV) in urban sewage. The detection of these viruses was carried out by polymerase chain reaction (PCR), and then the viral concentrations in the positive samples were quantified by quantitative PCR (qPCR). Additionally, HAdV and HPyV genotyping was also performed by PCR. A total of 38/60 (63.3%) positive samples were found. HAdV was the most prevalent virus (26/60; 43.3%), followed by HPyV (21/60; 35%) and HPV (21/60; 35%). The viral concentrations ranged from 3.56 × 102 to 7.55 × 107 genome copies/L. The most common dual viral agents was found between HAdV and HPyV, in eight samples (8/38, 21%). HAdV types 40 and 41 as well as HPyV types JC and BK were identified, with HAdV-40 and HPyV JC being the most prevalent types. Furthermore, the detection rates of HAdV, HPyV, and HPV were higher during the winter season than the other seasons. The high prevalence of HAdV and HPyV supports their suitability as viral indicators of sewage contamination. Furthermore, this study demonstrates the advantages of environmental surveillance as a tool to elucidate the community-circulating viruses. HIGHLIGHTS This study aimed to investigate the occurrence and seasonality variation of HAdV, HPyV, and HPV in raw sewage collected regularly over 12 months from sewage pump stations.; This study represents the first data about the occurrence of HAdV, HPyV, and HPV in Zagazig city, Al Sharqia Governorate, Egypt.; This study supports using both HAdV and HPyV as indicators than either of them as a single fecal indicator.;

Purpose: To maximize the therapeutic ratio, it is important to identify adverse prognostic features in men with prostate cancer, especially among those with intermediate risk disease, which represents a heterogeneous group. These men may benefit from treatment intensification. Prior studies have shown pretreatment mpMRI may predict biochemical failure in patients with intermediate and/or high-risk prostate cancer undergoing conventionally fractionated external beam radiation therapy and/or brachytherapy. This study aims to evaluate pretreatment mpMRI findings as a marker for outcome in patients undergoing stereotactic body radiation therapy (SBRT). Methods and Materials: We identified all patients treated at our institution with linear accelerator based SBRT to 3625 cGy in 5 fractions, with or without androgen deprivation therapy (ADT) from November 2015 to March 2021. All patients underwent pretreatment Magnetic Resonance Imaging (MRI). Posttreatment Prostate Specific Imaging (PSA) measurements were typically obtained 4 months after SBRT, followed by every 3 to 6 months thereafter. A 2 sample t test was used to compare preoperative mpMRI features with clinical outcomes. Results: One hundred twenty-three men were included in the study. Pretreatment MRI variables including median diameter of the largest intraprostatic lesion, median number of prostate lesions, and median maximal PI-RADS score, were each predictive of PSA nadir and time to PSA nadir (P < .0001). When separated by ADT treatment, this association remained for patients who were not treated with ADT (P < .001). In patients who received ADT, the pretreatment MRI variables were each significantly associated with time to PSA nadir (P < .01) but not with PSA nadir (P > 0.30). With a median follow-up time of 15.9 months (IQR: 8.5-23.3), only 3 patients (2.4%) experienced biochemical recurrence as defined by the Phoenix criteria. Conclusions: Our experience shows the significant ability of mpMRI for predicting PSA outcome in prostate cancer patients treated with SBRT with or without ADT. Since PSA nadir has been shown to correlate with biochemical failure, this information may help radiation oncologists better counsel their patients regarding outcome after SBRT and can help inform future studies regarding who may benefit from treatment intensification with, for example, ADT and/or boosts to dominant intraprostatic lesions.

Purpose: A scoring mechanism called the scorecard that objectively quantifies the dosimetric plan quality of pancreas stereotactic body radiation therapy treatment plans is introduced. Methods and Materials: A retrospective analysis of patients with pancreatic ductal adenocarcinoma receiving stereotactic body radiation therapy at our institution between November 2019 and November 2020 was performed. Ten patients were identified. All patients were treated to 36 Gy in 5 fractions, and organs at risk (OARs) were constrained based on Alliance A021501. The scorecard awarded points for OAR doses lower than those cited in Alliance A021501. A team of 3 treatment planners and 2 radiation oncologists, including a physician resident without plan optimization experience, discussed the relative importance of the goals of the treatment plan and added additional metrics for OARs and plan quality indexes to create a more rigorous scoring mechanism. The scorecard for this study consisted of 42 metrics, each with a unique piecewise linear scoring function which is summed to calculate the total score (maximum possible score of 365). The scorecard-guided plan, the planning and optimization for which were done exclusively by the physician resident with no prior plan optimization experience, was compared with the clinical plan, the planning and optimization for which were done by expert dosimetrists, using the Sign test. Results: Scorecard-guided plans had, on average, higher total scores than those clinically delivered for each patient, averaging 280.1 for plans clinically delivered and 311.7 for plans made using the scorecard (P = .003). Additionally, for most metrics, the average score of each metric across all 10 patients was higher for scorecard-guided plans than for clinically delivered plans. The scorecard guided the planner toward higher coverage, conformality, and OAR sparing. Conclusions: A scorecard tool can help clarify the goals of a treatment plan and provide an objective method for comparing the results of different plans. Our study suggests that a completely novice treatment planner can use a scorecard to create treatment plans with enhanced coverage, conformality, and improved OAR sparing, which may have significant effects on both tumor control and toxicity. These tools, including the scorecard used in this study, have been made freely available.

Clostridium perfringens epsilon toxin (ETX) is the third most lethal bacterial toxin and has been suggested to be an environmental trigger of multiple sclerosis, an immune-mediated disease of the human central nervous system. However, ETX cytotoxicity on primary human cells has not been investigated. In this article, we demonstrate that ETX preferentially binds to and kills human lymphocytes expressing increased levels of the myelin and lymphocyte protein MAL. Using flow cytometry, ETX binding was determined to be time and dose dependent and was highest for CD4+ cells, followed by CD8+ and then CD19+ cells. Similar results were seen with ETX-induced cytotoxicity. To determine if ETX preference for CD4+ cells was related to MAL expression, MAL gene expression was determined by RT-qPCR. CD4+ cells had the highest amount of Mal gene expression followed by CD8+ and CD19+ cells. These data indicate that primary human cells are susceptible to ETX and support the hypothesis that MAL is a main receptor for ETX. Interestingly, ETX bindings to human lymphocytes suggest that ETX may influence immune response in multiple sclerosis.

Abstract Background Neuroblastoma is the third most common childhood cancer. It is the most common extra-cranial solid tumor of childhood. It accounts for about 15% of all pediatric cancer fatalities. The International Neuroblastoma Risk Group (INRG) Project proposed a new staging system which is dependent on whether image-defined risk factors (IDRFs) are or are not present, and IDRFs are surgical risk factors, detected on images, that make total tumor excision risky or difficult. The purpose of the study is to assess the validity of using the image-defined risk factors (IDRFs) of abdominal neuroblastoma as predictors of the surgical resectability and complications. Methods We retrospectively studied the clinical, imaging, and surgical data of 43 patients with abdominal neuroblastoma, and then the results were correlated with each. For comparing categorical data, chi-square (χ 2) test was performed. P values less than 0.05 were considered as statistically significant. Results At least 1 pre-operative IDRF was present in 33 cases (76.7%), and they were absent in 10 cases (23.3%). There was statistical significant correlation between the pre-operative IDRFs and surgical resectability, and the complete resection rate if no IDRF was found was 80% in this study. Out of the 13 cases with surgical complications, pre-operative IDRFs were present in 12 cases. Conclusion The neuroblastoma IDRFs are useful predictors of the surgical resectability and the risk of surgical complications and should be considered in surgical planning.

Human Bocavirus (HBoV) has been identified from feces and respiratory samples from cases of both acute gastroenteritis and respiratory illness as well as in asymptomatic individuals.The aim of this study was to detect and characterize HBoV from fecal samples collected from hospitalized children aged less than five years old with no symptoms of respiratory tract infection (RTI) or acute gastroenteritis (AGE). The study involved 119 children and one fecal sample was collected from each participant between 2014 and 2015. HBoV was detected using Nested-PCR, and the viral type identified by genomic sequencing. HBoV-4 was identified from one sample obtained from a hospitalized child with soft tissue tumor of the submandibular region. This is the first report of HBoV-4 identification in Brazil, but we consider that this type may be circulating in the country similar to the other types and new investigations are necessary. Keywords: HBoV-4, Asymptomatic children, Tumor of the submandibular region

Abstract Background With the adoption of the English language in medical education, a gap in clinical communication may develop in countries where the native language is different from the language of medical education. This study investigates the association between medical education in a foreign language and students’ confidence in their history-taking skills in their native language. Methods This cross-sectional study consisted of a 17-question survey among medical students in clinical clerkships of Lebanese medical schools. The relationship between the language of medical education and confidence in conducting a medical history in Arabic (the native language) was evaluated (n = 457). Results The majority (88.5%) of students whose native language was Arabic were confident they could conduct a medical history in Arabic. Among participants enrolled in the first clinical year, high confidence in Arabic history-taking was independently associated with Arabic being the native language and with conducting medical history in Arabic either in the pre-clinical years or during extracurricular activities. Among students in their second clinical year, however, these factors were not associated with confidence levels. Conclusions Despite having their medical education in a foreign language, the majority of students in Lebanese medical schools are confident in conducting a medical history in their native language.

Background and Objectives: Dental caries is a chronic disease affecting young children and has multi-factorial risk factors. The purpose of this work was to identify sex-specific differences in the salivary microbiota within caries-active children. Design: Saliva specimens were collected from 85 children (boys: 41; girls: 44) between the ages of 2-12 years. Salivary microbial DNA was subjected to PCR amplification using V3-V4 16S rDNA-specific primers and next-generation sequencing. Results: Significant sex differences in salivary microbiota were found between caries-active boys versus caries-active girls. Neisseria flavescens, Rothia aeria, and Haemophilus pittmaniae were found at significantly higher levels in caries-active boys. In contrast, Lactococcus lactis, Selenomonas species HOT 126, Actinobaculum species HOT 183, Veillonella parvula, and Alloprevotella species HOT 473 were found at significantly higher levels in caries-active girls. Conclusion: We have found the acid-generating, cariogenic Lactococcus lactis to be much more abundant in caries-active girls than caries-active boys, indicating that this microorganism may play a more significant role in shaping the cariogenic microbiome in girls. In addition, in caries-active girls, Alloprevotella species HOT 473 was the only species that exhibited both significant sex differences (4.4-fold difference; p=0.0003) as well as high abundance in numbers (1.85% of the total microbial population).

The ISIS-led attacks on Paris, Beirut, and Baghdad in November 2015 were covered in a variety of ways by major news outlets globally. Coverage of the Paris attack was widespread, and layered with personal stories about those personally affected and analysis about the effects of terrorism on the French way of life. By comparison, little coverage was given to either the Beirut or Baghdad events, the experiences of those suffering on the ground, or the wider issue of the effects of terrorism within Lebanese and Iraqi communities. In this think piece, the bombings in Beirut are used as a lens for examining the politics and consequences of mediated silence or ‘forgetting’ of violence and suffering in the Middle East. We employ a critical humanitarianism, rooted in a social medicine analysis, to connect these media trends to the training of health professionals. Our approach helps build accountability for the inequalities present in the Western construction of suffering and the emotive aspects of global violence, and promotes a wider conversation about the long-term biomedical effects of violence.

Healthcare workers have a unique opportunity to recognize and provide support to HT/DV victims. The objective of this study is to determine if students are more prepared to identify and work with these patient populations after being trained on the topic by the International Rescue Committee (IRC). The IRC came to the University of Arizona College of Medicine- Phoenix (UACOMP) to do an optional one hour training of HT/DV in healthcare for current first and second year medical students. After IRB approval from the UACOMP Research Office for Medical Education (ROME), pre and post surveys were given to a total of 26 students who attended the training. Wilcoxon Signed-Rank tests adjusted for multiple comparisons were used to evaluate differences between pre- and post-training scores. Students had statistically significant improvement in self-reported comfort level scores for recommending resources, providing care, and calling the national hotline for individuals who have experienced human trafficking and domestic violence. The marked improvement in students’ comfort providing resources and care to HT/DV victims after just a 1 h training from the IRC on these topics demonstrates the impact that early exposure to HT/DV education can have in vulnerable patient populations.

ABSTRACT Clostridium perfringens epsilon toxin (ε-toxin) is responsible for a devastating multifocal central nervous system (CNS) white matter disease in ruminant animals. The mechanism by which ε-toxin causes white matter damage is poorly understood. In this study, we sought to determine the molecular and cellular mechanisms by which ε-toxin causes pathological changes to white matter. In primary CNS cultures, ε-toxin binds to and kills oligodendrocytes but not astrocytes, microglia, or neurons. In cerebellar organotypic culture, ε-toxin induces demyelination, which occurs in a time- and dose-dependent manner, while preserving neurons, astrocytes, and microglia. ε-Toxin specificity for oligodendrocytes was confirmed using enriched glial culture. Sensitivity to ε-toxin is developmentally regulated, as only mature oligodendrocytes are susceptible to ε-toxin; oligodendrocyte progenitor cells are not. ε-Toxin sensitivity is also dependent on oligodendrocyte expression of the proteolipid myelin and lymphocyte protein (MAL), as MAL-deficient oligodendrocytes are insensitive to ε-toxin. In addition, ε-toxin binding to white matter follows the spatial and temporal pattern of MAL expression. A neutralizing antibody against ε-toxin inhibits oligodendrocyte death and demyelination. This study provides several novel insights into the action of ε-toxin in the CNS. (i) ε-Toxin causes selective oligodendrocyte death while preserving all other neural elements. (ii) ε-Toxin-mediated oligodendrocyte death is a cell autonomous effect. (iii) The effects of ε-toxin on the oligodendrocyte lineage are restricted to mature oligodendrocytes. (iv) Expression of the developmentally regulated proteolipid MAL is required for the cytotoxic effects. (v) The cytotoxic effects of ε-toxin can be abrogated by an ε-toxin neutralizing antibody. IMPORTANCE Our intestinal tract is host to trillions of microorganisms that play an essential role in health and homeostasis. Disruption of this symbiotic relationship has been implicated in influencing or causing disease in distant organ systems such as the brain. Epsilon toxin (ε-toxin)-carrying Clostridium perfringens strains are responsible for a devastating white matter disease in ruminant animals that shares similar features with human multiple sclerosis. In this report, we define the mechanism by which ε-toxin causes white matter disease. We find that ε-toxin specifically targets the myelin-forming cells of the central nervous system (CNS), oligodendrocytes, leading to cell death. The selectivity of ε-toxin for oligodendrocytes is remarkable, as other cells of the CNS are unaffected. Importantly, ε-toxin-induced oligodendrocyte death results in demyelination and is dependent on expression of myelin and lymphocyte protein (MAL). These results help complete the mechanistic pathway from bacteria to brain by explaining the specific cellular target of ε-toxin within the CNS.

Clostridium perfringens ε-toxin (ETX) is a potent pore-forming toxin responsible for a central nervous system (CNS) disease in ruminant animals with characteristics of blood-brain barrier (BBB) dysfunction and white matter injury. ETX has been proposed as a potential causative agent for Multiple Sclerosis (MS), a human disease that begins with BBB breakdown and injury to myelin forming cells of the CNS. The receptor for ETX is unknown. Here we show that both binding of ETX to mammalian cells and cytotoxicity requires the tetraspan proteolipid Myelin and Lymphocyte protein (MAL). While native Chinese Hamster Ovary (CHO) cells are resistant to ETX, exogenous expression of MAL in CHO cells confers both ETX binding and susceptibility to ETX-mediated cell death. Cells expressing rat MAL are ~100 times more sensitive to ETX than cells expressing similar levels of human MAL. Insertion of the FLAG sequence into the second extracellular loop of MAL abolishes ETX binding and cytotoxicity. ETX is known to bind specifically and with high affinity to intestinal epithelium, renal tubules, brain endothelial cells and myelin. We identify specific binding of ETX to these structures and additionally show binding to retinal microvasculature and the squamous epithelial cells of the sclera in wild-type mice. In contrast, there is a complete absence of ETX binding to tissues from MAL knockout (MAL-/-) mice. Furthermore, MAL-/- mice exhibit complete resistance to ETX at doses in excess of 1000 times the symptomatic dose for wild-type mice. We conclude that MAL is required for both ETX binding and cytotoxicity.

We have isolated Clostridium perfringens type B, an epsilon toxin-secreting bacillus, from a young woman at clinical presentation of Multiple Sclerosis (MS) with actively enhancing lesions on brain MRI. This finding represents the first time that C. perfringens type B has been detected in a human. Epsilon toxin's tropism for the blood-brain barrier (BBB) and binding to oligodendrocytes/myelin makes it a provocative candidate for nascent lesion formation in MS. We examined a well-characterized population of MS patients and healthy controls for carriage of C. perfringens toxinotypes in the gastrointestinal tract. The human commensal Clostridium perfringens type A was present in approximately 50% of healthy human controls compared to only 23% in MS patients. We examined sera and CSF obtained from two tissue banks and found that immunoreactivity to ETX is 10 times more prevalent in people with MS than in healthy controls, indicating prior exposure to ETX in the MS population. C. perfringens epsilon toxin fits mechanistically with nascent MS lesion formation since these lesions are characterized by BBB permeability and oligodendrocyte cell death in the absence of an adaptive immune infiltrate.

The leading form of cancer affecting females globally is breast cancer, characterized by an unregulated growth of cells within the breast. Therefore, examining breast tissue is crucial in accurately identifying and treating this disease. Exosomes are very small enclosures bounded by a layer of cells and produced by a variety of cells present in the cancerous tissue surroundings. They play a crucial role in several biological functions in cancerous tumors. These exosomes carry non-coding RNAs (ncRNAs) and are discharged into the TME, where they are instrumental in the development and advancement of tumors. Additionally, the ncRNAs enclosed in exosomes act as significant mediators of communication within cells. Consequently, there is limited comprehension regarding the precise roles and targets of exosomal RNA in regulation, as research in this area is still in its preliminary phases. This piece provides a comprehensive overview of the latest studies on exosomes, delving into their impact on the behavior of cancer cells and immune cells. Moreover, it presents a compilation of the diverse forms of non-coding RNA molecules found in exosomes released by both cancerous and supportive cells, including circular RNAs, microRNAs, and long non-coding RNAs. Current research has proven the noteworthy influence that non-coding RNA molecules have on the progression, proliferation, drug resistance, and immune responses of breast cancer cells., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Breast cancer is the primary cause of cancer-related death and the most frequent malignancy among women in Western countries. Although there have been advancements in combination treatments and targeted therapies for the metastatic diseases management, metastatic breast cancer is still the second most common cause of cancer-related deaths among U.S. women. The routes of metastasis encompass invasion, intravasation, circulation, extravasation, infiltration into a remote location to establish a metastatic niche, and the formation of micro-metastases in a new environment. Each of these processes is regulated by changes in gene expression. MicroRNAs (miRNAs) are widely expressed by a variety of organisms and have a key role in cell activities including suppressing or promoting cancer through regulating various pathways. Target gene expression is post-transcriptionally regulated by miRNAs, which contribute to the development, spread, and metastasis of breast cancer. In this study, we comprehensively discussed the role of miRNAs as predictors of breast cancer metastasis, their correlation with the spread of the disease to certain organs, and their potential application as targets for breast cancer treatment. We also provided molecular mechanisms of miRNAs in the progression of breast cancer, as well as current challenges in miRNA-based therapeutic approaches. Furthermore, as one of the primary issues with the treatment of solid malignancies is the efficient delivery of miRNAs, we examined a number of cutting-edge carriers for miRNA-based therapies and CRISPR/Cas9 as a targeted therapy for breast cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Both women and men are now confronted with the grave threat of cancers caused by the human papillomavirus (HPV). It is estimated that 80% of women may encounter HPV over their lives. In the preponderance of cases involving anal, head and neck, oral, oropharyngeal, penile, vaginal, vulvar, and cervical malignancies, high-risk HPV (HR-HPV) is the causative agent. In 2019, HPV is believed to have been the cause of 620,000 new cases of cancer in women and 70,000 new cases of cancer in men worldwide. The bulk of the 530,000 cervical cancer cases (~ 270,000 fatalities) caused by HPV infection (86% of cases, 88% of deaths) happen in poor nations each year. Lipid metabolism is crucial in HPV infection and cancer development related to HPV. One of the most noticeable metabolic abnormalities in cancer is lipid metabolism reprogramming, in which cancer cells dysregulate lipid metabolism to obtain sufficient energy, building blocks for cell membranes, and signaling molecules necessary for invasion, metastasis, proliferation, and survival. Moreover, HPV proteins' stimulation of lipid production in infected cells will probably have a significant effect on oncogenesis. In addition, lipids are critical in producing cellular energy, the epithelial-mesenchymal transition (EMT) process, and therapy resistance of HPV-related cancers (HRCs). Therefore, lipids are essential in HPV infection and HRC development and may also be an important target for new approaches associated with treatments during HPV infection or cancer development. This review study looked at the role of lipids and lipid-lowering drugs in HPV and related cancers., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All author consent to publication. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Theranostics is a way of treating illness that blends medicine with testing. Specific characteristics should be present in the best theranostic agents for cancer: (1) the drugs should be safe and non-toxic; (2) they should be able to treat cancer selectively; and (3) they should be able to build up only in the cancerous tissue. Liposomes (LPs) are one of the most efficient drug delivery methods based on nanotechnology. Stealth LPs and commercial LPs have recently had an impact on cancer treatment. Using the valuable information from each imaging technique, along with the multimodality imaging functionality of liposomal therapeutic agents, makes them very appealing for personalized monitoring of how well therapeutic drugs are working against cancer in vivo and for predicting how well therapies will work. On the other hand, their use as nanoparticle delivery systems is currently in the research and development phase. Nanoscale delivery system innovation has made LP-nanoparticle hybrid structures very useful for combining therapeutic and imaging methods. LP-hybrid nanoparticles are better at killing cancer cells than their LP counterparts, making them excellent options for in vivo and in vitro drug delivery applications. Hybrid liposomes (HLs) could be used in the future as theranostic carriers to find and treat cancer targets. This would combine the best features of synthetic and biological drug delivery systems. Overarchingly, this article provided a comprehensive overview of the many LP types used in cancer detection, therapy, and theranostic analysis. An evaluation of the pros and cons of the many HLs types used in cancer detection and treatment has also been conducted. The study also included recent and significant research on HLs for cancer theranostic applications. We conclude by outlining the potential benefits and drawbacks of this theranostic approach to the concurrent detection and treatment of different malignancies, as well as its prospects., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All authors consent to the publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Among the most challenging diseases to treat is lung cancer (LC). While immunotherapy has a checkered history, it has lately shown great promise in the treatment of LC, and interest in this promising new approach is on the rise around the globe. Immunotherapy using mesenchymal stem cells (MSCs) is gaining popularity. Regenerative medicine, cell therapy, and immune modulation are three areas that have shown significant interest in MSCs. More than that, MSCs have recently attracted attention as potential anti-cancer drug delivery vehicles due to their inherent ability to go home to tumor locations. Making MSCs a double-edged sword in the fight against neoplastic illnesses, they are also known to impart pro-oncogenic properties. Additionally, multiple studies have proposed extracellular vesicles (EVs) secreted by MSCs as a potential therapeutic agent or method for delivering anti-cancer drugs. However, there has been conflicting evidence regarding the impact of MSCs or MSC-EV on the behavior of cancer cells, and the exact mechanism for this effect is still unknown. Our research has focused on MSCs and their key characteristics, such as their immunomodulatory capabilities for cancer therapy. Our research has also explored the potential of MSCs and their derivatives to treat small-cell and non-small-cell lung cancers (NSCLC and SCLC, respectively) by leveraging MSCs' immunomodulatory characteristics. At the end of this article, we covered the pros and cons of this therapy procedure, as well as what researchers want to do in the future to make it more suitable for clinical application in LC treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The primary source of short-chain fatty acids (SCFAs), now recognized as critical mediators of host health, particularly in the context of neurobiology and cancer development, is the gut microbiota's fermentation of dietary fibers. Recent research highlights the complex influence of SCFAs, such as acetate, propionate, and butyrate, on brain cancer progression. These SCFAs impact immune modulation and the tumor microenvironment, particularly in brain tumors like glioma. They play a critical role in regulating cellular processes, including apoptosis, cell differentiation, and inflammation. Moreover, studies have linked SCFAs to maintaining the integrity of the blood-brain barrier (BBB), suggesting a protective role in preventing tumor infiltration and enhancing anti-tumor immunity. As our understanding of the gut-brain axis deepens, it becomes increasingly important to investigate SCFAs' therapeutic potential in brain cancer management. Looking into how SCFAs affect brain tumor cells and the environment around them could lead to new ways to prevent and treat these diseases, which could lead to better outcomes for people who are dealing with these challenging cancers., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cyclooxygenase-2 (COX-2), a key enzyme in the inflammatory pathway, is the target for various nonsteroidal anti-inflammatory drugs (NSAIDs) and selective inhibitors known as coxibs. This study focuses on the development of novel imidazole derivatives as COX-2 inhibitors, utilizing a Structure-Activity Relationship (SAR) approach to enhance binding affinity and selectivity. Molecular docking was performed using Autodock Vina, revealing binding energies of -6.928, -7.187, and -7.244 kJ/mol for compounds 5b, 5d, and 5e, respectively. Molecular dynamics simulations using GROMACS provided insights into the stability and conformational changes of the protein-ligand complexes. Key metrics such as RMSD, RMSF, Rg, SASA, and hydrogen bond analysis were employed to assess the interactions. The binding free energy of the inhibitors was estimated using the MMPBSA method, highlighting compound 5b (N-[(3-benzyl-2-methylsulfonylimidazol-4-yl)methyl]-4-methoxyaniline) with the lowest binding energy of -162.014 kcal/mol. ADMET analysis revealed that compound 5b exhibited the most favorable pharmacokinetic properties and safety profile. Overall, this investigation underscores the potential of these novel imidazole derivatives as effective COX-2 inhibitors, with compound 5b emerging as the most promising candidate for further development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.)

The Flaviviridae family includes the dengue virus (DENV). About half of the world's population is in danger because of the estimated 390 million infections and 96 million symptomatic cases that occur each year. An effective treatment for dengue fever (DF) does not yet exist. Therefore, a better knowledge of how viral proteins and virus-targeted medicines may exert distinct functions depending on the exact cellular region addressed may aid in creating much-needed antiviral medications. Lipids facilitate the coordination of many viral replication phases, from entrance to dissemination. In addition, flaviviruses masterfully plan a significant rearrangement of the host cell's lipid metabolism to foster the growth of new viruses. Recent research has consistently shown the significance of certain lipid classes in flavivirus infections. For instance, in DENV-infected cells, overall cellular cholesterol (CHO) levels are only a little altered, and DENV replication is significantly reduced when CHO metabolism is inhibited. Moreover, statins significantly decrease DENV serotype 2 (DENV-2) titers, indicating that CHO is a prerequisite for the dengue viral cycle. Furthermore, many Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are now being evaluated in human research. A new pharmacological target for the management of high CHO is PCSK9. Moreover, suppression of PCSK9 has been proposed as a possible defense against DENV. Numerous studies have generally recommended the use of lipid-lowering medications to suppress the DENV. As a result, we have investigated the DENV and popular treatment techniques in this research. We have also examined how lipid metabolism, cellular lipids, and lipid receptors affect DENV replication regulation. Lastly, we have looked at how different lipid-lowering medications affect the DENV. This article also discusses the treatment method's future based on its benefits and drawbacks., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All authors are consent to the publication. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Gynecologic cancer, a prevalent and debilitating disease affecting women worldwide, is characterized by the uncontrolled proliferation of cells in the reproductive organs. The complex etiology of gynecologic cancer encompasses multiple subtypes, including cervical, ovarian, uterine, vaginal, and vulvar cancers. Despite optimal treatment strategies, which typically involve cytoreductive surgery and platinum-based chemotherapy, gynecologic cancer frequently exhibits recalcitrant relapse and poor prognosis. Recent studies have underscored the significance of the tumor microenvironment in ovarian carcinogenesis, particularly with regards to the discovery of aberrant genomic, transcriptomic, and proteomic profiles. Within this context, cancer-associated fibroblasts (CAFs) emerge as a crucial component of the stromal cell population, playing a pivotal role in oncogenesis and cancer progression. CAF-derived exosomes, small extracellular vesicles capable of conveying biological information between cells, have been implicated in a range of tumor-related processes, including tumorigenesis, cell proliferation, metastasis, drug resistance, and immune responses. Furthermore, aberrant expression of CAF-derived exosomal noncoding RNAs and proteins has been found to strongly correlate with clinical and pathological characteristics of gynecologic cancer patients. Our review provides a novel perspective on the role of CAF-derived exosomes in gynecologic cancer, highlighting their potential as diagnostic biomarkers and therapeutic targets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

The viability of probiotic cells decreases during passage through the gastrointestinal tract. The process of probiotics encapsulation with sodium alginate and chitosan polymers was carried out to protect the Lactobacillus plantarum in adverse conditions. Lactobacillus plantarum was entrapped in sodium alginate/chitosan (SA/BChi) and sodium alginate/nano-chitosan (SA/NChi) wall materials. Encapsulating L. plantarum with SA/BChi and SA/NChi resulted in a high encapsulation efficiency % of ~ 86.41 to 91.09%. In addition, coating bacteria cells in encapsulants improved the survivability of the cells under the simulated gastrointestinal fluids by ~ 52.61% in SA/Chi and 58.04% in SA/NChi compared to 29% for unencapsulated forms. Probiotic beads under field emission-scanning electron microscopy (FE-SEM) were morphologically compact with a cracked appearance of SA/NChi beads. The Fourier transform-infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) showed vigorous electrostatic interaction between polymers, as well as the high melting points, which corroborate the previous investigations in the field for using SA/BChi or SA/NChi as a promising encapsulating agent for ameliorating the survivability of probiotics under harsh conditions. The distinctive properties possessed by the two coatings make them excellent candidates for use as polymeric carriers in probiotic delivery systems., Competing Interests: Declarations. >Ethical Approval: The project was approved by the local ethical committee at the University of Tehran. Consent to Participate: Informed consent was obtained from all individual participants included in the study. Consent for Publication: We have read the final version and give our consent for the article to be published in (Applied Biochemistry and Biotechnology). Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Yersinia pestis is the perilous pandemics that occurred in Asia and Europe. The bacterium has shown drug resistance that can cause the future pandemic and destroy the drug treatment against plague. As known, effective therapeutics such as designing potent vaccine that can aid world to protect against plague. The immunoinformatics approaches was implemented via different server. The 4 potent antigens (F1 capsule, LcrV, OmpA, and PH6) were listed as essential protein target for creating the multi-epitope vaccine. These targets were selected for designing multi-epitope vaccine that predicted the CTL and HTL epitopes. The vaccine construct included different linkers such as EAAAK, AAY, GPGPG, and SSL that an adjuvant (Beta defensin-3) inserted at N-terminal of vaccine. The computational physiochemical properties and other immunological analysis showed stable, soluble, antigen, non-allergen, and non-toxin. The molecular docking confirmed the stable binding and good interaction and the iMODS server showed the stable binding. Furthermore, computational immune simulation of multi-epitope vaccine showed that vaccine can stimulate adaptive and innate responses after second doses. In this study, the vaccine designed for Y. pestis that in future require immunological examination to unveil real efficiency., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier B.V.)

Helicobacter pylori is a spiral-shaped, flagellated, microaerophilic bacteria found in the human gastric sub-mucosa. This study aimed to investigate the association between toll-like receptor markers (TLR2 and TLR4) and the infection with Helicobacter pylori . The study involved 224 participants randomly divided into 2 equal groups (n=112). The patient group (n=112) was involved with several gastrointestinal symptoms. They were compared to a control group (n=112) with negative H. pylori tests. Patients and control were subjected to upper digestive endoscopy with gastric biopsy for the rapid urease test, rapid diagnostic test, and ELISA test for TLR2 and TLR4 detection. The recorded data showed that 36 (32.1 %) patients with H. pylori were in the second to the third decades of their life (25-34 years), while 22 (19.6 %) positive H. pylori -infected individuals were in the age range of 15-24 years, which were very close to the participants in the age range of 35-44 years. On the other hand, it is revealed that 15 (13.4%) participants were in the fourth to fifth decades of life. This rate was very similar to the groups of patients within the sixth to seventh decades of their life (13 (11.6 %)), but the lowest number of cases with H. pylori patients found in the age range of 55-64 years were recorded 7.1%. In conclusion, the concentration of TLR2 and TLR4 is higher in H. pylori -positive participants compared to the control group. This might reflect the response of innate immunity of the body to the presence of H. pylori infection, and thus it may be used as an ancillary tool in the detection of the patient's susceptibility to this type of infection., Competing Interests: The authors declare that they have no conflict of interest.

This study included the role of Leuconostoc mesenteroides subsp. cremoris in oral diseases such as periodontitis. Material and Method . Isolation and identification of Leuconostoc mesenteroides subsp. cremoris from a saliva sample of twenty patients wearing fixed dental prostheses suffering from periodontitis followed by estimating susceptibility generally to the most common antibiotics and specifically to chlorhexidine (CHX) to determine the MIC of CHX and also screening of the strength of biofilm production under aerobic and anaerobic conditions; here, the study included six groups: Group I: screening of biofilm formation under aerobic condition, Group II: screening the MIC of CHX effect on biofilm formation under aerobic condition, Group III: screening of the MIC of CHX effect on preformed biofilm under aerobic condition, Group IV: screening of biofilm formation under anaerobic condition, Group V: screening of MIC of CHX effect on biofilm formation under anaerobic condition, and Group VI: screening of MIC of CHX effect on preformed biofilm under anaerobic condition. Results . The results showed that about 5 (25%) isolates were identified as L. mesenteroides subsp. cremoris, while 75% are other isolates. Furthermore, susceptibility results to antibiotic showed the sensitivity to penicillin (100%), azithromycin (100%), ciprofloxacin (100%), tetracycline (100%), gentamicin (100%), doxycycline (100%), vancomycin (100%), ofloxacin (60%), chloramphenicol (80%), ampicillin (80%), and cefoxitin (60%). On the other side, the biofilm production assays revealed that all isolates were moderate biofilm former under the aerobic and anaerobic conditions but for the biofilm treated with MIC of CHX, the current study noticed that the strength of the biofilm became weaker in aerobic and anaerobic conditions; regardless, the strength of the biofilm under anaerobic conditions was higher than in that under aerobic conditions, with no significant differences at p ≤ 0.05 depending on the statistical analysis ( T -test) before and after the treatment with MIC of CHX in aerobic and anaerobic conditions. Conclusions . The presence of mesenteroides subsp. cremoris in the oral cavity is due to eating foods and vegetables; based on the strength of the biofilm and sensitivity tests, the isolates have less pathogenicity in the oral cavity due to the weakness of the biofilm production and the lack of resistance to antibiotics., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Saif Ali Mohammed Hussein et al.)

Left ventricular posterior wall pseudoaneurysm after native mitral valve infective endocarditis is a very rare occurrence. We report such a case in a patient with HLA-B27-associated spondyloarthritis and normal coronary arteries. Excision of the aneurysm with left ventricular reconstruction and mitral valve replacement resulted in an excellent outcome.